|
1
|
He X, Zhang C, Ji J, Liu Y, Feng W, Luo L, Fan H, Guo L. Prognostic factors in hospitalized patients with COVID-19 pneumonia and effectiveness of prophylactic anticoagulant therapy: a single-center retrospective study. BMC Infect Dis 2025; 25:303. [PMID: 40033231 PMCID: PMC11877778 DOI: 10.1186/s12879-025-10666-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 02/18/2025] [Indexed: 03/05/2025] Open
Abstract
BACKGROUND COVID-19 pneumonia patients encounter the potential risk of venous thromboembolism (VTE) and mortality during hospitalization. This study aimed to analyzed risk factors of all-cause mortality in hospitalized patients with COVID-19 pneumonia, and investigated the effectiveness of prophylactic anticoagulation and hospital stays on the mortality in hospitalized patients with nonVTE. METHODS We retrospectively analyzed all COVID-19 pneumonia patients who were admitted to our medical center from December 2022 to January 2023. Clinical data and outcome events were collected from patients' electronic medical records. Cox regression was used to identify poor prognostic factors of COVID-19 pneumonia patients with VTE and nonVTE. Landmark analysis was conducted to identify time points of hospital stays between anticoagulation treatment and in-hospital survival outcomes in COVID-19 pneumonia patients with nonVTE. Binary logistic regression analysis was performed to investigate factors related to prolonged hospital stays. RESULTS Among 2,520 COVID-19 pneumonia patients, 1047 received prophylactic anticoagulation and 76 complicated with VTE during hospitalization. Survival curve analysis showed no statistically significant difference in mortality between COVID-19 pneumonia patients with VTE and nonVTE in prophylactic anticoagulant group (P = 0.63). Multivariate cox regression analysis revealed that male(HR = 1.398, 95%CI= [1.021,1.915]), BMI (HR = 0.935, 95%CI= [0.900,0.972]), lymphocytes (HR = 0.576, 95%CI= [0.409,0.809]), platelets (HR = 0.997, 95%CI= [0.995,0.999]), albumin (HR = 0.950, 95%CI= [0.926,0.975]), lactate dehydrogenase (HR = 1.001, 95%CI= [1.001,1.002]) were risk factors for mortality in COVID-19 pneumonia patients with nonVTE, while sCRP (HR = 1.010, 95%CI= [1.004,1.015]), anticoagulant therapy (HR = 0.247, 95%CI= [0.096,0.632]) were risk factors for mortality in COVID-19 pneumonia patients with VTE. Landmark analysis showed that for the hospital stays of 11 days, the difference in the impact of prophylactic anticoagulation on mortality was statistically significant in COVID-19 pneumonia patients with nonVTE (≤ 11days, P = 0.014; > 11days, P = 0.01). CVD (OR = 1.717, 95%CI= [1.248,2.363]), CRD (OR = 1.605, 95%CI= [1.133,2.274]), sCRP (OR = 1.003, 95%CI= [1.000,1.006]), Alb (OR = 0.959, 95%CI = [0.932,0.987]) and use of glucocorticoid (OR = 1.428, 95%CI= [1.057,1.930]) were independent factors associated with hospital stays > 11 days in anticoagulant group. CONCLUSIONS This study indicated that Male, lower BMI, peripheral blood lymphocytes, platelets, albumin and elevated lactate dehydrogenase were associated with poor hospitalisation outcomes in COVID-19 pneumonia patients with nonVTE. As for COVID-19 pneumonia patients with VTE, poor hospitalisation outcomes were associated with elevated sCRP levels and no given anticoagulant therapy. No significant difference in mortality between hospitalized COVID-19 pneumonia patients with VTE and nonVTE when receiving prophylactic anticoagulation. Prolonged hospital stays (> 11 days) may limit the effectiveness of prophylactic anticoagulation on lower in-hospital mortality for COVID-19 pneumonia patients with nonVTE.
Collapse
Affiliation(s)
- Xing He
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
- State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, China
| | - Chun Zhang
- Department of Pulmonary and Critical Care Medicine, School of Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Jiaqi Ji
- Department of Pulmonary and Critical Care Medicine, School of Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Yang Liu
- Department of Pulmonary and Critical Care Medicine, School of Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Wanjie Feng
- Department of Internal Medicine, Wenjiang District Third People's Hospital of Chengdu, Chengdu, 611130, China
| | - Linjie Luo
- Department of Critical Care Medicine, Wenjiang District People's Hospital of Chengdu, Chengdu, Sichuan, China
| | - Hong Fan
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
- State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, China
| | - Lu Guo
- Department of Pulmonary and Critical Care Medicine, School of Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
| |
Collapse
|
|
2
|
Ito H, Ito S, Hirose T, Kimura T, Mori T, Ito S. Severe influenza A viral pneumonia in a hemodialysis patient: successful treatment with steroid pulse therapy. CEN Case Rep 2024:10.1007/s13730-024-00951-6. [PMID: 39658702 DOI: 10.1007/s13730-024-00951-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 11/11/2024] [Indexed: 12/12/2024] Open
Abstract
Seasonal influenza is prevalent globally, particularly during winter months. It is well documented that this disease causes severe, often fatal complications in hemodialysis patients. While numerous reports have focused on novel influenza viruses, there is a paucity of case reports detailing seasonal influenza viral infections in this patient population. This case presents a 71-year-old male undergoing hemodialysis who developed severe seasonal influenza A pneumonia despite receiving the influenza vaccine and early antiviral treatment. Initially presenting with fever, cough, and myalgia, the patient was diagnosed with influenza A virus infection and hospitalized due to heightened risk associated with dialysis and an elevated inflammatory response. Despite treatment with two different antiviral medications, his condition deteriorated, leading to ARDS (acute respiratory distress syndrome). The administration of steroid pulse therapy resulted in significant clinical improvement. This case underscores the severe nature of influenza virus-related illnesses in dialysis patients, even with vaccination and early antiviral intervention. It also suggests the potential benefit of early steroid pulse therapy in managing severe influenza pneumonia in high-risk individuals.
Collapse
Affiliation(s)
- Hiroki Ito
- Division of Nephrology and Endocrinology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-Ku, Sendai, Miyagi, 983-8536, Japan.
- Katta General Hospital, Shiroishi, Japan.
| | | | - Takuo Hirose
- Division of Integrative Renal Replacement Therapy, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan
| | - Tomoyoshi Kimura
- Division of Nephrology and Endocrinology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-Ku, Sendai, Miyagi, 983-8536, Japan
| | - Takefumi Mori
- Division of Nephrology and Endocrinology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-Ku, Sendai, Miyagi, 983-8536, Japan
- Division of Integrative Renal Replacement Therapy, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan
| | - Sadayoshi Ito
- Katta General Hospital, Shiroishi, Japan
- Division of Nephrology, Endocrinology and Vascular Medicine, Graduate School of Medicine, Tohoku University School of Medicine, Sendai, Japan
| |
Collapse
|
|
3
|
Sarikaya ZT, Gucyetmez B, Tuzuner F, Dincer O, Sahan C, Dogan L, Yildirim SA, Zengin R, Kocagoz AS, Telci L, Akinci IO. The usage of immunosuppressant agents and secondary infections in patients with COVID-19 in the intensive care unit: a retrospective study. Sci Rep 2024; 14:20991. [PMID: 39251824 PMCID: PMC11385116 DOI: 10.1038/s41598-024-71912-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 09/02/2024] [Indexed: 09/11/2024] Open
Abstract
Although COVID-19 infection is an immunosuppressant disease, many immunosuppressant agents, such as pulse methylprednisolone (PMP), dexamethasone (DXM), and tocilizumab (TCZ), were used during the pandemic. Secondary infections in patients with COVID-19 have been reported recently. This study investigated these agents' effects on secondary infections and outcomes in patients with COVID-19 in intensive care units (ICUs). This study was designed retrospectively, and all data were collected from the tertiary intensive care units of six hospitals between March 2020 and October 2021. All patients were divided into three groups: Group I [GI, PMP (-), DXM (-) and TCZ (-)], Group II [GII, PMP (+), DXM (+)], and Group III [GIII, PMP (+), DXM (+), TCZ (+)]. Demographic data, PaO/FiO2 ratio, laboratory parameters, culture results, and outcomes were recorded. To compare GI-GII and GI-GIII, propensity score matching (PSM) was used by matching 14 parameters. Four hundred twelve patients with COVID-19 in the ICU were included in the study. The number of patients with microorganisms ≥ 2 was 279 (67.7%). After PSM, in GII and GIII, the number of (+) tracheal cultures and (+) bloodstream cultures detected different microorganisms ≥ 2 during the ICU period, neuropathy, tracheotomized patients, duration of IMV, and length of ICU stay were significantly higher than GI. The mortality rate was similar in GI and GII, whereas it was significantly higher in GIII than in GI. The use of immunosuppressant agents in COVID-19 patients may lead to an increase in secondary infections. In addition, increased secondary infections may lead to prolonged ICU stay, prolonged IMV duration, and increased mortality.
Collapse
Affiliation(s)
- Zeynep Tugce Sarikaya
- Department of Anesthesiology and Reanimation, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey.
- General Intensive Care Unit, Acibadem Altunizade Hospital, Istanbul, Turkey.
| | - Bulent Gucyetmez
- Department of Anesthesiology and Reanimation, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey
- General Intensive Care Unit, Acibadem International Hospital, Istanbul, Turkey
| | - Filiz Tuzuner
- General Intensive Care Unit, Acibadem Taksim Hospital, Istanbul, Turkey
| | - Ozlem Dincer
- General Intensive Care Unit, Acibadem Atakent Hospital, Istanbul, Turkey
- General Intensive Care Unit, Acibadem Bakırköy Hospital, Istanbul, Turkey
| | - Cenk Sahan
- General Intensive Care Unit, Acibadem Atakent Hospital, Istanbul, Turkey
- General Intensive Care Unit, Acibadem Maslak Hospital, Istanbul, Turkey
| | - Lerzan Dogan
- General Intensive Care Unit, Acibadem Altunizade Hospital, Istanbul, Turkey
| | - Serap Aktas Yildirim
- Department of Anesthesiology and Reanimation, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey
| | - Rehile Zengin
- Department of Infectious Diseases and Clinical Microbiology, Acibadem Altunizade Hospital, Istanbul, Turkey
| | - Ayse Sesin Kocagoz
- Department of Infectious Disease and Clinical Microbiology, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey
| | - Lutfi Telci
- General Intensive Care Unit, Acibadem International Hospital, Istanbul, Turkey
| | | |
Collapse
|
|
4
|
Rodríguez-Fernández A, Visos-Varela I, Zapata-Cachafeiro M, Pintos-Rodríguez S, García-Álvarez RM, Herdeiro TM, Piñeiro-Lamas M, Figueiras A, Salgado-Barreira Á. Outpatient glucocorticoid use and COVID-19 outcomes: a population-based study. Inflammopharmacology 2024; 32:2305-2315. [PMID: 38698179 PMCID: PMC11300658 DOI: 10.1007/s10787-024-01474-3] [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: 03/22/2024] [Accepted: 03/30/2024] [Indexed: 05/05/2024]
Abstract
INTRODUCTION Owing to controversy information surrounds effect of glucocorticoids on the evolution of COVID-19, we evaluate the effects of outpatient glucocorticoid use on the severity and progression of COVID-19 and risk of infection and analyse the effect of window of exposure and dose. METHODS We conducted a population-based case - control study, involving 4 substudies: (i) Hospitalisation; (ii) Mortality, using subjects hospitalised with a PCR + as cases and subjects without a PCR + as controls; (iii) Progression, including subjects with a PCR + (hospitalised versus non-hospitalised); and (iv) Susceptibility, with all subjects with a PCR + and subjects without a PCR + . Adjusted odds ratios (ORa) and their 95% confidence intervals (95% CI) were calculated. RESULTS The outpatient glucocorticoid use was associated with an increased risk of hospitalisation (aOR 1.79; 95% CI 1.56-2.05), mortality (aOR 2.30; 95% CI 1.68-3.15), progression (aOR 1.69; 95% CI 1.43-2.00) and susceptibility (aOR 1.29, 95% CI 1.19-1.41). Furthermore, the effects was observed to be greater at higher doses and the closer that drug use approached the outcome date, with an almost fourfold increase in mortality among users in the previous month (aOR 3.85; 95% CI 2.63-5.62). CONCLUSIONS According to the results of this real-world data study, outpatient glucocorticoid use should be considered in making decisions about intrahospital treatment.
Collapse
Affiliation(s)
- Almudena Rodríguez-Fernández
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Rúa de San Francisco, S/N, 15782, Santiago de Compostela (A Coruña), Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública - CIBERESP), Santiago de Compostela, Spain
- Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Irene Visos-Varela
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Rúa de San Francisco, S/N, 15782, Santiago de Compostela (A Coruña), Spain
| | - Maruxa Zapata-Cachafeiro
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Rúa de San Francisco, S/N, 15782, Santiago de Compostela (A Coruña), Spain.
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública - CIBERESP), Santiago de Compostela, Spain.
- Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
| | - Samuel Pintos-Rodríguez
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Rúa de San Francisco, S/N, 15782, Santiago de Compostela (A Coruña), Spain
| | - Rosa M García-Álvarez
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Rúa de San Francisco, S/N, 15782, Santiago de Compostela (A Coruña), Spain
- Service of Preventive Medicine and Public Health. Clinic Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Teresa M Herdeiro
- Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193, Aveiro, Portugal
| | - María Piñeiro-Lamas
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública - CIBERESP), Santiago de Compostela, Spain
- Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Adolfo Figueiras
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Rúa de San Francisco, S/N, 15782, Santiago de Compostela (A Coruña), Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública - CIBERESP), Santiago de Compostela, Spain
- Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Ángel Salgado-Barreira
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Rúa de San Francisco, S/N, 15782, Santiago de Compostela (A Coruña), Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública - CIBERESP), Santiago de Compostela, Spain
- Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain
| |
Collapse
|
|
5
|
Fakih TM, Darusman F, Apriliani R, Prahayati S, Ramadhan DSF, Fikri Hidayat A, Rizkita AD, Yuniarta TA. Predicting anti-COVID-19 potential: in silico analysis of Mauritine compound from Ziziphus-spina christi as a promising papain-like protease (PLpro) inhibitor. J Biomol Struct Dyn 2024:1-12. [PMID: 38529845 DOI: 10.1080/07391102.2024.2322627] [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: 11/28/2023] [Accepted: 02/19/2024] [Indexed: 03/27/2024]
Abstract
The COVID-19 pandemic caused by the SARS-CoV-2 virus, recognized by the World Health Organization (WHO), has led to 164,523,894 confirmed cases and 3,412,032 deaths globally as of May 20, 2021. SARS-CoV-2 encodes crucial proteases for its replication cycle, including the papain-like protease (PLpro), presenting a potential target for developing COVID-19 treatments. Mauritine, a cyclopeptide alkaloid found in the Ziziphus-spina christi plant, exhibits antiviral properties and was investigated for its affinity and toxicity towards PLpro using molecular docking through MGLTools 1.5.6 with Autodock Tools 4.2. Preceding this, toxicity and ADME prediction were performed via Toxtree 3.1.0 software and SwissADME servers. Results from molecular docking revealed free binding energy values of -8.58; -7.73; -8.36; -6.07; -6.67; -7.83; -7.67; -7.40; and -6.87 Kcal/mol for Mauritine-A, Mauritine-B, Mauritine-C, Mauritine-D, Mauritine-F, Mauritine-H, Mauritine-J, Mauritine-L, and Mauritine-M, respectively. Correspondingly, inhibition constants were 0.51724; 2.14; 0.7398; 35.43; 12.95; 1.83; 2.38; 3.80; and 9.17 µM, respectively. Interactions observed included hydrogen bonds, hydrophobic interactions, and electrostatic interactions between the Mauritine compounds and the receptor. Mauritine-A and Mauritine-C emerged as a promising anti-COVID-19 candidate due to its superior affinity compared to other derivatives, as indicated by research findings. Interestingly, Mauritine-A and Mauritine-C exhibits notable stability as depicted by the RMSD and RMSF graphs, along with a considerable MM-PBSA binding free energy value of -162.431 and -137.500 kJ/mol, respectively.
