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Alqahtani SA, Alshammari TM, Alzahrani EM, Alaohali AA, Alqahtani JS, Alzahrani YA, Alrawashdeh AA, Williams B, Aljumaan MA, Alsulaibikh AH, Alghamdi MA, Almulhim MA, Alqahtani SY, Al-Ahmadi S, Alshahrani MS. Outcomes of COVID-19 During the First Wave in Saudi Arabia: An Observational Study of ICU Cases from a Single Hospital. J Clin Med 2025; 14:1915. [PMID: 40142722 PMCID: PMC11942682 DOI: 10.3390/jcm14061915] [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: 02/04/2025] [Revised: 03/08/2025] [Accepted: 03/11/2025] [Indexed: 03/28/2025] Open
Abstract
Background/Objectives: Mortality from COVID-19 in intensive care units (ICUs) was not clearly reported in many regions during the first wave. We aimed to assess the characteristics and outcomes of ICU patients with COVID-19 in Saudi Arabia. Methods: This was a secondary data analysis of the Convalescent Plasma Trial. All patients who were recruited from King Fahad Hospital of the University (KFHU) in the Eastern Region of Saudi Arabia between 13 March 2020 and 13 September 2020 were included. Characteristics and outcomes, differences in characteristics and outcomes between Saudi and non-Saudi populations, and predictors of mortality were assessed. Results: The KFHU recruited 185 ICU patients with COVID-19. Of those, 90 (48.6%) were Saudi, and 95 (51.4%) were non-Saudi. The overall mean age was 56.7 years, and 71.9% were males. Compared with Saudis, non-Saudis were younger, with a mean age of 54.4 years, were more likely to be males (81.1%), and had a higher median respiratory rate (28.0 breaths/min vs. 24.0), a lower percentage of blood-oxygen saturation (86.0% vs. 91.0%), and higher median levels of ferritin per µg/L (820 vs. 550). The overall mortality rate was 33.0% (n = 61). The mortality rate in non-Saudis (42.1%) was higher than that in Saudis (23.3%). The variables associated with increased mortality included non-Saudi status (odds ratio [OR] 2.66; 95% CI: 1.05, 6.72), ferritin (OR 1.01; 95% CI: 1.00, 1.02), and intubation (OR 8.55; 95% CI: 2.92, 24.97). Conclusions: Since the mortality rate in non-Saudis was greater than that in Saudis, more efforts should be made to improve social determinants of health across non-Saudis in our region.
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Affiliation(s)
- Saeed A. Alqahtani
- Department of Emergency Medical Care, Prince Sultan Military College of Health Sciences, Dhahran 34313, Saudi Arabia (J.S.A.)
| | - Talal M. Alshammari
- Department of Emergency Medical Care, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia
| | - Eidan M. Alzahrani
- Department of Emergency Medical Care, Prince Sultan Military College of Health Sciences, Dhahran 34313, Saudi Arabia (J.S.A.)
| | - Abeer A. Alaohali
- Department of Emergency Medical Care, Prince Sultan Military College of Health Sciences, Dhahran 34313, Saudi Arabia (J.S.A.)
| | - Jaber S. Alqahtani
- Department of Emergency Medical Care, Prince Sultan Military College of Health Sciences, Dhahran 34313, Saudi Arabia (J.S.A.)
| | - Yahya A. Alzahrani
- Department of Emergency Medical Care, Prince Sultan Military College of Health Sciences, Dhahran 34313, Saudi Arabia (J.S.A.)
| | - Ahmad A. Alrawashdeh
- Department of Paramedics, Faculty of Allied Medical Sciences, Jordan University of Science and Technology, Ar-Ramtha 3030, Jordan
| | - Brett Williams
- Department of Paramedicine, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton, VIC 3168, Australia
| | - Mohammed A. Aljumaan
- Department of Emergency Medical Care, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia
- Department of Emergency Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia; (M.A.A.)
| | - Amal H. Alsulaibikh
- Department of Intensive Care, King Fahad Hospital of the University of Imam Abdulrahman bin Faisal, Dammam 34212, Saudi Arabia
| | - Mohannad A. Alghamdi
- Department of Emergency Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia; (M.A.A.)
| | - Mohammed A. Almulhim
- Department of Emergency Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia; (M.A.A.)
| | - Shaya Y. Alqahtani
- Department of Internal and Critical Care Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia
| | - Sarah Al-Ahmadi
- Department of Emergency Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia; (M.A.A.)
| | - Mohammed S. Alshahrani
- Department of Emergency Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia; (M.A.A.)
- Department of Intensive Care, King Fahad Hospital of the University of Imam Abdulrahman bin Faisal, Dammam 34212, Saudi Arabia
- Department of Internal and Critical Care Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia
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Abiri E, Mirzaii M, Moghbeli M, Atashi A, Harati AA. Investigating DNA damage caused by COVID-19 and influenza in post COVID-19. Mamm Genome 2025; 36:200-212. [PMID: 39537997 DOI: 10.1007/s00335-024-10082-z] [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: 04/02/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024]
Abstract
The SARS-CoV-2 virus (termed COVID-19) was responsible for over 34 million global deaths. Although the COVID-19 pandemic has subsided, infection by emerging mutant variants of SARS-CoV-2 poses a continuing threat to public health. COVID-19 infection has been associated with the development of cytokine storm syndrome, hypercoagulability, immunological dysregulation and direct viral invasion of organs, and the long-term consequences for the health of COVID-19 survivors are currently unknown. Our research focuses on the possible mutagenic aspects of infection by COVID-19 and measures their harmful effects on DNA composition. DNA damage was investigated, using the comet assay method, during two periods: in the epidemic peak of COVID-19 and during the post-COVID-19 period, both in patients infected with COVID-19 and in those with influenza. During the epidemic peak, the levels of DNA damage ranged from the highest to the lowest levels in the following groups, respectively: intubated-ICU, non-intubated-ICU, non-ICU, and influenza, with a discernible increase in DNA damage in ICU-treated patients. The levels of DNA damage in the post-COVID-19 period were significantly lower compared to those in the epidemic peak period but there was still a discernible increase in DNA damage in the ICU group. Our results indicate that levels of DNA damage may be an effective indicator in prognostic decision-making and may therefore help to reduce mortality. Given that DNA damage and impaired repair processes can contribute to chronic diseases like diabetes, cancer, and neurodegenerative conditions, it will be crucial to investigate potential similar effects in patients with COVID-19.
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Affiliation(s)
- Elaheh Abiri
- Department of Biology, Islamic Azad University Damghan, Damghan Branch, Damghan, Iran
| | - Mehdi Mirzaii
- School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
| | - Majid Moghbeli
- Department of Biology, Islamic Azad University Damghan, Damghan Branch, Damghan, Iran
| | - Amir Atashi
- School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Ahad Ali Harati
- Department of Biology, Islamic Azad University Damghan, Damghan Branch, Damghan, Iran
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Lee C, Khan R, Mantsounga CS, Sharma S, Pierce J, Amelotte E, Butler CA, Farinha A, Parry C, Caballero O, Morrison JA, Uppuluri S, Whyte JJ, Kennedy JL, Zhang X, Choudhary G, Olson RM, Morrison AR. IL-1β-driven NF-κB transcription of ACE2 as a Mechanism of Macrophage Infection by SARS-CoV-2. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2024.12.24.630260. [PMID: 39763770 PMCID: PMC11703209 DOI: 10.1101/2024.12.24.630260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
Coronavirus disease 2019 (COVID-19), caused by infection with the enveloped RNA betacoronavirus, SARS-CoV-2, led to a global pandemic involving over 7 million deaths. Macrophage inflammatory responses impact COVID-19 severity; however, it is unclear whether macrophages are infected by SARS-CoV-2. We sought to identify mechanisms regulating macrophage expression of ACE2, the primary receptor for SARS-CoV-2, and to determine if macrophages are susceptible to productive infection. We developed a humanized ACE2 (hACE2) mouse whereby hACE2 cDNA was cloned into the mouse ACE2 locus under control of the native promoter. We validated the susceptibility of hACE2 mice to SARS-CoV-2 infection relative to wild-type mice and an established K18-hACE2 model of acute fulminating disease. Intranasal exposure to SARS-CoV-2 led to pulmonary consolidations with cellular infiltrate, edema, and hemorrhage, consistent with pneumonia, yet unlike the K18-hACE2 model, hACE2 mice survived and maintained stable weight. Infected hACE2 mice also exhibited a unique plasma chemokine, cytokine, and growth factor inflammatory signature relative to K18-hACE2 mice. Infected hACE2 mice demonstrated evidence of viral replication in infiltrating lung macrophages, and infection of macrophages in vitro revealed a transcriptional profile indicative of altered RNA and ribosomal processing machinery as well as activated cellular antiviral defense. Macrophage IL-1β-driven NF-κB transcription of ACE2 was an important mechanism of dynamic ACE2 upregulation, promoting macrophage susceptibility to infection. Experimental models of COVID-19 that make use of native hACE2 expression will allow for mechanistic insight into factors that can either promote host resilience or increase susceptibility to worsening severity of infection.
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Affiliation(s)
- Cadence Lee
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| | - Rachel Khan
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| | - Chris S. Mantsounga
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| | - Sheila Sharma
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| | - Julia Pierce
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| | - Elizabeth Amelotte
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| | - Celia A. Butler
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| | - Andrew Farinha
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| | - Crystal Parry
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| | - Olivya Caballero
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| | - Jeremi A. Morrison
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| | - Saketh Uppuluri
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| | - Jeffrey J. Whyte
- Department of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA
- Laboratory for Infectious Disease Research, University of Missouri Division of Research, Innovation and Impact, Columbia, Missouri, USA
| | - Joshua L. Kennedy
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
- Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
- Arkansas Children’s Research Institute, Little Rock, Arkansas, USA
| | - Xuming Zhang
- Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Gaurav Choudhary
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
- Cardiovascular Research Center, Lifespan Cardiovascular Research Institute, Rhode Island Hospital, Providence, Rhode Island, USA
| | - Rachel M. Olson
- Department of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA
- Laboratory for Infectious Disease Research, University of Missouri Division of Research, Innovation and Impact, Columbia, Missouri, USA
| | - Alan R. Morrison
- Vascular Research Laboratory, Providence VA Medical Center, Providence, Rhode Island 02908, USA
- Ocean State Research Institute, Inc., Providence, Rhode Island 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
- Lead contact and corresponding author
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Jermakow N, Brodaczewska K, Kot J, Lubas A, Kłos K, Siewiera J. Bayesian Modeling of the Impact of HBOT on the Reduction in Cytokine Storms. J Clin Med 2025; 14:1180. [PMID: 40004710 PMCID: PMC11856955 DOI: 10.3390/jcm14041180] [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: 12/18/2024] [Revised: 01/29/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Since the initial identification of SARS-CoV-2 infections, numerous clinical challenges have arisen, revealing both acute and long-term effects associated with COVID-19. These effects impact various systems within the body, including the respiratory, cardiovascular, and nervous systems. Background/Objectives: This study aimed to investigate the immunological and inflammatory parameters in patients with severe COVID-19 and evaluate the effects of hyperbaric oxygen therapy (HBOT) on these parameters. Methods: This study enrolled thirty patients from the Military Medical Institute-National Research Institute in Warsaw, who were hospitalized for SARS-CoV-2 infection. Patients were screened for eligibility based on pre-defined inclusion criteria. The subjects were randomly assigned to one of two groups: hyperbaric oxygen therapy (HBOT) or a control group. Immune profiling was performed, measuring cytokine concentrations and leukocyte subpopulations in serum samples. Outcomes were assessed using Bayesian modeling. Results: Bayesian regression analysis confirmed previous findings, indicating that HBOT may reduce inflammatory cytokine levels while improving oxygen saturation (SpO2) in patients with moderate and severe COVID-19. Moreover, the analysis suggested a higher probability of HBOT success in modulating the immune response and reducing inflammatory parameters, particularly in T lymphocyte subpopulations. Conclusions: Hyperbaric oxygen therapy (HBOT) may serve as an effective adjunctive treatment for patients with COVID-19 by enhancing oxygen saturation and modulating the immune response. Further studies are needed to elucidate the underlying mechanisms of HBOT on inflammatory and immunological parameters in COVID-19 patients.
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Affiliation(s)
- Natalia Jermakow
- Department of Hyperbaric Medicine, Military Institute of Medicine, National Science Institute, Szaserów 128, 04-141 Warsaw, Poland;
| | - Klaudia Brodaczewska
- The Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, National Science Institute, Szaserów 128, 04-141 Warsaw, Poland;
| | - Jacek Kot
- National Centre for Hyperbaric Medicine, Institute of Maritime and Tropical Medicine, Medical University of Gdansk, Powstania Styczniowego 9B, 81-519 Gdynia, Poland;
| | - Arkadiusz Lubas
- Department of Internal Diseases Nephrology and Dialysis, Military Institute of Medicine, National Science Institute, Szaserów 128, 04-141 Warsaw, Poland;
| | - Krzysztof Kłos
- Department of Infectious Diseases and Allergology, Military Institute of Medicine, National Science Institute, Szaserów 128, 04-141 Warsaw, Poland;
| | - Jacek Siewiera
- Department of Hyperbaric Medicine, Military Institute of Medicine, National Science Institute, Szaserów 128, 04-141 Warsaw, Poland;
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Chen Y, Zhang C, Feng Y. Medicinal plants for the management of post-COVID-19 fatigue: A literature review on the role and mechanisms. J Tradit Complement Med 2025; 15:15-23. [PMID: 39807273 PMCID: PMC11725095 DOI: 10.1016/j.jtcme.2024.05.006] [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: 05/19/2024] [Accepted: 05/23/2024] [Indexed: 01/16/2025] Open
Abstract
Background COVID-19 infection has a lasting impact on human health, which is known as post-COVID-19 conditions. Fatigue is one of the most commonly reported post-COVID-19 conditions. Management of fatigue in the post-COVID-19 era is necessary and emerging. The use of medicinal plants may provide a strategy for the management of post-COVID-19 fatigue. Methods A literature search has been conducted by using PubMed, Embase and Cochrane library databases is performed for studies published up to March 2024. Keywords, such as "post-COVID-19 conditions, persistent COVID-19 symptoms, chronic COVID-19, long-term sequelae, fatigue, post-COVID-19 fatigue, herbal plants, medicinal herbs, traditional Chinese medicine, pharmacological mechanisms, pharmacological actions" are thoroughly searched in Englsih and Chinese. This study reviews the pathophysiology of post-COVID-19 fatigue and potential herbal plants for managing post-COVID-19 fatigue. Results and conclusion Representative medicinal plants that have been extensively investigated by previous studies are presented in the study. Three common mechanisms among the most extensively studied for post-COVID-19 fatigue, with each mechanism having medicinal plants as an example. The latest clinical studies concerning the management of post-COVID-19 fatigue using medicinal plants have also been summarized. The study shows the potential for improving post-COVID-19 fatigue by consuming medicinal plants.
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Affiliation(s)
- Yuanyuan Chen
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China
| | - Cheng Zhang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China
| | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China
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Xu QQ, Yu DD, Fan XD, Cui HR, Dai QQ, Zhong XY, Zhang XY, Zhao C, You LZ, Shang HC. Chinese Medicine for Treatment of COVID-19: A Review of Potential Pharmacological Components and Mechanisms. Chin J Integr Med 2025; 31:83-95. [PMID: 38958885 DOI: 10.1007/s11655-024-3909-z] [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] [Accepted: 08/02/2023] [Indexed: 07/04/2024]
Abstract
Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.
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Affiliation(s)
- Qian-Qian Xu
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Dong-Dong Yu
- The Geriatrics Center, First Affiliated Hospital, Anhui University of Chinese Medicine, Hefei, 230031, China
| | - Xiao-Dan Fan
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - He-Rong Cui
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Qian-Qian Dai
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Xiao-Ying Zhong
- School of Medical Information Engineering, Guangzhou University of Chinese Medicine, Guangzhou, 51006, China
| | - Xin-Yi Zhang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Chen Zhao
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Liang-Zhen You
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
| | - Hong-Cai Shang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
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Santella B, Aliberti SM, Fortino L, Donato A, Andretta V, Santoro E, Franci G, Capunzo M, Boccia G. Age Differences and Prevalence of Comorbidities for Death and Survival in Patients with COVID-19: A Single-Center Observational Study in a Region of Southern Italy. Life (Basel) 2024; 14:1376. [PMID: 39598175 PMCID: PMC11595941 DOI: 10.3390/life14111376] [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: 09/23/2024] [Revised: 10/21/2024] [Accepted: 10/24/2024] [Indexed: 11/29/2024] Open
Abstract
The SARS-CoV-2 outbreak has resulted in a considerable number of deaths worldwide. The virus damages the pulmonary artery endothelium, leading to a condition known as microvascular pulmonary inflammatory thrombotic syndrome (MPITS), which can be fatal and cause multiple organ failure. The presence of preexisting comorbidities has been shown to significantly impact the severity and prognosis of patients with SARS-CoV-2 infection. The objective of this study was to compare the age groups of patients with coronavirus disease 2019 (COVID-19) and to identify the prevalence of comorbidities associated with death and survival in an area of southern Italy. The data set consisted of 1985 patients with confirmed cases of SARS-CoV-2 infection who were admitted to the A.O.U. San Giovanni di Dio e Ruggi d'Aragona Hospital in Salerno between January 2021 and December 2022. The results were presented for the overall population and stratified by outcome and age group. All analyses were performed using the XLSTAT (Lumivero, 2024, Paris, France) and STATA software (release 16.1, StataCorp LLG, College Station, TX, USA, 2019) packages. In the study, population, 636 cases (32%) resulted in death, with a higher prevalence in the 60-79 age group, followed by the ≥80 and 30-59 age groups. The most prevalent diseases among deceased and surviving patients with confirmed cases of SARS-CoV-2 infection were those affecting the circulatory system (61.5% vs. 55.5%), the respiratory system (55.8% vs. 26.2%), and the metabolic system (25.9% vs. 25.4%). In patients aged 30-79, respiratory diseases were the primary cause of mortality, whereas in those aged ≥80, circulatory system diseases were more prevalent. Among survivors, cardiovascular diseases were the most common comorbidities across all age groups, followed by respiratory diseases and endocrine, metabolic, and immune disorders. Moreover, these comorbidities were associated with an elevated risk of mortality. The study emphasizes the substantial influence of age and comorbidities on the mortality associated with SARS-CoV-2 infection. These findings highlight the necessity for targeted interventions to manage comorbid conditions in patients with SARS-CoV-2 infection, particularly in older adults.
