1
|
Ramalhosa F, Lunardi F, Bernardinello N, Gori S, Pezzuto F, Tauro V, Del Vecchio C, Giraudo C, Balestro E, Calabrese F. Long COVID in Immunocompromised and Immunocompetent Patients: A Clinical, Morphologic, and Virologic Portrait. Arch Pathol Lab Med 2025; 149:535-541. [PMID: 39396825 DOI: 10.5858/arpa.2024-0043-oa] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/17/2024] [Indexed: 10/15/2024]
Abstract
CONTEXT.— Coronavirus disease 2019 (COVID) primarily affects the lung and can lead to chronic/post-COVID syndrome. Some insights about late pulmonary changes occurring in patients recovering from COVID have been published, but the evidence of detailed pathologic changes coming from follow-up care patients with long COVID is limited. OBJECTIVE.— To evaluate tissue morphologic and viral features in transbronchial biopsies of long COVID patients (immunocompetent and immunocompromised). DESIGN.— This retrospective observational study included 18 patients (9 immunocompetent and 9 immunocompromised) who were consecutively referred to our outpatient clinic for post-COVID pneumonia, undergoing transbronchial biopsy. Several histologic changes were analyzed by computer-assisted morphometric analysis. As organizing pneumonia (OP) was consistently detected, fibrosis and inflammation were also evaluated in transbronchial biopsies from 28 control patients with histologic confirmation of OP. Tissue SARS-CoV-2 and the subgenomic transcripts were investigated. Morphologic findings were correlated with clinical and radiologic data. RESULTS.— Long COVID patients showed lower inflammation than controls (P < .001) despite a similar fibrotic extension. When considering separately the 2 long COVID groups, the same inflammatory infiltrate extension was found, whereas a higher fibrotic remodeling characterized the immunocompetent subgroup (P = .05). Molecular investigation showed that SARS-CoV-2 was present in tissue samples obtained from 3 long COVID patients. CONCLUSIONS.— Long COVID patients showed a peculiar OP pattern, with more vascular and fibrotic changes. SARS-CoV-2 RNA, even in replicative status, can be detected in lung biopsies of both immunocompetent and immunocompromised patients. This pilot study is a forerunner of more in-depth lung tissue investigations to gain a better understanding of long COVID pathobiology.
Collapse
Affiliation(s)
- Fátima Ramalhosa
- From the Pathology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal (Ramalhosa)
| | - Francesca Lunardi
- the Departments of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy (Lunardi, Bernardinello, Pezzuto, Giraudo, Balestro, Calabrese)
| | - Nicol Bernardinello
- the Departments of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy (Lunardi, Bernardinello, Pezzuto, Giraudo, Balestro, Calabrese)
| | - Silvia Gori
- and the Immunology and Molecular Oncology Diagnostics Unit, Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy (Gori)
| | - Federica Pezzuto
- the Departments of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy (Lunardi, Bernardinello, Pezzuto, Giraudo, Balestro, Calabrese)
| | - Veronica Tauro
- Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (Tauro)
| | | | - Chiara Giraudo
- the Departments of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy (Lunardi, Bernardinello, Pezzuto, Giraudo, Balestro, Calabrese)
| | - Elisabetta Balestro
- the Departments of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy (Lunardi, Bernardinello, Pezzuto, Giraudo, Balestro, Calabrese)
| | - Fiorella Calabrese
- the Departments of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy (Lunardi, Bernardinello, Pezzuto, Giraudo, Balestro, Calabrese)
| |
Collapse
|
2
|
Huang Y, Wu Y, Zhou S, Que X, Jiang A, Shi D, Lu T, Chen Y, Lin Z, Liu C, Wen Y, Zhang S, Huang W. The characteristics of new-onset myasthenia gravis after COVID-19 outbreak: a cross-sectional study. Virol J 2025; 22:140. [PMID: 40361182 PMCID: PMC12070696 DOI: 10.1186/s12985-025-02774-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 05/06/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Little research has been conducted on new-onset myasthenia gravis (MG) patients following the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 surged in China on December 7th, 2022. This study aimed to explore the clinical characteristics of new-onset MG patients after COVID-19 and analyze factors affecting their disease improvement. METHODS All new-onset MG patients before (December 1st, 2021 to December 7th, 2022) and after COVID-19 outbreak (December 8th, 2022 to November 30th, 2023) were included in this study. Data was collected through the electronic medical record system and follow-up. Multivariate logistic regression was used to identify independent predictors of clinical improvement in patients with new-onset MG. RESULTS 359 new-onset MG patients (165 before COVID-19 outbreak and 194 after COVID-19 outbreak) were enrolled in this study. After COVID-19 outbreak, there was an increase in new-onset MG patients, with more cases occurring within the first three months. The rates of pulmonary inflammation (40.28%), COVID-19 vaccination (88.14%), and treatment with tacrolimus (15.98%) and MG duration (15 weeks, IQR: 5.75, 32) were higher, while rates of thymectomy (13.92%), baseline MG-ADL (3, IQR: 3, 6), and QMGS (7, IQR: 5,8) were lower compared to new-onset MG patients before COVID-19 outbreak. Multivariate logistic regression analysis showed that age at onset (OR 0.964, p < 0.001), baseline MG-ADL (OR 1.611, p < 0.001), and ocular MG (OR 0.401, p = 0.041) were independent predictors of clinical improvement in new-onset MG after the COVID-19 outbreak. CONCLUSION In this single-center cross-sectional study, new-onset MG patients following the COVID-19 outbreak showed altered seasonal onset patterns, milder disease severity, and higher OMG onset age. Age at onset is an independently negative predictor of improvement in new-onset MG patients after the COVID-19 outbreak. Whereas baseline MG-ADL is an independently positive predictor.
Collapse
Affiliation(s)
- Yanzhen Huang
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Yu Wu
- University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Shaodan Zhou
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Xianting Que
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Ailing Jiang
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Danli Shi
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Ting Lu
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Yanlan Chen
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Ziqun Lin
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Chao Liu
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Yishuang Wen
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Shuyi Zhang
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Wen Huang
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China.
| |
Collapse
|
3
|
Keen C, Grenier J, Šereš P, Stobbe R, White J, Beaulieu C, Sherrington R, Kirkham A, Paterson DI, Thompson R. MRI Assessment of Lung Water Density in Individuals Previously Infected With COVID-19: A Cross-Sectional Study. J Magn Reson Imaging 2025. [PMID: 40343427 DOI: 10.1002/jmri.29814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Revised: 04/28/2025] [Accepted: 04/28/2025] [Indexed: 05/11/2025] Open
Abstract
BACKGROUND Lung damage in post-acute COVID-19 is a common clinical finding. Lung water density (LWD) imaging using ultrashort echo time (UTE) MRI with proton-density weighting is sensitive to edema and fibrosis. PURPOSE To characterize LWD in COVID-19 survivors, compared with a healthy cohort. STUDY TYPE Retrospective cohort. POPULATIONS 185 COVID-19 survivors (63 male; age [median (interquartile range, IQR)]: 51 (25-83) years; 160 (66-363) days from COVID-19 infection to MRI) and 109 healthy controls (64 male; age: 52 (27-76) years) with no history of COVID-19 infection. FIELD STRENGTH/SEQUENCE 2.89T; Yarnball UTE pulse sequence. ASSESSMENT Free-breathing three-dimensional LWD images were acquired in both cohorts. Clinical demographics (age, sex, body mass index [BMI]), presence of comorbidities (hypertension, dyslipidemia, diabetes, obesity), COVID-19 hospitalization, pulmonary function, six-minute walking distance, and plasma biomarkers were recorded. STATISTICAL TESTS Student's t-tests or Mann-Whitney U tests were used to compare lung water metrics between cohorts. The effect of comorbidities was assessed using Kruskal-Wallis tests followed by pairwise Wilcoxon tests with Bonferroni correction. Categorical variables were compared using chi-squared tests. p < 0.05 was considered significant. RESULTS LWD (median (IQR)), was significantly greater in the post-COVID-19 cohort than in the healthy cohort, 31.3 (6.6)% versus 27.9 (6.5)% in men and 30.3 (7.4)% versus 27.5 (4.9)% in women. 37% of men and 24% of women in the post-COVID-19 cohort had LWD above the healthy cohort 95% confidence limit. Participants with elevated LWD had significantly higher BMI (kg/m2) (32 (5) versus 26 (4) in men, 33 (9) versus 26 (7) in women), incidence of comorbidities (78% vs. 50% in men, 72% vs. 38% in women), rates of COVID-19 hospitalization (52% vs. 23% in men, 38% vs. 18% in women), and elevated CRP (mg/L) (2.2 (3.4) vs. 1.1 (1.4) in men, 1.8 (4.2) vs. 1.2 (2.1) in women). DATA CONCLUSION MRI-derived LWD is elevated in COVID-19 survivors and is related to high BMI, COVID-19 hospitalization, inflammatory plasma biomarkers, and the presence of comorbidities. EVIDENCE LEVEL 2. TECHNICAL EFFICACY Stage 3.
Collapse
Affiliation(s)
- Christopher Keen
- Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada
| | - Justin Grenier
- Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada
| | - Peter Šereš
- Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada
| | - Robert Stobbe
- Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada
| | - James White
- Libin Cardiovascular Institute, University of Calgary, Calgary, Canada
| | - Christian Beaulieu
- Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada
- Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada
| | - Rachel Sherrington
- Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada
| | - Amy Kirkham
- Faculty of Kinesiology & Physical Education, University of Toronto, Toronto, Ontario, Canada
| | - D Ian Paterson
- Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Richard Thompson
- Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada
- Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada
| |
Collapse
|
4
|
Zhang Y, Zhu F, Zhang Z, Wang J, Liao T, Xi Y, Liu D, Zhang H, Lin H, Mao J, Tang W, Zhao L, Yuan P, Yan L, Liu Q, Hong K, Qiao J. Alterations in Semen Quality and Immune-Related Factors in Men with Infertility who Recovered from COVID-19. MedComm (Beijing) 2025; 6:e70179. [PMID: 40276648 PMCID: PMC12019875 DOI: 10.1002/mco2.70179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 03/13/2025] [Accepted: 03/14/2025] [Indexed: 04/26/2025] Open
Abstract
The emergence of coronavirus disease 2019 (COVID-19) has triggered research into its impact on male reproductive health. However, studies exploring the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on semen quality in infertile men remain limited. Herein, we enrolled 781 male infertile patients who recovered from COVID-19 and analyzed their semen and blood samples collected at different time points. We found that SARS-CoV-2 RNA was undetectable in semen samples. Compared with pre-COVID-19 status, total sperm count, sperm concentration, vitality, motility, and percentage of sperm cells with normal morphology decreased significantly in the first month post-COVID-19. However, these alterations were reversed in the third month. Furthermore, seminal plasma samples exhibited reduced proinflammatory cytokine levels and notable changes in amino acid, nucleic acid, and carbohydrate metabolism by the third month compared with those in the first month. By contrast, no significant alterations in reproductive hormone levels were found. Vitality, progressive motility, and total motility negatively correlated with body temperature when it was above 38°C. In conclusion, semen quality initially decreases post-COVID-19 but reverses after approximately 3 months, with a decline related to inflammatory and fever. These findings may provide guidance to infertile male patients who need assisted reproductive technology.
Collapse
Affiliation(s)
- Ying Zhang
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- State Key Laboratory of Female Fertility PromotionNational Clinical Research Center for Obstetrics and GynecologyKey Laboratory of Assisted Reproduction (Peking University)Ministry of EducationBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive TechnologyPeking University Third HospitalBeijingChina
| | - Feiyin Zhu
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- State Key Laboratory of Female Fertility PromotionNational Clinical Research Center for Obstetrics and GynecologyKey Laboratory of Assisted Reproduction (Peking University)Ministry of EducationBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive TechnologyPeking University Third HospitalBeijingChina
- Peking‐Tsinghua Center for Life SciencesPeking UniversityBeijingChina
| | - Zhe Zhang
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- Department of UrologyPeking University Third HospitalBeijingChina
| | - Jing Wang
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- State Key Laboratory of Female Fertility PromotionNational Clinical Research Center for Obstetrics and GynecologyKey Laboratory of Assisted Reproduction (Peking University)Ministry of EducationBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive TechnologyPeking University Third HospitalBeijingChina
| | - Tianyi Liao
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- State Key Laboratory of Female Fertility PromotionNational Clinical Research Center for Obstetrics and GynecologyKey Laboratory of Assisted Reproduction (Peking University)Ministry of EducationBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive TechnologyPeking University Third HospitalBeijingChina
- Peking‐Tsinghua Center for Life SciencesPeking UniversityBeijingChina
| | - Yu Xi
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- Department of UrologyPeking University Third HospitalBeijingChina
| | - Defeng Liu
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- Department of UrologyPeking University Third HospitalBeijingChina
| | - Haitao Zhang
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- Department of UrologyPeking University Third HospitalBeijingChina
| | - Haocheng Lin
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- Department of UrologyPeking University Third HospitalBeijingChina
| | - Jiaming Mao
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- Department of UrologyPeking University Third HospitalBeijingChina
| | - Wenhao Tang
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- Department of UrologyPeking University Third HospitalBeijingChina
| | - Lianming Zhao
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- Department of UrologyPeking University Third HospitalBeijingChina
| | - Peng Yuan
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- State Key Laboratory of Female Fertility PromotionNational Clinical Research Center for Obstetrics and GynecologyKey Laboratory of Assisted Reproduction (Peking University)Ministry of EducationBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive TechnologyPeking University Third HospitalBeijingChina
| | - Liying Yan
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- State Key Laboratory of Female Fertility PromotionNational Clinical Research Center for Obstetrics and GynecologyKey Laboratory of Assisted Reproduction (Peking University)Ministry of EducationBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive TechnologyPeking University Third HospitalBeijingChina
| | - Qiang Liu
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- State Key Laboratory of Female Fertility PromotionNational Clinical Research Center for Obstetrics and GynecologyKey Laboratory of Assisted Reproduction (Peking University)Ministry of EducationBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive TechnologyPeking University Third HospitalBeijingChina
| | - Kai Hong
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- Department of UrologyPeking University Third HospitalBeijingChina
| | - Jie Qiao
- Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijingChina
- State Key Laboratory of Female Fertility PromotionNational Clinical Research Center for Obstetrics and GynecologyKey Laboratory of Assisted Reproduction (Peking University)Ministry of EducationBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive TechnologyPeking University Third HospitalBeijingChina
- Peking‐Tsinghua Center for Life SciencesPeking UniversityBeijingChina
| |
Collapse
|
5
|
Expert Panel on Thoracic Imaging, Christensen JD, Harowicz M, Walker CM, Little BP, Batra K, Brixey AG, Carroll MB, Chelala L, Cox CW, Drummond MB, Geissen NM, Halpern J, Madan R, Gopalakrishnan VP, Shroff GS, Thornton CS, Zreloff J, Chung JH. ACR Appropriateness Criteria® Chronic Dyspnea-Noncardiovascular Origin: 2024 Update. J Am Coll Radiol 2025; 22:S163-S176. [PMID: 40409875 DOI: 10.1016/j.jacr.2025.02.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 02/24/2025] [Indexed: 05/25/2025]
Abstract
For patients with chronic dyspnea of noncardiovascular origin, chest radiography is usually appropriate as the first-line imaging modality. Chest CT without contrast is either usually appropriate or may be appropriate as a second-line option for conditions of unclear etiology or suspected chronic obstructive pulmonary disease, small airways disease, and post-COVID-19 complications. Chest CT with contrast may have a role in patients with pleura/chest wall disease or diaphragm dysfunction. Although MRI, fluoroscopy, and FDG-PET/CT have limited roles, special imaging techniques such as inspiratory/expiratory CT and hyperpolarized xenon gas MRI are noted for their specific uses. This document aims to help clinicians choose the most suitable imaging tests, enhancing diagnostic accuracy and patient care. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
Collapse
Affiliation(s)
| | | | | | | | - Brent P Little
- Panel Vice-Chair, Mayo Clinic Florida, Jacksonville, Florida
| | - Kiran Batra
- University of Texas Southwestern Medical Center, Dallas, Texas
| | - Anupama G Brixey
- Portland VA Healthcare System and Oregon Health & Science University, Portland, Oregon
| | | | - Lydia Chelala
- The University of Chicago Medicine, Chicago, Illinois
| | | | - M Bradley Drummond
- University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; American Thoracic Society
| | - Nicole M Geissen
- Rush University Medical Center, Chicago, Illinois; The Society of Thoracic Surgeons
| | - Jason Halpern
- The Warren Alpert Medical School of Brown University and Rhode Island Medical Imaging, Providence, Rhode Island; Commission on Nuclear Medicine and Molecular Imaging
| | - Rachna Madan
- Brigham & Women's Hospital, Boston, Massachusetts
| | | | - Girish S Shroff
- The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Christina S Thornton
- University of Calgary, Calgary, Alberta, Canada; American College of Chest Physicians
| | - Jennifer Zreloff
- Emory University, Atlanta, Georgia; Society of General Internal Medicine
| | | |
Collapse
|
6
|
Wang X, Zhou Z, Peng Y, Tang Y, Dai Q, Zheng J, Zhang J. Computed tomography characteristics of chronic bronchitis and its association with disease severity and clinical outcomes in viral pneumonia: a retrospective cohort study. J Thorac Dis 2025; 17:2503-2518. [PMID: 40400916 PMCID: PMC12090116 DOI: 10.21037/jtd-2025-638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2025] [Accepted: 04/23/2025] [Indexed: 05/23/2025]
Abstract
Background Chronic bronchitis (CB) patients' excessive mucus and airway changes may worsen viral pneumonia severity, but there is a lack of objective clinical/imaging assessment criteria. This study used quantitative computed tomography (CT) to link CB pathology with pneumonia severity/prognosis, guiding early interventions for high-risk groups. Methods This retrospective cohort study included 42 patients with CB diagnosed with viral pneumonia and 208 non-CB viral pneumonia controls. Baseline demographic, clinical, and laboratory parameters were collected alongside thoracic CT-derived metrics, including mucus plugging score (a bronchopulmonary segment-based scoring system quantifying mucus obstruction severity), CT severity score (range, 0-25 per lobe), and emphysema quantification. Follow-up CT imaging was performed at 3 months post-diagnosis to assess pulmonary structural remodeling, with longitudinal documentation of CT severity scores. Participants were stratified into two cohorts by mucus plugging score: high mucus burden (≥4, group 1) and low mucus burden (<4, group 2). Intergroup comparisons utilized Fisher's exact test for categorical variables, with continuous variables analyzed via independent t-tests (normally distributed) or Mann-Whitney U tests (non-parametric distributions). Multivariate logistic regression modeling identified independent predictors of disease progression. Results This study enrolled 260 patients who were categorized into group 1 (n=42; CB prevalence: 35.70%) and group 2 (n=218; CB prevalence:19.70%). Comparative analysis demonstrated that CB patients in group 2 were significantly older [70, interquartile range (IQR) (62, 77) vs. 79, IQR (74.5, 86.5) years; P<0.001] and exhibited a higher female predominance (74.4% vs. 25.6%; P=0.03), alongside lower red blood cell count (RBC) [3.73, IQR (3.39, 4.29)×1012/L vs. 4.05, IQR (3.81, 4.53)×1012/L; P=0.02] and hemoglobin levels [119, IQR (105.5, 131) vs. 124, IQR (115.5, 136) g/L; P=0.04] compared to non-CB counterparts. Imaging analysis revealed that non-CB patients had greater thoracic reticular patterns [6.02, IQR (1.42, 10.08) vs. 2.50, IQR (0.57, 6.19) cm3; P=0.02] and emphysema severity [0.21, IQR (0.04, 0.73) vs. 0.05, IQR (0.01, 0.19) cm3; P<0.001], whereas CB patients across both groups showed marked bronchial wall thickening [group 1: 21.60, IQR (10.30, 37.69) vs. 6.28, IQR (1.54, 15.71) cm3, P=0.03; group 2: 35.08, IQR (13.38, 51.59) vs. 18.90, IQR (3.43, 45.53) cm3, P=0.01]. Notably, CB patients in group 2 displayed larger bronchial lumen volumes [13.63, IQR (5.19, 25.29) vs. 5.00, IQR (0.67, 13.46) cm3; P<0.001]. Multivariate analysis of the low mucus burden group identified female sex [odds ratio (OR) =3.39], age (OR =1.06), and emphysema (OR =1.56) as independent risk factors for disease progression (all P<0.05). Longitudinal CT follow-up indicated stable severity scores in non-CB patients, whereas high mucus-secreting CB patients (group 1) demonstrated significant reductions in mucus plugging scores over time. Conclusions CB features-mucus hypersecretion, emphysema, and airway thickening-worsen viral pneumonia severity and prognosis. Key predictors include advanced age (OR =1.06), female sex (OR =3.39), and emphysema (OR =1.56). High-risk CB patients, especially with emphysema, need enhanced CT monitoring and therapies improving mucociliary clearance and airway repair.