Collapse
Affiliation(s)
- Taufik Muhammad Fakih
- Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Bandung, Indonesia
| | - Fitrianti Darusman
- Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Bandung, Indonesia
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia
| | - Riry Apriliani
- Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Bandung, Indonesia
| | - Syifa Prahayati
- Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Bandung, Indonesia
| | | | - Aulia Fikri Hidayat
- Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Bandung, Indonesia
| | - Aden Dhana Rizkita
- Department of Pharmacy, Sekolah Tinggi Ilmu Kesehatan (STIKES) Bogor Husada, Bogor, Indonesia
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Tegar Achsendo Yuniarta
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Surabaya, Surabaya, Indonesia
| |
Collapse
|
|
6
|
Einarsdottir MJ, Kibiwott Kirui B, Li H, Olsson D, Johannsson G, Nyberg F, Ragnarsson O. Impact of chronic oral glucocorticoid treatment on mortality in patients with COVID-19: analysis of a population-based cohort. BMJ Open 2024; 14:e080640. [PMID: 38490654 PMCID: PMC10946357 DOI: 10.1136/bmjopen-2023-080640] [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: 10/06/2023] [Accepted: 03/05/2024] [Indexed: 03/17/2024] Open
Abstract
OBJECTIVES While glucocorticoid (GC) treatment initiated for COVID-19 reduces mortality, it is unclear whether GC treatment prior to COVID-19 affects mortality. Long-term GC use raises infection and thromboembolic risks. We investigated if patients with oral GC use prior to COVID-19 had increased mortality overall and by selected causes. DESIGN Population-based observational cohort study. SETTINGS Population-based register data in Sweden. PARTICIPANTS All patients infected with COVID-19 in Sweden from January 2020 to November 2021 (n=1 200 153). OUTCOME MEASURES Any prior oral GC use was defined as ≥1 GC prescription during 12 months before index. High exposure was defined as ≥2 GC prescriptions with a cumulative prednisolone dose ≥750 mg or equivalent during 6 months before index. GC users were compared with COVID-19 patients who had not received GCs within 12 months before index. We used Cox proportional hazard models and 1:2 propensity score matching to estimate HRs and 95% CIs, controlling for the same confounders in all analyses. RESULTS 3378 deaths occurred in subjects with any prior GC exposure (n=48 806; 6.9%) and 14 850 among non-exposed (n=1 151 347; 1.3%). Both high (HR 1.98, 95% CI 1.87 to 2.09) and any exposure (1.58, 1.52 to 1.65) to GCs were associated with overall death. Deaths from pulmonary embolism, sepsis and COVID-19 were associated with high GC exposure and, similarly but weaker, with any exposure. High exposure to GCs was associated with increased deaths caused by stroke and myocardial infarction. CONCLUSION Patients on oral GC treatment prior to COVID-19 have increased mortality, particularly from pulmonary embolism, sepsis and COVID-19.
Collapse
Affiliation(s)
- Margret J Einarsdottir
- Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Goteborg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Goteborg, Sweden
| | - Brian Kibiwott Kirui
- School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden
| | - Huiqi Li
- School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden
| | - Daniel Olsson
- Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Goteborg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Goteborg, Sweden
- Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Gudmundur Johannsson
- Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Goteborg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Goteborg, Sweden
| | - Fredrik Nyberg
- School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden
| | - Oskar Ragnarsson
- Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Goteborg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Goteborg, Sweden
- Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
| |
Collapse
|
|
7
|
Wang Y, Guo L, Fan G, Han Y, Zhang Q, Ren L, Zhang H, Wang G, Zhang X, Huang T, Wang W, Chen L, Huang L, Gu X, Wang X, Zhong J, Wang Y, Li H, Yu J, Liu Z, Huang C, Cao B, Wang J. Impact of corticosteroids on initiation and half-year durability of humoral response in COVID-19 survivors. CHINESE MEDICAL JOURNAL PULMONARY AND CRITICAL CARE MEDICINE 2024; 2:48-55. [PMID: 39170961 PMCID: PMC11332893 DOI: 10.1016/j.pccm.2024.02.005] [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: 11/14/2023] [Indexed: 08/23/2024]
Abstract
Background The impact of corticosteroids on humoral responses in coronavirus disease 2019 (COVID-19) survivors during the acute phase and subsequent 6-month period remains unknown. This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset. Methods We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020, which involved adults hospitalized with severe COVID-19 (LOTUS, ChiCTR2000029308). Antibody samples were collected from 192 patients during hospitalization, and kinetic antibodies were monitored at all available time points after recruitment. Additionally, plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit. The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group. Results From illness onset to day 30, the median antibody titre areas under the receiver operating characteristic curve (AUCs) of nucleoprotein (N), spike protein (S), and receptor-binding domain (RBD) immunoglobulin G (IgG) were significantly lower in the corticosteroids group. The AUCs of N-, S-, and RBD-IgM as well as neutralizing antibodies (NAbs) were numerically lower in the corticosteroids group compared with the non-corticosteroid group. However, peak titres of N, S, RBD-IgM and -IgG and NAbs were not influenced by corticosteroids. During 6-month follow-up, we observed a delayed decline for most binding antibodies, except N-IgM (β -0.05, 95% CI [-0.10, 0.00]) in the corticosteroids group, though not reaching statistical significance. No significant difference was observed for NAbs. However, for the half-year seropositive rate, corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-, S-, and RBD-IgG or NAbs. Additionally, corticosteroids group showed a trend towards delayed viral clearance compared with the non-corticosteroid group, but the results were not statistically significant (adjusted hazard ratio 0.71, 95% CI 0.50-1.00; P = 0.0508). Conclusion Our findings suggested that corticosteroid therapy was associated with impaired initiation of the antibody response but this did not compromise the peak titres of binding and neutralizing antibodies. Throughout the decay phase, from the acute phase to the half-year follow-up visit, short-term and low-dose corticosteroids did not significantly affect humoral responses, except for accelerating the waning of short-lived antibodies.
Collapse
Affiliation(s)
- Yeming Wang
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; China-Japan Friendship Hospital, Beijing 100029, China
| | - Li Guo
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, China
- Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing 100029, China
| | - Guohui Fan
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College; State Key Laboratory of Respiratory Health and Multimorbidity; Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, Beijing 100730, China
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Clinical research and Data management, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yang Han
- Jin Yin-tan Hospital, Wuhan, Hubei 430023, China
| | - Qiao Zhang
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, China
- Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing 100029, China
| | - Lili Ren
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, China
- Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing 100029, China
| | - Hui Zhang
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; China-Japan Friendship Hospital, Beijing 100029, China
| | - Geng Wang
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, China
- Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing 100029, China
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Xueyang Zhang
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH); Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing 100730, China
| | - Tingxuan Huang
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, China
- Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing 100029, China
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Weiyang Wang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100029, China
| | - Lan Chen
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, China
- Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing 100029, China
| | | | - Xiaoying Gu
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Clinical research and Data management, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China
| | - Xinming Wang
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, China
- Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing 100029, China
| | - Jingchuan Zhong
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, China
- Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing 100029, China
| | - Ying Wang
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, China
- Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing 100029, China
| | - Hui Li
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; China-Japan Friendship Hospital, Beijing 100029, China
| | - Jiapei Yu
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; China-Japan Friendship Hospital, Beijing 100029, China
| | - Zhibo Liu
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; China-Japan Friendship Hospital, Beijing 100029, China
| | | | - Bin Cao
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; China-Japan Friendship Hospital, Beijing 100029, China
| | - Jianwei Wang
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, China
- Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing 100029, China
| |
Collapse
|
|
8
|
Gasmi A, Noor S, Menzel A, Khanyk N, Semenova Y, Lysiuk R, Beley N, Bolibrukh L, Gasmi Benahmed A, Storchylo O, Bjørklund G. Potential Drugs in COVID-19 Management. Curr Med Chem 2024; 31:3245-3264. [PMID: 37461346 DOI: 10.2174/0929867331666230717154101] [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: 12/19/2022] [Revised: 05/27/2023] [Accepted: 06/05/2023] [Indexed: 11/18/2023]
Abstract
The SARS-CoV-2 virus first emerged in China in December 2019 and quickly spread worldwide. Despite the absence of a vaccination or authorized drug specifically developed to combat this infection, certain medications recommended for other diseases have shown potential effectiveness in treating COVID-19, although without definitive confirmation. This review aims to evaluate the existing literature on the efficacy of these medications against COVID-19. The review encompasses various potential treatments, including antiviral medications, anti-malaria and anti-rheumatic drugs, vaccines, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), antipyretic and analgesic medicines, antiparasitic drugs, and statins. The analysis also addresses the potential benefits and drawbacks of these medications, as well as their effects on hypertension and diabetes. Although these therapies hold promise against COVID-19, further research, including suitable product production or clinical testing, is needed to establish their therapeutic efficacy.
Collapse
Affiliation(s)
- Amin Gasmi
- Société Francophone de Nutrithérapie et de Nutrigénétique Appliquée, Villeurbanne, France
| | - Sadaf Noor
- Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan
| | | | - Nataliia Khanyk
- Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
- CONEM Ukraine Life Science Research Group, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Yuliya Semenova
- Nazarbayev University School of Medicine, Astana, Kazakhstan
| | - Roman Lysiuk
- Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
- CONEM Ukraine Life Science Research Group, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Nataliya Beley
- I. Ya. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
| | | | | | - Olha Storchylo
- Medical Chemistry Department, Odessa National Medical University, Odesa, Ukraine
| | - Geir Bjørklund
- Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway
| |
Collapse
|
|
9
|
Aryanian Z, Balighi K, Sajad B, Esmaeli N, Daneshpazhooh M, Mazloumi Tootoonchi N, Beigmohammadi F, Mohseni Afshar Z, Hatami P. COVID outcome in pemphigus: Does rituximab make pemphigus patients susceptible to more severe COVID-19? J Cosmet Dermatol 2023; 22:2880-2888. [PMID: 37573477 DOI: 10.1111/jocd.15958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 06/11/2023] [Accepted: 08/01/2023] [Indexed: 08/14/2023]
Abstract
BACKGROUND The COVID-19 pandemic has raised some concerns regarding the management of chronic skin diseases, especially in patients on immunosuppressive therapy including patients with pemphigus vulgaris (PV). Literature review reveals conflicting results about the effect of monoclonal antibodies such as rituximab on clinical outcome of COVID-19. OBJECTIVES To assess the reciprocal interaction of COVID-19 and pemphigus and the effect of rituximab on prognosis of COVID-19 in patients. METHODS We set up a retrospective study on adult patients with a confirmed diagnosis of pemphigus vulgaris and a history of COVID-19 with or without symptoms during 2020. RESULTS Thirty-six adults with pemphigus vulgaris and SARS-CoV-2 infection were included. The SARS-CoV-2 infection was confirmed with positive RT-PCR test results in 31 cases (86.1%) and suspected in the 5 others (13.9%). Gender, total dose of rituximab, number of rituximab cycles, and involvement of head and neck were not associated to duration of COVID-19 symptoms (p values: 0.32, 0.23, 0.84, and 0.51, respectively), severity of disease (hospitalization) (p values: 0.46, 0.39, 0.23, and 0.72, respectively), or the percentage of lung involvement on CT scan (p values: 0.07, 0.36, 0.38, and 0.09, respectively). Regarding the impact of COVID-19 on pemphigus, the majority of patients did not experience any changes in their pemphigus regarding clinical phenotype (100%) or severity (83.3%), but PV was worsened in 6 (16.9%) patients which was controlled with increasing the prednisolone dosage. CONCLUSION Rituximab appears to be safe with no increased risk of severe form of COVID-19 in patients with pemphigus vulgaris.
Collapse
Affiliation(s)
- Zeinab Aryanian
- Autoimmune Bullous Diseases Research Center, Razi hospital, Tehran University of Medical Sciences, Tehran, Iran
- Department of Dermatology, Babol University of Medical Sciences, Babol, Iran
| | - Kamran Balighi
- Autoimmune Bullous Diseases Research Center, Razi hospital, Tehran University of Medical Sciences, Tehran, Iran
- Department of Dermatology, School of Medicine, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Baseerat Sajad
- Autoimmune Bullous Diseases Research Center, Razi hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Nafiseh Esmaeli
- Autoimmune Bullous Diseases Research Center, Razi hospital, Tehran University of Medical Sciences, Tehran, Iran
- Department of Dermatology, School of Medicine, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Daneshpazhooh
- Autoimmune Bullous Diseases Research Center, Razi hospital, Tehran University of Medical Sciences, Tehran, Iran
- Department of Dermatology, School of Medicine, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Nasim Mazloumi Tootoonchi
- Autoimmune Bullous Diseases Research Center, Razi hospital, Tehran University of Medical Sciences, Tehran, Iran
- Department of Dermatology, School of Medicine, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Fereshteh Beigmohammadi
- Autoimmune Bullous Diseases Research Center, Razi hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Zeinab Mohseni Afshar
- Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Parvaneh Hatami
- Autoimmune Bullous Diseases Research Center, Razi hospital, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
10
|
Augustin Y, Staines HM, Velavan TP, Kamarulzaman A, Kremsner PG, Krishna S. Drug repurposing for COVID-19: current evidence from randomized controlled adaptive platform trials and living systematic reviews. Br Med Bull 2023; 147:31-49. [PMID: 37312588 PMCID: PMC10502446 DOI: 10.1093/bmb/ldac037] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/04/2022] [Accepted: 11/17/2022] [Indexed: 06/15/2023]
Abstract
INTRODUCTION The coronavirus disease 2019 (COVID-19) pandemic resulted in a race to develop effective treatments largely through drug repurposing via adaptive platform trials on a global scale. Drug repurposing trials have focused on potential antiviral therapies aimed at preventing viral replication, anti-inflammatory agents, antithrombotic agents and immune modulators through a number of adaptive platform trials. Living systematic reviews have also enabled evidence synthesis and network meta-analysis as clinical trial data emerge globally. SOURCES OF DATA Recent published literature. AREAS OF AGREEMENT Corticosteroids and immunomodulators that antagonize the interleukin-6 (IL-6) receptor have been shown to play a critical role in modulating inflammation and improving clinical outcomes in hospitalized patients. Inhaled budesonide reduces the time to recovery in older patients with mild-to-moderate COVID-19 managed in the community. AREAS OF CONTROVERSY The clinical benefit of remdesivir remains controversial with conflicting evidence from different trials. Remdesivir led to a reduction in time to clinical recovery in the ACTT-1 trial. However, the World Health Organization SOLIDARITY and DISCOVERY trial did not find a significant benefit on 28-day mortality and clinical recovery. GROWING POINTS Other treatments currently being investigated include antidiabetic drug empagliflozin, antimalarial drug artesunate, tyrosine kinase inhibitor imatinib, immunomodulatory drug infliximab, antiviral drug favipiravir, antiparasitic drug ivermectin and antidepressant drug fluvoxamine. AREAS TIMELY FOR DEVELOPING RESEARCH The timing of therapeutic interventions based on postulated mechanisms of action and the selection of clinically meaningful primary end points remain important considerations in the design and implementation of COVID-19 therapeutic trials.
Collapse
Affiliation(s)
- Yolanda Augustin
- Institute of Infection and Immunity, St George’s University of London, London, UK
| | - Henry M Staines
- Institute of Infection and Immunity, St George’s University of London, London, UK
| | - Thirumalaisamy P Velavan
- Institute of Tropical Medicine, Universitätsklinikum Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, VG-CARE, Hanoi, Vietnam
| | | | - Peter G Kremsner
- Institute of Tropical Medicine, Universitätsklinikum Tübingen, Tübingen, Germany
- Centre de Recherches Médicales de Lambaréné (CERMEL), Lambarene, Gabon
| | - Sanjeev Krishna
- Institute of Infection and Immunity, St George’s University of London, London, UK
- Institute of Tropical Medicine, Universitätsklinikum Tübingen, Tübingen, Germany
- Centre de Recherches Médicales de Lambaréné (CERMEL), Lambarene, Gabon
| |
Collapse
|
|
11
|
Mwangi VI, Netto RLA, de Morais CEP, Silva AS, Silva BM, Lima AB, Neves JCF, Borba MGS, Val FFDAE, de Almeida ACG, Costa AG, Sampaio VDS, Gardinassi LG, de Lacerda MVG, Monteiro WM, de Melo GC. Temporal patterns of cytokine and injury biomarkers in hospitalized COVID-19 patients treated with methylprednisolone. Front Immunol 2023; 14:1229611. [PMID: 37662953 PMCID: PMC10468998 DOI: 10.3389/fimmu.2023.1229611] [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: 05/26/2023] [Accepted: 07/26/2023] [Indexed: 09/05/2023] Open
Abstract
Background The novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients. Methods Injury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1β) were quantified using cytometric bead array. Results At pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MP-group) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1β and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14. Conclusion These findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients.
Collapse
Affiliation(s)
- Victor Irungu Mwangi
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
| | | | - Carlos Eduardo Padron de Morais
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
| | - Arineia Soares Silva
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
| | - Bernardo Maia Silva
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
| | - Amanda Barros Lima
- Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
| | | | - Mayla Gabriela Silva Borba
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
| | - Fernando Fonseca de Almeida e Val
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
| | - Anne Cristine Gomes de Almeida
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
- Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás (UFG), Goiânia, Brazil
| | - Allyson Guimarães Costa
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
- Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Escola de Enfermagem de Manaus, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) Universidade do Estado do Amazonas (UEA), Manaus, Brazil
| | - Vanderson de Souza Sampaio
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
- Instituto Todos pela Saúde, São Paulo, São Paulo, Brazil
| | - Luiz Gustavo Gardinassi
- Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás (UFG), Goiânia, Brazil
| | - Marcus Vinicius Guimarães de Lacerda
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
- Instituto Leônidas & Maria Deane/Fundação Oswaldo Cruz (ILMD/Fiocruz Amazônia), Manaus, Brazil
| | - Wuelton Marcelo Monteiro
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
| | - Gisely Cardoso de Melo
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
- Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) Universidade do Estado do Amazonas (UEA), Manaus, Brazil
| |
Collapse
|
|
12
|
Liu W, Song Q, Li F, Cao Y, Han Y, Wu J, Hu Z, Zhang Y, Ma Y. Real-World Effectiveness of Nirmatrelvir/Ritonavir and Dexamethasone Among Hospitalized Patients with COVID-19: A Prospective Cohort Study. Infect Drug Resist 2023; 16:5223-5231. [PMID: 37589014 PMCID: PMC10426452 DOI: 10.2147/idr.s419373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 08/02/2023] [Indexed: 08/18/2023] Open
Abstract
Purpose Anti-viral and anti-inflammatory therapies were effective in altering virus repletion and immune dysregulation in Coronavirus Disease 2019 (COVID-19) patients. This study aimed to explore the effect of combination therapy on disease progression in a real-world setting. Patients and Methods A total of 836 patients confirmed with SARS-CoV-2 infection participated in the study from 15 November to 25 December 2022 at Beijing Youan Hospital, Capital Medical University. A prospective cohort study was implemented to investigate the prognostic effect of the combination therapy on virus shedding and clinical recovery. Results About 78% of patients used nirmatrelvir/ritonavir (N/R, Paxlovid®, Pfizer) negatively, 16% of patients were prescribed nirmatrelvir/ritonavir beyond five days of symptom onset, 4% of patients received N/R monotherapy within five days of symptom onset and 2% of patients received N/R combined with dexamethasone. Compared with untreated patients, N/R monotherapy reduced the median time to 10.0 days from 12.0 days according to the negative conversion of nucleic acid amplification test (NAAT), and combination therapy reduced the time to 7.0 days, and increased to a 1.99 (95% CI 0.92, 4.32) and 14.23-fold (95% CI 4.50, 44.95) probability of negative NAAT, respectively. N/R monotherapy reduced the clinical recovery time to 10.0 days from 13.0 days. Single-use and combined-use non-significantly increased the recovery probability by 61% and 69%, respectively. In mild and moderate patients, the HRs for clinical recovery increased to 1.69 (95% CI 0.73, 3.94) and 2.18 (95% CI 0.29, 16.62), respectively. Conclusion Combination therapy of N/R and dexamethasone increased negative conversion of NAAT and was associated with a non-significant improvement in clinical recovery. Further studies are warranted to confirm this efficacy.