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Affiliation(s)
- Biagio Santella
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (B.S.); (S.M.A.); (L.F.); (A.D.); (V.A.); (E.S.); (G.F.); (M.C.)
| | - Silvana Mirella Aliberti
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (B.S.); (S.M.A.); (L.F.); (A.D.); (V.A.); (E.S.); (G.F.); (M.C.)
| | - Luigi Fortino
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (B.S.); (S.M.A.); (L.F.); (A.D.); (V.A.); (E.S.); (G.F.); (M.C.)
| | - Antonio Donato
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (B.S.); (S.M.A.); (L.F.); (A.D.); (V.A.); (E.S.); (G.F.); (M.C.)
| | - Vincenzo Andretta
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (B.S.); (S.M.A.); (L.F.); (A.D.); (V.A.); (E.S.); (G.F.); (M.C.)
- DAI Department of Health Hygiene and Evaluative Medicine, A.O.U. San Giovanni di Dio e Ruggi d’Aragona, 84131 Salerno, Italy
| | - Emanuela Santoro
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (B.S.); (S.M.A.); (L.F.); (A.D.); (V.A.); (E.S.); (G.F.); (M.C.)
| | - Gianluigi Franci
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (B.S.); (S.M.A.); (L.F.); (A.D.); (V.A.); (E.S.); (G.F.); (M.C.)
- DAI Department of Health Hygiene and Evaluative Medicine, A.O.U. San Giovanni di Dio e Ruggi d’Aragona, 84131 Salerno, Italy
| | - Mario Capunzo
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (B.S.); (S.M.A.); (L.F.); (A.D.); (V.A.); (E.S.); (G.F.); (M.C.)
- DAI Department of Health Hygiene and Evaluative Medicine, A.O.U. San Giovanni di Dio e Ruggi d’Aragona, 84131 Salerno, Italy
| | - Giovanni Boccia
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (B.S.); (S.M.A.); (L.F.); (A.D.); (V.A.); (E.S.); (G.F.); (M.C.)
- DAI Department of Health Hygiene and Evaluative Medicine, A.O.U. San Giovanni di Dio e Ruggi d’Aragona, 84131 Salerno, Italy
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Deus MDC, Gadotti AC, Dias ES, Monte Alegre JB, Van Spitzenbergen BAK, Andrade GB, Tozoni SS, Stocco RB, Olandoski M, Tuon FFB, Pinho RA, de Noronha L, Baena CP, Moreno-Amaral AN. Prospective Variation of Cytokine Trends during COVID-19: A Progressive Approach from Disease Onset until Outcome. Int J Mol Sci 2024; 25:10578. [PMID: 39408907 PMCID: PMC11477561 DOI: 10.3390/ijms251910578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 09/19/2024] [Accepted: 09/28/2024] [Indexed: 10/20/2024] Open
Abstract
COVID-19 is characterized by pronounced hypercytokinemia. The cytokine switch, marked by an imbalance between pro-inflammatory and anti-inflammatory cytokines, emerged as a focal point of investigation throughout the COVID-19 pandemic. However, the kinetics and temporal dynamics of cytokine release remain contradictory, making the development of new therapeutics difficult, especially in severe cases. This study collected serum samples from SARS-CoV-2 infected patients at 72 h intervals and monitored them for various cytokines at each timepoint until hospital discharge or death. Cytokine levels were analyzed based on time since symptom onset and patient outcomes. All cytokines studied prospectively were strong predictors of mortality, particularly IL-4 (AUC = 0.98) and IL-1β (AUC = 0.96). First-timepoint evaluations showed elevated cytokine levels in the mortality group (p < 0.001). Interestingly, IFN-γ levels decreased over time in the death group but increased in the survival group. Patients who died exhibited sustained levels of IL-1β and IL-4 and increased IL-6 levels over time. These findings suggest cytokine elevation is crucial in predicting COVID-19 mortality. The dynamic interplay between IFN-γ and IL-4 highlights the balance between Th1/Th2 immune responses and underscores IFN-γ as a powerful indicator of immune dysregulation throughout the infection.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | - Andrea Novais Moreno-Amaral
- Programa de Pós-Graduação em Ciências da Saúde (PPGCS), Escola de Medicina, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba 80215-901, PR, Brazil; (M.d.C.D.); (A.C.G.); (E.S.D.); (J.B.M.A.); (B.A.K.V.S.); (G.B.A.); (S.S.T.); (R.B.S.); (M.O.); (F.F.B.T.); (R.A.P.); (L.d.N.); (C.P.B.)
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9
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Wang HI, Doran T, Crooks MG, Khunti K, Heightman M, Gonzalez-Izquierdo A, Qummer Ul Arfeen M, Loveless A, Banerjee A, Van Der Feltz-Cornelis C. Prevalence, risk factors and characterisation of individuals with long COVID using Electronic Health Records in over 1.5 million COVID cases in England. J Infect 2024; 89:106235. [PMID: 39121972 PMCID: PMC11409608 DOI: 10.1016/j.jinf.2024.106235] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 07/24/2024] [Accepted: 07/27/2024] [Indexed: 08/12/2024]
Abstract
OBJECTIVES This study examines clinically confirmed long-COVID symptoms and diagnosis among individuals with COVID in England, aiming to understand prevalence and associated risk factors using electronic health records. To further understand long COVID, the study also explored differences in risks and symptom profiles in three subgroups: hospitalised, non-hospitalised, and untreated COVID cases. METHODS A population-based longitudinal cohort study was conducted using data from 1,554,040 individuals with confirmed SARS-CoV-2 infection via Clinical Practice Research Datalink. Descriptive statistics explored the prevalence of long COVID symptoms 12 weeks post-infection, and Cox regression models analysed the associated risk factors. Sensitivity analysis was conducted to test the impact of right-censoring data. RESULTS During an average 400-day follow-up, 7.4% of individuals with COVID had at least one long-COVID symptom after acute phase, yet only 0.5% had long-COVID diagnostic codes. The most common long-COVID symptoms included cough (17.7%), back pain (15.2%), stomach-ache (11.2%), headache (11.1%), and sore throat (10.0%). The same trend was observed in all three subgroups. Risk factors associated with long-COVID symptoms were female sex, non-white ethnicity, obesity, and pre-existing medical conditions like anxiety, depression, type II diabetes, and somatic symptom disorders. CONCLUSIONS This study is the first to investigate the prevalence and risk factors of clinically confirmed long-COVID in the general population. The findings could help clinicians identify higher risk individuals for timely intervention and allow decision-makers to more efficiently allocate resources for managing long-COVID.
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Affiliation(s)
- Han-I Wang
- Department of Health Sciences, University of York, York, UK; Institute of Health Informatics, University College of London, London, UK.
| | - Tim Doran
- Department of Health Sciences, University of York, York, UK
| | | | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester, UK
| | - Melissa Heightman
- University College London Hospitals NHS Foundation Trust, London, UK
| | | | | | - Antony Loveless
- Patient and Public Involvement (PPI) member for STIMULATE-ICP Consortium, Institute of Health Informatics, University College of London, London, UK
| | - Amitava Banerjee
- Institute of Health Informatics, University College of London, London, UK
| | - Christina Van Der Feltz-Cornelis
- Department of Health Sciences, University of York, York, UK; Hull York Medical School, York, UK; Institute of Health Informatics, University College of London, London, UK
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10
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Wang Q, Shi P, Cao L, Li H, Chen X, Wang P, Zhang J. Unveiling the detrimental vicious cycle linking skeletal muscle and COVID-19: A systematic review and meta-analysis. J Evid Based Med 2024; 17:503-525. [PMID: 38975690 DOI: 10.1111/jebm.12629] [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: 01/02/2024] [Accepted: 06/18/2024] [Indexed: 07/09/2024]
Abstract
OBJECTIVE Skeletal muscle catabolism supports multiple organs and systems during severe trauma and infection, but its role in COVID-19 remains unclear. This study investigates the interactions between skeletal muscle and COVID-19. METHODS The PubMed, EMbase, and The Cochrane Library databases were systematically searched from January 2020 to August 2023 for cohort studies focusing on the impact of skeletal muscle on COVID-19 prevalence and outcomes, and longitudinal studies examining skeletal muscle changes caused by COVID-19. Skeletal muscle quantity (SMQN) and quality (SMQL) were assessed separately. The random-effect model was predominantly utilized for statistical analysis. RESULTS Seventy studies with moderate to high quality were included. Low SMQN/SMQL was associated with an increased risk of COVID-19 infection (OR = 1.62, p < 0.001). Both the low SMQN and SMQL predicted COVID-19-related mortality (OR = 1.53, p = 0.016; OR = 2.18, p = 0.001, respectively). Mortality risk decreased with increasing SMQN (OR = 0.979, p = 0.009) and SMQL (OR = 0.972, p = 0.034). Low SMQN and SMQL were also linked to the need for intensive care unit/mechanical ventilation, increased COVID-19 severity, and longer hospital stays. Significant skeletal muscle wasting, characterized by reduced volume and strength, was observed during COVID-19 infection and the pandemic. CONCLUSIONS This study reveals a detrimental vicious circle between skeletal muscle and COVID-19. Effective management of skeletal muscle could be beneficial for treating COVID-19 infections and addressing the broader pandemic. These findings have important implications for the management of future virus pandemics. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42023395476.
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Affiliation(s)
- Qin Wang
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Peipei Shi
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Lu Cao
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Haoran Li
- Department of Thoracic Surgery, Thoracic Oncology Institute, Peking University People's Hospital, Beijing, China
| | - Xiankai Chen
- Department of Thoracic Surgical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Peiyu Wang
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Department of Thoracic Surgery, Thoracic Oncology Institute, Peking University People's Hospital, Beijing, China
| | - Jianjiang Zhang
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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11
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Kallem CJ, Alghwiri AA, Yabes JG, Roumelioti ME, Erickson S, Rollman BL, Weisbord S, Unruh M, Vodovotz Y, Jhamb M, Steel JL. Association of Symptoms and Collaborative Care Intervention with Systemic Inflammation Biomarkers in ESKD. KIDNEY360 2024; 5:1299-1310. [PMID: 39012260 PMCID: PMC11441811 DOI: 10.34067/kid.0000000000000512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 07/10/2024] [Indexed: 07/17/2024]
Abstract
Key Points There were no associations between biomarkers and patient-reported pain, fatigue, and depression in a large ESKD cohort at baseline. Compared with control, the Technology-Assisted stepped Collaborative Care intervention had a short-term impact on reducing inflammatory burden. Treatment modified the association between changes in symptoms and in certain proinflammatory biomarkers (TNF-α and high sensitivity C-reactive protein) over time. Background Patient-reported symptoms are associated with inflammation biomarkers in many chronic diseases. We examined associations of inflammation biomarkers with pain, fatigue, and depression in patients with ESKD and the effects of a Technology-Assisted stepped Collaborative Care (TĀCcare) intervention on these biomarkers. Methods In the TĀCcare multisite randomized control trial, data on patient-reported symptoms were collected at baseline and 3 and 6 months. Anti-inflammatory (IL-1 receptor agonist, IL-10), proinflammatory (TNF-α , high sensitivity C-reactive protein, IL-6), and regulatory (IL-2) biomarkers were assayed. Linear mixed-effects modeling was used to examine within-group and between-group differences after adjusting for age, sex, race, and comorbidities. Results Among the 160 patients (mean age 58±14 years, 55% men, 52% white), there were no significant associations between inflammation biomarkers and pain, fatigue, or depression at baseline. Both intervention and control groups demonstrated reductions in IL-10 and IL-1 receptor agonist over 6 months (β range=−1.22 to −0.40, P range=<0.001–0.02) At 3 months, the treatment group exhibited decreases in TNF-α (β =−0.22, P < 0.001) and IL-2 (β =−0.71, P < 0.001), whereas the control group showed increases in IL-6/IL-10 ratio (β =0.33, P = 0.03). At 6 months, both groups exhibited decreases in IL-2 (β range=−0.66 to −0.57, P < 0.001); the control group showed significant increases in the ratio of IL-6/IL-10 (β =0.75, P < 0.001) and decrease in TNF-α (β =−0.16, P = 0.02). Compared with controls, the treatment group demonstrated significantly decreased IL-2 at 3 months (β =−0.53, P < 0.001). Significant interaction effects of treatment were observed on the association between changes in proinflammatory biomarkers (TNF-α and high sensitivity C-reactive protein) levels and changes in symptom scores from baseline to 6 months. Conclusions The TĀCcare intervention had a short-term impact on reducing inflammatory burden in patients with ESKD. More studies are needed to confirm our findings and to determine whether these biomarkers mediate the link between symptoms and disease progression. Clinical Trial registration number: ClinicalTrials.gov NCT03440853 .
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Affiliation(s)
- Cramer J. Kallem
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Alaa A. Alghwiri
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Jonathan G. Yabes
- Division of General Internal Medicine, Department of Medicine and Biostatistics, Center for Research on Heath Care Data Center, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Maria-Eleni Roumelioti
- Division of Nephrology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico
| | - Sarah Erickson
- Department of Psychology, University of New Mexico, Albuquerque, New Mexico
| | - Bruce L. Rollman
- Division of General Internal Medicine, Center for Behavioral Health, Media, and Technology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Steven Weisbord
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Renal Section and Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
| | - Mark Unruh
- Division of Nephrology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico
| | - Yoram Vodovotz
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Manisha Jhamb
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Jennifer L. Steel
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Department of Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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12
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Geanes ES, McLennan R, Pierce SH, Menden HL, Paul O, Sampath V, Bradley T. SARS-CoV-2 envelope protein regulates innate immune tolerance. iScience 2024; 27:109975. [PMID: 38827398 PMCID: PMC11140213 DOI: 10.1016/j.isci.2024.109975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 03/01/2024] [Accepted: 05/10/2024] [Indexed: 06/04/2024] Open
Abstract
Severe COVID-19 often leads to secondary infections and sepsis that contribute to long hospital stays and mortality. However, our understanding of the precise immune mechanisms driving severe complications after SARS-CoV-2 infection remains incompletely understood. Here, we provide evidence that the SARS-CoV-2 envelope (E) protein initiates innate immune inflammation, via toll-like receptor 2 signaling, and establishes a sustained state of innate immune tolerance following initial activation. Monocytes in this tolerant state exhibit reduced responsiveness to secondary stimuli, releasing lower levels of cytokines and chemokines. Mice exposed to E protein before secondary lipopolysaccharide challenge show diminished pro-inflammatory cytokine expression in the lung, indicating that E protein drives this tolerant state in vivo. These findings highlight the potential of the SARS-CoV-2 E protein to induce innate immune tolerance, contributing to long-term immune dysfunction that could lead to susceptibility to subsequent infections, and uncovers therapeutic targets aimed at restoring immune function following SARS-CoV-2 infection.
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Affiliation(s)
- Eric S. Geanes
- Genomic Medicine Center, Children’s Mercy Research Institute, Kansas City, MO, USA
| | - Rebecca McLennan
- Genomic Medicine Center, Children’s Mercy Research Institute, Kansas City, MO, USA
| | - Stephen H. Pierce
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Heather L. Menden
- Division of Neonatology, Children’s Mercy Research Institute, Kansas City, MO, USA
| | - Oishi Paul
- Genomic Medicine Center, Children’s Mercy Research Institute, Kansas City, MO, USA
| | - Venkatesh Sampath
- Division of Neonatology, Children’s Mercy Research Institute, Kansas City, MO, USA
- Department of Pediatrics, University of Missouri- Kansas City, Kansas City, MO, USA
| | - Todd Bradley
- Genomic Medicine Center, Children’s Mercy Research Institute, Kansas City, MO, USA
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA
- Department of Pediatrics, University of Missouri- Kansas City, Kansas City, MO, USA
- Department of Pediatrics, University of Kansas Medical Center, Kansas City, MO, USA
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13
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Maaß H, Ynga-Durand M, Milošević M, Krstanović F, Matešić MP, Žuža I, Jonjić S, Brizić I, Šustić A, Bloos F, Protić A, Čičin-Šain L. Serum cytokine dysregulation signatures associated with COVID-19 outcomes in high mortality intensive care unit cohorts across pandemic waves and variants. Sci Rep 2024; 14:13605. [PMID: 38871772 DOI: 10.1038/s41598-024-64384-y] [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: 10/10/2023] [Accepted: 06/07/2024] [Indexed: 06/15/2024] Open
Abstract
The aim of this study was to characterize the systemic cytokine signature of critically ill COVID-19 patients in a high mortality setting aiming to identify biomarkers of severity, and to explore their associations with viral loads and clinical characteristics. We studied two COVID-19 critically ill patient cohorts from a referral centre located in Central Europe. The cohorts were recruited during the pre-alpha/alpha (November 2020 to April 2021) and delta (end of 2021) period respectively. We determined both the serum and bronchoalveolar SARS-CoV-2 viral load and identified the variant of concern (VoC) involved. Using a cytokine multiplex assay, we quantified systemic cytokine concentrations and analyzed their relationship with clinical findings, routine laboratory workup and pulmonary function data obtained during the ICU stay. Patients who did not survive had a significantly higher systemic and pulmonary viral load. Patients infected with the pre-alpha VoC showed a significantly lower viral load in comparison to those infected with the alpha- and delta-variants. Levels of systemic CTACK, M-CSF and IL-18 were significantly higher in non-survivors in comparison to survivors. CTACK correlated directly with APACHE II scores. We observed differences in lung compliance and the association between cytokine levels and pulmonary function, dependent on the VoC identified. An intra-cytokine analysis revealed a loss of correlation in the non-survival group in comparison to survivors in both cohorts. Critically ill COVID-19 patients exhibited a distinct systemic cytokine profile based on their survival outcomes. CTACK, M-CSF and IL-18 were identified as mortality-associated analytes independently of the VoC involved. The Intra-cytokine correlation analysis suggested the potential role of a dysregulated systemic network of inflammatory mediators in severe COVID-19 mortality.
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Affiliation(s)
- Henrike Maaß
- Department of Viral Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany
- Centre for Individualized Infection Medicine (CiiM), a joint venture of Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany
| | - Mario Ynga-Durand
- Department of Viral Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany
- Centre for Individualized Infection Medicine (CiiM), a joint venture of Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany
| | - Marko Milošević
- Department of Anesthesiology, Faculty of Medicine, Reanimation, Intensive Care and Emergency Medicine, University of Rijeka, Rijeka, Croatia
| | - Fran Krstanović
- Faculty of Medicine, Center for Proteomics, University of Rijeka, Rijeka, Croatia
| | | | - Iva Žuža
- Department of Radiology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Stipan Jonjić
- Faculty of Medicine, Center for Proteomics, University of Rijeka, Rijeka, Croatia
| | - Ilija Brizić
- Faculty of Medicine, Center for Proteomics, University of Rijeka, Rijeka, Croatia
| | - Alan Šustić
- Department of Anesthesiology, Faculty of Medicine, Reanimation, Intensive Care and Emergency Medicine, University of Rijeka, Rijeka, Croatia
- Department of Clinical Medical Science II, Faculty of Health Studies, University of Rijeka, Rijeka, Croatia
| | - Frank Bloos
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany
| | - Alen Protić
- Department of Anesthesiology, Faculty of Medicine, Reanimation, Intensive Care and Emergency Medicine, University of Rijeka, Rijeka, Croatia
| | - Luka Čičin-Šain
- Department of Viral Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany.
