Cytokine storm induced by SARS-CoV-2

Abstract

Coronavirus disease 2019 , caused by the virus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread widely throughout the world. Despite the strict global outbreak management and quarantine measures that have been implemented, the incidence of COVID-19 continues to rise, resulting in more than 290,000 deaths and representing an extremely serious threat to human life and health. The clinical symptoms of the affected patients are heterogeneous, ranging from mild upper respiratory symptoms to severe pneumonitis and even acute respiratory distress syndrome (ARDS) or death. Systemic immune over activation due to SARS-CoV-2 infection causes the cytokine storm, which is especially noteworthy in severely ill patients with COVID-19. Pieces of evidence from current studies have shown that the cytokine storm may be an important factor in disease progression, even leading to multiple organ failure and death. This review provides an overview of the knowledge on the COVID-19 epidemiological profile, the molecular mechanisms of the SARS-CoV-2-induced cytokine storm and immune responses, the pathophysiological changes that occur during infection, the main antiviral compounds used in treatment strategies and the potential drugs for targeting cytokines, this information is presented to provide valuable guidance for further studies and for a therapeutic reduction of this excessive immune response.

Lethality of SARS-CoV-2 infection in K18 human angiotensin converting enzyme 2 transgenic mice

“…We next determined if SARS-CoV-2 infection of K18 hACE2 transgenic mice resulted in a cytokine storm, as described during the development of severe COVID-19 disease in humans (reviewed in [22][23][24][25][26] ). Multiple tissues were analyzed to define local and systemic inflammatory, TH1, TH17, and TH2 responses.…”

“…The 2-DPI correlative clusters in the lung were not maintained at 4-DPI but other smaller clusters were observed, the largest being led by IL-13 (Cluster-3, Fig 4A) correlating with IL1- (0.97) and IL-4 (0.93), suggestive of a rapidly developing immune response similar in nature, but not form, to the cytokine storm observed in humans. [22][23][24][25][26] The IL-10 cluster (Cluster-1) was also observed in the spleen at 2-DPI, correlating with IL-6 (0.96), IL-4 (0.95), IL-13 (0.93) and IL-1 (0.88); and at 4-DPI, correlating with IL-13 (0.92), IL-4 (0.89) and IL-1 (0.76)] (Fig 4B), but not in the brain (Fig 4C). Indeed, in the brain a correlation between IL-2, IL-4 and IL-13 was observed independent of IL-10 at 2-DPI (Cluster-4, Fig 4C).…”

May Medium Cut-Off Dialysis Membranes Have Impact on Outcome of COVID-19 Hemodialysis Patients?

“…Laboratory signs and symptoms of HLH-MAS include severe elevation in acute phase parameters such as CRP and ferritin, persistent fever, hepatosplenomegaly, cytopenias, hypertriglyceridemia, hypo brinogenemia and elevation of AST [20]. HLH-MAS causes organ dysfunction, which may cause death [16].…”

“…In addition, the activation of the monocyte-macrophage system, which is a vital part of in ammatory storm, stimulates ferritin production [15]. The cytokine storm causes organ dysfunction, which may cause death [16].…”

The Incidence of SARS-COV-2 Manifestations in the Central Nervous System: A Rapid Review and Meta-Analysis

“…It is generally accepted that a positive PCR result in the CSF is an indication of direct viral infection of the brain. However, one must bear in mind that during COVID-19, a marked systemic in ammatory response syndrome (SIRS) has been described [51]. In this context, the proin ammatory cytokine storm is likely to lead to an increased permeability of the blood-brain barrier [52].…”