Abstract

Coronavirus disease 2019 (COVID-19) remains a global threat to humanity. Its pathogenesis and different phases of disease progression are being elucidated under the pandemic. Active viral replication activates various immune cells and produces large amounts of inflammatory cytokines, which leads to the cytokine storm, a major cause of patient death. Therefore, viral inhibition is expected to be the most effective early in the course of the disease, while immunosuppressive treatment may be useful in the later stages to prevent disease progression. Based on the pathophysiology of rheumatic diseases, various immunomodulatory and immunosuppressive drugs are used for the diseases. Due to their mechanism of action, the antirheumatic drugs, including hydroxychloroquine, chloroquine, colchicine, calcineurin inhibitors (e.g., cyclosporine A and tacrolimus), glucocorticoids, cytokines inhibitors, such as anti-tumor necrosis factor-α (e.g., infliximab), anti-interleukin (IL)-6 (e.g., tocilizumab, sarilumab, and siltuximab), anti-IL-1 (e.g., anakinra and canakinumab) and Janus kinase inhibitors (e.g., baricitinib and tofacitinib), cytotoxic T lymphocyte-associated antigen 4 blockade agents (e.g., abatacept), and phosphodiesterase 4 inhibitors (e.g., apremilast), have been tried as a treatment for COVID-19. In this review, we discuss the mechanisms of action and clinical impact of these agents in the management of COVID-19.

Highlights

  • COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was initially identified in Wuhan, China in December 2019

  • The this review is to summarize the mechanisms of action antirheumatic drugs, including immunomodulatory and immunosuppressive drugs, for of antirheumatic drugs, including immunomodulatory and immunosuppressive drugs, the treatment of COVID-19, and the and evidence for itsfor efficacy in thein forpotential the potential treatment of COVID-19, andrationale the rationale and evidence its efficacy health emergency we are currently facing

  • In patients with moderate to severe disease, there was a greater cumulative clinical improvement in the Cyclosporine A (CsA) group (Nelson-Aalen curve, p = 0.001, Logrank test). These findings suggested that the addition of CsA to glucocorticoids improve outcomes and reduce mortality, mainly in patients with moderate to severe COVID-19

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Summary

Introduction

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was initially identified in Wuhan, China in December 2019. Develop severe symptoms, including acute respiratory disease syndrome (ARDS), systemic shock, and multi-organ failure [1,2,3]. In Stage II (pulmonary phase), viral multiplication and localized inflammation in the lungs are common During this stage, patients may develop viral pneumonia with fever and cough, and hypoxia. Stage III (hyperinflammation phase) is characterized by a hypersensitive response of the immune system In this stage, systemic inflammatory markers are elevated and characterized by a hypercoagulable state that may Pharmaceuticals 2021, 14, 1256. The this review is to summarize the mechanisms of action antirheumatic drugs, including immunomodulatory and immunosuppressive drugs, for of antirheumatic drugs, including immunomodulatory and immunosuppressive drugs, the treatment of COVID-19, and the and evidence for itsfor efficacy in thein forpotential the potential treatment of COVID-19, andrationale the rationale and evidence its efficacy health emergency we are currently facing. Antigen; IL, interleukin; JAK, Janus kinase; MOF, multiple organ failure; PDE, phosphodiesterase

Mechanisms of SARS-CoV-2 Infection
Pharmacotherapy
Colchicine
Calcineurin Inhibitors
Glucocorticoids
IL-6 Inhibitors
IL-1 Inhibitors
TNF Inhibitors
Findings
Conclusions
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