Collapse
Affiliation(s)
- Wei Liu
- Department of Pharmacy, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Qingkun Song
- Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Fang Li
- Department of Pharmacy, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Yu Cao
- Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Ying Han
- Center of Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Jiangping Wu
- Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Zhongjie Hu
- Department of Gastroenterology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Yonghong Zhang
- Department of Hepatic Intervention, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Yingmin Ma
- Department of Respiratory and Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China
| |
Collapse
|
|
13
|
Mahmoudi A, Alavizadeh SH, Hosseini SA, Meidany P, Doagooyan M, Abolhasani Y, Saadat Z, Amani F, Kesharwani P, Gheybi F, Sahebkar A. Harnessing aptamers against COVID-19: A therapeutic strategy. Drug Discov Today 2023; 28:103663. [PMID: 37315763 PMCID: PMC10266562 DOI: 10.1016/j.drudis.2023.103663] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 05/16/2023] [Accepted: 06/06/2023] [Indexed: 06/16/2023]
Abstract
The novel coronavirus crisis caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was a global pandemic. Although various therapeutic approaches were developed over the past 2 years, novel strategies with more efficient applicability are required to target new variants. Aptamers are single-stranded (ss)RNA or DNA oligonucleotides capable of folding into unique 3D structures with robust binding affinity to a wide variety of targets following structural recognition. Aptamer-based theranostics have proven excellent capability for diagnosing and treating various viral infections. Herein, we review the current status and future perspective of the potential of aptamers as COVID-19 therapies.
Collapse
Affiliation(s)
- Ali Mahmoudi
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
| | - Seyedeh Hoda Alavizadeh
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyedeh Atefeh Hosseini
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
| | - Pouria Meidany
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maham Doagooyan
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
| | - Yasaman Abolhasani
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
| | - Zakieh Saadat
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
| | - Fatemeh Amani
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
| | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India; Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Science, Chennai, India
| | - Fatemeh Gheybi
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
|
14
|
Okamoto M. Special Issue: "Respiratory Disease in the COVID-19 Era". MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59050886. [PMID: 37241118 DOI: 10.3390/medicina59050886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Accepted: 04/27/2023] [Indexed: 05/28/2023]
Abstract
The outbreak of the viral infection known as coronavirus disease 2019 (COVID-19), caused by the novel pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was first reported in Wuhan, China, in December 2019 [...].
Collapse
Affiliation(s)
- Masaki Okamoto
- Department of Respirology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
| |
Collapse
|
|
15
|
Nowotny HF, Bryce J, Ali SR, Giordano R, Baronio F, Chifu I, Tschaidse L, Cools M, van den Akker ELT, Falhammar H, Appelman-Dijkstra NM, Persani L, Beccuti G, Ross IL, Grozinsky-Glasberg S, Pereira AM, Husebye ES, Hahner S, Faisal Ahmed S, Reisch N. Outcome of COVID-19 infections in patients with adrenal insufficiency and excess. Endocr Connect 2023; 12:EC-22-0416. [PMID: 36715679 PMCID: PMC10083676 DOI: 10.1530/ec-22-0416] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 01/26/2023] [Indexed: 01/31/2023]
Abstract
BACKGROUND Information on clinical outcomes of coronavirus disease 19 (COVID-19) infection in patients with adrenal disorders is scarce. METHODS A collaboration between the European Society of Endocrinology (ESE) Rare Disease Committee and European Reference Network on Rare Endocrine Conditions via the European Registries for Rare Endocrine Conditions allowed the collection of data on 64 cases (57 adrenal insufficiency (AI), 7 Cushing's syndrome) that had been reported by 12 centres in 8 European countries between January 2020 and December 2021. RESULTS Of all 64 patients, 23 were males and 41 females (13 of those children) with a median age of 37 and 51 years. In 45/57 (95%) AI cases, COVID-19 infection was confirmed by testing. Primary insufficiency was present in 45/57 patients; 19 were affected by Addison's disease, 19 by congenital adrenal hyperplasia and 7 by primary AI (PAI) due to other causes. The most relevant comorbidities were hypertension (12%), obesity (n = 14%) and diabetes mellitus (9%). An increase by a median of 2.0 (IQR 1.4) times the daily replacement dose was reported in 42 (74%) patients. Two patients were administered i.m. injection of 100 mg hydrocortisone, and 11/64 were admitted to the hospital. Two patients had to be transferred to the intensive care unit, one with a fatal outcome. Four patients reported persistent SARS-CoV-2 infection, all others complete remission. CONCLUSION This European multicentre questionnaire is the first to collect data on the outcome of COVID-19 infection in patients with adrenal gland disorders. It suggests good clinical outcomes in case of duly dose adjustments and emphasizes the importance of patient education on sick day rules.
Collapse
Affiliation(s)
- Hanna F Nowotny
- Medizinische Klinik IV, Department of Endocrinology, Klinikum der Universität München, Munich, Germany
| | - Jillian Bryce
- Office for Rare Conditions, University of Glasgow, Glasgow, UK
| | - Salma R Ali
- Office for Rare Conditions, University of Glasgow, Glasgow, UK
| | - Roberta Giordano
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Federico Baronio
- Pediatric Unit, Department Hospital of Woman and Child, Endo-ERN Centre IT11, IRCSS AOU S.Orsola-Malpighi University Hospital, Bologna, Italy
| | - Irina Chifu
- Division of Endocrinology and Diabetology, Department of Internal Medicine I, University Hospital of Wuerzburg, University of Wuerzburg, Wuerzburg, Germany
| | - Lea Tschaidse
- Medizinische Klinik IV, Department of Endocrinology, Klinikum der Universität München, Munich, Germany
| | - Martine Cools
- Department of Paediatric Endocrinology, Ghent University Hospital, University of Ghent, Ghent, Belgium
| | - Erica LT van den Akker
- Department of Pediatrics, Division of Pediatric Endocrinology, Erasmus MC - Sophia Children’s Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Henrik Falhammar
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden
| | - Natasha M Appelman-Dijkstra
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
| | - Luca Persani
- Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan Italy
| | - Guglielmo Beccuti
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Ian L Ross
- Division of Endocrinology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Simona Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, ENETS Center of Excellence, Department of Endocrinology and Metabolism, Hadassah Medical Organisation and Faculty of Medicine, the Hebrew University, Jerusalem, Israel
| | - Alberto M Pereira
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
| | - Eystein S Husebye
- Department of Clinical Science and KG Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Stefanie Hahner
- Division of Endocrinology and Diabetology, Department of Internal Medicine I, University Hospital of Wuerzburg, University of Wuerzburg, Wuerzburg, Germany
| | - S Faisal Ahmed
- Office for Rare Conditions, University of Glasgow, Glasgow, UK
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Developmental Endocrinology Research Group, University of Glasgow, Glasgow, United Kingdom
| | - Nicole Reisch
- Medizinische Klinik IV, Department of Endocrinology, Klinikum der Universität München, Munich, Germany
- Correspondence should be addressed to N Reisch:
| |
Collapse
|
|
16
|
Issak ER, Amin MM. Timing of corticosteroids in non-severe non-hospitalized COVID-19 patients: open-label, two-center, randomized controlled study (TICS-COV19 study). Korean J Intern Med 2023; 38:207-217. [PMID: 36646988 PMCID: PMC9993104 DOI: 10.3904/kjim.2022.232] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 10/07/2022] [Accepted: 10/07/2022] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND/AIMS Corticosteroids (CSs) are frequently used in coronavirus disease 2019 (COVID-19); however, their utility remains controversial in mild to moderate cases. The timing of CSs initiation during the disease course remains unaddressed. The study aims to evaluate the impact of early CSs in non-severe COVID-19. METHODS A randomized controlled, open-label study was conducted on 754 COVID-19 patients randomized into a study group (n = 377) in which patients received CSs with COVID-19 protocol and a control group (n = 377) in which patients received COVID-19 protocol only. RESULTS Both groups were comparable regarding baseline characteristics, presenting symptoms, and inflammatory markers. The composite endpoint (need for O2, need for hospitalization or 28-day mortality) was significantly (p = 0.004) lower in the CS group 42 (11.14%) versus the control group 70 (18.67%) with odds ratio 0.55 (95% confidence interval [CI], 0.36 to 0.83), absolute risk reduction 7.53% (95% CI, 2.46% to 12.59%) and number needed to treat of 13.29 (95% CI, 7.94 to 40.61). Regarding severity at day 10, only (11.1%) of the study group patients were severe versus (18.7%) of the control group patients (p < 0.001). The median time-to-return to daily activity in the CS group was 8.0 days, while in the control group, it was 22.0 days (p < 0.001). CONCLUSION In non-severe COVID-19, CS may decrease hospitalization, severity, and mortality.
Collapse
Affiliation(s)
- Emad R. Issak
- Department of Internal Medicine, Allergy and Clinical Immunology, Faculty of Medicine, Ain Shams University, Cairo,
Egypt
- Department of Internal Medicine, Asalam Center, Cairo,
Egypt
| | - Mariam M. Amin
- Department of Internal Medicine, Allergy and Clinical Immunology, Faculty of Medicine, Ain Shams University, Cairo,
Egypt
| |
Collapse
|
|
17
|
Kabbani D, Sonpar A, Weyant B, Lau KCK, Robbins M, Campbell S, Doucette K, Abraldes JG, Lotfi T, Chaktoura M, Akl EA, Cervera C. Immune-Based Therapy for Hospitalized Patients With COVID-19 and Risk of Secondary Infections: A Systematic Review and Meta-analysis. Open Forum Infect Dis 2023; 10:ofac655. [PMID: 36628058 PMCID: PMC9825199 DOI: 10.1093/ofid/ofac655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 12/05/2022] [Indexed: 12/12/2022] Open
Abstract
Background Immune-based therapies are standard-of-care treatment for coronavirus disease 2019 (COVID-19) patients requiring hospitalization. However, safety concerns related to the potential risk of secondary infections may limit their use. Methods We searched OVID Medline, Ovid EMBASE, SCOPUS, Cochrane Library, clinicaltrials.gov, and PROSPERO in October 2020 and updated the search in November 2021. We included randomized controlled trials (RCTs). Pairs of reviewers screened abstracts and full studies and extracted data in an independent manner. We used RevMan to conduct a meta-analysis using random-effects models to calculate the pooled risk ratio (RR) and 95% CI for the incidence of infection. Statistical heterogeneity was determined using the I 2 statistic. We assessed risk of bias for all studies and rated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation methodology. We conducted a meta-regression using the R package to meta-explore whether age, sex, and invasive mechanical ventilation modified risk of infection with immune-based therapies. The protocol is registered with PROSPERO (CRD42021229406). Results This was a meta-analysis of 37 RCTs including 32 621 participants (mean age, 60 years; 64% male). The use of immune-based therapy for COVID-19 conferred mild protection for the occurrence of secondary infections (711/15 721, 4.5%, vs 616/16 900, 3.6%; RR, 0.82; 95% CI, 0.71-0.95; P = .008; I 2 = 28%). A subgroup analysis did not identify any subgroup effect by type of immune-based therapies (P = .85). A meta-regression revealed no impact of age, sex, or mechanical ventilation on the effect of immune-based therapies on risk of infection. Conclusions We identified moderate-certainty evidence that the use of immune-based therapies in COVID-19 requiring hospitalization does not increase the risk of secondary infections.
Collapse
Affiliation(s)
- Dima Kabbani
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Ashlesha Sonpar
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Benson Weyant
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Keith C K Lau
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Mark Robbins
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Sandra Campbell
- John W. Scott Health Sciences Library, University of Alberta, Edmonton, Canada
| | - Karen Doucette
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Juan G Abraldes
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Tamara Lotfi
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
| | - Marlene Chaktoura
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
| | - Elie A Akl
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
| | - Carlos Cervera
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| |
Collapse
|
|
18
|
Li X, Yuan X, Xu Z, Shi L, Huang L, Lu X, Fu J. Effect of Methylprednisolone on Mortality and Clinical Courses in Patients with Severe COVID-19: A Propensity Score Matching Analysis. INFECTIOUS DISEASES & IMMUNITY 2023; 3:20-28. [PMID: 36789030 PMCID: PMC9912987 DOI: 10.1097/id9.0000000000000076] [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: 06/24/2022] [Indexed: 06/18/2023]
Abstract
Background Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19. Methods This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants' epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors. Results Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% vs. 1.65%, P < 0.001), which was maintained after propensity score matching (13.98% vs. 5.38%, P = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242; 95% confidence interval [CI], 0.802 to 34.246; P = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327; 95% CI, 1.702 to 6.501; P < 0.001), lower lymphocyte count (OR, 0.076; 95% CI, 0.012 to 0.461; P = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008; 95% CI, 1.003 to 1.013; P = 0.002), and anticoagulation therapy (OR, 11.187; 95% CI, 2.459 to 50.900; P = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (β Value 0.081; 95% CI, -1.012 to 3.657; P = 0.265) or discharge (β Value 0.114; 95% CI, -0.723 to 6.408; P = 0.117). d-dimer (β Value, 0.144; 95% CI, 0.012 to 0.817; P = 0.044), LDH (β Value 0.260; 95% CI, 0.010 to 0.034; P < 0.001), and antiviral therapy (β Value 0.220; 95% CI, 1.373 to 6.263; P = 0.002) were associated with a longer length from admission to viral clearance. The lymphocyte count (β Value -0.206; 95% CI, -6.248 to -1.197; P = 0.004), LDH (β Value 0.231; 95% CI, 0.012 to 0.048; P = 0.001), antiviral therapy (β Value 0.143; 95% CI, 0.058 to 7.497; P = 0.047), and antibacterial therapy (β Value 0.152; 95% CI, 0.133 to 8.154; P = 0.043) were associated with a longer hospitalization duration from admission to discharge. Further stratified analysis revealed that the low daily dose group (≤60 mg/d) and the low total dose group (≤200 mg) had shorter duration from admission to viral clearance (Z=-2.362, P = 0.018; Z=-2.010, P = 0.044) and a shorter hospital stay (Z=-2.735, P = 0.006; Z=-3.858, P < 0.001). Conclusions In patients with severe COVID-19, methylprednisolone is safe and does not prolong the duration from admission to viral clearance or discharge. Low-dose, short-term methylprednisolone treatment may be more beneficial in shortening the disease course.
Collapse
Affiliation(s)
- Xiaoyan Li
- Medical School of Chinese PLA, Beijing 100853, China
- Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
- National Clinical Research Center for Infectious Diseases, Beijing 100039, China
| | - Xin Yuan
- Medical School of Chinese PLA, Beijing 100853, China
- Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
- National Clinical Research Center for Infectious Diseases, Beijing 100039, China
| | - Zhe Xu
- Medical School of Chinese PLA, Beijing 100853, China
- Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
- National Clinical Research Center for Infectious Diseases, Beijing 100039, China
| | - Lei Shi
- Medical School of Chinese PLA, Beijing 100853, China
- Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
- National Clinical Research Center for Infectious Diseases, Beijing 100039, China
| | - Lei Huang
- Medical School of Chinese PLA, Beijing 100853, China
- Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
- National Clinical Research Center for Infectious Diseases, Beijing 100039, China
| | - Xuechun Lu
- Department of Hematology, the Second Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Junliang Fu
- Medical School of Chinese PLA, Beijing 100853, China
- Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| |
Collapse
|
|
19
|
Sarriá-Landete AJ, Crespo-Matas JA, Domínguez-Quesada I, Castellanos-Monedero JJ, Marte-Acosta D, Arias-Arias ÁJ. Predicting the response to methylprednisolone pulses in patients with SARS-COV-2 infection. MEDICINA CLINICA (ENGLISH ED.) 2022; 159:557-562. [PMID: 36536623 PMCID: PMC9752105 DOI: 10.1016/j.medcle.2022.02.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 02/23/2022] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Treating systemic inflammation caused by SARS-COV 2 (COVID-19) has become a challenge for the clinician. Corticosteroids have been the turning point in the treatment of this disease. Preliminary data from Recovery clinical trial raises hope by showing that treatment with dexamethasone at doses of 6 mg/day shows a reduction on morbidity in patients requiring added oxygen therapy. However, both the start day or what kind of corticosteroid, are still questions to be clarified. Since the pandemic beginning, we have observed large differences in the type of corticosteroid, dose and initiation of treatment.Our objective is to assess the predictive capacity of the characteristics of patients treated with methylprednisolone pulses to predict hospital discharge. MATERIALS AND METHODS We presented a one-center observational study of a retrospective cohort. We included all patients admitted between 03/06/2020 and 05/15/2020 because of COVID-19. We have a total number of 1469 patients, of whom 322 received pulses of methylprednisolone. Previous analytical, radiographic, previous disease data were analyzed on these patients. The univariant analysis was performed using Chi-squared and the T test of Student according to the qualitative or quantitative nature of the variables respectively. For multivariate analysis, we have used binary logistic regression and ROC curves. RESULTS The analysis resulted statistically significant in dyspnea, high blood pressure, dyslipidemia, stroke, ischemic heart disease, cognitive impairment, solid tumor, C-reactive protein (CRP), lymphopenia and d-dimer within 5 days of admission. Radiological progression and FIO2 input are factors that are associated with a worst prognosis in COVID-19 that receive pulses of methylprednisolone. Multivariate analysis shows that age, dyspnea and C-reactive protein are markers of hospital discharge with an area below the curve of 0.816. CONCLUSIONS In patients with methylprednisolone pulses, the capacity of the predictive model for hospital discharge including variables collected at 5 days was (area under the curve) 0.816.