- Centre for Individualized Infection Medicine (CiiM), a joint venture of Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany.
- German Centre for Infection Research (DZIF), Partner Site Hannover/Braunschweig, Braunschweig, Germany.
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14
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Chen JI, Bui D, Iwashyna TJ, Shahoumian TA, Hickok A, Shepherd-Banigan M, Hawkins EJ, Naylor J, Govier DJ, Osborne TF, Smith VA, Bowling CB, Boyko EJ, Ioannou GN, Maciejewski ML, O'Hare AM, Viglianti EM, Bohnert ASB, Hynes DM. Impact of SARS-CoV-2 Infection on Long-Term Depression Symptoms among Veterans. J Gen Intern Med 2024; 39:1310-1316. [PMID: 38625482 PMCID: PMC11169300 DOI: 10.1007/s11606-024-08630-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 01/11/2024] [Indexed: 04/17/2024]
Abstract
BACKGROUND Prior research demonstrates that SARS-COV-2 infection can be associated with a broad range of mental health outcomes including depression symptoms. Veterans, in particular, may be at elevated risk of increased depression following SARS-COV-2 infection given their high rates of pre-existing mental and physical health comorbidities. However, few studies have tried to isolate SARS-COV-2 infection associations with long term, patient-reported depression symptoms from other factors (e.g., physical health comorbidities, pandemic-related stress). OBJECTIVE To evaluate the association between SARS-COV-2 infection and subsequent depression symptoms among United States Military Veterans. DESIGN Survey-based non-randomized cohort study with matched comparators. PARTICIPANTS A matched-dyadic sample from a larger, stratified random sample of participants with and without known to SARS-COV-2 infection were invited to participate in a survey evaluating mental health and wellness 18-months after their index infection date. Sampled participants were stratified by infection severity of the participant infected with SARS-COV-2 (hospitalized or not) and by month of index date. A total of 186 participants in each group agreed to participate in the survey and had sufficient data for inclusion in analyses. Those in the uninfected group who were later infected were excluded from analyses. MAIN MEASURES Participants were administered the Patient Health Questionnaire-9 as part of a phone interview survey. Demographics, physical and mental health comorbidities were extracted from VHA administrative data. KEY RESULTS Veterans infected with SARS-COV-2 had significantly higher depression symptoms scores compared with those uninfected. In particular, psychological symptoms (e.g., low mood, suicidal ideation) scores were elevated relative to the comparator group (MInfected = 3.16, 95%CI: 2.5, 3.8; MUninfected = 1.96, 95%CI: 1.4, 2.5). Findings were similar regardless of history of depression. CONCLUSION SARS-COV-2 infection was associated with more depression symptoms among Veterans at 18-months post-infection. Routine evaluation of depression symptoms over time following SARS-COV-2 infection is important to facilitate adequate assessment and treatment.
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Affiliation(s)
- Jason I Chen
- Center to Improve Veteran Involvement in Care (CIVIC), VA Portland Health Care System (HCS), Portland, OR, USA.
- Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA.
| | - David Bui
- Center to Improve Veteran Involvement in Care (CIVIC), VA Portland Health Care System (HCS), Portland, OR, USA
| | - Theodore J Iwashyna
- Departments of Medicine and Health Policy and Management, Johns Hopkins University, Baltimore, MD, USA
- Center for Clinical Management Research, VA Ann Arbor HCS, Ann Arbor, MI, USA
| | | | - Alex Hickok
- Center to Improve Veteran Involvement in Care (CIVIC), VA Portland Health Care System (HCS), Portland, OR, USA
| | - Megan Shepherd-Banigan
- Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT), Durham VA HCS, Durham, NC, USA
- Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA
| | - Eric J Hawkins
- Center of Innovation for Veteran-Centered and Value-Driven Care, VA Puget Sound HCS, Seattle, WA, USA
- Center of Excellence in Substance Addiction Treatment and Education, VA Puget Sound HCS, Seattle, WA, USA
- Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA
| | - Jennifer Naylor
- School of Medicine, Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
- VISN 6 Mental Illness Research, Education and Clinical Center, Durham, NC, USA
- Durham VA HCS, Durham, NC, USA
| | - Diana J Govier
- Center to Improve Veteran Involvement in Care (CIVIC), VA Portland Health Care System (HCS), Portland, OR, USA
- OHSU-Portland State University School of Public Health, Oregon Health & Science University, Portland, OR, USA
| | - Thomas F Osborne
- VA Palo Alto HCS, Palo Alto, CA, USA
- Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA
| | - Valerie A Smith
- Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT), Durham VA HCS, Durham, NC, USA
- Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA
- Department of Medicine, Duke University, Durham, NC, USA
| | - C Barrett Bowling
- Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT), Durham VA HCS, Durham, NC, USA
- Department of Medicine, Duke University, Durham, NC, USA
- Durham VA Geriatric Research Education and Clinical Center, Durham VA HCS, Durham, NC, USA
| | - Edward J Boyko
- Seattle Epidemiologic Research Information Center, VA Puget Sound HCS, Seattle, WA, USA
| | - George N Ioannou
- Center of Innovation for Veteran-Centered and Value-Driven Care, VA Puget Sound HCS, Seattle, WA, USA
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - Matthew L Maciejewski
- Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT), Durham VA HCS, Durham, NC, USA
- Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA
| | - Ann M O'Hare
- Center of Innovation for Veteran-Centered and Value-Driven Care, VA Puget Sound HCS, Seattle, WA, USA
- Hospital and Specialty Medicine Service, VA Puget Sound HCS, Seattle, WA, USA
- University of Washington, Seattle, WA, USA
| | - Elizabeth M Viglianti
- Center for Clinical Management Research, VA Ann Arbor HCS, Ann Arbor, MI, USA
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Amy S-B Bohnert
- Center for Clinical Management Research, VA Ann Arbor HCS, Ann Arbor, MI, USA
- Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Denise M Hynes
- Center to Improve Veteran Involvement in Care (CIVIC), VA Portland Health Care System (HCS), Portland, OR, USA
- College of Public Health and Human Sciences, and Center for Quantitative Life Sciences, Oregon State University, Corvallis, OR, USA
- School of Nursing, Oregon Health & Science University (OHSU), Portland, OR, USA
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15
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Deng X, Tang K, Wang Z, He S, Luo Z. Impacts of Inflammatory Cytokines Variants on Systemic Inflammatory Profile and COVID-19 Severity. J Epidemiol Glob Health 2024; 14:363-378. [PMID: 38376765 PMCID: PMC11176143 DOI: 10.1007/s44197-024-00204-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 01/30/2024] [Indexed: 02/21/2024] Open
Abstract
BACKGROUND Cytokine storm is known to impact the prognosis of coronavirus disease 2019 (COVID-19), since pro-inflammatory cytokine variants are associated with cytokine storm. It is tempting to speculate that pro-inflammatory cytokines variants may impact COVID-19 outcomes by modulating cytokine storm. Here, we verified this hypothesis via a comprehensive analysis. METHODS PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 15, 2023. Case-control or cohort studies that investigated the impacts of rs1800795 or rs1800629 on COVID-19 susceptibility, severity, mortality, IL-6, TNF-α, or CRP levels were included after an anonymous review by two independent reviewers and consultations of disagreement by a third independent reviewer. RESULTS 47 studies (8305 COVID-19 individuals and 17,846 non-COVID-19 individuals) were analyzed. The rs1800629 A allele (adenine at the -308 position of the promoter was encoded by the A allele) was associated with higher levels of tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). In contrast, the rs1800795 C allele (cytosine at the -174 position of the promoter was encoded by the C allele) was linked to higher levels of interleukin-6 (IL-6) and CRP. In addition, the A allele of rs1800629 increased the severity and mortality of COVID-19. However, the C allele of rs1800795 only increased COVID-19 susceptibility. CONCLUSIONS rs1800629 and rs1800795 variants of pro-inflammatory cytokines have significant impacts on systemic inflammatory profile and COVID-19 clinical outcomes. rs1800629 may serve as a genetic marker for severe COVID-19.
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Affiliation(s)
- XueJun Deng
- Department of Cardiology, Suining Central Hospital, Suining, 629000, Sichuan, China
| | - Kai Tang
- Department of Cardiology, Suining Central Hospital, Suining, 629000, Sichuan, China
| | - Zhiqiang Wang
- Orthopedic Center 1 Department of Orthopedic Trauma, Suining Central Hospital, Suining, Sichuan, China.
| | - Suyu He
- The Fourth Department of Digestive Disease Center, Suining Central Hospital, Suining, 629000, Sichuan, China.
| | - Zhi Luo
- Department of Cardiology, Suining Central Hospital, Suining, 629000, Sichuan, China.
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Ramos A, Martins S, Marinho AS, Norton P, Cardoso MJ, Guimarães JT. Evaluation of SARS-CoV-2 interferon gamma release assay in BNT162b2 vaccinated healthcare workers. PLoS One 2024; 19:e0303244. [PMID: 38728294 PMCID: PMC11086832 DOI: 10.1371/journal.pone.0303244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 04/22/2024] [Indexed: 05/12/2024] Open
Abstract
To predict protective immunity to SARS-CoV-2, cellular immunity seems to be more sensitive than humoral immunity. Through an Interferon-Gamma (IFN-γ) Release Assay (IGRA), we show that, despite a marked decrease in total antibodies, 94.3% of 123 healthcare workers have a positive cellular response 6 months after inoculation with the 2nd dose of BNT162b2 vaccine. Despite the qualitative relationship found, we did not observe a quantitative correlation between IFN-γ and IgG levels against SARS-CoV-2. Using stimulated whole blood from a subset of participants, we confirmed the specific T-cell response to SARS-CoV-2 by dosing elevated levels of the IL-6, IL-10 and TNF-α. Through a 20-month follow-up, we found that none of the infected participants had severe COVID-19 and that the first positive cases were only 12 months after the 2nd dose inoculation. Future studies are needed to understand if IGRA-SARS-CoV-2 can be a powerful diagnostic tool to predict future COVID-19 severe disease, guiding vaccination policies.
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Affiliation(s)
- Angélica Ramos
- Serviço de Patologia Clínica, Centro Hospitalar Universitário de São João, Porto, Portugal
- EPIUnit–Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Universidade do Porto, Porto, Portugal
| | - Sandra Martins
- Serviço de Patologia Clínica, Centro Hospitalar Universitário de São João, Porto, Portugal
- EPIUnit–Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Universidade do Porto, Porto, Portugal
| | - Ana Sofia Marinho
- Serviço de Patologia Clínica, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Pedro Norton
- EPIUnit–Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Universidade do Porto, Porto, Portugal
- Serviço de Saúde Ocupacional, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Maria João Cardoso
- Serviço de Patologia Clínica, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - João Tiago Guimarães
- Serviço de Patologia Clínica, Centro Hospitalar Universitário de São João, Porto, Portugal
- EPIUnit–Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Universidade do Porto, Porto, Portugal
- Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
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Felisberto M, Walter LO, Cardoso CC, Santos-Pirath ÍM, Costa HZ, Gartner R, Werle I, Mohr ETB, Salvan da Rosa J, Lubschinski TL, Kretzer IF, Masukawa II, de Almeida Vanny P, Luiz MC, Rabello de Moraes AC, Santos-Silva MC, Dalmarco EM. Lymphocyte B Subtypes in Peripheral Blood: A Prognostic Biomarker for COVID-19 Patients. J Appl Lab Med 2024; 9:456-467. [PMID: 38321537 DOI: 10.1093/jalm/jfad123] [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: 08/17/2023] [Accepted: 11/28/2023] [Indexed: 02/08/2024]
Abstract
BACKGROUND In view of the scientific gap in knowledge of the involvement of the B-cell compartment and clinical prognostic in SARS-CoV-2 infection, this work aims to evaluate the B-cell subsets and the presence of specific IgM and IgG, as well as neutralizing antibodies against SARS-CoV-2, in unvaccinated patients diagnosed with COVID-19. METHODS This study included 133 patients with COVID-19. Cellular components were assessed by flow cytometry, and immunoglobulin levels and reactivity were measured by indirect enzyme-linked immunosorbent assay. RESULTS Our results showed no changes in less differentiated B cells. However, non-switched memory B cells (NS-MBCs) and class-switched memory B cells (CS-MBCs) were reduced in the patients with moderate disease. Also, plasmablasts and double-negative (DN) or "atypical" memory B cells were increased in groups of patients with moderate to critical conditions. In addition, the production of IgM, IgG, and neutralizing antibodies against SARS-CoV-2 demonstrated a positive correlation between the positivity of antibodies against SARS-CoV-2 and disease severity. Besides being related to the development of a more severe course of the disease, the increase in DN B-cell count also contributed to a poorer disease outcome in patients with a higher percentage of these cells. On the other hand, we observed an increase in the absolute number of CS-MBCs in patients with greater chances of survival. CONCLUSIONS This study demonstrates that the B-cell compartment may contribute to the development of clinical symptoms of COVID-19, with changes in B-cell subset counts linked to disease course and patient prognosis.
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Affiliation(s)
- Mariano Felisberto
- Postgraduate Program in Pharmacy, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
- Clinical Analysis Department, Health Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Laura Otto Walter
- Postgraduate Program in Pharmacy, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
- Clinical Analysis Department, Health Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Chandra Chiappin Cardoso
- Clinical Analysis Department, Flow Cytometry Service, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Íris Mattos Santos-Pirath
- Clinical Analysis Department, Flow Cytometry Service, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Heloisa Zorzi Costa
- Clinical Analysis Department, Flow Cytometry Service, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Rafaela Gartner
- Clinical Analysis Department, Health Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Isabel Werle
- Clinical Analysis Department, Health Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Eduarda Talita Bramorski Mohr
- Postgraduate Program in Pharmacy, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
- Clinical Analysis Department, Health Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Julia Salvan da Rosa
- Postgraduate Program in Pharmacy, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
- Clinical Analysis Department, Health Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Tainá Larissa Lubschinski
- Postgraduate Program in Pharmacy, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
- Clinical Analysis Department, Health Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Iara Fabricia Kretzer
- Clinical Analysis Department, Health Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Ivete Ioshiko Masukawa
- Infectious Disease Service, University Hospital-Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
- Infectious Disease Service, State Health Department, Hospital Nereu Ramos, Florianópolis, SC, Brazil
| | - Patrícia de Almeida Vanny
- Infectious Disease Service, University Hospital-Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Magali Chaves Luiz
- Infectious Disease Service, State Health Department, Hospital Nereu Ramos, Florianópolis, SC, Brazil
| | - Ana Carolina Rabello de Moraes
- Postgraduate Program in Pharmacy, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
- Clinical Analysis Department, Health Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Maria Claudia Santos-Silva
- Postgraduate Program in Pharmacy, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
- Clinical Analysis Department, Flow Cytometry Service, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
- Clinical Analysis Department, Health Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Eduardo Monguilhott Dalmarco
- Postgraduate Program in Pharmacy, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
- Clinical Analysis Department, Health Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
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Megasari NLA, Khairunisa SQ, Arizandy RY, Wijaksana IKE, Wungu CDK. Cytokine profiles of mild-to-moderate SARS-CoV-2 infected and recovered pre-vaccinated individuals residing in Indonesia. PeerJ 2024; 12:e17257. [PMID: 38646483 PMCID: PMC11032655 DOI: 10.7717/peerj.17257] [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] [Received: 10/19/2023] [Accepted: 03/27/2024] [Indexed: 04/23/2024] Open
Abstract
Background Accumulating evidence suggests the involvement of cytokine-mediated inflammation, in clinical severity and death related to SARS-CoV-2 infection, especially among pre-vaccinated individuals. An increased risk of death was also described among SARS-CoV-2 recovered individuals, which might be correlated with prolonged inflammatory responses. Despite being among the countries with the highest cumulative deaths due to COVID-19, evidence regarding cytokine profiles among SARS-CoV-2 infected and recovered pre-vaccinated individuals in Indonesia is scarce. Thus, this study aimed to describe the cytokines profiles of pre-vaccinated individuals residing in Indonesia, with mild-to-moderate SARS-CoV-2 infection and those who recovered. Methods Sixty-one sera from 24 hospitalized patients with mild-to-moderate SARS-CoV-2 infection, 24 individuals recovered from asymptomatic-to-moderate SARS-CoV-2 infection, and 13 healthy controls unexposed to SARS-CoV-2 were used in this study. Quantification of serum cytokine levels, including IL-6, IL-8, IP-10, TNF-α, CCL-2, CCL-3, CCL-4, and CXCL-13, was performed using a Luminex multi-analyte-profiling (xMAP)-based assay. Results The levels of IL-8 along with CCL-2 and CCL-4, were significantly higher (p ≤ 0.01) in hospitalized patients with mild-to-moderate SARS-CoV-2 infection and recovered individuals compared to healthy controls. However, no significant difference was observed in these cytokine levels between infected and recovered individuals. On the other hand, there were no significant differences in several other cytokine levels, including IL-6, IL-10, TNF-α, CCL-3, and CXCL-13, among all groups. Conclusion IL-8, CCL-2, and CCL-4 were significantly elevated in pre-vaccinated Indonesian individuals with mild-to-moderate SARS-CoV-2 infection and those who recovered. The cytokine profiles described in this study might indicate inflammatory responses not only among SARS-CoV-2 infected, but also recovered individuals.
