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Nucleocapsid and Spike Proteins of the Coronavirus SARS-CoV-2 Induce IL6 in Monocytes and Macrophages-Potential Implications for Cytokine Storm Syndrome.

ABSTRACT: The pandemic of the new coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has led to the deaths of more than 1.5 million people worldwide. SARS-CoV-2 causes COVID-19, which exhibits wide variation in the course of disease in different people, ranging from asymptomatic and mild courses to very severe courses that can result in respiratory failure and death. Despite the rapid progression of knowledge, we still do not know how individual cells of the immune system interact with the virus or its components, or how immune homeostasis becomes disrupted, leading to the rapid deterioration of a patient's condition. In the present work, we show that SARS-CoV-2 proteins induce the expression and secretion of IL-6 by human monocytes and macrophages, the first line cells of antiviral immune responses. IL-6 may play a negative role in the course of COVID-19 by inhibiting Th1-dependent immunity and stimulating Th17 lymphocytes, thus leading to an increased probability of a cytokine storm.

SUBMITTER: Karwaciak I

PROVIDER: S-EPMC7830532 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Nucleocapsid and Spike Proteins of the Coronavirus SARS-CoV-2 Induce <i>IL6</i> in Monocytes and Macrophages-Potential Implications for Cytokine Storm Syndrome.

Karwaciak Iwona I Sałkowska Anna A Karaś Kaja K Dastych Jarosław J Ratajewski Marcin M

Vaccines 20210115 1

The pandemic of the new coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has led to the deaths of more than 1.5 million people worldwide. SARS-CoV-2 causes COVID-19, which exhibits wide variation in the course of disease in different people, ranging from asymptomatic and mild courses to very severe courses that can result in respiratory failure and death. Despite the rapid progression of knowledge, we still do not know how individual cells of the immune system interact wi ...[more]

PMID: 33467724

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Project description:Aim/objective/introductionCytokine storm or cytokine release syndrome (CRS) is inevitable in severe and critically ill patients with novel coronavirus disease-2019 (COVID-19). This review aimed to discuss current therapeutic options for the management of CRS in COVID-19.BackgroundCytokine storm is caused by the colossal release of proinflammatory cytokines [e.g., IL (interleukin)-2, IL-6, IL-8 TNF (tumor necrosis factor)-α, etc.] causing dysregulated, hyperimmune response. This immunopathogenesis leads to acute lung injury and acute respiratory distress syndrome (ARDS). Targeting cytokine storm with the therapies that are already available in India with the support of published guidelines and consensus can assist in achieving a better outcome in COVID-19.Review resultsWe predominantly included published guidelines or consensus recommendations about the management of cytokine storm in COVID-19. From the existing literature evidence, it is observed that among the currently available agents, low-dose corticosteroids and heparin can be beneficial in managing cytokine storm. The use of serine protease inhibitors such as ulinastatin has been advised by some experts. Though therapies such as high-dose vitamin C and interleukin-6 inhibitors (e.g., tocilizumab) have been advised, the evidence regarding their use for cytokine storm in COVID-19 is limited. Therapies such as Janus kinase inhibitors (JAK) inhibitors and Neurokinin-1 receptor (NK-1) antagonists are still in research. Besides, pharmaceutical treatments, use of blood purification strategies, and convalescent plasma may be life-saving options in some of the critically ill COVID-19 patients. For these therapies, there is a need to generate further evidence to substantiate their use in CRS management.ConclusionCurrent management of COVID-19 is preventive and supportive. Different therapies can be used to prevent and treat the cytokine storm. More research is needed for further supporting the use of these treatments in COVID-19.How to cite this articleMehta Y, Dixit SB, Zirpe KG, Ansari AS. Cytokine Storm in Novel Coronavirus Disease (COVID-19): Expert Management Considerations. Indian J Crit Care Med 2020;24(6):429-434.

