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. 2021 May 13;16(5):e0251651.
doi: 10.1371/journal.pone.0251651. eCollection 2021.

Phenome-wide association of 1809 phenotypes and COVID-19 disease progression in the Veterans Health Administration Million Veteran Program

Rebecca J Song  1   2 , Yuk-Lam Ho  1 , Petra Schubert  1 , Yojin Park  1 , Daniel Posner  1 , Emily M Lord  1 , Lauren Costa  1 , Hanna Gerlovin  1 , Katherine E Kurgansky  1 , Tori Anglin-Foote  3 , Scott DuVall  3   4   5 , Jennifer E Huffman  1 , Saiju Pyarajan  1   6   7 , Jean C Beckham  8   9   10 , Kyong-Mi Chang  11   12 , Katherine P Liao  1   7   13 , Luc Djousse  1   6   7 , David R Gagnon  1   14 , Stacey B Whitbourne  1   7 , Rachel Ramoni  4 , Sumitra Muralidhar  4 , Philip S Tsao  15   16 , Christopher J O'Donnell  1   7 , John Michael Gaziano  1   6   7 , Juan P Casas  1   6   7 , Kelly Cho  1   6   7 ; VA Million Veteran Program COVID-19 Science Initiative
Affiliations

Phenome-wide association of 1809 phenotypes and COVID-19 disease progression in the Veterans Health Administration Million Veteran Program

Rebecca J Song et al. PLoS One. .

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. STROBE diagram of study sample.
Flow diagram of Million Veteran Program participants included and excluded in each analysis, and number of participants who were SARS CoV-2 positive, hospitalized, admitted to the ICU, or died.
Fig 2
Fig 2
Phenome-wide associations with COVID-19 progression for (a) tested positive, (b) hospitalization, (c) intensive care unit admission, and (d) death.
Fig 3
Fig 3. Heat map of phenotypes associated with COVID-19 outcomes.
Blue indicates an increased risk and red indicates a decreased risk of the outcome.
Fig 4
Fig 4. Comparison of odds ratio for symptomatic SARS-CoV-2 infection and odds ratio for asymptomatic or symptomatic SARS-CoV-2 infected individuals.
See this image and copyright information in PMC

References

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