Collapse
Affiliation(s)
- Xiaofei Wang
- Department of Radiology, Ningbo No. 2 Hospital, Ningbo, China
- Health Science Center, Ningbo University, Ningbo, China
| | - Zhentao Zhou
- Department of Radiology, Ningbo No. 2 Hospital, Ningbo, China
- Department of Radiology, Xiangshan First People’s Hospital Medical and Health Group, Ningbo, China
| | - Yuting Peng
- Department of Radiology, Ningbo No. 2 Hospital, Ningbo, China
- School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Yinying Tang
- Department of Radiology, Ningbo No. 2 Hospital, Ningbo, China
- Health Science Center, Ningbo University, Ningbo, China
| | - Qi Dai
- Department of Radiology, Ningbo No. 2 Hospital, Ningbo, China
| | - Jianjun Zheng
- Department of Radiology, Ningbo No. 2 Hospital, Ningbo, China
| | - Jingfeng Zhang
- Department of Radiology, Ningbo No. 2 Hospital, Ningbo, China
| |
Collapse
|
7
|
Yang Y, Li D, Nie J, Wang J, Huang H, Hang X. A Nomogram for Predicting Survival in Patients with SARS-CoV-2 Omicron Variant Pneumonia Based on Admission Data. Infect Drug Resist 2025; 18:2093-2104. [PMID: 40303607 PMCID: PMC12039831 DOI: 10.2147/idr.s509178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 04/15/2025] [Indexed: 05/02/2025] Open
Abstract
Purpose Patients with severe SARS-CoV-2 omicron variant pneumonia pose a serious challenge. This study aimed to develop a nomogram for predicting survival using chest computed tomography (CT) imaging features and laboratory test results based on admission data. Patients and Methods A total of 436 patients with SARS-CoV-2 pneumonia (323 and 113 in the training and validation groups, respectively) were enrolled. Pneumonitis volume, assessed on chest CT scans at admission, was used to identify low- and high-risk groups. Risk analysis was performed using clinical symptoms, laboratory findings, and chest CT imaging features. A predictive algorithm was developed using Cox multivariate analysis. Results The high-risk group had a shorter survival duration than the low-risk group. Significant differences in mortality rate, neutrophil and lymphocyte counts, C-reactive protein (CRP) concentration, and urea nitrogen level were observed between the two groups. In the training group, age, pneumonia volume, total bilirubin, and blood urea nitrogen were independent prognostic factors. In the validation group, age, pneumonia volume, neutrophil count, and CRP were independent prognostic factors. A personalized prediction model for survival outcomes was developed using independent predictors. Conclusion A personalized prediction model was created to forecast the 5-, 10-, 15-, 20-, and 30-day survival rates of patients with COVID-19 omicron variant pneumonia based on admission data, and can be used to determine the survival rate and early treatment of severe patients.
Collapse
Affiliation(s)
- Yinghao Yang
- Department of Infectious Diseases, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China
- Department of Infectious Diseases, the 988th Hospital of the Joint Logistic Support Force, Zhengzhou, People’s Republic of China
| | - Dong Li
- Department of Infectious Diseases, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China
- Department of Gastroenterology, The 971th Hospital of PLA Navy, Qingdao, People’s Republic of China
| | - Jinqiu Nie
- Department of Infectious Diseases, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China
| | - Junxue Wang
- Department of Infectious Diseases, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China
| | - Huili Huang
- Department of Infectious Diseases, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China
| | - Xiaofeng Hang
- Department of Infectious Diseases, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China
| |
Collapse
|
8
|
Keskin Z, Yeşildağ M, Özberk Ö, Ödev K, Ateş F, Bakdık BÖ, Kardaş ŞÇ. Long-Term Effects of COVID-19: Analysis of Imaging Findings in Patients Evaluated by Computed Tomography from 2020 to 2024. Tomography 2025; 11:49. [PMID: 40423251 DOI: 10.3390/tomography11050049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2025] [Revised: 04/19/2025] [Accepted: 04/23/2025] [Indexed: 05/28/2025] Open
Abstract
Background: This study aims to systematically evaluate the findings from computed tomography (CT) examinations conducted at least three months post-diagnosis of COVID-19 in patients diagnosed between 2020 and 2024. Objective: To determine the frequency and characteristics of CT findings in the post-COVID-19 period, analyze long-term effects on lung parenchyma, and contribute to the development of clinical follow-up and treatment strategies based on the collected data. Materials and Methods: Ethical approval was obtained for this retrospective study, and individual consent was waived. A total of 76 patients were included in the study, aged 18 and older, diagnosed with COVID-19 between March 2020 and November 2024, who underwent follow-up chest CT scans at 3-6 months, 6-12 months, and/or 12 months post-diagnosis. CT images were obtained in the supine position without contrast and evaluated by two experienced radiologists using a CT severity score (CT-SS) system, which quantifies lung involvement. Statistical analyses were performed using IBM SPSS 23.0, with significance set at p < 0.05. Results: The results indicated a mean CT-SS of 10.58 ± 0.659. Significant associations were found between age, CT scores, and the necessity for intensive care or mechanical ventilation. The most common CT findings included ground-glass opacities, reticular patterns, and traction bronchiectasis, particularly increasing with age and over time. Conclusion: This study emphasizes the persistent alterations in lung parenchyma following COVID-19, highlighting the importance of continuous monitoring and tailored treatment strategies for affected patients to improve long-term outcomes.
Collapse
Affiliation(s)
- Zeynep Keskin
- Department of Radiology, Konya City Hospital, Konya 42020, Turkey
| | - Mihrican Yeşildağ
- Department of Chest Diseases, T.C. Ministry of Health Meram State Hospital, Konya 42090, Turkey
| | - Ömer Özberk
- Department of Radiology, Konya City Hospital, Konya 42020, Turkey
| | - Kemal Ödev
- Department of Radiology, Faculty of Medicine, Konya Chamber of Commerce Karatay University, Konya 42020, Turkey
| | - Fatih Ateş
- Department of Radiology, Konya City Hospital, Konya 42020, Turkey
| | - Bengü Özkan Bakdık
- Department of Chest Diseases, T.C. Ministry of Health Meram State Hospital, Konya 42090, Turkey
| | | |
Collapse
|
9
|
Gysan MR, Lehmann A, Bernitzky D, Zech A, Brugger J, Prosch H, Idzko M, Gompelmann D. Immunophenotyping of bronchoalveolar lavage and functional impairment in post-COVID syndrome : Insights from a prospective cohort trial. Wien Klin Wochenschr 2025:10.1007/s00508-025-02531-9. [PMID: 40263177 DOI: 10.1007/s00508-025-02531-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Accepted: 03/19/2025] [Indexed: 04/24/2025]
Abstract
OBJECTIVE Following recovery from COVID-19, there is evidence for pulmonary sequelae and functional impairment. Data regarding the immunopathological mechanisms are limited. This study aimed to investigate the relationship between bronchoalveolar lavage fluid (BALF) cellularity, lung function impairment and high-resolution computed tomography (HRCT) changes in post-COVID syndrome patients. METHODS Patients with post-COVID syndrome were enrolled in this Austrian single-center prospective observational cohort study. All patients underwent a pulmonary function test (PFT) and chest HRCT. Those with pathological HRCT findings underwent bronchoscopy with BALF sampling for differential cell count and fluorescence-activated cell sorting analysis. RESULTS In this study 26 patients with post-COVID syndrome underwent bronchoscopy with BAL. The HRCT showed ground-glass opacifications (69.2%), organizing pneumonia (7.7%) or both (11.5%). The PFT revealed restrictive lung disease in 38.5% and reduced diffusion capacity in 68%, 19.2% showed a pathological BAL cell pattern predominantly consisting of CD4+ T‑cells. The BALF lymphocyte count was associated with reduced forced vital capacity (p = 0.016) and an elevated alveolar-arterial oxygen gradient (p = 0.04). CONCLUSION A notable percentage of patients with post-COVID syndrome with persistent HRCT changes showed T‑helper lymphocytic inflammation in the lungs. The degree of alveolar lymphocytosis was associated with lung function impairment. This could suggest that a prolonged inflammatory response in the alveolar compartment contributes to the pathogenesis of post-COVID syndrome.
Collapse
Affiliation(s)
- Maximilian Robert Gysan
- Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
| | - Antje Lehmann
- Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Dominik Bernitzky
- Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Andreas Zech
- Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Jonas Brugger
- Institute for Medical Statistics, Medical University of Vienna, Vienna, Austria
| | - Helmut Prosch
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Marco Idzko
- Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Daniela Gompelmann
- Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
- Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
10
|
Verbeeck Mendez S, Do Orozco IL, Gavilanez-Chavez GE, Nava-Zavala AH, Zavala-Cerna MG. Challenges and Opportunities for Post-COVID Pulmonary Disease: A Focused Review of Immunomodulation. Int J Mol Sci 2025; 26:3850. [PMID: 40332501 PMCID: PMC12027742 DOI: 10.3390/ijms26083850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 04/02/2025] [Accepted: 04/14/2025] [Indexed: 05/08/2025] Open
Abstract
The resolution of the recent COVID-19 pandemic still requires attention, since the consequences of having suffered the infection, even in mild cases, are associated with several acute and chronic pathological conditions referred to as post-COVID syndrome (PCS). PCS often manifests with pulmonary disease and, in up to 9% of cases, a more serious complication known as post-COVID-19 pulmonary fibrosis (PC19-PF), which has a similar clinical course as idiopathic pulmonary fibrosis (IPF). Generating knowledge to provide robust evidence about the clinical benefits of different therapeutic strategies to treat the pulmonary effects of PCS can provide new insights to amplify therapeutic options for these patients. We present evidence found after a scoping review, following extended PRIMSA guidelines, for the use of immunomodulators in pulmonary PCS. We start with a brief description of the immunomodulatory properties of the relevant drugs, their clinically proven efficacy for viral infections and chronic inflammatory conditions, and their use during the COVID-19 pandemic. We emphasize the need for well-designed clinical trials to improve our understanding the physiopathology of pulmonary PCS and PC19-PF and also to determine the efficacy and safety of candidate treatments.
Collapse
Affiliation(s)
| | - Isabella L. Do Orozco
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;
| | - Guadalupe E. Gavilanez-Chavez
- Hospital General Regional 46, Órgano de Operación Administrativa Desconcentrada Jalisco, Instituto Mexicano del Seguro Social, Guadalajara 44329, Mexico;
| | - Arnulfo Hernán Nava-Zavala
- Unidad de Investigación Epidemiológica y en Servicios de Salud, Centro Médico Nacional de Occidente Órgano de Operación Administrativa Desconcentrada Jalisco, Instituto Mexicano del Seguro Social, Guadalajara 44329, Mexico;
- Programa Internacional de Medicina, Universidad Autónoma de Guadalajara, Guadalajara 45129, Mexico
- Departamento de Inmunología y Reumatología, Hospital General de Occidente, Secretaría de Salud Jalisco, Zapopan 45170, Mexico
| | - Maria G. Zavala-Cerna
- Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara 45129, Mexico;
| |
Collapse
|
11
|
Bermudo-Peloche G, Del Rio B, Vicens-Zygmunt V, Bordas-Martinez J, Hernández M, Valenzuela C, Laporta R, Rigual Bobillo J, Portillo K, Millán-Billi P, Balcells E, Badenes-Bonet D, Bolivar S, Rodríguez-Portal JA, López Ramirez C, Tomás L, Fernández de Roitegi K, Sellarés J, Castillo D, González J, Barril S, Gutiérrez-Rodríguez Y, Caballero P, Alarcon J, Peñafiel J, Sanz-Santos J, Blavia R, Caupena C, Segovia P, Santos-Pérez S, Ferrer-Artola A, Badia MB, Hereu P, Fuentes M, Montes-Worboys A, Franquet T, Luburich P, Molina-Molina M. Pirfenidone in post-COVID-19 pulmonary fibrosis (FIBRO-COVID): a phase 2 randomised clinical trial. Eur Respir J 2025; 65:2402249. [PMID: 40154560 PMCID: PMC12018760 DOI: 10.1183/13993003.02249-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 01/09/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Patients with severe COVID-19 may develop lung fibrosis. Pirfenidone is an anti-fibrotic drug approved for idiopathic pulmonary fibrosis. The efficacy and safety of pirfenidone in patients with fibrotic interstitial lung changes after recovery from severe COVID-19 pneumonia were evaluated. METHODS This was a phase 2, double-blind, placebo-controlled, Spanish multicentre clinical trial. Patients were randomised to receive pirfenidone or placebo (2:1) for 24 weeks. The primary end-point was the proportion of patients that improved, considered when percentage change in forced vital capacity (FVC) was ≥10% and/or any reduction in the fibrotic score on chest high-resolution computed tomography (HRCT). Secondary end-points included health-related quality of life (HRQoL), exercise capacity and drug safety profile. RESULTS From 119 eligible patients, 113 were randomised and 103 were analysed (pirfenidone n=69 and placebo n=34). Most patients were male (73.5%) and were receiving low-dose prednisone; mean age was 63.7 years and mean body mass index was 29 kg·m-2. The percentage of patients that improved was similar in the pirfenidone and placebo groups (79.7% versus 82.3%, respectively). The mean predicted FVC increased by 12.74±20.6% with pirfenidone and 4.35±22.3% with placebo (p=0.071), and the HRCT (%) fibrotic score decreased by 5.44±3.69% with pirfenidone and 2.57±2.59% with placebo (p=0.52). Clinically meaningful improvement in HRQoL was not statistically different (55.2% in the pirfenidone group and 39.4% in the placebo group). Exercise capacity, adverse events and hospitalisations were similar between groups. No deaths were reported. CONCLUSIONS The overall improvements in lung function and HRCT fibrotic score after 6 months with pirfenidone were not significantly different than with placebo.
Collapse
Affiliation(s)
- Guadalupe Bermudo-Peloche
- Interstitial Lung Disease Unit, Respiratory Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Belén Del Rio
- Interstitial Lung Disease Unit, Radiology Department, Bellvitge University Hospital, University of Barcelona - L'Hospitalet de Llobregat, Barcelona, Spain
| | - Vanesa Vicens-Zygmunt
- Interstitial Lung Disease Unit, Respiratory Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Jaume Bordas-Martinez
- Interstitial Lung Disease Unit, Respiratory Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
| | - Marta Hernández
- Interstitial Lung Disease Unit, Respiratory Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Claudia Valenzuela
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Interstitial Lung Disease Unit, Respiratory Department, Hospital La Princesa, Madrid, Spain
| | - Rosalía Laporta
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Respiratory Department, Hospital Puerta Hierro, Majadahonda, Spain
| | - Juan Rigual Bobillo
- Respiratory Department, Universidad de Alcalá-IRYCIS, Hospital Ramón y Cajal, Madrid, Spain
| | - Karina Portillo
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Respiratory Department, Hospital Germans Trias i Pujol, Badalona, Spain
| | | | - Eva Balcells
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Respiratory Department, Hospital del Mar, Department of Medicine and Life Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain
| | - Diana Badenes-Bonet
- Respiratory Department, Hospital del Mar, Department of Medicine and Life Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain
| | - Santi Bolivar
- Interstitial Lung Disease Unit, Radiology Department, Bellvitge University Hospital, University of Barcelona - L'Hospitalet de Llobregat, Barcelona, Spain
| | - José-Antonio Rodríguez-Portal
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Interstitial Lung Disease Unit, Respiratory Department, Hospital Virgen del Rocío, Sevilla, Spain
| | - Cecilia López Ramirez
- Interstitial Lung Disease Unit, Respiratory Department, Hospital Virgen del Rocío, Sevilla, Spain
| | - Laura Tomás
- Respiratory Department, Hospital Txagorritxu, Vitoria, Spain
| | | | - Jacobo Sellarés
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Interstitial Lung Disease Unit, Respiratory Department, Hospital Clínic, Barcelona, Spain
| | - Diego Castillo
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Respiratory Department, Hospital Sant Pau i Santa Creu, Barcelona, Spain
| | - Jessica González
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain
| | - Silvia Barril
- Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain
| | - Yasmina Gutiérrez-Rodríguez
- Interstitial Lung Disease Unit, Respiratory Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Paloma Caballero
- Interstitial Lung Disease Unit, Radiology Department, Hospital La Princesa, Madrid, Spain
| | - Javier Alarcon
- Interstitial Lung Disease Unit, Department of Radiology, Hospital Ramón y Cajal, Madrid, Spain
| | - Judith Peñafiel
- Department of Biostatistics, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Jose Sanz-Santos
- Respiratory Department, Hospital Mutua Terrassa, Terrassa, Spain
| | - Rosana Blavia
- Respiratory Department, Hospital Moises Broggi, Sant Joan d'Espí, Spain
| | - Cristina Caupena
- Respiratory Department, Hospital General del Parc Sanitari Sant Joan de Dèu, Sant Boi de Llobregat, Spain
| | - Pilar Segovia
- Respiratory Department, Hospital de Figueres, Figueres, Spain
| | - Salud Santos-Pérez
- Interstitial Lung Disease Unit, Respiratory Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Anna Ferrer-Artola
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
- Department of Pharmacy, University Hospital of Bellvitge, Grupo de Investigación Farmacoterapia, Farmacogenética y Tecnología Farmacéutica, Programa de Sistema Digestivo, Diagnóstico, Farmacogenética, Enfermería y Prevención, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Maria B Badia
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
- Department of Pharmacy, University Hospital of Bellvitge, Grupo de Investigación Farmacoterapia, Farmacogenética y Tecnología Farmacéutica, Programa de Sistema Digestivo, Diagnóstico, Farmacogenética, Enfermería y Prevención, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Pilar Hereu
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
- Clinical Pharmacology Department, Bellvitge University Hospital, IDIBELL, Clinical Research and Clinical Trial Unit-IDIBELL, University of Barcelona, Barcelona, Spain
| | - Mireya Fuentes
- Interstitial Lung Disease Unit, Respiratory Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Ana Montes-Worboys
- Interstitial Lung Disease Unit, Respiratory Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Tomás Franquet
- Department of Radiology, Hospital Sant Pau i Santa Creu, Barcelona, Spain
| | - Patricio Luburich
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
- Interstitial Lung Disease Unit, Radiology Department, Bellvitge University Hospital, University of Barcelona - L'Hospitalet de Llobregat, Barcelona, Spain
| | - María Molina-Molina
- Interstitial Lung Disease Unit, Respiratory Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
- National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| |
Collapse
|
12
|
Mattone M, Masci GM, Landini N, Zingaropoli MA, Catalano C, Ciardi MR, Panebianco V. MMP-9 metalloproteinase and its regulator are not associated with mid-term CT residual abnormalities in patients with COVID-19 pneumonia. Acta Radiol Open 2025; 14:20584601251330563. [PMID: 40291835 PMCID: PMC12033756 DOI: 10.1177/20584601251330563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 03/12/2025] [Indexed: 04/30/2025] Open
Abstract
Background COVID-19 patients may have residual pulmonary alterations after the acute disease, with fibrotic-like alterations. Since metalloproteinases (MMP) and their regulators may be involved in inflammation and abnormal repair processing, we aimed to investigate the correlations between MMP-9, a tissue inhibitor of metalloproteinases (TIMP-1) and chest CT abnormalities in acute phase and mid-term follow-up. Methods COVID-19 patients with plasma analyses and CT scans performed at acute onset and 3 months after discharge (T post) were evaluated. MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio were analyzed. CT extents of COVID-19 pneumonia and fibrotic-like alterations were visually scored (score range 0-25). Spearman rank correlation analysis (p-value <.05) was computed between acute and mid-term plasma analyses and CT scores. Results 39 patients were enrolled. At hospital admission, MMP-9, TIMP-1, and MMP-9/TIMP-1 had a median of 240.5 ng/mL, 258.8 ng/mL, and 0.9. The median CT global and fibrotic-like scores were 9 and 6. At T post, MMP-9 and TIMP-1 were not statistically different (p-value <.05). There was a reduction of CT global score (p-value = .00007). A significant correlation was found between MMP-9 and CT global score at hospital admission (ρ = 0.456, p-value = .003) and between MMP-9/TIMP-1 ratio and CT global score at hospital admission (ρ = 0.406, p-value = .009). No other significant correlations were found between plasma enzymes and CT alterations, both in acute and mid-term follow-up. Conclusion MMP-9 plasma levels and MMP-9/TIMP-1 ratio correlate with lung involvement during the acute phase. None of the levels of MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio may be adopted as predictors of residual pulmonary alterations in mid-term follow-up.