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Affiliation(s)
- Ni Luh Ayu Megasari
- Institute of Tropical Disease, Airlangga University, Surabaya, Indonesia
- Postgraduate School, Airlangga University, Surabaya, Indonesia
| | | | | | - I. Komang Evan Wijaksana
- Department of Periodontology, Faculty of Dental Medicine, Airlangga University, Surabaya, Indonesia
| | - Citrawati Dyah Kencono Wungu
- Institute of Tropical Disease, Airlangga University, Surabaya, Indonesia
- Department of Physiology and Medical Biochemistry, Faculty of Medicine, Airlangga University, Surabaya, Indonesia
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Roser LP, Samanapally H, Ali T, Xu Q, Han Y, Salunkhe V, Deepti F, McGuffin T, Huang EC, Furmanek S, Glynn A, Ramirez J, Jones CM, Mariyappa R, Hogue RJ, Williams AM, Huang JJ, Arnold FW, Clifford SP, Pahwa S, Kong M, Huang J. Different clinical characteristics and outcomes of adult hospitalized SARS-CoV-2 pneumonia patients complicated by cardiovascular events during the first, delta and omicron waves of COVID-19. FRONTIERS IN EPIDEMIOLOGY 2024; 4:1342917. [PMID: 38699405 PMCID: PMC11064795 DOI: 10.3389/fepid.2024.1342917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 03/04/2024] [Indexed: 05/05/2024]
Abstract
Background The effects of SARS-CoV-2 have varied between significant waves of hospitalization. Research question Are cardiovascular complications different among the first, delta and omicron waves of hospitalized COVID-19 pneumonia patients? Study design and methods This was a multi-centre retrospective study of patients hospitalized with SARS-CoV-2 pneumonia: 632 were hospitalized during the first wave (March-July 2020), 1013 during the delta wave (September 2020-March 2021), and 323 during the omicron wave (January 2022-July 2022). Patients were stratified by wave and occurrence of cardiovascular events. Results Among all hospitalized patients with cardiovascular events, patients in the omicron wave were younger (62.4 ± 14 years) than patients in the first wave (67.4 ± 7.8 years) and the delta wave (66.9 ± 12.6 years) and had a higher proportion of non-Hispanic White people than in the first wave (78.6% vs. 61.7%). For COVID-19 patients who suffered from cardiovascular events, the omicron wave patients had significantly higher neutrophil/lymphocyte ratio, white blood cell and platelet counts when compared to the first wave. Omicron wave patients had significantly lower albumin and B-type natriuretic peptide levels (only 5.8% of the first wave and 14.6% of the delta wave) when compared to either the first wave or delta wave patients. In COVID-19 patients who suffered cardiovascular events during hospitalization, mortality rate in the omicron wave (26.8%) was significantly lower than the first wave (48.3%), time to mortality for non-survivors of COVID-19 patients who suffered cardiovascular events was significantly longer in the omicron wave (median 16 days) than in the first wave (median 10 days). Conclusions Younger and white patients were affected with cardiovascular complications more often by the omicron variant. Despite higher neutrophil/lymphocyte ratio and WBC counts, the omicron patients with cardiovascular events showed lower heart injuries, lower mortality and longer time to mortality for non-survivors when compared to the first and delta waves.
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Affiliation(s)
- Lynn P. Roser
- School of Nursing, University of Louisville, Louisville, KY, United States
| | - Harideep Samanapally
- Division of Infectious Diseases, Centre of Excellence for Research in Infectious Diseases (CERID), University of Louisville, Louisville, KY, United States
| | - T’shura Ali
- Division of Infectious Diseases, Centre of Excellence for Research in Infectious Diseases (CERID), University of Louisville, Louisville, KY, United States
| | - Qian Xu
- Department of Bioinformatics and Biostatistics, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, United States
| | - Yuchen Han
- Department of Bioinformatics and Biostatistics, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, United States
| | - Vidyulata Salunkhe
- Division of Infectious Diseases, Centre of Excellence for Research in Infectious Diseases (CERID), University of Louisville, Louisville, KY, United States
| | - Fnu Deepti
- Division of Infectious Diseases, Centre of Excellence for Research in Infectious Diseases (CERID), University of Louisville, Louisville, KY, United States
| | - Trevor McGuffin
- School of Nursing, University of Louisville, Louisville, KY, United States
| | - Emma C. Huang
- Department of Anesthesiology, Duke University, Durham, NC, United States
| | - Stephen Furmanek
- Division of Infectious Diseases, Centre of Excellence for Research in Infectious Diseases (CERID), University of Louisville, Louisville, KY, United States
| | - Alex Glynn
- Kornhauser Health Sciences Library, University of Louisville, Louisville, KY, United States
| | - Julio Ramirez
- Division of Infectious Diseases, Centre of Excellence for Research in Infectious Diseases (CERID), University of Louisville, Louisville, KY, United States
| | - Christopher M. Jones
- Division of Transplantation, Department of Surgery, University of Louisville, Louisville, KY, United States
| | - Ramesh Mariyappa
- Department of Anesthesiology & Perioperative Medicine, University of Louisville, Louisville, KY, United States
| | - Ryan J. Hogue
- Department of Anesthesiology & Perioperative Medicine, University of Louisville, Louisville, KY, United States
| | - Alexander M. Williams
- Department of Anesthesiology & Perioperative Medicine, University of Louisville, Louisville, KY, United States
| | - Justin J. Huang
- Department of Anesthesiology & Perioperative Medicine, University of Louisville, Louisville, KY, United States
| | - Forest W. Arnold
- Division of Infectious Diseases, Centre of Excellence for Research in Infectious Diseases (CERID), University of Louisville, Louisville, KY, United States
| | - Sean P. Clifford
- Department of Anesthesiology & Perioperative Medicine, University of Louisville, Louisville, KY, United States
| | - Siddharth Pahwa
- Department of Cardiovascular & Thoracic Surgery, University of Louisville, Louisville, KY, United States
| | - Maiying Kong
- Department of Bioinformatics and Biostatistics, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, United States
| | - Jiapeng Huang
- Division of Infectious Diseases, Centre of Excellence for Research in Infectious Diseases (CERID), University of Louisville, Louisville, KY, United States
- Department of Anesthesiology & Perioperative Medicine, University of Louisville, Louisville, KY, United States
- Department of Cardiovascular & Thoracic Surgery, University of Louisville, Louisville, KY, United States
- Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, United States
- Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, KY, United States
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Cadore NA, Lord VO, Recamonde-Mendoza M, Kowalski TW, Vianna FSL. Meta-analysis of Transcriptomic Data from Lung Autopsy and Cellular Models of SARS-CoV-2 Infection. Biochem Genet 2024; 62:892-914. [PMID: 37486510 DOI: 10.1007/s10528-023-10453-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 07/12/2023] [Indexed: 07/25/2023]
Abstract
Severe COVID-19 is a systemic disorder involving excessive inflammatory response, metabolic dysfunction, multi-organ damage, and several clinical features. Here, we performed a transcriptome meta-analysis investigating genes and molecular mechanisms related to COVID-19 severity and outcomes. First, transcriptomic data of cellular models of SARS-CoV-2 infection were compiled to understand the first response to the infection. Then, transcriptomic data from lung autopsies of patients deceased due to COVID-19 were compiled to analyze altered genes of damaged lung tissue. These analyses were followed by functional enrichment analyses and gene-phenotype association. A biological network was constructed using the disturbed genes in the lung autopsy meta-analysis. Central genes were defined considering closeness and betweenness centrality degrees. A sub-network phenotype-gene interaction analysis was performed. The meta-analysis of cellular models found genes mainly associated with cytokine signaling and other pathogen response pathways. The meta-analysis of lung autopsy tissue found genes associated with coagulopathy, lung fibrosis, multi-organ damage, and long COVID-19. Only genes DNAH9 and FAM216B were found perturbed in both meta-analyses. BLNK, FABP4, GRIA1, ATF3, TREM2, TPPP, TPPP3, FOS, ALB, JUNB, LMNA, ADRB2, PPARG, TNNC1, and EGR1 were identified as central elements among perturbed genes in lung autopsy and were found associated with several clinical features of severe COVID-19. Central elements were suggested as interesting targets to investigate the relation with features of COVID-19 severity, such as coagulopathy, lung fibrosis, and organ damage.
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Affiliation(s)
- Nathan Araujo Cadore
- Laboratory of Genomic Medicine, Center of Experimental Research, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
- Laboratory of Immunobiology and Immunogenetics, Department of Genetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Post-Graduation Program in Genetics and Molecular Biology, Department of Genetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Vinicius Oliveira Lord
- Laboratory of Genomic Medicine, Center of Experimental Research, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
- Centro Universitário CESUCA, Cachoeirinha, Brazil
| | - Mariana Recamonde-Mendoza
- Bioinformatics Core, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
- Institute of Informatics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Thayne Woycinck Kowalski
- Laboratory of Genomic Medicine, Center of Experimental Research, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
- Post-Graduation Program in Genetics and Molecular Biology, Department of Genetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Centro Universitário CESUCA, Cachoeirinha, Brazil
- Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
| | - Fernanda Sales Luiz Vianna
- Laboratory of Genomic Medicine, Center of Experimental Research, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
- Laboratory of Immunobiology and Immunogenetics, Department of Genetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
- Post-Graduation Program in Genetics and Molecular Biology, Department of Genetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
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Cai W, Zhao Y, Mallappa S. Scoping Review of Clinical Presentations and Outcomes in Patients with Concomitant COVID-19 Infection and Acute Mesenteric Ischaemia. Viruses 2024; 16:506. [PMID: 38675849 PMCID: PMC11054494 DOI: 10.3390/v16040506] [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: 01/15/2024] [Revised: 03/21/2024] [Accepted: 03/22/2024] [Indexed: 04/28/2024] Open
Abstract
OBJECTIVES COVID-19 infection confers an increased risk of coagulation dysfunction (1) predisposing to thromboembolism in many anatomical sites including the gastrointestinal tract (GIT) (2). This study investigates the clinical presentation and outcome in patients presenting with concurrent COVID-19 infection and gastrointestinal tract ischaemia. Furthermore, differentiation and comparisons are drawn between those with arterial and venous aetiology for mesenteric ischaemia. METHODS A systematic search was undertaken on EMBASE, PubMed, and MEDLINE. Two independent reviewers screened titles, abstracts, and full-text articles according to the inclusion criteria and extracted relevant data. Data analyses were conducted using Excel®. RESULTS Forty-one studies were included in the data analyses, yielding 44 patients. Twenty-six patients had mesenteric arterial occlusion, sixteen patients had mesenteric venous occlusion, and two patients had both arterial and venous mesenteric occlusion. All patients had concurrent COVID-19 infection. The survival rate in patients with arterial aetiology was 38.5% in contrast to 68.8% in patients with venous aetiology. Twelve patients (29.3%) experienced respiratory symptoms in the community before the onset of gastrointestinal symptoms, and five (12.2%) developed gastrointestinal symptoms during their inpatient stay for COVID-19 pneumonitis. CONCLUSIONS Acute mesenteric ischaemia presents a clinical challenge to diagnose due to its non-specific symptoms. Concurrent COVID-19 infection with its predominant respiratory symptoms adds a further challenge in recognising the non-specific symptoms of mesenteric ischaemia. Our study draws attention to the increased thromboembolic risk posed by COVID-19 infection and the need for a high index of suspicion to aid prompt diagnosis and management of acute mesenteric ischaemia, even in the post-pandemic era.
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Affiliation(s)
- Wenyi Cai
- East Suffolk and North Essex Foundation Trust, Colchester CO4 5JL, UK
- Colchester General Hospital, Turner Road, Colchester CO4 5JL, UK
| | - Yi Zhao
- Imperial College London School of Medicine, London SW7 2DD, UK;
| | - Sreelakshmi Mallappa
- West Hertfordshire Teaching Hospitals NHS Trust, Hertfordshire WD18 0HB, UK;
- The Hillingdon Hospitals NHS Foundation Trust, Uxbridge UB8 3NN, UK
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22
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Christopher S, Dutta S, Gopal TVS. Bilateral pericapsular end nerve blocks for steroid-induced avascular necrosis following COVID-19 infection requiring bilateral total hip replacement. World J Anesthesiol 2024; 13:90514. [DOI: 10.5313/wja.v13.i1.90514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 01/05/2024] [Accepted: 02/25/2024] [Indexed: 03/08/2024] Open
Abstract
BACKGROUND Osteonecrosis or avascular necrosis (AVN) of the hip was one of the dreaded complications of coronavirus disease 2019 (COVID-19), which emerged in patients who received steroid therapy. Corticosteroids have been a mainstay in the treatment protocol of COVID-19 patients. Popular corticosteroid drugs used in patients suffering from COVID-19 were intravenous (IV) or oral dexamethasone, methylprednisolone or hydrocortisone. The use of such high doses of corticosteroids has shown very positive results and has been lifesaving in many cases. Still, long-term consequences were drug-induced diabetes, osteoporosis, Cushing syndrome, muscle wasting, peripheral fat mobilization, AVN, hirsutism, sleep disturbances and poor wound healing. A significant number of young patients were admitted for bilateral total hip replacements (THR) secondary to AVN following steroid use for COVID-19 treatment.
AIM To assess the efficacy of bilateral pericapsular end nerve group (PENG) blocks in patients posted for bilateral THR post-steroid therapy after COVID-19 infection and assess the time taken to first ambulate after surgery.
METHODS This prospective observational study was conducted between January 2023 and August 2023 at Care Hospitals, Hyderabad, India. Twenty young patients 30-35 years of age who underwent bilateral THR were studied after due consent over 8 months. All the patients received spinal anaesthesia for surgery and bilateral PENG blocks for postoperative analgesia.
RESULTS The duration of surgery was 2.5 h on average. Seventeen out of twenty patients (85%) had a Visual Analog Score (VAS) of less than 2 and did not require any supplementation. One patient was removed from the study, as he required re-exploration. The remaining two patients had a VAS of more than 8 and received IV morphine post-operatively as a rescue analgesic drug. Fifteen out of seventeen patients (88.2%) could be mobilized 12 h after the procedure.
CONCLUSION Osteonecrosis or AVN of the hip was one of the dreaded complications of COVID-19, which surfaced in patients who received steroid therapy requiring surgical intervention. Bilateral PENG block is an effective technique to provide post-operative analgesia resulting in early mobilization and enhanced recovery after surgery.
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Affiliation(s)
| | - Sweety Dutta
- Department of Anaesthesiology, Care Hospitals, Hyderabad 500025, India
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23
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Perkins RK, Lavin KM, Raue U, Jemiolo B, Trappe SW, Trappe TA. Effects of aging and lifelong aerobic exercise on expression of innate immune components in skeletal muscle of women. J Appl Physiol (1985) 2024; 136:482-491. [PMID: 38205547 PMCID: PMC11212804 DOI: 10.1152/japplphysiol.00444.2023] [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: 07/03/2023] [Revised: 12/21/2023] [Accepted: 01/04/2024] [Indexed: 01/12/2024] Open
Abstract
This study examined the effects of aging and lifelong aerobic exercise on innate immune system components in the skeletal muscle of healthy women in the basal state and after an unaccustomed resistance exercise (RE) challenge. We also made exploratory between-sex comparisons with our previous report on men. Three groups of women were studied: young exercisers (YE, n = 10, 25 ± 1 yr, V̇o2max: 44 ± 2 mL/kg/min), lifelong aerobic exercisers with a 48 ± 2 yr training history (LLE, n = 7, 72 ± 2 yr, V̇o2max: 26 ± 2 mL/kg/min), and old healthy nonexercisers (OH, n = 10, 75 ± 1 yr, V̇o2max: 18 ± 1 mL/kg/min). Ten Toll-like receptors (TLRs)1-10, TLR adaptors (Myd88, TRIF), and NF-κB pathway components (IκBα, IKKβ) were assessed at the mRNA level in vastus lateralis biopsies before and 4 h after RE [3×10 repetitions, 70% 1-repetition maximum (1RM)]. Basal TLR1-10 expression was minimally influenced by age or LLE in women (TLR9 only; OH > YE, +43%, P < 0.05; OH > LLE, +30%, P < 0.10) and was on average 24% higher in women versus men. Similarly, basal adaptor expression was not influenced (P > 0.05) by age or LLE in women but was on average 26% higher (myeloid differentiation primary response 88, Myd88) and 23% lower [Toll interleukin (IL)-1 receptor-containing adaptor-inducing interferon-γ, TRIF] in women versus men. RE-induced changes in women, independent of the group, in TLR3, TLR4, TLR6 (∼2.1-fold, P < 0.05), Myd88 (∼1.2-fold, P < 0.10), and IκBα (∼0.3-fold, P < 0.05). Although there were some similar RE responses in men (TLR4: 2.1-fold, Myd88: 1.2-fold, IκBα: 0.4-fold), several components responded only in men to RE (TLR1, TLR8, TRIF, and IKKβ). Our findings support the sexual dimorphism of immunity, with women having greater basal skeletal muscle TLR expression and differential response to unaccustomed exercise than men.NEW & NOTEWORTHY We recently reported that aging increases basal expression of many Toll-like receptors (TLRs) in men and lifelong aerobic exercise does not prevent this effect. In addition, a resistance exercise (RE) challenge increased the expression of many TLRs. Here we show that basal TLR expression is minimally influenced by aging in women and findings support the sexual dimorphism of immunity, with women having greater basal skeletal muscle TLR expression and a differential response to unaccustomed exercise than men.
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Affiliation(s)
- Ryan K Perkins
- Human Performance Laboratory, Ball State University, Muncie, Indiana, United States
| | - Kaleen M Lavin
- Human Performance Laboratory, Ball State University, Muncie, Indiana, United States
| | - Ulrika Raue
- Human Performance Laboratory, Ball State University, Muncie, Indiana, United States
| | - Bozena Jemiolo
- Human Performance Laboratory, Ball State University, Muncie, Indiana, United States
| | - Scott W Trappe
- Human Performance Laboratory, Ball State University, Muncie, Indiana, United States
| | - Todd A Trappe
- Human Performance Laboratory, Ball State University, Muncie, Indiana, United States
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24
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Fernández-de-las-Peñas C, Díaz-Gil G, Gil-Crujera A, Gómez-Sánchez SM, Ambite-Quesada S, Torres-Macho J, Ryan-Murua P, Franco-Moreno AI, Pellicer-Valero OJ, Arendt-Nielsen L, Giordano R. Inflammatory Polymorphisms (IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252) Are Not Associated with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors. Viruses 2024; 16:275. [PMID: 38400050 PMCID: PMC10891518 DOI: 10.3390/v16020275] [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: 01/11/2024] [Revised: 02/05/2024] [Accepted: 02/08/2024] [Indexed: 02/25/2024] Open
Abstract
The aim of this study was to identify the association between four selected inflammatory polymorphisms with the development of long-term post-COVID symptoms in subjects who had been hospitalized due to SARS-CoV-2 infection during the first wave of the pandemic. These polymorphisms were selected as they are associated with severe COVID-19 disease and cytokine storm, so they could be important to prognoses post-COVID. A total of 408 (48.5% female, age: 58.5 ± 14.0 years) previously hospitalized COVID-19 survivors participated. The three potential genotypes of the following four single-nucleotide polymorphisms, IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252, were obtained from non-stimulated saliva samples of the participants. The participants were asked to self-report the presence of any post-COVID symptoms (defined as symptoms that had started no later than one month after SARS-CoV-2 acute infection) and whether the symptoms persisted at the time of the study. At the time of the study (mean: 15.6, SD: 5.6 months after discharge), 89.4% of patients reported at least one post-COVID symptom (mean number of symptoms: 3.0; SD: 1.7). Fatigue (69.3%), pain (40.9%), and memory loss (27.2%) were the most prevalent post-COVID symptoms in the total sample. Overall, no differences in the post-COVID symptoms depending on the IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252 genotypes were seen. The four SNPs assessed, albeit having been previously associated with inflammation and COVID-19 severity, did not cause a predisposition to the development of post-COVID symptoms in the previously hospitalized COVID-19 survivors.
