|
1
|
Pariente E, Martín-Millán M, Nan D, Martínez-Revuelta D, Basterrechea H, Pardo J, Bonome M, Solares S, Ramos C, Olmos-Martinez JM, Pascua R, Martínez-Taboada VM, Hernández JL. Unravelling the pandemic: impaired bone metabolism and risk of SARS-CoV-2 infection. Curr Med Res Opin 2025:1-13. [PMID: 40094222 DOI: 10.1080/03007995.2025.2479782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 01/06/2025] [Accepted: 03/10/2025] [Indexed: 03/19/2025]
Abstract
INTRODUCTION While the impact of COVID-19 on bone metabolism has been extensively studied, the inverse relationship remains less understood. This study investigates whether impaired bone metabolism is associated with an increased risk of COVID-19 infection. METHODS We conducted a nested case-control study within a population-based cohort, incorporating Kaplan-Meier analysis (KMA) to assess time to infection (TTI) differences. Propensity score matching (1:2) was performed and validated through standardized mean differences (<0.10), variance ratio (=1), and McFadden's pseudo-R2 (=0), ensuring balanced covariates. Bone status was evaluated using a composite index (AOMI), which included five components: P1NP and CTX (bone turnover markers), total hip bone mineral density (BMD-TH), trabecular bone score (TBS), and integral volumetric BMD (IvBMD). Inflammation and insulin resistance (IR) were assessed by albumin-to-globulin ratio (AGR <1.50) and the TG/HDL ratio (>2.50 in women and >2.80 in men), respectively. RESULTS We analysed 294 COVID-19 cases and 528 controls. AOMI+ individuals had a higher prevalence of COVID-19 (41.5% vs. 33.2%; p = 0.031), an adverse lipid pattern ("A" profile: high ApoB, LDL and TC) and pronounced bone changes (higher P1NP and CTX, lower BMD-TH, TBS, and IvBMD). AOMI - individuals were more likely to have metabolic syndrome, displayed a different lipid profile ("B" profile: elevated TG, AIP, and TG/HDL ratio), fewer bone alterations, and lower COVID-19 prevalence. TG/HDL ratio was 1.66 ± 1 in "A" profile, while it was 2.85 ± 1.4 in "B" profile individuals (p = 0.0001). Age acted as an effect modifier, and lowest tercile significantly increased COVID-19 risk associated with AOMI+ [Mantel-Haenszel OR = 1.42 (95%CI: 1.08-1.9); p = 0.022]. KMA identified AOMI+ men and individuals of both sexes in lowest age tercile, as groups with shorter TTI: These younger individuals had high CTX (women), low TBS (men), and high ApoB (both). In multivariable analyses, plasma CTX levels negatively correlated with TTI (adjusted β= -0.325; p = 0.0001). AOMI+ status was associated with increased COVID-19 risk after controlling for confounders, including IR (adjusted OR = 1.51; 95%CI: 1.04-2.10; p = 0.027), although this association weakened when adjusting for AGR (95%CI: 0.99-2.28; p = 0.055). ANCOVA-estimated adjusted TBS means were lower in COVID-19 cases compared to controls (1.259 vs. 1.294; p = 0.013). CONCLUSIONS Impaired bone metabolism was found to be associated with increased COVID-19 risk, in a relationship potentially mediated by underlying inflammation. Elevated osteoclastic activity and a defined lipid profile with high ApoB, TC, LDL levels, played a crucial role in the results. Bone quality parameters more accurately captured COVID-19-related bone changes than BMD.
Collapse
Affiliation(s)
- Emilio Pariente
- Healthcare Center Camargo Interior, Cantabria Health Service, Santander, Spain
- Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain
- Immunopathology Research Unit, Instituto de Investigación Valdecilla, Santander, Spain
| | - Marta Martín-Millán
- Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain
- Immunopathology Research Unit, Instituto de Investigación Valdecilla, Santander, Spain
- Bone Metabolism Unit, Department of Internal Medicine, Hospital Marqués de Valdecilla, Santander, Spain
| | - Daniel Nan
- Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain
- Immunopathology Research Unit, Instituto de Investigación Valdecilla, Santander, Spain
- Bone Metabolism Unit, Department of Internal Medicine, Hospital Marqués de Valdecilla, Santander, Spain
| | | | - Hector Basterrechea
- Healthcare Center Camargo Interior, Cantabria Health Service, Santander, Spain
| | - Javier Pardo
- Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain
- Immunopathology Research Unit, Instituto de Investigación Valdecilla, Santander, Spain
- Bone Metabolism Unit, Department of Internal Medicine, Hospital Marqués de Valdecilla, Santander, Spain
| | - Merelyn Bonome
- Healthcare Center Camargo Interior, Cantabria Health Service, Santander, Spain
| | - Sandra Solares
- Healthcare Center Camargo Interior, Cantabria Health Service, Santander, Spain
| | - Carmen Ramos
- Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain
- Immunopathology Research Unit, Instituto de Investigación Valdecilla, Santander, Spain
- Healthcare Center Camargo Costa, Cantabria Health Service, Santander, Spain
| | - Jose-Manuel Olmos-Martinez
- Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain
- Immunopathology Research Unit, Instituto de Investigación Valdecilla, Santander, Spain
- Bone Metabolism Unit, Department of Internal Medicine, Hospital Marqués de Valdecilla, Santander, Spain
| | - Raquel Pascua
- Immunopathology Research Unit, Instituto de Investigación Valdecilla, Santander, Spain
| | - Victor M Martínez-Taboada
- Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain
- Immunopathology Research Unit, Instituto de Investigación Valdecilla, Santander, Spain
- Division of Rheumatology, Hospital Marqués de Valdecilla, Santander, Spain
| | - José Luis Hernández
- Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain
- Immunopathology Research Unit, Instituto de Investigación Valdecilla, Santander, Spain
- Bone Metabolism Unit, Department of Internal Medicine, Hospital Marqués de Valdecilla, Santander, Spain
| |
Collapse
|
|
2
|
Gonda K, Hai T, Suzuki K, Ozaki A, Shibusa T, Takenoshita S, Maejima Y, Shimomura K. Effect of Ficus pumila L. on Improving Insulin Secretory Capacity and Resistance in Elderly Patients Aged 80 Years Old or Older Who Develop Diabetes After COVID-19 Infection. Nutrients 2025; 17:290. [PMID: 39861420 PMCID: PMC11767592 DOI: 10.3390/nu17020290] [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: 11/23/2024] [Revised: 01/08/2025] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
(1) Background: It has been reported that people affected by COVID-19, an infectious disease caused by SARS-CoV-2, suffer from various diseases, after infection. One of the most serious problems is the increased risk of developing diabetes after COVID-19 infection. However, a treatment for post-COVID-19 infection diabetes has not yet been established. In this study, we investigated the effects of Ficus pumila L. extract, which has traditionally been used to reduce blood glucose levels in Okinawa, on patients who developed diabetes after COVID-19 infection. (2) Methods: In total, 128 rehabilitation patients aged 80 years old or older who developed diabetes after COVID-19 infection were included. The HOMA-β (Homeostatic model assessment of β-cell function) and HOMA-IR (Homeostatic model assessment of insulin resistance) were assessed to evaluate the glucose tolerance. (3) Results: The HOMA-β decreased and HOMA-IR increased in patients who developed after diabetes after COVID-19 infection. Subsequently, 59 patients were given Ficus pumila L. extract and their HOMA-β and HOMA-IR improved after ingestion. On the other hand, the control group of patients who did not consume Ficus pumila L. showed no improvement in both HOMA-β and HOMA-IR. (4) Conclusions: Ficus pumila L. extract, ingested by patients who developed diabetes after COVID-19 infection, stimulated insulin secretion capacity and improved insulin resistance.
Collapse
Affiliation(s)
- Kenji Gonda
- Department of Breast and Thyroid Surgery, Jyoban Hospital of Tokiwa Foundation, Iwaki City 972-8322, Fukushima, Japan;
- Department of Gastrointestinal Tract Surgery, Fukushima Medical University, 1 Hikarigaoka, Fukushima City 960-1295, Fukushima, Japan
- Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima City 960-1295, Fukushima, Japan; (K.S.); (Y.M.); (K.S.)
| | - Takeshi Hai
- Department of Internal Medicine, Daido Central Hospital, 1-1-37 Asato, Naha City 902-0067, Okinawa, Japan;
| | - Kouichi Suzuki
- Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima City 960-1295, Fukushima, Japan; (K.S.); (Y.M.); (K.S.)
- Department of Internal Medicine, Daido Central Hospital, 1-1-37 Asato, Naha City 902-0067, Okinawa, Japan;
| | - Akihiko Ozaki
- Department of Breast and Thyroid Surgery, Jyoban Hospital of Tokiwa Foundation, Iwaki City 972-8322, Fukushima, Japan;
- Department of Gastrointestinal Tract Surgery, Fukushima Medical University, 1 Hikarigaoka, Fukushima City 960-1295, Fukushima, Japan
| | - Takashi Shibusa
- Department of Internal Medicine, Jyoban Hospital of Tokiwa Foundation, Iwaki City 972-8322, Fukushima, Japan;
| | - Seiichi Takenoshita
- Department of Drug Research for Astatine-221 Targeted Alfa Therapy, Fukushima Medical University, 1 Hikarigaoka, Fukushima City 960-1295, Fukushima, Japan;
| | - Yuko Maejima
- Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima City 960-1295, Fukushima, Japan; (K.S.); (Y.M.); (K.S.)
| | - Kenjyu Shimomura
- Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima City 960-1295, Fukushima, Japan; (K.S.); (Y.M.); (K.S.)
| |
Collapse
|
|
3
|
Miao X, Alidadipour A, Saed V, Sayyadi F, Jadidi Y, Davoudi M, Amraee F, Jadidi N, Afrisham R. Hepatokines: unveiling the molecular and cellular mechanisms connecting hepatic tissue to insulin resistance and inflammation. Acta Diabetol 2024; 61:1339-1361. [PMID: 39031190 DOI: 10.1007/s00592-024-02335-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 07/06/2024] [Indexed: 07/22/2024]
Abstract
Insulin resistance arising from Non-Alcoholic Fatty Liver Disease (NAFLD) stands as a prevalent global ailment, a manifestation within societies stemming from individuals' suboptimal dietary habits and lifestyles. This form of insulin resistance emerges as a pivotal factor in the development of type 2 diabetes mellitus (T2DM). Emerging evidence underscores the significant role of hepatokines, as hepatic-secreted hormone-like entities, in the genesis of insulin resistance and eventual onset of type 2 diabetes. Hepatokines exert influence over extrahepatic metabolism regulation. Their principal functions encompass impacting adipocytes, pancreatic cells, muscles, and the brain, thereby playing a crucial role in shaping body metabolism through signaling to target tissues. This review explores the most important hepatokines, each with distinct influences. Our review shows that Fetuin-A promotes lipid-induced insulin resistance by acting as an endogenous ligand for Toll-like receptor 4 (TLR-4). FGF21 reduces inflammation in diabetes by blocking the nuclear translocation of nuclear factor-κB (NF-κB) in adipocytes and adipose tissue, while also improving glucose metabolism. ANGPTL6 enhances AMPK and insulin signaling in muscle, and suppresses gluconeogenesis. Follistatin can influence insulin resistance and inflammation by interacting with members of the TGF-β family. Adropin show a positive correlation with phosphoenolpyruvate carboxykinase 1 (PCK1), a key regulator of gluconeogenesis. This article delves into hepatokines' impact on NAFLD, inflammation, and T2DM, with a specific focus on insulin resistance. The aim is to comprehend the influence of these recently identified hormones on disease development and their underlying physiological and pathological mechanisms.
Collapse
Affiliation(s)
- Xiaolei Miao
- School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, China
| | - Arian Alidadipour
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Vian Saed
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Firooze Sayyadi
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Yasaman Jadidi
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Davoudi
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Amraee
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Nastaran Jadidi
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Afrisham
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
4
|
Shabestari M, Azizi R, Ghadiri-Anari A. Type 2 diabetes and susceptibility to COVID-19: a machine learning analysis. BMC Endocr Disord 2024; 24:221. [PMID: 39434075 PMCID: PMC11492751 DOI: 10.1186/s12902-024-01758-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 10/16/2024] [Indexed: 10/23/2024] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) was one of the most prevalent comorbidities among patients with coronavirus disease 2019 (COVID-19). Interactions between different metabolic parameters contribute to the susceptibility to the virus; thereby, this study aimed to rank the importance of clinical and laboratory variables as risk factors for COVID-19 or as protective factors against it by applying machine learning methods. METHOD This study is a retrospective cohort conducted at a single center, focusing on a population with T2DM. The patients attended the Yazd Diabetes Research Center in Yazd, Iran, from February 20, 2020, to October 21, 2020. Clinical and laboratory data were collected within three months before the onset of the COVID-19 pandemic in Iran. 59 patients were infected with COVID-19, while 59 were not. The dataset was split into 70% training and 30% test sets. Principal Component Analysis (PCA) was applied to the data. The most important components were selected using a 'sequential feature selector' and scored by a Linear Discriminant Analysis model. PCA loadings were then multiplied by the PCs' scores to determine the importance of the original variables in contracting COVID-19. RESULTS HDL-C, followed by eGFR, showed a strong negative correlation with the risk of contracting the virus. Higher levels of HDL-C and eGFR offer protection against COVID-19 in the T2DM population. But, the ratio of BUN to creatinine did not show any correlation. Conversely, the AIP, TyG index and TG showed the most positive correlation with susceptibility to COVID-19 in such a way that higher levels of these factors increase the risk of contracting the virus. The positive correlation of diastolic BP, TyG-BMI index, MAP, BMI, weight, TC, FPG, HbA1C, Cr, systolic BP, BUN, and LDL-C with the risk of COVID-19 decreased, respectively. CONCLUSION The atherogenic index of plasma, triglyceride glucose index, and triglyceride levels are the most significant risk factors for COVID-19 contracting in individuals with T2DM. Meanwhile, high-density lipoprotein cholesterol is the most protective factor.
Collapse
Affiliation(s)
| | - Reyhaneh Azizi
- Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Akram Ghadiri-Anari
- Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
| |
Collapse
|
|
5
|
Mîndru DE, Țarcă E, Adumitrăchioaiei H, Anton-Păduraru DT, Ștreangă V, Frăsinariu OE, Sidoreac A, Stoica C, Bernic V, Luca AC. Obesity as a Risk Factor for the Severity of COVID-19 in Pediatric Patients: Possible Mechanisms-A Narrative Review. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1203. [PMID: 39457167 PMCID: PMC11506776 DOI: 10.3390/children11101203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 09/23/2024] [Accepted: 09/27/2024] [Indexed: 10/28/2024]
Abstract
Obesity, the current pandemic, is associated with alarming rises among children and adolescents, and the forecasts for the near future are worrying. The present paper aims to draw attention to the short-term effects of the excess adipose tissue in the presence of a viral infection, which can be life-threatening for pediatric patients, given that the course of viral infections is often severe, if not critical. The COVID-19 pandemic has been the basis of these statements, which opened the door to the study of the repercussions of obesity in the presence of a viral infection. Since 2003, with the discovery of SARS-CoV-1, interest in the study of coronaviruses has steadily increased, with a peak during the pandemic. Thus, obesity has been identified as an independent risk factor for COVID-19 infection and is correlated with a heightened risk of severe outcomes in pediatric patients. We sought to determine the main mechanisms through which obesity is responsible for the unfavorable evolution in the presence of a viral infection, with emphasis on the disease caused by SARS-CoV-2, in the hope that future studies will further elucidate this aspect, enabling prompt and effective intervention in obese patients with viral infections, whose clinical progression is likely to be favorable.