Collapse
Affiliation(s)
- Antonio J. Sarriá-Landete
- Departamento de Medicina Interna, Hospital La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain,Corresponding author
| | - José A. Crespo-Matas
- Departamento de Medicina Interna, Hospital La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain
| | | | | | - Dinés Marte-Acosta
- Departamento de Neumología, Hospital La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain
| | - Ángel J. Arias-Arias
- Departamento de Investigación, Hospital La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain
| |
Collapse
|
|
20
|
Zeng Y, Zeng W, Yang B, Liu Z. Effectiveness of corticosteroids to treat coronavirus disease 2019 symptoms: A meta-analysis. MEDICINA CLINICA (ENGLISH ED.) 2022; 159:575-583. [PMID: 36536622 PMCID: PMC9752099 DOI: 10.1016/j.medcle.2022.03.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 03/09/2022] [Indexed: 12/23/2022]
Abstract
OBJECTIVE Currently, corticosteroids are widely used to treat coronavirus disease 2019 (COVID-19) symptoms. However, the therapeutic role of corticosteroids remains highly controversial. To that end, we aimed to assess the efficacy of corticosteroids in treating COVID-19 patients. METHOD We searched PubMed, Embase, and Cochrane Library to select suitable studies. Our primary study endpoint was all-cause mortality. The secondary study endpoint was the length of hospital stay. RESULTS A total of 9 randomized controlled trials (RCTs) with 7907 patients were assessed. The pooled result indicated that corticosteroids treatment could significantly reduce all-cause mortality in patients with COVID-19 (RR = 0.88, 95% CI [0.82, 0.95], P = 0.002). When subgroup analyses were performed, we found that corticosteroids were associated with decreased all-cause mortality in severe COVID-19 patients (RR = 0.77, 95% CI [0.68, 0.88], P < 0.0001), however no obvious difference was observed in all-cause mortality of non-severe COVID-19 patients between the corticosteroid and control group (RR = 0.96, 95% CI [0.86, 1.06], P = 0.41), meanwhile, a low dose (RR = 0.89, 95% CI [0.82, 0.97], P = 0.007) of dexamethasone (RR = 0.9, 95% CI [0.83, 0.98], P = 0.01) with a long treatment course (RR = 0.89, 95% CI [0.82, 0.98], P = 0.02) was beneficial for all-cause mortality in COVID-19 patients. Additionally, we found that corticosteroids might be associated with a longer length of hospital stay in non-severe COVID-19 patients (MD = 3.83, 95% CI [1.11, 6.56], P = 0.006). CONCLUSION Our results showed that corticosteroid therapy was related to a reduction in all-cause mortality in severe COVID-19 patients. However, in patients with non-severe COVID-19, the use of corticosteroids did not decrease all-cause mortality and may prolong the duration of hospital stay. In addition, we revealed that a low dose of dexamethasone with a long treatment course could reduce all-cause mortality in COVID-19 patients.
Collapse
Affiliation(s)
- Yiqian Zeng
- Department of Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, Hunan, China
| | - Weizhong Zeng
- Department of Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, Hunan, China
| | - Bihui Yang
- Department of Hematology, Zhuzhou Central Hospital, Zhuzhou, Hunan, China
| | - Zhao Liu
- Department of Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, Hunan, China,Corresponding author
| |
Collapse
|
|
21
|
Zeng Y, Zeng W, Yang B, Liu Z. Effectiveness of corticosteroids to treat coronavirus disease 2019 symptoms: A meta-analysis. Med Clin (Barc) 2022; 159:575-583. [PMID: 35618496 PMCID: PMC9061135 DOI: 10.1016/j.medcli.2022.03.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 03/05/2022] [Accepted: 03/09/2022] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Currently, corticosteroids are widely used to treat coronavirus disease 2019 (COVID-19) symptoms. However, the therapeutic role of corticosteroids remains highly controversial. To that end, we aimed to assess the efficacy of corticosteroids in treating COVID-19 patients. METHOD We searched PubMed, Embase, and Cochrane Library to select suitable studies. Our primary study endpoint was all-cause mortality. The secondary study endpoint was the length of hospital stay. RESULTS A total of 9 randomized controlled trials (RCTs) with 7907 patients were assessed. The pooled result indicated that corticosteroids treatment could significantly reduce all-cause mortality in patients with COVID-19 (RR=0.88, 95% CI [0.82, 0.95], P=0.002). When subgroup analyses were performed, we found that corticosteroids were associated with decreased all-cause mortality in severe COVID-19 patients (RR=0.77, 95% CI [0.68, 0.88], P<0.0001), however no obvious difference was observed in all-cause mortality of non-severe COVID-19 patients between the corticosteroid and control group (RR=0.96, 95% CI [0.86, 1.06], P=0.41), meanwhile, a low dose (RR=0.89, 95% CI [0.82, 0.97], P=0.007) of dexamethasone (RR=0.9, 95% CI [0.83, 0.98], P=0.01) with a long treatment course (RR=0.89, 95% CI [0.82, 0.98], P=0.02) was beneficial for all-cause mortality in COVID-19 patients. Additionally, we found that corticosteroids might be associated with a longer length of hospital stay in non-severe COVID-19 patients (MD=3.83, 95% CI [1.11, 6.56], P=0.006). CONCLUSION Our results showed that corticosteroid therapy was related to a reduction in all-cause mortality in severe COVID-19 patients. However, in patients with non-severe COVID-19, the use of corticosteroids did not decrease all-cause mortality and may prolong the duration of hospital stay. In addition, we revealed that a low dose of dexamethasone with a long treatment course could reduce all-cause mortality in COVID-19 patients.
Collapse
Affiliation(s)
- Yiqian Zeng
- Department of Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, Hunan, China
| | - Weizhong Zeng
- Department of Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, Hunan, China
| | - Bihui Yang
- Department of Hematology, Zhuzhou Central Hospital, Zhuzhou, Hunan, China
| | - Zhao Liu
- Department of Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, Hunan, China,Corresponding author
| |
Collapse
|
|
22
|
Sarriá-Landete AJ, Crespo-Matas JA, Domínguez-Quesada I, Castellanos-Monedero JJ, Marte-Acosta D, Arias-Arias ÁJ. Predicting the response to methylprednisolone pulses in patients with SARS-COV-2 infection. Med Clin (Barc) 2022; 159:557-562. [PMID: 35718548 PMCID: PMC9212640 DOI: 10.1016/j.medcli.2022.02.025] [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: 07/11/2021] [Revised: 02/16/2022] [Accepted: 02/23/2022] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Treating systemic inflammation caused by SARS-COV 2 (COVID-19) has become a challenge for the clinician. Corticosteroids have been the turning point in the treatment of this disease. Preliminary data from Recovery clinical trial raises hope by showing that treatment with dexamethasone at doses of 6mg/day shows a reduction on morbidity in patients requiring added oxygen therapy. However, both the start day or what kind of corticosteroid, are still questions to be clarified. Since the pandemic beginning, we have observed large differences in the type of corticosteroid, dose and initiation of treatment. Our objective is to assess the predictive capacity of the characteristics of patients treated with methylprednisolone pulses to predict hospital discharge. MATERIALS AND METHODS We presented a one-center observational study of a retrospective cohort. We included all patients admitted between 03/06/2020 and 05/15/2020 because of COVID-19. We have a total number of 1469 patients, of whom 322 received pulses of methylprednisolone. Previous analytical, radiographic, previous disease data were analyzed on these patients. The univariant analysis was performed using Chi-squared and the T test of Student according to the qualitative or quantitative nature of the variables respectively. For multivariate analysis, we have used binary logistic regression and ROC curves. RESULTS The analysis resulted statistically significant in dyspnea, high blood pressure, dyslipidemia, stroke, ischemic heart disease, cognitive impairment, solid tumor, C-reactive protein (CRP), lymphopenia and d-dimer within 5 days of admission. Radiological progression and FIO2 input are factors that are associated with a worst prognosis in COVID-19 that receive pulses of methylprednisolone. Multivariate analysis shows that age, dyspnea and C-reactive protein are markers of hospital discharge with an area below the curve of 0.816. CONCLUSIONS In patients with methylprednisolone pulses, the capacity of the predictive model for hospital discharge including variables collected at 5 days was (area under the curve) 0.816.
Collapse
Affiliation(s)
- Antonio J. Sarriá-Landete
- Departamento de Medicina Interna, Hospital La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain,Corresponding author
| | - José A. Crespo-Matas
- Departamento de Medicina Interna, Hospital La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain
| | | | | | - Dinés Marte-Acosta
- Departamento de Neumología, Hospital La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain
| | - Ángel J. Arias-Arias
- Departamento de Investigación, Hospital La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain
| |
Collapse
|
|
23
|
Li H, Liu J, Hu X, Wei S, Jun W. Practices, Knowledge, and Attitudes of Chinese University Students Toward Traditional Chinese Herbal Medicine for the Control of COVID-19. Infect Drug Resist 2022; 15:6951-6962. [PMID: 36474905 PMCID: PMC9719682 DOI: 10.2147/idr.s387292] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 11/23/2022] [Indexed: 02/05/2024] Open
Abstract
BACKGROUND The application of traditional Chinese herbal medicine has been officially recommended and strongly promoted in China as an important complement to conventional prevention and treatment for COVID-19. Capturing the practices, knowledge and attitudes of young adult population toward using Chinese herbs for COVID-19 is important for understanding the future of Chinese herbal medicine over the coming decades. METHODS This cross-sectional questionnaire-based study was conducted from May to June, 2022, among 313 student volunteers in Wuhan University of Science and Technology, a provincial comprehensive university in China. RESULTS Results showed that only 18% of students had used Chinese herbs to prevent COVID-19. The main information sources were social media, the students' family members, relatives, friends, etc. as well as the healthcare professionals. However, most students only sometimes paid close attention to related reports and news articles in social media. Clear pharmacological and toxicological properties of herbs were considered by 43% students as the most important factor to promote their own application of Chinese herbs to fight COVID-19. The mean knowledge score was 1.64 out of 5. Students' overall attitudes toward application of Chinese herbal medicine to fight COVID-19 were very positive. CONCLUSION These data suggests most university young adults had a positive attitude but lack of practices and knowledge towards traditional Chinese herbal medicine for COVID-19 control.
Collapse
Affiliation(s)
- Hao Li
- Department of Pharmacy, Medical College, Wuhan University of Science and Technology, Wuhan, People’s Republic of China
| | - Juan Liu
- Department of Pharmacy, Medical College, Wuhan University of Science and Technology, Wuhan, People’s Republic of China
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, People’s Republic of China
| | - Xinyi Hu
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, People’s Republic of China
| | - Songyi Wei
- Department of Pharmacy, Medical College, Wuhan University of Science and Technology, Wuhan, People’s Republic of China
| | - Wang Jun
- Department of Pharmacy, Medical College, Wuhan University of Science and Technology, Wuhan, People’s Republic of China
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, People’s Republic of China
| |
Collapse
|
|
24
|
Hach T, Shakeri-Nejad K, Bigaud M, Dahlke F, de Micco M, Petricoul O, Graham G, Piani-Meier D, Turrini R, Brinkmann V, Nicoletti F. Rationale for Use of Sphingosine-1-Phosphate Receptor Modulators in COVID-19 Patients: Overview of Scientific Evidence. J Interferon Cytokine Res 2022. [DOI: 10.1089/jir.2022.0078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Affiliation(s)
- Thomas Hach
- Patient Engagement, Novartis Pharma AG, Basel, Switzerland
| | - Kasra Shakeri-Nejad
- Department of Clinical Pharmacology; Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Marc Bigaud
- Department of Autoimmunity, Transplantation & Inflammation; Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Frank Dahlke
- Patient Engagement, Novartis Pharma AG, Basel, Switzerland
| | | | - Olivier Petricoul
- Department of Neuroscience; Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Gordon Graham
- Patient Engagement, Novartis Pharma AG, Basel, Switzerland
| | | | - Renato Turrini
- Department of Autoimmunity, Transplantation & Inflammation; Novartis Institutes for Biomedical Research, Basel, Switzerland
| | | | - Ferdinando Nicoletti
- Department of Physiology and Pharmacology, University Sapienza of Rome, Rome, Italy
- Department of Molecular Neuropharmacology, IRCCS Neuromed, Pozzilli, Italy
| |
Collapse
|
|
25
|
Kocivnik N, Velnar T. A Review Pertaining to SARS-CoV-2 and Autoimmune Diseases: What Is the Connection? Life (Basel) 2022; 12:1918. [PMID: 36431053 PMCID: PMC9698792 DOI: 10.3390/life12111918] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/11/2022] [Accepted: 11/15/2022] [Indexed: 11/19/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is an infectious viral disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It is known that infection with SARS-CoV-2 can lead to various autoimmune and autoinflammatory diseases. There are few reports in the literature on the association between SARS-CoV-2 and autoimmune diseases, and the number of reports has been increasing since 2020. Autoimmune diseases and SARS-CoV-2 infections are intertwined in several ways. Both conditions lead to immune-mediated tissue damage, the immune response is accompanied by the increased secretion of inflammatory cytokines and both conditions can be treated using immunomodulatory drugs. Patients with certain autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, cardiac sarcoidosis, idiopathic pulmonary fibrosis, autoimmune hepatitis, multiple sclerosis and others, are more susceptible to SARS-CoV-2 infection, either because of the active autoimmune disease or because of the medications used to treat it. Conversely, SARS-CoV-2 infection can also cause certain autoimmune diseases. In this paper, we describe the development of autoimmune diseases after COVID-19 and the recovery from COVID-19 in people with autoimmune diseases.
Collapse
Affiliation(s)
- Nina Kocivnik
- Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Tomaz Velnar
- Department of Neurosurgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| |
Collapse
|
|
26
|
Variability of Steroid Prescription for COVID-19 Associated Pneumonia in Real-Life, Non-Trial Settings. J Crit Care Med (Targu Mures) 2022; 8:259-265. [DOI: 10.2478/jccm-2022-0025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 09/11/2022] [Indexed: 11/13/2022] Open
Abstract
Abstract
The RECOVERY study documented lower 28-day mortality with the use of dexamethasone in hospitalized patients on invasive mechanical ventilation or oxygen with COVID-19 Pneumonia. We aimed to examine the practice patterns of steroids use, and their impact on mortality and length of stay in ICU. We retrospectively examined records of all patients with confirmed Covid 19 pneumonia admitted to the ICU of Dubai hospital from January 1st, 2020 – June 30th, 2020. We assigned patients to four groups (No steroids, low dose, medium dose, and high dose steroids). The primary clinical variable of interest was doses of steroids. Secondary outcomes were 28-day mortality and length of stay in ICU”. We found variability in doses of steroid treatment. The most frequently used dose was the high dose. Patients who survived were on significantly higher doses of steroids and had significantly longer stays in ICU. The prescription of steroids in Covid-19 ARDS is variable. The dose of steroids impacts mortality rate and length of stay in ICU, although patients treated with high dose steroids seem to stay more days in ICU.
Collapse
|
|
27
|
Caira-Chuquineyra B, Fernandez-Guzman D, Alvarez-Arias PM, Zarate-Curi ÁA, Herrera-Añazco P, Benites-Zapata VA. Association between prehospital medication and fatal outcomes in a cohort of hospitalized patients due to coronavirus disease-2019 in a referral hospital in Peru. Travel Med Infect Dis 2022; 50:102472. [PMID: 36257588 PMCID: PMC9573861 DOI: 10.1016/j.tmaid.2022.102472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 09/26/2022] [Accepted: 10/03/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND To explore the association between the use of prehospital medications and the development of fatal outcomes in patients who required hospitalization due to coronavirus disease-2019 (COVID-19). METHODS This retrospective cohort study included adult patients who were hospitalized due to COVID-19. Demographic, clinical, and laboratory data, prehospital medication history, and fatal outcome development (use of high-flow oxygen therapy, intensive care unit [ICU] admission, or mortality) were extracted from the medical records of patients who were admitted due to COVID-19 to the Carlos Seguín Escobedo National Hospital of Arequipa, Peru during July to September 2021, the period after the second wave of COVID-19 cases in Peru. Survival was analyzed using the Cox proportional hazards model, and crude hazard ratios and adjusted hazard ratios (aHR) with their respective 95% confidence intervals (95% CI) were calculated. RESULTS A total of 192 patients were evaluated, of whom 62% were males and 46.9% did not require oxygen support at admission. Additionally, 64.6% used nonsteroidal anti-inflammatory drugs, 35.4% used corticosteroids, 28.1% used macrolides or ceftriaxone, 24.5% used ivermectin, and 21.9% used warfarin before hospitalization. Of the patients, 30.2% developed a fatal outcome during follow-up. The multivariate analysis revealed that prehospital corticosteroid use was independently associated with the fatal outcome due to COVID-19 with an aHR = 5.29 (95%CI: 1.63-17.2). CONCLUSION Prehospital corticosteroid use was associated with a 5-fold increased risk of fatal outcome development.
