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

Abstract

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.

The intersection of COVID-19 and autoimmunity

“…If so, can patients with acute disease or PASC be immunologically profiled to identify those who might benefit from immune-modulating therapies? Answering these questions will require the generation of multi-ethnic biospecimen repositories from COVID-19 patients, such as the Collaborative Cohort of Cohorts for COVID-19 Research (C4R), which includes information from before, during, and after SARS-CoV-2 infection that can potentially enable the necessary longitudinal investigations (115). Analysis of large-scale electronic health record data (EHR) (116)(117)(118) will likely also be needed to determine clinical associations with COVID-19, such as autoimmune manifestations.…”

Increasing COVID-19 testing and vaccination among Spanish speakers in the USA: protocol for the development and evaluation of theNuestra Comunidad Saludableintervention using a group-randomised trial design

“…Spanish-speaking Latine communities face a myriad of challenges related to COVID-19 testing and vaccination resulting in disparities in COVID-19-related morbidity and mortality 2 7–10. Innovative, culturally congruent interventions are critically needed to reduce disparities.…”

“…Ongoing testing and vaccination are critical to effective control of the pandemic; however, complex issues contribute to low rates of COVID-19 testing and vaccination within Spanish-speaking Latine communities 2 7–10. Latine persons may lack access to culturally congruent information about COVID-19 testing and vaccination, including eligibility and ways to access these services; and assume that they must pay for testing or vaccination.…”

Central nervous system outcomes of COVID-19

“…This is where the ongoing NIH cohort studies, with extensive historic data, could add important information about pre-clinical states that might increase susceptibility. Studies like C4R (The Collaborative Cohort of Cohorts for COVID-19 Research) 97 , a collaboration of 14 such studies that have historic data and stored specimens from over 50,000 multi-ethnic participants from across the United States, can add some information on susceptibility. These participants have consented to COVID-19 questionnaires and medical records extraction, as well as providing blood spots for serologic testing.…”