Collapse
Affiliation(s)
- Dana Elena Mîndru
- Department of Mother and Child Medicine, University of Medicine and Pharmacy “Gr.T.Popa”, 700115 Iasi, Romania; (D.E.M.); (D.T.A.-P.); (V.Ș.); (O.E.F.); (A.-C.L.)
| | - Elena Țarcă
- Department of Surgery II—Pediatric Surgery, University of Medicine and Pharmacy “Gr.T.Popa”, 700115 Iasi, Romania
| | - Heidrun Adumitrăchioaiei
- Department of Pediatrics, University of Medicine, Pharmacy, Sciences and Technology “George Emil Palade”, Târgu Mureș, Str. Gheorghe Marinescu Nr. 38, 540136 Târgu Mureș, Romania;
| | - Dana Teodora Anton-Păduraru
- Department of Mother and Child Medicine, University of Medicine and Pharmacy “Gr.T.Popa”, 700115 Iasi, Romania; (D.E.M.); (D.T.A.-P.); (V.Ș.); (O.E.F.); (A.-C.L.)
| | - Violeta Ștreangă
- Department of Mother and Child Medicine, University of Medicine and Pharmacy “Gr.T.Popa”, 700115 Iasi, Romania; (D.E.M.); (D.T.A.-P.); (V.Ș.); (O.E.F.); (A.-C.L.)
| | - Otilia Elena Frăsinariu
- Department of Mother and Child Medicine, University of Medicine and Pharmacy “Gr.T.Popa”, 700115 Iasi, Romania; (D.E.M.); (D.T.A.-P.); (V.Ș.); (O.E.F.); (A.-C.L.)
| | - Alexandra Sidoreac
- Emergency Clinical Hospital for Children “Sfanta Maria” Iasi, 700309 Iași, Romania; (A.S.); (C.S.)
| | - Cristina Stoica
- Emergency Clinical Hospital for Children “Sfanta Maria” Iasi, 700309 Iași, Romania; (A.S.); (C.S.)
| | - Valentin Bernic
- Department of Surgery II, “Saint Spiridon” Hospital, University Street, No 16, 700115 Iasi, Romania;
| | - Alina-Costina Luca
- Department of Mother and Child Medicine, University of Medicine and Pharmacy “Gr.T.Popa”, 700115 Iasi, Romania; (D.E.M.); (D.T.A.-P.); (V.Ș.); (O.E.F.); (A.-C.L.)
| |
Collapse
|
|
6
|
Grosman-Dziewiszek P, Jęśkowiak-Kossakowska I, Szeląg A, Wiatrak B. Patterns of Dietary Supplement Use during the COVID-19 Pandemic in Poland: Focus on Vitamin D and Magnesium. Nutrients 2024; 16:3225. [PMID: 39408194 PMCID: PMC11478616 DOI: 10.3390/nu16193225] [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: 08/25/2024] [Revised: 09/13/2024] [Accepted: 09/18/2024] [Indexed: 10/20/2024] Open
Abstract
Background: The COVID-19 pandemic has brought significant attention to the role of dietary supplements, particularly Vitamin D, in enhancing immunity and possibly mitigating the severity of the disease. The pandemic has highlighted the importance of nutritional health in preventing severe outcomes from infections. Objective: This study aimed to assess consumption patterns of dietary supplements, with a focus on Vitamin D, among the Polish population during the COVID-19 pandemic and to identify the demographic factors influencing these patterns. Methods: An anonymous survey was conducted in March 2021 among 926 pharmacy patients in Poland. The study analyzed the use of dietary supplements such as vitamin D, magnesium, and others in relation to variables like age, gender, and education level. Statistical analyses were performed using the Pearson chi-square test. Results: The study revealed that 77.1% of the respondents reported using dietary supplements, with Vitamin D being the most frequently mentioned, used by 64.6% of participants. Magnesium was also widely used, with a higher overall prevalence of 67.3%, making it the most commonly consumed supplement. The use of supplements was significantly higher among women and individuals with higher education. Younger age groups, particularly those aged 18-30, were more likely to use supplements. Conclusions: The use of supplements was significantly higher among women, individuals with higher education, and those aged 18-30. However, the findings also indicate a growing awareness and increased use across the general population. This trend reflects increased public awareness of the potential health benefits of these supplements in boosting immunity. However, the study also highlights the need for public education on the risks of over-supplementation and the importance of appropriate dosages.
Collapse
Affiliation(s)
| | - Izabela Jęśkowiak-Kossakowska
- Department of Pharmacology, Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 2, 50-345 Wroclaw, Poland; (P.G.-D.); (A.S.); (B.W.)
| | | | | |
Collapse
|
|
7
|
de Sousa Neto AL, Mendes-Rodrigues C, Pedroso RDS, Röder DVDDB. Revisiting the COVID-19 Pandemic: Mortality and Predictors of Death in Adult Patients in the Intensive Care Unit. Life (Basel) 2024; 14:1027. [PMID: 39202769 PMCID: PMC11355258 DOI: 10.3390/life14081027] [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: 07/17/2024] [Revised: 07/29/2024] [Accepted: 08/14/2024] [Indexed: 09/03/2024] Open
Abstract
COVID-19 has generated a global impact due to its contagiousness and high lethality rates, with a large number of deaths occurring in intensive care units (ICUs). This study aimed to verify the occurrence of and understand the factors related to mortality in adult patients with COVID-19 admitted to the ICU in a tertiary hospital. This is a retrospective cohort study, which included COVID-19 patients admitted between March 2020 and December 2021. A total of 588 patients were included, of whom the majority (55.27%) did not survive. Invasive mechanical ventilation was the strongest predictor of the risk of death in the ICU with OR = 97.85 (95% CI = 39.10-244.86; p < 0.001), along with age and Simplified Acute Physiology Score 3 (SAPS3). The length of the ICU stay was protective. Evaluating patients on invasive mechanical ventilation in isolation, using an adjusted model, we found the following risk factors: use of vasopressin, renal replacement therapy, red cell distribution width > 15, use of hydrocortisone, and age in years. Protective factors included the days of mechanical ventilation use, being admitted from another service, and being of female sex. Identifying early predictors of mortality in patients with COVID-19 who require hospitalization is essential in the search for actions to prevent and manage complications, which can increase the survival of these patients and reduce the impact on health services.
Collapse
Affiliation(s)
- Adriana Lemos de Sousa Neto
- Technical School of Health, Federal University of Uberlândia, Uberlândia 38400902, Brazil; (A.L.d.S.N.); (R.d.S.P.)
| | | | - Reginaldo dos Santos Pedroso
- Technical School of Health, Federal University of Uberlândia, Uberlândia 38400902, Brazil; (A.L.d.S.N.); (R.d.S.P.)
| | | |
Collapse
|
|
8
|
Hanifehpour H, Ashrafi F, Siasi E, Fallahi S. Evaluation and comparison of one-step real-time PCR and one-step RT-LAMP methods for detection of SARS-CoV-2. BMC Infect Dis 2024; 24:679. [PMID: 38982392 PMCID: PMC11232332 DOI: 10.1186/s12879-024-09574-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 06/27/2024] [Indexed: 07/11/2024] Open
Abstract
BACKGROUND There is an increasing disease trend for SARS-COV-2, so need a quick and affordable diagnostic method. It should be highly accurate and save costs compared to other methods. The purpose of this research is to achieve these goals. METHODS This study analyzed 342 samples using TaqMan One-Step RT-qPCR and fast One-Step RT-LAMP (Reverse Transcriptase Loop-Mediated Isothermal Amplification). The One-Step LAMP assay was conducted to assess the sensitivity and specificity. RESULTS The research reported positive samples using two different methods. In the RT-LAMP method, saliva had 92 positive samples (26.9%) and 250 negative samples (73.09%) and nasopharynx had 94 positive samples (27.4%) and 248 negative samples (72.51%). In the RT-qPCR method, saliva had 86 positive samples (25.1%) and 256 negative samples (74.8%) and nasopharynx had 93 positive samples (27.1%) and 249 negative samples (72.8%). The agreement between the two tests in saliva and nasopharynx samples was 93% and 94% respectively, based on Cohen's kappa coefficient (κ) (P < 0.001). The rate of sensitivity in this technique was reported at a dilution of 1 × 101 and 100% specificity. CONCLUSIONS Based on the results of the study the One-Step LAMP assay has multiple advantages. These include simplicity, cost-effectiveness, high sensitivity, and specificity. The One-Step LAMP assay shows promise as a diagnostic tool. It can help manage disease outbreaks, ensure prompt treatment, and safeguard public health by providing rapid, easy-to-use testing.
Collapse
Affiliation(s)
- Hooman Hanifehpour
- Department of Microbiology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Fatemeh Ashrafi
- Department of Microbiology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Elham Siasi
- Department of Microbiology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Shirzad Fallahi
- Hepatitis Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.
- Department of Parasitology and Mycology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
| |
Collapse
|
|
9
|
Mehraeen E, Abbaspour F, Banach M, SeyedAlinaghi S, Zarebidoki A, Tamehri Zadeh SS. The prognostic significance of insulin resistance in COVID-19: a review. J Diabetes Metab Disord 2024; 23:305-322. [PMID: 38932824 PMCID: PMC11196450 DOI: 10.1007/s40200-024-01385-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 12/31/2023] [Indexed: 06/28/2024]
Abstract
Objectives Emerging publications indicate that diabetes predisposes patients with COVID-19 to more severe complications, which is partly attributed to inflammatory condition. In the current review, we reviewed recent published literature to provide evidence on the role of insulin resistance (IR) in diabetes, the association between diabetes and COVID-19 severity and mortality, the impact of COVID-19 infection on incident new-onset diabetes, mechanisms responsible for IR in COVID-19 patients, and the predictive value of different surrogates of IR in COVID-19. Method The literature search performs to find out studies that have assessed the association between IR surrogates and morbidity and mortality in patients with COVID-19. Results We showed that there is a bulk of evidence in support of the fact that diabetes is a potent risk factor for enhanced morbidity and mortality in COVID-19 patients. COVID-19 patients with diabetes are more prone to remarkable dysglycemia compared to those without diabetes, which is associated with an unfavourable prognosis. Furthermore, SARS-COV2 can make patients predispose to IR and diabetes via activating ISR, affecting RAAS signaling pathway, provoking inflammation, and changing the expression of PPARɣ and SREBP-1. Additionally, higher IR is associated with increased morbidity and mortality in COVID-19 patients and different surrogates of IR can be utilized as a prognostic biomarker for COVID-19 patients. Conclusion Different surrogates of IR can be utilized as predictors of COVID-19 complications and death.
Collapse
Affiliation(s)
- Esmaeil Mehraeen
- Department of Health Information Technology, Khalkhal University of Medical Sciences, Khalkhal, Iran
| | - Faeze Abbaspour
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), 93338 Lodz, Poland
| | - SeyedAhmad SeyedAlinaghi
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
| | - Ameneh Zarebidoki
- School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Seyed Saeed Tamehri Zadeh
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Parvaneh Street, Velenjak, P.O. Box 19395-4763, Tehran, Iran
| |
Collapse
|
|
10
|
Nahalka J. 1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit. Int J Mol Sci 2024; 25:4440. [PMID: 38674024 PMCID: PMC11049929 DOI: 10.3390/ijms25084440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 04/10/2024] [Accepted: 04/17/2024] [Indexed: 04/28/2024] Open
Abstract
The COVID-19 pandemic prompted rapid research on SARS-CoV-2 pathogenicity. Consequently, new data can be used to advance the molecular understanding of SARS-CoV-2 infection. The present bioinformatics study discusses the "spikeopathy" at the molecular level and focuses on the possible post-transcriptional regulation of the SARS-CoV-2 spike protein S1 subunit in the host cell/tissue. A theoretical protein-RNA recognition code was used to check the compatibility of the SARS-CoV-2 spike protein S1 subunit with mRNAs in the human transcriptome (1-L transcription). The principle for this method is elucidated on the defined RNA binding protein GEMIN5 (gem nuclear organelle-associated protein 5) and RNU2-1 (U2 spliceosomal RNA). Using the method described here, it was shown that 45% of the genes/proteins identified by 1-L transcription of the SARS-CoV-2 spike protein S1 subunit are directly linked to COVID-19, 39% are indirectly linked to COVID-19, and 16% cannot currently be associated with COVID-19. The identified genes/proteins are associated with stroke, diabetes, and cardiac injury.
Collapse
Affiliation(s)
- Jozef Nahalka
- Institute of Chemistry, Centre for Glycomics, Slovak Academy of Sciences, Dubravska Cesta 9, SK-84538 Bratislava, Slovakia;
- Institute of Chemistry, Centre of Excellence for White-Green Biotechnology, Slovak Academy of Sciences, Trieda Andreja Hlinku 2, SK-94976 Nitra, Slovakia
| |
Collapse
|
|
11
|
Shukla AK, Awasthi K, Usman K, Banerjee M. Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus. World J Diabetes 2024; 15:606-622. [PMID: 38680697 PMCID: PMC11045416 DOI: 10.4239/wjd.v15.i4.606] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 01/22/2024] [Accepted: 02/27/2024] [Indexed: 04/11/2024] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It has affected over 768 million people worldwide, resulting in approximately 6900000 deaths. High-risk groups, identified by the Centers for Disease Control and Prevention, include individuals with conditions like type 2 diabetes mellitus (T2DM), obesity, chronic lung disease, serious heart conditions, and chronic kidney disease. Research indicates that those with T2DM face a heightened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals. Examining the renin-angiotensin system (RAS), a vital regulator of blood pressure and pulmonary stability, reveals the significance of the angiotensin-converting enzyme (ACE) and ACE2 enzymes. ACE converts angiotensin-I to the vasoconstrictor angiotensin-II, while ACE2 counters this by converting angiotensin-II to angiotensin 1-7, a vasodilator. Reduced ACE2 expression, common in diabetes, intensifies RAS activity, contributing to conditions like inflammation and fibrosis. Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels, concerns arise regarding the potential elevation of ACE2 receptors on cell membranes, potentially facilitating COVID-19 entry. This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome coronavirus 2 infection and associated complications in T2DM. Potential treatment strategies, including recombinant human ACE2 therapy, broad-spectrum antiviral drugs, and epigenetic signature detection, are discussed as promising avenues in the battle against this pandemic.
Collapse
Affiliation(s)
- Ashwin Kumar Shukla
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
| | - Komal Awasthi
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
| | - Kauser Usman
- Department of Medicine, King Georges’ Medical University, Lucknow 226003, Uttar Pradesh, India
| | - Monisha Banerjee
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
- Institute of Advanced Molecular Genetics, and Infectious Diseases (IAMGID), University of Lucknow, Lucknow 226007, Uttar Pradesh, India
| |
Collapse
|
|
12
|
Nhau PT, Gamede M, Sibiya N. COVID-19-Induced Diabetes Mellitus: Comprehensive Cellular and Molecular Mechanistic Insights. PATHOPHYSIOLOGY 2024; 31:197-209. [PMID: 38651404 PMCID: PMC11036300 DOI: 10.3390/pathophysiology31020016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 04/06/2024] [Accepted: 04/07/2024] [Indexed: 04/25/2024] Open
Abstract
Despite evidence demonstrating the risks of developing diabetes mellitus because of SARS-CoV-2, there is, however, insufficient scientific data available to elucidate the relationship between diabetes mellitus and COVID-19. Research indicates that SARS-CoV-2 infection is associated with persistent damage to organ systems due to the systemic inflammatory response. Since COVID-19 is known to induce these conditions, further investigation is necessary to fully understand its long-term effects on human health. Consequently, it is essential to consider the effect of the COVID-19 pandemic when predicting the prevalence of diabetes mellitus in the future, especially since the incidence of diabetes mellitus was already on the rise before the pandemic. Additional research is required to fully comprehend the impact of SARS-CoV-2 infection on glucose tolerance and insulin sensitivity. Therefore, this article delves deeper into the current literature and links the perceived relationship between SARS-CoV-2 and diabetes. In addition, the article highlights the necessity for further research to fully grasp the mechanisms that SARS-CoV-2 utilises to induce new-onset diabetes. Where understanding and consensus are reached, therapeutic interventions to prevent the onset of diabetes could be proposed. Lastly, we propose advocating for the regular screening of diabetes and pre-diabetes, particularly for the high-risk population with a history of COVID-19 infection.
