Evidence has shown that there are asymptomatic carriers of COVID-19 who can transmit the disease to others. The virus incubation time shows a wide range (0–24 days) and the virus displays a high infectivity. It is therefore urgent to develop an effective therapy to treat patients with COVID-19 and to control the spread of the causative agent, severe respiratory syndrome coronavirus 2. Repurposing of approved drugs is widely adopted to fight newly emerged diseases such as COVID-19, as these drugs have known pharmacokinetic and safety profiles. As pathological examination has confirmed the involvement of immune hyperactivation and acute respiratory distress syndrome in fatal cases of COVID-19, several disease-modifying anti-rheumatic drugs (DMARDS), such as hydroxychloroquine and tocilizumab, have been proposed as potential therapies for the treatment of COVID-19. In this Review, we discuss the immunological aspects of COVID-19 and the potential implication of DMARDs in treating this disease.
SARS-CoV-2 has spread rapidly since it first emerged in December, 2019, and COVID-19 is characterised as a pandemic by WHO. As a new emerging virus, there is no approved effective drug or vaccine. As of April 16, 2020, several existing drugs are being repurposed for the treatment of patients with COVID-19, with dozens of ongoing clinical trials assessing their potential efficacy. DMARDs, due to their immune-modulating nature, could be a potential treatment option for severe COVID-19. However, there are several issues that need to be taken into consideration. First, the issue of hyperinflammation versus viral replication. Although effective anti-viral immunity is required for the clearance of pathogens, hyperactivation of immune response causes tissue damage and organ failure. Similarly, there are two sides of immunomodulation therapy in COVID-19, and clinicians should determine in which circumstance to use such medications. Second, there are questions about the timing for immunomodulation therapy. As noted, immunosuppressants could affect anti-viral immune response and the timing should be carefully considered. Although early intervention is considered as a key factor for the success of immunomodulation therapy in infection-associated hyperinflammation,direct evidence from RCTs are required to determine the appropriate timing for patients with COVID-19. Finally, the pharmacokinetics of oral medications in crucially ill patients merit consideration, as physiological alterations in these patients can substantially affect the pharmacokinetics. Some drugs will need to be given parenterally due to gastrointestinal failure (eg, chloroquine has been used parenterally to treat severely ill patients with malaria, although it is absorbed reliably in these patients).Compared with the oral route, parenteral administration of chloroquine results in rapid absorption and transient high plasma concentrations, which is associated with increased risk of acute toxicity.In addition, impaired clearance of the drugs might be problematic in patients with hepatic dysfunction and renal failure. Therefore, smaller and more frequent doses, continuous intravenous infusion, or choosing a less toxic drug (eg, using hydroxychloroquine instead of chloroquine) should be considered in patients who are severely ill. The many ongoing trials will hopefully provide a better understanding of the potential effects of immunomodulation therapy on COVID-19-associated hyperinflammation.
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