Immunosuppressive Drugs and COVID-19: A Review

• Published in: Frontiers in pharmacology Vol. 11; p. 1333
• Main Authors: Schoot, Tessa S, Kerckhoffs, Angèle P M, Hilbrands, Luuk B, van Marum, Rob J
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28.08.2020
• Subjects: coronavirus; corticosteroids; COVID-19; immunosuppressive drugs; mycophenolic acid; Pharmacology; SARS-CoV-2; COVID-19; SARS-CoV-2; corticosteroids; mycophenolic acid; mTOR inhibitors; coronavirus; immunosuppressive drugs; calcineurin inhibitors
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2020.01333

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. 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). 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 studies and animal studies with a control group. Sixty-nine studies were included. Interestingly, MPA inhibits SARS-CoV-2 replication . Clinical studies are needed to confirm the inhibitory effect of MPA on SARS-CoV-2 replication . 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 studies with SARS-CoV and MERS-CoV, it would be interesting to investigate their effects on SARS-CoV-2 replication.