Collapse
Affiliation(s)
- Praise Tatenda Nhau
- Pharmacology Division, Faculty of Pharmacy, Rhodes University, Makhanda 6139, South Africa;
| | - Mlindeli Gamede
- Human Physiology Department, University of Pretoria, Pretoria 0028, South Africa;
| | - Ntethelelo Sibiya
- Pharmacology Division, Faculty of Pharmacy, Rhodes University, Makhanda 6139, South Africa;
| |
Collapse
|
|
13
|
Igwe JK, Alaribe U. Cannabis use associated with lower mortality among hospitalized Covid-19 patients using the national inpatient sample: an epidemiological study. J Cannabis Res 2024; 6:18. [PMID: 38582889 PMCID: PMC10998318 DOI: 10.1186/s42238-024-00228-w] [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: 11/09/2023] [Accepted: 03/20/2024] [Indexed: 04/08/2024] Open
Abstract
BACKGROUND Prior reports indicate that modulation of the endocannabinoid system (ECS) may have a protective benefit for Covid-19 patients. However, associations between cannabis use (CU) or CU not in remission (active cannabis use (ACU)), and Covid-19-related outcomes among hospitalized patients is unknown. METHODS In this multicenter retrospective observational cohort analysis of adults (≥ 18 years-old) identified from 2020 National Inpatient Sample database, we utilize multivariable regression analyses and propensity score matching analysis (PSM) to analyze trends and outcomes among Covid-19-related hospitalizations with CU and without CU (N-CU) for primary outcome of interest: Covid-19-related mortality; and secondary outcomes: Covid-19-related hospitalization, mechanical ventilation (MV), and acute pulmonary embolism (PE) compared to all-cause admissions; for CU vs N-CU; and for ACU vs N-ACU. RESULTS There were 1,698,560 Covid-19-related hospitalizations which were associated with higher mortality (13.44% vs 2.53%, p ≤ 0.001) and worse secondary outcomes generally. Among all-cause hospitalizations, 1.56% of CU and 6.29% of N-CU were hospitalized with Covid-19 (p ≤ 0.001). ACU was associated with lower odds of MV, PE, and death among the Covid-19 population. On PSM, ACU(N(unweighted) = 2,382) was associated with 83.97% lower odds of death compared to others(N(unweighted) = 282,085) (2.77% vs 3.95%, respectively; aOR:0.16, [0.10-0.25], p ≤ 0.001). CONCLUSIONS These findings suggest that the ECS may represent a viable target for modulation of Covid-19. Additional studies are needed to further explore these findings.
Collapse
Affiliation(s)
- Joseph-Kevin Igwe
- Department of Medicine, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA.
| | - Ugo Alaribe
- Caribbean Medical University School of Medicine, 5600 N River Rd Suite 800, Rosemont, IL, 60018, USA
| |
Collapse
|
|
14
|
Whiley L, Lawler NG, Zeng AX, Lee A, Chin ST, Bizkarguenaga M, Bruzzone C, Embade N, Wist J, Holmes E, Millet O, Nicholson JK, Gray N. Cross-Validation of Metabolic Phenotypes in SARS-CoV-2 Infected Subpopulations Using Targeted Liquid Chromatography-Mass Spectrometry (LC-MS). J Proteome Res 2024; 23:1313-1327. [PMID: 38484742 PMCID: PMC11002931 DOI: 10.1021/acs.jproteome.3c00797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 02/21/2024] [Accepted: 02/23/2024] [Indexed: 04/06/2024]
Abstract
To ensure biological validity in metabolic phenotyping, findings must be replicated in independent sample sets. Targeted workflows have long been heralded as ideal platforms for such validation due to their robust quantitative capability. We evaluated the capability of liquid chromatography-mass spectrometry (LC-MS) assays targeting organic acids and bile acids to validate metabolic phenotypes of SARS-CoV-2 infection. Two independent sample sets were collected: (1) Australia: plasma, SARS-CoV-2 positive (n = 20), noninfected healthy controls (n = 22) and COVID-19 disease-like symptoms but negative for SARS-CoV-2 infection (n = 22). (2) Spain: serum, SARS-CoV-2 positive (n = 33) and noninfected healthy controls (n = 39). Multivariate modeling using orthogonal projections to latent structures discriminant analyses (OPLS-DA) classified healthy controls from SARS-CoV-2 positive (Australia; R2 = 0.17, ROC-AUC = 1; Spain R2 = 0.20, ROC-AUC = 1). Univariate analyses revealed 23 significantly different (p < 0.05) metabolites between healthy controls and SARS-CoV-2 positive individuals across both cohorts. Significant metabolites revealed consistent perturbations in cellular energy metabolism (pyruvic acid, and 2-oxoglutaric acid), oxidative stress (lactic acid, 2-hydroxybutyric acid), hypoxia (2-hydroxyglutaric acid, 5-aminolevulinic acid), liver activity (primary bile acids), and host-gut microbial cometabolism (hippuric acid, phenylpropionic acid, indole-3-propionic acid). These data support targeted LC-MS metabolic phenotyping workflows for biological validation in independent sample sets.
Collapse
Affiliation(s)
- Luke Whiley
- Australian
National Phenome Centre, Health Futures Institute Harry Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
- Centre
for Computational and Systems Medicine, Health Futures Institute Harry
Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
| | - Nathan G. Lawler
- Australian
National Phenome Centre, Health Futures Institute Harry Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
- Centre
for Computational and Systems Medicine, Health Futures Institute Harry
Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
| | - Annie Xu Zeng
- Australian
National Phenome Centre, Health Futures Institute Harry Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
| | - Alex Lee
- Australian
National Phenome Centre, Health Futures Institute Harry Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
| | - Sung-Tong Chin
- Australian
National Phenome Centre, Health Futures Institute Harry Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
| | - Maider Bizkarguenaga
- Centro
de Investigación Cooperativa en Biociencias—CIC bioGUNE,
Precision Medicine and Metabolism Laboratory, Basque Research and
Technology Alliance, Bizkaia Science and
Technology Park, Building
800, 48160 Derio, Spain
| | - Chiara Bruzzone
- Centro
de Investigación Cooperativa en Biociencias—CIC bioGUNE,
Precision Medicine and Metabolism Laboratory, Basque Research and
Technology Alliance, Bizkaia Science and
Technology Park, Building
800, 48160 Derio, Spain
| | - Nieves Embade
- Centro
de Investigación Cooperativa en Biociencias—CIC bioGUNE,
Precision Medicine and Metabolism Laboratory, Basque Research and
Technology Alliance, Bizkaia Science and
Technology Park, Building
800, 48160 Derio, Spain
| | - Julien Wist
- Australian
National Phenome Centre, Health Futures Institute Harry Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
- Centre
for Computational and Systems Medicine, Health Futures Institute Harry
Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
- Chemistry
Department, Universidad del Valle, Cali 76001, Colombia
| | - Elaine Holmes
- Australian
National Phenome Centre, Health Futures Institute Harry Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
- Centre
for Computational and Systems Medicine, Health Futures Institute Harry
Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
- Department
of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial
College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, U.K.
| | - Oscar Millet
- Centro
de Investigación Cooperativa en Biociencias—CIC bioGUNE,
Precision Medicine and Metabolism Laboratory, Basque Research and
Technology Alliance, Bizkaia Science and
Technology Park, Building
800, 48160 Derio, Spain
| | - Jeremy K. Nicholson
- Australian
National Phenome Centre, Health Futures Institute Harry Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
- Centre
for Computational and Systems Medicine, Health Futures Institute Harry
Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
- Institute
of Global Health Innovation, Faculty Building South Kensington Campus, Imperial College London, London SW7 2AZ, U.K.
| | - Nicola Gray
- Australian
National Phenome Centre, Health Futures Institute Harry Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
- Centre
for Computational and Systems Medicine, Health Futures Institute Harry
Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
| |
Collapse
|
|
15
|
Lonati C, Berezhnoy G, Lawler N, Masuda R, Kulkarni A, Sala S, Nitschke P, Zizmare L, Bucci D, Cannet C, Schäfer H, Singh Y, Gray N, Lodge S, Nicholson J, Merle U, Wist J, Trautwein C. Urinary phenotyping of SARS-CoV-2 infection connects clinical diagnostics with metabolomics and uncovers impaired NAD + pathway and SIRT1 activation. Clin Chem Lab Med 2024; 62:770-788. [PMID: 37955280 DOI: 10.1515/cclm-2023-1017] [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: 09/12/2023] [Accepted: 10/22/2023] [Indexed: 11/14/2023]
Abstract
OBJECTIVES The stratification of individuals suffering from acute and post-acute SARS-CoV-2 infection remains a critical challenge. Notably, biomarkers able to specifically monitor viral progression, providing details about patient clinical status, are still not available. Herein, quantitative metabolomics is progressively recognized as a useful tool to describe the consequences of virus-host interactions considering also clinical metadata. METHODS The present study characterized the urinary metabolic profile of 243 infected individuals by quantitative nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography mass spectrometry (LC-MS). Results were compared with a historical cohort of noninfected subjects. Moreover, we assessed the concentration of recently identified antiviral nucleosides and their association with other metabolites and clinical data. RESULTS Urinary metabolomics can stratify patients into classes of disease severity, with a discrimination ability comparable to that of clinical biomarkers. Kynurenines showed the highest fold change in clinically-deteriorated patients and higher-risk subjects. Unique metabolite clusters were also generated based on age, sex, and body mass index (BMI). Changes in the concentration of antiviral nucleosides were associated with either other metabolites or clinical variables. Increased kynurenines and reduced trigonelline excretion indicated a disrupted nicotinamide adenine nucleotide (NAD+) and sirtuin 1 (SIRT1) pathway. CONCLUSIONS Our results confirm the potential of urinary metabolomics for noninvasive diagnostic/prognostic screening and show that the antiviral nucleosides could represent novel biomarkers linking viral load, immune response, and metabolism. Moreover, we established for the first time a casual link between kynurenine accumulation and deranged NAD+/SIRT1, offering a novel mechanism through which SARS-CoV-2 manipulates host physiology.
Collapse
Affiliation(s)
- Caterina Lonati
- Center for Preclinical Research, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen, Germany
| | - Georgy Berezhnoy
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen, Germany
| | - Nathan Lawler
- Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University Perth, Australia
| | - Reika Masuda
- Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University Perth, Australia
| | - Aditi Kulkarni
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen, Germany
| | - Samuele Sala
- Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University Perth, Australia
| | - Philipp Nitschke
- Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University Perth, Australia
| | - Laimdota Zizmare
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen, Germany
| | - Daniele Bucci
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen, Germany
| | - Claire Cannet
- Bruker BioSpin GmbH, AIC Division, Ettlingen, Germany
| | | | - Yogesh Singh
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Nicola Gray
- Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University Perth, Australia
| | - Samantha Lodge
- Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University Perth, Australia
| | - Jeremy Nicholson
- Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University Perth, Australia
| | - Uta Merle
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
| | - Julien Wist
- Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University Perth, Australia
| | - Christoph Trautwein
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen, Germany
| |
Collapse
|
|
16
|
Li L, Li L, Cai X, Pan Z. New Insights into the Effects of SARS-CoV-2 on Metabolic Organs: A Narrative Review of COVID-19 Induced Diabetes. Diabetes Metab Syndr Obes 2024; 17:1383-1389. [PMID: 38529167 PMCID: PMC10962470 DOI: 10.2147/dmso.s454408] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 02/15/2024] [Indexed: 03/27/2024] Open
Abstract
Coronavirus disease 2019 (COVID-19)-induced new-onset diabetes has raised widespread concerns. Increased glucose concentration and insulin resistance levels were observed in the COVID-19 patients. COVID-19 patients with newly diagnosed diabetes may have worse clinical outcomes and can have serious consequences. The types and exact mechanisms of COVID-19-caused diabetes are not well understood. Understanding the direct effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pancreatic beta cells and insulin target metabolism organs, such as the liver, muscle, and adipose tissues, will provide new ideas for preventing and treating the new-onset diabetes induced by COVID-19.
Collapse
Affiliation(s)
- Lu Li
- Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
| | - Lin Li
- Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
| | - Xianhui Cai
- Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
| | - Zongfu Pan
- Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China
| |
Collapse
|
|
17
|
Huecksteadt TP, Myers EJ, Aamodt SE, Trivedi S, Warren KJ. An Evaluation of Type 1 Interferon Related Genes in Male and Female-Matched, SARS-CoV-2 Infected Individuals Early in the COVID-19 Pandemic. Viruses 2024; 16:472. [PMID: 38543837 PMCID: PMC10975322 DOI: 10.3390/v16030472] [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: 12/01/2023] [Revised: 03/08/2024] [Accepted: 03/16/2024] [Indexed: 05/23/2024] Open
Abstract
SARS-CoV-2 infection has claimed just over 1.1 million lives in the US since 2020. Globally, the SARS-CoV-2 respiratory infection spread to 771 million people and caused mortality in 6.9 million individuals to date. Much of the early literature showed that SARS-CoV-2 immunity was defective in the early stages of the pandemic, leading to heightened and, sometimes, chronic inflammatory responses in the lungs. This lung-associated 'cytokine storm' or 'cytokine release syndrome' led to the need for oxygen supplementation, respiratory distress syndrome, and mechanical ventilation in a relatively high number of people. In this study, we evaluated circulating PBMC from non-hospitalized, male and female, COVID-19+ individuals over the course of infection, from the day of diagnosis (day 0) to one-week post diagnosis (day 7), and finally 4 weeks after diagnosis (day 28). In our early studies, we included hospitalized and critically care patient PBMC; however, most of these individuals were lymphopenic, which limited our assessments of their immune integrity. We chose a panel of 30 interferon-stimulated genes (ISG) to evaluate by PCR and completed flow analysis for immune populations present in those PBMC. Lastly, we assessed immune activation by stimulating PBMC with common TLR ligands. We identified changes in innate cells, primarily the innate lymphoid cells (ILC, NK cells) and adaptive immune cells (CD4+ and CD8+ T cells) over this time course of infection. We found that the TLR-7 agonist, Resiquimod, and the TLR-4 ligand, LPS, induced significantly better IFNα and IFNγ responses in the later phase (day 28) of SARS-CoV-2 infection in those non-hospitalized COVID-19+ individuals as compared to early infection (day 0 and day 7). We concluded that TLR-7 and TLR-4 agonists may be effective adjuvants in COVID-19 vaccines for mounting immunity that is long-lasting against SARS-CoV-2 infection.
Collapse
Affiliation(s)
- Tom P. Huecksteadt
- Salt Lake City VA Medical Center, Salt Lake City, UT 84148, USA; (T.P.H.); (E.J.M.); (S.E.A.); (S.T.)
| | - Elizabeth J. Myers
- Salt Lake City VA Medical Center, Salt Lake City, UT 84148, USA; (T.P.H.); (E.J.M.); (S.E.A.); (S.T.)
- Department of Neurology, University of Utah, Salt Lake City, UT 84132, USA
| | - Samuel E. Aamodt
- Salt Lake City VA Medical Center, Salt Lake City, UT 84148, USA; (T.P.H.); (E.J.M.); (S.E.A.); (S.T.)
- Department of Internal Medicine, Pulmonary Division, University of Utah Health Science Center, Salt Lake City, UT 84132, USA
| | - Shubhanshi Trivedi
- Salt Lake City VA Medical Center, Salt Lake City, UT 84148, USA; (T.P.H.); (E.J.M.); (S.E.A.); (S.T.)
- Department of Internal Medicine, Pulmonary Division, University of Utah Health Science Center, Salt Lake City, UT 84132, USA
- Division of Infectious Diseases, University of Utah, Salt Lake City, UT 84132, USA
| | - Kristi J. Warren
- Salt Lake City VA Medical Center, Salt Lake City, UT 84148, USA; (T.P.H.); (E.J.M.); (S.E.A.); (S.T.)
