Subject(s)
COVID-19 , Oxygen , Humans , Oxygen/therapeutic use , Hypoxia/etiology , Hypoxia/therapy , OximetryABSTRACT
OBJECTIVE: Lopinavir/ritonavir has been used for the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) coronavirus infections. It has been suggested that, based on this experience, this drug should also be studied in SARS-CoV2 infection. MATERIALS AND METHODS: We performed a systematic review of the literature regarding the use of lopinavir/ritonavir for the treatment of these three infections. We systematically searched the PubMed database from inception to April 30th, 2020, to identify in-vitro and animal studies and any reports of human use of lopinavir/ritonavir for the treatment of SARS, MERS and COVID-19. We also searched the Clinicatrial.gov to identify ongoing trials. RESULTS: Five in-vitro studies evaluated the effect of lopinavir/ritonavir in SARS. Three additional in-vitro studies reported the EC50 of the antiviral activity of lopinavir/ritonavir in MERS. We identified no in vitro studies evaluating the effect of lopinavir/ritonavir on the novel coronavirus. Two retrospective matched-cohort studies reported the use of lopinavir/ritonavir in combination with ribavirin for SARS patients. Three case reports and one retrospective study described the use of lopinavir/ritonavir in MERS. Twenty-two papers describe the use of lopinavir/ritonavir in adult patients with COVID-19. CONCLUSIONS: The existing literature does not suffice for assessing whether Lopinavir/ritonavir has any benefit in SARS, MERS or COVID-19.
Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Lopinavir/therapeutic use , Middle East Respiratory Syndrome Coronavirus/drug effects , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , Severe Acute Respiratory Syndrome/drug therapy , Betacoronavirus/isolation & purification , COVID-19 , Clinical Studies as Topic , Coronavirus Infections/pathology , Coronavirus Infections/virology , Databases, Factual , Humans , Middle East Respiratory Syndrome Coronavirus/metabolism , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS-CoV-2 , Severe Acute Respiratory Syndrome/pathologyABSTRACT
BACKGROUND: Tocilizumab is an IL-6 receptor-blocking agent proposed for the treatment of severe COVID-19. The aim of this systematic review was to describe the rationale for the use of tocilizumab for the treatment of COVID-19 and to summarize the available evidence regarding its efficacy and safety. METHODS: MEDLINE, PubMed, EMBASE, pre-print repositories (bioRxiv and medRxiv) and two trial Registries were searched for studies on the use of tocilizumab in COVID-19 or SARS-CoV-2 infection, viral pneumonia, and/or sepsis until 20th June 2020. RESULTS: We identified 3 indirect pre-clinical studies and 28 clinical studies including 5776 patients with COVID-19 (13 with a comparison group, 15 single-arm). To date, no randomized trials have been published. We retrieved no studies at low risk of bias. Forty-five ongoing studies were retrieved from trial registries. CONCLUSIONS: There is insufficient evidence regarding the clinical efficacy and safety of tocilizumab in patients with COVID-19. Its use should be considered experimental, requiring ethical approval and clinical trial oversight.