Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ebiom.2021.103262
Title: Temporal dynamics of the host molecular responses underlying severe COVID-19 progression and disease resolution
Authors: Ong, Eugenia Z. 
Kalimuddin, Shirin 
Chia, Wen Chong
Ooi, Sarah H.
Koh, Clara Wt 
Tan, Hwee Cheng 
Zhang, Summer L. 
Low, Jenny G. 
Ooi, Eng Eong 
Chan, Kuan Rong 
Keywords: COVID-19 pathogenesis
COVID-19 recovery
SARS-CoV-2
Transcriptome profiling
Issue Date: 1-Mar-2021
Publisher: Elsevier B.V.
Citation: Ong, Eugenia Z., Kalimuddin, Shirin, Chia, Wen Chong, Ooi, Sarah H., Koh, Clara Wt, Tan, Hwee Cheng, Zhang, Summer L., Low, Jenny G., Ooi, Eng Eong, Chan, Kuan Rong (2021-03-01). Temporal dynamics of the host molecular responses underlying severe COVID-19 progression and disease resolution. EBioMedicine 65 : 103262. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ebiom.2021.103262
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Abstract: 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. © 2021 The Authors
Source Title: EBioMedicine
URI: https://scholarbank.nus.edu.sg/handle/10635/233230
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2021.103262
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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