1. Phenome-wide association of 1809 phenotypes and COVID-19 disease progression in the Veterans Health Administration Million Veteran Program
- Author
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Philip S. Tsao, Stacey B. Whitbourne, Tori Anglin-Foote, Saiju Pyarajan, Christopher J. O'Donnell, Petra Schubert, Juan P. Casas, Kyong-Mi Chang, Jennifer E. Huffman, John Michael Gaziano, Rebecca J Song, Yuk-Lam Ho, Hanna Gerlovin, Rachel Ramoni, Katherine P. Liao, Sumitra Muralidhar, Jean C. Beckham, Yojin Park, Scott L. DuVall, Daniel C Posner, Kelly Cho, Emily M. Lord, Lauren Costa, David R. Gagnon, Katherine E. Kurgansky, and Luc Djoussé
- Subjects
Male ,RNA viruses ,Viral Diseases ,Pulmonology ,Coronaviruses ,Epidemiology ,Electronic Medical Records ,Disease ,030204 cardiovascular system & hematology ,law.invention ,Body Mass Index ,0302 clinical medicine ,Medical Conditions ,Endocrinology ,law ,Risk Factors ,Medicine and Health Sciences ,030212 general & internal medicine ,Longitudinal Studies ,Pathology and laboratory medicine ,Veterans ,Virus Testing ,Aged, 80 and over ,Multidisciplinary ,Age Factors ,Middle Aged ,Medical microbiology ,Intensive care unit ,Hospitals ,Type 2 Diabetes ,Hospitalization ,Intensive Care Units ,Infectious Diseases ,Viruses ,Disease Progression ,Medicine ,Female ,SARS CoV 2 ,Pathogens ,Type 2 Diabetes Risk ,Information Technology ,Research Article ,medicine.medical_specialty ,Computer and Information Sciences ,SARS coronavirus ,Endocrine Disorders ,Science ,Veterans Health ,Lower risk ,Microbiology ,Sepsis ,03 medical and health sciences ,Respiratory Disorders ,Sex Factors ,Diagnostic Medicine ,Internal medicine ,medicine ,Diabetes Mellitus ,Humans ,Aged ,Biology and life sciences ,business.industry ,SARS-CoV-2 ,Organisms ,Viral pathogens ,COVID-19 ,Covid 19 ,Health Information Technology ,Odds ratio ,medicine.disease ,United States ,Microbial pathogens ,Health Care ,Respiratory failure ,Health Care Facilities ,Medical Risk Factors ,Metabolic Disorders ,Respiratory Infections ,business ,Body mass index - Abstract
Background The risk factors associated with the stages of Coronavirus Disease-2019 (COVID-19) disease progression are not well known. We aim to identify risk factors specific to each state of COVID-19 progression from SARS-CoV-2 infection through death. Methods and results We included 648,202 participants from the Veteran Affairs Million Veteran Program (2011-). We identified characteristics and 1,809 ICD code-based phenotypes from the electronic health record. We used logistic regression to examine the association of age, sex, body mass index (BMI), race, and prevalent phenotypes to the stages of COVID-19 disease progression: infection, hospitalization, intensive care unit (ICU) admission, and 30-day mortality (separate models for each). Models were adjusted for age, sex, race, ethnicity, number of visit months and ICD codes, state infection rate and controlled for multiple testing using false discovery rate (≤0.1). As of August 10, 2020, 5,929 individuals were SARS-CoV-2 positive and among those, 1,463 (25%) were hospitalized, 579 (10%) were in ICU, and 398 (7%) died. We observed a lower risk in women vs. men for ICU and mortality (Odds Ratio (95% CI): 0.48 (0.30–0.76) and 0.59 (0.31–1.15), respectively) and a higher risk in Black vs. Other race patients for hospitalization and ICU (OR (95%CI): 1.53 (1.32–1.77) and 1.63 (1.32–2.02), respectively). We observed an increased risk of all COVID-19 disease states with older age and BMI ≥35 vs. 20–24 kg/m2. Renal failure, respiratory failure, morbid obesity, acid-base balance disorder, white blood cell diseases, hydronephrosis and bacterial infections were associated with an increased risk of ICU admissions; sepsis, chronic skin ulcers, acid-base balance disorder and acidosis were associated with mortality. Conclusions Older age, higher BMI, males and patients with a history of respiratory, kidney, bacterial or metabolic comorbidities experienced greater COVID-19 severity. Future studies to investigate the underlying mechanisms associated with these phenotype clusters and COVID-19 are warranted.
- Published
- 2021