Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment

Abstract

COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-α agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.

SARS-CoV-2 nsp1: Bioinformatics, Potential Structural and Functional Features, and Implications for Drug/Vaccine Designs

“…Exuberant proinflammatory cytokine and chemokine production accompanied by impaired antiviral innate immune responses likely is the defining feature of COVID-19 and drives the disease development ( Acharya et al, 2020 ; Blanco-Melo et al, 2020 ; Soy et al, 2020 ). Similarly, SARS-CoV infection could also lead to the immune dysregulation characterized with excessive stimulation of various inflammatory cytokines along with hampered antiviral IFN responses ( Channappanavar et al, 2016 ; Kindler and Thiel, 2016 ; Wong et al, 2016 ).…”

Low-dose Whole-lung Irradiation for COVID-19 Pneumonia: Short Course Results

“…Four phases are proposed for the pathogenesis of SARS-CoV-2, including suppression of interferon type 1 (IFN-1) production, blockage of IFN-1 signaling, massive in ammatory response (so-called cytokine storm), and immune exhaustion [4]. The lethality of COVID-19 mainly pertains to the cytokine storm-induced thrombotic dysregulation and multi-organ failure [5]. During the cytokine storm, monocytes and macrophages mainly recruit, which may explain elevated levels of pro-in ammatory cytokines such as interleukin-6 (IL-6) [5].…”

“…The lethality of COVID-19 mainly pertains to the cytokine storm-induced thrombotic dysregulation and multi-organ failure [5]. During the cytokine storm, monocytes and macrophages mainly recruit, which may explain elevated levels of pro-in ammatory cytokines such as interleukin-6 (IL-6) [5]. Suppression of cytokine storm can potentially reduce the morbidity and mortality of COVID-19 [6].…”

COVID-19 Pandemic in Women–Rheumatologist’s Perspective

“…8 This, in turn, leads to excessive type 2 interferon response and activation of monocyte/macrophages and consequent cytokine release syndrome (CRS). 9…”