Collapse
Affiliation(s)
- Monica Mattone
- Department of Radiological Sciences, Oncology and Pathology, Policlinico Umberto I, “Sapienza” University, Rome, Italy
| | - Giorgio Maria Masci
- Department of Radiological Sciences, Oncology and Pathology, Policlinico Umberto I, “Sapienza” University, Rome, Italy
| | - Nicholas Landini
- Department of Radiological Sciences, Oncology and Pathology, Policlinico Umberto I, “Sapienza” University, Rome, Italy
| | - Maria Antonella Zingaropoli
- Department of Public Health and Infectious Diseases, Policlinico Umberto I, “Sapienza” University, Rome, Italy
| | - Carlo Catalano
- Department of Radiological Sciences, Oncology and Pathology, Policlinico Umberto I, “Sapienza” University, Rome, Italy
| | - Maria Rosa Ciardi
- Department of Public Health and Infectious Diseases, Policlinico Umberto I, “Sapienza” University, Rome, Italy
| | - Valeria Panebianco
- Department of Radiological Sciences, Oncology and Pathology, Policlinico Umberto I, “Sapienza” University, Rome, Italy
| |
Collapse
|
13
|
Taher MK, Salzman T, Banal A, Morissette K, Domingo FR, Cheung AM, Cooper CL, Boland L, Zuckermann AM, Mullah MA, Laprise C, Colonna R, Hashi A, Rahman P, Collins E, Corrin T, Waddell LA, Pagaduan JE, Ahmad R, Jaramillo Garcia AP. Global prevalence of post-COVID-19 condition: a systematic review and meta-analysis of prospective evidence. Health Promot Chronic Dis Prev Can 2025; 45:112-138. [PMID: 40073162 PMCID: PMC12039764 DOI: 10.24095/hpcdp.45.3.02] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/14/2025]
Abstract
INTRODUCTION We investigated the prevalence of new or persistent manifestations experienced by COVID-19 survivors at 3 or more months after their initial infection, collectively known as post-COVID-19 condition (PCC). METHODS We searched four electronic databases and major grey literature resources for prospective studies, systematic reviews, authoritative reports and population surveys. A random-effects meta-analysis pooled the prevalence data of 22 symptoms and outcomes. The GRADE approach was used to assess the certainty of evidence. PROSPERO CRD42021231476. RESULTS Of 20 731 identified references, 194 met our inclusion criteria. These studies followed 483 531 individuals with confirmed COVID-19 diagnosis over periods of up to 2 years. Most focused on adults, nearly two-thirds were conducted in Europe and 63% were of high or moderate quality. The supplementary search identified 17 systematic reviews, five authoritative reports and four population surveys that reported on PCC prevalence. Our analysis revealed that more than half of COVID-19 survivors experienced one or more symptoms more than a year after their initial infection. The most common symptoms were fatiguedyspneamemory, sleep or concentration disturbances; depressionand pain. Limitation in returning to work was the most common outcome. Prevalence tended to be higher among females, individuals hospitalized during their initial infection and those who experienced severe COVID-19 illness. CONCLUSION PCC presents a significant health burden, affecting some groups more than others. This information will help inform health care system policies and services for people living with PCC and those caring for them.
Collapse
Affiliation(s)
- Mohamed Kadry Taher
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Talia Salzman
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Allyson Banal
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Kate Morissette
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Francesca R Domingo
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Angela M Cheung
- Department of Medicine and Joint Department of Medical Imaging, University Health Network and Sinai Health System, University of Toronto, Toronto, Ontario, Canada
- Toronto General Hospital Research Institute and Schroeder Arthritis Institute, Toronto, Ontario, Canada
| | - Curtis L Cooper
- Department of Medicine, University of OttawaOttawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Laura Boland
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Alexandra M Zuckermann
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Muhammad A Mullah
- Infectious Disease and Vaccination Programs Branch, Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Claudie Laprise
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
- Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Montréal, Quebec, Canada
| | - Roberto Colonna
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Ayan Hashi
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Prinon Rahman
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Erin Collins
- Population Health Modelling Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario,Canada
| | - Tricia Corrin
- Public Health Risk Sciences Division, National Microbiology Laboratory, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - Lisa A Waddell
- Public Health Risk Sciences Division, National Microbiology Laboratory, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - Jason E Pagaduan
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Rukshanda Ahmad
- Risk Assessment Division, Centre for Surveillance, Integrated Insights and Risk Assessment, Data, Surveillance and Foresight Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Alejandra P Jaramillo Garcia
- Evidence Synthesis and Knowledge Translation Unit, Centre for Surveillance and Applied Research, Health Promotion and Chronic Disease Prevention Branch, Public Health Agency of Canada, Ottawa, Ontario, Canada
| |
Collapse
|
14
|
Fang X, Li J, Zhang Y, Lv W, Liu L, Feng Y, Liu L, Pan F, Zhang J. Assessment of chest CT abnormalities and pulmonary function at 6-month and 1-year after hospital discharge in Chinese patients of COVID-19 pneumonia at the turn of 2022-2023. Front Med (Lausanne) 2025; 12:1463320. [PMID: 40078387 PMCID: PMC11896869 DOI: 10.3389/fmed.2025.1463320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 02/17/2025] [Indexed: 03/14/2025] Open
Abstract
Objective This study aimed to assess chest CT abnormalities and pulmonary function at 6-month and 1-year follow-ups in coronavirus disease 2019 (COVID-19) pneumonia patients of the China epidemic in the turn of 2022-2023. Methods A total of 156 hospitalized patients with COVID-19 pneumonia admitted between 29 November 2022 and 10 February 2023 were prospectively assessed at 6-month and 1-year follow-ups. Characteristics and CT scores of pulmonary abnormalities and pulmonary function were compared between different follow-up time points. The correlation of CT abnormalities and pulmonary function at 1-year were evaluated. Results Over 1 year, the proportion of pulmonary abnormalities gradually decreased (initial, 100%, 156/156; 6-month, 57.1%, 89/156; and 1-year, 37.8%, 59/156; P < 0.001), whereas fibrotic changes increased (initial, 6.4%, 10/156; 6-month, 14.1%, 22/156; and 1-year, 14.7%, 23/56; P < 0.001). Compared to participants of the subgroup with nonfibrotic changes, diffusion capacity of the lung for carbon monoxide (DLCO)(P = 0.01) and DLCO less than 80% predicted (P < 0.001) showed significantly decrease in participants of the subgroup with fibrotic changes. The extent of fibrotic changes was strongly correlated with lower DLCO (r = -0.734, P < 0.001). Conclusion Fibrotic changes might show a tendency to persist over time and correlate strongly with impairment of diffusion function, thus requiring more attention in future follow-ups.
Collapse
Affiliation(s)
- Xingyu Fang
- Department of Radiology, The 305 Hospital of People Liberation Army, Beijing, China
| | - Jialin Li
- Department of Laboratory, The 305 Hospital of People Liberation Army, Beijing, China
| | - Yijun Zhang
- Department of Radiology, The 305 Hospital of People Liberation Army, Beijing, China
| | - Wei Lv
- Department of Radiology, The 305 Hospital of People Liberation Army, Beijing, China
| | - Lin Liu
- Department of Radiology, The 305 Hospital of People Liberation Army, Beijing, China
| | - Yun Feng
- Department of Radiology, The 305 Hospital of People Liberation Army, Beijing, China
| | - Li Liu
- Department of Radiology, The 305 Hospital of People Liberation Army, Beijing, China
| | - Feng Pan
- Department of Radiology, The 305 Hospital of People Liberation Army, Beijing, China
| | - Jinping Zhang
- Department of Health Care, The 305 Hospital of People Liberation Army, Beijing, China
| |
Collapse
|
15
|
Roig-Martí C, Navarro-Ballester A, Fernández-García MP, Pérez-Catalán I, Segura-Fábrega A, Varea-Villanueva M, Folgado-Escudero S, Herrero-Rodríguez G, Domínguez-Bajo E, Fabra-Juana S, Esteve-Gimeno MJ, Mateu-Campos ML, Usó-Blasco J, Ramos-Rincón JM. Presence and Evolution of Radiological Changes at 6 and 12 Months After COVID-19 Pneumonia and Their Risk Factors. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:382. [PMID: 40142194 PMCID: PMC11943743 DOI: 10.3390/medicina61030382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 02/10/2025] [Accepted: 02/20/2025] [Indexed: 03/28/2025]
Abstract
Background and Objectives: The pulmonary sequelae of COVID-19 and their evolution are of interest to the scientific community. We aimed to determine the radiological changes at 6 and 12 months after COVID-19 pneumonia, its evolution and its risk factors. Materials and Methods: This retrospective longitudinal study included adults admitted for COVID-19 pneumonia from 1 March 2020 to 30 April 2021 who had a high-resolution computed tomography (HRCT) scan at 6 months and 12 months after hospital discharge. The primary outcome was the appearance of radiological abnormalities on HRCT and the number of lung segments affected by them at 6 and 12 months, while the main explanatory variables were about the disease course, analytical parameters and treatment. Results: This study included n = 108 patients, with a mean age of 64 years. There was a decrease in the percentage of patients presenting parenchymal (93.5% to 88.9%, p < 0.001) and reticular (63% to 62%, p < 0.001) patterns on HRCT at 12 months compared to 6, and an increase in those presenting a fibrotic pattern (62% to 63.9%, p < 0.001). Ground-glass opacities were the most frequent radiological change at 6 and 12 months (91.7% and 87%, respectively). There was a significant reduction in the total number of lung segments with ground-glass opacities (445 to 382, p < 0.001) and consolidation (158 to 136, p = 0.019) and an increase in those with bronchiectasis (66 to 80, p = 0.033) between the two moments. After multivariate analysis, high-flow oxygen therapy (HFOT), highest ferritin levels, hypertension and ≥71 years showed an association with the development of subpleural parenchymal bands, consolidation, bronchiectasis and septal thickening at 6 and 12 months. Conclusions: Parenchymal patterns seem to be more frequent than reticular and fibrotic patterns after COVID-19 pneumonia. The fibrotic pattern was the only one that worsened significantly over time, with bronchiectasis being the only change that increased at 12 months. Older age, hypertension, the need for HFOT, and high levels of ferritin may be directly associated with worse radiological outcomes after COVID-19 pneumonia.
Collapse
Affiliation(s)
- Celia Roig-Martí
- Internal Medicine Department, Castellón General University Hospital, 12004 Castellón, Spain
| | | | | | - Ignacio Pérez-Catalán
- Internal Medicine Department, Castellón General University Hospital, 12004 Castellón, Spain
| | - Ana Segura-Fábrega
- Internal Medicine Department, Castellón General University Hospital, 12004 Castellón, Spain
| | - María Varea-Villanueva
- Internal Medicine Department, Castellón General University Hospital, 12004 Castellón, Spain
| | - Sofía Folgado-Escudero
- Internal Medicine Department, Castellón General University Hospital, 12004 Castellón, Spain
| | | | - Elena Domínguez-Bajo
- Internal Medicine Department, Castellón General University Hospital, 12004 Castellón, Spain
| | - Sergio Fabra-Juana
- Internal Medicine Department, Castellón General University Hospital, 12004 Castellón, Spain
| | | | | | - Jorge Usó-Blasco
- Internal Medicine Department, Castellón General University Hospital, 12004 Castellón, Spain
| | - José-Manuel Ramos-Rincón
- Internal Medicine Department, Alicante General University Hospital, 03010 Alicante, Spain
- Alicante Institute of Health and Biomedical Research (ISABIAL), 03010 Alicante, Spain
- Clinical Medicine Department, Miguel Hernández University of Elche, 03202 Elche, Spain
| |
Collapse
|
16
|
Li Y, Tian X, Sun C, Wei Y, Jiang W, He L, Li C, Zhang L, Wang G, Lu X. Outcome of COVID-19 in patients with idiopathic inflammatory myopathy during the Omicron wave in China: A longitudinal observational study. PLoS One 2025; 20:e0317319. [PMID: 39928605 PMCID: PMC11809795 DOI: 10.1371/journal.pone.0317319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 12/25/2024] [Indexed: 02/12/2025] Open
Abstract
OBJECTIVE The coronavirus disease pandemic brought unknown challenges to patients with idiopathic inflammatory myopathy, who are often heavily immunosuppressed and have comorbidities. We aimed to investigate the outcomes and risk factors of coronavirus disease in Chinese patients with idiopathic inflammatory myopathy during the Omicron wave. METHODS This observational study included patients with idiopathic inflammatory myopathy who visited the China-Japan Friendship Hospital. Data on baseline characteristics and coronavirus disease-related information were collected through medical records and surveys, and subsequently analysed. RESULTS Overall, 204 patients with idiopathic inflammatory myopathy were identified; dermatomyositis was the most common idiopathic inflammatory myopathy subtype. Data were collected from 185 patients with idiopathic inflammatory myopathy who tested positive for severe acute respiratory syndrome coronavirus 2 via polymerase chain reaction or antigen tests; of these, 20 experienced a severe course of the disease, and 9 died. All patients with severe coronavirus disease had idiopathic inflammatory myopathy-associated interstitial lung disease, and the most common antibodies observed in patients with mortality were anti-aminoacyl tRNA synthetase and anti-MDA-5 antibodies. Furthermore, 45.0% of patients in the severe disease group took > 15.0 mg of prednisone daily before infection, a significantly higher proportion than that in the non-severe disease group. Advanced age, mechanics' hands, dyspnoea, chronic cough and fever during the course of myositis, low lymphocyte count, low serum albumin level, and high D-dimer and ferritin levels before infection were prominent in patients with severe coronavirus disease. Albumin levels below 35.0 g/L and ferritin levels above 306.8 ng/mL were independent risk factors of severe coronavirus disease. CONCLUSION Omicron did not worsen the overall outcomes of coronavirus disease for patients with idiopathic inflammatory myopathy; however, specific risk factors were identified, highlighting the need for targeted management strategies.
Collapse
Affiliation(s)
- Ying Li
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China
- Department of Rheumatology, Key Lab of Myositis, China-Japan Friendship Hospital, Beijing, People’s Republic of China
| | - Xiaolan Tian
- Department of Rheumatology, Key Lab of Myositis, China-Japan Friendship Hospital, Beijing, People’s Republic of China
| | - Chao Sun
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China
- Department of Rheumatology, Key Lab of Myositis, China-Japan Friendship Hospital, Beijing, People’s Republic of China
| | - Yangyang Wei
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China
- Department of Rheumatology, Key Lab of Myositis, China-Japan Friendship Hospital, Beijing, People’s Republic of China
| | - Wei Jiang
- Department of Rheumatology, Key Lab of Myositis, China-Japan Friendship Hospital, Beijing, People’s Republic of China
| | - Linrong He
- Department of Rheumatology, Key Lab of Myositis, China-Japan Friendship Hospital, Beijing, People’s Republic of China
| | - Chunjia Li
- Department of Rheumatology, Key Lab of Myositis, China-Japan Friendship Hospital, Beijing, People’s Republic of China
| | - Lu Zhang
- Department of Rheumatology, Key Lab of Myositis, China-Japan Friendship Hospital, Beijing, People’s Republic of China
| | - Guochun Wang
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China
- Department of Rheumatology, Key Lab of Myositis, China-Japan Friendship Hospital, Beijing, People’s Republic of China
| | - Xin Lu
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China
- Department of Rheumatology, Key Lab of Myositis, China-Japan Friendship Hospital, Beijing, People’s Republic of China
| |
Collapse
|
17
|
Yao X, Xu H, Du Q, Lu X, Wang Q. A novel method for detecting SARS-CoV-2 IgM and IgG based on the gold immune chromatography assay. Sci Rep 2025; 15:4995. [PMID: 39929938 PMCID: PMC11811196 DOI: 10.1038/s41598-025-89012-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Accepted: 02/03/2025] [Indexed: 02/13/2025] Open
Abstract
A novel method was proposed based on gold immune chromatography assay (GICA) including the detection of antibodies targeting different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitopes to improve the SARS-CoV-2 IgM and IgG detection performance. Sera from 282 confirmed Coronavirus Disease 2019 (COVID-19) patients were obtained at different times as the SARS-CoV-2 IgM or IgG experimental group. Sera from 148 uninfected and unvaccinated individuals were used as the control. The serum single-epitope IgM and IgG antibodies against SARS-CoV-2 were detected via GICA; the two epitope antibodies with high detection performance were used to construct a novel method, and then compared with the chemiluminescence immunoassay (CLIA). The diagnostic specificity and screening sensitivity of S2-IgM and N-IgM combined detection of serum SARS-CoV-2 IgM antibodies based on GICA were 99.32% and 98.81%, respectively, which were higher than those of the CLIA test (83.78% and 82.14%; P < 0.001). The diagnostic specificity of RBD-IgG and N-IgG combined detection in the serum was 100.00%, the same as that of CLIA. The novel method showed excellent screening sensitivity and diagnostic specificity for serum SARS-CoV-2 IgM and IgG, effectively avoiding omissions and misdiagnoses in the early clinical stages of screening and diagnosing COVID-19.
Collapse
Affiliation(s)
- Xiaoqin Yao
- Department of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
- Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, Sichuan, China
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, Sichuan, China
- Department of Laboratory Medicine, The Sixth People's Hospital of Yibin, Yibin, Sichuan, China
| | - Hao Xu
- Department of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
- Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, Sichuan, China
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Qin Du
- Department of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
- Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, Sichuan, China
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Xiaolan Lu
- Department of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
- Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, Sichuan, China
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Qiang Wang
- Department of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
- Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, Sichuan, China.
