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

TitleThe dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals.
Publication TypeJournal Article
Year of Publication2022
AuthorsButler-Laporte G, Gonzalez-Kozlova E, Su C-Y, Zhou S, Nakanishi T, Brunet-Ratnasingham E, Morrison D, Laurent L, Afilalo J, Afilalo M, Henry D, Chen Y, Carrasco-Zanini J, Farjoun Y, Pietzner M, Kimchi N, Afrasiabi Z, Rezk N, Bouab M, Petitjean L, Guzman C, Xue X, Tselios C, Vulesevic B, Adeleye O, Abdullah T, Almamlouk N, Moussa Y, DeLuca C, Duggan N, Schurr E, Brassard N, Durand M, Del Valle DMarie, Thompson R, Cedillo MA, Schadt E, Nie K, Simons NW, Mouskas K, Zaki N, Patel M, Xie H, Harris J, Marvin R, Cheng E, Tuballes K, Argueta K, Scott I, Greenwood CMT, Paterson C, Hinterberg M, Langenberg C, Forgetta V, Mooser V, Marron T, Beckmann N, Kenigsberg E, Charney AW, Kim-Schulze S, Merad M, Kaufmann DE, Gnjatic S, J Richards B
Corporate AuthorsMount Sinai COVID-19 Biobank Team
JournalClin Proteomics
Volume19
Issue1
Pagination34
Date Published2022 Sep 28
ISSN1542-6416
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.

DOI10.1186/s12014-022-09371-z
Alternate JournalClin Proteomics
PubMed ID36171541
PubMed Central IDPMC9516500
Grant ListMC_UU_00006/1 / MRC_ / Medical Research Council / United Kingdom
U24 CA224319 / CA / NCI NIH HHS / United States
Related Faculty: 
Esther Cheng, D.O.

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