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CC16 and Resilience to COVID-19

Rafael de Cid, PhD. GCAT Chief Scientist, Genomes for Life-GCAT Lab






In this project, we seek to determine the role of Club cell secretory protein (CC16) in providing resilience to Coronavirus disease 2019 (COVID-19). CC16 is a homodimeric pneumoprotein mainly produced by club cells and other non-ciliated epithelial cells in the airways that can be readily measured in circulation1-8. Based on a large and growing body of evidence, we hypothesize that CC16 exerts protective effects against development and severity of COVID-19.

The principal aim of the project is to determine whether circulating CC16 levels predict susceptibility to development and severity of COVID-19. For this purpouse, we will conduct a nested case-control study. Based on available information from GCAT project,  the GCAT participants will be classified as: (1) individuals who did not develop COVID-19; (2) those who developed mild COVID-19; and (3) those who developed moderate/severe COVID-19. In statistical analyses, we will test the hypothesis that pre-COVID deficits of circulating CC16 predict development of clinically manifested COVID-19 and increase the likelihood for developing moderate/severe forms of the disease. Levels of circulating CC16 in pre-COVID serum samples collected in 2014-2017 will be compared between 150 GCAT participants who developed COVID-19 and 300 participants who did not. Among participants who developed COVID-19, secondary analyses will be completed to determine wheher CC16 levels are associated with disease severity.

Of note, GWAS data are available for a large proportion of GCAT participants and will be used to test whether the risk for symptomatic COVID-19 is also associated with any of the single nucleotide polymorphisms that in preliminary studies have been identified as being strong protein quantitative trait loci for circulating CC16 levels.

Case definition. Case are defined by the ocurrence of a positive results for any of the molecular test for Covid19 (PCR, Serologic test or Quick test)

Controls will be randomly selected from the same region if possible to mimic virus exposition and adjustment for potential confounders will be achieved using multivariate statistical analyses.

CC16 assays will be completed in all (prepandemic) serum samples using a commercially available ELISA kit (BioVendor, Czech Republic).  Proteomic assays will  be performed at IGTP.

These studies are designed to provide new insights for a priori risk stratification for COVID-19 and novel evidence in support of an underlying involvement of CC16 in COVID-19 susceptibility and severity.