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, Sichuan, China.
| |
Collapse
|
18
|
Chimera D, Maio S, Romei C, De Liperi A, Barbieri G, Tavanti L, Pancani R, Marchi G, Desideri M, Carpenè N, Gabbrielli L, Celi A, Aquilini F, Baldacci S, Cristofano M, Ghiadoni L, Carrozzi L, Pistelli F. COVID-19 pulmonary phenotypes and longitudinal patterns in the first wave of the pandemic. Respir Med 2025; 237:107952. [PMID: 39826763 DOI: 10.1016/j.rmed.2025.107952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 11/21/2024] [Accepted: 01/15/2025] [Indexed: 01/22/2025]
Abstract
BACKGROUND The long-term evolution of COVID-19 in patients hospitalized during the pandemic's first wave remains largely unexplored. This study aimed to identify COVID-19 pulmonary phenotypes and their longitudinal patterns over a 12-month follow-up. METHODS COVID-19 patients discharged from Pisa University Hospital (Italy) between March-September 2020, were evaluated at T3, T12, and T24 months post-discharge. Assessments included spirometry, lung volumes, DLCO, and chest CT for those with persistent pneumonia signs (PS). Latent transition analysis (LTA) identified COVID-19 phenotypes and longitudinal patterns based on PS and lung function (PFTs). Risk factors for these patterns were evaluated using multinomial logistic regression. RESULTS Of 307 discharged patients, 175, 136, and 33 were followed-up at T3, T12, and T24, respectively. At T12, 21.6 % had impaired DLCO, 4.4 % a restrictive ventilatory pattern, and 31,6 % still had PS, persisting until T24. LTA identified three cross-sectional phenotypes at both T3 and T12 (no PS with normal PFTs; PS with normal PFTs; PS with impaired PFTs), and four longitudinal patterns from T3 to T12: persistence of no PS with normal PFTs (47.9 %); resolution of both PS and PFTs (15.4 %); persistent PS (36.7 %), either with (11 %) or without (25.7 %) impaired PFTs. The last two patterns correlated significantly with longer hospitalization, more comorbidities, and severe COVID-19. CONCLUSIONS In our cohort of COVID-19 patients hospitalized during the pandemic's first wave, we observed distinct pulmonary phenotypes and longitudinal recovery patterns. More comorbidities and severe acute disease correlated with worse progression up to 24 months, suggesting long-term monitoring for such patients.
Collapse
Affiliation(s)
- Davide Chimera
- Pulmonary Unit, Cardiothoracic and Vascular Department, Pisa University Hospital, Pisa, Italy.
| | - Sara Maio
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
| | - Chiara Romei
- 2nd Radiology Unit, Radiology Department, Pisa University Hospital, Pisa, Italy
| | - Annalisa De Liperi
- 2nd Radiology Unit, Radiology Department, Pisa University Hospital, Pisa, Italy
| | - Greta Barbieri
- Emergency Medicine Department, Pisa University Hospital, Pisa, Italy
| | - Laura Tavanti
- Pulmonary Unit, Cardiothoracic and Vascular Department, Pisa University Hospital, Pisa, Italy
| | - Roberta Pancani
- Pulmonary Unit, Cardiothoracic and Vascular Department, Pisa University Hospital, Pisa, Italy
| | - Guido Marchi
- Pulmonary Unit, Cardiothoracic and Vascular Department, Pisa University Hospital, Pisa, Italy
| | - Massimiliano Desideri
- Pulmonary Unit, Cardiothoracic and Vascular Department, Pisa University Hospital, Pisa, Italy
| | - Nicoletta Carpenè
- Pulmonary Unit, Cardiothoracic and Vascular Department, Pisa University Hospital, Pisa, Italy
| | - Luciano Gabbrielli
- Pulmonary Unit, Cardiothoracic and Vascular Department, Pisa University Hospital, Pisa, Italy
| | - Alessandro Celi
- Pulmonary Unit, Cardiothoracic and Vascular Department, Pisa University Hospital, Pisa, Italy; Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | | | - Sandra Baldacci
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
| | | | - Lorenzo Ghiadoni
- Emergency Medicine Department, Pisa University Hospital, Pisa, Italy; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Laura Carrozzi
- Pulmonary Unit, Cardiothoracic and Vascular Department, Pisa University Hospital, Pisa, Italy; Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Francesco Pistelli
- Pulmonary Unit, Cardiothoracic and Vascular Department, Pisa University Hospital, Pisa, Italy; Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| |
Collapse
|
19
|
Zhang Y, Chen H, Li Y, Luo C, Zhu Y, Zhou X, Wang R, He J, Guo H, Xu X, Qiu M, Li J. Animal Models for Long COVID: Current Advances, Limitations, and Future Directions. J Med Virol 2025; 97:e70237. [PMID: 39981885 DOI: 10.1002/jmv.70237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 01/25/2025] [Accepted: 02/05/2025] [Indexed: 02/22/2025]
Abstract
Long COVID (LC) represents a chronic, systemic, and often disabling condition that poses a significant ongoing threat to public health. Foundational scientific studies are needed to unravel the underlying mechanisms, with the ultimate goal of developing effective preventative and therapeutic strategies. Therefore, there is an urgent demand for animal models that can accurately replicate the clinical features of LC. This review integrates clinical epidemiological data to summarize the pathological changes in extrapulmonary systems involved in LC. Additionally, it critically examines the capacity of existing animal models, including nonhuman primates, genetically modified mice, and Syrian hamsters, to exhibit enduring postinfection symptoms that align with human clinical manifestations, and identifies key areas requiring further development. The objective is to offer insights that will aid in the development of next-generation animal models, thereby accelerating our understanding of how acute respiratory viral infections transition into chronic conditions, and ensuring preparedness for future pandemics.
Collapse
Affiliation(s)
- Yu Zhang
- Department of Biosafety, School of Basic Medicine, Army Medical University, Chongqing, China
| | - Huan Chen
- Department of Teaching Experiment Center, College of Basic Medicine, Army Medical University, Chongqing, China
| | - Yumeng Li
- Department of Biosafety, School of Basic Medicine, Army Medical University, Chongqing, China
| | - Chenxi Luo
- The Fifth Camp of Cadet Brigade, School of Basic Medicine, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yunkai Zhu
- Department of Biosafety, School of Basic Medicine, Army Medical University, Chongqing, China
| | - Xiaoyang Zhou
- Department of Biosafety, School of Basic Medicine, Army Medical University, Chongqing, China
| | - Ruixuan Wang
- Department of Biosafety, School of Basic Medicine, Army Medical University, Chongqing, China
| | - Jiuxiang He
- Department of Biosafety, School of Basic Medicine, Army Medical University, Chongqing, China
| | - Hongxia Guo
- Department of Biosafety, School of Basic Medicine, Army Medical University, Chongqing, China
| | - Xiaofeng Xu
- Department of Biosafety, School of Basic Medicine, Army Medical University, Chongqing, China
| | - Minyue Qiu
- Department of Biosafety, School of Basic Medicine, Army Medical University, Chongqing, China
| | - Jintao Li
- Department of Biosafety, School of Basic Medicine, Army Medical University, Chongqing, China
| |
Collapse
|
20
|
Navarro-Romero F, Olalla-Sierra J, Martín-Escalante MD. Potential role of lung ultrasonography in outpatient follow-up of patients with COVID-19. A systematic review. Rev Clin Esp 2025; 225:101-110. [PMID: 39613099 DOI: 10.1016/j.rceng.2024.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 10/19/2024] [Indexed: 12/01/2024]
Abstract
INTRODUCTION AND AIM Currently, the usefulness of lung ultrasound in the follow-up of patients after hospital discharge for SARS-CoV-2 pneumonia is not well known. The main objective of this systematic review is to investigate the persistence of alterations in lung ultrasound of patients who have had COVID-19 pneumonia. METHODS A systematic review has been carried out following the PRISMA regulations in the PubMed, EMBASE, Web of Science and Google Scholar database from January 2020 to May 2023 using the combination of MeSH terms: "lung ultrasound", "ultrasonography", "lung alterations", "persistence", "follow-up", "consequences", "hospital discharge", "COVID", "COVID-19", "SARS-CoV-2". Studies were selected that described alterations in the lung ultrasound of patients after having suffered from COVID-19 pneumonia. The JBI Critical Appraisal Tools were used to assess the risk of bias of the studies. No meta-analysis techniques were performed, the results being compared narratively. RESULTS From two to six months after COVID-19 pneumonia, pulmonary ultrasound abnormalities appear frequently and are proportional to the intensity of the initial episode. The most frequent anomalies are irregularities in the pleural line, the presence of B lines and/or subpleural consolidations, predominantly in the basal regions of the thorax. These findings seem to correlate with those of the chest CT. CONCLUSIONS Lung ultrasound offers technical and economic advantages that should be considered for the study of patients after hospital discharge for COVID-19.
Collapse
Affiliation(s)
- F Navarro-Romero
- Servicio de Medicina Interna, Hospital Costa del Sol, 29603 Málaga, Spain; Facultad de Medicina, Universidad de Málaga, 29010 Málaga, Spain.
| | - J Olalla-Sierra
- Servicio de Medicina Interna, Hospital Costa del Sol, 29603 Málaga, Spain
| | | |
Collapse
|
21
|
Uzel FI, Peker Y, Atceken Z, Karatas F, Atasoy C, Caglayan B. Association of Pulmonary Involvement at Baseline with Exercise Intolerance and Worse Physical Functioning 8 Months Following COVID-19 Pneumonia. J Clin Med 2025; 14:475. [PMID: 39860481 PMCID: PMC11765862 DOI: 10.3390/jcm14020475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 01/06/2025] [Accepted: 01/08/2025] [Indexed: 01/27/2025] Open
Abstract
Objectives: We aimed to describe the cardiopulmonary function during exercise and the health-related quality of life (HRQoL) in patients with a history of COVID-19 pneumonia, stratified by chest computed tomography (CT) findings at baseline. Methods: Among 77 consecutive patients with COVID-19 who were discharged from the Pulmonology Ward between March 2020 and April 2021, 28 (mean age 54.3 ± 8.6 years, 8 females) agreed to participate to the current study. The participants were analyzed in two groups based on pulmonary involvement (PI) at baseline chest CT applying a threshold of 25%. A consequent artificial intelligence (AI)-guided total opacity score (TOS) was calculated in a subgroup of 22 patients. A cardiopulmonary exercise test (CPET) was conducted on average 8.4 (±1.9) months after discharge from the hospital. HRQoL was defined using the short-form (SF-36) questionnaire. The primary outcome was exercise intolerance that was defined as a peak oxygen uptake (V'O2peak) < 80% predicted. Secondary outcomes were ventilatory limitation, defined as breathing reserve < 15%, circulatory limitation, defined as oxygen pulse predicted below 80%, and deconditioning, defined as exercise intolerance in the absence of ventilatory and circulatory limitations. Other secondary outcomes included the SF-36 domains. Results: In all, 15 patients had at least 25% PI (53.6%) at baseline chest CT. Exercise intolerance was observed in ten patients (35.7%), six due to deconditioning and four due to circulatory limitation; none had ventilatory limitation. AI-guided TOS was 30.1 ± 24.4% vs. 6.1 ± 4.8% (p < 0.001) at baseline, and 1.7 ± 3.0% vs. 0.2 ± 0.7% (nonsignificant) at follow-up in high and low PI groups, respectively. The physical functioning (PF) domain score of the SF-36 questionnaire was 66.3 ± 19.4 vs. 85.0 ± 13.1 in high and low PI groups, respectively (p = 0.007). Other SF-36 domains did not differ significantly between the groups. A high PI at baseline was inversely correlated with V'O2peak (standardized β coefficient = -0.436; 95% CI -26.1; -0.7; p = 0.040) and with PF scores (standardized β coefficient -0.654; 95% CI -41.3; -7.6; p = 0.006) adjusted for age, sex, body mass index and lung diffusion capacity. Conclusions: One-third of participants experienced exercise intolerance eight months after COVID-19 pneumonia. A higher PI at baseline was significantly associated with exercise intolerance and PF. Notwithstanding, the radiological PI was resolved, and the exercise intolerance was mainly explained not by ventilatory limitation but by circulatory limitation and deconditioning.
Collapse
Affiliation(s)
- Fatma Isil Uzel
- Department of Pulmonary Medicine, School of Medicine, Koc University, Istanbul 34010, Türkiye; (F.I.U.); (F.K.)
| | - Yüksel Peker
- Department of Pulmonary Medicine, School of Medicine, Koc University, Istanbul 34010, Türkiye; (F.I.U.); (F.K.)
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
- Department of Clinical Sciences, Respiratory Medicine and Allergology, Faculty of Medicine, Lund University, 22185 Lund, Sweden
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Zeynep Atceken
- Department of Radiology, Koc University School of Medicine, Istanbul 34010, Türkiye; (Z.A.); (C.A.)
| | - Ferhan Karatas
- Department of Pulmonary Medicine, School of Medicine, Koc University, Istanbul 34010, Türkiye; (F.I.U.); (F.K.)
| | - Cetin Atasoy
- Department of Radiology, Koc University School of Medicine, Istanbul 34010, Türkiye; (Z.A.); (C.A.)
| | - Benan Caglayan
- Department of Pulmonary Medicine, Istanbul Oncology Hospital, Istanbul 34846, Türkiye;
| |
Collapse
|
22
|
Antonogiannaki EM, Grigoropoulos I, Manali ED, Thomas K, Kallieri M, Alexopoulou P, Papaioannou AI, Prountzos S, Karachaliou A, Kontopoulou C, Karageorgou V, Lampadakis S, Blizou M, Tomos I, Grigoropoulou S, Kavatha D, Loukides S, Antoniadou A, Papiris SA. Long-Term Lung Sequelae in Survivors of Severe/Critical COVID-19 Pneumonia: The "Non-Steroid", "Non-Interventional" Approach. J Clin Med 2025; 14:347. [PMID: 39860353 PMCID: PMC11766020 DOI: 10.3390/jcm14020347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 01/02/2025] [Accepted: 01/05/2025] [Indexed: 01/27/2025] Open
Abstract
Introduction: Long-term lung sequelae in severe COVID-19 survivors, as well as their treatment, are poorly described in the current literature. Objective: To investigate lung fibrotic sequelae in survivors of severe/critical COVID-19 pneumonia and their fate according to a "non-interventional" approach. Methods: Prospective study of the above COVID-19 survivors after hospital discharge from March 2020 to October 2022. Re-evaluation lasted 3-12 months and included chest HRCT, PFTs, dyspnea, and overall health evaluation by modified Medical Research Council (mMRC) and St. George's Respiratory Questionnaire (SGRQ), respectively. Results: In this study, 198 patients (61.1% male) with a median age of 57 years (IQR 49-66). After 3 months, 187 (94.4%) patients were assessed; after 6 months, 82 (41.1%) patients were assessed; and after 12 months, 16 (8%) patients were assessed. At each time point, a significant reduction was observed in the extent of COVID-19-associated opacities (p < 0.001 and p = 0.002) and of parenchymal bands (p = 0.014 and p = 0.025). Persisting fibrotic-like changes were observed in 18 (9%) patients (apical findings in 2 patients, fibrotic non-specific interstitial pneumonia-like changes in 14 patients, minimal fibrotic changes in 2 patients). At 3 months, the predicted median FVC% was 93% (80-100%) and the predicted DLCO% was 65% (58-78%) with a statistically significant improvement at 6 months in both (p = 0.001). Moreover, 81.1% had mMRC ≤ 1 and the median SGRQ was 11.65 [0-24.3] with a significant reduction at 6 months in both dyspnea (p < 0.001) and SGRQ (p = 0.027) persisting at 12 months. Conclusions: This prospective study, including only survivors of severe/critical COVID-19 pneumonia, documented the significant improvement in all imaging, functional, and clinical parameters by applying the "non-interventional" approach. These data do not indicate any post-COVID-19 severe/critical pneumonia and "epidemic of widespread pulmonary fibrosis".
Collapse
Affiliation(s)
- Elvira-Markela Antonogiannaki
- 2nd Pulmonary Department, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.-M.A.); (E.D.M.); (M.K.); (V.K.); (S.L.); (M.B.); (S.A.P.)
| | - Ioannis Grigoropoulos
- 4th Department of Internal Medicine, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (I.G.); (K.T.); (P.A.); (S.G.); (D.K.); (A.A.)
| | - Effrosyni D. Manali
- 2nd Pulmonary Department, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.-M.A.); (E.D.M.); (M.K.); (V.K.); (S.L.); (M.B.); (S.A.P.)
| | - Konstantinos Thomas
- 4th Department of Internal Medicine, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (I.G.); (K.T.); (P.A.); (S.G.); (D.K.); (A.A.)
| | - Maria Kallieri
- 2nd Pulmonary Department, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.-M.A.); (E.D.M.); (M.K.); (V.K.); (S.L.); (M.B.); (S.A.P.)
| | - Panagiota Alexopoulou
- 4th Department of Internal Medicine, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (I.G.); (K.T.); (P.A.); (S.G.); (D.K.); (A.A.)
| | - Andriana I. Papaioannou
- 1st Respiratory Department, Athens Chest Hospital “Sotiria”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Spyridon Prountzos
- 2nd Department of Radiology, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (C.K.)
| | - Anastasia Karachaliou
- 2nd Department of Radiology, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (C.K.)
| | - Christina Kontopoulou
- 2nd Department of Radiology, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (C.K.)
| | - Vagia Karageorgou
- 2nd Pulmonary Department, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.-M.A.); (E.D.M.); (M.K.); (V.K.); (S.L.); (M.B.); (S.A.P.)
| | - Stefanos Lampadakis
- 2nd Pulmonary Department, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.-M.A.); (E.D.M.); (M.K.); (V.K.); (S.L.); (M.B.); (S.A.P.)
| | - Myrto Blizou
- 2nd Pulmonary Department, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.-M.A.); (E.D.M.); (M.K.); (V.K.); (S.L.); (M.B.); (S.A.P.)
| | - Ioannis Tomos
- 5th Respiratory Department, Athens Chest Hospital “Sotiria”, 11527 Athens, Greece;
| | - Sotiria Grigoropoulou
- 4th Department of Internal Medicine, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (I.G.); (K.T.); (P.A.); (S.G.); (D.K.); (A.A.)
| | - Dimitra Kavatha
- 4th Department of Internal Medicine, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (I.G.); (K.T.); (P.A.); (S.G.); (D.K.); (A.A.)
| | - Stelios Loukides
- 2nd Pulmonary Department, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.-M.A.); (E.D.M.); (M.K.); (V.K.); (S.L.); (M.B.); (S.A.P.)
| | - Anastasia Antoniadou
- 4th Department of Internal Medicine, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (I.G.); (K.T.); (P.A.); (S.G.); (D.K.); (A.A.)
| | - Spyros A. Papiris
- 2nd Pulmonary Department, General University Hospital “Attikon”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.-M.A.); (E.D.M.); (M.K.); (V.K.); (S.L.); (M.B.); (S.A.P.)
| |
Collapse
|
23
|
Espejo D, Pilia F, Romero-Mesones C, Ojanguren I, Cruz MJ, Muñoz X. Respiratory sequelae in patients with bronchial asthma after SARS-CoV-2 pneumonia: a retrospective study in a large academic centre in 2020. ERJ Open Res 2025; 11:00510-2024. [PMID: 39931665 PMCID: PMC11808931 DOI: 10.1183/23120541.00510-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Accepted: 08/01/2024] [Indexed: 02/13/2025] Open
Abstract
Patients with asthma do not present more respiratory sequelae than a control population after SARS-CoV-2 pneumonia. However, patients with asthma do seem to present more symptoms and a distinct involvement of the airway https://bit.ly/47E6Hze.