- Department of Internal Medicine, Pulmonary Division, University of Utah Health Science Center, Salt Lake City, UT 84132, USA
| |
Collapse
|
|
18
|
Wan EYF, Mathur S, Zhang R, Lam AHY, Wang B, Yan VKC, Chui CSL, Li X, Wong CKH, Lai FTT, Cheung CL, Chan EWY, Tan KCB, Wong ICK. Long-term effects of coronavirus disease 2019 on diabetes complications and mortality in people with diabetes: Two cohorts in the UK and Hong Kong. Diabetes Obes Metab 2023; 25:3807-3816. [PMID: 37735816 DOI: 10.1111/dom.15279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 08/22/2023] [Accepted: 08/28/2023] [Indexed: 09/23/2023]
Abstract
AIM To evaluate the long-term associations between coronavirus disease 2019 (COVID-19) and diabetes complications and mortality, in patients with diabetes. MATERIALS AND METHODS People with diabetes diagnosed with COVID-19 infection (exposed group), from 16 March 2020 to 31 May 2021 from the UK Biobank (UKB cohort; n = 2456), and from 1 April 2020 to 31 May 2022 from the electronic health records in Hong Kong (HK cohort; n = 80 546), were recruited. Each patient was randomly matched with participants with diabetes but without COVID-19 (unexposed group), based on age and sex (UKB, n = 41 801; HK, n = 391 849). Patients were followed for up to 18 months until 31 August 2021 for UKB, and up to 28 months until 15 August 2022 for HK. Characteristics between cohorts were further adjusted with Inverse Probability Treatment Weighting. Long-term association of COVID-19 with multi-organ disease complications and all-cause mortality after 21 days of diagnosis was evaluated by Cox regression. RESULTS Compared with uninfected participants, patients with COVID-19 infection with diabetes were consistently associated with higher risks of cardiovascular diseases (coronary heart disease [CHD]: hazard ratio [HR] [UKB]: 1.6 [95% confidence interval {CI}: 1.0, 2.4], HR [HK]: 1.2 [95% CI: 1.0, 1.5]; and stroke: HR [UKB]: 2.0 [95% CI: 1.1, 3.6], HR [HK]: 1.5 [95% CI: 1.3, 1.8]), microvascular disease (end stage renal disease: HR [UKB]: 2.1 [95% CI: 1.1, 4.0], HR [HK]: 1.2 [95% CI: 1.1, 1.4]) and all-cause mortality (HR [UKB]: 4.6 [95% CI: 3.8, 5.5], HR [HK]: 2.6 [95% CI: 2.5, 2.8]), in both cohorts. CONCLUSIONS COVID-19 infection is associated with long-term increased risks of diabetes complications (especially cardiovascular complications, and mortality) in people with diabetes. Monitoring for signs/symptoms of developing these long-term complications post-COVID-19 infection in the infected patient population of people with diabetes may be beneficial in minimizing their morbidity and mortality.
Collapse
Affiliation(s)
- Eric Yuk Fai Wan
- Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong, China
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Sukriti Mathur
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Ran Zhang
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Athene Hoi Ying Lam
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Boyuan Wang
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Vincent Ka Chun Yan
- Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Celine Sze Ling Chui
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong, China
- School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Xue Li
- Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong, China
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Carlos King Ho Wong
- Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong, China
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Francisco Tsz Tsun Lai
- Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong, China
| | - Ching Lung Cheung
- Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong, China
| | - Esther Wai Yin Chan
- Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong, China
- Department of Pharmacy, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- The University of Hong Kong Shenzhen Institute of Research and Innovation, Shenzhen, China
| | - Kathryn Choon Beng Tan
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Ian Chi Kei Wong
- Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong, China
- The University of Hong Kong Shenzhen Institute of Research and Innovation, Shenzhen, China
- Aston Pharmacy School, Aston University, Birmingham, UK
| |
Collapse
|
|
19
|
Karonova TL, Mikhailova AA, Lagutina DI, Vorobeva OM, Grigoreva DO, Sterkhova KA, Malko VA, Mikheeva AG, Chernikova AT, Mitrofanova LB, Shlyakhto EV. Glucose metabolism disorders associated with COVID-19: clinical and morphological study. DIABETES MELLITUS 2023; 26:515-525. [DOI: 10.14341/dm13041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/02/2024]
Abstract
BACKGROUND. Glucose metabolism disorders (GMD) were detected both in acute and in post-COVID, however, its pathogenic aspects remain unclear.AIM. To analyze the occurrence of GMD in post-COVID patients who have had moderate and severe COVID-19 without previously known GMD disorders, and evaluate expression of SARS-CoV-2 proteins and its entry factors in pancreas in acute COVID-19.METHODS. Among 187 hospitalized patients with confirmed COVID-19 141 patients without previously diagnosed GMD underwent follow-up post-COVID visits. The examination for all patients included anthropometric measurement with calculation of BMI, level of HbA1c and fasting plasma glucose, for 106 patients level of insulin and HOMA-IR index was analyzed. For histological examination, pancreas fragments of 20 patients with fatal outcome were selected. Immunohistochemical study was performed with antibodies to SARS-CoV-2, ACE2, DPP4, as well as double-labeled immunofluorescence microscopy (insulin-SARS-CoV-2, insulin-ACE2, insulin-DPP4).RESULTS. Among 141 patients in post-COVID period, 9 (6.3%) had HbA1c or fasting plasma glucose levels that met criteria for diabetes mellitus, 38 (26.9%) — exceeded normal values (WHO), and 84 (59.6%) had GMD according to criteria of the ADA. In post-COVID, patients with GMD had a higher BMI and HOMA-IR index (p=0.001) compared to patients with normal glycemic levels. Only 40.4% of people had HOMA-IR index above 2.7. Patients with GMD had higher level of CRP (p=0.007) and a maximum glucose level (p=0.019) in the acute period. Positive relationship was found between BMI and HOMA index both in acute (p<0.001; r=0.389) and post-COVID (p<0.001; r=0.412) periods, as well as the level of HbA1c in acute period (p=0.019, r=0.202) and in post-COVID (p=0.004, r=0.242).Histological and immunohistochemical studies showed the expression of SARS-CoV-2 proteins in 1.85% [0–15.4] and 11.1% [5.3–14.8] cells of the Langerhans islets in patients who died on the second and third waves, respectively. The expression of ACE2 and DPP4 in the islets of Langerhans did not exceed 0.4% [0–1.7] and 0.5% [0–0.8] of cells, respectively. Double-labeled immunofluorescence microscopy showed co-localization of SARS-CoV-2, ACE2, DPP4 with insulin.CONCLUSION. Post-COVID Glucose metabolism disorders may be explained by direct cytotoxic effect of SARS-COV-2, increased glucose toxicity and insulin resistance because of the acute infection and its complex therapy.
Collapse
|
|
20
|
Alicandro G, La Vecchia C, Islam N, Pizzato M. A comprehensive analysis of all-cause and cause-specific excess deaths in 30 countries during 2020. Eur J Epidemiol 2023; 38:1153-1164. [PMID: 37684387 PMCID: PMC10663248 DOI: 10.1007/s10654-023-01044-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 08/12/2023] [Indexed: 09/10/2023]
Abstract
The impact of COVID-19 on mortality from specific causes of death remains poorly understood. This study analysed cause-of-death data provided by the World Health Organization from 2011 to 2019 to estimate excess deaths in 2020 in 30 countries. Over-dispersed Poisson regression models were used to estimate the number of deaths that would have been expected if the pandemic had not occurred, separately for men and women. The models included year and age categories to account for temporal trends and changes in size and age structure of the populations. Excess deaths were calculated by subtracting observed deaths from expected ones. Our analysis revealed significant excess deaths from ischemic heart diseases (IHD) (in 10 countries), cerebrovascular diseases (CVD) (in 10 countries), and diabetes (in 19 countries). The majority of countries experienced excess mortality greater than 10%, including Mexico (+ 38·8% for IHD, + 34·9% for diabetes), Guatemala (+ 30·0% for IHD, + 10·2% for CVD, + 39·7% for diabetes), Cuba (+ 18·8% for diabetes), Brazil (+ 12·9% for diabetes), the USA (+ 15·1% for diabetes), Slovenia (+ 33·8% for diabetes), Poland (+ 30·2% for IHD, + 19·5% for CVD, + 26 1% for diabetes), Estonia (+ 26·9% for CVD, + 34·7% for diabetes), Bulgaria (+ 22·8% for IHD, + 11·4% for diabetes), Spain (+ 19·7% for diabetes), Italy (+ 18·0% for diabetes), Lithuania (+ 17·6% for diabetes), Finland (+ 13·2% for diabetes) and Georgia (+ 10·7% for IHD, + 19·0% for diabetes). In 2020, 22 out of 30 countries had a significant increase in total mortality. Some of this excess was attributed to COVID-19, but a substantial increase was also observed in deaths attributed to cardiovascular diseases and diabetes.
Collapse
Affiliation(s)
- Gianfranco Alicandro
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
- Cystic Fibrosis Centre, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Nazrul Islam
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
- School of Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, UK
| | - Margherita Pizzato
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| |
Collapse
|
|
21
|
Alves LI, Bosco AA, Rosa AA, Correia MRS, Matioli SR, da Silva MER. Diabetes related phenotypes and their influence on outcomes of patients with corona virus disease 2019 (COVID-19). Diabetol Metab Syndr 2023; 15:203. [PMID: 37845766 PMCID: PMC10577940 DOI: 10.1186/s13098-023-01168-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Accepted: 09/21/2023] [Indexed: 10/18/2023] Open
Abstract
INTRODUCTION Diabetes mellitus (DM) is associated with severe forms of COVID-19 but little is known about the diabetes-related phenotype considering pre-admission, on-admission and data covering the entire hospitalization period. METHODS We analyzed COVID-19 inpatients (n = 3327) aged 61.2(48.2-71.4) years attended from March to September 2020 in a public hospital. RESULTS DM group (n = 1218) differed from Non-DM group (n = 2109) by higher age, body mass index (BMI), systolic blood pressure and lower O2 saturation on admission. Gender, ethnicity and COVID-19-related symptoms were similar. Glucose and several markers of inflammation, tissue injury and organ dysfunction were higher among patients with diabetes: troponin, lactate dehydrogenase, creatine phosphokinase (CPK), C-reactive protein (CRP), lactate, brain natriuretic peptide, urea, creatinine, sodium, potassium but lower albumin levels. Hospital (12 × 11 days) and intensive care unit permanence (10 × 9 days) were similar but DM group needed more vasoactive, anticoagulant and anti-platelet drugs, oxygen therapy, endotracheal intubation and dialysis. Lethality was higher in patients with diabetes (39.3% × 30.7%) and increased with glucose levels and age, in male sex and with BMI < 30 kg/m2 in both groups (obesity paradox). It was lower with previous treatment with ACEi/BRA in both groups. Ethnicity and education level did not result in different outcomes between groups. Higher frequency of comorbidities (hypertension, cardiovascular/renal disease, stroke), of inflammatory (higher leucocyte number, RCP, LDH, troponin) and renal markers (urea, creatinine, potassium levels and lower sodium, magnesium) differentiated lethality risk between patients with and without diabetes. CONCLUSIONS Comorbidities, inflammatory markers and renal disfunction but not Covid-19-related symptoms, obesity, ethnicity and education level differentiated lethality risk between patients with and without diabetes.
Collapse
Affiliation(s)
- Lais Isidoro Alves
- Laboratório de Carboidratos e Radioimunoensaio LIM-18, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Adriana Aparecida Bosco
- Laboratório de Carboidratos e Radioimunoensaio LIM-18, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Adriana Aparecida Rosa
- Laboratório de Carboidratos e Radioimunoensaio LIM-18, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Marcia Regina Soares Correia
- Laboratório de Carboidratos e Radioimunoensaio LIM-18, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Sergio Russo Matioli
- Departamento de Genética e Biologia Evolutiva, Instituto de Biociências da Universidade de São Paulo, São Paulo, Brazil
| | - Maria Elizabeth Rossi da Silva
- Laboratório de Carboidratos e Radioimunoensaio LIM-18, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
| |
Collapse
|
|
22
|
Granados AA, Bucher S, Song H, Agrawal A, Chen AT, Peng T, Neff N, Pisco AO, Huang F, Wang B. Single-nuclei characterization of pervasive transcriptional signatures across organs in response to COVID-19. eLife 2023; 12:e81090. [PMID: 37830426 PMCID: PMC10575628 DOI: 10.7554/elife.81090] [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: 06/15/2022] [Accepted: 07/16/2023] [Indexed: 10/14/2023] Open
Abstract
Background Infection by coronavirus SARS-CoV2 is a severe and often deadly disease that has implications for the respiratory system and multiple organs across the human body. While the effects in the lung have been extensively studied, less is known about the impact COVID-19 has across other organs. Methods Here, we contribute a single-nuclei RNA-sequencing atlas comprising six human organs across 20 autopsies where we analyzed the transcriptional changes due to COVID-19 in multiple cell types. The integration of data from multiple organs enabled the identification of systemic transcriptional changes. Results Computational cross-organ analysis for endothelial cells and macrophages identified systemic transcriptional changes in these cell types in COVID-19 samples. In addition, analysis of gene modules showed enrichment of specific signaling pathways across multiple organs in COVID-19 autopsies. Conclusions Altogether, the COVID Tissue Atlas enables the investigation of both cell type-specific and cross-organ transcriptional responses to COVID-19, providing insights into the molecular networks affected by the disease and highlighting novel potential targets for therapies and drug development. Funding The Chan-Zuckerberg Initiative, The Chan-Zuckerberg Biohub.
Collapse
Affiliation(s)
| | - Simon Bucher
- Division of Gastroenterology, Department of Medicine, University of California, San FranciscoSan FranciscoUnited States
| | - Hanbing Song
- Department of Medicine, San Francisco Veterans Affairs Medical Center, University of California San FranciscoSan FranciscoUnited States
| | | | | | - Tien Peng
- Yale UniversityNew HavenUnited States
| | - Norma Neff
- Chan-Zuckerberg BiohubSan FranciscoUnited States
| | | | - Franklin Huang
- Department of Medicine, San Francisco Veterans Affairs Medical Center, University of California San FranciscoSan FranciscoUnited States
| | - Bruce Wang
- Division of Gastroenterology, Department of Medicine, University of California, San FranciscoSan FranciscoUnited States
| |
Collapse
|
|
23
|
Gałgańska H, Jarmuszkiewicz W, Gałgański Ł. Carbon dioxide and MAPK signalling: towards therapy for inflammation. Cell Commun Signal 2023; 21:280. [PMID: 37817178 PMCID: PMC10566067 DOI: 10.1186/s12964-023-01306-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 09/05/2023] [Indexed: 10/12/2023] Open
Abstract
Inflammation, although necessary to fight infections, becomes a threat when it exceeds the capability of the immune system to control it. In addition, inflammation is a cause and/or symptom of many different disorders, including metabolic, neurodegenerative, autoimmune and cardiovascular diseases. Comorbidities and advanced age are typical predictors of more severe cases of seasonal viral infection, with COVID-19 a clear example. The primary importance of mitogen-activated protein kinases (MAPKs) in the course of COVID-19 is evident in the mechanisms by which cells are infected with SARS-CoV-2; the cytokine storm that profoundly worsens a patient's condition; the pathogenesis of diseases, such as diabetes, obesity, and hypertension, that contribute to a worsened prognosis; and post-COVID-19 complications, such as brain fog and thrombosis. An increasing number of reports have revealed that MAPKs are regulated by carbon dioxide (CO2); hence, we reviewed the literature to identify associations between CO2 and MAPKs and possible therapeutic benefits resulting from the elevation of CO2 levels. CO2 regulates key processes leading to and resulting from inflammation, and the therapeutic effects of CO2 (or bicarbonate, HCO3-) have been documented in all of the abovementioned comorbidities and complications of COVID-19 in which MAPKs play roles. The overlapping MAPK and CO2 signalling pathways in the contexts of allergy, apoptosis and cell survival, pulmonary oedema (alveolar fluid resorption), and mechanical ventilation-induced responses in lungs and related to mitochondria are also discussed. Video Abstract.
Collapse
Affiliation(s)
- Hanna Gałgańska
- Faculty of Biology, Molecular Biology Techniques Laboratory, Adam Mickiewicz University in Poznan, Uniwersytetu Poznanskiego 6, 61-614, Poznan, Poland
| | - Wieslawa Jarmuszkiewicz
- Faculty of Biology, Department of Bioenergetics, Adam Mickiewicz University in Poznan, Institute of Molecular Biology and Biotechnology, Uniwersytetu Poznanskiego 6, 61-614, Poznan, Poland
| | - Łukasz Gałgański
- Faculty of Biology, Department of Bioenergetics, Adam Mickiewicz University in Poznan, Institute of Molecular Biology and Biotechnology, Uniwersytetu Poznanskiego 6, 61-614, Poznan, Poland.
| |
Collapse
|
|
24
|
Sivaprakasam DR, Ohiri HO, Asif MS, Jahangir MS, Khan MKG, Nabeel MA, Abdullah RM. COVID-19 Vaccination and Its Relation to New-Onset Diabetes: A Narrative Review. Cureus 2023; 15:e47056. [PMID: 38022276 PMCID: PMC10644121 DOI: 10.7759/cureus.47056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/14/2023] [Indexed: 12/01/2023] Open
Abstract
The COVID-19 vaccination has been effective in preventing a lot of complications caused by SARS-CoV-2 and its variants. Meanwhile, diabetes mellitus, one of the root causes of many co-morbidities, exhibited itself during the COVID-19 pandemic and after COVID-19 vaccination. Diabetes mellitus introduced itself in a new perspective, leading to a variety of presentations and causing a significant number of emergency admissions. Many of the pre-diabetes patients with no prior history of diabetes developed fulminant type 1 diabetes mellitus (T1DM) after the COVID-19 vaccination. Some cases of conversion of type 2 diabetes mellitus (T2DM) into T1DM were reported. Some prediabetes/diabetes patients presented with the development of diabetic ketoacidosis after COVID-19 vaccination, whereas some previously healthy people with no relation to diabetes also developed acute exacerbations of new-onset T1DM or T2DM along with lethal ketoacidosis. The purpose of writing this review was to explore what kind of people are more prone to develop new-onset diabetes or diabetic complications, including diabetic ketoacidosis, the typical presentation of these patients, possible mechanisms that lead to these complications occurring after the COVID-19 vaccination, how they can be managed, and whether there is a good prognosis after management or not.
