Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Blood Leukocyte Transcriptional Modules and Differentially Expressed Genes Associated with Disease Severity and Age in COVID-19 Patients

Version 1 : Received: 8 August 2022 / Approved: 9 August 2022 / Online: 9 August 2022 (14:59:44 CEST)

How to cite: Bando, S.Y.; Bertonha, F.B.; Vieira, S.E.; Oliveira, D.B.L.; Chalup, V.N.; Durigon, E.L.; Palmeira, P.; Curi, A.C.P.; Faria, C.S.; Antonangelo, L.; Lauterbach, G.D.P.; Regalio, F.A.; Cesar Jr, R.M.; Moreira-Filho, C.A. Blood Leukocyte Transcriptional Modules and Differentially Expressed Genes Associated with Disease Severity and Age in COVID-19 Patients. Preprints 2022, 2022080181 (doi: 10.20944/preprints202208.0181.v1). Bando, S.Y.; Bertonha, F.B.; Vieira, S.E.; Oliveira, D.B.L.; Chalup, V.N.; Durigon, E.L.; Palmeira, P.; Curi, A.C.P.; Faria, C.S.; Antonangelo, L.; Lauterbach, G.D.P.; Regalio, F.A.; Cesar Jr, R.M.; Moreira-Filho, C.A. Blood Leukocyte Transcriptional Modules and Differentially Expressed Genes Associated with Disease Severity and Age in COVID-19 Patients. Preprints 2022, 2022080181 (doi: 10.20944/preprints202208.0181.v1).

Abstract

The transcriptional response of human blood leukocytes to SARS-CoV-2 infection was investigated focusing on the differences between mild and severe cases and between age subgroups. Weighted gene co-expression network analysis and comparative gene expression analysis were used. Three transcriptional modules positively associated with the traits of interest and their respective high hierarchy genes were identified. Enrichment analyses showed that the yellow module, associated with severe cases and older patients, had an overrepresentation of genes involved in inflammatory and innate immune responses, and neutrophil activation. The magenta and black modules, associated with disease severity and younger patients, contained genes related to innate immunity and inflammation and genes that regulate those responses. Subnetworks for these modules were constructed using genes enriched for innate immunity, inflammation, immunoregulation and differentially expressed genes (severe vs. mild). Their analysis evidenced that immunoregulatory functions are more activated in the modules associated with younger patients, what may help to explain the better disease course and faster recovery observed in younger COVID-19 patients. Comparative gene expression analysis between severe and mild groups, followed by gene enrichment and normalized gene expression analyses, revelated a set of 23 potential biomarkers for COVID-19 severity, of which 13 are newly described.

Keywords

COVID-19; SARS-CoV-2; disease severity; blood leukocyte transcriptome; WGCNA; transcriptional modules; differentially expressed genes; COVID-19 transcriptional markers

Subject

LIFE SCIENCES, Other

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