Collapse
Affiliation(s)
- David Espejo
- Pulmonology Service, Department of Medicine, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain
- CIBER of Respiratory Diseases (CIBERES), Barcelona, Spain
| | - Florencia Pilia
- Pulmonology Service, Department of Medicine, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain
| | - Christian Romero-Mesones
- Pulmonology Service, Department of Medicine, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain
- CIBER of Respiratory Diseases (CIBERES), Barcelona, Spain
| | - Inigo Ojanguren
- Pulmonology Service, Department of Medicine, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain
- CIBER of Respiratory Diseases (CIBERES), Barcelona, Spain
| | - María-Jesús Cruz
- Pulmonology Service, Department of Medicine, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain
- CIBER of Respiratory Diseases (CIBERES), Barcelona, Spain
| | - Xavier Muñoz
- Pulmonology Service, Department of Medicine, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain
- CIBER of Respiratory Diseases (CIBERES), Barcelona, Spain
- Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Barcelona, Spain
| |
Collapse
|
24
|
Di X, Li Y, Wei J, Li T, Liao B. Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2410416. [PMID: 39665319 PMCID: PMC11744640 DOI: 10.1002/advs.202410416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 10/27/2024] [Indexed: 12/13/2024]
Abstract
As the final stage of disease-related tissue injury and repair, fibrosis is characterized by excessive accumulation of the extracellular matrix. Unrestricted accumulation of stromal cells and matrix during fibrosis impairs the structure and function of organs, ultimately leading to organ failure. The major etiology of fibrosis is an injury caused by genetic heterogeneity, trauma, virus infection, alcohol, mechanical stimuli, and drug. Persistent abnormal activation of "quiescent" fibroblasts that interact with or do not interact with the immune system via complicated signaling cascades, in which parenchymal cells are also triggered, is identified as the main mechanism involved in the initiation and progression of fibrosis. Although the mechanisms of fibrosis are still largely unknown, multiple therapeutic strategies targeting identified molecular mechanisms have greatly attenuated fibrotic lesions in clinical trials. In this review, the organ-specific molecular mechanisms of fibrosis is systematically summarized, including cardiac fibrosis, hepatic fibrosis, renal fibrosis, and pulmonary fibrosis. Some important signaling pathways associated with fibrosis are also introduced. Finally, the current antifibrotic strategies based on therapeutic targets and clinical trials are discussed. A comprehensive interpretation of the current mechanisms and therapeutic strategies targeting fibrosis will provide the fundamental theoretical basis not only for fibrosis but also for the development of antifibrotic therapies.
Collapse
Affiliation(s)
- Xingpeng Di
- Department of Urology and Institute of UrologyWest China HospitalSichuan UniversityChengduP.R. China
| | - Ya Li
- Department of Urology and Institute of UrologyWest China HospitalSichuan UniversityChengduP.R. China
| | - Jingwen Wei
- Department of Urology and Institute of UrologyWest China HospitalSichuan UniversityChengduP.R. China
| | - Tianyue Li
- Department of Urology and Institute of UrologyWest China HospitalSichuan UniversityChengduP.R. China
| | - Banghua Liao
- Department of Urology and Institute of UrologyWest China HospitalSichuan UniversityChengduP.R. China
| |
Collapse
|
25
|
Chen J, Yue B, Chen J, Huang M. ICU-acquired muscle weakness in COVID-19 patients who underwent lung transplantation. World J Emerg Med 2025; 16:94-96. [PMID: 39906099 PMCID: PMC11788104 DOI: 10.5847/wjem.j.1920-8642.2025.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 10/26/2024] [Indexed: 02/06/2025] Open
Affiliation(s)
- Juan Chen
- General Intensive Care Unit, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310014, China
- Lung Transplantation Laboratory, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310014, China
- Key Laboratory of Multiple Organ Failure (Zhejiang University), Ministry of Education, Hangzhou 310014, China
| | - Bingqing Yue
- Lung Transplantation Laboratory, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310014, China
- Department of Lung Transplantation, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310014, China
- Key Laboratory of Multiple Organ Failure (Zhejiang University), Ministry of Education, Hangzhou 310014, China
| | - Jingyu Chen
- Lung Transplantation Laboratory, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310014, China
- Department of Lung Transplantation, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310014, China
- Key Laboratory of Multiple Organ Failure (Zhejiang University), Ministry of Education, Hangzhou 310014, China
- Wuxi Lung Transplant Center, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214043, China
| | - Man Huang
- General Intensive Care Unit, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310014, China
- Lung Transplantation Laboratory, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310014, China
- Department of Lung Transplantation, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310014, China
- Key Laboratory of Multiple Organ Failure (Zhejiang University), Ministry of Education, Hangzhou 310014, China
| |
Collapse
|
26
|
Lazar M, Barbu EC, Chitu CE, Buzoianu M, Petre AC, Tiliscan C, Arama SS, Arama V, Ion DA, Olariu MC. Surviving COVID-19 and Battling Fibrosis: A Retrospective Cohort Study Across Three Pandemic Waves. Diagnostics (Basel) 2024; 14:2811. [PMID: 39767173 PMCID: PMC11674708 DOI: 10.3390/diagnostics14242811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 11/28/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND/OBJECTIVES We aimed to characterize the fibrosis following COVID-19 pneumonia, using quantitative analysis, after three months and subsequently, after two years of patients' release from the hospital, and to identify the risk factors for pulmonary fibrosis. METHODS We performed a retrospective, observational cohort study on 420 patients with severe forms of COVID-19. For all patients, we registered demographic, inflammatory and biochemical parameters, complete blood count and D-dimers; all patients underwent three computed tomography scans (at admittance, at 3 months and at 2 years). RESULTS We found fibrosis in 67.9% of patients at the 3-month evaluation and in 42.4% of patients at the 2-year evaluation, registering a significant decrease in the severe and moderate fibrosis cases, with a slight increase in the mild fibrosis cases. The risk of fibrosis was found to be proportional to the values of age, duration of hospital stay, inflammatory markers (ESR, fibrinogen), cytolytic markers (LDH, AST) and D-dimers. The highest correlations with lung fibrosis were registered for interstitial pulmonary involvement (for the 3-month evaluation) and total pulmonary involvement (for the 2-year evaluation). CONCLUSIONS Lung fibrosis represents a significant post-COVID-19 complication found in 42% of patients with severe forms of pneumonia at the 2-year evaluation. A significant overall decrease in the severity of lung fibrosis was registered at the 2-year evaluation compared to the 3-month evaluation. We consider that the amount of interstitial pulmonary involvement represents the optimal parameter to estimate the risk of lung fibrosis following SARS-CoV-2 pneumonia.
Collapse
Affiliation(s)
- Mihai Lazar
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, No. 37, Dionisie Lupu Street, Sector 2, 020021 Bucharest, Romania; (M.L.); (C.E.C.); (C.T.); (S.S.A.); (V.A.); (D.A.I.); (M.C.O.)
- National Institute for Infectious Diseases Prof. Dr. Matei Bals, No. 1, Calistrat Grozovici Street, Sector 2, 021105 Bucharest, Romania;
| | - Ecaterina Constanta Barbu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, No. 37, Dionisie Lupu Street, Sector 2, 020021 Bucharest, Romania; (M.L.); (C.E.C.); (C.T.); (S.S.A.); (V.A.); (D.A.I.); (M.C.O.)
| | - Cristina Emilia Chitu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, No. 37, Dionisie Lupu Street, Sector 2, 020021 Bucharest, Romania; (M.L.); (C.E.C.); (C.T.); (S.S.A.); (V.A.); (D.A.I.); (M.C.O.)
| | - Mihaela Buzoianu
- National Institute for Infectious Diseases Prof. Dr. Matei Bals, No. 1, Calistrat Grozovici Street, Sector 2, 021105 Bucharest, Romania;
| | - Andreea Catalina Petre
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, No. 37, Dionisie Lupu Street, Sector 2, 020021 Bucharest, Romania; (M.L.); (C.E.C.); (C.T.); (S.S.A.); (V.A.); (D.A.I.); (M.C.O.)
| | - Catalin Tiliscan
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, No. 37, Dionisie Lupu Street, Sector 2, 020021 Bucharest, Romania; (M.L.); (C.E.C.); (C.T.); (S.S.A.); (V.A.); (D.A.I.); (M.C.O.)
- National Institute for Infectious Diseases Prof. Dr. Matei Bals, No. 1, Calistrat Grozovici Street, Sector 2, 021105 Bucharest, Romania;
| | - Stefan Sorin Arama
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, No. 37, Dionisie Lupu Street, Sector 2, 020021 Bucharest, Romania; (M.L.); (C.E.C.); (C.T.); (S.S.A.); (V.A.); (D.A.I.); (M.C.O.)
- National Institute for Infectious Diseases Prof. Dr. Matei Bals, No. 1, Calistrat Grozovici Street, Sector 2, 021105 Bucharest, Romania;
| | - Victoria Arama
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, No. 37, Dionisie Lupu Street, Sector 2, 020021 Bucharest, Romania; (M.L.); (C.E.C.); (C.T.); (S.S.A.); (V.A.); (D.A.I.); (M.C.O.)
- National Institute for Infectious Diseases Prof. Dr. Matei Bals, No. 1, Calistrat Grozovici Street, Sector 2, 021105 Bucharest, Romania;
| | - Daniela Adriana Ion
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, No. 37, Dionisie Lupu Street, Sector 2, 020021 Bucharest, Romania; (M.L.); (C.E.C.); (C.T.); (S.S.A.); (V.A.); (D.A.I.); (M.C.O.)
| | - Mihaela Cristina Olariu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, No. 37, Dionisie Lupu Street, Sector 2, 020021 Bucharest, Romania; (M.L.); (C.E.C.); (C.T.); (S.S.A.); (V.A.); (D.A.I.); (M.C.O.)
- National Institute for Infectious Diseases Prof. Dr. Matei Bals, No. 1, Calistrat Grozovici Street, Sector 2, 021105 Bucharest, Romania;
| |
Collapse
|
27
|
Rebouças ERN, Ramos TR, Sousa BGD, Costa RFD, Gouveia SSV, Silva IC, Mont'Alverne DGB, Campos NG. Long COVID: a cross-sectional study of respiratory muscle strength, lung function, and persistent symptoms at one year after hospital discharge. J Bras Pneumol 2024; 50:e20240246. [PMID: 39661840 PMCID: PMC11601093 DOI: 10.36416/1806-3756/e20240246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2024] Open
Affiliation(s)
- Ellys Rhaiara Nunes Rebouças
- . Programa de Pós-Graduação em Fisioterapia e Funcionalidade, Universidade Federal do Ceará - UFC - Fortaleza (CE) Brasil
- . Grupo de Pesquisa Inspirafisio, Universidade Federal do Ceará - UFC - Fortaleza (CE) Brasil
| | - Taynara Rodrigues Ramos
- . Programa de Pós-Graduação em Fisioterapia e Funcionalidade, Universidade Federal do Ceará - UFC - Fortaleza (CE) Brasil
- . Grupo de Pesquisa Inspirafisio, Universidade Federal do Ceará - UFC - Fortaleza (CE) Brasil
| | - Barbara Galdino de Sousa
- . Programa de Pós-Graduação em Fisioterapia e Funcionalidade, Universidade Federal do Ceará - UFC - Fortaleza (CE) Brasil
- . Grupo de Pesquisa Inspirafisio, Universidade Federal do Ceará - UFC - Fortaleza (CE) Brasil
| | - Rayana Fialho da Costa
- . Grupo de Pesquisa Inspirafisio, Universidade Federal do Ceará - UFC - Fortaleza (CE) Brasil
- . Programa de Pós-Graduação em Ciências Médicas, Departamento de Medicina Clínica, Universidade Federal do Ceará - UFC - Fortaleza (CE) Brasil
| | | | - Italo Caldas Silva
- . Grupo de Pesquisa Inspirafisio, Universidade Federal do Ceará - UFC - Fortaleza (CE) Brasil
- . Programa de Pós-Graduação em Ciências Médicas, Departamento de Medicina Clínica, Universidade Federal do Ceará - UFC - Fortaleza (CE) Brasil
| | - Daniela Gardano Bucharles Mont'Alverne
- . Programa de Pós-Graduação em Fisioterapia e Funcionalidade, Universidade Federal do Ceará - UFC - Fortaleza (CE) Brasil
- . Departamento de Fisioterapia, Universidade Federal do Ceará - UFC - Fortaleza (CE) Brasil
| | | |
Collapse
|
28
|
Megha KB, Reshma S, Amir S, Krishnan MJA, Shimona A, Alka R, Mohanan PV. Comprehensive Risk Assessment of Infection Induced by SARS-CoV-2. Mol Neurobiol 2024; 61:9851-9872. [PMID: 37817031 DOI: 10.1007/s12035-023-03682-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 09/28/2023] [Indexed: 10/12/2023]
Abstract
The pandemic COVID-19 (coronavirus disease 2019) is caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which devastated the global economy and healthcare system. The infection caused an unforeseen rise in COVID-19 patients and increased the mortality rate globally. This study gives an overall idea about host-pathogen interaction, immune responses to COVID-19, recovery status of infection, targeted organs and complications associated, and comparison of post-infection immunity in convalescent subjects and non-infected individuals. The emergence of the variants and episodes of COVID-19 infections made the situation worsen. The timely introduction of vaccines and precautionary measures helped control the infection's severity. Later, the population that recovered from COVID-19 grew significantly. However, understanding the impact of healthcare issues resulting after infection is paramount for improving an individual's health status. It is now recognised that COVID-19 infection affects multiple organs and exhibits a broad range of clinical manifestations. So, post COVID-19 infection creates a high risk in individuals with already prevailing health complications. The identification of post-COVID-19-related health issues and their appropriate management is of greater importance to improving patient's quality of life. The persistence, sequelae and other medical complications that normally last from weeks to months after the recovery of the initial infection are involved with COVID-19. A multi-disciplinary approach is necessary for the development of preventive measures, techniques for rehabilitation and strategies for clinical management when it comes to long-term care.
Collapse
Affiliation(s)
- K B Megha
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum, Kerala, 695 012, India
| | - S Reshma
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum, Kerala, 695 012, India
| | - S Amir
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum, Kerala, 695 012, India
| | - M J Ajai Krishnan
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum, Kerala, 695 012, India
| | - A Shimona
- CSIR-Institute of Microbial Technology, Sector 39-A, Chandigarh, 160036, India
- Academy of Scientific and Innovation Research (AcSIR), Ghaziabad, 201002, India
| | - Rao Alka
- CSIR-Institute of Microbial Technology, Sector 39-A, Chandigarh, 160036, India
- Academy of Scientific and Innovation Research (AcSIR), Ghaziabad, 201002, India
| | - P V Mohanan
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum, Kerala, 695 012, India.
| |
Collapse
|
29
|
Cortes‐Telles A, Solís‐Díaz LA, Mateos‐Toledo H, Guenette JA, Zavorsky GS. Mexican Hispanics show significant improvement in lung function approximately 1 year after having severe COVID-19. Exp Physiol 2024; 109:2147-2157. [PMID: 39446094 PMCID: PMC11607618 DOI: 10.1113/ep091934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 09/16/2024] [Indexed: 10/25/2024]
Abstract
The long-term effects of COVID-19 on lung function are not understood, especially for periods extending beyond 1 year after infection. This observational, longitudinal study investigated lung function in Mexican Hispanics who experienced severe COVID-19, focusing on how the length of recovery affects lung function improvements. At a specialized COVID-19 follow-up clinic in Yucatan, Mexico, lung function and symptoms were assessed in patients who had recovered from severe COVID-19. We used z-scores, and Wilcoxon's signed rank test to analyse changes in lung function over time. Lung function was measured twice in 82 patients: the first and second measurements were taken a median of 94 and 362 days after COVID-19 diagnosis, respectively. Initially, 61% of patients exhibited at least one of several pulmonary function abnormalities (lower limit of normal = -1.645), which decreased to 22% of patients by 390 days post-recovery. Considering day-to-day variability in lung function, 68% of patients showed improvement by the final visit, while 30% had unchanged lung function from the initial assessment. Computed tomography (CT) scans revealed ground-glass opacities in 33% of patients. One year after infection, diffusing capacity of the lungs for carbon monoxide z-scores accounted for 30% of the variation in CT fibrosis scores. There was no significant correlation between the length of recovery and improvement in lung function based on z-scores. In conclusion, 22% of patients who recovered from severe COVID-19 continued to show at least one lung function abnormality 1 year after recovery, indicating a prolonged impact of COVID-19 on lung health.
Collapse
Affiliation(s)
- Arturo Cortes‐Telles
- Clínica de Enfermedades Respiratorias, Hospital Regional de Alta Especialidad de la Península de Yucatán, IMSS‐BienestarMéridaMexico
| | - Luis Alberto Solís‐Díaz
- Clínica de Enfermedades Respiratorias, Hospital Regional de Alta Especialidad de la Península de Yucatán, IMSS‐BienestarMéridaMexico
| | - Heidegger Mateos‐Toledo
- Clínica de Enfermedades Intersticiales del Pulmón, Instituto Nacional de Enfermedades RespiratoriasCdMxMexico
| | - Jordan A. Guenette
- Centre for Heart Lung Innovation, Providence ResearchThe University of British Columbia and St. Paul's HospitalVancouverCanada
- Department of Physical TherapyThe University of British ColumbiaVancouverCanada
| | - Gerald Stanley Zavorsky
- Department of Physiology and Membrane BiologyUniversity of California at DavisDavisCaliforniaUSA
| |
Collapse
|
30
|
Birtolo LI, Di Pietro G, Ciuffreda A, Improta R, Monosilio S, Prosperi S, Cimino S, Galea N, Severino P, Galardo G, Colaiacomo MC, Pasculli P, Petroianni A, Palange P, Mastroianni CM, de Vito L, Catalano C, Pugliese F, Ciardi MR, Celli P, Badagliacca R, Fedele F, Vizza CD, Maestrini V, Mancone M. The impact of vaccination status on post-acute sequelae in hospitalized COVID-19 survivors using a multi-disciplinary approach: An observational single center study. Heliyon 2024; 10:e40409. [PMID: 39641021 PMCID: PMC11617281 DOI: 10.1016/j.heliyon.2024.e40409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 11/12/2024] [Accepted: 11/13/2024] [Indexed: 12/07/2024] Open
Abstract
Background COVID-19 vaccines reduced mortality, hospitalizations and ICUs admissions. Conversely, the impact of vaccination on Long COVID-19 syndrome is still unclear. This study compared the prevalence of post-acute sequelae at short and long-term follow-up among hospitalized unvaccinated and vaccinated COVID-19 survivors through a multidisciplinary approach. Methods After 2 months from discharge, unvaccinated and vaccinated COVID-19 survivors underwent a follow-up visit at a dedicated "post-COVID-19 Outpatient Clinic". The follow-up visit included a cardiovascular evaluation, blood tests, chest computed tomography, 6-min walking test (6MWT), spirometry. A one-year telephone follow-up was performed to assess re-hospitalizations, death and long-lasting symptoms. An additional 1:1 case-control matching analysis adjusted for baseline characteristics was performed. Results Between June 2020 and June 2022, a total of 458 unvaccinated and vaccinated patients (229 per group) underwent the follow-up visit. Vaccinated patients had lower rates of ICU admissions (1.7 % vs 9.6 %, p= <0.001) and severe respiratory complications requiring intubation (1.3 % vs 7 %, p = 0.002) or non-invasive ventilation such as high-flow nasal oxygen therapy (1.7 % vs 7.9 %, p = 0.02), CPAP (1.3 % vs 20.1 %, p= < 0.001), and low-flow oxygen therapy (3.5 % vs 63.3 %, p= <0.001) compared to unvaccinated ones. At 2-month follow-up, vaccinated patients had fewer persistent ground-glass opacities (2.6 % vs 52.8 %, p= <0.001) or consolidations (0.9 % vs 8.3 %, p= <0.001). Additionally, unvaccinated patients experienced more frequent myocarditis (4.8 % vs 0.9 %, p = 0.013) and pulmonary embolism (1.8 % vs 0 %, p = 0.042) and exhibited more significant respiratory impairment as evidenced by desaturation during the 6MWT(10.2 % vs 3.5 %, p = 0.005) and altered spirometry (14 % vs 8.7 %, p = 0.043) compared to vaccinated ones. At one-year, unvaccinated patients reported more symptoms such as dyspnea (20.5 % vs 10 %, p = 0.002), psychological symptoms (10 % vs 3.5 %, p = 0.005) and chronic rhinosinusitis/cough (6,6 % vs 2,6 %, p = 0.04) as compared to vaccinated ones. The 1:1 case-control matching analysis also confirmed these results. Conclusions COVID-19 vaccines improve short-term outcomes and may reduce Long COVID-19 prevalence.
