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The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals.

Published version
Peer-reviewed

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Authors

Butler-Laporte, Guillaume 
Gonzalez-Kozlova, Edgar 
Su, Chen-Yang 
Zhou, Sirui 
Nakanishi, Tomoko 

Abstract

INTRODUCTION: Severe COVID-19 leads to important changes in circulating immune-related proteins. To date it has been difficult to understand their temporal relationship and identify cytokines that are drivers of severe COVID-19 outcomes and underlie differences in outcomes between sexes. Here, we measured 147 immune-related proteins during acute COVID-19 to investigate these questions. METHODS: We measured circulating protein abundances using the SOMAscan nucleic acid aptamer panel in two large independent hospital-based COVID-19 cohorts in Canada and the United States. We fit generalized additive models with cubic splines from the start of symptom onset to identify protein levels over the first 14 days of infection which were different between severe cases and controls, adjusting for age and sex. Severe cases were defined as individuals with COVID-19 requiring invasive or non-invasive mechanical respiratory support. RESULTS: 580 individuals were included in the analysis. Mean subject age was 64.3 (sd 18.1), and 47% were male. Of the 147 proteins, 69 showed a significant difference between cases and controls (p < 3.4 × 10-4). Three clusters were formed by 108 highly correlated proteins that replicated in both cohorts, making it difficult to determine which proteins have a true causal effect on severe COVID-19. Six proteins showed sex differences in levels over time, of which 3 were also associated with severe COVID-19: CCL26, IL1RL2, and IL3RA, providing insights to better understand the marked differences in outcomes by sex. CONCLUSIONS: Severe COVID-19 is associated with large changes in 69 immune-related proteins. Further, five proteins were associated with sex differences in outcomes. These results provide direct insights into immune-related proteins that are strongly influenced by severe COVID-19 infection.

Description

Funder: Public health agency of Canada


Funder: Canadian institute for health research


Funder: Génome Québec; doi: http://dx.doi.org/10.13039/100013062


Funder: Fonds de Recherche du Québec - Santé; doi: http://dx.doi.org/10.13039/501100000156

Keywords

Research, COVID-19, Proteomics, SOMAscan, Immunity

Journal Title

Clin Proteomics

Conference Name

Journal ISSN

1542-6416
1559-0275

Volume Title

Publisher

Springer Science and Business Media LLC
Sponsorship
MRC (MC_UU_00006/1)