Abstract
Coronavirus disease 2019 (COVID-19) is a condition caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe cases of COVID-19 result in acute respiratory distress syndrome and death. A detrimental, hyper-inflammatory immune response with excess release of cytokines is the main driver of disease development and of tissue damage in these patients. Thus, repurposing of biologic agents and other pharmacological inhibitors of cytokines used for the treatment of various inflammatory conditions emerged as a logical therapeutic strategy to quench inflammation and improve the clinical outcome of COVID-19 patients. Evaluated agents include the interleukin one receptor blocker anakinra, monoclonal antibodies inhibiting IL-6 tocilizumab and sarilumab, monoclonal antibodies inhibiting granulocyte-monocyte colony stimulating factor and tumor necrosis factor, and Janus kinase inhibitors. In this review, we discuss the efficacy and safety of these therapeutic options based on direct personal experience and on published evidence from observational studies and randomized clinical trials.
Highlights
The pathogenesis of severe Coronavirus disease 2019 (COVID-19) involves an excessive, maladaptive host inflammatory response to the causative virus SARS-CoV-2 (Mehta et al, 2020; Ruan et al, 2020) (Figure 1)
The detrimental immune response developing in a subgroup of COVID-19 patients is mediated by the innate immune system, and is characterized by marked increases in systemic cytokines, and is paralleled by elevations in inflammatory biomarkers, such as C-reactive protein (CRP) and ferritin
A maladaptive, hyper-inflammatory host immune response to the virus is recognized as the main driver of disease severity in a subset of COVID-19 patients
Summary
The pathogenesis of severe Coronavirus disease 2019 (COVID-19) involves an excessive, maladaptive host inflammatory response to the causative virus SARS-CoV-2 (Mehta et al, 2020; Ruan et al, 2020) (Figure 1). Guaraldi et al reported the results of a large retrospective observational cohort study evaluating the efficacy of tocilizumab in the treatment of severe COVID-19 patients They found no difference in need for mechanical ventilation between groups (16% of the standard of care group vs 18% of the tocilizumab group, p 0.41), but reported a statistically significant reduction in mortality in the tocilizumab group (7% vs 20%, p < 0.001). These findings were partially confirmed by another large RCT of COVID-19 patients (Hermine et al, 2020) In this trial, tocilizumab (administered at the dose of 8 mg/kg) led to a reduction in mechanical ventilation and death rate at 14 days; mortality at 28 days did not differ between treated patients and controls. PAP might not be an issue when treating COVID-19 patients, because a single intravenous dose of monoclonal antibodies typically wears off in a month, at variance with the chronic deficiency of GM-CSF observed in PAP (Bonaventura et al, 2020)
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