Immunosuppressive Drugs and COVID-19: A Review

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.

Secondary hemophagocytic lymphohistiocytosis and severe liver injury induced by hepatic SARS-CoV-2 infection unmasking Wilson’s disease: Balancing immunosuppression

“…( Horby et al, 2020 , Sterne et al, 2020 ) Concerning SARS-CoV-2 clearance in patients treated with corticosteriods, several studies report conflicting data maybe due to different doses of steriods used. ( Schoot et al, 2020 ) While higher doses of steriods seem to be associated with prolonged viral shedding ( Li et al, 2020b ), current COVID-19 treatment guidelines do not state a recommendation on monitoring SARS-CoV-2 viral load in critical COVID-patients receiving immunosuppressive therapies ( COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines.…”

Perspective: Reducing SARS-CoV2 Infectivity and Its Associated Immunopathology

“…However, such cells could acquire proinflammatory roles when home to the inflammatory sites because of their plasticity (53). Therefore, approaches that could promote endogenous Treg responses or stabilize their phenotype could help dampen the inflammation (54). Such approaches could be more valuable when the virus is adequately controlled.…”

A Review to Summarize the Available Evidences on Turmeric's (Curcuma Longa) Medicinal Properties to Understand the Scope of Its Efficacy in the Treatment and Prevention of Covid19 Diseases.

“…In this phase, an overshoot of the host immune response (the "cytokine storm") can cause ARDS, multi organ failure and mortality. [41] Turmeric as an Immunomodulator Curcumin exerts proimmune activity in several autoimmune disorders including Alzheimer's disease, multiple sclerosis, cardiovascular disease, diabetes, allergy, asthma, inammatory bowel disease, rheumatoid arthritis, renal ischemia, psoriasis, and scleroderma. Overall, these ndings suggest that curcumin warrants further consideration as a potential immune-regulatory treatment in various immune disorders.…”