Author:
Su Chen-Yang,Zhou Sirui,Gonzalez-Kozlova Edgar,Butler-Laporte Guillaume,Brunet-Ratnasingham Elsa,Nakanishi Tomoko,Jeon Wonseok,Morrison David R.,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,Greenwood Celia M. T.,Paterson Clare,Hinterberg Michael A.,Langenberg Claudia,Forgetta Vincenzo,Pineau Joelle,Mooser Vincent,Marron Thomas,Beckmann Noam D.,Kim-schulze Seunghee,Charney Alexander W.,Gnjatic Sacha,Kaufmann Daniel E.,Merad Miriam,Richards J. Brent,
Abstract
AbstractPredicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured 4701 circulating human protein abundances in two independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict COVID-19 severity in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the 4701 unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different COVID-19 severity were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of COVID-19 severity. Further research is needed to understand how to incorporate protein measurement into clinical care.
Funder
Canadian Institutes of Health Research
Publisher
Springer Science and Business Media LLC