Project description:BackgroundCOVID-19 was first identified in Wuhan, China, in December 2019, spreading to the rest of the globe, becoming a pandemic. Some studies have shown an association between pregnancy status and severe COVID-19 with a cytokine storm, whereas others have shown contrasting results.ObjectiveThe aim of this study was to examine the relationship between pregnancy status and the clinical COVID-19 severity characterized by the cytokine storm through a systematic review and meta-analysis.MethodsWe searched the Google Scholar, PubMed, Scopus, Web of Science, and Embase databases to identify clinical studies suitable for inclusion in this meta-analysis. Studies reporting pregnancy status and comparing the COVID-19 severity cytokine storm outcome were included. COVID-19 severity characterized by a cytokine storm was described using parameters such as intensive care unit admission, invasive mechanical ventilation, mechanical ventilation, hospital admission, pro- and anti-inflammatory cytokine levels, consolidation on chest computed tomography scan, pulmonary infiltration, extreme fevers as characteristic of a cytokine storm, syndromic severity, higher neutrophil count indicative of a cytokine storm, and severe COVID-19 presentation.ResultsA total of 17 articles including data for 840,332 women with COVID-19 were included. This meta-analysis revealed a correlation between positive pregnancy status and severe COVID-19 with a cytokine storm (random-effects model odds ratio [OR] 2.47, 95% CI 1.63-3.73; P<.001), with a cumulative incidence of 6432 (14.1%) and 24,352 (3.1%) among pregnant and nonpregnant women with COVID-19, respectively. The fixed-effects model also showed a correlation between pregnancy status and severe COVID-19 with a cytokine storm (OR 7.41, 95% CI 7.02-7.83; P<.001). Considerable heterogeneity was found among all pooled studies (I²=98%, P<.001). Furthermore, the updated analysis showed substantially low heterogeneity (I²=29 %, P=.19), and the funnel plot revealed no publication bias. The subanalysis between single-center and multicenter studies demonstrated similar heterogeneity (I2=72% and 98%, respectively). Sensitivity analysis on each subgroup revealed that pregnancy was significantly related to severe COVID-19 with a cytokine storm from single-center studies (fixed-effects model OR 3.97, 95% CI 2.26-6.95; P<.001) with very low heterogeneity (I²=2%, P=.42).ConclusionsBeing pregnant is clearly associated with experiencing a severe course of COVID-19 characterized by a cytokine storm. The COVID-19 pandemic should serve as an impetus for further research on pregnant women diagnosed with COVID-19 to map out the salient risk factors associated with its severity.Trial registrationPROSPERO CRD42021242011; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242011.

Project description:BackgroundCytokine storm is a marker of coronavirus disease 2019 (COVID-19) illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes.Research questionDo immunomodulatory therapies improve survival in patients with COVID-19 cytokine storm (CCS)?Study design and methodsWe conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 patients hospitalized between March 1, 2020, and April 24, 2020, were included. CCS was defined by inflammatory markers: ferritin, > 700 ng/mL; C-reactive protein (CRP), > 30 mg/dL; or lactate dehydrogenase (LDH), > 300 U/L. Patients were subdivided into six groups: no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti-IL-6 antibody (tocilizumab), or anti-IL-1 therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality.ResultsFive thousand seven hundred seventy-six patients met the inclusion criteria. The most common comorbidities were hypertension (44%-59%), diabetes (32%-46%), and cardiovascular disease (5%-14%). Patients most frequently met criteria with high LDH (76.2%) alone or in combination, followed by ferritin (63.2%) and CRP (8.4%). More than 80% of patients showed an elevated D-dimer. Patients treated with corticosteroids and tocilizumab combination showed lower mortality compared with patients receiving standard-of-care (SoC) treatment (hazard ratio [HR], 0.44; 95% CI, 0.35-0.55; P < .0001) and with patients treated with corticosteroids alone (HR, 0.66; 95% CI, 0.53-0.83; P = .004) or in combination with anakinra (HR, 0.64; 95% CI, 0.50-0.81; P = .003). Corticosteroids when administered alone (HR, 0.66; 95% CI, 0.57-0.76; P < .0001) or in combination with tocilizumab (HR, 0.43; 95% CI, 0.35-0.55; P < .0001) or anakinra (HR, 0.68; 95% CI, 0.57-0.81; P < .0001) improved hospital survival compared with SoC treatment.InterpretationThe combination of corticosteroids with tocilizumab showed superior survival outcome when compared with SoC treatment as well as treatment with corticosteroids alone or in combination with anakinra. Furthermore, corticosteroid use either alone or in combination with tocilizumab or anakinra was associated with reduced hospital mortality for patients with CCS compared with patients receiving SoC treatment.

Dataset Information

Nucleocapsid and Spike Proteins of the Coronavirus SARS-CoV-2 Induce IL6 in Monocytes and Macrophages-Potential Implications for Cytokine Storm Syndrome.

Publications

Nucleocapsid and Spike Proteins of the Coronavirus SARS-CoV-2 Induce <i>IL6</i> in Monocytes and Macrophages-Potential Implications for Cytokine Storm Syndrome.

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