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Affiliation(s)
- César Fernández-de-las-Peñas
- Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain;
- Center for Neuroplasticity and Pain (CNAP), Sensory Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark; (L.A.-N.); (R.G.)
| | - Gema Díaz-Gil
- Research group GAMDES, Department of Basic Health Sciences, Universidad Rey Juan Carlos (URJC), 28933 Madrid, Spain; (G.D.-G.); (A.G.-C.); (S.M.G.-S.)
| | - Antonio Gil-Crujera
- Research group GAMDES, Department of Basic Health Sciences, Universidad Rey Juan Carlos (URJC), 28933 Madrid, Spain; (G.D.-G.); (A.G.-C.); (S.M.G.-S.)
| | - Stella M. Gómez-Sánchez
- Research group GAMDES, Department of Basic Health Sciences, Universidad Rey Juan Carlos (URJC), 28933 Madrid, Spain; (G.D.-G.); (A.G.-C.); (S.M.G.-S.)
| | - Silvia Ambite-Quesada
- Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain;
| | - Juan Torres-Macho
- Department of Internal Medicine, Hospital Universitario Infanta Leonor-Virgen de la Torre, 28031 Madrid, Spain; (J.T.-M.); (P.R.-M.); (A.I.F.-M.)
- Department of Medicine, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Pablo Ryan-Murua
- Department of Internal Medicine, Hospital Universitario Infanta Leonor-Virgen de la Torre, 28031 Madrid, Spain; (J.T.-M.); (P.R.-M.); (A.I.F.-M.)
| | - Ana I. Franco-Moreno
- Department of Internal Medicine, Hospital Universitario Infanta Leonor-Virgen de la Torre, 28031 Madrid, Spain; (J.T.-M.); (P.R.-M.); (A.I.F.-M.)
| | - Oscar J. Pellicer-Valero
- Image Processing Laboratory (IPL), Universitat de València, Parc Científic, Paterna, 46100 València, Spain;
| | - Lars Arendt-Nielsen
- Center for Neuroplasticity and Pain (CNAP), Sensory Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark; (L.A.-N.); (R.G.)
- Department of Gastroenterology & Hepatology, Mech-Sense, Clinical Institute, Aalborg University Hospital, DK-9000 Aalborg, Denmark
- Steno Diabetes Center North Denmark, Clinical Institute, Aalborg University Hospital, DK-9000 Aalborg, Denmark
| | - Rocco Giordano
- Center for Neuroplasticity and Pain (CNAP), Sensory Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark; (L.A.-N.); (R.G.)
- Department of Oral and Maxillofacial Surgery, Aalborg University Hospital, DK-9000 Aalborg, Denmark
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25
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Mageau A, Helary A, Ruckly S, Strukov A, Papo T, Timsit JF, Sacre K. High incidence of immune-mediated inflammatory diseases in sepsis survivors: A nationwide exposed-nonexposed epidemiological study. J Intern Med 2024; 295:242-252. [PMID: 37983848 DOI: 10.1111/joim.13745] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2023]
Abstract
OBJECTIVE Sepsis is characterized by an excessive release of inflammatory cytokines. Cytokine dysregulation is pivotal to the pathophysiology of immune-mediated inflammatory diseases (IMIDs). We aimed to analyze the incidence of IMIDs in patients who survived sepsis. METHODS We performed a matched-cohort study using the National Medico-Administrative Hospital database in order to analyze the association between sepsis and incident IMIDs in 2020 in France. Sepsis was defined by the combination of at least one infection diagnosis code and one organ failure code. Patients with a first sepsis diagnosed in 2020 were randomly matched with patients admitted during the same period for acute myocardial infarction (AMI) with an exact matching procedure using age, gender, and comorbidities as matching variables. The main outcome was an IMID diagnosis in a 9-month follow-up period starting the first day of hospitalization for sepsis or AMI. RESULTS In France, the incidence rate of IMIDs after a sepsis in 2020-analyzed in 62,257 patients-was of 7956 (95% confidence interval [95% CI] 7392-8520) per 100,000 patient-years. As compared to the AMI population, we observed an increased risk for IMIDs of 2.80 (hazard ratio [HR]; 95% CI [2.22-3.54]) starting from day 16 after admission in the sepsis population. The risk of IMIDs onset in sepsis survivors depended on the type of IMIDs and was higher for immune thrombocytopenia (5.51 [1.97-15.4]), autoimmune hemolytic anemia (HR 4.83 [1.45-16.1]), and antineutrophil cytoplasmic antibody-associated vasculitis (4.66 [2.05-10.6]). Association between sepsis and IMIDs onset appeared well balanced across pathogen categories. CONCLUSION Our study shows a high incidence of IMIDs among sepsis survivors.
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Affiliation(s)
- Arthur Mageau
- IAME, UMR 1137 INSERM, Team Descid Université Paris Cité and Université Sorbonne Paris Nord, Paris, France
- Département de Médecine Interne, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France
- CRI, UMR 1149 INSERM, ERL 8252 CNRS, LabEx Inflamex, Université Paris Cité, Paris, France
| | - Aloïs Helary
- IAME, UMR 1137 INSERM, Team Descid Université Paris Cité and Université Sorbonne Paris Nord, Paris, France
- Département de Médecine Interne, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France
| | - Stephane Ruckly
- IAME, UMR 1137 INSERM, Team Descid Université Paris Cité and Université Sorbonne Paris Nord, Paris, France
- OUTCOME REA network, Drancy, France
| | - Andrey Strukov
- Département d'Information Médicale, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France
| | - Thomas Papo
- Département de Médecine Interne, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France
- CRI, UMR 1149 INSERM, ERL 8252 CNRS, LabEx Inflamex, Université Paris Cité, Paris, France
| | - Jean-François Timsit
- IAME, UMR 1137 INSERM, Team Descid Université Paris Cité and Université Sorbonne Paris Nord, Paris, France
- Département de Réanimation Médicale et Infectieuse, AP-HP, Hôpital Bichat-Claude-Bernard, Paris, France
| | - Karim Sacre
- Département de Médecine Interne, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France
- CRI, UMR 1149 INSERM, ERL 8252 CNRS, LabEx Inflamex, Université Paris Cité, Paris, France
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26
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Fernández-de-Las-Peñas C, Torres-Macho J, Catahay JA, Macasaet R, Velasco JV, Macapagal S, Caldararo M, Henry BM, Lippi G, Franco-Moreno A, Notarte KI. Is antiviral treatment at the acute phase of COVID-19 effective for decreasing the risk of long-COVID? A systematic review. Infection 2024; 52:43-58. [PMID: 38113020 DOI: 10.1007/s15010-023-02154-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 12/04/2023] [Indexed: 12/21/2023]
Abstract
PURPOSE Preliminary evidence suggests a potential effect of antiviral medication used during the acute COVID-19 phase for preventing long-COVID. This review investigates if having received pharmacological treatment during acute SARS-CoV-2 infection may reduce the risk of long-COVID. METHODS MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to July 15th, 2023. Articles comparing the presence of long-COVID symptoms between individuals who received or not a specific medication, particularly antivirals, during the acute phase of SARS-CoV-2 infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool. RESULTS From 517 studies identified, 6 peer-reviewed studies and one preprint met all inclusion criteria. The sample included 2683 (n = 4) hospitalized COVID-19 survivors and 307,409 (n = 3) non-hospitalized patients. The methodological quality was high in 71% of studies (n = 5/7). Two studies investigating the effects of Nirmaltrevir/Ritonavir and three studies the effect of Remdesivir reported conflicting results on effectiveness for preventing long-COVID. Three studies investigating the effects of other medication such as Dexamethasone (n = 2) or Metformin (n = 1) found positive results of these medications for preventing long-COVID. CONCLUSION Available evidence about the effect of medication treatment with antivirals during acute COVID-19 and reduced risk of developing long-COVID is conflicting. Heterogeneous evidence suggests that Remdesivir or Nirmaltrevir/Ritonavir could have a potential protective effect for long-COVID. A limited number of studies demonstrated a potential benefit of other medications such as Dexamethasone or Metformin, but more studies are needed.
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Affiliation(s)
- César Fernández-de-Las-Peñas
- Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos (URJC), Universidad Rey Juan Carlos, Avenida de Atenas S/N, 28922, Alcorcón, Madrid, Spain.
| | - Juan Torres-Macho
- Department of Internal Medicine, Hospital Universitario Infanta Leonor-Virgen de La Torre, Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | | | - Raymart Macasaet
- Department of Medicine, Monmouth Medical Center, Long Branch, NJ, USA
| | | | - Sharina Macapagal
- Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, USA
| | - Mario Caldararo
- Department of Medicine, Saint Peter's University Hospital, New Brunswick, NJ, USA
| | - Brandon Michael Henry
- Clinical Laboratory, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy
| | - Ana Franco-Moreno
- Department of Internal Medicine, Hospital Universitario Infanta Leonor-Virgen de La Torre, Madrid, Spain
| | - Kin Israel Notarte
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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27
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Eldesouki RE, Kishk RM, Abd El-Fadeal NM, Mahran RI, Kamel N, Riad E, Nemr N, Kishk SM, Mohammed EAM. Association of IL-10-592 C > A /-1082 A > G and the TNFα -308 G > A with susceptibility to COVID-19 and clinical outcomes. BMC Med Genomics 2024; 17:40. [PMID: 38287362 PMCID: PMC10826193 DOI: 10.1186/s12920-023-01793-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Accepted: 12/31/2023] [Indexed: 01/31/2024] Open
Abstract
BACKGROUND Variation in host immune responses to SARS-CoV-2 is regulated by multiple genes involved in innate viral response and cytokine storm emergence like IL-10 and TNFa gene polymorphisms. We hypothesize that IL-10; -592 C > A and - 1082 A > G and TNFa-308 G > A are associated with the risk of SARS-COV2 infections and clinical outcome. METHODS Genotyping, laboratory and radiological investigations were done to 110 COVID-19 patients and 110 healthy subjects, in Ismailia, Egypt. RESULTS A significant association between the - 592 A allele, A containing genotypes under all models (p < 0.0001), and TNFa A allele with risk to infection was observed but not with the G allele of the - 1082. The - 592 /-1082 CG and the - 592 /-1082/ -308 CGG haplotypes showed higher odds in COVID-19 patients. Severe lung affection was negatively associated with - 592, while positive association was observed with - 1082. Higher D-dimer levels were strongly associated with the - 1082 GG genotype. Survival outcomes were strongly associated with the GA genotype of TNFa. -308 as well as AGG and AAA haplotypes. CONCLUSION IL-10 and TNFa polymorphisms should be considered for clinical and epidemiological evaluation of COVID-19 patients.
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Affiliation(s)
- Raghda E Eldesouki
- Genetics Unit, Histology Department, Faculty of Medicine, Suez Canal University, 41522, Ismailia, Egypt.
| | - Rania M Kishk
- Microbiology and immunology Department, Faculty of Medicine, Suez Canal University, Ismaila, Egypt
| | - Noha M Abd El-Fadeal
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Suez Canal University, Ismaila, Egypt
- Biochemistry Department, Ibn Sina National College for Medical Studies, Jeddah, Kingdom of Saudi Arabia
| | - Rama I Mahran
- Clinical Pharmacology Department, Faculty of Medicine, Suez Canal University, Ismaila, Egypt
| | - Noha Kamel
- Clinical Pathology Department, Faculty of Medicine, Suez Canal University, Ismaila, Egypt
| | - Eman Riad
- Pulmonology Unit, Internal Medicine Department, Faculty of Medicine, Suez Canal University, Ismaila, Egypt
| | - Nader Nemr
- Endemic and Infectious Diseases Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Safaa M Kishk
- Pharmaceutical Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
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28
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van de Veerdonk FL. COVID-19 Pneumonia and Cytokine Storm Syndrome. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1448:307-319. [PMID: 39117824 DOI: 10.1007/978-3-031-59815-9_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/10/2024]
Abstract
Virus-associated cytokine storm syndrome (CSS) has been recognized for a long time and the classic viruses associated are the herpes viruses EBV, CMV, and HHV-8 as described in chapters IVa,b. In addition, pandemic viruses such as influenza, SARS, and MERS can result in severe CSS that might ultimately lead to severe acute respiratory distress syndrome (ARDS) and death [1-3]. A new pandemic caused by SARS-CoV-2 that started in 2019 has defined another chapter in the virus-associated CSS. The clinical spectrum of SARS-CoV-2 infection has many faces. In most people, it will be asymptomatic, but it can also result in severe COVID-19 pneumonia, ARDS, and multiorgan failure depending on age, comorbidities, and immune status [4]. In addition, this pandemic has known many different stages and developed in a unique way in the first 2 years. It started in a setting where there was no immunity to the virus and after a year, highly effective vaccines were introduced and herd immunity built up over time. However, vaccine effectiveness was waning over time depending on multiple factors, and novel variant strains of the virus circulated across different areas in the world. Antiviral therapy was developed and introduced, and treatment changed from giving no immunomodulatory treatment, followed by the introduction of corticosteroids [5], and later the addition of more targeted strategies such as JAK inhibitors [6] and blocking IL-6 signaling [7]. Therefore, the scientific literature published on COVID-19 must be seen in the context of a highly dynamic and rapidly changing pandemic, making it difficult to compare results from early studies to more recent reports even within 2 years. Still, a lot has been learned over a very short period. It has become apparent that severe COVID-19 is predominantly a disease of immune dysregulation with components that can be defined as CSS. It has unique features and overlapping characteristics with other CSSs, and immunological treatment addressing the CSS has been extensively explored, which will be described here.
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29
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Leeyaphan C, Jirawattanadon P, Bunyaratavej S, Panjapakkul W, Hutachoke T, Nanchaipruek Y, Phumariyapong P. Herpes Zoster after COVID-19 Infection or Vaccination: A Prospective Cohort Study in a Tertiary Dermatology Clinic. Dermatol Res Pract 2023; 2023:2206498. [PMID: 38188702 PMCID: PMC10771922 DOI: 10.1155/2023/2206498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 10/24/2023] [Accepted: 11/25/2023] [Indexed: 01/09/2024] Open
Abstract
Background Herpes zoster (HZ) has been observed to occur after COVID-19 infection and vaccination; however, knowledge regarding the demographic data, clinical presentations, and treatment outcomes of HZ is limited. Objective To compare the demographic data, clinical manifestations, treatments, and outcomes of patients with and without HZ within 14 days of COVID-19 infection or vaccination. Methods This prospective cohort study involving patients diagnosed with cutaneous HZ was conducted at a dermatology clinic from October 2021 to January 2023. Results Among a total of 232 patients with HZ, the median age was 62.0 years and 59.1% were female. HZ developed in 23 (9.9%) and four (1.7%) patients after COVID-19 vaccination and infection, respectively. The mean duration from vaccination and the median duration from infection to HZ onset were 5.7 and 8.5 days, respectively. The proportion of female patients was significantly higher in the group of patients with COVID-19 vaccination or infection than in those without such a history (P = 0.035). Patients who developed HZ following the recent COVID-19 infection had a median age of 42.5 years, which was lower than that of the other groups. Dissemination occurred in 8.7% of the patients after COVID-19 vaccination. HZ recurrence was reported in five cases, of which 80% had been vaccinated or infected with COVID-19 during the previous 21 days. All patients had similar durations of antiviral treatment, crust-off time, and duration of neuralgia. Conclusions HZ after COVID-19 vaccination is more frequently observed in females, while HZ after COVID-19 infection tends to occur in younger patients. Disseminated HZ is more common in patients recently vaccinated against COVID-19. COVID-19 vaccination or infection may trigger recurrent HZ infection.
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Affiliation(s)
- Charussri Leeyaphan
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Pattriya Jirawattanadon
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sumanas Bunyaratavej
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Waratchaya Panjapakkul
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Thrit Hutachoke
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Yanisorn Nanchaipruek
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Phumithep Phumariyapong
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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30
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Castaldo M, Ebbesen BD, Fernández-DE-Las-Peñas C, Arendt-Nielsen L, Giordano R. COVID-19 and musculoskeletal pain: an overview of the current knowledge. Minerva Anestesiol 2023; 89:1134-1142. [PMID: 38019176 DOI: 10.23736/s0375-9393.23.17471-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2023]
Abstract
The Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has provoked billions of infections worldwide. Several meta-analyses have observed that up to 50% of individuals who had survived to a SARS-CoV-2 acute infection suffer from post-COVID symptoms lasting for weeks or months and up to one year after infection. The prevalence of post-COVID pain ranges between 10% to 20% when assessed with other overall post-COVID symptoms and can reach up to 50% to 60% when investigated specifically. The most common musculoskeletal manifestations of post-COVID-19 condition include fatigue, myalgia, arthralgia or back pain. Despite pain of musculoskeletal origin is one of the most prevalent post-COVID pain symptoms, the exact pathophysiological mechanisms of musculoskeletal post-COVID pain are not completely understood. Studies have reported the complexity of post-COVID pain including immune, biological, and psychological factors, and more recently, they have suggested that genetic and epigenetic factors may also play a potential role, highlighting the need for further investigation into these mechanisms. Its management is still controversial, as no specific guideline for treating musculoskeletal post-COVID pain has been proposed with only general consideration about the relevance of multidisciplinary and multimodal treatment approaches. In this paper we will highlight the clinical features, the mechanism, and the management possibilities of musculoskeletal post-COVID pain.
