Collaborative Cohort of Cohorts for COVID-19 Research (C4R): Genetic Epidemiology of COPD Study (COPDGene)

Adverse effects of the coronavirus disease 2019 (COVID19) pandemic on US society, health, and economy are widespread. The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) aims to advance our knowledge on the impact of the COVID-19 pandemic in the United States. C4R is a diverse national prospective study comprising 14 long-standing prospective cohort studies and over 49,000 participants with extensive pre-COVID-19 phenotype data. C4R links pre-pandemic data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health, to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and post-acute COVID-related illness. Ascertainment of COVID-19 infection occurs via standardized questionnaires, adjudication of COVID-related hospitalizations and deaths, and SARS-CoV-2 serosurvey via dried blood spot cards. C4R is investigating the following research questions: 1) how pre-existing health conditions affect risk of severe or prolonged COVID-19 related illness; 2) how SARS-CoV-2 infection and COVID-19 illness affect long-term health; and 3) how the pandemic has affected health-related behaviors and non-COVID health outcomes. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and long-term health effects.

Cohort Description
The Genetic Epidemiology of COPD (COPDGene) study is a non-interventional, multicenter, longitudinal, case-control study at 21 US sites of smokers with a ≥10 pack-year history of smoking, with and without COPD, and healthy never smokers. The initial goal was to characterize disease-related phenotypes and explore associations with susceptibility genes.

Data Being Submitted
Wave 1 questionnaire data includes 397 variables for up to 3683 COPDGene participants in C4R.
Wave 2 questionnaire data includes 447 variables for up to 2191 COPDGene participants in C4R.
Dried Blood Spot/Serosurvey data includes 7 variables for up to 1692 COPDGene participants in C4R.
Derived data includes 43 variables for up to 4082 COPDGene participants in C4R.
Phenotype data includes 113 variables for up to 4082 COPDGene participants in C4R.

• Study Weblinks:
  • C4R
  • COPDGene
• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Longitudinal Cohort
  • Prospective
• Total number of consented subjects: 4191
• Subject Sample Telemetry Report (SSTR)

• PubMed
• MeSH
• PMC
• Clinical Trials
  • NCT02445183

COPD Cases:

Inclusion Criteria:

• Age 45 - 80 years
• Smoking history of > 10 pack-years
• Diagnosis of COPD Stages 2, 3 and 4 by GOLD criteria (post-bronchodilator FEV1/FVC < 0.70 and FEV1 < 80% predicted)
• Non-Hispanic White or non-Hispanic African American

Exclusion Criteria:

• Concomitant respiratory disorder other than asthma or COPD (such as, but not limited to, diffuse bronchiectasis, cystic fibrosis, or interstitial lung disease)
• Lung surgery with removal of a lobe or more (including lung volume reduction surgery or lung transplantation)
• Lung cancer, known or suspected
• Surgical or bronchoscopic lung volume reduction
• Pregnancy or suspected pregnancy
• Uncontrolled cancer, defined as ongoing radiation therapy, ongoing chemotherapy, narcotics for pain control, or known metastatic disease
• History of radiation therapy to the chest (other than for breast cancer)
• Use of antibiotics and/or systemic steroids (new prescription or increased dose) for a COPD exacerbation or respiratory infection within the last month
• Inability to use albuterol
• First or second degree relative (parent, brother, sister, daughter, son, aunt, uncle, nephew, niece, half-sibling, grandparent, grandchild) of a subject enrolled in COPDGene
• Subjects who indicate they are in more than one racial category
• Metal objects that may interfere with chest CT quantification including presence of a cardiac pacemaker, defibrillator, metal prosthetic heart valve, or metal shoulder prosthesis
• Subjects with affirmative answers to the following:
  • Chest or abdominal surgery in the past three months
  • Heart attack in the last three months
  • Detached retina or eye surgery in the past three months
  • Hospitalization for any other heart problem in the past month
• Participation in the ECLIPSE study, Boston Early-Onset COPD Study, or International COPD Genetics Network (Selected replication cohorts)

Smokers without COPD:

Inclusion Criteria:

• Age 45 - 80 years
• History (current or formerly) of cigarette smoking > 10 pack-years
• Post-bronchodilator FEV1/FVC > 0.70 and FEV1 > 80% predicted.
• Non-Hispanic White or non-Hispanic African American

Exclusion Criteria:

• Physician diagnosed respiratory disease other than COPD or asthma (based on subject report)
• Lung surgery with removal of a lobe or more (including lung volume reduction surgery and lung transplantation)
• Pregnancy or suspected pregnancy
• Lung cancer, known or suspected
• Uncontrolled cancer, defined as ongoing radiation therapy, ongoing chemotherapy, narcotics for pain control, or known metastatic disease
• History of radiation therapy to the chest
• Use of antibiotics (new prescription or increased dose) for a respiratory infection within the past month
• Use of systemic corticosteroids (new prescription or increased dose) for a respiratory process within the past month
• Inability to use albuterol
• First or second degree relative (parent, brother, sister, daughter, son, aunt, uncle, nephew, niece, half-sibling, grandparent, or grandchild) of a subject enrolled in COPDGene
• Subjects who indicate they are in more than one racial category
• Metal objects that may interfere with chest CT quantification including presence of a cardiac pacemaker, defibrillator, metal prosthetic heart valve, or metal shoulder prosthesis
• Subjects with affirmative answers to the following:
  • Chest or abdominal surgery in the past three months
  • Heart attack in the last three months
  • Detached retina or eye surgery in the past three months
  • Hospitalization for any other heart problem in the past month
• Participation in the ECLIPSE study, the Boston Early-Onset COPD Study, or the International COPD Genetics Network (selected replication cohorts)

This study was funded by the NHLBI in October 2007 as two U01 grants—one to National Jewish Medical and Research Center (PI: James D. Crapo) and one to Brigham and Women’s Hospital (PI: Edwin K. Silverman). After a pilot study in 2007, study recruitment began in February 2008 at 21 clinical centers throughout the United States.

• Primary Phenotype: COVID-19
• SARS-CoV-2
• COVID-19 Serological Testing
• COVID-19 Testing
• COVID-19 Vaccines
• COPD

• Principal Investigator
  • Elizabeth C. Oelsner, MD, MPH. Columbia University Irving Medical Center, New York, NY, USA.
• Co-Principal Investigator
  • R. Graham Barr, MD, DrPH. Columbia University Irving Medical Center, New York, NY, USA.
• Co-Investigator
  • Pallavi Balte, MBBS, MPH, PhD. Columbia University Irving Medical Center, New York, NY, USA.
• Cohort Principal Investigators
  • Barry J. Make, MD. National Jewish Health, Denver, CO, USA.
  • Elizabeth A. Regan, MD, PhD. National Jewish Health, Denver, CO, USA.
• Data Manager
  • Carla Wilson. National Jewish Health, Denver, CO, USA.