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Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review.
Drugs. 2020 Dec; 80(18):1929-1946.D

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.

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.

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.

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.

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.

Authors+Show Affiliations

Department of Rheumatology, Azienda USL Toscana Centro, Hospital of Prato, Prato, Italy. fbrzcantini@gmail.com.Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Department of Rheumatology, Azienda USL Toscana Centro, Hospital of Prato, Prato, Italy.Rheumatology Unit, Vittorio-Emanuele University Hospital of Catania, Catania, Italy.

Pub Type(s)

Journal Article
Systematic Review

Language

eng

PubMed ID

33068263

Citation

Cantini, Fabrizio, et al. "Immune Therapy, or Antiviral Therapy, or Both for COVID-19: a Systematic Review." Drugs, vol. 80, no. 18, 2020, pp. 1929-1946.
Cantini F, Goletti D, Petrone L, et al. Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review. Drugs. 2020;80(18):1929-1946.
Cantini, F., Goletti, D., Petrone, L., Najafi Fard, S., Niccoli, L., & Foti, R. (2020). Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review. Drugs, 80(18), 1929-1946. https://doi.org/10.1007/s40265-020-01421-w
Cantini F, et al. Immune Therapy, or Antiviral Therapy, or Both for COVID-19: a Systematic Review. Drugs. 2020;80(18):1929-1946. PubMed PMID: 33068263.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review. AU - Cantini,Fabrizio, AU - Goletti,Delia, AU - Petrone,Linda, AU - Najafi Fard,Saied, AU - Niccoli,Laura, AU - Foti,Rosario, PY - 2020/10/18/pubmed PY - 2020/12/22/medline PY - 2020/10/17/entrez SP - 1929 EP - 1946 JF - Drugs JO - Drugs VL - 80 IS - 18 N2 - 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. 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. 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. 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. 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. SN - 1179-1950 UR - https://www.unboundmedicine.com/medline/citation/33068263/Immune_Therapy_or_Antiviral_Therapy_or_Both_for_COVID_19:_A_Systematic_Review_ L2 - https://dx.doi.org/10.1007/s40265-020-01421-w DB - PRIME DP - Unbound Medicine ER -