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Affiliation(s)
- Matteo Castaldo
- School of Medicine, Center for Neuroplasticity and Pain, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark -
| | - Brian D Ebbesen
- School of Medicine, Center for Neuroplasticity and Pain, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
- Department of Gastroenterology and Hepatology, Mech-Sense, Aalborg University Hospital, Aalborg, Denmark
| | - César Fernández-DE-Las-Peñas
- School of Medicine, Center for Neuroplasticity and Pain, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
- Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos (URJC), Alcorcón, Spain
| | - Lars Arendt-Nielsen
- School of Medicine, Center for Neuroplasticity and Pain, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
- Department of Gastroenterology and Hepatology, Mech-Sense, Aalborg University Hospital, Aalborg, Denmark
- Steno Diabetes Center North Denmark, Clinical Institute, Aalborg University Hospital, Aalborg, Denmark
| | - Rocco Giordano
- School of Medicine, Center for Neuroplasticity and Pain, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
- Department of Oral and Maxillofacial Surgery, Aalborg University Hospital, Aalborg, Denmark
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Hoang Roberts L, Zwaans BM, Jabbar K, Bartolone SN, Padmanabhan P, Peters KM. Fibrin microthrombi in bladder urothelium after SARS-CoV-2 infection: Case report. Urol Case Rep 2023; 51:102575. [PMID: 37829494 PMCID: PMC10565678 DOI: 10.1016/j.eucr.2023.102575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 09/24/2023] [Indexed: 10/14/2023] Open
Abstract
A 45-year-old male with diabetes, hypertension and hyperlipidemia was referred to urology due to persistent symptoms of urinary frequency, urgency, nocturia, erectile dysfunction, and constant pain localized to the bladder, pelvis, and perineal area, 3-4 months after SARS-CoV-2 infection. A bladder biopsy showed urothelial mucosa and submucosa with hemorrhage and fibrin microthrombi in blood vessels. Hydrodistention of the bladder and pelvic floor physical therapy resolved symptoms, though bladder and pain symptoms returned upon reinfection with SARS-CoV-2. Urinalysis revealed elevated urinary interleukin-8, which may indicate localized bladder inflammation.
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Affiliation(s)
| | - Bernadette M.M. Zwaans
- Department of Urology, Corewell Health, Royal Oak, MI, USA
- Oakland University William Beaumont School of Medicine, Rochester, MI, USA
| | - Kausar Jabbar
- Department of Pathology, Beaumont Health, Royal Oak, MI, USA
| | | | - Priya Padmanabhan
- Department of Urology, Corewell Health, Royal Oak, MI, USA
- Oakland University William Beaumont School of Medicine, Rochester, MI, USA
| | - Kenneth M. Peters
- Department of Urology, Corewell Health, Royal Oak, MI, USA
- Oakland University William Beaumont School of Medicine, Rochester, MI, USA
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Jain S, Allen IE, Song D, Piao X. Cytokine responses to SARS-COV2 infection in mother-infant dyads: a systematic review and meta-analysis. Front Pediatr 2023; 11:1277697. [PMID: 37915987 PMCID: PMC10616592 DOI: 10.3389/fped.2023.1277697] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 09/25/2023] [Indexed: 11/03/2023] Open
Abstract
Background The COVID-19 pandemic has affected a significant number of pregnant women worldwide, but studies on immune responses have presented conflicting results. This study aims to systematically review cytokine profiles in pregnant women with SARS-CoV-2 infection and their infants to evaluate immune responses and potential transplacental transfer of cytokines. Materials and methods A comprehensive search of 4 databases was conducted to identify relevant studies. Inclusion criteria included studies measuring individual cytokines in pregnant women and/or their neonates. Studies were evaluated for quality, and data were extracted for analysis. Meta-analyses were performed using the random-effects model. Results Seventeen studies met the inclusion criteria, including data from 748 pregnant women and 287 infants. More than three of these studies evaluated data of 20 cytokines in maternal serum, and data of 10 cytokines was available from cord blood samples. Only the serum level of CXCL10 was significantly up-regulated in SARS-CoV-2 positive pregnant women (n = 339) compared to SARS-CoV-2 negative pregnant women (n = 409). Subset analysis of maternal samples (n = 183) collected during the acute phase of COVID-19 infection showed elevated CXCL10 and IFN-γ. No significant differences in cytokine levels were found between cord blood samples collected from infants born to mothers with (n = 97) and without (n = 190) COVID-19 during gestation. Subset analysis of cord blood samples collected during the acute phase of maternal infection was limited by insufficient data. The heterogeneity among the studies was substantial. Conclusion The findings suggest that maternal cytokines responses to SARS-CoV-2 infection during pregnancy are not significantly dysregulated, except for CXCL10 and IFN-γ during the acute phase of illness. No evidence of increased cytokine levels in cord blood samples was observed, although this could be impacted by the time period between initial maternal infection and cord blood collection. These results provide some reassurance to parents and healthcare providers but should be interpreted cautiously due to study variations and limitations.
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Affiliation(s)
- Samhita Jain
- Division of Neonatology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, United States
| | - Isabel Elaine Allen
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States
| | - Dongli Song
- Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, CA, United States
- Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, United States
| | - Xianhua Piao
- Division of Neonatology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, United States
- Newborn Brain Research Institute, University of California, San Francisco, San Francisco, CA, United States
- Weill Institute for Neuroscience, University of California, San Francisco, San Francisco CA, United States
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Fernández-de-las-Peñas C, Guijarro C, Torres-Macho J, Pellicer-Valero OJ, Franco-Moreno A, Nijs J, Velasco-Arribas M. Serological Biomarkers at Hospital Admission and Hospitalization Treatments Are Not Related to Sensitization-Associated Symptoms in Patients with Post-COVID Pain. Pathogens 2023; 12:1235. [PMID: 37887751 PMCID: PMC10610051 DOI: 10.3390/pathogens12101235] [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: 09/08/2023] [Revised: 10/03/2023] [Accepted: 10/09/2023] [Indexed: 10/28/2023] Open
Abstract
Current evidence suggests that a group of patients who had survived coronavirus disease, 2019 (COVID-19) and developed post-COVID pain can exhibit altered nociceptive processing. The role of serological biomarkers and hospitalization treatments in post-COVID pain is unclear. This study aimed to investigate the association of serological biomarkers and treatments received during hospitalization with sensitization-associated symptoms in COVID-19 survivors with post-COVID pain. One hundred and eighty-three (n = 183) patients who had been hospitalized due to COVID-19 in one urban hospital of Madrid (Spain) during the first wave of the pandemic were assessed in a face-to-face interview 9.4 (SD 3.4) months after hospitalization. Levels of 19 serological biomarkers, hospitalization data, and treatments during hospitalization were obtained from hospital records. Sensitization-associated symptoms (Central Sensitization Inventory, CSI), sleep quality (Pittsburgh Sleep Quality Index, PSQI), pain catastrophism (Pain Catastrophizing Scale), and anxiety/depressive level (Hospital Anxiety and Depression Scale, HADS) were assessed. The prevalence of post-COVID pain was 40.9% (n = 75). Twenty-nine (38.6%) patients had sensitization-associated symptoms. Overall, no differences in hospitalization data and serological biomarkers were identified according to the presence of sensitization-associated symptoms. The analysis revealed that patients with sensitization-associated symptoms exhibited higher lymphocyte count and lower urea levels than those without sensitization-associated symptoms, but differences were small. Pain catastrophism and depressive levels, but not fatigue, dyspnea, brain fog, anxiety levels, or poor sleep, were higher in individuals with sensitization-associated symptoms. In conclusion, this study revealed that sensitization-associated post-COVID pain symptoms are not associated with serological biomarkers at hospital admission and hospitalization treatments received.
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Affiliation(s)
- César Fernández-de-las-Peñas
- Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos (URJC), 28922 Madrid, Spain
| | - Carlos Guijarro
- Department of Internal Medicine-Infectious Department, Research Department, Hospital Universitario Fundación Alcorcón, 28922 Madrid, Spain; (C.G.); (M.V.-A.)
- Department of Medicine, Universidad Rey Juan Carlos (URJC), 28922 Madrid, Spain
| | - Juan Torres-Macho
- Department of Internal Medicine, Hospital Universitario Infanta Leonor-Virgen de la Torre, 28031 Madrid, Spain; (J.T.-M.); (A.F.-M.)
- Department of Medicine, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Oscar J. Pellicer-Valero
- Image Processing Laboratory (IPL), Universitat de València, Parc Científic, 46980 València, Spain;
| | - Ana Franco-Moreno
- Department of Internal Medicine, Hospital Universitario Infanta Leonor-Virgen de la Torre, 28031 Madrid, Spain; (J.T.-M.); (A.F.-M.)
| | - Jo Nijs
- Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, 1050 Ixelles, Belgium;
- Chronic Pain Rehabilitation Center, Department of Physical Medicine and Physiotherapy, University Hospital Brussels, 1050 Ixelles, Belgium
- Department of Health and Rehabilitation, Unit of Physiotherapy, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 41390 Göterbog, Sweden
| | - María Velasco-Arribas
- Department of Internal Medicine-Infectious Department, Research Department, Hospital Universitario Fundación Alcorcón, 28922 Madrid, Spain; (C.G.); (M.V.-A.)
- Department of Medicine, Universidad Rey Juan Carlos (URJC), 28922 Madrid, Spain
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Sanhueza S, Vidal MA, Hernandez MA, Henriquez-Beltran ME, Cabrera C, Quiroga R, Antilef BE, Aguilar KP, Castillo DA, Llerena FJ, Fraga Figueroa M, Nazal M, Castro E, Lagos P, Moreno A, Lastra JJ, Gajardo J, Garcés P, Riffo B, Buchert J, Sanhueza R, Ormazába V, Saldivia P, Vargas C, Nourdin G, Koch E, Zuñiga FA, Lamperti L, Bustos P, Guzmán-Gutiérrez E, Tapia CA, Ferrada L, Cerda G, Woehlbier U, Riquelme E, Yuseff MI, Muñoz Ramirez BA, Lombardi G, De Gonzalo-Calvo D, Salomon C, Verdugo RA, Quiñones LA, Colombo A, Barría MI, Labarca G, Nova-Lamperti E. Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome. Front Med (Lausanne) 2023; 10:1271863. [PMID: 37869162 PMCID: PMC10590130 DOI: 10.3389/fmed.2023.1271863] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 09/18/2023] [Indexed: 10/24/2023] Open
Abstract
Introduction Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling. Methods Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection. Results Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups. Discussion Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.
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Affiliation(s)
- Sergio Sanhueza
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Mabel A. Vidal
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Facultad de Ingeniería, Diseño y Arquitectura, Universidad San Sebastián, Concepción, Chile
| | | | - Mario E. Henriquez-Beltran
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Núcleo de Investigación en Ciencias de la Salud, Universidad Adventista de Chile, Chillán, Chile
- Kinesiology School, Escuela de Kinesiología, Facultad de Salud, Universidad Santo Tomás, Los Ángeles, Chile
- Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain
| | - Camilo Cabrera
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Romina Quiroga
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Bárbara E. Antilef
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Kevin P. Aguilar
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Daniela A. Castillo
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Faryd J. Llerena
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Marco Fraga Figueroa
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Mauricio Nazal
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Eritson Castro
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Paola Lagos
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Alexa Moreno
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Jaime J. Lastra
- Internal Medicine Department, Hospital Guillermo Grant Benavente and Medicine Faculty, University of Concepción, Concepción, Chile
| | - Jorge Gajardo
- Internal Medicine Department, Hospital Guillermo Grant Benavente and Medicine Faculty, University of Concepción, Concepción, Chile
| | - Pamela Garcés
- Internal Medicine Department, Hospital Guillermo Grant Benavente and Medicine Faculty, University of Concepción, Concepción, Chile
| | | | | | - Rocío Sanhueza
- Kinesiology School, Escuela de Kinesiología, Facultad de Salud, Universidad Santo Tomás, Los Ángeles, Chile
| | - Valeska Ormazába
- Department of Pharmacology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile
| | - Pablo Saldivia
- Division of Biotechnology, MELISA Institute, San Pedro de la Paz, Chile
| | - Cristian Vargas
- Division of Biotechnology, MELISA Institute, San Pedro de la Paz, Chile
| | - Guillermo Nourdin
- Division of Biotechnology, MELISA Institute, San Pedro de la Paz, Chile
| | - Elard Koch
- Division of Biotechnology, MELISA Institute, San Pedro de la Paz, Chile
| | - Felipe A. Zuñiga
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Liliana Lamperti
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Paula Bustos
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Enrique Guzmán-Gutiérrez
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Claudio A. Tapia
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
| | - Luciano Ferrada
- CMA Bío-Bío - Advanced Microscopy Center, University of Concepción, Concepción, Chile
| | - Gustavo Cerda
- CMA Bío-Bío - Advanced Microscopy Center, University of Concepción, Concepción, Chile
| | - Ute Woehlbier
- Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile
| | - Erick Riquelme
- Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile
| | - Maria-Isabel Yuseff
- Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Braulio A. Muñoz Ramirez
- Department of Pharmacology and Toxicology, School of Medicine, Indiana University Bloomington, Bloomington, IN, United States
| | - Giovanna Lombardi
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom
| | - David De Gonzalo-Calvo
- Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain
- CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain
| | - Carlos Salomon
- Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women’s Hospital, Medicine and Biomedical Science Faculty, The University of Queensland, Brisbane, QLD, Australia
| | - Ricardo A. Verdugo
- Instituto de Investigación Interdisciplinaria y Escuela de Medicina, Universidad de Talca, Talca, Chile
| | - Luis A. Quiñones
- Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile, Santiago, Chile
- Department of Pharmaceutical Sciences and Technology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile
- Latin American Network for Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago, Chile
| | - Alicia Colombo
- Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile, Santiago, Chile
- Servicio de Anatomía Patológica, Hospital Clínico, Universidad de Chile, Santiago, Chile
| | - Maria I. Barría
- Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt, Chile
| | - Gonzalo Labarca
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Internal Medicine, Complejo Asistencial Dr. Víctor Ríos Ruiz, Los Ángeles, Chile
- Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Estefania Nova-Lamperti
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
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Fernández-de-Las-Peñas C, Nijs J, Giordano R, Arendt-Nielsen L. Precision management of post-COVID pain: An evidence and clinical-based approach. Eur J Pain 2023; 27:1107-1125. [PMID: 36852606 DOI: 10.1002/ejp.2095] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/11/2023] [Accepted: 02/13/2023] [Indexed: 03/01/2023]
Abstract
Background Pain after a SARS-CoV-2 acute infection (post-COVID pain) is becoming a new healthcare emergency but remains underestimated and most likely undertreated due to a lack of recognition of the phenomenon and knowledge of the underlying pain mechanisms. Evidence supporting any particular treatment approach for the management of post-COVID pain is lacking. Large variability in the patient response to any standard pain treatments is clinically observed, which has led to calls for a personalized, tailored approach to treating patients with chronic post-COVID pain (i.e. 'precision pain medicine'). Applying the global concerted action towards precision medicine to post-COVID pain could help guide clinical decision-making and aid in more effective treatments. Methods The current position paper discusses factors to be considered by clinicians for managing post-COVID pain ranging from identification of the pain phenotype to genetic consideration. Results The ability of clinicians to phenotype post-COVID pain into nociceptive, neuropathic, nociplastic or mixed type is suggested as the first step to better planification of a treatment programme. Further, the consideration of other factors, such as gender, comorbidities, treatments received at the acute phase of infection for onset-associated COVID-19 symptoms, factors during hospitalization or the presence of emotional disturbances should be implemented into a treatment programme. Conclusions Accordingly, considering these factors, management of post-COVID pain should include multimodal pharmacological and non-pharmacological modalities targeting emotional/cognitive aspects (i.e. psychological and/or coping strategies), central sensitization-associated mechanisms (i.e. pain neuroscience education), exercise programmes as well as lifestyle interventions (e.g. nutritional support and sleep management). SIGNIFICANCE: This position paper presents an evidence-based clinical reasoning approach for precision management of post-COVID pain.
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Affiliation(s)
- César Fernández-de-Las-Peñas
- Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos (URJC), Madrid, Spain
- Center for Neuroplasticity and Pain (CNAP), SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
| | - Jo Nijs
- Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium
- Chronic pain rehabilitation, Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Brussels, Belgium
- Department of Health and Rehabilitation, Unit of Physiotherapy, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Brussels, Sweden
| | - Rocco Giordano
- Center for Neuroplasticity and Pain (CNAP), SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
| | - Lars Arendt-Nielsen
- Center for Neuroplasticity and Pain (CNAP), SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
- Department of Medical Gastroenterology, Mech-Sense, Aalborg University Hospital, Aalborg, Denmark
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Wang Y, Wang Z, Liu Y, Yu Q, Liu Y, Luo C, Wang S, Liu H, Liu M, Zhang G, Fan Y, Li K, Huang L, Duan M, Zhou F. Reconstructing the cytokine view for the multi-view prediction of COVID-19 mortality. BMC Infect Dis 2023; 23:622. [PMID: 37735372 PMCID: PMC10514938 DOI: 10.1186/s12879-023-08291-z] [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: 06/20/2022] [Accepted: 04/28/2023] [Indexed: 09/23/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is a rapidly developing and sometimes lethal pulmonary disease. Accurately predicting COVID-19 mortality will facilitate optimal patient treatment and medical resource deployment, but the clinical practice still needs to address it. Both complete blood counts and cytokine levels were observed to be modified by COVID-19 infection. This study aimed to use inexpensive and easily accessible complete blood counts to build an accurate COVID-19 mortality prediction model. The cytokine fluctuations reflect the inflammatory storm induced by COVID-19, but their levels are not as commonly accessible as complete blood counts. Therefore, this study explored the possibility of predicting cytokine levels based on complete blood counts. METHODS We used complete blood counts to predict cytokine levels. The predictive model includes an autoencoder, principal component analysis, and linear regression models. We used classifiers such as support vector machine and feature selection models such as adaptive boost to predict the mortality of COVID-19 patients. RESULTS Complete blood counts and original cytokine levels reached the COVID-19 mortality classification area under the curve (AUC) values of 0.9678 and 0.9111, respectively, and the cytokine levels predicted by the feature set alone reached the classification AUC value of 0.9844. The predicted cytokine levels were more significantly associated with COVID-19 mortality than the original values. CONCLUSIONS Integrating the predicted cytokine levels and complete blood counts improved a COVID-19 mortality prediction model using complete blood counts only. Both the cytokine level prediction models and the COVID-19 mortality prediction models are publicly available at http://www.healthinformaticslab.org/supp/resources.php .
