Severe coronavirus disease 2019 (COVID-19) is characterized by systemic hyper-inflammation, acute respiratory distress syndrome, and multiple organ failure. Cytokine storm refers to a set of clinical conditions caused by excessive immune reactions and has been recognized as a leading cause of severe COVID-19. While comparisons have been made between COVID-19 cytokine storm and other kinds of cytokine storm such as hemophagocytic lymphohistiocytosis and cytokine release syndrome, the pathogenesis of cytokine storm has not been clearly elucidated yet. Recent studies have shown that impaired response of type-1 IFNs in early stage of COVID-19 infection played a major role in the development of cytokine storm, and various cytokines such as IL-6 and IL-1 were involved in severe COVID-19. Furthermore, many clinical evidences have indicated the importance of anti-inflammatory therapy in severe COVID-19. Several approaches are currently being used to treat the observed cytokine storm associated with COVID-19, and expectations are especially high for new cytokine-targeted therapies, such as tocilizumab, anakinra, and baricitinib. Although a number of studies have been conducted on anti-inflammatory treatments for severe COVID-19, no specific recommendations have been made on which drugs should be used for which patients and when. In this review, we provide an overview of cytokine storm in COVID-19 and treatments currently being used to address it. In addition, we discuss the potential therapeutic role of extracorporeal cytokine removal to treat the cytokine storm associated with COVID-19.

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Highlights Asymptomatic patients with COVID-19 tend to be younger and may be more socially active. Laboratory findings in most asymptomatic cases were unremarkable. Around half of the cases had lung opacities, most frequently ground glass opacities. Patients with normal CT were younger than patients with abnormal CT.

To assess the association of public interest in coronavirus infections with the actual number of infected cases for selected countries across the globe. Methods: We performed a Google Trends TM search for "Coronavirus" and compared Relative Search Volumes (RSV) indices to the number of reported COVID-19 cases by the European Center for Disease Control (ECDC) using time-lag correlation analysis. Results: Worldwide public interest in Coronavirus reached its first peak end of January when numbers of newly infected patients started to increase exponentially in China. The worldwide Google Trends TM index reached its peak on the 12th of March 2020 at a time when numbers of infected patients started to increase in Europe and COVID-19 was declared a pandemic. At this time the general interest in China but also the Republic of Korea has already been significantly decreased as compared to end of January. Correlations between RSV indices and number of new COVID-19 cases were observed across all investigated countries with highest correlations observed with a time lag of À11.5 days, i.e. highest interest in coronavirus observed 11.5 days before the peak of newly infected cases. This pattern was very consistent across European countries but also holds true for the US. In Brazil and Australia, highest correlations were observed with a time lag of À7 days. In Egypt the highest correlation is given with a time lag of 0, potentially indicating that in this country, numbers of newly infected patients will increase exponentially within the course of April. Conclusions: Public interest indicated by RSV indices can help to monitor the progression of an outbreak such as the current COVID-19 pandemic. Public interest is on average highest 11.5 days before the peak of newly infected cases.

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The increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western lifestyle. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis. We report that small intestinal epithelial cells (IECs) in Crohn's disease (CD) exhibit impaired GPX4 activity and signs of LPO. PUFAs and specifically AA trigger a cytokine response of IECs which is restricted by GPX4. While GPX4 does not control AA metabolism, cytokine production is governed by similar mechanisms as ferroptosis. A PUFA-enriched Western diet triggers focal granuloma-like neutrophilic enteritis in mice that lack one allele of Gpx4 in IECs. Our study identifies dietary PUFAs as a trigger of GPX4-restricted mucosal inflammation phenocopying aspects of human CD.

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Background A cytokine storm conceivably contributes to manifestations of corona virus disease (COVID-19). Inflammatory cytokines such as interleukin-6 (IL-6) cause acute liver injury while serum detectability indicates systemic inflammation. Aims We explored a link between systemic IL-6, related acute phase proteins and liver injury in hospitalized COVID-19 patients. Methods 655 patients with suspected COVID-19 were screened in the emergency department at the University Hospital of Innsbruck, Austria, between February and April 2020. 96 patients (∼15%) were hospitalized with COVID-19. 15 patients required intensive-care treatment (ICT). Plasma aminotransferases, alkaline phosphatase, bilirubin, and gamma glutamyl transferase, as well as IL-6, C-reactive protein (CRP), ferritin and lactate dehydrogenase (LDH) were determined by standard clinical assays. Results Of all hospitalized COVID-19 patients, 41 (42%) showed elevated aspartate aminotransferase (AST) concentration. COVID-19 patients with elevated AST exhibited significantly higher IL-6 ( p < 0.001), ferritin ( p < 0.001), LDH ( p < 0.001) and CRP ( p < 0.05) serum concentrations compared to patients with normal AST. Liver injury correlated with systemic IL-6 ( p < 0.001), CRP ( p < 0.001), ferritin ( p < 0.001) and LDH ( p < 0.001) concentration. In COVID-19 patients requiring ICT, correlations were more pronounced. Conclusion Systemic inflammation could be a fuel for hepatic injury in COVID-19.