tetano
Editor, Senior Moderator
Front Pharmacol
. 2020 Aug 28;11:1333.
doi: 10.3389/fphar.2020.01333. eCollection 2020.
Immunosuppressive Drugs and COVID-19: A Review
Tessa S Schoot[SUP] 1 2 [/SUP], Ang?le P M Kerckhoffs[SUP] 2 3 [/SUP], Luuk B Hilbrands[SUP] 1 [/SUP], Rob J van Marum[SUP] 3 4 5 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; calcineurin inhibitors; coronavirus; corticosteroids; immunosuppressive drugs; mTOR inhibitors; mycophenolic acid.
. 2020 Aug 28;11:1333.
doi: 10.3389/fphar.2020.01333. eCollection 2020.
Immunosuppressive Drugs and COVID-19: A Review
Tessa S Schoot[SUP] 1 2 [/SUP], Ang?le P M Kerckhoffs[SUP] 2 3 [/SUP], Luuk B Hilbrands[SUP] 1 [/SUP], Rob J van Marum[SUP] 3 4 5 [/SUP]
Affiliations
- PMID: 32982743
- PMCID: PMC7485413
- DOI: 10.3389/fphar.2020.01333
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; calcineurin inhibitors; coronavirus; corticosteroids; immunosuppressive drugs; mTOR inhibitors; mycophenolic acid.