Collapse
Affiliation(s)
- Lucia Ilaria Birtolo
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Gianluca Di Pietro
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Antonella Ciuffreda
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Riccardo Improta
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Sara Monosilio
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Silvia Prosperi
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Sara Cimino
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Nicola Galea
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Paolo Severino
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | | | - Maria Chiara Colaiacomo
- Radiology DEA Department, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Patrizia Pasculli
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Angelo Petroianni
- Department of Public Health and Infectious Diseases, Division of Pulmonary Medicine, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Paolo Palange
- Department of Public Health and Infectious Diseases, Division of Pulmonary Medicine, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Claudio Maria Mastroianni
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | | | - Carlo Catalano
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Francesco Pugliese
- Department of Anaesthesia and Intensive Care Medicine, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Maria Rosa Ciardi
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Paola Celli
- Department of Anaesthesia and Intensive Care Medicine, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Roberto Badagliacca
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Francesco Fedele
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Carmine Dario Vizza
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Viviana Maestrini
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| | - Massimo Mancone
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, “Policlinico Umberto I” Hospital, Rome, Italy
| |
Collapse
|
31
|
Yao X, Wu J, Zou W, Lin X, Xie B. A predictive model for post-COVID-19 pulmonary parenchymal abnormalities based on dual-center data. Sci Rep 2024; 14:29257. [PMID: 39587159 PMCID: PMC11589148 DOI: 10.1038/s41598-024-79715-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 11/12/2024] [Indexed: 11/27/2024] Open
Abstract
Documented radiological and physiological anomalies among coronavirus disease 2019 survivors necessitate prompt recognition of residual pulmonary parenchymal abnormalities for effective management of chronic pulmonary consequences. This study aimed to devise a predictive model to identify patients at risk of such abnormalities post-COVID-19. Our prognostic model was derived from a dual-center retrospective cohort comprising 501 hospitalized COVID-19 cases from July 2022 to March 2023. Of these, 240 patients underwent Chest CT scans three months post-infection. A predictive model was developed using stepwise regression based on the Akaike Information Criterion, incorporating clinical and laboratory parameters. The model was trained and validated on a split dataset, revealing a 33.3% incidence of pulmonary abnormalities. It achieved strong discriminatory power in the training set (area under the curve: 0.885, 95% confidence interval 0.832-0.938), with excellent calibration and decision curve analysis suggesting substantial net benefits across various threshold settings. We have successfully developed a reliable prognostic tool, complemented by a user-friendly nomogram, to estimate the probability of residual pulmonary parenchymal abnormalities three months post-COVID-19 infection. This model, demonstrating high performance, holds promise for guiding clinical interventions and improving the management of COVID-19-related pulmonary sequela.
Collapse
Affiliation(s)
- Xiujuan Yao
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China
- Department of Pulmonary and Critical Care Medicine, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Jianman Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China
- Radiology department, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Wei Zou
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China
- Department of Pulmonary and Critical Care Medicine, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Xiaohong Lin
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China
- Department of Pulmonary and Critical Care Medicine, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Baosong Xie
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
- Department of Pulmonary and Critical Care Medicine, Fujian Provincial Hospital, Fuzhou, 350001, China.
| |
Collapse
|
32
|
Azour L, Segal LN, Condos R, Moore WH, Landini N, Collazo D, Sterman DH, Young I, Ko J, Brosnahan S, Babb J, Chandarana H. Low-field MRI lung opacity severity associated with decreased DLCO in post-acute Covid-19 patients. Clin Imaging 2024; 115:110307. [PMID: 39383681 DOI: 10.1016/j.clinimag.2024.110307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 09/26/2024] [Accepted: 09/28/2024] [Indexed: 10/11/2024]
Abstract
OBJECTIVES To evaluate the clinical significance of low-field MRI lung opacity severity. METHODS Retrospective cross-sectional analysis of post-acute Covid-19 patients imaged with low-field MRI from 9/2020 through 9/2022, and within 1 month of pulmonary function tests (PFTs), 6-min walk test (6mWT), and symptom inventory (SI), and/or within 3 months of St. George Respiratory Questionnaire (SGRQ) was performed. Univariate and correlative analyses were performed with Wilcoxon, Chi-square, and Spearman tests. The association between disease and demographic factors and MR opacity severity, PFTs, 6mWT, SI, and SGRQ, and association between MR opacity severity with functional and patient-reported outcomes (PROs), was evaluated with mixed model analysis of variance, covariance and generalized estimating equations. Two-sided 5 % significance level was used, with Bonferroni multiple comparison correction. RESULTS 81 MRI exams in 62 post-acute Covid-19 patients (median age 57, IQR 41-64; 25 women) were included. Exams were a median of 8 months from initial illness. Univariate analysis showed lung opacity severity was associated with decreased %DLCO (ρ = -0.55, P = .0125), and lung opacity severity quartile was associated with decreased %DLCO, predicted TLC, FVC, and increased FEV1/FVC. Multivariable analysis adjusting for sex, initial disease severity, and interval from Covid-19 diagnosis showed MR lung opacity severity was associated with decreased %DLCO (P < .001). Lung opacity severity was not associated with PROs. CONCLUSION Low-field MRI lung opacity severity correlated with decreased %DLCO in post-acute Covid-19 patients, but was not associated with PROs.
Collapse
Affiliation(s)
- Lea Azour
- Department of Radiology, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America; Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America.
| | - Leopoldo N Segal
- Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America
| | - Rany Condos
- Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America
| | - William H Moore
- Department of Radiology, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America
| | - Nicholas Landini
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University/Policlinico Umberto, Rome, Italy
| | - Destiny Collazo
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America; Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America
| | - Daniel H Sterman
- Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America
| | - Isabel Young
- Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America
| | - Jane Ko
- Department of Radiology, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America
| | - Shari Brosnahan
- Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America; Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America
| | - James Babb
- Department of Radiology, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America
| | - Hersh Chandarana
- Department of Radiology, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, United States of America
| |
Collapse
|
33
|
Kumar A, Mark ZF, Carbajal MP, DeLima DS, Chamberlain N, Walzer J, Ruban M, Chandrasekaran R, Daphtary N, Aliyeva M, Poynter ME, Janssen-Heininger YMW, Bates JH, Alcorn JF, Britto CJ, Dela Cruz CS, Jegga AG, Anathy V. The protein disulfide isomerase A3 and osteopontin axis promotes influenza-induced lung remodelling. Br J Pharmacol 2024; 181:4610-4627. [PMID: 39118388 DOI: 10.1111/bph.16511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 06/07/2024] [Accepted: 06/24/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND AND PURPOSE Fibrotic lung remodelling after a respiratory viral infection represents a debilitating clinical sequela. Studying or managing viral-fibrotic sequela remains challenging, due to limited therapeutic options and lack of understanding of mechanisms. This study determined whether protein disulfide isomerase A3 (PDIA3) and secreted phosphoprotein 1 (SPP1), which are associated with pulmonary fibrosis, can promote influenza-induced lung fibrotic remodelling and whether inhibition of PDIA3 or SPP1 can resolve viral-mediated fibrotic remodelling. EXPERIMENTAL APPROACH A retrospective analysis of TriNetX data sets was conducted. Serum from healthy controls and influenza A virus (IAV)-infected patients was analysed. An inhibitor of PDIA3, punicalagin, and a neutralizing antibody for SPP1 were administered in mice. Macrophage cells treated with macrophage colony-stimulating factor (M-CSF) were used as a cell culture model. KEY RESULTS The TriNetX data set showed an increase in lung fibrosis and decline in lung function in flu-infected acute respiratory distress syndrome (ARDS) patients compared with non-ARDS patients. Serum samples revealed a significant increase in SPP1 and PDIA3 in influenza-infected patients. Lung PDIA3 and SPP1 expression increased following viral infection in mouse models. Punicalagin administration 2 weeks after IAV infection in mice caused a significant decrease in lung fibrosis and improved oxygen saturation. Administration of neutralizing SPP1 antibody decreased lung fibrosis. Inhibition of PDIA3 decreased SPP1secretion from macrophages, in association with diminished disulfide bonds in SPP1. CONCLUSION AND IMPLICATIONS The PDIA3-SPP1 axis promotes post-influenza lung fibrosis in mice and that pharmacological inhibition of PDIA3 or SPP1 can treat virus-induced lung fibrotic sequela.
Collapse
Affiliation(s)
- Amit Kumar
- Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - Zoe F Mark
- Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - Morgan P Carbajal
- Division of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - Dhemerson Souza DeLima
- Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - Nicolas Chamberlain
- Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - Joseph Walzer
- Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - Mona Ruban
- Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - Ravishankar Chandrasekaran
- Division of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - Nirav Daphtary
- Division of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - Minara Aliyeva
- Division of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - Matthew E Poynter
- Division of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - Yvonne M W Janssen-Heininger
- Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - Jason H Bates
- Division of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| | - John F Alcorn
- Division of Pulmonary Medicine, Allergy, and Immunology, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Clemente J Britto
- Department of Pulmonary, Critical Care and Sleep Medicine, Yale University, New Haven, Connecticut, USA
| | - Charles S Dela Cruz
- Department of Pulmonary, Critical Care and Sleep Medicine, Yale University, New Haven, Connecticut, USA
| | - Anil G Jegga
- Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
- Department of Computer Science, University of Cincinnati College of Engineering and Applied Science, Cincinnati, Ohio, USA
| | - Vikas Anathy
- Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA
| |
Collapse
|
34
|
Zaremba S, Miller AJ, Ovrom EA, Senefeld JW, Wiggins CC, Dominelli PB, Ganesh R, Hurt RT, Bartholmai BJ, Welch BT, Ripoll JG, Joyner MJ, Ramsook AH. Increased luminal area of large conducting airways in patients with COVID-19 and post-acute sequelae of COVID-19: a retrospective case-control study. J Appl Physiol (1985) 2024; 137:1168-1174. [PMID: 39298620 PMCID: PMC11573277 DOI: 10.1152/japplphysiol.00573.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 09/06/2024] [Accepted: 09/09/2024] [Indexed: 09/22/2024] Open
Abstract
Coronavirus disease 2019 (COVID-19) is associated with enlarged luminal areas of large conducting airways. In 10-30% of patients with acute COVID-19 infection, symptoms persist for more than 4 wk (referred to as post-acute sequelae of COVID 19, or PASC), and it is unknown if airway changes are associated with this persistence. Thus, we aim to investigate whether luminal area of large conducting airways is different between patients with PASC and COVID-19 and healthy controls. In this retrospective case-control study, 75 patients with PASC (48 females) were age-, height-, and sex-matched to 75 patients with COVID-19 and 75 healthy controls. Using three-dimensional digital reconstruction from computed tomography imaging, we measured luminal areas of seven conducting airways, including trachea, right and left main bronchi, bronchus intermediate, right and left upper lobe, and left lower lobe bronchi. Kruskal-Wallis H test was used to compare measurements between the three groups, as appropriate. Airway luminal areas between COVID-19 and PASC groups were not different (all, P > 0.66). There were no group differences in airway luminal area (PASC vs. control) for trachea and right main bronchus. However, in the remaining five airways, airway luminal areas were 12-39% larger among patients with PASC than in controls (all, P < 0.05). Patients diagnosed with COVID-19 and PASC have greater airway luminal area in most large conducting airways compared with healthy controls. No differences in luminal area between patients with COVID-19 and PASC suggest persistence of changes or insufficient time for reversal of changes.NEW & NOTEWORTHY Three-dimensional reconstruction of airways has shown increased luminal area in patients with COVID-19 and post-acute sequelae of COVID-19 when compared with healthy controls. These findings suggest the role of large conducting airways in the pathogenesis of post-acute sequelae of COVID 19.
Collapse
Affiliation(s)
- Solomiia Zaremba
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Alex J Miller
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Erik A Ovrom
- Alix School of Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Jonathon W Senefeld
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
- Department of Health and Kinesiology, University of Illinois Urbana-Champaign, Urbana, Illinois, United States
| | - Chad C Wiggins
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
- Department of Kinesiology, Michigan State University, East Lansing, Michigan, United States
| | - Paolo B Dominelli
- Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, Ontario, Canada
| | - Ravindra Ganesh
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Ryan T Hurt
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Brian J Bartholmai
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States
| | - Brian T Welch
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States
| | - Juan G Ripoll
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Michael J Joyner
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Andrew H Ramsook
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| |
Collapse
|
35
|
Sheshadri A, Evans SE. Respiratory Syncytial Virus Vaccination in the Adult Pulmonary Patient. Chest 2024; 166:963-974. [PMID: 38885895 DOI: 10.1016/j.chest.2024.05.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 05/13/2024] [Accepted: 05/23/2024] [Indexed: 06/20/2024] Open
Abstract
TOPIC IMPORTANCE Since its discovery in 1957, respiratory syncytial virus (RSV) has been widely recognized as a common and deadly pathogen. Although early studies focused on the impact of RSV on the health of children, more recent data show that RSV imposes a significant burden on individuals aged ≥ 70 years. RSV also substantially harms the health of individuals with cardiopulmonary diseases. REVIEW FINDINGS Early efforts to develop an RSV vaccine were hampered by toxicity due to antibody-enhanced viral pneumonia and a lack of efficacy in vaccines that targeted the postfusion configuration of the F fusion protein, which is crucial to the pathogenesis of RSV-mediated injury. A newer wave of vaccines has targeted a stabilized prefusion F protein, generating effective neutralizing antibodies and reducing the burden of mild and severe RSV lower respiratory tract injury. This review focuses on the burden of RSV in patients with pulmonary diseases, highlights the tumultuous path from the early days of RSV vaccine development to the modern era, and offers insights into key gaps in knowledge that must be addressed to adequately protect the vulnerable population of patients with severe pulmonary diseases. SUMMARY RSV vaccination with bivalent RSVPreF or RSVPreF3OA, which target the stabilized prefusion F protein, can be broadly recommended to adults aged ≥ 60 years with pulmonary diseases. However, more data are needed to understand how these vaccinations affect key clinical outcomes in individuals with pulmonary disease.
Collapse
Affiliation(s)
- Ajay Sheshadri
- Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
| | - Scott E Evans
- Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| |
Collapse
|
36
|
Gogoll C, Peters E, Köllner V, Koczulla R. [S1 guideline long/post-COVID syndrome]. UROLOGIE (HEIDELBERG, GERMANY) 2024; 63:1158-1161. [PMID: 38886205 DOI: 10.1007/s00120-024-02373-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/16/2024] [Indexed: 06/20/2024]
Affiliation(s)
- Christian Gogoll
- Ambulante Dienste, Ev. Lungenklinik Berlin, Berlin, Deutschland.
| | - Eva Peters
- Universitätsklinik Gießen und Marburg, Gießen und Marburg, Deutschland
- Schwerpunkt Psychoneuroimmunologie, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Volker Köllner
- Forschungsgruppe Psychosomatische Rehabilitation & Rehazentrum Seehof der Deutschen Rentenversicherung mit aktuell Entwicklung eines kardiopsychosomatischen ambulanten Rehakonzeptes für Post-COVID Patienten, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Rembert Koczulla
- Schön Klinik Berchtesgadener Land, Forschungsinstitut für Pneumologische Rehabilitation, Philipps-Universität Marburg, Marburg, Deutschland
| |
Collapse
|
37
|
Yoo JW, Kim WY, Chung CR, Cho YJ, Lee J, Jegal Y, Kim J, Joh JS, Park TY, Baek AR, Park JH, Chae G, Hwang JH, Song JW. Early pulmonary fibrosis-like changes between delta and pre-delta periods in patients with severe COVID-19 pneumonia on mechanical ventilation. Sci Rep 2024; 14:26101. [PMID: 39478105 PMCID: PMC11525473 DOI: 10.1038/s41598-024-77405-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 10/22/2024] [Indexed: 11/02/2024] Open
Abstract
It remains unclear whether pulmonary fibrosis-like changes differ in patients with different SARS-CoV-2 variants. This study aimed to compare pulmonary fibrotic changes between two SARS-CoV-2 variant periods (delta vs. pre-delta) in critically ill patients with SARS-CoV-2 pneumonia. Clinical data and chest CT images of patients with SARS-CoV-2 pneumonia receiving mechanical ventilation were collected from 10 hospitals in South Korea over two periods: delta (July-December, 2021; n = 64) and pre-delta (February, 2020-June, 2021; n = 120). Fibrotic changes on chest CT were evaluated through visual assessment. Of 184 patients, the mean age was 64.6 years, and 60.5% were ale. Fibrosis-like changes on chest CT (median 51 days from enrollment to follow up CT scan, interquartile range 27-76 days) were identified in 75.3%. Delta group showed more fibrosis-like changes (≥ 2) (69.8% vs. 43.1%, P = 0.001) and more frequent reticulation and architectural distortion+/-parenchymal band than pre-delta group. Even after propensity score matching with clinical variables, delta group had more severe (≥ 2) fibrosis-like changes (71.4% vs. 38.8%, P = 0.001), and more frequent reticulation and architectural distortion+/-parenchymal band than pre-delta group. Our data suggest that critically ill patients with SARS-CoV-2 in delta period had more severe pulmonary fibrosis-like changes than those in pre-delta period.
Collapse
Affiliation(s)
- Jung-Wan Yoo
- Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Won-Young Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chung Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Chi Ryang Chung
- Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
| | - Young-Jae Cho
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jinwoo Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yangjin Jegal
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
| | - Junghyun Kim
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Joon-Sung Joh
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, National Medical Center, Seoul, Republic of Korea
| | - Tae Yun Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Ae-Rin Baek
- Division of Allergy and Pulmonology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea
| | - Joo Hun Park
- Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Ganghee Chae
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
| | - Jung Hwa Hwang
- Department of Radiology, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
| | - Jin Woo Song
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu 05505, Seoul, Republic of Korea.
| |
Collapse
|
38
|
Zhao J, Yu W, Zhou D, Liu Y, Wei J, Bi L, Zhao S, He J, Liu J, Su J, Jin H, Liu Y, Shan H, Li M, Zhang Y, Li Y. Delineating, Imaging, and Assessing Pulmonary Fibrosis Remodeling via Collagen Hybridization. ACS NANO 2024; 18:27997-28011. [PMID: 39361472 DOI: 10.1021/acsnano.4c06139] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/05/2024]
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening disease with no early detection, few treatments, and dismal outcomes. Although collagen overdeposition is a hallmark of lung fibrosis, current research mostly focuses on the cellular aspect, leaving collagen, particularly its dynamic remodeling (i.e., degradation and turnover), largely unexplored. Here, using a collagen hybridizing peptide (CHP) that specifically binds unfolded collagen chains, we reveal vast collagen denaturation in human IPF lungs and delineate the spatiotemporal progression of collagen denaturation three-dimensionally within fibrotic lungs in mice. Transcriptomic analyses support that lung collagen denaturation is strongly associated with up-regulated collagen catabolism in mice and patients. We thus show that CHP probing differentiates remodeling responses to antifibrotics and highlights the resolution of established fibrosis by agents up-regulating collagen catabolism. We further develop a radioactive CHP that detects fibrosis in vivo in mice as early as 7 days postlung-injury (Ashcroft score: 2-3) by positron emission tomography (PET) imaging and ex vivo in clinical lung specimens. These findings establish collagen denaturation as a promising marker of fibrotic remodeling for the investigation, diagnosis, and therapeutic development of pulmonary fibrosis.