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Affiliation(s)
- Yueying Wang
- College of Computer Science and Technology, Jilin University, 130012, Changchun, China
- School of Biology and Engineering, Guizhou Medical University, 550025, Guiyang, Guizhou, China
- Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, 130012, Changchun, China
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 130021, Changchun, Jilin Province, China
| | - Zhao Wang
- College of Software, Jilin University, 130012, Changchun, China
| | - Yaqing Liu
- College of Computer Science and Technology, Jilin University, 130012, Changchun, China
| | - Qiong Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 130021, Changchun, Jilin Province, China
| | - Yujia Liu
- College of Software, Jilin University, 130012, Changchun, China
| | - Changfan Luo
- College of Software, Jilin University, 130012, Changchun, China
| | - Siyang Wang
- College of Software, Jilin University, 130012, Changchun, China
| | - Hongmei Liu
- School of Biology and Engineering, Guizhou Medical University, 550025, Guiyang, Guizhou, China
- Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, 130012, Changchun, China
- Engineering Research Center of Medical Biotechnology, Guizhou Medical University, 550025, Guiyang, Guizhou, China
| | - Mingyou Liu
- School of Biology and Engineering, Guizhou Medical University, 550025, Guiyang, Guizhou, China
| | - Gongyou Zhang
- School of Biology and Engineering, Guizhou Medical University, 550025, Guiyang, Guizhou, China
| | - Yusi Fan
- College of Software, Jilin University, 130012, Changchun, China
| | - Kewei Li
- College of Computer Science and Technology, Jilin University, 130012, Changchun, China
- School of Biology and Engineering, Guizhou Medical University, 550025, Guiyang, Guizhou, China
| | - Lan Huang
- College of Computer Science and Technology, Jilin University, 130012, Changchun, China
- School of Biology and Engineering, Guizhou Medical University, 550025, Guiyang, Guizhou, China
| | - Meiyu Duan
- College of Computer Science and Technology, Jilin University, 130012, Changchun, China.
- Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, 130012, Changchun, China.
| | - Fengfeng Zhou
- College of Computer Science and Technology, Jilin University, 130012, Changchun, China.
- School of Biology and Engineering, Guizhou Medical University, 550025, Guiyang, Guizhou, China.
- Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, 130012, Changchun, China.
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López-López L, Calvache-Mateo A, Ortiz-Rubio A, Granados-Santiago M, Heredia-Ciuró A, Martín-Núñez J, Valenza MC. Differences of Disabling Symptoms between Previously Hospitalized or Non-Hospitalized Currently Working Long-COVID Survivors One Year after Infection: A Descriptive Study. Healthcare (Basel) 2023; 11:2306. [PMID: 37628505 PMCID: PMC10454028 DOI: 10.3390/healthcare11162306] [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: 07/21/2023] [Revised: 08/04/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
This study aimed to describe the presence of disabling symptoms in currently working Long-COVID survivors by comparing the hospitalized and non-hospitalized one year after infection. Patients with Long-COVID syndrome (LCS) that have been infected by COVID-19 a year ago and were actually working were included. Participants that had been hospitalized due to COVID-19 were included in the LCS hospitalized group, and participants that had not been hospitalized were included in the LCS non-hospitalized group. The eligible patients were prompted to complete the latest self-report version of the COVID-19 Yorkshire Rehabilitation Screening Tool (C19-YRS). A total of 465 subjects were included in the study. Participants in the LCS hospitalized group were significantly older, had a significantly higher BMI, and had a significantly higher prevalence of women compared to the LCS non-hospitalized group. Additionally, participants in the LCS hospitalized group had obtained significantly worse results in symptom severity, functional disability, and global health perceived subscales of C19-YRS compared to the participants included in the LCS non-hospitalized group. We concluded that disabling symptoms are presented in patients with LCS at working age one year after infection and are higher in LCS hospitalized patients compared to LCS non-hospitalized patients.
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Affiliation(s)
- Laura López-López
- Physiotherapy Department, Faculty of Health Sciences, University of Granada, 18016 Granada, Spain; (L.L.-L.); (A.C.-M.); (A.O.-R.); (A.H.-C.); (J.M.-N.); (M.C.V.)
| | - Andrés Calvache-Mateo
- Physiotherapy Department, Faculty of Health Sciences, University of Granada, 18016 Granada, Spain; (L.L.-L.); (A.C.-M.); (A.O.-R.); (A.H.-C.); (J.M.-N.); (M.C.V.)
| | - Araceli Ortiz-Rubio
- Physiotherapy Department, Faculty of Health Sciences, University of Granada, 18016 Granada, Spain; (L.L.-L.); (A.C.-M.); (A.O.-R.); (A.H.-C.); (J.M.-N.); (M.C.V.)
| | | | - Alejandro Heredia-Ciuró
- Physiotherapy Department, Faculty of Health Sciences, University of Granada, 18016 Granada, Spain; (L.L.-L.); (A.C.-M.); (A.O.-R.); (A.H.-C.); (J.M.-N.); (M.C.V.)
| | - Javier Martín-Núñez
- Physiotherapy Department, Faculty of Health Sciences, University of Granada, 18016 Granada, Spain; (L.L.-L.); (A.C.-M.); (A.O.-R.); (A.H.-C.); (J.M.-N.); (M.C.V.)
| | - Marie Carmen Valenza
- Physiotherapy Department, Faculty of Health Sciences, University of Granada, 18016 Granada, Spain; (L.L.-L.); (A.C.-M.); (A.O.-R.); (A.H.-C.); (J.M.-N.); (M.C.V.)
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Pawar VA, Tyagi A, Verma C, Sharma KP, Ansari S, Mani I, Srivastva SK, Shukla PK, Kumar A, Kumar V. Unlocking therapeutic potential: integration of drug repurposing and immunotherapy for various disease targeting. Am J Transl Res 2023; 15:4984-5006. [PMID: 37692967 PMCID: PMC10492070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 07/31/2023] [Indexed: 09/12/2023]
Abstract
Drug repurposing, also known as drug repositioning, entails the application of pre-approved or formerly assessed drugs having potentially functional therapeutic amalgams for curing various disorders or disease conditions distinctive from their original remedial indication. It has surfaced as a substitute for the development of drugs for treating cancer, cardiovascular diseases, neurodegenerative disorders, and various infectious diseases like Covid-19. Although the earlier lines of findings in this area were serendipitous, recent advancements are based on patient centered approaches following systematic, translational, drug targeting practices that explore pathophysiological ailment mechanisms. The presence of definite information and numerous records with respect to beneficial properties, harmfulness, and pharmacologic characteristics of repurposed drugs increase the chances of approval in the clinical trial stages. The last few years have showcased the successful emergence of repurposed drug immunotherapy in treating various diseases. In this light, the present review emphasises on incorporation of drug repositioning with Immunotherapy targeted for several disorders.
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Affiliation(s)
| | - Anuradha Tyagi
- Department of cBRN, Institute of Nuclear Medicine and Allied ScienceDelhi 110054, India
| | - Chaitenya Verma
- Department of Pathology, Wexner Medical Center, Ohio State UniversityColumbus, Ohio 43201, USA
| | - Kanti Prakash Sharma
- Department of Nutrition Biology, Central University of HaryanaMahendragarh 123029, India
| | - Sekhu Ansari
- Division of Pathology, Cincinnati Children’s Hospital Medical CenterCincinnati, Ohio 45229, USA
| | - Indra Mani
- Department of Microbiology, Gargi College, University of DelhiNew Delhi 110049, India
| | | | - Pradeep Kumar Shukla
- Department of Biological Sciences, Faculty of Science, Sam Higginbottom University of Agriculture, Technology of SciencePrayagraj 211007, UP, India
| | - Antresh Kumar
- Department of Biochemistry, Central University of HaryanaMahendergarh 123031, Haryana, India
| | - Vinay Kumar
- Department of Physiology and Cell Biology, The Ohio State University Wexner Medical CenterColumbus, Ohio 43210, USA
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Moradi Haghgoo J, Torkzaban P, Farhadian M, Moosavi Sedeh SA. Association between the severity of periodontitis, COVID-19, C-reactive protein and interleukin-6 levels in hospitalized patients: a case‒control study. BMC Oral Health 2023; 23:556. [PMID: 37568161 PMCID: PMC10422752 DOI: 10.1186/s12903-023-03270-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 07/31/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND The COVID-19 pandemic is perhaps one of the most important events of the 21st century. Periodontitis is one of the most prevalent diseases of the oral cavity. Due to possible pathways of interaction between these two diseases, we investigated their association. METHODS The study population consisted of hospitalized patients with established COVID-19 diagnoses. Patients with mild to moderate COVID-19 were considered controls, while cases had severe to critical COVID-19. Periodontal examination and serum and saliva sampling were performed for each patient. Relevant medical data were extracted from patients' hospital files. RESULTS Of the enrolled patients, 122 were included in the statistical analyses. The severity of periodontitis was directly and significantly correlated with the severity of COVID-19 (P < 0.001). Patients with generalized stage III or IV periodontitis displayed an adjusted odds ratio of 4.24 for severe to critical COVID-19. Salivary and serum interleukin-6 levels were significantly associated with COVID-19 severity (P values: 0.002 and 0.004, respectively). Hospitalization length was significantly associated with the severity of periodontitis (P = 0.004). Clinical attachment level and gingival index were associated with increased odds for adverse events (P values: 0.004 and 0.035, respectively), while number of remaining teeth was associated with decreased odds for adverse events (P = 0.023). CONCLUSIONS This study showed that the severity of periodontitis is associated with the severity of COVID-19. This association might manifest as increased odds of adverse events. COVID-19 severity was associated with higher levels of salivary and serum interleukin-6 levels.
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Affiliation(s)
- Janet Moradi Haghgoo
- Department of Periodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Parviz Torkzaban
- Department of Periodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Maryam Farhadian
- Department of Biostatistics, School of Public Health and Research Center for Health Sciences, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Sayed Ali Moosavi Sedeh
- Department of Periodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran.
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Zizza A, Sedile R, Bagordo F, Panico A, Guido M, Grassi T, Banchelli F, Grima P. Factors Associated with Pneumonia in Patients Hospitalized with COVID-19 and the Role of Vaccination. Vaccines (Basel) 2023; 11:1342. [PMID: 37631910 PMCID: PMC10458032 DOI: 10.3390/vaccines11081342] [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: 06/28/2023] [Revised: 08/04/2023] [Accepted: 08/07/2023] [Indexed: 08/29/2023] Open
Abstract
Patients with COVID-19 can develop different forms of the illness with more or less severe symptoms. A 2-year retrospective cohort study was conducted to evaluate the factors associated with the development of pneumonia in patients hospitalized with COVID-19 from March 2020 to February 2022. A total of 385 patients (59.0% males) with a mean age of 69.0 ± 16.0 years were included. At hospital admission, 318 patients (82.6%) reported one or more comorbidities, namely 201 (52.2%) subjects were affected by hypertension, 98 (25.5%) type 2 diabetes, 84 (21.8%) obesity, 36 (9.4%) cancer, and 14 (3.6%) suffered from kidney disease and were being treated with dialysis, and 76 (19.7%) resulted in being vaccinated with a higher prevalence of BNT162b2 vaccine (15.0%). Pneumonia was diagnosed in 276 (71.7%) patients. Multivariate regression analysis showed that pneumonia in COVID-19 patients was positively associated with type 2 diabetes (OR 1.81; 95% CI 1.00-3.27), obesity (OR 2.52; 95% CI 1.27-4.98), and negatively with hypertension (OR 0.58; 95% CI 0.35-0.96). Vaccination against SARS-CoV-2 resulted in a strongly protective factor against the development of pneumonia in COVID-19 patients (OR 0.49; 95% CI 0.28-0.85).
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Affiliation(s)
- Antonella Zizza
- Institute of Clinical Physiology, National Research Council, 73100 Lecce, Italy;
| | - Raffaella Sedile
- Institute of Clinical Physiology, National Research Council, 73100 Lecce, Italy;
| | - Francesco Bagordo
- Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, 70121 Bari, Italy
| | - Alessandra Panico
- Department of Biological and Environmental Science and Technology, University of Salento, 73100 Lecce, Italy; (A.P.); (M.G.); (T.G.)
| | - Marcello Guido
- Department of Biological and Environmental Science and Technology, University of Salento, 73100 Lecce, Italy; (A.P.); (M.G.); (T.G.)
| | - Tiziana Grassi
- Department of Biological and Environmental Science and Technology, University of Salento, 73100 Lecce, Italy; (A.P.); (M.G.); (T.G.)
| | - Federico Banchelli
- Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41121 Modena, Italy;
- Unit of Statistical and Methodological Support to Clinical Research, University Hospital of Modena, 41121 Modena, Italy
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Ndoricyimpaye EL, Van Snick J, Robert R, Bikorimana E, Majyambere O, Mukantwari E, Nshimiyimana T, Mbonigaba V, Coutelier JP, Rujeni N. Cytokine Kinetics during Progression of COVID-19 in Rwanda Patients: Could IL-9/IFNγ Ratio Predict Disease Severity? Int J Mol Sci 2023; 24:12272. [PMID: 37569646 PMCID: PMC10418469 DOI: 10.3390/ijms241512272] [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: 05/08/2023] [Revised: 06/27/2023] [Accepted: 06/28/2023] [Indexed: 08/13/2023] Open
Abstract
For effective treatments and preventive measures against severe COVID-19, it is essential to determine early markers of disease severity in different populations. We analysed the cytokine kinetics of 129 COVID-19 patients with mild symptoms, 68 severe cases, and 20 healthy controls for the first time in Rwanda. Pro-inflammatory (IFNγ, IL-6, TNFα), Treg (IL-10, TGFβ1, TGFβ3), Th9 (IL-9), Th17 (IL-17), and Th2 (IL-4, IL-13) cytokines, total IgM and IgG, as well as gene expressions of FoxP3, STAT5+, IFNγ-R1, and ROR alpha+, were measured at day 1, day 7, day 14, day 21, and day 28 post-infection. Severe cases showed a significantly stronger increase than mild patients in levels of all cytokines (except IL-9) and all gene expression on day 1 of infection. Some cytokine levels dropped to levels comparable to mild cases at later time points. Further analysis identified IFNγ as a marker of severity throughout the disease course, while TGFβ1, IL-6, and IL-17 were markers of severity only at an early phase. Importantly, this study revealed a striking low IL-9 level and high IFNγ/IL-9 ratio in the plasma of patients who later died compared to mild and severe cases who recovered, suggesting that this could be an important biomarker for predicting the severity of COVID-19 and post-COVID-19 syndrome.
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Affiliation(s)
- Ella Larissa Ndoricyimpaye
- Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda; (E.L.N.); (R.R.); (O.M.); (T.N.); (J.P.C.)
- de Duve Institute, Université Catholique de Louvain, 1348 Brussels, Belgium
| | - Jacques Van Snick
- Ludwig Institute for Cancer Research, Universite Catholique de Louvain, 1348 Brussels, Belgium;
| | - Rutayisire Robert
- Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda; (E.L.N.); (R.R.); (O.M.); (T.N.); (J.P.C.)
- National Reference Laboratory, Rwanda Biomedical Center, Kigali P.O. Box 4285, Rwanda; (E.M.); (V.M.)
| | - Emmanuel Bikorimana
- Department of General Nursing, School of Nursing, College of Medicine and Health Science, University of Rwanda, Kigali P.O. Box 3248, Rwanda;
| | - Onesphore Majyambere
- Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda; (E.L.N.); (R.R.); (O.M.); (T.N.); (J.P.C.)
| | - Enatha Mukantwari
- National Reference Laboratory, Rwanda Biomedical Center, Kigali P.O. Box 4285, Rwanda; (E.M.); (V.M.)
| | - Thaddée Nshimiyimana
- Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda; (E.L.N.); (R.R.); (O.M.); (T.N.); (J.P.C.)
| | - Valens Mbonigaba
- National Reference Laboratory, Rwanda Biomedical Center, Kigali P.O. Box 4285, Rwanda; (E.M.); (V.M.)
| | - Jean Paul Coutelier
- Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda; (E.L.N.); (R.R.); (O.M.); (T.N.); (J.P.C.)
- de Duve Institute, Université Catholique de Louvain, 1348 Brussels, Belgium
| | - Nadine Rujeni
- Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda; (E.L.N.); (R.R.); (O.M.); (T.N.); (J.P.C.)
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Moradi Haghgoo J, Torkzaban P, Farhadian M, Rabienejad N, Moosavi Sedeh SA. Hematologic tests and their association with the severity of COVID-19 and periodontitis in hospitalized patients: a case-control study. BMC Oral Health 2023; 23:473. [PMID: 37434176 PMCID: PMC10334521 DOI: 10.1186/s12903-023-03208-3] [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: 04/10/2023] [Accepted: 07/06/2023] [Indexed: 07/13/2023] Open
Abstract
BACKGROUND The presence of comorbidities, especially those with a chronic inflammatory nature such as periodontitis, can facilitate COVID-19 progression toward more severe forms. Both of these diseases can affect systemic health and alter hematological test results. In this study, we decided to investigate COVID-19 and periodontitis' possible interaction with these alterations. METHODS Hospitalized patients with a definitive diagnosis of COVID-19 were included. Controls had mild to moderate COVID-19, while cases had severe to critical COVID-19. Periodontal examination was done for each patient. Relevant medical and hematological data were extracted from patient's hospital files. RESULTS A total of 122 patients entered the final analysis. The minimum white blood cell counts were associated with the severity of periodontitis. The interaction between periodontitis and COVID-19 was associated with increased minimum white blood cell counts and decreased platelet counts. COVID-19 severity was associated with increased venous oxygen saturation, prothrombin time, the maximum partial thromboplastin time, the maximum and average urea, the maximum creatinine, the maximum potassium, and lactate dehydrogenase, and decreased sodium levels. CONCLUSIONS Results of this study showed that several blood parameters were associated with periodontitis, COVID-19, or the interaction between them.
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Affiliation(s)
- Janet Moradi Haghgoo
- Department of Periodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran
- Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Parviz Torkzaban
- Department of Periodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran
- Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Maryam Farhadian
- Department of Biostatistics, School of Public Health and Research Center for Health Sciences, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Nazli Rabienejad
- Department of Periodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran
- Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Sayed Ali Moosavi Sedeh
- Department of Periodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran.
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Xu J, Li XX, Yuan N, Li C, Yang JG, Cheng LM, Lu ZX, Hou HY, Zhang B, Hu H, Qian Y, Liu XX, Li GC, Wang YD, Chu M, Dong CR, Liu F, Ge QG, Yang YJ. T cell receptor β repertoires in patients with COVID-19 reveal disease severity signatures. Front Immunol 2023; 14:1190844. [PMID: 37475855 PMCID: PMC10355153 DOI: 10.3389/fimmu.2023.1190844] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 06/06/2023] [Indexed: 07/22/2023] Open
Abstract
Background The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity. Methods In this study, we employed high-throughput T cell receptor (TCR) β repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes. Results We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression. Conclusions Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR β repertoires in monitoring disease development and indicating disease severity.
