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10.1016/j.ebiom.2021.103262 http://scihub22266oqcxt.onion/10.1016/j.ebiom.2021.103262 33691247!7937043!33691247     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       EBioMedicine 2021 ; 65 (ä): 103262 Nephropedia Template TP {{tp|p=33691247|t=2021. Temporal dynamics of the host molecular responses underlying severe COVID-19 progression and disease resolution |pdf=|usr=}}{{33691247}} gab.com Text Temporal dynamics of the host molecular responses underlying severe COVID-19 progression and disease resolution JO: EBioMedicine http://www.kidney.de/pget.php?&tw=1&pmid=33691247 #FOAvip BACKGROUND: The coronavirus disease-19 (COVID-19) pandemic has cost lives and economic hardships globally. Various studies have found a number of different factors, such as hyperinflammation and exhausted/suppressed T cell responses to the etiological SARS coronavirus-2 (SARS-CoV-2), being associated with severe COVID-19. However, sieving the causative from associative factors of respiratory dysfunction has remained rudimentary. METHODS: We postulated that the host responses causative of respiratory dysfunction would track most closely with disease progression and resolution and thus be differentiated from other factors that are statistically associated with but not causative of severe COVID-19. To track the temporal dynamics of the host responses involved, we examined the changes in gene expression in whole blood of 6 severe and 4 non-severe COVID-19 patients across 15 different timepoints spanning the nadir of respiratory function. FINDINGS: We found that neutrophil activation but not type I interferon signaling transcripts tracked most closely with disease progression and resolution. Moreover, transcripts encoding for protein phosphorylation, particularly the serine-threonine kinases, many of which have known T cell proliferation and activation functions, were increased after and may thus contribute to the upswing of respiratory function. Notably, these associative genes were targeted by dexamethasone, but not methylprednisolone, which is consistent with efficacy outcomes in clinical trials. INTERPRETATION: Our findings suggest neutrophil activation as a critical factor of respiratory dysfunction in COVID-19. Drugs that target this pathway could be potentially repurposed for the treatment of severe COVID-19. FUNDING: This study was sponsored in part by a generous gift from The Hour Glass. EEO and JGL are funded by the National Medical Research Council of Singapore, through the Clinician Scientist Awards awarded by the National Research Foundation of Singapore. Twit Text FOAVip Temporal dynamics of the host molecular responses underlying severe COVID-19 progression and disease resolution ????EBioMedicine http://www.kidney.de/pget.php?&tw=1&pmid=33691247 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33691247 #FOAvip English Wikipedia <ref>{{Cite pmid|33691247}}</ref> Temporal dynamics of the host molecular responses underlying severe COVID-19 progression and disease resolution #MMPMID33691247 Ong EZ; Kalimuddin S; Chia WC; Ooi SH; Koh CW; Tan HC; Zhang SL; Low JG; Ooi EE; Chan KR EBioMedicine 2021[Mar]; 65 (ä): 103262 PMID33691247show ga BACKGROUND: The coronavirus disease-19 (COVID-19) pandemic has cost lives and economic hardships globally. Various studies have found a number of different factors, such as hyperinflammation and exhausted/suppressed T cell responses to the etiological SARS coronavirus-2 (SARS-CoV-2), being associated with severe COVID-19. However, sieving the causative from associative factors of respiratory dysfunction has remained rudimentary. METHODS: We postulated that the host responses causative of respiratory dysfunction would track most closely with disease progression and resolution and thus be differentiated from other factors that are statistically associated with but not causative of severe COVID-19. To track the temporal dynamics of the host responses involved, we examined the changes in gene expression in whole blood of 6 severe and 4 non-severe COVID-19 patients across 15 different timepoints spanning the nadir of respiratory function. FINDINGS: We found that neutrophil activation but not type I interferon signaling transcripts tracked most closely with disease progression and resolution. Moreover, transcripts encoding for protein phosphorylation, particularly the serine-threonine kinases, many of which have known T cell proliferation and activation functions, were increased after and may thus contribute to the upswing of respiratory function. Notably, these associative genes were targeted by dexamethasone, but not methylprednisolone, which is consistent with efficacy outcomes in clinical trials. INTERPRETATION: Our findings suggest neutrophil activation as a critical factor of respiratory dysfunction in COVID-19. Drugs that target this pathway could be potentially repurposed for the treatment of severe COVID-19. FUNDING: This study was sponsored in part by a generous gift from The Hour Glass. EEO and JGL are funded by the National Medical Research Council of Singapore, through the Clinician Scientist Awards awarded by the National Research Foundation of Singapore. |Adult[MESH] |Aged[MESH] |COVID-19/*pathology[MESH] |Disease Progression[MESH] |Drug Repositioning[MESH] |Female[MESH] |Gene Expression Profiling[MESH] |Gene Expression/genetics[MESH] |Humans[MESH] |Lymphocyte Activation/*immunology[MESH] |Male[MESH] |Middle Aged[MESH] |Neutrophil Activation/*immunology[MESH] |Neutrophils/immunology[MESH] |Prospective Studies[MESH] |SARS-CoV-2/*genetics/*immunology[MESH]Temporal dynamics of the host molecular responses underlying severe CO(epmc).pdf DeepDyve Pubget Overpricing