Collapse
Affiliation(s)
| | | | - Mohammad S Asif
- Medicine Department, University College of Medicine and Dentistry, Lahore, PAK
| | | | | | | | | |
Collapse
|
|
25
|
Kashfi K, Anbardar N, Asadipooya A, Asadipooya K. Type 1 Diabetes and COVID-19: A Literature Review and Possible Management. Int J Endocrinol Metab 2023; 21:e139768. [PMID: 38666042 PMCID: PMC11041820 DOI: 10.5812/ijem-139768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 09/27/2023] [Accepted: 09/30/2023] [Indexed: 04/28/2024] Open
Abstract
Context Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection normally damages the respiratory system but might likewise impair endocrine organs' function. Thyroid dysfunction and hyperglycemia are common endocrine complications of SARS-CoV-2 infection. The onset of type 1 diabetes (T1D) and associated complications, including diabetic ketoacidosis (DKA), hospitalization, and death, are thought to have increased during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to review the available data about the incidence rate of T1D and accompanying complications since the beginning of the COVID-19 pandemic. Evidence Acquisition A literature review was conducted using the electronic databases PubMed and Google Scholar. The keywords "T1D, T1DM, Type 1 DM or Type 1 Diabetes", "Coronavirus, SARS-CoV-2 or COVID-19" were used to search these databases. Titles and abstracts were screened for selection, and then relevant studies were reviewed in full text. Results A total of 25 manuscripts out of 304 identified studies were selected. There were 15 (60%) multicenter or nationwide studies. The data about the incidence rate of T1D, hospitalization, and death are not consistent across countries; however, DKA incidence and severity seem to be higher during the COVID-19 pandemic. The present study's data collection demonstrated that COVID-19 might or might not increase the incidence of T1D. Nevertheless, it is associated with the higher incidence and severity of DKA in T1D patients. This finding might indicate that antivirals are not fully protective against the endocrine complications of SARS-CoV-2 infection, which promotes the application of an alternative approach. Conclusions Combining medications that reduce SARS-CoV-2 entry into the cells and modulate the immune response to infection is an alternative practical approach to treating COVID-19.
Collapse
Affiliation(s)
- Kebria Kashfi
- Department of Clinical Medicine, Florida International University AUACOM, Florida, USA
| | - Narges Anbardar
- Department of Clinical Medicine, SMUSOM, Cleveland Clinic Lerner College of Medicine, Ohio, USA
| | - Artin Asadipooya
- Department of Neuroscience, University of Kentucky, Lexington, Kentucky, USA
| | - Kamyar Asadipooya
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Barnstable Brown Diabetes and Obesity Center, University of Kentucky, Lexington, Kentucky, USA
| |
Collapse
|
|
26
|
Corona-Meraz FI, Quintero-Castillo BP, Hernández-Palma LA, Machado-Sulbaran AC. Long COVID-19 and Insulin Autoimmune Syndrome: A Case Report. Clin Ther 2023; 45:e187-e192. [PMID: 37524570 DOI: 10.1016/j.clinthera.2023.06.026] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 06/25/2023] [Accepted: 06/30/2023] [Indexed: 08/02/2023]
Abstract
PURPOSE To describe a case report of a patient with symptoms associated with metabolic alterations 1 month after having COVID-19. METHODS Laboratory tests, clinical evaluations, and body composition assessments were performed by specialists. FINDINGS The patient presented excessive sweating, hot flashes, dizziness, blurred vision, and seizure. Laboratory tests indicated low glucose levels after convulsions (50, 42.7, and 55 mg/dL), high insulin levels (basal, 638 µIU/mL; 2-hour, >1000 µU/mL), and positivity for anti-insulin antibodies. The patient was diagnosed with insulin autoimmune syndrome. Treatment with azathioprine and nutritional recommendations improved remission. IMPLICATIONS SARS-CoV-2 infection or vaccination might induce insulin tolerance failure.
Collapse
Affiliation(s)
- Fernanda Isadora Corona-Meraz
- Departamento de Ciencias Biomédicas, Centro Universitario de Tonalá, Universidad de Guadalajara, Guadalajara, México
| | | | - Luis Alexis Hernández-Palma
- Instituto de Investigaciones en Comportamiento Alimentario y Nutrición, Centro Universitario del Sur, Universidad de Guadalajara, Guadalajara, México
| | - Andrea Carolina Machado-Sulbaran
- Instituto de Investigación en Cáncer en la Infancia y Adolescencia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México.
| |
Collapse
|
|
27
|
Grubišić B, Švitek L, Ormanac K, Sabo D, Mihaljević I, Bilić-Ćurčić I, Omanović Kolarić T. Molecular Mechanisms Responsible for Diabetogenic Effects of COVID-19 Infection-Induction of Autoimmune Dysregulation and Metabolic Disturbances. Int J Mol Sci 2023; 24:11576. [PMID: 37511334 PMCID: PMC10380525 DOI: 10.3390/ijms241411576] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/16/2023] [Accepted: 07/16/2023] [Indexed: 07/30/2023] Open
Abstract
The COVID-19 pandemic has revealed a significant association between SARS-CoV-2 infection and diabetes, whereby individuals with diabetes are more susceptible to severe disease and higher mortality rates. Interestingly, recent findings suggest a reciprocal relationship between COVID-19 and diabetes, wherein COVID-19 may contribute to developing new-onset diabetes and worsen existing metabolic abnormalities. This narrative review aims to shed light on the intricate molecular mechanisms underlying the diabetogenic effects of COVID-19. Specifically, the review explores the potential role of various factors, including direct damage to β-cells, insulin resistance triggered by systemic inflammation, and disturbances in hormonal regulation, aiming to enhance our understanding of the COVID-19 impact on the development and progression of diabetes. By analysing these mechanisms, the aim is to enhance our understanding of the impact of COVID-19 on the development and progression of diabetes. The binding of SARS-CoV-2 to angiotensin-converting enzyme 2 (ACE2) receptors, which are present in key metabolic organs and tissues, may interfere with glucometabolic pathways, leading to hyperglycaemia, and potentially contribute to the development of new disease mechanisms. The virus's impact on β-cells through direct invasion or systemic inflammation may induce insulin resistance and disrupt glucose homeostasis. Furthermore, glucocorticoids, commonly used to treat COVID-19, may exacerbate hyperglycaemia and insulin resistance, potentially contributing to new-onset diabetes. The long-term effects of COVID-19 on glucose metabolism are still unknown, necessitating further research into the possibility of developing a novel type of diabetes. This article provides a comprehensive overview of the current understanding of the interaction between COVID-19 and diabetes, highlighting potential areas for future research and therapeutic interventions.
Collapse
Affiliation(s)
- Barbara Grubišić
- Department of Infectious Diseases, University Hospital Centre Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
| | - Luka Švitek
- Department of Infectious Diseases, University Hospital Centre Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
| | - Klara Ormanac
- Department of Pharmacology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
| | - Dea Sabo
- Department of Pharmacology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
| | - Ivica Mihaljević
- Clinical Institute of Nuclear Medicine and Radiation Protection, University Hospital Centre Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
- Department for Nuclear Medicine and Oncology, Faculty of Medicine, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
- Academy of Medical Sciences of Croatia, 15 Kaptol Street, HR-10000 Zagreb, Croatia
| | - Ines Bilić-Ćurčić
- Department of Pharmacology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
- Department of Endocrinology and Metabolism Disorders, Internal Medicine Clinic, University Hospital Centre Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
| | - Tea Omanović Kolarić
- Department of Pharmacology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
- Faculty of Dental Medicine and Health Osijek, University of Osijek, 21 Crkvena Street, HR-31000 Osijek, Croatia
| |
Collapse
|
|
28
|
Wierzchowska-Opoka M, Grunwald A, Rekowska AK, Łomża A, Mekler J, Santiago M, Kabała Z, Kimber-Trojnar Ż, Leszczyńska-Gorzelak B. Impact of Obesity and Diabetes in Pregnant Women on Their Immunity and Vaccination. Vaccines (Basel) 2023; 11:1247. [PMID: 37515062 PMCID: PMC10385489 DOI: 10.3390/vaccines11071247] [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: 06/15/2023] [Revised: 07/14/2023] [Accepted: 07/15/2023] [Indexed: 07/30/2023] Open
Abstract
Pregnant women with obesity and diabetes are at increased risk of developing infections and other complications during pregnancy. Several mechanisms are involved in the immunological mechanisms that contribute to reduced immunity in these populations. Both obesity and diabetes are associated with chronic low-grade inflammation that can lead to an overactive immune response. Pregnant women with obesity and diabetes often have an increase in pro-inflammatory cytokines and adipokines, such as TNF-α, IL-6, IL-1β, leptin, and resistin, which are involved in the inflammatory response. Insulin resistance can also affect the functioning of immune cells. Furthermore, both conditions alter the composition of the gut microbiome, which produces a variety of biomolecules, including short-chain fatty acids, lipopolysaccharides, and other metabolites. These substances may contribute to immune dysfunction. In addition to increasing the risk of infections, obesity and diabetes can also affect the efficacy of vaccinations in pregnant women. Pregnant women with obesity and diabetes are at increased risk of developing severe illness and complications from COVID-19, but COVID-19 vaccination may help protect them and their fetuses from infection and its associated risks. Since both obesity and diabetes classify a pregnancy as high risk, it is important to elucidate the impact of these diseases on immunity and vaccination during pregnancy. Research examining the efficacy of the COVID-19 vaccine in a high-risk pregnant population should be of particular value to obstetricians whose patients are hesitant to vaccinate during pregnancy. Further research is needed to better understand these mechanisms and to develop effective interventions to improve immune function in these populations.
Collapse
Affiliation(s)
| | - Arkadiusz Grunwald
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Anna K Rekowska
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Aleksandra Łomża
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Julia Mekler
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Miracle Santiago
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Zuzanna Kabała
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Żaneta Kimber-Trojnar
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | | |
Collapse
|
|
29
|
Warpechowski J, Leszczyńska P, Juchnicka D, Olichwier A, Szczerbiński Ł, Krętowski AJ. Assessment of the Immune Response in Patients with Insulin Resistance, Obesity, and Diabetes to COVID-19 Vaccination. Vaccines (Basel) 2023; 11:1203. [PMID: 37515018 PMCID: PMC10383449 DOI: 10.3390/vaccines11071203] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 07/01/2023] [Accepted: 07/03/2023] [Indexed: 07/30/2023] Open
Abstract
The SARS-CoV-19 pandemic overwhelmed multiple healthcare systems across the world. Patients with underlying medical conditions such as obesity or diabetes were particularly vulnerable, had more severe symptoms, and were more frequently hospitalized. To date, there have been many studies on the severity of SARS-CoV-2 in patients with metabolic disorders, but data on the efficiency of vaccines against COVID-19 are still limited. This paper aims to provide a comprehensive overview of the effectiveness of COVID-19 vaccines in individuals with diabetes, insulin resistance, and obesity. A comparison is made between the immune response after vaccination in patients with and without metabolic comorbidities. Additionally, an attempt is made to highlight the mechanisms of immune stimulation affected by SARS-CoV-2 vaccines and how metabolic comorbidities modulate these mechanisms. The focus is on the most common COVID-19 vaccines, which include mRNA vaccines such as Pfizer-BioNTech and Moderna, as well as viral vector vaccines such as AstraZeneca and Johnson & Johnson. Furthermore, an effort is made to clarify how the functional differences between these vaccines may impact the response in individuals with metabolic disorders, drawing from available experimental data. This review summarizes the current knowledge regarding the post-vaccination response to COVID-19 in the context of metabolic comorbidities such as diabetes, insulin resistance, and obesity.
Collapse
Affiliation(s)
- Jędrzej Warpechowski
- Clinical Research Centre, Medical University of Bialystok, Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland
| | - Paula Leszczyńska
- Clinical Research Centre, Medical University of Bialystok, Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland
| | - Dominika Juchnicka
- Clinical Research Centre, Medical University of Bialystok, Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland
| | - Adam Olichwier
- Clinical Research Centre, Medical University of Bialystok, Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland
- Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
| | - Łukasz Szczerbiński
- Clinical Research Centre, Medical University of Bialystok, Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland
- Department of Endocrinology, Diabetology and Internal Diseases, Medical University of Bialystok, Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland
- Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA
- Programs in Metabolism and Medical and Population Genetics, Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA 02142, USA
| | - Adam Jacek Krętowski
- Clinical Research Centre, Medical University of Bialystok, Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland
- Department of Endocrinology, Diabetology and Internal Diseases, Medical University of Bialystok, Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland
| |
Collapse
|
|
30
|
Chang Y, Jeon J, Song TJ, Kim J. Association of triglyceride/high-density lipoprotein cholesterol ratio with severe complications of COVID-19. Heliyon 2023; 9:e17428. [PMID: 37366523 PMCID: PMC10275776 DOI: 10.1016/j.heliyon.2023.e17428] [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: 12/29/2022] [Revised: 06/13/2023] [Accepted: 06/16/2023] [Indexed: 06/28/2023] Open
Abstract
Background The coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can lead to serious complications such as respiratory failure, requiring mechanical ventilation or ICU care, and can even result in death, especially in older patients with comorbidities. The ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL), a biomarker of atherosclerotic dyslipidemia and insulin resistance, is related to cardiovascular mortality and morbidity. We aimed to evaluate the link between serious complications of COVID-19 and TG/HDL in the general population. Methods We conducted a comprehensive analysis of 3,933 COVID-19 patients from a nationwide cohort in Korea spanning from January 1 to June 4, 2020. TG/HDL ratio was calculated from the national health screening examination data underwent before the COVID-19 infection. Serious complications of COVID-19 were defined as a composite of high-flow oxygen therapy, mechanical ventilation, admission to the intensive care unit (ICU), and mortality. We employed logistic regression analysis to investigate the relationship between the TG/HDL ratio and the likelihood of developing severe complications within 2 months of the diagnosis. To visualize this association, we used a smoothing spline plot based on the generalized additive regression model. Multivariate analysis was performed with adjustment for age, gender, body mass index, lifestyle measures, and comorbidities. Results Among the 3,933 COVID-19 patients, the proportion of serious complications was 7.53%. Regarding individual outcomes, the number of patients who received high-flow oxygen therapy, mechanical ventilation, ICU care, and died was 84 (2.14%), 122 (3.10%), 173 (4.40%), and 118 (3.00%), respectively. In the multivariable logistic regression, a positive association was found between TG/HDL ratio and serious complications of COVID-19 (adjusted OR, 1.09; 95% CI [1.03-1.15], p = 0.004). Conclusion Our study revealed a significant positive association between TG/HDL ratio and the risk of developing severe complications in COVID-19-infected patients. While this finding provides valuable insight into the potential prognostic role of TG/HDL ratio in COVID-19, further studies are needed to fully elucidate the underlying mechanisms behind this relationship.
