@Article{info:doi/10.2196/31400,
author="Weber, Griffin M
and Zhang, Harrison G
and L'Yi, Sehi
and Bonzel, Clara-Lea
and Hong, Chuan
and Avillach, Paul
and Guti{\'e}rrez-Sacrist{\'a}n, Alba
and Palmer, Nathan P
and Tan, Amelia Li Min
and Wang, Xuan
and Yuan, William
and Gehlenborg, Nils
and Alloni, Anna
and Amendola, Danilo F
and Bellasi, Antonio
and Bellazzi, Riccardo
and Beraghi, Michele
and Bucalo, Mauro
and Chiovato, Luca
and Cho, Kelly
and Dagliati, Arianna
and Estiri, Hossein
and Follett, Robert W
and Garc{\'i}a Barrio, Noelia
and Hanauer, David A
and Henderson, Darren W
and Ho, Yuk-Lam
and Holmes, John H
and Hutch, Meghan R
and Kavuluru, Ramakanth
and Kirchoff, Katie
and Klann, Jeffrey G
and Krishnamurthy, Ashok K
and Le, Trang T
and Liu, Molei
and Loh, Ne Hooi Will
and Lozano-Zahonero, Sara
and Luo, Yuan
and Maidlow, Sarah
and Makoudjou, Adeline
and Malovini, Alberto
and Martins, Marcelo Roberto
and Moal, Bertrand
and Morris, Michele
and Mowery, Danielle L
and Murphy, Shawn N
and Neuraz, Antoine
and Ngiam, Kee Yuan
and Okoshi, Marina P
and Omenn, Gilbert S
and Patel, Lav P
and Pedrera Jim{\'e}nez, Miguel
and Prudente, Robson A
and Samayamuthu, Malarkodi Jebathilagam
and Sanz Vidorreta, Fernando J
and Schriver, Emily R
and Schubert, Petra
and Serrano Balazote, Pablo
and Tan, Byorn WL
and Tanni, Suzana E
and Tibollo, Valentina
and Visweswaran, Shyam
and Wagholikar, Kavishwar B
and Xia, Zongqi
and Z{\"o}ller, Daniela
and Kohane, Isaac S
and Cai, Tianxi
and South, Andrew M
and Brat, Gabriel A",
title="International Changes in COVID-19 Clinical Trajectories Across 315 Hospitals and 6 Countries: Retrospective Cohort Study",
journal="J Med Internet Res",
year="2021",
month="Oct",
day="11",
volume="23",
number="10",
pages="e31400",
keywords="SARS-CoV-2; electronic health records; federated study; retrospective cohort study; meta-analysis; COVID-19; severe COVID-19; laboratory trajectory",
abstract="Background: Many countries have experienced 2 predominant waves of COVID-19--related hospitalizations. Comparing the clinical trajectories of patients hospitalized in separate waves of the pandemic enables further understanding of the evolving epidemiology, pathophysiology, and health care dynamics of the COVID-19 pandemic. Objective: In this retrospective cohort study, we analyzed electronic health record (EHR) data from patients with SARS-CoV-2 infections hospitalized in participating health care systems representing 315 hospitals across 6 countries. We compared hospitalization rates, severe COVID-19 risk, and mean laboratory values between patients hospitalized during the first and second waves of the pandemic. Methods: Using a federated approach, each participating health care system extracted patient-level clinical data on their first and second wave cohorts and submitted aggregated data to the central site. Data quality control steps were adopted at the central site to correct for implausible values and harmonize units. Statistical analyses were performed by computing individual health care system effect sizes and synthesizing these using random effect meta-analyses to account for heterogeneity. We focused the laboratory analysis on C-reactive protein (CRP), ferritin, fibrinogen, procalcitonin, D-dimer, and creatinine based on their reported associations with severe COVID-19. Results: Data were available for 79,613 patients, of which 32,467 were hospitalized in the first wave and 47,146 in the second wave. The prevalence of male patients and patients aged 50 to 69 years decreased significantly between the first and second waves. Patients hospitalized in the second wave had a 9.9{\%} reduction in the risk of severe COVID-19 compared to patients hospitalized in the first wave (95{\%} CI 8.5{\%}-11.3{\%}). Demographic subgroup analyses indicated that patients aged 26 to 49 years and 50 to 69 years; male and female patients; and black patients had significantly lower risk for severe disease in the second wave than in the first wave. At admission, the mean values of CRP were significantly lower in the second wave than in the first wave. On the seventh hospital day, the mean values of CRP, ferritin, fibrinogen, and procalcitonin were significantly lower in the second wave than in the first wave. In general, countries exhibited variable changes in laboratory testing rates from the first to the second wave. At admission, there was a significantly higher testing rate for D-dimer in France, Germany, and Spain. Conclusions: Patients hospitalized in the second wave were at significantly lower risk for severe COVID-19. This corresponded to mean laboratory values in the second wave that were more likely to be in typical physiological ranges on the seventh hospital day compared to the first wave. Our federated approach demonstrated the feasibility and power of harmonizing heterogeneous EHR data from multiple international health care systems to rapidly conduct large-scale studies to characterize how COVID-19 clinical trajectories evolve. ",
issn="1438-8871",
doi="10.2196/31400",
url="https://www.jmir.org/2021/10/e31400",
url="https://doi.org/10.2196/31400",
url="http://www.ncbi.nlm.nih.gov/pubmed/34533459"
}