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


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.

SUBMITTER: Butler-Laporte G 

PROVIDER: S-EPMC9516500 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Butler-Laporte Guillaume G   Gonzalez-Kozlova Edgar E   Su Chen-Yang CY   Zhou Sirui S   Nakanishi Tomoko T   Brunet-Ratnasingham Elsa E   Morrison David D   Laurent Laetitia L   Afilalo Jonathan J   Afilalo Marc M   Henry Danielle D   Chen Yiheng Y   Carrasco-Zanini Julia J   Farjoun Yossi Y   Pietzner Maik M   Kimchi Nofar N   Afrasiabi Zaman Z   Rezk Nardin N   Bouab Meriem M   Petitjean Louis L   Guzman Charlotte C   Xue Xiaoqing X   Tselios Chris C   Vulesevic Branka B   Adeleye Olumide O   Abdullah Tala T   Almamlouk Noor N   Moussa Yara Y   DeLuca Chantal C   Duggan Naomi N   Schurr Erwin E   Brassard Nathalie N   Durand Madeleine M   Del Valle Diane Marie DM   Thompson Ryan R   Cedillo Mario A MA   Schadt Eric E   Nie Kai K   Simons Nicole W NW   Mouskas Konstantinos K   Zaki Nicolas N   Patel Manishkumar M   Xie Hui H   Harris Jocelyn J   Marvin Robert R   Cheng Esther E   Tuballes Kevin K   Argueta Kimberly K   Scott Ieisha I   Greenwood Celia M T CMT   Paterson Clare C   Hinterberg Michael M   Langenberg Claudia C   Forgetta Vincenzo V   Mooser Vincent V   Marron Thomas T   Beckmann Noam N   Kenigsberg Ephraim E   Charney Alexander W AW   Kim-Schulze Seunghee S   Merad Miriam M   Kaufmann Daniel E DE   Gnjatic Sacha S   Richards J Brent JB  

Clinical proteomics 20220928 1


<h4>Introduction</h4>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.<h4>Methods</h4>We measured circulating protein abundances using the SOMAscan nucleic acid aptamer panel  ...[more]

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