Collapse
Affiliation(s)
- Yoonkyung Chang
- Department of Neurology, Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea
| | - Jimin Jeon
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si, Republic of Korea
| | - Tae-Jin Song
- Department of Neurology, Seoul Hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea
| | - Jinkwon Kim
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si, Republic of Korea
| |
Collapse
|
|
31
|
Al-Hakeim HK, Al-Rubaye HT, Jubran AS, Almulla AF, Moustafa SR, Maes M. Increased insulin resistance due to Long COVID is associated with depressive symptoms and partly predicted by the inflammatory response during acute infection. REVISTA BRASILEIRA DE PSIQUIATRIA (SAO PAULO, BRAZIL : 1999) 2023; 45:205-215. [PMID: 36917827 PMCID: PMC10288478 DOI: 10.47626/1516-4446-2022-3002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 02/03/2023] [Indexed: 03/06/2023]
Abstract
OBJECTIVE Some months after the remission of acute COVID-19, some individuals show depressive symptoms, which are predicted by increased peak body temperature (PBT) and decreased blood oxygen saturation (SpO2). The present study aimed to examine data on whether long COVID is associated with increased insulin resistance (IR) in association with neuroimmune and oxidative (NIO) processes during the acute infectious and long COVID phases. METHODS This case-control, retrospective cohort study used the Homeostasis Model Assessment 2 (HOMA2) calculator© to compute ß-cell function (HOMA2%B) and insulin sensitivity (HOMA2%S) and resistance (HOMA2-IR) and administered the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAMD) to 86 patients with long COVID and 39 controls. RESULTS Long COVID (3-4 months after the acute infection) is accompanied by increased HOMA2-IR, fasting blood glucose (FBG), and insulin levels; 33.7% of the patients vs. 0% of the controls had HOMA2-IR values > 1.8, suggesting IR. Increased IR was predicted by PBT during acute infection and associated with depressive symptoms above and beyond the effects of NIO pathways (nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 [NLRP3] inflammasome, myeloperoxidase [MPO], protein oxidation). There were no significant associations between increased IR and the activated NIO pathways during long COVID. CONCLUSION Long COVID is associated with new-onset IR, which may contribute to onset of depressive symptoms due to long COVID by enhancing overall neurotoxicity.
Collapse
Affiliation(s)
| | | | | | - Abbas F. Almulla
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq
| | - Shatha Rouf Moustafa
- Clinical Analysis Department, College of Pharmacy, Hawler Medical University, Erbil, Iraq
| | - Michael Maes
- Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria
- Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Australia
| |
Collapse
|
|
32
|
Zahedi M, Kordrostami S, Kalantarhormozi M, Bagheri M. A Review of Hyperglycemia in COVID-19. Cureus 2023; 15:e37487. [PMID: 37187644 PMCID: PMC10181889 DOI: 10.7759/cureus.37487] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/12/2023] [Indexed: 05/17/2023] Open
Abstract
Diabetes mellitus (DM) is one of the most common chronic metabolic disorders worldwide, which increases the risk of common and opportunistic infections. Following the coronavirus disease 2019 (COVID-19) pandemic, a higher incidence rate, more severe forms of the disease, and exacerbation of hyperglycemia and its complications have been observed in patients with DM. Moreover, stress-induced hyperglycemia has been observed in many hospitalized nondiabetic patients after contracting COVID-19. Hyperglycemia worsens prognosis in both diabetic and nondiabetic patients. In this study, the mechanism of new-onset or exacerbation of hyperglycemia, the effect of the treatments used for COVID-19 on hyperglycemia, the importance and appropriate method of blood glucose (blood sugar (BS)) control during the disease, and the possible fate of new-onset hyperglycemia after recovery from COVID-19 to some extent is expressed.
Collapse
Affiliation(s)
- Maryam Zahedi
- Department of Internal Medicine, Endocrinology, and Metabolism, Clinical Research Development Unit (CRDU) 5 Azar Hospital, Golestan University of Medical Sciences, Gorgan, IRN
| | - Saba Kordrostami
- Department of Endocrinology and Diabetes, Clinical Research Development Unit (CRDU) 5 Azar Hospital, Golestan University of Medical Sciences, Gorgan, IRN
| | | | - Marziyeh Bagheri
- Department of Internal Medicine, Bushehr University of Medical Sciences, Bushehr, IRN
| |
Collapse
|
|
33
|
Cure E, Cumhur Cure M. Insulin may increase disease severity and mortality of COVID-19 through Na +/H + exchanger in patients with type 1 and type 2 diabetes mellitus. J Endocrinol Invest 2023; 46:845-847. [PMID: 36318448 PMCID: PMC9628438 DOI: 10.1007/s40618-022-01951-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 10/22/2022] [Indexed: 11/21/2022]
Affiliation(s)
- E. Cure
- Department of Internal Medicine, Bagcilar Medilife Hospital, Fevzicakmak Mh, Osmangazi Cd, Istanbul, Turkey
| | - M. Cumhur Cure
- Department of Biochemistry, Private Tanfer Hospital, Istanbul, Turkey
| |
Collapse
|
|
34
|
Jain A, Gupta P, Mittal AA, Sengar NS, Chaurasia R, Banoria N, Kankane A, Saxena A, Brijendra, Sharma M. Long-term quality of life and work ability among severe COVID-19 survivors: A multicenter study. DIALOGUES IN HEALTH 2023; 2:100124. [PMID: 36968307 PMCID: PMC10010834 DOI: 10.1016/j.dialog.2023.100124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 03/10/2023] [Accepted: 03/10/2023] [Indexed: 03/16/2023]
Abstract
Background Coronavirus disease 2019 (COVID-19), is known for its variable severity and high infectivity. Though fewer than 15% of infected cases develop severe disease, a major proportion had prolonged stay in the intensive care unit (ICU). Prolonged ICU stay is known to have a long-term impact on behavior and quality of life.8 Therefore, it is likely that patients discharged after severe COVID-19 have issues that persist for long term. The current study aimed to assess the long-term impact of severe COVID-19 on the Quality of life (QOL), sleep pattern, behavior, and workability. Methods The current multicenter study adopted a cross-sectional design to analyze data from two tertiary care COVID-19 dedicated hospitals. All experimental procedures were approved by the ethics committee of the M.L.B Medical College. Participants were 20–60 age group who had been admitted to the ICU because of severe COVID-19 and had elapsed at least one and a half year since their discharge. After informed written consent the participants were assessed for: EUROHIS-QOL 8-item index; Workability Score; Quality of sleep; The major depression inventory (MDI) questionnaire; Generalized anxiety disorder 7 item scale (GAD-7); Current global health status score: an innovative subjective scale (1−10) to determine the current global health status when 5 is the status before COVID-19. Findings 491 participants were assessed, the median follow-up time after discharge from the hospital was 561·0 days (range, 548–580 days). The mean duration of ICU stay was 8·72 ± 2·85 days. There was significant reduction in the prevalence of obesity, diabetes, and hypertension as compared with discharge time. The mean of EUROHIS-QOL score, workability score, current global health status score was 3·28 ± 0·98, 6·87 ± 0·85, 4·53 ± 1·36 respectively. The mean MDI and anxiety scores were 4·12 ± 1·45 and 18·63 ± 3·28, respectively. Interpretation Severe COVID-19 survivors have new-onset psychological disorders and sleep disturbances. Long term quality of life and work ability remains poor after prolong ICU admission secondary to severe COVID-19.
Collapse
Affiliation(s)
- Anshul Jain
- Department of Anaesthesiology Maharani Laxmi Bai Medical College, AH-2/9 Veerangna Nagar Jhansi, 284128, India,Corresponding author at: AH-2/9 Veerangna Nagar, Jhansi 284128, India
| | - Prashant Gupta
- Department of Surgery, S.N Medical College Agra, 27, Pushpanjali Enclave, Loha Mandi, Agra 282002, India
| | - Apurva Abhinandan Mittal
- Department of Anaesthesiology & Critical Care, S.N Medical College Agra, 503C Padam Pride Apartment Sector 16, Awas Vikas Colony, Agra 282002, India
| | - Narendra Singh Sengar
- Department of Nephrology, Maharani Laxmi Bai Medical College, Shree Ji Hospital, Veerangna Nagar Jhansi, 284128, India
| | - Rachna Chaurasia
- Department of Radiodiagnosis Maharani Laxmi Bai Medical College, Jhansi 284128, India
| | - Neeraj Banoria
- Department of Surgery M.L.B medical College Jhansi, PR -3, Maharani Laxmi Bai Medical College Campus, Jhansi 284128, India
| | - Arvind Kankane
- Department of Neurology M.L.B medical College Jhansi, PR Residence 14, Maharani Laxmi Bai Medical College Campus, Jhansi 284128, India
| | - Arpita Saxena
- Department of Anaesthesiology, S.N Medical College, Agra 282002, India
| | - Brijendra
- Department of Anaesthesiology Maharani Laxmi Bai Medical College, 80PG Hostel, Maharani Laxmi Bai Medical College Campus, Jhansi 284128, India
| | - Mrinal Sharma
- Department of Anaesthesiology S.N Medical College, Senior Boys Hostel, S.N Medical College Campus, Agra 284128, India
| |
Collapse
|
|
35
|
Popovic DS, Papanas N, Koufakis T, Kotsa K, Mahmeed WA, Al-Rasadi K, Al-Alawi K, Banach M, Banerjee Y, Ceriello A, Cesur M, Cosentino F, Firenze A, Galia M, Goh SY, Janez A, Kalra S, Kempler P, Kapoor N, Lessan N, Lotufo P, Rizvi AA, Sahebkar A, Santos RD, Stoian AP, Toth PP, Viswanathan V, Rizzo M. Glucometabolic Perturbations in Type 2 Diabetes Mellitus and Coronavirus Disease 2019: Causes, Consequences, and How to Counter Them Using Novel Antidiabetic Drugs - The CAPISCO International Expert Panel. Exp Clin Endocrinol Diabetes 2023; 131:260-267. [PMID: 36693416 DOI: 10.1055/a-2019-1111] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
The growing amount of evidence suggests the existence of a bidirectional relation between coronavirus disease 2019 (COVID-19) and type 2 diabetes mellitus (T2DM), as these two conditions exacerbate each other, causing a significant healthcare and socioeconomic burden. The alterations in innate and adaptive cellular immunity, adipose tissue, alveolar and endothelial dysfunction, hypercoagulation, the propensity to an increased viral load, and chronic diabetic complications are all associated with glucometabolic perturbations of T2DM patients that predispose them to severe forms of COVID-19 and mortality. Severe acute respiratory syndrome coronavirus 2 infection negatively impacts glucose homeostasis due to its effects on insulin sensitivity and β-cell function, further aggravating the preexisting glucometabolic perturbations in individuals with T2DM. Thus, the most effective ways are urgently needed for countering these glucometabolic disturbances occurring during acute COVID-19 illness in T2DM patients. The novel classes of antidiabetic medications (dipeptidyl peptidase 4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are considered candidate drugs for this purpose. This review article summarizes current knowledge regarding glucometabolic disturbances during acute COVID-19 illness in T2DM patients and the potential ways to tackle them using novel antidiabetic medications. Recent observational data suggest that preadmission use of GLP-1 RAs and SGLT-2is are associated with decreased patient mortality, while DPP-4is is associated with increased in-hospital mortality of T2DM patients with COVID-19. Although these results provide further evidence for the widespread use of these two classes of medications in this COVID-19 era, dedicated randomized controlled trials analyzing the effects of in-hospital use of novel antidiabetic agents in T2DM patients with COVID-19 are needed.
Collapse
Affiliation(s)
- Djordje S Popovic
- Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre of Vojvodina, Novi Sad, Serbia.,Medical Faculty, University of Novi Sad, Novi Sad, Serbia
| | - Nikolaos Papanas
- Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece
| | - Theocharis Koufakis
- Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
| | - Kalliopi Kotsa
- Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
| | - Wael Al Mahmeed
- Heart and Vascular Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates
| | | | - Kamila Al-Alawi
- Department of Training and Studies, Royal Hospital, Ministry of Health, Muscat, Oman
| | - Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Poland.,Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.,Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland
| | - Yajnavalka Banerjee
- Department of Biochemistry, Mohammed Bin Rashid University, Dubai, United Arab Emirates
| | | | - Mustafa Cesur
- Clinic of Endocrinology, Ankara Güven Hospital, Ankara, Turkey
| | - Francesco Cosentino
- Unit of Cardiology, Karolinska Institute and Karolinska University Hospital, University of Stockholm, Sweden
| | - Alberto Firenze
- Unit of Research and International Cooperation, University Hospital of Palermo, Italy
| | - Massimo Galia
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (Bind), University of Palermo, Italy
| | - Su-Yen Goh
- Department of Endocrinology, Singapore General Hospital, Singapore
| | - Andrej Janez
- Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, Slovenia
| | - Sanjay Kalra
- Department of Endocrinology, Bharti Hospital, Karnal, India
| | - Peter Kempler
- Department of Medicine and Oncology, Semmelweis University, Budapest, Hungary
| | - Nitin Kapoor
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India.,Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | - Nader Lessan
- The Research Institute, Imperial College London Diabetes Centre, Abu Dhabi, United Arab Emirates
| | - Paulo Lotufo
- Center for Clinical and Epidemiological Research, University Hospital, University of São Paulo, Brazil
| | - Ali A Rizvi
- Department of Medicine, University of Central Florida College of Medicine, Orlando, Florida, USA
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Raul D Santos
- Heart Institute (InCor) University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil.,Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Anca Pantea Stoian
- Faculty of Medicine, Diabetes, Nutrition and Metabolic Diseases, Carol Davila University, Bucharest, Romania
| | - Peter P Toth
- Cicarrone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | | | - Manfredi Rizzo
- Department of Biochemistry, Mohammed Bin Rashid University, Dubai, United Arab Emirates.,Faculty of Medicine, Diabetes, Nutrition and Metabolic Diseases, Carol Davila University, Bucharest, Romania.,Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), School of Medicine, University of Palermo, Italy
| |
Collapse
|
|
36
|
Huq AKMM, Roney M, Imran S, Khan SU, Uddin MN, Htar TT, Baig AA, Bhuiyan MA, Zakaria ZA, Aluwi MFFM, Tajuddin SN. Virtual screening of bioactive anti-SARS-CoV natural products and identification of 3β,12-diacetoxyabieta-6,8,11,13-tetraene as a potential inhibitor of SARS-CoV-2 virus and its infection related pathways by MD simulation and network pharmacology. J Biomol Struct Dyn 2023; 41:13923-13936. [PMID: 36786766 DOI: 10.1080/07391102.2023.2176926] [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: 11/02/2022] [Accepted: 01/28/2023] [Indexed: 02/15/2023]
Abstract
Since the first prevalence of COVID-19 in 2019, it still remains the most devastating pandemic throughout the world. The current research aimed to find potential natural products to inhibit the novel coronavirus and associated infection by MD simulation and network pharmacology approach. Molecular docking was performed for 39 natural products having potent anti-SARS-CoV activity. Five natural products showed high binding interaction with the viral main protease for the SARS-CoV-2 virus, where 3β,12-diacetoxyabieta-6,8,11,13 tetraene showed stable binding in MD simulation until 100 ns. Both 3β,12-diacetoxyabieta-6,8,11,13 tetraene and tomentin A targeted 11 common genes that are related to COVID-19 and interact with each other. Gene ontology development analysis further showed that all these 11 genes are attached to various biological processes. The KEGG pathway analysis also showed that the proteins that are targeted by 3β,12-diacetoxyabieta-6,8,11,13 tetraene and tomentin A are associated with multiple pathways related to COVID-19 infection. Furthermore, the ADMET and MDS studies reveals 3β,12-diacetoxyabieta-6,8,11,13 as the best-suited compound for oral drug delivery.Communicated by Ramaswamy H. Sarma.