Collapse
Affiliation(s)
- Brenda Caira-Chuquineyra
- Grupo Peruano de Investigación Epidemiológica, Unidad para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima, Peru; Facultad de Medicina, Universidad Nacional de San Agustín de Arequipa, Arequipa, Peru
| | - Daniel Fernandez-Guzman
- Grupo Peruano de Investigación Epidemiológica, Unidad para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima, Peru; Escuela Profesional de Medicina Humana, Universidad Nacional de San Antonio Abad del Cusco, Cusco, Peru
| | | | - Ángel A Zarate-Curi
- Facultad de Medicina, Universidad Nacional de San Agustín de Arequipa, Arequipa, Peru; Servicio de Medicina Interna, Hospital Nacional Carlos Alberto Seguín Escobedo, EsSalud, Arequipa, Peru
| | - Percy Herrera-Añazco
- Universidad Privada San Juan Bautista, Lima, Peru; Red Internacional en Salud Colectiva y Salud Intercultural, Ciudad de México, Mexico; Instituto de Evaluación de Tecnologías en Salud e Investigación, EsSalud, Lima, Peru
| | - Vicente A Benites-Zapata
- Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Vicerrectorado de Investigación, Universidad San Ignacio de Loyola, Lima, Peru.
| |
Collapse
|
|
28
|
Zhang Q, Zhang H, Yan X, Ma S, Yao X, Shi Y, Ping Y, Cao M, Peng C, Wang S, Luo M, Yan C, Zhang S, Han Y, Bian X. Neutrophil infiltration and myocarditis in patients with severe COVID-19: A post-mortem study. Front Cardiovasc Med 2022; 9:1026866. [PMID: 36312241 PMCID: PMC9614157 DOI: 10.3389/fcvm.2022.1026866] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 09/26/2022] [Indexed: 12/15/2022] Open
Abstract
Aims To investigate cardiac pathology in critically ill patients with coronavirus disease 2019 (COVID-19) and identify associations between pathological changes and clinical characteristics. Methods The present autopsy cohort study included hearts from 26 deceased patients hospitalized in intensive care units due to COVID-19, and was conducted at four sites in Wuhan, China. Cases were divided into a neutrophil infiltration group and a no-neutrophil group based on the presence or absence of histopathologically identified neutrophilic infiltrates. Results Among the 26 patients, histopathological examination identified active myocarditis in four patients. All patients with myocarditis exhibited extensive accompanying neutrophil infiltration, and all patients without myocarditis did not. The neutrophil infiltration group exhibited significantly higher rates of detection of interleukin-6 (100 vs. 4.6%) and tumor necrosis factor-alpha (100 vs. 31.8%) than the no-neutrophil group (both p < 0.05). On admission, four patients with neutrophil infiltration in myocardium had significantly higher baseline levels of aspartate aminotransferase, D dimer, and high-sensitivity C reactive protein than the other 22 patients (all p < 0.05). During hospitalization, patients with neutrophil infiltration had significantly higher maximum creatine kinase-MB (median 280.0 IU/L vs. 38.7 IU/L, p = 0.04) and higher troponin I (median 1.112 ng/ml vs. 0.220 ng/ml, p = 0.56) than patients without neutrophil infiltration. Conclusion Active myocarditis was frequently associated with neutrophil infiltration in the hearts of deceased patients with severe COVID-19. Patients with neutrophil-infiltrated myocarditis had a series of severely abnormal laboratory test results on admission, and high maximum creatine kinase-MB during hospitalization. The role of neutrophils in severe heart injury and systemic conditions in patients with COVID-19 should be emphasized.
Collapse
Affiliation(s)
- Quanyu Zhang
- Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
| | - Huarong Zhang
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Beijing, China
| | - Xiaowei Yan
- Division of Cardiology, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Sicong Ma
- Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
| | - Xiaohong Yao
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Beijing, China
| | - Yu Shi
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Beijing, China
| | - Yifang Ping
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Beijing, China
| | - Mianfu Cao
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Beijing, China
| | - Chengfei Peng
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Beijing, China
| | - Shuai Wang
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Beijing, China
| | - Min Luo
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Beijing, China
| | - Chenghui Yan
- Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
| | - Shuyang Zhang
- Division of Cardiology, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Yaling Han
- Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
| | - Xiuwu Bian
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Beijing, China
| |
Collapse
|
|
29
|
Kapil K, Muntode Gharde P. A Review on Effectiveness of Plasma Therapy in Severe COVID-19 Patients. Cureus 2022; 14:e28914. [PMID: 36237760 PMCID: PMC9547123 DOI: 10.7759/cureus.28914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 09/07/2022] [Indexed: 12/04/2022] Open
Abstract
Coronavirus 2019 has created a big threat to the modern world. Many researchers and scientists had taken the burden of finding information about this entity, its structure, its transmission, and also about the treatment that can be given to individuals infected by it. There has been use of different medicines at different times simultaneously researching about them, starting with only symptomatic and supportive treatment, then antimalarial agents like chloroquine and hydroxychloroquine, then going to favipavir, and other antivirals, then came the use of vaccines and also convalescent plasma therapy for COVID-19. The most advanced is convalescent plasma use for the treating coronavirus. Using plasma of patients who have remitted from this disease and putting it into those individuals who are dealing with the disease or are critically ill for improvement of their health status. This treatment has been used for many other diseases too and has been proven efficacious. So, this technique is being used and studied for coronavirus 2019 as well. There have been set certain criteria for those who can donate plasma and also criteria for the recipients of this technique. Also, there can be adverse reactions or even side effects with this, like transfusion-related acute lung injury (TRALI), so they should also be kept in mind during treatment with this method. So, though there are many methods to date to treat these individuals but one of the latest ones is using plasma, which is proven to be efficacious but still many studies are under process for the same.
Collapse
|
|
30
|
Lan Y, Wang H, Wu J, Meng X. Cytokine storm-calming property of the isoquinoline alkaloids in Coptis chinensis Franch. Front Pharmacol 2022; 13:973587. [PMID: 36147356 PMCID: PMC9485943 DOI: 10.3389/fphar.2022.973587] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 08/16/2022] [Indexed: 11/18/2022] Open
Abstract
Coronavirus disease (COVID-19) has spread worldwide and its effects have been more devastating than any other infectious disease. Importantly, patients with severe COVID-19 show conspicuous increases in cytokines, including interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, IL-8, tumor necrosis factor (TNF)-α, IL-1, IL-18, and IL-17, with characteristics of the cytokine storm (CS). Although recently studied cytokine inhibitors are considered as potent and targeted approaches, once an immunological complication like CS happens, anti-viral or anti-inflammation based monotherapy alone is not enough. Interestingly, certain isoquinoline alkaloids in Coptis chinensis Franch. (CCFIAs) exerted a multitude of biological activities such as anti-inflammatory, antioxidant, antibacterial, and immunomodulatory etc, revealing a great potential for calming CS. Therefore, in this timeline review, we report and compare the effects of CCFIAs to attenuate the exacerbation of inflammatory responses by modulating signaling pathways like NF-ĸB, mitogen-activated protein kinase, JAK/STAT, and NLRP3. In addition, we also discuss the role of berberine (BBR) in two different triggers of CS, namely sepsis and viral infections, as well as its clinical applications. These evidence provide a rationale for considering CCFIAs as therapeutic agents against inflammatory CS and this suggestion requires further validation with clinical studies.
Collapse
Affiliation(s)
- Yuejia Lan
- State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Huan Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jiasi Wu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- *Correspondence: Jiasi Wu, ; Xianli Meng,
| | - Xianli Meng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- *Correspondence: Jiasi Wu, ; Xianli Meng,
| |
Collapse
|
|
31
|
Zhao M, Gao QH, Liu SJ, Deng YJ, Wang H, Yu WX, Guo J. Quality assessment and relevant clinical impact of randomized controlled trials on chronic prostatitis/chronic pelvic pain syndrome. BMC Urol 2022; 22:122. [PMID: 35941610 PMCID: PMC9361679 DOI: 10.1186/s12894-022-01078-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 07/27/2022] [Indexed: 11/16/2022] Open
Abstract
Objective This study evaluated the quality of randomized controlled trials (RCTs) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods We searched PubMed, Web of Science, and Embase for RCTs (original articles) on CP/CPPS published from database establishment to 2021. The RCT quality assessment was performed using the Consolidated Standards of Reporting of Trials (CONSORT) statement and the improved Jadad scale. Results In total, 77 RCTs were included. According to the evaluation, 26 (33.77%) papers presented the description of the specific random methods, only 6 (7.79%) papers described the allocation concealment methods, and 26 (33.77%) articles referred to the “blind method”. Of the RCTs, 34 (44.16%) papers recorded the number of patients who withdrew from the study, and 67 (87.01%) papers reported adverse reactions. However, few reports mentioned the sample size calculation, clinical trial registration, or information about the relevant research programs and funding. In addition, 19 (24.68%) reports had Jadad scale scores of ≥ 4 points, and 58 (75.32%) reports had Jadad scale scores of ≤ 3 points. Conclusion To date, the quality of RCT reports on CP/CPPS needs to be further improved, and the results of the RCTs should be accepted and utilized cautiously. It is suggested that researchers should follow the CONSORT statement and the improved Jadad scale to standardize the design and implementation of RCTs to improve the quality of RCTs and provide reliable evidence for the treatment of CP/CPPS.
Collapse
Affiliation(s)
- Ming Zhao
- Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China.,Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Qing-He Gao
- Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Sheng-Jing Liu
- Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Ying-Jun Deng
- Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Hao Wang
- Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Wen-Xiao Yu
- Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Jun Guo
- Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China.
| |
Collapse
|
|
32
|
Alotaibi N, Alroomi M, Aboelhassan W, Hussein S, Rajan R, AlNasrallah N, Al Saleh M, Ramadhan M, Zhanna KD, Pan J, Malhas H, Abdelnaby H, Almutairi F, Al-Bader B, Alsaber A, Abdullah M. In-hospital mortality in SARS-CoV-2 stratified by the use of corticosteroid. Ann Med Surg (Lond) 2022; 80:104105. [PMID: 35784615 PMCID: PMC9239918 DOI: 10.1016/j.amsu.2022.104105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 06/25/2022] [Accepted: 06/25/2022] [Indexed: 12/15/2022] Open
Abstract
Objective To investigate COVID-19 related mоrtаlity according to the use of corticosteroid therapy. Design Retrospective cohort study. Setting Two tertiary hospitals in Kuwait. Participants Overall, 962 patients with confirmed SARS-CoV-2 infection, were stratified according to whether they were treated with corticosteroids (dexamethasone or methylprednisolone). The mean age of the patients was 50.2 ± 15.9 years and 344/962 (35.9%) were female. Main outcome measures In-hospital mortality and cumulative all-cause mortality. Results Compared to non-corticosteroid therapy patients, corticosteroid therapy patients had a higher prevalence of hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, and chronic kidney disease; a longer hospital stay (median [IQR]: 17.0 [5.0–57.3] days vs 14.0 [2.0–50.2] days); and a higher in-hospital mortality (51/199 [25.6%] vs 36/763 [4.7%]). Logistic regression analysis showed a higher in-hospital mortality in the corticosteroid group (adjusted odds ratio [aOR]: 4.57, 95% confidence interval [CI]: 2.64–8.02, p < 0.001). Cox proportional hazards regression showed that corticosteroid use was a significant predictor of mortality (hazard ratio [HR]: 3.96, p < 0.001). Conclusions In-hospital mortality in patients with SARS-CoV-2 on corticosteroid therapy was 4.6 times higher than in those without corticosteroid therapy.
In-hospital mortality in patients with SARS-CoV-2 on corticosteroid was evaluated. Risk of mortality was 4.6 times higher in those with corticosteroid therapy. Corticosteroid therapy patients had a longer hospital stay.
Collapse
Affiliation(s)
- Naser Alotaibi
- Department of Medicine, Al Adan Hospital, Hadiya, Kuwait
| | - Moudhi Alroomi
- Department of Infectious Diseases, Infectious Diseases Hospital, Shuwaikh Medical Area, Kuwait
- Corresponding author. Department of Infectious Diseases, Infectious Diseases Hospital Shuwaikh Medical Area, P. O. Box 4710, Safat, 13048, Kuwait.
| | - Wael Aboelhassan
- Division of Gastroenterology, Department of Medicine, Jaber Al Ahmed Hospital, South Surra, Kuwait
| | - Soumoud Hussein
- Department of Medicine, Al Amiri Hospital, Kuwait City, Kuwait
| | - Rajesh Rajan
- Department of Cardiology, Sabah Al Ahmed Cardiac Centre, Al Amiri Hospital, Kuwait City, Kuwait
| | | | | | - Maryam Ramadhan
- Department of Obstetrics and Gynaecology, Maternity Hospital, Shuwaikh Medical Area, Kuwait
| | - Kobalava D. Zhanna
- Department of Internal Medicine with the Subspecialty of Cardiology and Functional Diagnostics Named after V.S. Moiseev, Institute of Medicine, Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation
| | - Jiazhu Pan
- Department of Mathematics and Statistics, University of Strathclyde, Glasgow, United Kingdom
| | - Haya Malhas
- Department of Medicine, Mubarak Al-Kabeer Hospital, Jabriya, Kuwait
| | - Hassan Abdelnaby
- Department of Endemic and Infectious Diseases, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
- Division of Gastroenterology, Department of Medicine, Al Sabah Hospital, Shuwaikh Medical Area, Kuwait
| | - Farah Almutairi
- Department of Medicine, Farwaniya Hospital, Farwaniya, Kuwait
| | - Bader Al-Bader
- Department of Medicine, Farwaniya Hospital, Farwaniya, Kuwait
| | - Ahmad Alsaber
- Department of Mathematics and Statistics, University of Strathclyde, Glasgow, United Kingdom
| | - Mohammed Abdullah
- Department of Infectious Diseases, Infectious Diseases Hospital, Shuwaikh Medical Area, Kuwait
| |
Collapse
|
|
33
|
Bian DJH, Sabri S, Abdulkarim BS. Interactions between COVID-19 and Lung Cancer: Lessons Learned during the Pandemic. Cancers (Basel) 2022; 14:cancers14153598. [PMID: 35892857 PMCID: PMC9367272 DOI: 10.3390/cancers14153598] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/16/2022] [Accepted: 07/20/2022] [Indexed: 01/27/2023] Open
Abstract
Simple Summary COVID-19 is a respiratory infectious disease caused by the coronavirus SARS-CoV-2. Lung cancer is the leading cause of all cancer-related deaths worldwide. As both SARS-CoV-2 and lung cancer affect the lungs, the aim of this narrative review is to provide a consolidation of lessons learned throughout the pandemic regarding lung cancer and COVID-19. Risk factors found in lung cancer patients, such as advanced cancers, smoking, male, etc., have been associated with severe COVID-19. The cancer treatments hormonal therapy, immunotherapy, and targeted therapy have shown no association with severe COVID-19 disease, but chemotherapy and radiation therapy have shown conflicting results. Logistical changes and modifications in treatment plans were instituted during the pandemic to minimize SARS-CoV-2 exposure while maintaining life-saving cancer care. Finally, medications have been developed to treat early COVID-19, which can be highly beneficial in vulnerable cancer patients, with paxlovid being the most efficacious drug currently available. Abstract Cancer patients, specifically lung cancer patients, show heightened vulnerability to severe COVID-19 outcomes. The immunological and inflammatory pathophysiological similarities between lung cancer and COVID-19-related ARDS might explain the predisposition of cancer patients to severe COVID-19, while multiple risk factors in lung cancer patients have been associated with worse COVID-19 outcomes, including smoking status, older age, etc. Recent cancer treatments have also been urgently evaluated during the pandemic as potential risk factors for severe COVID-19, with conflicting findings regarding systemic chemotherapy and radiation therapy, while other therapies were not associated with altered outcomes. Given this vulnerability of lung cancer patients for severe COVID-19, the delivery of cancer care was significantly modified during the pandemic to both proceed with cancer care and minimize SARS-CoV-2 infection risk. However, COVID-19-related delays and patients’ aversion to clinical settings have led to increased diagnosis of more advanced tumors, with an expected increase in cancer mortality. Waning immunity and vaccine breakthroughs related to novel variants of concern threaten to further impede the delivery of cancer services. Cancer patients have a high risk of severe COVID-19, despite being fully vaccinated. Numerous treatments for early COVID-19 have been developed to prevent disease progression and are crucial for infected cancer patients to minimize severe COVID-19 outcomes and resume cancer care. In this literature review, we will explore the lessons learned during the COVID-19 pandemic to specifically mitigate COVID-19 treatment decisions and the clinical management of lung cancer patients.
Collapse
Affiliation(s)
- David J. H. Bian
- Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, Canada;
| | - Siham Sabri
- Cancer Research Program, Research Institute, McGill University Health Center Glen Site, McGill University, Montreal, QC H4A 3J1, Canada;
| | - Bassam S. Abdulkarim
- Cancer Research Program, Research Institute, and Department of Oncology, Cedars Cancer Center, McGill University Health Center Glen Site, McGill University, Montreal, QC H4A 3J1, Canada
- Correspondence:
| |
Collapse
|
|
34
|
Liu J, Dong J, Yu Y, Yang X, Shu J, Bao H. Corticosteroids showed more efficacy in treating hospitalized patients with COVID-19 than standard care but the effect is minimal: A systematic review and meta-analysis. Front Public Health 2022; 10:847695. [PMID: 35937252 PMCID: PMC9352924 DOI: 10.3389/fpubh.2022.847695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 06/27/2022] [Indexed: 12/15/2022] Open
Abstract
Background During the ongoing coronavirus disease 2019 (COVID-19) pandemic, the use of corticosteroids for COVID-19 has ignited worldwide debate. Previous systematic reviews, including randomized controlled trials (RCTs) and retrospective observational studies, found that corticosteroids have beneficial effects in treating COVID-19. Aim This systematic review and meta-analysis only included RCTs to assess the effectiveness and safety of corticosteroids in hospitalized patients with COVID-19. Methods Comprehensive research strategies (PubMed, Embase, MEDLINE, and Coherence Library) were used to search for RCTs from December 2019 to January 2021. Results Five RCTs were included with 7,235 patients, of which 2,508 patients were receiving corticosteroid treatments (dexamethasone or methylprednisolone), and 4,727 received standard care. The primary outcome was mortality within 28 days. The use of corticosteroids decreased the 28-day mortality of patients with COVID-19, but the findings were not statistically significant (RR, 0.91; 95% CI, 0.78–1.06, p = 0.24). The secondary outcome was the duration of hospitalization; no differences were found between the corticosteroid and standard care groups. However, corticosteroids were associated with a higher hospital discharge rate than standard treatment, but the result was not statistically significant (RR, 1.36; 95% CI, 0.95–1.96, p = 0.09). Conclusions The results suggest that corticosteroids are comparable to standard care in terms of safety in treating COVID-19. Corticosteroids showed greater efficacy than standard care; however, the effect was minimal.
Collapse
Affiliation(s)
- Jixin Liu
- Medical Service Center, Gansu Provincial Hospital, Lanzhou, China
| | - Jing Dong
- Geriatric Respiratory Department, First Hospital of Lanzhou University, Lanzhou, China
| | - Yage Yu
- Geriatric Respiratory Department, First Hospital of Lanzhou University, Lanzhou, China
| | - Xinna Yang
- Geriatric Respiratory Department, First Hospital of Lanzhou University, Lanzhou, China
| | - Juan Shu
- Geriatric Respiratory Department, First Hospital of Lanzhou University, Lanzhou, China
| | - Hairong Bao
- Geriatric Respiratory Department, First Hospital of Lanzhou University, Lanzhou, China
- *Correspondence: Hairong Bao
| |
Collapse
|
|
35
|
Zhou F, Deng J, Heybati K, Zuo QK, Ali S, Hou W, Wong CY, Ramaraju HB, Chang O, Dhivagaran T, Silver Z. Efficacy and safety of corticosteroid regimens for the treatment of hospitalized COVID-19 patients: a meta-analysis. Future Virol 2022; 17:463-489. [PMID: 35814934 PMCID: PMC9249165 DOI: 10.2217/fvl-2021-0244] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Accepted: 04/08/2022] [Indexed: 12/15/2022]
Abstract
Aim To evaluate the efficacy and safety of corticosteroids for treating hospitalized COVID-19 patients. Materials & methods Efficacy outcomes included time to negative SARS-CoV-2 tests, length of stay, duration and incidence of intensive unit care stay, incidence of mortality and duration and incidence of mechanical ventilation. Safety outcomes included the incidence of adverse events and severe adverse events, incidence of hyperglycemia and incidence of nosocomial infections. Results Ninety-five randomized controlled trials (RCTs) and observational studies (n = 42,205) were included. Corticosteroids were associated with increased length of stay (based on RCT only), increased time to negative tests, decreased length of mechanical ventilation and increased odds of hyperglycemia. Conclusion Corticosteroids should be considered in patients requiring mechanical ventilation, and glycemic monitoring may be needed when administering corticosteroids.
Collapse
Affiliation(s)
- Fangwen Zhou
- Faculty of Health Sciences, McMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada
| | - Jiawen Deng
- Faculty of Health Sciences, McMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada
| | - Kiyan Heybati
- Mayo Clinic Alix School of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
| | - Qi Kang Zuo
- Department of Anesthesiology, Rutgers, New Jersey Medical School, 185 S Orange Ave, Newark, NJ 07103, USA
- Faculty of Science, McGill University, 845 Sherbrooke St W, Montreal, QC, H3A 0G5, Canada
| | - Saif Ali
- Faculty of Health Sciences, McMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada
| | - Wenteng Hou
- Faculty of Health Sciences, McMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada
| | - Chi Yi Wong
- Faculty of Health Sciences, McMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada
| | | | - Oswin Chang
- Faculty of Health Sciences, McMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada
| | - Thanansayan Dhivagaran
- Faculty of Health Sciences, McMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada
- Integrated Biomedical Engineering & Health Sciences Program (iBioMed), McMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada
| | - Zachary Silver
- Faculty of Science, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada
| |
Collapse
|
|
36
|
Porta L, Huang SS, Wei C, Su CH, Hsu WT, Sheng WH, Lee CC. Effect of methylprednisolone treatment on COVID-19: An inverse probability of treatment weighting analysis. PLoS One 2022; 17:e0266901. [PMID: 35714141 PMCID: PMC9205494 DOI: 10.1371/journal.pone.0266901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 03/29/2022] [Indexed: 11/18/2022] Open
Abstract
Objectives
While corticosteroids have been hypothesized to exert protective benefits in patients infected with SARS-CoV-2, data remain mixed. This study sought to investigate the outcomes of methylprednisone administration in an Italian cohort of hospitalized patients with confirmed SARS-CoV-2 infection.
Methods
Patients with confirmatory testing for SARS-CoV-2 were retrospectively enrolled from a tertiary university hospital in Milan, Italy from March 1st to April 30th, 2020 and divided into two groups by administration of corticosteroids. Methylprednisolone was administered to patients not responding to pharmacological therapy and ventilatory support at 0.5-1mg/kg/day for 4 to 7 days. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences between the steroid and non-steroid cohorts via inverse probability of treatment weight. Primary outcomes included acute respiratory failure (ARF), shock, and 30-day mortality among surviving patients.
Results
Among 311 patients enrolled, 71 patients received steroids and 240 did not receive steroids. The mean age was 63.1 years, 35.4% were female, and hypertension, diabetes, heart disease, and chronic pulmonary disease were present in 3.5%, 1.3%, 14.8% and 12.2% respectively. Crude analysis revealed no statistically significant reduction in the incidence of 30-day mortality (36,6% vs 21,7%; OR, 2.09; 95% CI, 1.18–3.70; p = 0.011), shock (2.8% vs 4.6%; OR, 0.60; 95% CI = 0.13–2.79; p = 0.514) or ARF (12.7% vs 15%; OR, 0.82; 95% CI = 0.38–1.80; p = 0.625) between the steroid and non-steroid groups. After IPTW analysis, the steroid-group had lower incidence of shock (0.9% vs 4.1%; OR, 0.21; 95% CI,0.06–0.77; p = 0.010), ARF (6.6% vs 16.0%; OR, 0.37; 95% CI, 0.22–0.64; p<0.001) and 30-day mortality (20.3% vs 22.8%; OR 0.86; 95% CI, 0.59–1.26 p = 0.436); even though, for the latter no statistical significance was reached. Steroid use was also associated with increased length of hospital stay both in crude and IPTW analyses. Subgroup analysis revealed that patients with cardiovascular comorbidities or chronic lung diseases were more likely to be steroid responsive. No significant survival benefit was seen after steroid treatment.
Conclusions
Physicians should avoid routine methylprednisolone use in SARS-CoV-2 patients, since it does not reduce 30-day mortality. However, they must consider its use for severe patients with cardiovascular or respiratory comorbidities in order to reduce the incidence of either shock or acute respiratory failure.
Collapse
Affiliation(s)
- Lorenzo Porta
- School of Medicine and Surgery, Department of Emergency Medicine, Università degli studi di Milano Bicocca, Milano, Italy
| | - Sih-Shiang Huang
- Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen Wei
- Department of Medicine, Harvard Medical School, Boston, MA, United States of America
- Department of Internal Medicine, Stanford Health Care, Stanford, CA, United States of America
| | - Chin-Hua Su
- Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Ting Hsu
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America
| | - Wang-Huei Sheng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Chang Lee
- Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
- The Centre for Intelligent Healthcare, National Taiwan University Hospital, Taipei, Taiwan
- Byers Center for Biodesign, Stanford University, Stanford, CA, United States of America
- * E-mail: ,
| |
Collapse
|
|
37
|
Peter L, Wendering DJ, Schlickeiser S, Hoffmann H, Noster R, Wagner DL, Zarrinrad G, Münch S, Picht S, Schulenberg S, Moradian H, Mashreghi MF, Klein O, Gossen M, Roch T, Babel N, Reinke P, Volk HD, Amini L, Schmueck-Henneresse M. Tacrolimus-resistant SARS-CoV-2-specific T cell products to prevent and treat severe COVID-19 in immunosuppressed patients. Mol Ther Methods Clin Dev 2022; 25:52-73. [PMID: 35252469 PMCID: PMC8882037 DOI: 10.1016/j.omtm.2022.02.012] [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: 02/16/2022] [Accepted: 02/25/2022] [Indexed: 12/15/2022]
Abstract
Solid organ transplant (SOT) recipients receive therapeutic immunosuppression that compromises their immune response to infections and vaccines. For this reason, SOT patients have a high risk of developing severe coronavirus disease 2019 (COVID-19) and an increased risk of death from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Moreover, the efficiency of immunotherapies and vaccines is reduced due to the constant immunosuppression in this patient group. Here, we propose adoptive transfer of SARS-CoV-2-specific T cells made resistant to a common immunosuppressant, tacrolimus, for optimized performance in the immunosuppressed patient. Using a ribonucleoprotein approach of CRISPR-Cas9 technology, we have generated tacrolimus-resistant SARS-CoV-2-specific T cell products from convalescent donors and demonstrate their specificity and function through characterizations at the single-cell level, including flow cytometry, single-cell RNA (scRNA) Cellular Indexing of Transcriptomes and Epitopes (CITE), and T cell receptor (TCR) sequencing analyses. Based on the promising results, we aim for clinical validation of this approach in transplant recipients. Additionally, we propose a combinatory approach with tacrolimus, to prevent an overshooting immune response manifested as bystander T cell activation in the setting of severe COVID-19 immunopathology, and tacrolimus-resistant SARS-CoV-2-specific T cell products, allowing for efficient clearance of viral infection. Our strategy has the potential to prevent severe COVID-19 courses in SOT or autoimmunity settings and to prevent immunopathology while providing viral clearance in severe non-transplant COVID-19 cases.
Collapse
Affiliation(s)
- Lena Peter
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Einstein Center for Regenerative Therapies at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Désirée Jacqueline Wendering
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany
| | - Stephan Schlickeiser
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Henrike Hoffmann
- Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Rebecca Noster
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany
| | - Dimitrios Laurin Wagner
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.,Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353 Berlin, Germany.,Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Transfusion Medicine, Charitéplatz 1, 10117 Berlin, Germany
| | - Ghazaleh Zarrinrad
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Einstein Center for Regenerative Therapies at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Sandra Münch
- Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Samira Picht
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany
| | - Sarah Schulenberg
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Einstein Center for Regenerative Therapies at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Hanieh Moradian
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Institute of Active Polymers, Helmholtz-Zentrum Hereon, Kantstr. 55, 14513 Teltow, Germany.,Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany
| | - Mir-Farzin Mashreghi
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Deutsches Rheuma-Forschungszentrum Berlin, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany
| | - Oliver Klein
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany
| | - Manfred Gossen
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Institute of Active Polymers, Helmholtz-Zentrum Hereon, Kantstr. 55, 14513 Teltow, Germany
| | - Toralf Roch
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353 Berlin, Germany.,Center for Translational Medicine, Immunology, and Transplantation, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Hölkeskampring 40, 44625 Herne, Germany
| | - Nina Babel
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353 Berlin, Germany.,Center for Translational Medicine, Immunology, and Transplantation, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Hölkeskampring 40, 44625 Herne, Germany
| | - Petra Reinke
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Hans-Dieter Volk
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.,Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Leila Amini
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Michael Schmueck-Henneresse
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| |
Collapse
|
|
38
|
Eskandarian Boroujeni M, Sekrecka A, Antonczyk A, Hassani S, Sekrecki M, Nowicka H, Lopacinska N, Olya A, Kluzek K, Wesoly J, Bluyssen HAR. Dysregulated Interferon Response and Immune Hyperactivation in Severe COVID-19: Targeting STATs as a Novel Therapeutic Strategy. Front Immunol 2022; 13:888897. [PMID: 35663932 PMCID: PMC9156796 DOI: 10.3389/fimmu.2022.888897] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 04/13/2022] [Indexed: 01/08/2023] Open
Abstract
A disease outbreak in December 2019, caused by a novel coronavirus SARS-CoV-2, was named COVID-19. SARS-CoV-2 infects cells from the upper and lower respiratory tract system and is transmitted by inhalation or contact with infected droplets. Common clinical symptoms include fatigue, fever, and cough, but also shortness of breath and lung abnormalities. Still, some 5% of SARS-CoV-2 infections progress to severe pneumonia and acute respiratory distress syndrome (ARDS), with pulmonary edema, acute kidney injury, and/or multiple organ failure as important consequences, which can lead to death. The innate immune system recognizes viral RNAs and triggers the expression of interferons (IFN). IFNs activate anti-viral effectors and components of the adaptive immune system by activating members of the STAT and IRF families that induce the expression of IFN-stimulated genes (ISG)s. Among other coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV, common strategies have been identified to antagonize IFN signaling. This typically coincides with hyperactive inflammatory host responses known as the “cytokine storm” that mediate severe lung damage. Likewise, SARS-CoV-2 infection combines a dysregulated IFN response with excessive production of inflammatory cytokines in the lungs. This excessive inflammatory response in the lungs is associated with the local recruitment of immune cells that create a pathogenic inflammatory loop. Together, it causes severe lung pathology, including ARDS, as well as damage to other vulnerable organs, like the heart, spleen, lymph nodes, and kidney, as well as the brain. This can rapidly progress to multiple organ exhaustion and correlates with a poor prognosis in COVID-19 patients. In this review, we focus on the crucial role of different types of IFN that underlies the progression of SARS-CoV-2 infection and leads to immune cell hyper-activation in the lungs, exuberant systemic inflammation, and multiple organ damage. Consequently, to protect from systemic inflammation, it will be critical to interfere with signaling cascades activated by IFNs and other inflammatory cytokines. Targeting members of the STAT family could therefore be proposed as a novel therapeutic strategy in patients with severe COVID-19.
Collapse
Affiliation(s)
- Mahdi Eskandarian Boroujeni
- Laboratory of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
| | - Agata Sekrecka
- Laboratory of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
| | - Aleksandra Antonczyk
- Laboratory of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
| | - Sanaz Hassani
- Laboratory of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
| | - Michal Sekrecki
- Laboratory of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
| | - Hanna Nowicka
- Laboratory of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
| | - Natalia Lopacinska
- Laboratory of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
| | - Arta Olya
- Laboratory of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
| | - Katarzyna Kluzek
- Laboratory of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
| | - Joanna Wesoly
- Laboratory of High Throughput Technologies, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
| | - Hans A R Bluyssen
- Laboratory of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
| |
Collapse
|
|
39
|
Wang SC, Zhang F, Zhu H, Yang H, Liu Y, Wang P, Parpura V, Wang YF. Potential of Endogenous Oxytocin in Endocrine Treatment and Prevention of COVID-19. Front Endocrinol (Lausanne) 2022; 13:799521. [PMID: 35592777 PMCID: PMC9110836 DOI: 10.3389/fendo.2022.799521] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 03/14/2022] [Indexed: 01/09/2023] Open
Abstract
Coronavirus disease 2019 or COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a significant threat to the health of human beings. While wearing mask, maintaining social distance and performing self-quarantine can reduce virus spreading passively, vaccination actively enhances immune defense against COVID-19. However, mutations of SARS-CoV-2 and presence of asymptomatic carriers frustrate the effort of completely conquering COVID-19. A strategy that can reduce the susceptibility and thus prevent COVID-19 while blocking viral invasion and pathogenesis independent of viral antigen stability is highly desirable. In the pathogenesis of COVID-19, endocrine disorders have been implicated. Correspondingly, many hormones have been identified to possess therapeutic potential of treating COVID-19, such as estrogen, melatonin, corticosteroids, thyroid hormone and oxytocin. Among them, oxytocin has the potential of both treatment and prevention of COVID-19. This is based on oxytocin promotion of immune-metabolic homeostasis, suppression of inflammation and pre-existing comorbidities, acceleration of damage repair, and reduction of individuals' susceptibility to pathogen infection. Oxytocin may specifically inactivate SARS-COV-2 spike protein and block viral entry into cells via angiotensin-converting enzyme 2 by suppressing serine protease and increasing interferon levels and number of T-lymphocytes. In addition, oxytocin can promote parasympathetic outflow and the secretion of body fluids that could dilute and even inactivate SARS-CoV-2 on the surface of cornea, oral cavity and gastrointestinal tract. What we need to do now is clinical trials. Such trials should fully balance the advantages and disadvantages of oxytocin application, consider the time- and dose-dependency of oxytocin effects, optimize the dosage form and administration approach, combine oxytocin with inhibitors of SARS-CoV-2 replication, apply specific passive immunization, and timely utilize efficient vaccines. Meanwhile, blocking COVID-19 transmission chain and developing other efficient anti-SARS-CoV-2 drugs are also important. In addition, relative to the complex issues with drug applications over a long term, oxytocin can be mobilized through many physiological stimuli, and thus used as a general prevention measure. In this review, we explore the potential of oxytocin for treatment and prevention of COVID-19 and perhaps other similar pathogens.