Collapse
Affiliation(s)
- Jie Zhao
- Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Wenjun Yu
- Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Daoning Zhou
- Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Yinghua Liu
- Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Jingyue Wei
- Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
- Biobank and Department of Information Technology and Data Center, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Lei Bi
- Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Suwen Zhao
- Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Jianzhong He
- Department of Pathology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Jing Liu
- Department of Pulmonary and Critical Care Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Jin Su
- State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China
| | - Hongjun Jin
- Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Ye Liu
- Department of Pathology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Hong Shan
- Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
- Department of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Man Li
- Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
- Biobank and Department of Information Technology and Data Center, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Yaqin Zhang
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Yang Li
- Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| |
Collapse
|
39
|
Kim J, Chae G, Kim WY, Chung CR, Cho Y, Lee J, Jegal Y, Joh JS, Park TY, Hwang JH, Nam BD, Yoon HY, Song JW. Pulmonary fibrosis followed by severe pneumonia in patients with COVID-19 infection requiring mechanical ventilation: a prospective multicentre study. BMJ Open Respir Res 2024; 11:e002538. [PMID: 39366721 PMCID: PMC11481150 DOI: 10.1136/bmjresp-2024-002538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 09/09/2024] [Indexed: 10/06/2024] Open
Abstract
BACKGROUNDS The management of lung complications, especially fibrosis, after COVID-19 pneumonia, is an important issue in the COVID-19 post-pandemic era. We aimed to investigate risk factors for pulmonary fibrosis development in patients with severe COVID-19 pneumonia. METHODS Clinical and radiological data were prospectively collected from 64 patients who required mechanical ventilation due to COVID-19 pneumonia and were enrolled from eight hospitals in South Korea. Fibrotic changes on chest CT were evaluated by visual assessment, and extent of fibrosis (mixed disease score) was measured using automatic quantification system. RESULTS 64 patients were enrolled, and their mean age was 58.2 years (64.1% were males). On chest CT (median interval: 60 days [IQR; 41-78 days] from enrolment), 35 (54.7%) patients showed ≥3 fibrotic lesions. The most frequent fibrotic change was traction bronchiectasis (47 patients, 73.4 %). Median extent of fibrosis measured by automatic quantification was 10.6% (IQR, 3.8-40.7%). In a multivariable Cox proportional hazard model, which included nine variables with a p value of <0.10 in an unadjusted analysis as well as age, sex and Body Mass Index, male sex (HR, 3.01; 95% CI, 1.27 to 7.11) and higher initial Sequential Organ Failure Assessment (SOFA) score (HR, 1.18; 95% CI, 1.02 to 1.37) were independently associated with pulmonary fibrosis (≥3 fibrotic lesions). CONCLUSION Our data suggests that male gender and higher SOFA score at intensive care unit admission were associated with pulmonary fibrosis in patients with severe COVID-19 pneumonia requiring mechanical ventilation.
Collapse
Affiliation(s)
- Junghyun Kim
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University College of Medicine, Dongtan Sacred Heart Hospital, Hwaseong, Korea (the Republic of)
| | - Ganghee Chae
- Division of Pulmonology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea (the Republic of)
| | - Won-Young Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea (the Republic of)
| | - Chi-Ryang Chung
- Department of Critical Care Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Suwon, Korea (the Republic of)
| | - Young‑Jae Cho
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea (the Republic of)
| | - Jinwoo Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)
| | - Yangjin Jegal
- Division of Pulmonology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea (the Republic of)
| | - Joon-Sung Joh
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Medical Centre, Seoul, Korea (the Republic of)
| | - Tae Yun Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Dongjak-gu, Seoul, Korea (the Republic of)
| | - Jung Hwa Hwang
- Department of Radiology, Soonchunhyang University Hospital, Yongsan-gu, Korea (the Republic of)
| | - Bo Da Nam
- Department of Radiology, Soonchunhyang University Hospital, Yongsan-gu, Korea (the Republic of)
| | - Hee-Young Yoon
- Division of Allergy and Respiratory Diseases, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea (the Republic of)
| | - Jin Woo Song
- Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Korea (the Republic of)
| |
Collapse
|
40
|
Kern AL, Pink I, Bonifacius A, Kaireit T, Speth M, Behrendt L, Klimeš F, Voskrebenzev A, Hohlfeld JM, Hoeper MM, Welte T, Wacker F, Eiz-Vesper B, Vogel-Claussen J. Alveolar membrane and capillary function in COVID-19 convalescents: insights from chest MRI. Eur Radiol 2024; 34:6502-6513. [PMID: 38460013 PMCID: PMC11399308 DOI: 10.1007/s00330-024-10669-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 01/22/2024] [Accepted: 02/10/2024] [Indexed: 03/11/2024]
Abstract
OBJECTIVES To investigate potential presence and resolution of longer-term pulmonary diffusion limitation and microvascular perfusion impairment in COVID-19 convalescents. MATERIALS AND METHODS This prospective, longitudinal study was carried out between May 2020 and April 2023. COVID-19 convalescents repeatedly and age/sex-matched healthy controls once underwent MRI including hyperpolarized 129Xe MRI. Blood samples were obtained in COVID-19 convalescents for immunophenotyping. Ratios of 129Xe in red blood cells (RBC), tissue/plasma (TP), and gas phase (GP) as well as lung surface-volume ratio were quantified and correlations with CD4+/CD8+ T cell frequencies were assessed using Pearson's correlation coefficient. Signed-rank tests were used for longitudinal and U tests for group comparisons. RESULTS Thirty-five participants were recruited. Twenty-three COVID-19 convalescents (age 52.1 ± 19.4 years, 13 men) underwent baseline MRI 12.6 ± 4.2 weeks after symptom onset. Fourteen COVID-19 convalescents underwent follow-up MRI and 12 were included for longitudinal comparison (baseline MRI at 11.5 ± 2.7 weeks and follow-up 38.0 ± 5.5 weeks). Twelve matched controls were included for comparison. In COVID-19 convalescents, RBC-TP was increased at follow-up (p = 0.04). Baseline RBC-TP was lower in patients treated on intensive care unit (p = 0.03) and in patients with severe/critical disease (p = 0.006). RBC-TP correlated with CD4+/CD8+ T cell frequencies (R = 0.61/ - 0.60) at baseline. RBC-TP was not significantly different compared to matched controls at follow-up (p = 0.25). CONCLUSION Impaired microvascular pulmonary perfusion and alveolar membrane function persisted 12 weeks after symptom onset and resolved within 38 weeks after COVID-19 symptom onset. CLINICAL RELEVANCE STATEMENT 129Xe MRI shows improvement of microvascular pulmonary perfusion and alveolar membrane function between 11.5 ± 2.7 weeks and 38.0 ± 5.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease. KEY POINTS • The study aims to investigate long-term effects of COVID-19 on lung function, in particular gas uptake efficiency, and on the cardiovascular system. • In COVID-19 convalescents, the ratio of 129Xe in red blood cells/tissue plasma increased longitudinally (p = 0.04), but was not different from matched controls at follow-up (p = 0.25). • Microvascular pulmonary perfusion and alveolar membrane function are impaired 11.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease at 38.0 weeks.
Collapse
Affiliation(s)
- Agilo Luitger Kern
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
- Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
- Medizinische Hochschule Hannover, Carl-Neuberg-Straße 1, Hannover, 30625, Germany.
| | - Isabell Pink
- Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Agnes Bonifacius
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- German Center for Infection Research (DZIF), Partner Site Hannover/Brunswick, Inhoffenstr. 7, 38124, Braunschweig, Germany
| | - Till Kaireit
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Milan Speth
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Lea Behrendt
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Filip Klimeš
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Andreas Voskrebenzev
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Jens M Hohlfeld
- Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- Medizinische Hochschule Hannover, Carl-Neuberg-Straße 1, Hannover, 30625, Germany
- Department of Clinical Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1, 30625, Hannover, Germany
| | - Marius M Hoeper
- Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Tobias Welte
- Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Frank Wacker
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Britta Eiz-Vesper
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- German Center for Infection Research (DZIF), Partner Site Hannover/Brunswick, Inhoffenstr. 7, 38124, Braunschweig, Germany
| | - Jens Vogel-Claussen
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
- Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| |
Collapse
|
41
|
Soni S, Antonescu L, Ro K, Horowitz JC, Mebratu YA, Nho RS. Influenza, SARS-CoV-2, and Their Impact on Chronic Lung Diseases and Fibrosis: Exploring Therapeutic Options. THE AMERICAN JOURNAL OF PATHOLOGY 2024; 194:1807-1822. [PMID: 39032604 PMCID: PMC11423761 DOI: 10.1016/j.ajpath.2024.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 06/11/2024] [Accepted: 06/26/2024] [Indexed: 07/23/2024]
Abstract
Respiratory tract infections represent a significant global public health concern, disproportionately affecting vulnerable populations such as children, the elderly, and immunocompromised individuals. RNA viruses, particularly influenza viruses and coronaviruses, significantly contribute to respiratory illnesses, especially in immunosuppressed and elderly individuals. Influenza A viruses (IAVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to pose global health threats due to their capacity to cause annual epidemics, with profound implications for public health. In addition, the increase in global life expectancy is influencing the dynamics and outcomes of respiratory viral infections. Understanding the molecular mechanisms by which IAVs and SARS-CoV-2 contribute to lung disease progression is therefore crucial. The aim of this review is to comprehensively explore the impact of IAVs and SARS-CoV-2 on chronic lung diseases, with a specific focus on pulmonary fibrosis in the elderly. It also outlines potential preventive and therapeutic strategies and suggests directions for future research.
Collapse
Affiliation(s)
- Sourabh Soni
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine and The Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio
| | - Laura Antonescu
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine and The Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio
| | - Kaylin Ro
- Scripps Research Institute, San Diego, California
| | - Jeffrey C Horowitz
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine and The Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio
| | - Yohannes A Mebratu
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine and The Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio.
| | - Richard S Nho
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine and The Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio.
| |
Collapse
|
42
|
Yüksel A, Karadoğan D, Hürsoy N, Telatar TG, Kabil NK, Marım F, Kaya İ, Er AB, Erçelik M, Yuluğ DP, Şenel MY, İlgar C, Gültekin Ö, Karakaya SÇ, Kara BY, Özçelik N, Selimoğlu İ, Er KU, Kotan A, Keskin HV, Akgün M. Post-COVID Interstitial Lung Disease: How do We Deal with This New Entity? Balkan Med J 2024; 41:377-386. [PMID: 39192585 PMCID: PMC11588920 DOI: 10.4274/balkanmedj.galenos.2024.2024-3-82] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 07/18/2024] [Indexed: 08/29/2024] Open
Abstract
Background In the postacute phase of coronavirus disease-2019 (COVID-19), survivors may have persistent symptoms, lung function abnormalities, and sequelae lesions on thoracic computed tomography (CT). This new entity has been defined as post-COVID interstitial lung disease (ILD) or residual disease. Aims To evaluate the characteristics, risk factors and clinical significance of post-COVID ILD. Study Design Multicenter cross-sectional analysis of data from a randomized clinical study. Methods In this study, patients with persistent respiratory symptoms 3 months after recovery from COVID-19 were evaluated by two pulmonologists and a radiologist. post-COVID ILD was defined as the presence of respiratory symptoms, hypoxemia, restrictive defect on lung function tests, and interstitial changes on follow-up high-resolution computed tomography (HRCT). Results At the three-month follow-up, 375 patients with post-COVID-19 syndrome were evaluated, and 262 patients were found to have post-COVID ILD. The most prevalent complaints were dyspnea (n = 238, 90.8%), exercise intolerance (n = 166, 63.4%), fatigue (n = 142, 54.2%), and cough (n = 136, 52%). The mean Medical Research Council dyspnea score was 2.1 ± 0.9, oxygen saturation was 92.2 ± 5.9%, and 6-minute walking distance was 360 ± 140 meters. The mean diffusing capacity of the lung for carbon monoxide was 58 ± 21, and the forced vital capacity was 70% ± 19%. Ground glass opacities and fibrotic bands were the most common findings on thoracic HRCT. Fibrosis-like lesions such as interlobular septal thickening and traction bronchiectasis were observed in 38.3% and 27.9% of the patients, respectively. No honeycomb cysts were observed. Active smoking [odds ratio (OR), 1.96; 95% confidence interval (CI), 1.44-2.67), intensive care unit admission during the acute phase (OR, 1.46; 95% CI, 1.1-1.95), need for high-flow nasal oxygen (OR, 1.55; 95% CI, 1.42-1.9) or non-invasive ventilation (OR, 1.31; 95% CI, 0.8-2.07), and elevated serum lactate dehydrogenase levels (OR, 1.23; 95% CI 1.18-1.28) were associated with the development of post-COVID ILD. At the 6-month follow-up, the respiratory symptoms and pulmonary functions had improved spontaneously without any specific treatment in 35 patients (13.4%). The radiological interstitial lesions had spontaneously regressed in 54 patients (20.6%). Conclusion The co-existence of respiratory symptoms, radiological parenchymal lesions, and pulmonary functional abnormalities which suggest a restrictive ventilatory defect should be defined as post-COVID-19 ILD. However, the term “fibrosis” should be used carefully. Active smoking, severe COVID-19, and elevated lactate dehydrogenase level are the main risk factors of this condition. These post-COVID functional and radiological changes could disappear over time in 20% of the patients.
Collapse
Affiliation(s)
- Aycan Yüksel
- Department of Respiratory Medicine Başkent University Faculty of Medicine, Ankara, Türkiye
| | - Dilek Karadoğan
- Department of Respiratory Medicine Recep Tayyip Erdoğan University Faculty of Medicine, Rize, Türkiye
| | - Nur Hürsoy
- Department of Radiology Recep Tayyip Erdoğan University Faculty of Medicine, Rize, Türkiye
| | - Tahsin Gökhan Telatar
- Department of Public Health Recep Tayyip Erdoğan University Faculty of Medicine, Rize, Türkiye
| | - Neslihan Köse Kabil
- Department of Respiratory Medicine Yalova Training and Research Hospital, Yalova, Türkiye
| | - Feride Marım
- Department of Respiratory Medicine Kütahya Health Sciences University Faculty of Medicine, Kütahya, Türkiye
| | - İlknur Kaya
- Department of Respiratory Medicine Kütahya Health Sciences University Faculty of Medicine, Kütahya, Türkiye
| | - Aslıhan Banu Er
- Department of Respiratory Medicine Uşak University Faculty of Medicine, Uşak, Türkiye
| | - Merve Erçelik
- Department of Respiratory Medicine Süleyman Demirel University Faculty of Medicine, Isparta, Türkiye
| | - Demet Polat Yuluğ
- Department of Respiratory Medicine Mersin City Hospital, Mersin, Türkiye
| | - Merve Yumrukuz Şenel
- Department of Respiratory Medicine Balıkesir University Faculty of Medicine, Balıkesir, Türkiye
| | - Ceren İlgar
- Department of Respiratory Medicine Ufuk University Faculty of Medicine, Ankara, Türkiye
| | - Ökkeş Gültekin
- Department of Respiratory Medicine Oltu State Hospital, Erzurum, Türkiye
| | - Selin Çakmakcı Karakaya
- Subdivision of Work and Occupational Diseases Hacettepe University Faculty of Medicine, Ankara Türkiye
| | - Bilge Yılmaz Kara
- Department of Respiratory Medicine Recep Tayyip Erdoğan University Faculty of Medicine, Rize, Türkiye
| | - Neslihan Özçelik
- Department of Respiratory Medicine Recep Tayyip Erdoğan University Faculty of Medicine, Rize, Türkiye
| | - İnci Selimoğlu
- Department of Respiratory Medicine Recep Tayyip Erdoğan University Faculty of Medicine, Rize, Türkiye
| | - Kübra Uyar Er
- Department of Respiratory Medicine Recep Tayyip Erdoğan University Faculty of Medicine, Rize, Türkiye
| | - Abdurrahman Kotan
- Department of Respiratory Medicine Recep Tayyip Erdoğan University Faculty of Medicine, Rize, Türkiye
| | - Hasan Veysel Keskin
- Department of Respiratory Medicine Recep Tayyip Erdoğan University Faculty of Medicine, Rize, Türkiye
| | - Metin Akgün
- Department of Respiratory Medicine Ağrı İbrahim Çeçen University Faculty of Medicine, Ağrı, Türkiye
| |
Collapse
|
43
|
Salisbury ML, Markin CR, Fadely TH, Guttentag AR, Kropski JA, Blackwell TS. Impact of the COVID-19 Pandemic on a Program to Screen for Subclinical Familial Pulmonary Fibrosis. Am J Respir Crit Care Med 2024; 210:669-672. [PMID: 38762792 PMCID: PMC11389563 DOI: 10.1164/rccm.202401-0034le] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 05/16/2024] [Indexed: 05/20/2024] Open
Affiliation(s)
| | | | | | - Adam R. Guttentag
- Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jonathan A. Kropski
- Department of Medicine and
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; and
- Department of Veterans Affairs Medical Center, Nashville, Tennessee
| | - Timothy S. Blackwell
- Department of Medicine and
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; and
- Department of Veterans Affairs Medical Center, Nashville, Tennessee
| |
Collapse
|
44
|
Kratzer B, Gattinger P, Trapin D, Ettel P, Körmöczi U, Rottal A, Stieger RB, Sehgal ANA, Feichter M, Borochova K, Tulaeva I, Grabmeier-Pfistershammer K, Tauber PA, Perkmann T, Fae I, Wenda S, Kundi M, Fischer GF, Valenta R, Pickl WF. Differential decline of SARS-CoV-2-specific antibody levels, innate and adaptive immune cells, and shift of Th1/inflammatory to Th2 serum cytokine levels long after first COVID-19. Allergy 2024; 79:2482-2501. [PMID: 39003594 DOI: 10.1111/all.16210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 05/23/2024] [Accepted: 05/25/2024] [Indexed: 07/15/2024]
Abstract
BACKGROUND SARS-CoV-2 has triggered a pandemic and contributes to long-lasting morbidity. Several studies have investigated immediate cellular and humoral immune responses during acute infection. However, little is known about long-term effects of COVID-19 on the immune system. METHODS We performed a longitudinal investigation of cellular and humoral immune parameters in 106 non-vaccinated subjects ten weeks (10 w) and ten months (10 m) after their first SARS-CoV-2 infection. Peripheral blood immune cells were analyzed by multiparametric flow cytometry, serum cytokines were examined by multiplex technology. Antibodies specific for the Spike protein (S), the receptor-binding domain (RBD) and the nucleocapsid protein (NC) were determined. All parameters measured 10 w and 10 m after infection were compared with those of a matched, noninfected control group (n = 98). RESULTS Whole blood flow cytometric analyses revealed that 10 m after COVID-19, convalescent patients compared to controls had reduced absolute granulocyte, monocyte, and lymphocyte counts, involving T, B, and NK cells, in particular CD3+CD45RA+CD62L+CD31+ recent thymic emigrant T cells and non-class-switched CD19+IgD+CD27+ memory B cells. Cellular changes were associated with a reversal from Th1- to Th2-dominated serum cytokine patterns. Strong declines of NC- and S-specific antibody levels were associated with younger age (by 10.3 years, p < .01) and fewer CD3-CD56+ NK and CD19+CD27+ B memory cells. Changes of T-cell subsets at 10 m such as normalization of effector and Treg numbers, decline of RTE, and increase of central memory T cell numbers were independent of antibody decline pattern. CONCLUSIONS COVID-19 causes long-term reduction of innate and adaptive immune cells which is associated with a Th2 serum cytokine profile. This may provide an immunological mechanism for long-term sequelae after COVID-19.
