Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design
Authors: Oelsner Elizabeth C , Krishnaswamy Akshaya , Balte Pallavi P , Allen Norrina Bai , Ali Tauqeer , Anugu Pramod , Andrews Howard F , Arora Komal , Asaro Alyssa , Barr R Graham , Bertoni Alain G , Bon Jessica , Boyle Rebekah , Chang Arunee A , Chen Grace , Coady Sean , Cole Shelley A , Coresh Josef , Cornell Elaine , Correa Adolfo , Couper David , Cushman Mary , Demmer Ryan T , Elkind Mitchell S V , Folsom Aaron R , Fretts Amanda M , Gabriel Kelley P , Gallo Linda C , Gutierrez Jose , Han Mei Lan K , Henderson Joel M , Howard Virginia J , Isasi Carmen R , Jacobs Jr David R , Judd Suzanne E , Mukaz Debora Kamin , Kanaya Alka M , Kandula Namratha R , Kaplan Robert C , Kinney Gregory L , Kucharska-Newton Anna , Lee Joyce S , Lewis Cora E , Levine Deborah A , Levitan Emily B , Levy Bruce D , Make Barry J , Malloy Kimberly , Manly Jennifer J , Mendoza-Puccini Carolina , Meyer Katie A , Min Yuan-I Nancy , Moll Matthew R , Moore Wendy C , Mauger David , Ortega Victor E , Palta Priya , Parker Monica M , Phipatanakul Wanda , Post Wendy S , Postow Lisa , Psaty Bruce M , Regan Elizabeth A , Ring Kimberly , Roger Véronique L , Rotter Jerome I , Rundek Tatjana , Sacco Ralph L , Schembri Michael , Schwartz David A , Seshadri Sudha , Shikany James M , Sims Mario , Hinckley Stukovsky Karen D , Talavera Gregory A , Tracy Russell P , Umans Jason G , Vasan Ramachandran S , Watson Karol E , Wenzel Sally E , Winters Karen , Woodruff Prescott G , Xanthakis Vanessa , Zhang Ying , Zhang Yiyi ,   for the C4R Investigators
Published: February 2022

Abstract
The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre–coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18–108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories.