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Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review.
- Source :
-
Drugs [Drugs] 2020 Dec; Vol. 80 (18), pp. 1929-1946. - Publication Year :
- 2020
-
Abstract
- Background: Based on current evidence, recent guidelines of the National Institute of Health, USA indicated the use of remdesivir and dexamethasone for the treatment of COVID-19 patients with mild-moderate disease, not requiring high-flow oxygen. No therapeutic agent directed against the immunologic pathogenic mechanisms related to the cytokine release syndrome complicating the disease was indicated.<br />Objectives: The purpose of this review was to assess the clinical impact of different therapies for COVID-19; thus, helping to identify the optimal management of the disease. To explain the rationale for the different therapeutic approaches, the characteristics of SARS-CoV-2, the pathogenesis of COVID-19, and the immune response triggered by SARS-CoV-2 infection were reported.<br />Methods: The efficacy assessment of the different treatments was performed by a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Available English language published articles including randomised controlled trials, open-label trials of antivirals and immune therapies extracted from Medline, Google Scholar, and MedRxiv databases were analysed. For inclusion, the primary end point of the trials had to be the efficacy as measured by the improvement of clinical features, or mortality, or the Intensive Care Unit Admission rate, or the discharge number. Case reports, paediatric studies, and studies without control group were excluded. The literature search was extended up to August 15, 2020.<br />Results: After the removal of duplicate articles, and the exclusion of studies not meeting the eligibility criteria, 2 trials of lopinavir/ritonavir, 1 of favipiravir, 3 of remdesivir, 1 of dexamethasone, 3 of hydroxychloroquine, 2 of colchicine, 6 of tocilizumab, 1 of sarilumab, 1 of siltuximab, 2 of anakinra, 3 of baricitinib, 1 of ruxolitinib, 1 of mavrilimumab, and 1 of itolizumab were suitable for the review. Among antivirals, only remdesivir significantly reduced the time to recovery, and mortality. Data for chloroquine and hydroxychloroquine were largely inconclusive. In a large trial, dexamethasone 6 mg/day reduced mortality by one-third. Trials of tocilizumab and sarilumab did not definitively demonstrate efficacy. Anakinra significantly reduced the mortality in 2 trials. Three retrospective trials on a cumulative number of 145 patients, reported the efficacy of baricitinib, with significant reduction of intensive care unit admission, and deaths. These results were recently confirmed by the ACTT-2 trial. Due to paucity of studies and to the small size clinical series, the results of other immune therapies were not conclusive.<br />Conclusions: Beyond the supportive therapy, up to now the best therapeutic approach for COVID-19 may be a three-step combination therapy, including remdesivir 100 mg/day (200 mg loading dose on first day) in the first stage of the disease, and combined dexamethasone 6 mg/day plus baricitinib 4 mg/day to target the immune dysregulation triggered by the SARS-CoV-2 infection. The promising results of anakinra should be confirmed by the ongoing RCTs.
- Subjects :
- Adenosine Monophosphate analogs & derivatives
Adenosine Monophosphate therapeutic use
Alanine analogs & derivatives
Alanine therapeutic use
Anti-Inflammatory Agents administration & dosage
Antibodies, Monoclonal, Humanized
Antiviral Agents administration & dosage
Biological Products administration & dosage
COVID-19 therapy
Cytokines drug effects
Cytokines metabolism
Dexamethasone therapeutic use
Drug Therapy, Combination
Humans
Inflammation Mediators metabolism
Intensive Care Units
Pandemics
Retrospective Studies
SARS-CoV-2
Anti-Inflammatory Agents therapeutic use
Antiviral Agents therapeutic use
Biological Products therapeutic use
COVID-19 Drug Treatment
Subjects
Details
- Language :
- English
- ISSN :
- 1179-1950
- Volume :
- 80
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Drugs
- Publication Type :
- Academic Journal
- Accession number :
- 33068263
- Full Text :
- https://doi.org/10.1007/s40265-020-01421-w