Collapse
Affiliation(s)
- Bernhard Kratzer
- Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
| | - Pia Gattinger
- Center for Pathophysiology, Infectiology and Immunology, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Doris Trapin
- Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
| | - Paul Ettel
- Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
| | - Ulrike Körmöczi
- Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
| | - Arno Rottal
- Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
| | - Robert B Stieger
- Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
| | - Al Nasar Ahmed Sehgal
- Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
| | - Melanie Feichter
- Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
| | - Kristina Borochova
- Center for Pathophysiology, Infectiology and Immunology, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Inna Tulaeva
- Center for Pathophysiology, Infectiology and Immunology, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
- Laboratory for Immunopathology, Department of Clinical Immunology and Allergology, I. M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | | | - Peter A Tauber
- Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
| | - Thomas Perkmann
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Ingrid Fae
- Department of Transfusion Medicine and Cell Therapy, Medical University of Vienna, Vienna, Austria
| | - Sabine Wenda
- Department of Transfusion Medicine and Cell Therapy, Medical University of Vienna, Vienna, Austria
| | - Michael Kundi
- Center for Public Health, Department for Environmental Health, Medical University of Vienna, Vienna, Austria
| | - Gottfried F Fischer
- Department of Transfusion Medicine and Cell Therapy, Medical University of Vienna, Vienna, Austria
| | - Rudolf Valenta
- Center for Pathophysiology, Infectiology and Immunology, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
- Laboratory for Immunopathology, Department of Clinical Immunology and Allergology, I. M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- NRC Institute of Immunology FMBA of Russia, Moscow, Russia
- Karl Landsteiner University of Health Sciences, Krems, Austria
| | - Winfried F Pickl
- Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria
- Karl Landsteiner University of Health Sciences, Krems, Austria
| |
Collapse
|
45
|
Kumar S, Ramaraju K, Kakarla MS, Eranezhath SS, Chenthamarakshan C, Alagesan M, Satheesan B, Unniappan I, Wilhalme H, Pīrāgs V, Furst DE. Evaluating Personalized Add-On Ayurveda Therapy in Oxygen-Dependent Diabetic COVID-19 Patients: A 60-Day Study of Symptoms, Inflammation, and Radiological Changes. Cureus 2024; 16:e68392. [PMID: 39355453 PMCID: PMC11444340 DOI: 10.7759/cureus.68392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/30/2024] [Indexed: 10/03/2024] Open
Abstract
Background Effective management of both acute and post-acute sequelae of SARS-CoV-2 is essential, particularly for type 2 diabetes mellitus (T2DM) patients, who are at increased risk of severe pro-inflammatory responses and complications. Persistent symptoms and residual lung and cardiovascular damage in post-coronavirus disease (COVID-19) individuals highlight the need for comprehensive long-term treatment strategies. Conventional treatments, including Remdesivir and glucocorticoids, have limitations, suggesting that further investigation into Ayurvedic therapies could be beneficial, though controlled trials are currently limited. Objectives Evaluate the effectiveness and safety of Ayurveda with the standard of care (SOC) versus SOC in improving symptoms, moderating immune responses (interleukin-6 (IL-6), C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), and radiological outcomes in oxygen-dependent, high-risk, non-vaccinated type 2 diabetes COVID-19 patients over 60 days, and thus addressing their heightened vulnerability to severe infections. Methods A controlled trial with 50 diabetic COVID-19 patients, aged 18-80, with an NLR of >= 4, primarily on Remdesivir, was assigned to Group 1 (Add-on Ayurveda+SOC, n=30) or Group 2 (SOC, n=20) based on their voluntary choice with follow-up on days 14, 28, and 60. Parametric outcomes in group analysis were assessed with robust regression and non-parametric outcomes with Cochran-Mantel-Haenszel, log-rank test, and chi-square tests at 95% confidence interval (CI). Results Group 1 exhibited statistically significant improvements in fever, cough, diarrhea, as well as NLR, IL-6, and CRP by 14 days, and in anosmia, loss of taste, shortness of breath, general weakness, and headache by 60 days. Though the sample size is small, notable improvements can be seen in troponin levels in Group 1 at 28 and 60 days. High-resolution computer tomography COVID-19 reporting and data system (HRCT CO-RADS) scores improved more slowly in Group 2 than in Group 1. Survival rates were 96.4% for Group 1 and 90% for Group 2. Numbers were too small for reliable comparisons at 60 days. Conclusion The add-on Ayurveda group showed a better symptomatic response, and faster normalization in inflammatory markers, including IL-6 and NLR by 14 days, and cardiac markers by 28 days. Minimal clinical and no laboratory adverse events were observed. This study supports the need for a randomized, double-blind trial.
Collapse
Affiliation(s)
- Somit Kumar
- Clinical Research, AVP Research Foundation, Coimbatore, IND
- Research and Development, The Arya Vaidya Pharmacy, Coimbatore, IND
| | - Karthikeyan Ramaraju
- Respiratory Medicine, PSG Institute of Medical Sciences and Research, Coimbatore, IND
| | | | | | | | - Murali Alagesan
- General Medicine, PSG Institute of Medical Sciences and Research, Coimbatore, IND
| | - Balagopal Satheesan
- Ayurveda and Integrative Medicine, Saranya Ayurveda Hospital, Coimbatore, IND
| | - Indulal Unniappan
- Ayurveda and Integrative Medicine, AVP Research Foundation, Coimbatore, IND
| | - Holly Wilhalme
- Statistics, University of California Los Angeles, Los Angeles, USA
| | | | - Daniel E Furst
- Rheumatology, University of California Los Angeles, Los Angeles, USA
- Rheumatology, University of Washington, Seattle, USA
- Rheumatology, University of Florence, Florence, ITA
| |
Collapse
|
46
|
Roig-Martí C, Pérez-Catalán I, Varea-Villanueva M, Folgado-Escudero S, Navarro-Ballester A, Fernández-García MP, Segura-Fábrega A, Herrero-Rodríguez G, Domínguez-Bajo E, Fabra-Juana S, Esteve-Gimeno MJ, Mateu-Campos ML, Usó-Blasco J, Ramos-Rincón JM. Predictors of the presence of radiological abnormalities 6 months after severe COVID-19 pneumonia. BMC Infect Dis 2024; 24:883. [PMID: 39210255 PMCID: PMC11360858 DOI: 10.1186/s12879-024-09767-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 08/20/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND SARS-CoV-2 pneumonia can cause significant long-term radiological changes, even resembling pulmonary fibrosis. However, the risk factors for these long-term effects are unknown. This study aims to assess radiological abnormalities and their possible risk factors six months after hospital discharge due to COVID-19 pneumonia. MATERIAL AND METHODS This cross-sectional study in a tertiary hospital included adults admitted for COVID-19 pneumonia from March 2020 to February 2021, who underwent high-resolution computed tomography (HRCT) scans of the chest six months after hospital discharge. The primary outcome was radiological abnormalities on HRCT, while the main explanatory variables were drawn from the patient's medical history along with the disease course, analytical indicators, and the treatment received during admission. RESULTS The 189 included patients had a mean age of 61.5 years; 70.9% were male, and hypertension was the main comorbidity (45%). About two-thirds (67.2%) presented acute respiratory distress syndrome (ARDS). Most (97.9%) received systemic corticosteroid therapy, and 81% presented pathological findings on HRCT, most commonly ground glass (63.5%), followed by bronchial dilatation (36%) and subpleural bands (25.4%). The multivariable analysis showed that age was the main risk factor, associated with most radiological changes. Other factors were the duration of corticosteroid therapy for ground glass (adjusted odds ratio [aOR] 1.020) as well as a longer stay in the intensive care unit (ICU) (aOR 1.290) and high levels of IL-6 for bronchial dilation (aOR 1.002). CONCLUSION Radiological involvement of the lungs six months after COVID-19 pneumonia is frequent, especially ground glass. Elderly patients with prolonged ICU admission and a significant inflammatory response measured by IL-6 are more likely to present worse radiological evolution and are candidates for radiological follow-up after COVID-19 pneumonia.
Collapse
Affiliation(s)
- Celia Roig-Martí
- Internal Medicine Department, Castellón General University Hospital, Castellón, Spain.
| | - Ignacio Pérez-Catalán
- Internal Medicine Department, Castellón General University Hospital, Castellón, Spain.
| | | | | | | | | | - Ana Segura-Fábrega
- Internal Medicine Department, Castellón General University Hospital, Castellón, Spain
| | | | - Elena Domínguez-Bajo
- Internal Medicine Department, Castellón General University Hospital, Castellón, Spain
| | - Sergio Fabra-Juana
- Internal Medicine Department, Castellón General University Hospital, Castellón, Spain
| | | | | | - Jorge Usó-Blasco
- Internal Medicine Department, Castellón General University Hospital, Castellón, Spain
| | - José-Manuel Ramos-Rincón
- Internal Medicine Department, Alicante General University Hospital, Alicante Institute of Health and Biomedical Research (ISABIAL), Alicante, Spain
- Clinical Medicine Department, Miguel Hernández University of Elche, Elche, Spain
| |
Collapse
|
47
|
Kim C, Seok H, Kim J, Park DW, van Assen M, De Cecco CN, Choi H, Kim C, Hwang SH, Yong HS, Oh YW, Choi WS. COVID-19's Radiologic, Functional, and Serologic Consequences at 6-Month and 18-Month Follow-up: A Prospective Cohort Study. J Korean Med Sci 2024; 39:e228. [PMID: 39164053 PMCID: PMC11333807 DOI: 10.3346/jkms.2024.39.e228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 06/27/2024] [Indexed: 08/22/2024] Open
Abstract
BACKGROUND We evaluated the radiologic, pulmonary functional, and antibody statuses of coronavirus disease 2019 (COVID-19) patients 6 and 18 months after discharge, comparing changes in status and focusing on risk factors for residual computed tomography (CT) abnormalities. METHODS This prospective cohort study was conducted on COVID-19 patients discharged between April 2020 and January 2021. Chest CT, pulmonary function testing (PFT), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements were performed 6 and 18 months after discharge. We evaluated factors associated with residual CT abnormalities and the correlation between lesion volume in CT (lesionvolume), PFT, and IgG levels. RESULTS This study included 68 and 42 participants evaluated 6 and 18 months, respectively, after hospitalizations for COVID-19. CT abnormalities were noted in 22 participants (32.4%) at 6 months and 13 participants (31.0%) at 18 months. Lesionvolume was significantly lower at 18 months than 6 months (P < 0.001). Patients with CT abnormalities at 6 months showed lower forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC), and patients with CT abnormalities at 18 months exhibited lower FVC. FVC significantly improved between 6 and 18 months of follow-up (all P < 0.0001). SARS-CoV-2 IgG levels were significantly higher in patients with CT abnormalities at 6 and 18 months (P < 0.001). At 18-month follow-up assessments, age was associated with CT abnormalities (odds ratio, 1.17; 95% confidence interval, 1.03-1.32; P = 0.01), and lesionvolume showed a positive correlation with IgG level (r = 0.643, P < 0.001). CONCLUSION At 18-month follow-up assessments, 31.0% of participants exhibited residual CT abnormalities. Age and higher SARS-CoV-2 IgG levels were significant predictors, and FVC was related to abnormal CT findings at 18 months. Lesionvolume and FVC improved between 6 and 18 months. TRIAL REGISTRATION Clinical Research Information Service Identifier: KCT0008573.
Collapse
Affiliation(s)
- Cherry Kim
- Department of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Hyeri Seok
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Jooyun Kim
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Dae Won Park
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Marly van Assen
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
- Translational Laboratory for Cardiothoracic Imaging and Artificial Intelligence, Emory University School of Medicine, Atlanta, GA, USA
| | - Carlo N De Cecco
- Translational Laboratory for Cardiothoracic Imaging and Artificial Intelligence, Emory University School of Medicine, Atlanta, GA, USA
- Division of Cardiothoracic Imaging, Department of Radiology, Emory University, Atlanta, GA, USA
| | - Hangseok Choi
- Medical Science Research Center, Korea University College of Medicine, Seoul, Korea
| | - Chohee Kim
- Department of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Sung Ho Hwang
- Department of Radiology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Hwan Seok Yong
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Yu-Whan Oh
- Department of Radiology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Won Suk Choi
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
| |
Collapse
|
48
|
Behera N, Patra JK, Dash BK, Pattnaik M, Sahu D, Rambhoopal Reddy B. Clinico-radiological and pulmonary function assessment of post-COVID-19 patients with respiratory symptoms. J Family Med Prim Care 2024; 13:2912-2920. [PMID: 39228580 PMCID: PMC11368303 DOI: 10.4103/jfmpc.jfmpc_1721_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 01/02/2024] [Accepted: 01/08/2024] [Indexed: 09/05/2024] Open
Abstract
Background Respiratory symptoms may persist for several weeks following the initial coronavirus disease 2019 (COVID-19) infection. The aims and objectives were to assess the clinical symptoms, pulmonary functions, and radiological changes and to assess the cardio-vascular complications in post-COVID-19 patients. Methods This observational study was conducted in the Department of Pulmonary Medicine in collaboration with the Department of Cardiology, SCBMCH, Cuttack, from March 2021 to August 2022 on 75 post-COVID-19 patients with respiratory symptoms from 4 weeks to 2 years after treatment for COVID-19 infection. Post-COVID patients having previous respiratory diseases were excluded from the study. Results Among 75 patients, the most common age group was 18-30 years with a male-to-female ratio of 2.5:1. Based on O2 requirement, patients were divided into the mild symptomatic group and moderate to severe pneumonia group. The most common respiratory symptom was dyspnea, followed by cough with expectoration. Bilateral crepitations were found in 17% of cases. C-reactive protein (CRP) and D-dimer were increased in 38.6% and 32% of patients, respectively. 42.6% had abnormal chest X-ray, and the most common abnormal finding was reticular thickening. In spirometry, the restrictive pattern and mixed pattern were the predominant types documented in 49.3% and 13.3% of cases, respectively, which were significant in the moderate-severe group. Diffusion capacity of the lungs for carbon monoxide (DLCO) was performed in only 19 patients (mild group 13 and moderate-severe group 6). Twelve (63.2%) patients had abnormal DLCO. P- values were significant for RV (0.0482) and RV/TLC (0.0394). High-resolution computed tomography (HRCT) of the thorax was abnormal in 55.7% with the most common abnormalities as inter- and intra-lobular septal thickening. The left ventricular ejection fraction was preserved in all patients, with right atrium and right ventricle enlargement in 2.6% and pulmonary hypertension in 4.0% of participants. Conclusion All post-COVID-19 patients having respiratory symptoms after recovery from acute COVID-19 may be referred by family care physicians to a dedicated post-COVID center for further evaluation, management, and early rehabilitation to decrease the morbidity in recovered patients. Persistent increased blood parameters like TLC, N/L ratio, RBS, CRP, and D-dimer seen in recovered post-COVID-19 patients. The long-term impact of CT findings on respiratory symptoms, pulmonary functions, and quality of life is unknown. Cardiovascular abnormalities in post-COVID-19 patients are infrequent.
Collapse
Affiliation(s)
- Nilakantha Behera
- Department of Pulmonary Medicine, SCB Medical College and Hospital, Cuttack, Odisha, India
| | - Jeetendra Kumar Patra
- Department of Pulmonary Medicine, SCB Medical College and Hospital, Cuttack, Odisha, India
| | - Bijay Kumar Dash
- Department of Cardiology, SCB Medical College and Hospital, Cuttack, Odisha, India
| | - Manoranjan Pattnaik
- Department of Pulmonary Medicine, SCB Medical College and Hospital, Cuttack, Odisha, India
| | - Deepak Sahu
- Department of Community Medicine, SJ Medical College and Hospital, Puri, Odisha, India
| | | |
Collapse
|
49
|
Wei B, Li H, Wang C, Hu J. Global research status and trends of interactions between Traditional Chinese medicine and pulmonary fibrosis: A new dawn in treatment. Heliyon 2024; 10:e34592. [PMID: 39149021 PMCID: PMC11325230 DOI: 10.1016/j.heliyon.2024.e34592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 06/05/2024] [Accepted: 07/12/2024] [Indexed: 08/17/2024] Open
Abstract
Background Pulmonary fibrosis (PF) remains a major sequela of COVID-19, yet its pharmacotherapy remains unsatisfactory. Recently, Traditional Chinese medicine (TCM) has garnered increasing recognition among patients and researchers because of its few side effects and efficacy. The objective of this study is to use bibliometric analysis to explore the current research landscape and emerging trajectories of TCM treating PF(TCM/PF) researches, and comprehensively evaluate publications with substantial citations within the domain of TCM/PF. Materials and methods TCM/PF publications from 1996 to June 15, 2023 were identified by a comprehensive search of the Web of Science Core Collection (WoSCC). The Bibliometrix of Origin, CiteSpace, Gephi, dycharts and VOSviewer were used for bibliometric analysis. Results A total of 358 papers were included. A rapid increase in the number of papers after 2013 was observed. China had the highest publication output and research contributions in this field. Beijing University of Traditional Chinese Medicine and Nanjing University of Traditional Chinese Medicineare leaders in productive research of this field. Nanjing University of Traditional Chinese Medicine had the highest citations (227). LI JIANSHENG from Henan University of Chinese Medicine was the most prolific author (8), with the highest number of citations (61), and TONG XIAO LIN from China Academy of Chinese Medical Sciences had the highest H-index (30). The leading journal publishing the most research (37) is Frontiers in Pharmacology and the Journal of Ethnopharmacology had the highest total citations (486). Burst analysis of keywords revealed three distinct phases of research. 1996 to 2013 marked the nascent stage of TCM/PF research; from 2014 to 2018, studies gradually focused on the underlying mechanisms governing TCM/PF. The most significant phase occurred from 2019 onward, where TCM/PF exhibited an explosive growth trend. This progression signifies a transition from foundational explorations to a comprehensive understanding of the mechanisms involved, ultimately leading to the current surge in research activities focused on TCM/PF. Notable research teams of this stage, led by LI JIAN SHENG and TONG XIAO LIN, have been at the forefront of advancing TCM/PF research. Their studies on Jinshui Huanxian formula and Qimai Feiluoping decoction have been pivotal in advancing the frontier of research in this domain. Furthermore, the monomeric compounds, including emodin, curcumin, salvianolic acid, baicalin, and oxymatrine, have sustained longstanding prominence. Conclusions This study gained insight into the research status, focal areas and evolving trends of global TCM/PF research. It also identified the most cited articles in TCM/PF and analyzed their characteristics, which may hold significant relevance for both clinical researchers and practitioners on future directions in this field.
Collapse
Affiliation(s)
- Bokai Wei
- School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200# Cailun Rd., Shanghai, 201203, PR China
| | - Haozheng Li
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, 130# Dongan Road, Shanghai, 200032, PR China
- Department of Rehabilitation Medicine, Huanshan Hospital, Fudan University, 12# Wulumuqi Road, Shanghai, 200040, PR China
| | - Chengyu Wang
- School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200# Cailun Rd., Shanghai, 201203, PR China
| | - Jing Hu
- School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200# Cailun Rd., Shanghai, 201203, PR China
| |
Collapse
|
50
|
Rettew A, Garrahy I, Rahimian S, Brown R, Sangha N. COVID-19 Coagulopathy. Life (Basel) 2024; 14:953. [PMID: 39202695 PMCID: PMC11355811 DOI: 10.3390/life14080953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 07/25/2024] [Accepted: 07/26/2024] [Indexed: 09/03/2024] Open
Abstract
Coronavirus disease of 2019 (COVID-19) is the respiratory viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite being a primary respiratory illness, it is commonly complicated by systemic involvement of the vasculature leading to arterial and venous thrombosis. In this review, we will focus on the association between COVID-19 and thrombosis. We will highlight the pathophysiology of COVID-19 coagulopathy. The clinical manifestations of COVID-19 vasculopathy will be discussed with a focus on venous and arterial thromboembolic events. COVID-19 vasculopathy and disseminated intravascular coagulation (DIC) are distinguished within, as well as areas of controversy, such as "long COVID". Finally, the current professional guidelines on prevention and treatment of thrombosis associated with SARS-CoV-2 infection will be discussed.
Collapse
Affiliation(s)
| | - Ian Garrahy
- Tower Health System, Reading Hospital, West Reading, PA 19611, USA; (A.R.); (S.R.); (R.B.); (N.S.)
| | | | | | | |
Collapse
|