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Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design

By Elizabeth C. Oelsner, Norinna Bai Allen, Tauqueer Ali, Pramod Anugu, Howard Andrews, Alyssa Asaro, Pallavi P Balte, R. Graham Barr, Alain Bertoni, Jessica Bon, Rebekah Boyle, Arunee A Chang, Grace Chen, Shelley A Cole, Josef Coresh, Elaine Cornell, Adolfo Correa, David Couper, Mary Cushman, Ryan T. Demmer, Mitchell S Elkind, Aaron R Folsom, Amanda M Fretts, Kelley Pettee Gabriel, Linda Gallo, Jose Gutierrez Contreras, Meilan K Han, Joel M Henderson, Virginia J Howard, Carmen R. Isasi, David R. Jacobs, Suzanne E Judd, Debora Kamin Mukaz, Alka M Kanaya, Namratha R Kandula, Robert C. Kaplan, Akshaya Krishnaswamy, Gregory L Kinney, Anna Kucharska-Newton, Joyce S Lee, Cora E Lewis, Deborah A Levine, Emily B Levitan, Bruce Levy, Barry Make, Kimberly Malloy, Jennifer J Manly, Katie A. Meyer, Yuan-I Min, Matthew Moll, Wendy C Moore, Dave Mauger, Victor E Ortega, Priya Palta, Monica M Parker, Wanda Phipatanakul, Wendy Post, Bruce M Psaty, Elizabeth A Regan, Kimberly Ring, Veronique L Roger, Jerome I Rotter, Tatjana Rundek, Ralph L Sacco, Michael Schembri, David A. Schwartz, Sudha Seshadri, James M Shikany, Mario Sims, Karen D Hinckley Stukovsky, Gregory A Talavera, Russell P Tracy, Jason G Umans, Vasan Ramachandran, Karol Watson, Sally E Wenzel, Karen Winters, Prescott G. Woodruff, Vanessa Xanthakis, Ying Zhang, Yiyi Zhang, The C4R Investigators

Posted 20 Mar 2021
medRxiv DOI: 10.1101/2021.03.19.21253986

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.

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