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Journal ArticleDOI

SARS-CoV-2: a storm is raging.

01 May 2020-Journal of Clinical Investigation (American Society for Clinical Investigation)-Vol. 130, Iss: 5, pp 2202-2205
TL;DR: Overall, this study characterized the cytokine storm in severe COVID-19 and provides insights into immune therapeutics and vaccine design and the authors found that respiratory distress on admission is associated with unfavorable outcomes.
Abstract: The pandemic coronavirus infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading across the globe. In this issue of the JCI, Chen and colleagues compared the clinical and immunological characteristics between moderate and severe COVID-19. The authors found that respiratory distress on admission is associated with unfavorable outcomes. Increased cytokine levels (IL-6, IL-10, and TNF-α), lymphopenia (in CD4+ and CD8+ T cells), and decreased IFN-γ expression in CD4+ T cells are associated with severe COVID-19. Overall, this study characterized the cytokine storm in severe COVID-19 and provides insights into immune therapeutics and vaccine design.
Citations
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Journal ArticleDOI
13 Jul 2020-Science
TL;DR: The results of this trio of studies suggest that the location, timing, and duration of IFN exposure are critical parameters underlying the success or failure of therapeutics for viral respiratory infections.
Abstract: Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression suggesting diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A unique phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-β and low IFN-α production and activity), associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor NF-κB and characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling. These data suggest that type-I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.

2,171 citations

Journal ArticleDOI
TL;DR: Sera from patients with COVID-19 have elevated levels of cell-free DNA, myeloperoxidase(MPO)-DNA, and citrullinated histone H3 (Cit-H3); the latter two are highly specific markers of NETs, which may contribute to cytokine release and respiratory failure.
Abstract: In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have the potential to propagate inflammation and microvascular thrombosis - including in the lungs of patients with acute respiratory distress syndrome. We now report that sera from patients with COVID-19 have elevated levels of cell-free DNA, myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (Cit-H3); the latter 2 are specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute-phase reactants, including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.

1,046 citations


Cites background from "SARS-CoV-2: a storm is raging."

  • ...(ARDS) and even multiorgan failure in some individuals (2)....

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Journal ArticleDOI
01 Aug 2020
TL;DR: Assessment of the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment found it to be associated with a reduced risk.
Abstract: Summary Background No therapy is approved for COVID-19 pneumonia The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment Methods This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020 All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable The primary endpoint was a composite of invasive mechanical ventilation or death Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score Findings Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously) 73 (20%) patients in the standard care group died, compared with 13 (7%; p Interpretation Treatment with tocilizumab, whether administered intravenously or subcutaneously, might reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia Funding None

775 citations

Journal ArticleDOI
TL;DR: This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit to support the design of more effective approaches to the management of CO VID-19.

769 citations


Cites background from "SARS-CoV-2: a storm is raging."

  • ...Various authors have detected this interleukin in patients with COVID-19 and related its levels to disease severity and progression, as in the case of other cytokines [17,43,57,64,82,83,86,88,89] and it has been reported to have possible prognostic value [54]....

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  • ...Pedersen & Ho [86] Literature review To describe the cytokine storm that occurs in severe SARS-...

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Journal ArticleDOI
06 Aug 2020-Cell
TL;DR: A quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells reveals dramatic rewiring of phosphorylation on host and viral proteins, revealing potential COVID-19 therapies.

723 citations

References
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Journal ArticleDOI
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.

36,578 citations


"SARS-CoV-2: a storm is raging." refers background in this paper

  • ...This new coronavirus infectious disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 1, 2020 and identified as a previously unknown betacoronavirus (1, 2)....

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  • ...These laboratory changes have been previously reported in COVID-19 patients requiring intensive care unit (ICU) admissions (1)....

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Journal ArticleDOI
TL;DR: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness, and patients often presented without fever, and many did not have abnormal radiologic findings.
Abstract: Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of...

22,622 citations

Journal ArticleDOI
TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Abstract: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).

21,455 citations

Journal ArticleDOI
TL;DR: There is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019 and considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere.
Abstract: Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the...

13,101 citations

Journal ArticleDOI
TL;DR: The phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans.

9,474 citations


"SARS-CoV-2: a storm is raging." refers background in this paper

  • ...SARS-CoV-2 is closely related to two bat-derived SARS-like coronaviruses and SARS-CoV in phylogenetic distance (11)....

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