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Immunosuppressive Drugs and COVID-19: A Review #MMPMID32982743
Schoot TS; Kerckhoffs APM; Hilbrands LB; van Marum RJ
Front Pharmacol 2020[]; 11 (?): 1333 PMID32982743show ga
BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is currently unknown whether immunosuppressive drugs are advantageous or detrimental in patients with COVID-19. Immunosuppressive drugs could be harmful in the initial phase of COVID-19. In this phase, the host immune response is necessary to inhibit viral replication. However, immunosuppressive drugs might have a beneficial effect in the later, more severe phase of COVID-19. In this phase, an overshoot of the host immune response (the "cytokine storm") can cause ARDS, multiorgan failure and mortality. AIM: To summarize the available evidence on the effect of immunosuppressive drugs on infection with SARS-CoV-2. The effects of immunosuppressive drugs on similar pandemic coronaviruses may resemble the effects on SARS-CoV-2. Thus, we also included studies on the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). METHODS: The study protocol was registered in PROSPERO (registration number CRD42020181137). We included randomized controlled trials (RCTs), cohort studies with a control group and case-control studies concerning humans >/= 18 years old. We also included in-vitro studies and animal studies with a control group. RESULTS AND CONCLUSION: Sixty-nine studies were included. Interestingly, MPA inhibits SARS-CoV-2 replication in-vitro. Clinical studies are needed to confirm the inhibitory effect of MPA on SARS-CoV-2 replication in-vivo. There are indications that corticosteroids and IL-6 inhibitors, like tocilizumab, can reduce mortality and prevent mechanical ventilation in patients with COVID-19. However, observational studies have contradictory results and the risk of bias is high. Thus, these results have to be confirmed in high-quality clinical trials before these drugs can be implemented as standard care. Based on the positive results of CNIs, mTOR inhibitors and thiopurine analogues in in-vitro studies with SARS-CoV and MERS-CoV, it would be interesting to investigate their effects on SARS-CoV-2 replication.
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Front+Pharmacol 2020 ; 11 (?): 1333
