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10.21203/rs.3.rs-1083825/v1 http://scihub22266oqcxt.onion/10.21203/rs.3.rs-1083825/v1 34845442!8629200!34845442     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=34845442&cmd=llinks): Failed to open stream: HTTP request failed! 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Severe COVID-19 infection is associated with aberrant cytokine production by infected lung epithelial cells rather than by systemic immune dysfunction |pdf=|usr=}}{{34845442}} gab.com Text Severe COVID-19 infection is associated with aberrant cytokine production by infected lung epithelial cells rather than by systemic immune dysfunction JO: Res Sq http://www.kidney.de/pget.php?&tw=1&pmid=34845442 #FOAvip The mechanisms explaining progression to severe COVID-19 remain poorly understood. It has been proposed that immune system dysregulation/over-stimulation may be implicated, but it is not clear how such processes would lead to respiratory failure. We performed comprehensive multiparameter immune monitoring in a tightly controlled cohort of 128 COVID-19 patients, and used the ratio of oxygen saturation to fraction of inspired oxygen (SpO2 / FiO2) as a physiologic measure of disease severity. Machine learning algorithms integrating 139 parameters identified IL-6 and CCL2 as two factors predictive of severe disease, consistent with the therapeutic benefit observed with anti-IL6-R antibody treatment. However, transcripts encoding these cytokines were not detected among circulating immune cells. Rather, in situ analysis of lung specimens using RNAscope and immunofluorescent staining revealed that elevated IL-6 and CCL2 were dominantly produced by infected lung type II pneumocytes. Severe disease was not associated with higher viral load, deficient antibody responses, or dysfunctional T cell responses. These results refine our understanding of severe COVID-19 pathophysiology, indicating that aberrant cytokine production by infected lung epithelial cells is a major driver of immunopathology. We propose that these factors cause local immune regulation towards the benefit of the virus. Twit Text FOAVip Severe COVID-19 infection is associated with aberrant cytokine production by infected lung epithelial cells rather than by systemic immune dysfunction ????Res Sq http://www.kidney.de/pget.php?&tw=1&pmid=34845442 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34845442 #FOAvip English Wikipedia <ref>{{Cite pmid|34845442}}</ref> Severe COVID-19 infection is associated with aberrant cytokine production by infected lung epithelial cells rather than by systemic immune dysfunction #MMPMID34845442 Rouhani SJ; Trujillo JA; Pyzer AR; Yu J; Fessler J; Cabanov A; Higgs EF; Cron KR; Zha Y; Lu Y; Bloodworth JC; Abasiyanik MF; Okrah S; Flood BA; Hatogai K; Leung MY; Pezeshk A; Kozloff L; Reschke R; Strohbehn GW; Chervin CS; Kumar M; Schrantz S; Madariaga ML; Beavis KG; Yeo KJ; Sweis RF; Segal J; Tay S; Izumchenko E; Mueller J; Chen LS; Gajewski TF Res Sq 2021[Nov]; � (�): � PMID34845442show ga The mechanisms explaining progression to severe COVID-19 remain poorly understood. It has been proposed that immune system dysregulation/over-stimulation may be implicated, but it is not clear how such processes would lead to respiratory failure. We performed comprehensive multiparameter immune monitoring in a tightly controlled cohort of 128 COVID-19 patients, and used the ratio of oxygen saturation to fraction of inspired oxygen (SpO2 / FiO2) as a physiologic measure of disease severity. Machine learning algorithms integrating 139 parameters identified IL-6 and CCL2 as two factors predictive of severe disease, consistent with the therapeutic benefit observed with anti-IL6-R antibody treatment. However, transcripts encoding these cytokines were not detected among circulating immune cells. Rather, in situ analysis of lung specimens using RNAscope and immunofluorescent staining revealed that elevated IL-6 and CCL2 were dominantly produced by infected lung type II pneumocytes. Severe disease was not associated with higher viral load, deficient antibody responses, or dysfunctional T cell responses. These results refine our understanding of severe COVID-19 pathophysiology, indicating that aberrant cytokine production by infected lung epithelial cells is a major driver of immunopathology. We propose that these factors cause local immune regulation towards the benefit of the virus. �Severe COVID-19 infection is associated with aberrant cytokine product(epmc).pdf DeepDyve Pubget Overpricing