Collapse
Affiliation(s)
- A K M Moyeenul Huq
- Bio Aromatic Research Centre, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia
- School of Medicine, Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
| | - Miah Roney
- Bio Aromatic Research Centre, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia
- Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia
| | - Syahrul Imran
- Atta-ur-Rahman Institute for Natural Product Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Puncak Alam, Selangor, Malaysia
- Faculty of Applied Science, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia
| | - Shafi Ullah Khan
- Product & Process Innovation Department, Qarshi Brands (Pvt) Ltd, Haripur, KPK, Pakistan
| | - Md Nazim Uddin
- Institute of Food Science and Technology, Bangladesh Council of Scientific and Industrial Research, Dhaka, Bangladesh
| | - Thet Thet Htar
- School of Pharmacy, Monash University Malaysia, Subang Jaya, Selangor, Malaysia
| | - Atif Amin Baig
- Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu, Terengannu, Malaysia
| | | | - Zainul Amiruddin Zakaria
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu, Sabah, Malaysia
| | - Mohd Fadhlizil Fasihi Mohd Aluwi
- Bio Aromatic Research Centre, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia
- Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia
| | - Saiful Nizam Tajuddin
- Bio Aromatic Research Centre, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia
- Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia
| |
Collapse
|
|
37
|
Aedh AI, Alshahrani MS, Huneif MA, Pryme IF, Oruch R. A Glimpse into Milestones of Insulin Resistance and an Updated Review of Its Management. Nutrients 2023; 15:nu15040921. [PMID: 36839279 PMCID: PMC9960458 DOI: 10.3390/nu15040921] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 02/03/2023] [Accepted: 02/08/2023] [Indexed: 02/15/2023] Open
Abstract
Insulin is the main metabolic regulator of fuel molecules in the diet, such as carbohydrates, lipids, and proteins. It does so by facilitating glucose influx from the circulation into the liver, adipose tissue, and skeletal myocytes. The outcome of which is subjected to glycogenesis in skeletal muscle and lipogenesis in adipose tissue, as well as in the liver. Therefore, insulin has an anabolic action while, on the contrary, hypoinsulinemia promotes the reverse process. Protein breakdown in myocytes is also encountered during the late stages of diabetes mellitus. The balance of the blood glucose level in physiological conditions is maintained by virtue of the interactive functions of insulin and glucagon. In insulin resistance (IR), the balance is disturbed because glucose transporters (GLUTs) of cell membranes fail to respond to this peptide hormone, meaning that glucose molecules cannot be internalized into the cells, the consequence of which is hyperglycemia. To develop the full state of diabetes mellitus, IR should be associated with the impairment of insulin release from beta-cells of the pancreas. Periodic screening of individuals of high risk, such as those with obesity, hypercholesterolemia, and pregnant nulliparous women in antenatal control, is vital, as these are important checkpoints to detect cases of insulin resistance. This is pivotal as IR can be reversed, provided it is detected in its early stages, through healthy dietary habits, regular exercise, and the use of hypoglycemic agents. In this review, we discuss the pathophysiology, etiology, diagnosis, preventive methods, and management of IR in brief.
Collapse
Affiliation(s)
- Abdullah I. Aedh
- Department of Internal Medicine, School of Medicine, Najran University, Najran 66324, Saudi Arabia
| | - Majed S. Alshahrani
- Department of Obstetrics & Gynecology, School of Medicine, Najran University, Najran 66324, Saudi Arabia
| | - Mohammed A. Huneif
- Department of Pediatrics, School of Medicine, Najran University, Najran 66324, Saudi Arabia
| | - Ian F. Pryme
- Department of Biomedicine, School of Medicine, University of Bergen, 5020 Bergen, Norway
| | - Ramadhan Oruch
- Department of Biochemistry and Molecular Biology, School of Medicine, Najran University, Najran 66324, Saudi Arabia
- Correspondence: ; Tel.: +966-562144606
| |
Collapse
|
|
38
|
Galstyan GR. The use of long-acting insulin degludec in adult patients with type 2 diabetes mellitus in real clinical practice in Russia. DIABETES MELLITUS 2023. [DOI: 10.14341/dm12976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
BACKGROUND: Effective glycaemic control remains the most important task in managing the risks of Diabetes type 2 complications development. In this regard, the choice of insulin preparations with minimal variability of action is of utmost importance since this approach allows achieving the maximum treatment effectiveness and adequate safety level.AIM: The aim of this study was to investigate insulin degludec treatment effect on glycemic control in adult patients with Diabetes Mellitus (DM) type 2 in a real-world clinical setting in the Russian Federation.MATERIALS AND METHODS: The open prospective study was conducted in 2020–2021 in 35 clinical centers in 31 cities of the Russian Federation. The study included adult patients with type 2 DM treated according to Russian routine clinical practice. The prospective follow-up period was 26 weeks. The main study endpoints were changes in HbA1c level, fasting plasma glucose, insulin daily doses, number, and characteristics of different types of hypoglycaemia episodes and adverse events (AEs), and patient preferences compared to previous treatment.RESULTS: The study enrolled 494 patients. By the end of follow-up period:The mean HbA1c decrease was 1.6% (p<0.0001).Fasting plasma glucose level decreased by 3.4 mmol/L (p<0.0001).Daily basal and prandial insulin doses decreased by 1.6 IU/day (p<0.0001) and 2.1 IU/day (p<0.01), respectively.Severe episodes of hypoglycemia did not occur, while the incidence of nonsevere episodes decreased significantly.76 patients (15.4%) had 105 AEs, of which 41 (in 33 patients, 6.7%) were serious.COVID-19 was the most frequent AE reported in 21 patients (4.3%).Only in one case insulin degludec was withdrawn due to the patient’s pregnancy and the AEs that arose from it.Most patients (98.6%) preferred insulin degludec to previous treatment.CONCLUSION: The study demonstrated a statistically significant improvement in glycemic control, accompanied by basal insulin dose decrease combined with the absence of severe episodes of hypoglycemia, and significant decrease of nonsevere episodes (total and nocturnal). These results led to a large proportion of patients wanting to continue insulin degludec treatment preferring the medicine over previous treatment.
Collapse
|
|
39
|
Huang P, Zhang LY, Tan YY, Chen SD. Links between COVID-19 and Parkinson's disease/Alzheimer's disease: reciprocal impacts, medical care strategies and underlying mechanisms. Transl Neurodegener 2023; 12:5. [PMID: 36717892 PMCID: PMC9885419 DOI: 10.1186/s40035-023-00337-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 01/12/2023] [Indexed: 01/31/2023] Open
Abstract
The impact of coronavirus disease 2019 (COVID-19) pandemic on patients with neurodegenerative diseases and the specific neurological manifestations of COVID-19 have aroused great interest. However, there are still many issues of concern to be clarified. Therefore, we review the current literature on the complex relationship between COVID-19 and neurodegenerative diseases with an emphasis on Parkinson's disease (PD) and Alzheimer's disease (AD). We summarize the impact of COVID-19 infection on symptom severity, disease progression, and mortality rate of PD and AD, and discuss whether COVID-19 infection could trigger PD and AD. In addition, the susceptibility to and the prognosis of COVID-19 in PD patients and AD patients are also included. In order to achieve better management of PD and AD patients, modifications of care strategies, specific drug therapies, and vaccines during the pandemic are also listed. At last, mechanisms underlying the link of COVID-19 with PD and AD are reviewed.
Collapse
Affiliation(s)
- Pei Huang
- grid.16821.3c0000 0004 0368 8293Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Lin-Yuan Zhang
- grid.412478.c0000 0004 1760 4628Department of Neurology, Shanghai General Hospital, Shanghai, 200080 China
| | - Yu-Yan Tan
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Sheng-Di Chen
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. .,Lab for Translational Research of Neurodegenerative Diseases, Shanghai Institute for Advanced Immunochemical Studies (SIAIS), Shanghai Tech University, Shanghai, 201210, China.
| |
Collapse
|
|
40
|
Dallavalasa S, Tulimilli SV, Prakash J, Ramachandra R, Madhunapantula SV, Veeranna RP. COVID-19: Diabetes Perspective-Pathophysiology and Management. Pathogens 2023; 12:pathogens12020184. [PMID: 36839456 PMCID: PMC9967788 DOI: 10.3390/pathogens12020184] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/05/2023] [Accepted: 01/19/2023] [Indexed: 01/26/2023] Open
Abstract
Recent evidence relating to the impact of COVID-19 on people with diabetes is limited but continues to emerge. COVID-19 pneumonia is a newly identified illness spreading rapidly throughout the world and causes many disabilities and fatal deaths. Over the ensuing 2 years, the indirect effects of the pandemic on healthcare delivery have become prominent, along with the lingering effects of the virus on those directly infected. Diabetes is a commonly identified risk factor that contributes not only to the severity and mortality of COVID-19 patients, but also to the associated complications, including acute respiratory distress syndrome (ARDS) and multi-organ failure. Diabetic patients are highly affected due to increased viral entry into the cells and decreased immunity. Several hypotheses to explain the increased incidence and severity of COVID-19 infection in people with diabetes have been proposed and explained in detail recently. On the other hand, 20-50% of COVID-19 patients reported new-onset hyperglycemia without diabetes and new-onset diabetes, suggesting the two-way interactions between COVID-19 and diabetes. A systematic review is required to confirm diabetes as a complication in those patients diagnosed with COVID-19. Diabetes and diabetes-related complications in COVID-19 patients are primarily due to the acute illness caused during the SARS-CoV-2 infection followed by the release of glucocorticoids, catecholamines, and pro-inflammatory cytokines, which have been shown to drive hyperglycemia positively. This review provides brief insights into the potential mechanisms linking COVID-19 and diabetes, and presents clinical management recommendations for better handling of the disease.
Collapse
Affiliation(s)
- Siva Dallavalasa
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory (DST-FIST Supported Centre), Department of Biochemistry (DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education and Research (JSS AHER), Mysuru 570015, India
| | - SubbaRao V. Tulimilli
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory (DST-FIST Supported Centre), Department of Biochemistry (DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education and Research (JSS AHER), Mysuru 570015, India
| | - Janhavi Prakash
- Department of Biochemistry, Council of Scientific and Industrial Research (CSIR)-Central Food Technological Research Institute (CFTRI), Mysuru 570020, India
| | - Ramya Ramachandra
- Department of Biochemistry, Council of Scientific and Industrial Research (CSIR)-Central Food Technological Research Institute (CFTRI), Mysuru 570020, India
| | - SubbaRao V. Madhunapantula
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory (DST-FIST Supported Centre), Department of Biochemistry (DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education and Research (JSS AHER), Mysuru 570015, India
- Leader, Special Interest Group in Cancer Biology and Cancer Stem Cells (SIG-CBCSC), JSS Medical College, JSS Academy of Higher Education and Research (JSS AHER), Mysuru 570015, India
| | - Ravindra P. Veeranna
- Department of Biochemistry, Council of Scientific and Industrial Research (CSIR)-Central Food Technological Research Institute (CFTRI), Mysuru 570020, India
- Correspondence:
| |
Collapse
|
|
41
|
Raber J, Rhea EM, Banks WA. The Effects of Viruses on Insulin Sensitivity and Blood-Brain Barrier Function. Int J Mol Sci 2023; 24:2377. [PMID: 36768699 PMCID: PMC9917142 DOI: 10.3390/ijms24032377] [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: 01/02/2023] [Revised: 01/19/2023] [Accepted: 01/23/2023] [Indexed: 01/27/2023] Open
Abstract
In this review manuscript, we discuss the effects of select common viruses on insulin sensitivity and blood-brain barrier (BBB) function and the potential overlapping and distinct mechanisms involved in these effects. More specifically, we discuss the effects of human immunodeficiency virus (HIV), herpes, hepatitis, influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 viruses on insulin sensitivity and BBB function and the proposed underlying mechanisms. These viruses differ in their ability to be transported across the BBB, disrupt the BBB, and/or alter the function of the BBB. For RSV and SARS-CoV-2, diabetes increases the risk of infection with the virus, in addition to viral infection increasing the risk for development of diabetes. For HIV and hepatitis C and E, enhanced TNF-a levels play a role in the detrimental effects. The winter of 2022-2023 has been labeled as a tridemic as influenza, RSV, and COVID-19 are all of concern during this flu season. There is an ongoing discussion about whether combined viral exposures of influenza, RSV, and COVID-19 have additive, synergistic, or interference effects. Therefore, increased efforts are warranted to determine how combined viral exposures affect insulin sensitivity and BBB function.
Collapse
Affiliation(s)
- Jacob Raber
- Departments of Behavioral Neuroscience, Neurology and Radiation Medicine; Affiliate Scientist, Division of Neuroscience, ONPRC, Oregon Health & Science University, Portland, OR 97239, USA
| | - Elizabeth M. Rhea
- Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA
- Department of Medicine, University of Washington, Seattle, WA 98108, USA
| | - William A. Banks
- Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA
- Department of Medicine, University of Washington, Seattle, WA 98108, USA
| |
Collapse
|
|
42
|
Asaduzzaman M, Romel Bhuia M, Zabed Jillul Bari M, Nazmul Alam Z, Rahman K, Hossain E, Alam MMJ. Predictors of mortality and ICU requirement in hospitalized COVID-19 patients with diabetes: A multicentre study. Nurs Open 2022; 10:3178-3190. [PMID: 36575597 PMCID: PMC9880734 DOI: 10.1002/nop2.1567] [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: 08/04/2022] [Revised: 11/15/2022] [Accepted: 12/10/2022] [Indexed: 12/29/2022] Open
Abstract
AIM This study aimed to identify the predictors of mortality and ICU requirements in hospitalized COVID-19 Patients with Diabetes. DESIGN Cross-sectional study. METHODS It was a retrospective study of patients hospitalized with COVID-19 infection from October 2020-February 2021 in four hospitals in Sylhet, Bangladesh. Logistic regression analysis was applied to explore the predictors of ICU requirement and in-hospital mortality. RESULTS In the whole cohort (n = 500), 11% of patients died and 24% of patients required intensive care unit (ICU) support. Non-survivors had significantly higher prevalence of lymphopenia, thrombocytopenia and leukocytosis. Significant predictors of in-hospital mortality were older age, neutrophil count, platelet count and admission peripheral capillary oxygen saturation (SpO2). Older age, ischemic heart disease, WBC count, D-dimer and admission SpO2 were identified as significant predictors for ICU requirement. PATIENT OR PUBLIC CONTRIBUTION No.
Collapse
Affiliation(s)
- Md Asaduzzaman
- Department of MedicineSylhet MAG Osmani Medical College HospitalSylhetBangladesh
| | - Mohammad Romel Bhuia
- Department of StatisticsShahjalal University of Science and TechnologySylhetBangladesh
| | | | - Zhm Nazmul Alam
- Department of MedicineSylhet MAG Osmani Medical College HospitalSylhetBangladesh
| | - Khalidur Rahman
- Department of StatisticsShahjalal University of Science and TechnologySylhetBangladesh
| | - Enayet Hossain
- Department of MedicineSylhet MAG Osmani Medical CollegeSylhetBangladesh
| | | |
Collapse
|
|
43
|
Song LG, Bai SR, Hui DH, Ding LP, Sun L. Association of COVID-19 patient’s condition with fasting blood glucose and body mass index: A retrospective study. Technol Health Care 2022; 30:1287-1298. [DOI: 10.3233/thc-220248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND: The COVID-19 pandemic broke out in 2019 and rapidly spread across the globe. Most of the severe and dead cases are middle-aged and elderly patients with chronic systemic diseases. OBJECTIVE: This study aimed to assess the association between fasting blood glucose (FPG) and body mass index (BMI) levels in patients with coronavirus disease 2019 (COVID-19) under different conditions. METHODS: Experimental-related information (age, gender, BMI, and FPG on the second day of admission) from 86 COVID-19 cases (47 males and 39 females) with an average age of (39 ± 17) years was collected in April and November 2020. These cases were divided into three groups according to the most severe classification of each case determined by the clinical early warning indicators of severe-critically illness, the degree of progression, and the treatment plan shown in the diagnosis and treatment plan of COVID-19 pneumonia. Statistical models were used to analyze the differences in the levels of FPG and BMI, age, and gender among the three groups. RESULTS: 1. Experimental group: 21 patients with asymptomatic or and mild symptoms (group A), 45 patients with common non-progression (group B), and 20 patients with common progression and severe symptoms (group C). 2. The age differences among the three groups were statistically significant and elderly patients had a higher risk of severe disease (t= 4.1404, 3.3933, 9.2123, P= 0.0001, 0.0012, 0.0000). There was a higher proportion of females than males in the normal progression and severe disease cases (χ2= 5.512, P= 0.019). 3. The level of FPG was significantly higher in group C than in group A (t= 3.1655, P= 0.0030) and B (t= 2.0212, P= 0.0475). The number of diabetes or IFG in group C was significantly higher than in group A (χ2= 5.979, P= 0.014) and group B (χ2= 6.088, P= 0.014). 4. BMI was significantly higher in group C than in groups A (t= 3.8839, P= 0.0004) and B (t= 3.8188, P= 0.0003). The number of overweight or obese patients in group C was significantly higher than in groups A (χ2= 8.838, P= 0.003) and B (χ2= 10.794, P= 0.001). 5. Patients’ age, gender, and FPG were independent risk factors for COVID-19 disease progression (β= 0.380, 0.191, 0.186; P= 0.000, 0.034, 0.045). CONCLUSION: The levels of FPG and BMI were significantly increased in the population with common progressive and severe COVID-19. FPG and age are independent risk factors for the progression of COVID-19.
