Presence of Genetic Variants Among Young Men With Severe COVID-19

Made, Caspar I. van der; Simons, Annet; Schuurs-Hoeijmakers, Janneke; Heuvel, Guus van den; Mantere, Tuomo; Kersten, Simone; Deuren, Rosanne C. van; Steehouwer, Marloes; Reijmersdal, Simon V. van; Jaeger, Martin; Hofste, Tom; Astuti, Galuh D.N.; Galbany, Jordi Corominas; Schoot, Vyne van der; Hoeven, Hans van der; Have, Wanda Hagmolen of ten; Klijn, Eva; Meer, Catrien van den; Fiddelaers, Jeroen; Mast, Quirijn de; Bleeker‐Rovers, Chantal P.; Joosten, Leo A. B.; Yntema, Helger G.; Gilissen, Christian; Nelen, Marcel; Meer, J.W.M. van der; Brunner, Han G.; Netea, Mihai G.; Veerdonk, Frank L. van de; Hoischen, Alexander

doi:10.1001/jama.2020.13719

Cited by 692 publications

(695 citation statements)

References 40 publications

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“…Thus, type I IFN and proinflammatory cytokines including IL-1β are produced from coronavirus-infected cells. A recent genetic analysis of young cases of severe COVID-19 [41] has revealed decreased type I and type II IFN responses in the absence of TLR7 expression due to a 4-nucleotide deletion or a missense mutation within the X-chromosomal TLR7 gene. Although TLR7 stimulation with SARS-CoV-2 was not directly examined, this study suggests that TLR7mediated IFN responses might protect against COVID-19 progression.…”

Section: Replication Of Sars-cov-2 and Clinical Course Of Its Infectionmentioning

confidence: 99%

Immunopathogenesis of SARS-CoV-2-induced pneumonia: lessons from influenza virus infection

Miyazawa

2020

Inflamm Regener

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Factors determining the progression of frequently mild or asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection into life-threatening pneumonia remain poorly understood. Viral and host factors involved in the development of diffuse alveolar damage have been extensively studied in influenza virus infection. Influenza is a self-limited upper respiratory tract infection that causes acute and severe systemic symptoms and its spread to the lungs is limited by CD4+ T-cell responses. A vicious cycle of CCL2- and CXCL2-mediated inflammatory monocyte and neutrophil infiltration and activation and resultant massive production of effector molecules including tumor necrosis factor (TNF)-α, nitric oxide, and TNF-related apoptosis-inducing ligand are involved in the pathogenesis of progressive tissue injury. SARS-CoV-2 directly infects alveolar epithelial cells and macrophages and induces foci of pulmonary lesions even in asymptomatic individuals. Mechanisms of tissue injury in SARS-CoV-2-induced pneumonia share some aspects with influenza virus infection, but IL-1β seems to play more important roles along with CCL2 and impaired type I interferon signaling might be associated with delayed virus clearance and disease severity. Further, data indicate that preexisting memory CD8+ T cells may play important roles in limiting viral spread in the lungs and prevent progression from mild to severe or critical pneumonia. However, it is also possible that T-cell responses are involved in alveolar interstitial inflammation and perhaps endothelial cell injury, the latter of which is characteristic of SARS-CoV-2-induced pathology.

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Section: Replication Of Sars-cov-2 and Clinical Course Of Its Infectionmentioning

confidence: 99%

Immunopathogenesis of SARS-CoV-2-induced pneumonia: lessons from influenza virus infection

Miyazawa

2020

Inflamm Regener

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“…14) Although people of all ages are prone to infection by this virus, elderly people with co-morbidities (underlying health conditions and compromised immune system) are more susceptible to severe infection and death. Presence of genetic variants among young men with severe COVID-19 have been confirmed in [34] -using whole-exome sequencing performed to identify potential monogenic cause. But uncertainty did set in among medical practitioners on whether COVID-19 is a viral disease or the response to a person's immune system that invariably damages a patient's organs.…”

Section: Sars-cov-2: Existing Assertions and Developmentsmentioning

confidence: 99%

Real Time Viral Sub-Strains Discovery in Emerging Infectious Disease Situation – The African Perspective

Ekpenyong¹,

Uzoka²,

Edoho³

et al. 2020

Preprint

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BackgroundThe increased number of accessible genomes has prompted large-scale comparative studies for decerning evolutionary knowledge of infectious diseases, but challenges such as non-availability of close reference sequence(s), incompletely assembled or large number of genomes, preclude real time multiple sequence alignment and sub-strain(s) discovery. This paper introduces a cooperatively inspired open-source framework, for intelligent mining of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomes. We situate this study within the African context, to drive advancement on state-of-the-art, towards intelligent infectious disease characterization and prediction. The outcome is an enriched Knowledge Base, sufficient to provide deep understanding of the viral sub-strains’ identification problem. We also open investigation by gender, which to the best of our knowledge has been ignored in related research. Data for the study came from the Global Initiative on Sharing All Influenza Data database (https://gisaid.org) and processed for precise discovery of viral sub-strains transmission between and within African countries. To localize the transmission route(s) of each isolate excavated and provide appropriate links to similar isolate strain(s), a cognitive solution was imposed on the genome expression patterns discovered by unsupervised self-organizing map (SOM) component planes visualization. The Freidman-Nemenyi’s test was finally performed to validate our claim.ResultsEvidence of inter- and intra-genome diversity was noticed. While some isolates (or genomes) clustered differently, implying different evolutionary source (or high-diversity), others clustered closely together, indicating similar evolutionary source (or less-diversity). SOM component planes analysis revealed multiple sub-strains patterns, strongly suggesting local or intra-community and country to country transmissions. Cognitive maps of both male and female isolates revealed multiple transmission routes. Statistical results indicate significant difference between the various isolate groups at the 0.05 level of significance.ConclusionThe proposed framework offers explanations to SARS-CoV-2 diversity and provides real time identification to disease transmission routes, as well as rapid decision support for facilitating inter- and intra-country contact tracing of infected case(s). Intermediate data produced in this paper are helpful to enrich the genome datasets for intelligent characterization and prediction of COVID-19 and related pandemics, as well as the construction of intelligent device for accurate infectious disease monitoring.

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“…IL-6, ferritin, sIL-2R and IL-18 are elevated but levels remain relatively modest. [8][9][10][11] Transaminitis and cytopaenias are comparatively mild, aside from lymphopaenia that is likely a direct effect of SARS-CoV-2. Splenomegaly is largely absent.…”

Section: Covid-19 Cytokine Storm: What Is In a Name?mentioning

confidence: 99%

COVID-19 cytokine storm: what is in a name?

Nigrovic

2020

Ann Rheum Dis

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Presence of Genetic Variants Among Young Men With Severe COVID-19

Cited by 692 publications

References 40 publications

Immunopathogenesis of SARS-CoV-2-induced pneumonia: lessons from influenza virus infection

Immunopathogenesis of SARS-CoV-2-induced pneumonia: lessons from influenza virus infection

Real Time Viral Sub-Strains Discovery in Emerging Infectious Disease Situation – The African Perspective

COVID-19 cytokine storm: what is in a name?

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