Collapse
Affiliation(s)
- Stephani C. Wang
- Division of Cardiology, Department of Medicine, University of California-Irvine, Irvine, CA, United States
| | - Fengmin Zhang
- Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China
| | - Hui Zhu
- Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China
| | - Haipeng Yang
- Neonatal Division of the Department of Pediatrics, Harbin Medical University The Fourth Affiliated Hospital, Harbin, China
| | - Yang Liu
- Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China
| | - Ping Wang
- Department of Genetics, School of Basic Medical Sciences, Harbin Medical University, Harbin, China
| | - Vladimir Parpura
- Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, AL, United States
| | - Yu-Feng Wang
- Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China
| |
Collapse
|
|
40
|
López Montesinos I, Arrieta-Aldea I, Dicastillo A, Zuccarino F, Sorli L, Guerri-Fernández R, Arnau-Barrés I, Milagro Montero M, Siverio-Parès A, Durán X, del Mar Arenas M, Brasé Arnau A, Cañas-Ruano E, Castañeda S, Domingo Kamber I, Gómez-Junyent J, Pelegrín I, Sánchez Martínez F, Sendra E, Suaya Leiro L, Villar-García J, Nogués X, Grau S, Knobel H, Gomez-Zorrilla S, Pablo Horcajada J, COVID-MAR Group. Comparison of Hospitalized Coronavirus Disease 2019 and Influenza Patients Requiring Supplemental Oxygen in a Cohort Study: Clinical Impact and Resource Consumption. Clin Infect Dis 2022; 75:2225-2238. [PMID: 35442442 PMCID: PMC9047197 DOI: 10.1093/cid/ciac314] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 04/07/2022] [Accepted: 04/15/2022] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND To compare clinical characteristics, outcomes, and resource consumption of patients with coronavirus disease 2019 (COVID-19) and seasonal influenza requiring supplemental oxygen. METHODS Retrospective cohort study conducted at a tertiary-care hospital. Patients admitted because of seasonal influenza between 2017 and 2019, or with COVID-19 between March and May 2020 requiring supplemental oxygen were compared. Primary outcome: 30-day mortality. Secondary outcomes: 90-day mortality and hospitalization costs. Attempted sample size to detect an 11% difference in mortality was 187 patients per group. RESULTS COVID-19 cases were younger (median years of age, 67; interquartile range [IQR] 54-78 vs 76 [IQR 64-83]; P < .001) and more frequently overweight, whereas influenza cases had more hypertension, immunosuppression, and chronic heart, respiratory, and renal disease. Compared with influenza, COVID-19 cases had more pneumonia (98% vs 60%, <.001), higher Modified Early Warning Score (MEWS) and CURB-65 (confusion, blood urea nitrogen, respiratory rate, systolic blood pressure, and age >65 years) scores and were more likely to show worse progression on the World Health Organization ordinal scale (33% vs 4%; P < .001). The 30-day mortality rate was higher for COVID-19 than for influenza: 15% vs 5% (P = .001). The median age of nonsurviving cases was 81 (IQR 74-88) and 77.5 (IQR 65-84) (P = .385), respectively. COVID-19 was independently associated with 30-day (hazard ratio [HR], 4.6; 95% confidence interval [CI], 2-10.4) and 90-day (HR, 5.2; 95% CI, 2.4-11.4) mortality. Sensitivity and subgroup analyses, including a subgroup considering only patients with pneumonia, did not show different trends. Regarding resource consumption, COVID-19 patients had longer hospital stays and higher critical care, pharmacy, and complementary test costs. CONCLUSIONS Although influenza patients were older and had more comorbidities, COVID-19 cases requiring supplemental oxygen on admission had worse clinical and economic outcomes.
Collapse
Affiliation(s)
- Inmaculada López Montesinos
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Itziar Arrieta-Aldea
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Aitor Dicastillo
- Universitat Pompeu Fabra (UPF), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Flavio Zuccarino
- Department of Radiology, Hospital del Mar, Hospital Sant Joan de Deu, Barcelona, Spain
| | - Luisa Sorli
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Roberto Guerri-Fernández
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | | | - Maria Milagro Montero
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Ana Siverio-Parès
- Microbiology Service, Laboratori de Referència de Catalunya, El Prat de Llobregat (Barcelona), 08820, Spain
| | - Xavier Durán
- Methodology and Biostatistics Support Unit, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, 08003, Spain
| | - Maria del Mar Arenas
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Ariadna Brasé Arnau
- Internal Medicine Service, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Barcelona, 08003, Spain
| | - Esperanza Cañas-Ruano
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Silvia Castañeda
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Ignacio Domingo Kamber
- Internal Medicine Service, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Barcelona, 08003, Spain
| | - Joan Gómez-Junyent
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Iván Pelegrín
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Francisca Sánchez Martínez
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Elena Sendra
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Lucía Suaya Leiro
- Internal Medicine Service, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Barcelona, 08003, Spain
| | - Judit Villar-García
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Xavier Nogués
- Internal Medicine Service, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Barcelona, 08003, Spain
| | - Santiago Grau
- Pharmacy Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain
| | - Hernando Knobel
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | - Silvia Gomez-Zorrilla
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain,Corresponding author information Silvia Gómez-Zorrilla Infectious Diseases Service, Hospital del Mar (Barcelona, Spain). Passeig Marítim de la Barceloneta, 25-29, 08003, Barcelona, Spain.
| | - Juan Pablo Horcajada
- Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Spanish Network for Research in Infectious Diseases (REIPI), Barcelona, 08003, Spain
| | | |
Collapse
|
|
41
|
Cytokine Profile and Anti-Inflammatory Activity of a Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells (PRS CK STORM). Biomolecules 2022; 12:biom12040534. [PMID: 35454123 PMCID: PMC9029939 DOI: 10.3390/biom12040534] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/27/2022] [Accepted: 03/29/2022] [Indexed: 02/01/2023] Open
Abstract
Intercellular communication between monocytes/macrophages and cells involved in tissue regeneration, such as mesenchymal stromal cells (MSCs) and primary tissue cells, is essential for tissue regeneration and recovery of homeostasis. Typically, in the final phase of the inflammation-resolving process, this intercellular communication drives an anti-inflammatory immunomodulatory response. To obtain a safe and effective treatment to counteract the cytokine storm associated with a disproportionate immune response to severe infections, including that associated with COVID-19, by means of naturally balanced immunomodulation, our group has standardized the production under GMP-like conditions of a secretome by coculture of macrophages and MSCs. To characterize this proteome, we determined the expression of molecules related to cellular immune response and tissue regeneration, as well as its possible toxicity and anti-inflammatory potency. The results show a specific molecular pattern of interaction between the two cell types studied, with an anti-inflammatory and regenerative profile. In addition, the secretome is not toxic by itself on human PBMC or on THP-1 monocytes and prevents lipopolysaccharide (LPS)-induced growth effects on those cell types. Finally, PRS CK STORM prevents LPS-induced TNF-A and IL-1Β secretion from PBMC and from THP-1 cells at the same level as hydrocortisone, demonstrating its anti-inflammatory potency.
Collapse
|
|
42
|
Arcani R, Cauchois R, Suchon P, Jean R, Jarrot P, Pinho QGD, Dalmas J, Jean E, Andre B, Veit V, Koubi M, Kaplanski G. Factors associated with dexamethasone efficacy in COVID‐19. A retrospective investigative cohort study. J Med Virol 2022; 94:3169-3175. [PMID: 35277862 PMCID: PMC9088322 DOI: 10.1002/jmv.27712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/28/2022] [Accepted: 03/10/2022] [Indexed: 11/09/2022]
Abstract
Dexamethasone has demonstrated efficacy in reducing mortality in COVID‐19. However, its practical use is badly defined. We aimed to investigate factors associated with dexamethasone efficacy in real life. Our retrospective study was conducted in two university hospitals between September and November 2020 and included all the consecutive hospitalized patients with a laboratory‐confirmed SARS‐CoV‐2 infection assessed by RT‐PCR, treated with intravenous dexamethasone (6 mg/day). Among 111 patients, 10.6% necessitated a transfer into the intensive care unit (ICU) and the 28‐day mortality rate was 17.1%. The 28‐day mortality rate was significantly lower in patients who demonstrated improvement at 48 h (hazard ratio [HR]: 0.17, 95% confidence interval [CI]: 0.04–0.78, p = 0.02) and 96 h (HR: 0.07, 95% CI: 0.02–0.31, p = 0.0005) after dexamethasone initiation. Apart from well‐known risk factors (age, hypertension, active cancer, severe lesions on chest computed tomography [CT] scan), we found that a high viral load in nasopharyngeal swab (Cycle threshold <30) at dexamethasone initiation was associated with higher 28‐day mortality (66.6% vs. 36.7%, p = 0.03). Patients who did not receive antibiotics at dexamethasone initiation had a higher rate of transfer into the ICU (55.6% vs. 23.5%, p = 0.045) with a trend towards higher mortality in case of severe or critical lesions on CT scan (75.0% vs. 25.0%, p = 0.053). Patients who did not improve within 2–4 days after steroid initiation have a bad prognosis and should receive additional anti‐inflammatory drugs. Our data suggest better efficacy of dexamethasone in patients with a low or negative viral load, receiving broad‐spectrum antibiotics.
At dexamethasone initiation, a high viral load was associated with higher mortality. Patients without antibiotics were more transferred into the ICU. Mortality was lower when improvement 48 h and 96 h after dexamethasone initiation.
Collapse
Affiliation(s)
- Robin Arcani
- Department of Internal Medicine and Clinical Immunology, CHU La ConceptionAssistance Publique‐Hôpitaux de Marseille (AP‐HM)147 Boulevard Baille13005MarseilleFrance
- Center for Cardiovascular and Nutrition research (C2VN), INRA 1260, INSERM UMR_S 1263Aix‐Marseille University27 Boulevard Jean Moulin13385MarseilleFrance
| | - Raphael Cauchois
- Department of Internal Medicine and Clinical Immunology, CHU La ConceptionAssistance Publique‐Hôpitaux de Marseille (AP‐HM)147 Boulevard Baille13005MarseilleFrance
- Center for Cardiovascular and Nutrition research (C2VN), INRA 1260, INSERM UMR_S 1263Aix‐Marseille University27 Boulevard Jean Moulin13385MarseilleFrance
| | - Pierre Suchon
- Hematology Laboratory, CHU La Timone, Assistance Publique‐Hôpitaux de Marseille (AP‐HM)264 Rue Saint‐Pierre13005MarseilleFrance
| | - Rodolphe Jean
- Department of Internal Medicine and Clinical Immunology, CHU La ConceptionAssistance Publique‐Hôpitaux de Marseille (AP‐HM)147 Boulevard Baille13005MarseilleFrance
| | - Pierre‐André Jarrot
- Department of Internal Medicine and Clinical Immunology, CHU La ConceptionAssistance Publique‐Hôpitaux de Marseille (AP‐HM)147 Boulevard Baille13005MarseilleFrance
- Center for Cardiovascular and Nutrition research (C2VN), INRA 1260, INSERM UMR_S 1263Aix‐Marseille University27 Boulevard Jean Moulin13385MarseilleFrance
| | - Quentin Gomes De Pinho
- Department of Internal Medicine and Clinical Immunology, CHU La ConceptionAssistance Publique‐Hôpitaux de Marseille (AP‐HM)147 Boulevard Baille13005MarseilleFrance
| | - Jean‐Baptiste Dalmas
- Department of Internal Medicine and Clinical Immunology, CHU La ConceptionAssistance Publique‐Hôpitaux de Marseille (AP‐HM)147 Boulevard Baille13005MarseilleFrance
| | - Estelle Jean
- Department of Internal Medicine, CHU La TimoneAssistance Publique‐Hôpitaux de Marseille (AP‐HM)264 Rue Saint‐Pierre13005MarseilleFrance
| | - Baptiste Andre
- Department of Internal Medicine, CHU La TimoneAssistance Publique‐Hôpitaux de Marseille (AP‐HM)264 Rue Saint‐Pierre13005MarseilleFrance
| | - Véronique Veit
- Department of Internal Medicine, CHU La TimoneAssistance Publique‐Hôpitaux de Marseille (AP‐HM)264 Rue Saint‐Pierre13005MarseilleFrance
| | - Marie Koubi
- Department of Internal Medicine and Clinical Immunology, CHU La ConceptionAssistance Publique‐Hôpitaux de Marseille (AP‐HM)147 Boulevard Baille13005MarseilleFrance
| | - Gilles Kaplanski
- Department of Internal Medicine and Clinical Immunology, CHU La ConceptionAssistance Publique‐Hôpitaux de Marseille (AP‐HM)147 Boulevard Baille13005MarseilleFrance
- Center for Cardiovascular and Nutrition research (C2VN), INRA 1260, INSERM UMR_S 1263Aix‐Marseille University27 Boulevard Jean Moulin13385MarseilleFrance
| |
Collapse
|
|
43
|
Sarzani R, Spannella F, Giulietti F, Di Pentima C, Giordano P, Giacometti A. Possible harm from glucocorticoid drugs misuse in the early phase of SARS-CoV-2 infection: a narrative review of the evidence. Intern Emerg Med 2022; 17:329-338. [PMID: 34718937 PMCID: PMC8557262 DOI: 10.1007/s11739-021-02860-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Accepted: 09/26/2021] [Indexed: 12/15/2022]
Abstract
Since the publication of the RECOVERY trial, the use of glucocorticoid drugs (GC) has spread for the treatment of severe COVID-19 worldwide. However, the benefit of dexamethasone was largest in patients who received mechanical ventilation or supplemental oxygen therapy, while no benefit was found among patients without hypoxemia. In addition, a positive outcome was found in patients who received dexamethasone after several days of symptoms, while possible harm could exist if administered early. The right time interval for GC administration is still a matter of debate. Previous studies showed that an early GC use during the first phase of the disease, when viral replication peaks, may negatively affect the innate immune response through several mechanisms, such as the inhibition of pro-inflammatory and antiviral cytokine production and signaling pathway, including type I interferon, that is fundamental to counteract the virus and that was found to be impaired in several patients with life-threatening COVID-19. The GC misuse can lead to a more severe disease even in patients who do not have the established risk factors, such as obesity and cardiovascular diseases. In our focused review, we describe the role of immune response in viral infections, especially SARS-CoV-2, and discuss the potential harms of GC misuse in COVID-19.
Collapse
Affiliation(s)
- Riccardo Sarzani
- Internal Medicine and Geriatrics, Italian National Research Centre on Aging, Hospital "U. Sestilli", IRCCS INRCA, via della Montagnola n. 81, 60127, Ancona, Italy.
- Department of Clinical and Molecular Sciences, University "Politecnica Delle Marche", Via Tronto 10/a, Ancona, Italy.
| | - Francesco Spannella
- Internal Medicine and Geriatrics, Italian National Research Centre on Aging, Hospital "U. Sestilli", IRCCS INRCA, via della Montagnola n. 81, 60127, Ancona, Italy
- Department of Clinical and Molecular Sciences, University "Politecnica Delle Marche", Via Tronto 10/a, Ancona, Italy
| | - Federico Giulietti
- Internal Medicine and Geriatrics, Italian National Research Centre on Aging, Hospital "U. Sestilli", IRCCS INRCA, via della Montagnola n. 81, 60127, Ancona, Italy
- Department of Clinical and Molecular Sciences, University "Politecnica Delle Marche", Via Tronto 10/a, Ancona, Italy
| | - Chiara Di Pentima
- Internal Medicine and Geriatrics, Italian National Research Centre on Aging, Hospital "U. Sestilli", IRCCS INRCA, via della Montagnola n. 81, 60127, Ancona, Italy
- Department of Clinical and Molecular Sciences, University "Politecnica Delle Marche", Via Tronto 10/a, Ancona, Italy
| | - Piero Giordano
- Internal Medicine and Geriatrics, Italian National Research Centre on Aging, Hospital "U. Sestilli", IRCCS INRCA, via della Montagnola n. 81, 60127, Ancona, Italy
| | - Andrea Giacometti
- Department of Biological Sciences and Public Health, Infectious Diseases Clinic, University "Politecnica Delle Marche", Via Tronto 10/a, Ancona, Italy
| |
Collapse
|
|
44
|
Fuest KE, Erber J, Berg-Johnson W, Heim M, Hoffmann D, Kapfer B, Kriescher S, Ulm B, Schmid RM, Rasch S, Lahmer T. Risk factors for <em>Herpes simplex</em> virus (HSV) and <em>Cytomegalovirus</em> (CMV) infections in critically-ill COVID-19 patients. Multidiscip Respir Med 2022; 17:815. [PMID: 35340709 PMCID: PMC8941339 DOI: 10.4081/mrm.2022.815] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 12/07/2021] [Indexed: 12/12/2022] Open
Abstract
Background To assess the prevalence of Herpes simplex and Cytomegalovirus infection in respiratory samples of critically-ill COVID-19 patients, its role in outcome and mortality and the influence of dexamethasone treatment in the early stage of SARS-CoV-2 infection. Methods All mechanically ventilated COVID-19 patients treated on ICU between March 2020 and January 2021 were included. Respiratory specimens were tested for Herpes simplex virus (HSV) type 1, 2 and Cytomegalovirus (CMV) by quantitative real-time PCR. Clinical parameters were compared in the cohorts with and without HSV-1- infection. Results 134 patients with a median age of 72.5 years (73.0% male, n=98) were included. HSV-1 reactivation occurred in 61 patients (45.5%), after median 9 (7-13) days of mechanical ventilation. The main factor for reactivation was length of stay on ICU (24 days vs 13 days, p<0.001) and duration of mechanical ventilation (417 vs 214 hours, p<0.001). Treatment with dexamethasone and a history of immunosuppression did not associate with HSV-infection in the univariate analysis (39 vs 41, p=0.462 and 27.9% vs 23.3%, p=0.561, respectively). Both ICU and hospital mortality were not significantly different in the cohorts with and without HSV-infection (57.4% vs 45.2%, p=0.219). Conclusions Our study shows a high prevalence of HSV-infection in critically-ill COVID-19 patients which was unexpectedly higher than the prevalence of CMV-infections and unrelated to dexamethasone treatment. The main risk factors for HSV and CMV in the studied cohorts were the length of ICU stay and duration of mechanical ventilation. Therefore, we recommend routine monitoring of critically ill COVID-19 patients for these viral co-infections and consider treatment in those patients.