Collapse
Affiliation(s)
- Li-Gang Song
- Department of Endocrinology, HuLun Buir People’s Hospital, HuLun Buir, Inner Mongolia, China
| | - Su-Rong Bai
- Department of Endocrinology, HuLun Buir People’s Hospital, HuLun Buir, Inner Mongolia, China
| | - Deng-Hua Hui
- Department of Work Ability Appraisal, HuLun Buir Human Resources and Social Development, HuLun Buir, Inner Mongolia, China
| | - Li-Ping Ding
- Department of Endocrinology, HuLun Buir People’s Hospital, HuLun Buir, Inner Mongolia, China
| | - Lu Sun
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| |
Collapse
|
|
44
|
van den Boom L, Kostev K, Kuss O, Rathmann W, Rosenbauer J. Type 1 diabetes incidence in children and adolescents during the COVID-19 pandemic in Germany. Diabetes Res Clin Pract 2022; 193:110146. [PMID: 36347421 PMCID: PMC9637016 DOI: 10.1016/j.diabres.2022.110146] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 10/30/2022] [Accepted: 11/01/2022] [Indexed: 11/08/2022]
Abstract
AIMS/HYPOTHESIS The aim of this study was to analyze the incidence of type 1 diabetes in children and adolescents (<20 years of age) during the COVID-19 pandemic (3/2020 to 12/2021) in Germany. METHODS The present study was based on the IQVIA longitudinal prescription database (LRx), All persons (age ≤ 20 years) with new insulin prescriptions from 2016 to 2021 (index date) were selected and stratified by age group. Weekly (age-specific) data were used to forecast the prescription incidence for the pandemic period based on pre-pandemic data and to explore the relationship between weekly reported age-specific COVID-19 incidences and type 1 diabetes incidence and rate ratios of observed vs. predicted diabetes incidence respectively. RESULTS During the pre-pandemic period, there was a stable higher insulin prescription incidence during the winter period and a lower insulin prescription incidence during summer. During the pandemic period, there was less seasonal variation in incidence related to the finding that the observed incidence during summer in 2002 and 2021 was 44 % and 65 %, higher, respectively, than the expected incidence based on pre-pandemic year. We did not find any cross-correlations between the COVID-19 incidence and the type 1 diabetes incidence for any age group. Likewise, there were no cross-correlations between the COVID-19 incidence and the incidence rate ratios of observed incidences to predicted incidences. CONCLUSIONS/INTERPRETATION During the COVID-19 pandemic, there was less seasonal variation in the incidence of type 1 diabetes (defined by new insulin prescriptions), with higher observed than expected incidences during summer. We found no evidence that the increase in type 1 diabetes incidence during the COVID-19 pandemic relates to direct effects of COVID-19 pandemic.
Collapse
Affiliation(s)
- Louisa van den Boom
- Division of Pediatrics, DRK Hospital, Kirchen, Germany; Division of Pediatric Diabetology, Endocrinology, Metabolism and Obesity, Children's Hospital, University of Bonn, Bonn, Germany
| | | | - Oliver Kuss
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research, München-Neuherberg, Germany; Centre for Health and Society, Faculty of Medicine, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Wolfgang Rathmann
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research, München-Neuherberg, Germany
| | - Joachim Rosenbauer
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research, München-Neuherberg, Germany
| |
Collapse
|
|
45
|
Muacevic A, Adler JR. COVID-19 and Diabetes Mellitus: From Pathophysiology to Clinical Management. Cureus 2022; 14:e31895. [PMID: 36579192 PMCID: PMC9792302 DOI: 10.7759/cureus.31895] [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: 09/15/2022] [Accepted: 11/25/2022] [Indexed: 11/27/2022] Open
Abstract
An increase in the severity of the coronavirus disease 2019 (COVID-19) was observed in patients infected with the acute severe metabolism syndrome coronavirus type 2 (SARS-CoV-2). Patients who have COVID-19 infection may also be more susceptible to hyperglycemia. When paired with other risk factors, hyperglycemia might alter immune and inflammatory responses, predisposing people to significant COVID-19 and perhaps deadly outcomes. Angiotensin-converting accelerator 2 (ACE2), a component of the renin-angiotensin-aldosterone system (RAAS), is the principal entry receptor for SARS-CoV-2; nevertheless, dipeptidyl enzyme 4 (DPP4) may potentially serve as a binding target. However, preliminary data did not indicate a substantial effect on the susceptibility to SARS-CoV-2 using glucose-lowering DPP4 inhibitors. Because of their pharmacologic characteristics, salt-glucose cotransporter 2 (SGLT2) inhibitors should not be advised for COVID-19 patients because they may have adverse effects. Currently, taking a hypoglycemic drug should be the most efficient way to manage acute glycemia. The majority of market proof is said to categorize two diabetes mellitus (DM) and fails to distinguish between the two primary categories of DM due to its widespread use. For grouping one DM and COVID-19, there is now some constrained proof available. Most of those findings are just preliminary, so further research will undoubtedly be required to determine the best course of action for DM patients.
Collapse
|
|
46
|
Fakhrolmobasheri M, Vakhshoori M, Heidarpour M, Najimi A, Mozafari AM, Rezvanian H. Hypophosphatemia in Coronavirus Disease 2019 (COVID-19), Complications, and Considerations: A Systematic Review. BIOMED RESEARCH INTERNATIONAL 2022; 2022:1468786. [PMID: 36312855 PMCID: PMC9616661 DOI: 10.1155/2022/1468786] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 08/07/2022] [Accepted: 09/16/2022] [Indexed: 01/10/2023]
Abstract
Coronavirus disease 2019 (COVID-19) has various manifestations on different body organs, including the lungs, heart, kidneys, and central nervous system. However, the frequency of electrolyte abnormalities, especially hypophosphatemia, is still debated in this pandemic. Our main aim in this review is to evaluate the frequency and complications of hypophosphatemia in COVID-19-infected individuals. A systematic literature review was performed in Web of Science, Scopus, PubMed, EMBASE, and Cochrane electronic databases with the combination of different keywords till October 2021. We recruited all relevant published records (including cross-sectional and case-control studies as well as editorials and brief reports) assessing hypophosphatemia among patients with COVID-19 infection. After assessing all 928 recruited records and discarding duplicates, 4 records met the inclusion criteria. Three articles were further included during a manual search of the literature. Overall, the included studies reported 1757 subjects (males: 51.3%), with the mean age ranging from 37.2 ± 13.6 years to 65.9 ± 13.9 years. Hypophosphatemia prevalence has been reported from 7.6% to 19.5%. Patients with the severe status of COVID-19 had a higher prevalence of low serum phosphate levels than those with moderate infection. This review indicates that hypophosphatemia might be categorized as a complication in clinical settings during the COVID-19 pandemic, requiring a high clinical suspicion to implement appropriate diagnostic and therapeutic interventions to prevent life-threatening outcomes. However, it needs to be more elucidated by further studies whether hypophosphatemia in severe COVID-19 is directly related to COVID-19 or is just a complication of severe illness.
Collapse
Affiliation(s)
- Mohammad Fakhrolmobasheri
- Heart Failure Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehrbod Vakhshoori
- Heart Failure Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Maryam Heidarpour
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Arash Najimi
- Medical Education Department, Medical Education Research Center, Education Development Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amir Mohamad Mozafari
- Health Information Technology Research Center, Clinical Informationist Research Group, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hassan Rezvanian
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| |
Collapse
|
|
47
|
Carrondo MC, Moita JJ. Clinical profile of patients with type 2 diabetes after COVID-19 vaccination: A prospective study. OBESITY MEDICINE 2022; 35:100458. [PMID: 36268222 PMCID: PMC9561417 DOI: 10.1016/j.obmed.2022.100458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/23/2022] [Accepted: 10/10/2022] [Indexed: 11/17/2022]
Abstract
The purpose of this study was to characterize the clinical profile of patients with type 2 diabetes after COVID-19 vaccination. This prospective study has involved 100 adult diabetic patients followed in the primary health care. SARS-CoV-2 infection after COVID-19 vaccination was the outcome indicator.
Collapse
Affiliation(s)
- Maria Cristina Carrondo
- Polytechnic Institute of Coimbra College of Health Technology of Coimbra, Department Medical, Social, and Human Sciences, Portugal
| | | |
Collapse
|
|
48
|
Fukushima T, Chubachi S, Namkoong H, Otake S, Nakagawara K, Tanaka H, Lee H, Morita A, Watase M, Kusumoto T, Masaki K, Kamata H, Ishii M, Hasegawa N, Harada N, Ueda T, Ueda S, Ishiguro T, Arimura K, Saito F, Yoshiyama T, Nakano Y, Mutoh Y, Suzuki Y, Murakami K, Okada Y, Koike R, Kitagawa Y, Kimura A, Imoto S, Miyano S, Ogawa S, Kanai T, Fukunaga K. U-shaped association between abnormal serum uric acid levels and COVID-19 severity: reports from the Japan COVID-19 Task Force. Int J Infect Dis 2022; 122:747-754. [PMID: 35811077 PMCID: PMC9262647 DOI: 10.1016/j.ijid.2022.07.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 05/28/2022] [Accepted: 07/04/2022] [Indexed: 01/25/2023] Open
Abstract
OBJECTIVES This study aimed to identify the relationship between abnormal serum uric acid levels or a history of hyperuricemia and COVID-19 severity in the Japanese population. METHODS We included 1523 patients enrolled in the Japan COVID-19 Task Force cohort between February 2020 and May 2021. We compared the clinical characteristics, including co-morbidities, laboratory findings, and outcomes, particularly invasive mechanical ventilation (IMV), among patients with and without abnormal uric acid levels or a history of hyperuricemia. RESULTS Patients with high serum uric acid levels were older and had higher body weight and body mass index than those without. In addition, the multiple logistic regression analysis revealed a significant association between high serum uric acid levels or a history of hyperuricemia and an increased risk of IMV (odds ratio [OR] = 1.77; P = 0.03/OR = 1.56; P = 0.04). Moreover, patients with low uric acid levels on admission were also associated significantly with the requirement of IMV (OR = 5.09; P <0.0001). CONCLUSION Abnormal serum uric acid levels or a history of hyperuricemia were significantly associated with COVID-19 severity in the Japanese cohort.
Collapse
Affiliation(s)
- Takahiro Fukushima
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Shotaro Chubachi
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan,Corresponding author: Shotaro Chubachi, Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine. 35 Shinanomachi, Tokyo 160-8582, Japan, Telephone: 03-5363-3793; Fax: 03-3353-2502
| | - Ho Namkoong
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Shiro Otake
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Kensuke Nakagawara
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Hiromu Tanaka
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Ho Lee
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Atsuho Morita
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Mayuko Watase
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Tatsuya Kusumoto
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Katsunori Masaki
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Hirofumi Kamata
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Makoto Ishii
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Naoki Hasegawa
- Department of Infectious Diseases, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Norihiro Harada
- Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan
| | - Tetsuya Ueda
- Department of Respiratory Medicine, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
| | - Soichiro Ueda
- JCHO (Japan Community Health Care Organization) Saitama Medical Center, Internal Medicine, Saitama, Japan
| | - Takashi Ishiguro
- Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Kumagaya, Japan
| | - Ken Arimura
- Department of Respiratory Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Fukuki Saito
- Department of Emergency and Critical Care Medicine, Kansai Medical University General Medical Center, Moriguchi, Japan
| | - Takashi Yoshiyama
- Department of Respiratory Medicine, Fukujuji hospital, Kiyose, Japan
| | - Yasushi Nakano
- Department of Internal Medicine, Kawasaki Municipal Ida Hospital, Kawasaki, Japan
| | - Yoshikazu Mutoh
- Department of Infectious Diseases, Tosei General Hospital, Seto, Japan
| | - Yusuke Suzuki
- Department of Respiratory Medicine, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Koji Murakami
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yukinori Okada
- Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan,Department of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan,Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan
| | - Ryuji Koike
- Medical Innovation Promotion Center, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Akinori Kimura
- Institute of Research, Tokyo Medical and Dental University, Tokyo, Japan
| | - Seiya Imoto
- Division of Health Medical Intelligence, Human Genome Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan
| | - Satoru Miyano
- M&D Data Science Center, Tokyo Medical and Dental University, Tokyo, Japan
| | - Seishi Ogawa
- Department of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan,Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Koichi Fukunaga
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | | |
Collapse
|
|
49
|
Amorim MJB, Gomes SIL, Bicho RCS, Scott-Fordsmand JJ. On virus and nanomaterials - Lessons learned from the innate immune system - ACE activation in the invertebrate model Enchytraeus crypticus. JOURNAL OF HAZARDOUS MATERIALS 2022; 436:129173. [PMID: 35739709 PMCID: PMC9116975 DOI: 10.1016/j.jhazmat.2022.129173] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 05/13/2022] [Accepted: 05/15/2022] [Indexed: 06/03/2023]
Abstract
Current human research on COVID-19 - SARS-CoV-2 (Severe Acute Respiratory Syndrome-Corona Virus) showed that ACE2 (Angiotensin Converting Enzyme 2) is a functional receptor to which the spike proteins attach. Invertebrates have been exposed to a wide array of threats for millennia and their immune system has evolved to deal with these efficiently. The annelid Enchytraeus crypticus, a standard ecotoxicological species, is an invertebrate species where extensive mechanisms of response studies are available, covering all levels from gene to population responses. Nanomaterials (NMs) are often perceived as invaders (e.g. virus) and can enter the cell covered by a corona, triggering similar responses. We created a database on E. crypticus ACE gene expression, aiming to analyse the potential knowledge transfer between invertebrates and vertebrates. Total exposure experiments sum 87 stress conditions for 18 different nanomaterials (NMs). ACE expression following TiO2 NM exposure was clearly different from other NMs showing a clear (6-7 fold) ACE down-regulation, not observed for any other NMs. Other NMs, notably Ag NMs, and to some extent Cu NMs, caused ACE up-regulation (up to 4 fold). The extensive knowledge from response to NMs can support the immuno-research community, especially to develop therapies for virus that trigger the innate immune system.
Collapse
Affiliation(s)
- M J B Amorim
- Departament of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal.
| | - S I L Gomes
- Departament of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal
| | - R C S Bicho
- Departament of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal
| | - J J Scott-Fordsmand
- Department of Ecoscience, Aarhus University, C.F. Møllers Alle, DK-8000, Aarhus, Denmark
| |
Collapse
|
|
50
|
Association of triglyceride-glucose index with prognosis of COVID-19: A population-based study. J Infect Public Health 2022; 15:837-844. [PMID: 35779467 PMCID: PMC9225941 DOI: 10.1016/j.jiph.2022.06.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 11/22/2022] Open
Abstract
Background Triglyceride-glucose (TyG) index is a simple and reliable surrogate marker for insulin resistance. Epidemiology studies have shown that insulin resistance is a risk factor for various infectious diseases. We evaluated the prognostic value of TyG index measured before the COVID-19 infection in COVID-19 infected patients. Methods From a nationwide COVID-19 cohort dataset in Korea, we included COVID-19 patients diagnosed between Jan and Jun 2020. Based on the nationwide health screening data between 2015 and 2018, TyG index was calculated as ln [triglyceride (mg/dL) × fasting glucose level (mg/dL)/2]. Primary outcome is development of severe complications of COVID-19 defined as composite of mechanical ventilation, intensive care unit care, high-flow oxygen therapy, and mortality within two months after the diagnosis of COVID-19. Results This study included 3887 patients with COVID-19 confirmed by reverse transcription polymerase chain reaction. Mean ± standard deviation of TyG index was 8.54 ± 0.61. Severe complications of COVID-19 were noted in 289 (7.44%) patients. In the multivariate logistic regression, TyG index was positively associated with severe complications of COVID-19 (adjusted odds ratio: 1.42, 95% confidence interval [1.12–1.79]). Conclusions In COVID-19 infected patients, high TyG index was associated with increased risk for severe complications. TyG index might be useful predictor for the severity of COVID-19 infection.
Collapse
|