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Affiliation(s)
- Jing Xu
- State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital & National Center for Cardiovascular Diseases, Beijing, China
- Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Xiao-xiao Li
- Department of Pharmacy and Department of Intensive Care Unit, Peking University Third Hospital, Beijing, China
| | - Na Yuan
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Chao Li
- Department of Pharmacy and Department of Intensive Care Unit, Peking University Third Hospital, Beijing, China
| | - Jin-gang Yang
- State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital & National Center for Cardiovascular Diseases, Beijing, China
- Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Li-ming Cheng
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhong-xin Lu
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hong-yan Hou
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bo Zhang
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hui Hu
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Qian
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- China National Center for Bioinformation, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Xin-xuan Liu
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- China National Center for Bioinformation, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Guo-chao Li
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- China National Center for Bioinformation, Beijing, China
| | - Yue-dan Wang
- Department of Immunology, School of Basic Medical Sciences, Peking University, NHC Key Laboratory of Medical Immunology (Peking University), Beijing, China
| | - Ming Chu
- Department of Immunology, School of Basic Medical Sciences, Peking University, NHC Key Laboratory of Medical Immunology (Peking University), Beijing, China
| | - Chao-ran Dong
- Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Liu
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- Department of Forensic Sciences, College of Criminal Justice, Naif Arab University of Security Sciences, Riyadh, Saudi Arabia
| | - Qing-gang Ge
- Department of Pharmacy and Department of Intensive Care Unit, Peking University Third Hospital, Beijing, China
| | - Yue-jin Yang
- State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital & National Center for Cardiovascular Diseases, Beijing, China
- Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
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Valdés-López JF, Urcuqui-Inchima S. Antiviral response and immunopathogenesis of interleukin 27 in COVID-19. Arch Virol 2023; 168:178. [PMID: 37310504 DOI: 10.1007/s00705-023-05792-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 04/11/2023] [Indexed: 06/14/2023]
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a high mortality rate. The clinical course is attributed to the severity of pneumonia and systemic complications. In COVID-19 patients and murine models of SARS-CoV-2 infection, the disease may be accompanied by excessive production of cytokines, leading to an accumulation of immune cells in affected organs such as lungs. Previous reports have shown that SARS-CoV-2 infection antagonizes interferon (IFN)-dependent antiviral response, thereby preventing the expression of IFN-stimulated genes (ISGs). Lower IFN levels have been linked to more-severe COVID-19. Interleukin 27 (IL27) is a heterodimeric cytokine composed of IL27p28 and EBI3 subunits, which induce both pro- and anti-inflammatory responses. Recently, we and others have reported that IL27 also induces a strong antiviral response in an IFN-independent manner. Here, we investigated transcription levels of both IL27 subunits in COVID-19 patients. The results show that SARS-CoV-2 infection modulates TLR1/2-MyD88 signaling in PBMCs and monocytes and induces NF-κB activation and expression of NF-κB-target genes that are dependent on a robust pro-inflammatory response, including EBI3; and activates IRF1 signaling which induces IL27p28 mRNA expression. The results suggest that IL27 induces a robust STAT1-dependent pro-inflammatory and antiviral response in an IFN-independent manner in COVID-derived PBMCs and monocytes as a function of a severe clinical course of COVID-19. Similar results were observed in macrophages stimulated with the SARS-CoV-2 spike protein. Thus, IL27 can trigger an antiviral response in the host, suggesting the possibility of novel therapeutics against SARS-CoV-2 infection in humans.
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Affiliation(s)
- Juan Felipe Valdés-López
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia
| | - Silvio Urcuqui-Inchima
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
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Carlini V, Noonan DM, Abdalalem E, Goletti D, Sansone C, Calabrone L, Albini A. The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions. Front Immunol 2023; 14:1161067. [PMID: 37359549 PMCID: PMC10287165 DOI: 10.3389/fimmu.2023.1161067] [Citation(s) in RCA: 151] [Impact Index Per Article: 75.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 05/24/2023] [Indexed: 06/28/2023] Open
Abstract
Interleukin-10 (IL-10) is a pleiotropic cytokine that has a fundamental role in modulating inflammation and in maintaining cell homeostasis. It primarily acts as an anti-inflammatory cytokine, protecting the body from an uncontrolled immune response, mostly through the Jak1/Tyk2 and STAT3 signaling pathway. On the other hand, IL-10 can also have immunostimulating functions under certain conditions. Given the pivotal role of IL-10 in immune modulation, this cytokine could have relevant implications in pathologies characterized by hyperinflammatory state, such as cancer, or infectious diseases as in the case of COVID-19 and Post-COVID-19 syndrome. Recent evidence proposed IL-10 as a predictor of severity and mortality for patients with acute or post-acute SARS-CoV-2 infection. In this context, IL-10 can act as an endogenous danger signal, released by tissues undergoing damage in an attempt to protect the organism from harmful hyperinflammation. Pharmacological strategies aimed to potentiate or restore IL-10 immunomodulatory action may represent novel promising avenues to counteract cytokine storm arising from hyperinflammation and effectively mitigate severe complications. Natural bioactive compounds, derived from terrestrial or marine photosynthetic organisms and able to increase IL-10 expression, could represent a useful prevention strategy to curb inflammation through IL-10 elevation and will be discussed here. However, the multifaceted nature of IL-10 has to be taken into account in the attempts to modulate its levels.
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Affiliation(s)
- Valentina Carlini
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), MultiMedica, Milan, Italy
| | - Douglas M. Noonan
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), MultiMedica, Milan, Italy
- Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
| | - Eslam Abdalalem
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), MultiMedica, Milan, Italy
| | - Delia Goletti
- Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Clementina Sansone
- Stazione Zoologica Anton Dohrn, Istituto Nazionale di Biologia, Ecologia e Biotecnologie Marine, Napoli, Italy
| | - Luana Calabrone
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), MultiMedica, Milan, Italy
| | - Adriana Albini
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) European Institute of Oncology IEO-, Milan, Italy
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Szarpak L, Feduniw S, Pruc M, Ciebiera M, Cander B, Rahnama-Hezavah M, Szarpak Ł. The Vitamin D Serum Levels in Pregnant Women Affected by COVID-19: A Systematic Review and Meta-Analysis. Nutrients 2023; 15:nu15112588. [PMID: 37299555 DOI: 10.3390/nu15112588] [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: 05/04/2023] [Revised: 05/27/2023] [Accepted: 05/30/2023] [Indexed: 06/12/2023] Open
Abstract
Vitamin D can modulate immune responses, and its deficiency is linked to increased autoimmunity and susceptibility to infection. In the general population, it has been observed that serum vitamin D levels are connected with the risk of COVID-19 and its severity. Our study aims to examine reported findings on the effect of vitamin D serum levels on infection of COVID-19 during pregnancy. PubMed, Web of Science, Embase, and Cochrane Library were searched for relevant studies. Serum vitamin D serum levels in COVID-19-positive and COVID-19-negative pregnant women were 24.61 ± 20.86 ng/mL and 24.12 ± 17.33 ng/mL, respectively. In mild vs. moderate to critical COVID-19 pregnant women, vitamin D serum levels were 16.71 ± 9.04 ng/mL vs. 10.7 ± 9.37 ng/mL and severe vs. non-severe were 13.21 ± 11.47 ng/mL vs. 15.76 ± 10.0 ng/mL. Only one study reported vitamin D serum levels in the placenta of COVID-19-positive pregnant women compared with the control and results varied and amounted to 14.06 ± 0.51 ng/mL vs. 12.45 ± 0.58 ng/mL, respectively. Vitamin D deficiency tends to be common in pregnant women who have COVID-19, and the level of this vitamin has been demonstrated to have a strong correlation with the severity of the illness. As vitamin D serum levels correlate with COVID-19 symptoms and even with its occurrence, appropriate vitamin D supplementation in the prenatal period is suggested.
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Affiliation(s)
- Luiza Szarpak
- Research Unit, Polish Society of Disaster Medicine, 05-806 Warsaw, Poland
| | - Stepan Feduniw
- Department of Obstetrics, University Hospital Zurich, Frauenklinikstrasse 10, 8091 Zurich, Switzerland
- Department of Gynecology, University Hospital Zurich, Frauenklinikstrasse 10, 8091 Zurich, Switzerland
| | - Michal Pruc
- Research Unit, Polish Society of Disaster Medicine, 05-806 Warsaw, Poland
- Research Unit, International Academy of Ecology and Medicine, 02091 Kyiv, Ukraine
| | - Michal Ciebiera
- Second Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, 00-189 Warsaw, Poland
| | - Basar Cander
- Department of Emergency Medicine, Bezmialem Vakif University, Fatih, 34093 Istanbul, Turkey
| | - Mansur Rahnama-Hezavah
- Chair and Department of Oral Surgery, Medical University of Lublin, 20-093 Lublin, Poland
| | - Łukasz Szarpak
- Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX 77030, USA
- Research Unit, Maria Sklodowska-Curie Bialystok Oncology Center, 15-027 Bialystok, Poland
- Institute of Outcomes Research, Maria Sklodowska-Curie Medical Academy, 00-136 Warsaw, Poland
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47
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McGovern J, Wadsworth J, Catchpole A, Richards C, McMillan DC, Kelliher T, Goodall E, Murray E, Melaugh T, McPhillips S, Brice K, Barbour K, Robinson S, Moffitt P, Kemp O, Talwar D, Maguire D. The relationship between micronutrient status, frailty, systemic inflammation, and clinical outcomes in patients admitted to hospital with COVID-19. J Transl Med 2023; 21:284. [PMID: 37118813 PMCID: PMC10139911 DOI: 10.1186/s12967-023-04138-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 04/16/2023] [Indexed: 04/30/2023] Open
Abstract
BACKGROUND Micronutrients have been associated with disease severity and poorer clinical outcomes in patients with COVID-19. However, there is a paucity of studies examining if the relationship with micronutrient status and clinical outcomes is independent of recognised prognostic factors, specifically frailty and the systemic inflammatory response (SIR). The aim of the present study was to examine the relationship between micronutrient status, frailty, systemic inflammation, and clinical outcomes in patients admitted with COVID-19. METHODS Retrospective analysis of prospectively collected data was performed on patients with confirmed COVID-19, admitted to hospital between the 1st April 2020-6th July 2020. Clinicopathological characteristics, frailty assessment, biochemical and micronutrient laboratory results were recorded. Frailty status was determined using the Clinical Frailty scale. SIR was determined using serum CRP. Clinical outcomes of interest were oxygen requirement, ITU admission and 30-day mortality. Categorical variables were analysed using chi-square test and binary logistics regression analysis. Continuous variables were analysed using the Mann-Whitney U or Kruskal Wallis tests. RESULTS 281 patients were included. 55% (n = 155) were aged ≥ 70 years and 39% (n = 109) were male. 49% (n = 138) of patients were frail (CFS > 3). 86% (n = 242) of patients had a serum CRP > 10 mg/L. On univariate analysis, frailty was significantly associated with thirty-day mortality (p < 0.001). On univariate analysis, serum CRP was found to be significantly associated with an oxygen requirement on admission in non-frail patients (p = 0.004). Over a third (36%) of non-frail patients had a low vitamin B1, despite having normal reference range values of red cell B2, B6 and selenium. Furthermore, serum CRP was found to be significantly associated with a lower median red cell vitamin B1 (p = 0.029). CONCLUSION Vitamin B1 stores may be depleted in COVID-19 patients experiencing a significant SIR and providing rationale for thiamine supplementation. Further longitudinal studies are warranted to delineate the trend in thiamine status following COVID-19.
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Affiliation(s)
- Josh McGovern
- Academic Unit of Surgery, School of Medicine, University of Glasgow, Level 2, New Lister Building, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK.
| | - John Wadsworth
- Clinical Biochemistry Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | - Anthony Catchpole
- Clinical Biochemistry Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | - Conor Richards
- Emergency Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | - Donald C McMillan
- Academic Unit of Surgery, School of Medicine, University of Glasgow, Level 2, New Lister Building, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK
| | - Tadhg Kelliher
- Emergency Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | - Emma Goodall
- Emergency Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | - Ellie Murray
- Emergency Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | - Terry Melaugh
- Emergency Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | | | - Kathryn Brice
- Emergency Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | - Katie Barbour
- Emergency Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | - Sophie Robinson
- Emergency Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | - Peter Moffitt
- Emergency Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | - Olivia Kemp
- Emergency Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | - Dinesh Talwar
- Clinical Biochemistry Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
| | - Donogh Maguire
- Emergency Department, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK
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48
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Nayak SS, Naidu A, Sudhakaran SL, Vino S, Selvaraj G. Prospects of Novel and Repurposed Immunomodulatory Drugs against Acute Respiratory Distress Syndrome (ARDS) Associated with COVID-19 Disease. J Pers Med 2023; 13:664. [PMID: 37109050 PMCID: PMC10142859 DOI: 10.3390/jpm13040664] [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: 02/13/2023] [Revised: 04/09/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
Acute respiratory distress syndrome (ARDS) is intricately linked with SARS-CoV-2-associated disease severity and mortality, especially in patients with co-morbidities. Lung tissue injury caused as a consequence of ARDS leads to fluid build-up in the alveolar sacs, which in turn affects oxygen supply from the capillaries. ARDS is a result of a hyperinflammatory, non-specific local immune response (cytokine storm), which is aggravated as the virus evades and meddles with protective anti-viral innate immune responses. Treatment and management of ARDS remain a major challenge, first, because the condition develops as the virus keeps replicating and, therefore, immunomodulatory drugs are required to be used with caution. Second, the hyperinflammatory responses observed during ARDS are quite heterogeneous and dependent on the stage of the disease and the clinical history of the patients. In this review, we present different anti-rheumatic drugs, natural compounds, monoclonal antibodies, and RNA therapeutics and discuss their application in the management of ARDS. We also discuss on the suitability of each of these drug classes at different stages of the disease. In the last section, we discuss the potential applications of advanced computational approaches in identifying reliable drug targets and in screening out credible lead compounds against ARDS.
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Affiliation(s)
- Smruti Sudha Nayak
- Department of Bio-Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India
| | - Akshayata Naidu
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India
| | - Sajitha Lulu Sudhakaran
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India
| | - Sundararajan Vino
- Department of Bio-Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India
| | - Gurudeeban Selvaraj
- Centre for Research in Molecular Modeling, Department of Chemistry and Biochemistry, Concordia University-Loyola Campus, Montreal, QC H4B 1R6, Canada
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49
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Alomair BM, Al‐Kuraishy HM, Al‐Gareeb AI, Al‐Buhadily AK, Alexiou A, Papadakis M, Alshammari MA, Saad HM, Batiha GE. Mixed storm in SARS-CoV-2 infection: A narrative review and new term in the Covid-19 era. Immun Inflamm Dis 2023; 11:e838. [PMID: 37102645 PMCID: PMC10132185 DOI: 10.1002/iid3.838] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 03/22/2023] [Accepted: 03/27/2023] [Indexed: 04/28/2023] Open
Abstract
Coronavirus disease 2019 (Covid-19) is caused by a novel severe acute respiratory syndrome coronavirus virus type 2 (SARS-CoV-2) leading to the global pandemic worldwide. Systemic complications in Covid-19 are mainly related to the direct SARS-CoV-2 cytopathic effects, associated hyperinflammation, hypercytokinemia, and the development of cytokine storm (CS). As well, Covid-19 complications are developed due to the propagation of oxidative and thrombotic events which may progress to a severe state called oxidative storm and thrombotic storm (TS), respectively. In addition, inflammatory and lipid storms are also developed in Covid-19 due to the activation of inflammatory cells and the release of bioactive lipids correspondingly. Therefore, the present narrative review aimed to elucidate the interrelated relationship between different storm types in Covid-19 and the development of the mixed storm (MS). In conclusion, SARS-CoV-2 infection induces various storm types including CS, inflammatory storm, lipid storm, TS and oxidative storm. These storms are not developing alone since there is a close relationship between them. Therefore, the MS seems to be more appropriate to be related to severe Covid-19 than CS, since it develops in Covid-19 due to the intricate interface between reactive oxygen species, proinflammatory cytokines, complement activation, coagulation disorders, and activated inflammatory signaling pathway.
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Affiliation(s)
- Basil Mohammed Alomair
- Department of Medicine, College of Medicine, Internal Medicine and EndocrinologyJouf UniversityAl‐JoufSaudi Arabia
| | - Hayder M. Al‐Kuraishy
- Department of Clinical Pharmacology and Medicine, College of MedicineAl‐Mustansiriya UniversityBaghdadIraq
| | - Ali I. Al‐Gareeb
- Department of Clinical Pharmacology and Medicine, College of MedicineAl‐Mustansiriya UniversityBaghdadIraq
| | - Ali K. Al‐Buhadily
- Department of Clinical Pharmacology, Medicine, and Therapeutic, Medical Faculty, College of MedicineAl‐Mustansiriyah UniversityBaghdadIraq
| | - Athanasios Alexiou
- Department of Science and EngineeringNovel Global Community Educational FoundationHebershamNew South WalesAustralia
- AFNP MedWienAustria
| | - Marios Papadakis
- Department of Surgery II, University Hospital Witten‐HerdeckeUniversity of Witten‐HerdeckeWuppertalGermany
| | - Majed Ayed Alshammari
- Department of MedicinePrince Mohammed Bin Abdulaziz Medical CitySakakaAl‐JoufSaudi Arabia
| | - Hebatallah M. Saad
- Department of Pathology, Faculty of Veterinary MedicineMatrouh UniversityMarsaMatruhEgypt
| | - Gaber El‐Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary MedicineDamanhour UniversityDamanhourEgypt
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Abstract
OBJECTIVE Interindividual variability in the clinical progression of COVID-19 may be explained by host genetics. Emerging literature supports a potential inherited predisposition to severe forms of COVID-19. Demographic and inflammatory characteristics of COVID-19 suggest that acquired hematologic mutations leading to clonal hematopoiesis (CH) may further increase vulnerability to adverse sequelae. This review summarizes the available literature examining genetic predispositions to severe COVID-19 and describes how these findings could eventually be used to improve its clinical management. DATA SOURCES A PubMed literature search was performed. STUDY SELECTION Studies examining the significance of inherited genetic variation or acquired CH mutations in severe COVID-19 were selected for inclusion. DATA EXTRACTION Relevant genetic association data and aspects of study design were qualitatively assessed and narratively synthesized. DATA SYNTHESIS Genetic variants affecting inflammatory responses may increase susceptibility to severe COVID-19. Genome-wide association studies and candidate gene approaches have identified a list of inherited mutations, which likely alter cytokine and interferon secretion, and lung-specific mechanisms of immunity in COVID-19. The potential role of CH in COVID-19 is more uncertain at present; however, the available evidence suggests that the various types of acquired mutations and their differential influence on immune cell function must be carefully considered. CONCLUSIONS The current literature supports the hypothesis that host genetic factors affect vulnerability to severe COVID-19. Further research is required to confirm the full scope of relevant variants and the causal mechanisms underlying these associations. Clinical approaches, which consider the genetic basis of interindividual variability in COVID-19 and potentially other causes of critical illness, could optimize hospital resource allocation, predict responsiveness to treatment, identify more efficacious drug targets, and ultimately improve outcomes.
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