Collapse
|
|
45
|
Wüstner S, Hogger S, Gartner-Freyer D, Lebioda A, Schley K, Leverkus F. Clinical Evidence Informing Treatment Guidelines on Repurposed Drugs for Hospitalized Patients During the Early COVID-19 Pandemic: Corticosteroids, Anticoagulants, (Hydroxy)chloroquine. Front Public Health 2022; 10:804404. [PMID: 35252090 PMCID: PMC8896497 DOI: 10.3389/fpubh.2022.804404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 01/24/2022] [Indexed: 01/03/2023] Open
Abstract
INTRODUCTION In early 2020, the coronavirus disease 2019 (COVID-19) pandemic spread worldwide, overwhelming hospitals with severely ill patients and posing the urgent need for clinical evidence to guide patient care. First treatment options available were repurposed drugs to fight inflammation, coagulopathy, and viral replication. A vast number of clinical studies were launched globally to test their efficacy and safety. Our analysis describes the development of global evidence on repurposed drugs, in particular corticosteroids, anticoagulants, and (hydroxy)chloroquine in hospitalized COVID-19 patients based on different study types. We track the incorporation of clinical data in international and national treatment guidelines and identify factors that characterize studies and analyses with the greatest impact on treatment recommendations. METHODS A literature search in MEDLINE was conducted to assess the clinical evidence on treatment with corticosteroids, anticoagulants, and (hydroxy)chloroquine in hospitalized COVID-19 patients during the first year of the pandemic. Adoption of the evidence from this clinical data in treatment guidelines of the World Health Organization (WHO), Germany, and United States (US) was evaluated over time. RESULTS We identified 106 studies on corticosteroids, 141 studies on anticoagulants, and 115 studies on (hydroxy)chloroquine. Most studies were retrospective cohort studies; some were randomized clinical trials (RCTs), and a few were platform trials. These studies were compared to studies directly and indirectly referred to in WHO (7 versions), German (5 versions), and US (21 versions) guidelines. We found that initially large, well-adjusted, mainly retrospective cohort studies and ultimately large platform trials or coordinated meta-analyses of RCTs provided best available clinical evidence supporting treatment recommendations. DISCUSSION Particularly early in the pandemic, evidence for the efficacy and safety of repurposed drugs was of low quality, since time and scientific rigor seemed to be competing factors. Pandemic preparedness, coordinated efforts, and combined analyses were crucial to generating timely and robust clinical evidence that informed national and international treatment guidelines on corticosteroids, anticoagulants, and (hydroxy)chloroquine. Multi-arm platform trials with master protocols and coordinated meta-analyses proved particularly successful, with researchers joining forces to answer the most pressing questions as quickly as possible.
Collapse
Affiliation(s)
| | - Sara Hogger
- AMS Advanced Medical Services GmbH, Munich, Germany
| | | | | | | | | |
Collapse
|
|
46
|
Rossi A, Magri F, Caro G, Federico A, Di Fraia M, Muscianese M, Fortuna MC, Carlesimo M. Recommendations on trichological treatments during COVID-19 pandemic. J DERMATOL TREAT 2022; 33:792-797. [DOI: 10.1080/09546634.2020.1781046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Affiliation(s)
- Alfredo Rossi
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Francesca Magri
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Gemma Caro
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Alessandro Federico
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Marco Di Fraia
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Marta Muscianese
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Maria Caterina Fortuna
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Marta Carlesimo
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| |
Collapse
|
|
47
|
Rocha SM, Fagre AC, Latham AS, Cummings JE, Aboellail TA, Reigan P, Aldaz DA, McDermott CP, Popichak KA, Kading RC, Schountz T, Theise ND, Slayden RA, Tjalkens RB. A Novel Glucocorticoid and Androgen Receptor Modulator Reduces Viral Entry and Innate Immune Inflammatory Responses in the Syrian Hamster Model of SARS-CoV-2 Infection. Front Immunol 2022; 13:811430. [PMID: 35250984 PMCID: PMC8889105 DOI: 10.3389/fimmu.2022.811430] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 01/25/2022] [Indexed: 12/15/2022] Open
Abstract
Despite significant research efforts, treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain limited. This is due in part to a lack of therapeutics that increase host defense to the virus. Replication of SARS-CoV-2 in lung tissue is associated with marked infiltration of macrophages and activation of innate immune inflammatory responses that amplify tissue injury. Antagonists of the androgen (AR) and glucocorticoid (GR) receptors have shown efficacy in models of COVID-19 and in clinical studies because the cell surface proteins required for viral entry, angiotensin converting enzyme 2 (ACE2) and the transmembrane protease, serine 2 (TMPRSS2), are transcriptionally regulated by these receptors. We postulated that the GR and AR modulator, PT150, would reduce infectivity of SARS-CoV-2 and prevent inflammatory lung injury in the Syrian golden hamster model of COVID-19 by down-regulating expression of critical genes regulated through these receptors. Animals were infected intranasally with 2.5 × 104 TCID50/ml equivalents of SARS-CoV-2 (strain 2019-nCoV/USA-WA1/2020) and PT150 was administered by oral gavage at 30 and 100 mg/Kg/day for a total of 7 days. Animals were examined at 3, 5 and 7 days post-infection (DPI) for lung histopathology, viral load and production of proteins regulating the progression of SARS-CoV-2 infection. Results indicated that oral administration of PT150 caused a dose-dependent decrease in replication of SARS-CoV-2 in lung, as well as in expression of ACE2 and TMPRSS2. Lung hypercellularity and infiltration of macrophages and CD4+ T-cells were dramatically decreased in PT150-treated animals, as was tissue damage and expression of IL-6. Molecular docking studies suggest that PT150 binds to the co-activator interface of the ligand-binding domain of both AR and GR, thereby acting as an allosteric modulator and transcriptional repressor of these receptors. Phylogenetic analysis of AR and GR revealed a high degree of sequence identity maintained across multiple species, including humans, suggesting that the mechanism of action and therapeutic efficacy observed in Syrian hamsters would likely be predictive of positive outcomes in patients. PT150 is therefore a strong candidate for further clinical development for the treatment of COVID-19 across variants of SARS-CoV-2.
Collapse
Affiliation(s)
- Savannah M. Rocha
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States
- Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, United States
| | - Anna C. Fagre
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States
| | - Amanda S. Latham
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States
- Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, United States
| | - Jason E. Cummings
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States
| | - Tawfik A. Aboellail
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States
| | - Philip Reigan
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Denver, CO, United States
| | - Devin A. Aldaz
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States
| | - Casey P. McDermott
- Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, United States
| | - Katriana A. Popichak
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States
| | - Rebekah C. Kading
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States
| | - Tony Schountz
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States
| | - Neil D. Theise
- Depatment of Pathology, New York University (NYU)-Grossman School of Medicine, New York, NY, United States
| | - Richard A. Slayden
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States
| | - Ronald B. Tjalkens
- Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, United States
| |
Collapse
|
|
48
|
Caiazzo E, Rezig AOM, Bruzzese D, Ialenti A, Cicala C, Cleland JGF, Guzik TJ, Maffia P, Pellicori P. Systemic administration of glucocorticoids, cardiovascular complications and mortality in patients hospitalised with COVID-19, SARS, MERS or influenza: A systematic review and meta-analysis of randomised trials. Pharmacol Res 2022; 176:106053. [PMID: 34979235 PMCID: PMC8719379 DOI: 10.1016/j.phrs.2021.106053] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/28/2021] [Accepted: 12/29/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Administration of glucocorticoids might reduce mortality in patients with severe COVID-19 but have adverse cardiometabolic effects. OBJECTIVES to investigate the effect of systemic administration of glucocorticoids on cardiovascular complications and all-cause mortality in patients hospitalised with respiratory viral infections, including COVID-19, SARS, MERS and influenza. METHODS We identified randomised trials published prior to July 28th, 2021. The Mantel-Haenszel random effects method and the Hartung and Knapp adjustment were used to obtain pooled estimates of treatment effect with 95% confidence intervals. RESULTS No randomised trials of glucocorticoids for SARS, MERS or influenza reported relevant outcomes. We included eleven COVID-19 randomised trials (8109 patients). Overall, compared to placebo or standard care, glucocorticoids were not associated with a reduction of in-hospital mortality (p = 0.09). In a pre-specified sub-analysis, in-hospital mortality was reduced by 19% when follow-up was restricted to 14 days from randomisation (5/11 trials, 1329 patients, p = 0.02). With longer follow-up (9/11 trials, 7874 patients), administration of glucocorticoids was associated with a trend to benefit for those requiring mechanical ventilation (RR 0.86; 95% CI 0.57-1.27) but possible harm for those not receiving oxygen at randomisation (RR 1.27; 95% CI 1.00 - 1.61), an effect that was significantly different amongst subgroups (p = 0.0359). Glucocorticoids reduced the risk of worsening renal function by 37% (4/11 trials); reported rate of other cardiovascular complications was low. CONCLUSIONS Administration of systemic glucocorticoids to patients hospitalised with COVID-19 does not lower mortality overall but may reduce it in those requiring respiratory support and increase it in those who do not.
Collapse
Affiliation(s)
- Elisabetta Caiazzo
- Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Asma O M Rezig
- Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK
| | - Dario Bruzzese
- Department of Public health, University of Naples Federico II, Naples, Italy
| | - Armando Ialenti
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Carla Cicala
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - John G F Cleland
- Robertson Centre for Biostatistics, and Glasgow Clinical Trials Unit, Institute of Health and Wellbeing, University of Glasgow, UK; National Heart & Lung Institute, Imperial College London, UK
| | - Tomasz J Guzik
- Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Department of Internal and Agricultural Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Pasquale Maffia
- Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK.
| | - Pierpaolo Pellicori
- Robertson Centre for Biostatistics, and Glasgow Clinical Trials Unit, Institute of Health and Wellbeing, University of Glasgow, UK.
| |
Collapse
|
|
49
|
Khan MA, Bin Islam S, Rakib MU, Alam D, Hossen MM, Tania M, Asad A. Major Drugs Used in COVID-19 Treatment: Molecular Mechanisms, Validation
and Current Progress in Trials. CORONAVIRUSES 2022; 3. [DOI: 10.2174/2666796701999201204122819] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 11/16/2020] [Accepted: 11/11/2020] [Indexed: 07/28/2024]
Abstract
Background:
Currently, the present world is facing a new deadly challenge against a pandemic disease called
COVID-19, which is caused by a coronavirus, named SARS-CoV-2. To date, there is no drug or vaccine that can treat
COVID-19 completely, but some drugs have been used primarily, and they are in different stages of clinical trials. This
review article discussed and compared those drugs which are running ahead in COVID-19 treatments.
Methods:
We have explored PUBMED, SCOPUS, WEB OF SCIENCE, as well as press release of WHO, NIH and FDA for
articles about COVID-19, and reviewed them.
Results:
Drugs like favipiravir, remdesivir, lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin,
corticosteroids and interferons have been found effective in some extents, and partially approved by FDA and WHO to treat
COVID-19 at different phases of pandemic. However, some of these drugs have been disapproved later, although clinical
trials are going on. In parallel, plasma therapy has been found fruitful in some extents too, and a number of vaccine trails are
going on.
Conclusions:
This review article discussed the epidemiologic and mechanistic characteristics of SARS-CoV-2, and how
drugs could act on this virus with the comparative discussion on progress and backwards of major drugs used till date,
which might be beneficial for choosing therapies against COVID-19 in different countries.
Collapse
Affiliation(s)
- Md. Asaduzzaman Khan
- The Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical
University, Luzhou, Sichuan 646000, China
| | - Shad Bin Islam
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest
Medical University, Luzhou, Sichuan 646000, China
| | - Mejbah Uddin Rakib
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest
Medical University, Luzhou, Sichuan 646000, China
| | - Didarul Alam
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest
Medical University, Luzhou, Sichuan 646000, China
| | - Md. Munnaf Hossen
- Department of Immunology, Health Science Center, Shenzhen,
University, Shenzhen, Guangdong 518060, China
| | - Mousumi Tania
- Division of Molecular Cancer, Red Green Research Center,
Dhaka, Bangladesh
| | - Asaduzzaman Asad
- Department of Biochemistry and Molecular Biology, Jahangirnagar University; and International
Center for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| |
Collapse
|
|
50
|
Yin J, Li C, Ye C, Ruan Z, Liang Y, Li Y, Wu J, Luo Z. Advances in the development of therapeutic strategies against COVID-19 and perspectives in the drug design for emerging SARS-CoV-2 variants. Comput Struct Biotechnol J 2022; 20:824-837. [PMID: 35126885 PMCID: PMC8802458 DOI: 10.1016/j.csbj.2022.01.026] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 01/18/2022] [Accepted: 01/27/2022] [Indexed: 12/15/2022] Open
Abstract
Since Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was identified in late 2019, the coronavirus disease 2019 (COVID-19) pandemic has challenged public health around the world. Currently, there is an urgent need to explore antiviral therapeutic targets and effective clinical drugs. In this study, we systematically summarized two main therapeutic strategies against COVID-19, namely drugs targeting the SARS-CoV-2 life cycle and SARS-CoV-2-induced inflammation in host cells. The development of above two strategies is implemented by repurposing drugs and exploring potential targets. A comprehensive summary of promising drugs, especially cytokine inhibitors, and traditional Chinese medicine (TCM), provides recommendations for clinicians as evidence-based medicine in the actual clinical COVID-19 treatment. Considering the emerging SARS-CoV-2 variants greatly impact the effectiveness of drugs and vaccines, we reviewed the appearance and details of SARS-CoV-2 variants for further perspectives in drug design, which brings updating clues to develop therapeutical agents against the variants. Based on this, the development of broadly antiviral drugs, combined with immunomodulatory, or holistic therapy in the host, is prior to being considered for therapeutic interventions on mutant strains of SARS-CoV-2. Therefore, it is highly acclaimed the requirements of the concerted efforts from multi-disciplinary basic studies and clinical trials, which improves the accurate treatment of COVID-19 and optimizes the contingency measures to emerging SARS-CoV-2 variants.
Collapse
Key Words
- ACE2, Angiotensin-converting enzyme 2
- ARDS, acute respiratory distress syndrome
- CEP, Cepharanthine
- COVID-19 pandemic
- COVID-19, coronavirus disease 2019
- CRS, cytokine release syndrome
- CTD, C-terminal domain
- Drug target
- EMA, European Medicines Agency
- ERGIC, endoplasmic reticulum-Golgi intermediate compartment
- FDA, U.S. Food and Drug Administration
- JAK, Janus kinase
- MODS, multiple organ dysfunction syndrome
- NMPA, National Medical Products Administration
- NTD, N-terminal domain
- Nbs, nanobodies
- RBD, receptor-binding domain
- RdRp, RNA dependent RNA polymerase
- SARS-CoV-2
- SARS-CoV-2 variants
- SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2
- STAT, Signal Transducer and Activator of Transcription
- TCM, traditional Chinese medicine
- TCZ, Tocilizumab
- Therapeutic strategies
- VOC, variants of concern
- VOI, variants of interest
- VUM, variants under monitoring
- mAb, monoclonal antibody
- α1AT, alpha-1 antitrypsin
Collapse
Affiliation(s)
- Jialing Yin
- Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, PR China
| | - Chengcheng Li
- Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, PR China
| | - Chunhong Ye
- Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, PR China
| | - Zhihui Ruan
- Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, PR China
- Foshan Institute of Medical Microbiology, Foshan 528315, PR China
| | - Yicong Liang
- Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, PR China
| | - Yongkui Li
- Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, PR China
| | - Jianguo Wu
- Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, PR China
- Foshan Institute of Medical Microbiology, Foshan 528315, PR China
| | - Zhen Luo
- Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, PR China
- Foshan Institute of Medical Microbiology, Foshan 528315, PR China
| |
Collapse
|