The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals.
Creators: name: Butler-Laporte, Guillaume
name: Gonzalez-Kozlova, Edgar
name: Su, Chen-Yang
name: Zhou, Sirui
name: Nakanishi, Tomoko
name: Brunet-Ratnasingham, Elsa
name: Morrison, David
name: Laurent, Laetitia
name: Afilalo, Jonathan
name: Afilalo, Marc
name: Henry, Danielle
name: Chen, Yiheng
name: Carrasco-Zanini, Julia
name: Farjoun, Yossi
name: Pietzner, Maik
name: Kimchi, Nofar
name: Afrasiabi, Zaman
name: Rezk, Nardin
name: Bouab, Meriem
name: Petitjean, Louis
name: Guzman, Charlotte
name: Xue, Xiaoqing
name: Tselios, Chris
name: Vulesevic, Branka
name: Adeleye, Olumide
name: Abdullah, Tala
name: Almamlouk, Noor
name: Moussa, Yara
name: DeLuca, Chantal
name: Duggan, Naomi
name: Schurr, Erwin
name: Brassard, Nathalie
name: Durand, Madeleine
name: Del Valle, Diane Marie
name: Thompson, Ryan
name: Cedillo, Mario A
name: Schadt, Eric
name: Nie, Kai
name: Simons, Nicole W
name: Mouskas, Konstantinos
name: Zaki, Nicolas
name: Patel, Manishkumar
name: Xie, Hui
name: Harris, Jocelyn
name: Marvin, Robert
name: Cheng, Esther
name: Tuballes, Kevin
name: Argueta, Kimberly
name: Scott, Ieisha
name: Mount Sinai COVID-19 Biobank Team
name: Greenwood, Celia MT
name: Paterson, Clare
name: Hinterberg, Michael
name: Langenberg, Claudia
name: Forgetta, Vincenzo
name: Mooser, Vincent
name: Marron, Thomas
name: Beckmann, Noam
name: Kenigsberg, Ephraim
name: Charney, Alexander W
name: Kim-Schulze, Seunghee
name: Merad, Miriam
name: Kaufmann, Daniel E
name: Gnjatic, Sacha
name: Richards, J Brent
Publisher: name: Apollo - University of Cambridge Repository
Year: 2022
Subjects: Research
COVID-19
Proteomics
SOMAscan
Immunity

description: Funder: Public health agency of Canada
description: Funder: Canadian institute for health research
description: Funder: Génome Québec; doi: http://dx.doi.org/10.13039/100013062
description: Funder: Fonds de Recherche du Québec - Santé; doi: http://dx.doi.org/10.13039/501100000156
description: 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 &lt; 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.