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

Butler-Laporte, Guillaume; Gonzalez-Kozlova, Edgar; Su, Chen-Yang; Zhou, Sirui; Nakanishi, Tomoko; Brunet-Ratnasingham, Elsa; Morrison, David; Laurent, Laetitia; Afilalo, Jonathan; Afilalo, Marc; Henry, Danielle; Chen, Yiheng; Carrasco-Zanini, Julia; Farjoun, Yossi; Pietzner, Maik; Kimchi, Nofar; Afrasiabi, Zaman; Rezk, Nardin; Bouab, Meriem; Petitjean, Louis; Guzman, Charlotte; Xue, Xiaoqing; Tselios, Chris; Vulesevic, Branka; Adeleye, Olumide; Abdullah, Tala; Almamlouk, Noor; Moussa, Yara; DeLuca, Chantal; Duggan, Naomi; Schurr, Erwin; Brassard, Nathalie; Durand, Madeleine; Del Valle, Diane Marie; Thompson, Ryan; Cedillo, Mario A.; Schadt, Eric; Nie, Kai; Simons, Nicole W.; Mouskas, Konstantinos; Zaki, Nicolas; Patel, Manishkumar; Xie, Hui; Harris, Jocelyn; Marvin, Robert; Cheng, Esther; Tuballes, Kevin; Argueta, Kimberly; Scott, Ieisha; The Mount Sinai COVID-19 Biobank Team; Greenwood, Celia M. T.; Paterson, Clare; Hinterberg, Michael; Langenberg, Claudia; Forgetta, Vincenzo; Mooser, Vincent; Marron, Thomas; Beckmann, Noam; Kenigsberg, Ephraim; Charney, Alexander W.; Kim-schulze, Seunghee; Merad, Miriam; Kaufmann, Daniel E.; Gnjatic, Sacha; Richards, J. Brent

doi:https://open-science.canada.ca/handle/123456789/3355

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

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dc.contributor.author: Butler-Laporte, Guillaume; Gonzalez-Kozlova, Edgar; Su, Chen-Yang; Zhou, Sirui; Nakanishi, Tomoko; Brunet-Ratnasingham, Elsa; Morrison, David; Laurent, Laetitia; Afilalo, Jonathan; Afilalo, Marc; Henry, Danielle; Chen, Yiheng; Carrasco-Zanini, Julia; Farjoun, Yossi; Pietzner, Maik; Kimchi, Nofar; Afrasiabi, Zaman; Rezk, Nardin; Bouab, Meriem; Petitjean, Louis; Guzman, Charlotte; Xue, Xiaoqing; Tselios, Chris; Vulesevic, Branka; Adeleye, Olumide; Abdullah, Tala; Almamlouk, Noor; Moussa, Yara; DeLuca, Chantal; Duggan, Naomi; Schurr, Erwin; Brassard, Nathalie; Durand, Madeleine; Del Valle, Diane Marie; Thompson, Ryan; Cedillo, Mario A.; Schadt, Eric; Nie, Kai; Simons, Nicole W.; Mouskas, Konstantinos; Zaki, Nicolas; Patel, Manishkumar; Xie, Hui; Harris, Jocelyn; Marvin, Robert; Cheng, Esther; Tuballes, Kevin; Argueta, Kimberly; Scott, Ieisha; The Mount Sinai COVID-19 Biobank Team; Greenwood, Celia M. T.; Paterson, Clare; Hinterberg, Michael; Langenberg, Claudia; Forgetta, Vincenzo; Mooser, Vincent; Marron, Thomas; Beckmann, Noam; Kenigsberg, Ephraim; Charney, Alexander W.; Kim-schulze, Seunghee; Merad, Miriam; Kaufmann, Daniel E.; Gnjatic, Sacha; Richards, J. Brent
dc.date.accessioned: 2025-01-24T21:15:52Z
dc.date.available: 2025-01-24T21:15:52Z
dc.date.issued: 2022-09-28
dc.description.abstract - en: 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.
dc.description.sponsorship: The Richards research group is supported by the Canadian Institutes of Health Research (CIHR: 365825; 409511, 100558), the Lady Davis Institute of the Jewish General Hospital, the Jewish General Hospital Foundation, the Canadian Foundation for Innovation, the NIH Foundation, Cancer Research UK, Genome Québec, the Public Health Agency of Canada, McGill University, Cancer Research UK [grant number C18281/A29019], and the Fonds de Recherche Québec Santé (FRQS). The Kaufmann lab’s COVID-19 work is supported by the Canadian Institutes of Health Research /CITF (VR2-173203 and VS1-175561), the American Foundation for AIDS Research (AmFAR 110068–68-RGCV), the Canadian Foundation for Innovation, and FRQS. Support from Calcul Québec and Compute Canada is acknowledged. These funding agencies had no role in the design, implementation, or interpretation of this study. The measurement of proteomics using the SomaLogic panel was supported by the McGill Interdisciplinary Initiative in Infection and Immunity (MI4). J.B.R. and D.E.K. are supported by FRQS Mérite Clinical Research Scholarships. C.-Y.S. is supported by a Lady Davis Institute / TD Bank Studentship Award. S.Z. is supported by a CIHR fellowship and a FRQS postdoctoral scholarship. G.B.L. is supported by a CIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarship. T.N. is supported by Research Fellowships of the Japan Society for the Promotion of Science (JSPS) for Young Scientists. M.D. is supported by a clinician-researcher salary award from the FRQS. V.M. is supported by a Canada Excellence Research Chair.
dc.identifier.doi: https://doi.org/10.1186/s12014-022-09371-z
dc.identifier.issn: 1559-0275
dc.identifier.pubmedID: 36171541
dc.identifier.uri: https://open-science.canada.ca/handle/123456789/3355
dc.language.iso: en
dc.publisher - en: BioMed Central Ltd.
dc.rights - en: Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.rights - fr: Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.rights.openaccesslevel - en: Gold
dc.rights.openaccesslevel - fr: Or
dc.rights.uri - en: https://creativecommons.org/licenses/by/4.0/
dc.rights.uri - fr: https://creativecommons.org/licenses/by/4.0/deed.fr
dc.subject - en: Health; Coronavirus diseases
dc.subject - fr: Santé; Maladie à coronavirus
dc.subject.en - en: Health; Coronavirus diseases
dc.subject.fr - fr: Santé; Maladie à coronavirus
dc.title - en: The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals
dc.type - en: Article
dc.type - fr: Article
local.acceptedmanuscript.articlenum: 34
local.article.journaltitle - en: Clinical Proteomics
local.article.journalvolume: 19
local.pagination: 1-11
local.peerreview - en: Yes
local.peerreview - fr: Oui

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