Integration of individualized and population-level molecular epidemiology data to model COVID-19 outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with enhanced transmissibility and immune escape have emerged periodically throughout the coronavirus disease 2019 (COVID-19) pandemic, but the impact of these variants on disease severity has remained unclear. In this single-center, retrospective cohort study, we examined the association between SARS-CoV-2 clade and patient outcome over a two-year period in Chicago, Illinois. Between March 2020 and March 2022, 14,252 residual diagnostic specimens were collected from SARS-CoV-2-positive inpatients and outpatients alongside linked clinical and demographic metadata, of which 2,114 were processed for viral whole-genome sequencing. When controlling for patient demographics and vaccination status, several viral clades were associated with risk for hospitalization, but this association was negated by the inclusion of population-level confounders, including case count, sampling bias, and shifting standards of care. These data highlight the importance of integrating non-virological factors into disease severity and outcome models for the accurate assessment of patient risk.
Competing Interests: Declaration of interests M.G.I. has received research support, paid to Northwestern University, from AiCuris, GlaxoSmithKline Janssen, and Shire. M.G.I. is a paid consultant for Adagio, AlloVir, Celltrion, Cidara, Genentech, Roche, Janssen, Shionogi, Takeda, and Viracor Eurofins. M.G.I. is a paid member of the data and safety monitoring boards (DSMBs) of CSL Berhring, Janssen, Merck, SAB Biotherapeutics, Sequiris, and Takeda. J.F.H. has received research support, paid to Northwestern University, from Gilead Sciences and is a paid consultant for Merck.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)