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. 2021 Oct 11;23(10):e31400.
doi: 10.2196/31400.

International Changes in COVID-19 Clinical Trajectories Across 315 Hospitals and 6 Countries: Retrospective Cohort Study

Griffin M Weber #  1 , Harrison G Zhang #  1 , Sehi L'Yi #  1 , Clara-Lea Bonzel  1 , Chuan Hong  1 , Paul Avillach  1 , Alba Gutiérrez-Sacristán  1 , Nathan P Palmer  1 , Amelia Li Min Tan  1 , Xuan Wang  1 , William Yuan  1 , Nils Gehlenborg  1 , Anna Alloni  2 , Danilo F Amendola  3 , Antonio Bellasi  4 , Riccardo Bellazzi  5 , Michele Beraghi  6 , Mauro Bucalo  2 , Luca Chiovato  7 , Kelly Cho  8 , Arianna Dagliati  9 , Hossein Estiri  10 , Robert W Follett  11 , Noelia García Barrio  12 , David A Hanauer  13 , Darren W Henderson  14 , Yuk-Lam Ho  8 , John H Holmes  15   16 , Meghan R Hutch  17 , Ramakanth Kavuluru  18 , Katie Kirchoff  19 , Jeffrey G Klann  10 , Ashok K Krishnamurthy  20 , Trang T Le  15 , Molei Liu  21 , Ne Hooi Will Loh  22 , Sara Lozano-Zahonero  23 , Yuan Luo  17 , Sarah Maidlow  24 , Adeline Makoudjou  23 , Alberto Malovini  25 , Marcelo Roberto Martins  26 , Bertrand Moal  27 , Michele Morris  28 , Danielle L Mowery  15 , Shawn N Murphy  29 , Antoine Neuraz  30 , Kee Yuan Ngiam  31 , Marina P Okoshi  32 , Gilbert S Omenn  33 , Lav P Patel  34 , Miguel Pedrera Jiménez  12 , Robson A Prudente  32 , Malarkodi Jebathilagam Samayamuthu  28 , Fernando J Sanz Vidorreta  11 , Emily R Schriver  35 , Petra Schubert  8 , Pablo Serrano Balazote  12 , Byorn Wl Tan  36 , Suzana E Tanni  32 , Valentina Tibollo  25 , Shyam Visweswaran  28 , Kavishwar B Wagholikar  10 , Zongqi Xia  37 , Daniela Zöller  23 ; Consortium For Clinical Characterization Of COVID-19 By EHR (4CE)  38 ; Isaac S Kohane  1 , Tianxi Cai #  1 , Andrew M South #  39 , Gabriel A Brat #  1
Collaborators, Affiliations

International Changes in COVID-19 Clinical Trajectories Across 315 Hospitals and 6 Countries: Retrospective Cohort Study

Griffin M Weber et al. J Med Internet Res. .

Erratum in

  • Authorship Correction: International Changes in COVID-19 Clinical Trajectories Across 315 Hospitals and 6 Countries: Retrospective Cohort Study.
    Weber GM, Zhang HG, L'Yi S, Bonzel CL, Hong C, Avillach P, Gutiérrez-Sacristán A, Palmer NP, Tan ALM, Wang X, Yuan W, Gehlenborg N, Alloni A, Amendola DF, Bellasi A, Bellazzi R, Beraghi M, Bucalo M, Chiovato L, Cho K, Dagliati A, Estiri H, Follett RW, García Barrio N, Hanauer DA, Henderson DW, Ho YL, Holmes JH, Hutch MR, Kavuluru R, Kirchoff K, Klann JG, Krishnamurthy AK, Le TT, Liu M, Loh NHW, Lozano-Zahonero S, Luo Y, Maidlow S, Makoudjou A, Malovini A, Martins MR, Moal B, Morris M, Mowery DL, Murphy SN, Neuraz A, Ngiam KY, Okoshi MP, Omenn GS, Patel LP, Pedrera Jiménez M, Prudente RA, Samayamuthu MJ, Sanz Vidorreta FJ, Schriver ER, Schubert P, Serrano Balazote P, Tan BW, Tanni SE, Tibollo V, Visweswaran S, Wagholikar KB, Xia Z, Zöller D; Consortium for Clinical Characterization of COVID-19 by EHR (4CE); Kohane IS, Cai T, South AM, Brat GA. Weber GM, et al. J Med Internet Res. 2021 Nov 30;23(11):e34625. doi: 10.2196/34625. J Med Internet Res. 2021. PMID: 34889759 Free PMC article.

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.

Keywords: COVID-19; SARS-CoV-2; electronic health records; federated study; laboratory trajectory; meta-analysis; retrospective cohort study; severe COVID-19.

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Conflict of interest statement

Conflicts of Interest: None declared.

Figures

Figure 1
Figure 1
(A) World map with health care systems. (B) Schematic of the federated electronic health record (EHR)-based study involving health care systems from 6 countries. 4CE: Consortium for Clinical Characterization of COVID-19 by EHR; ICD: International Classification of Diseases.
Figure 2
Figure 2
(A) Total hospitalizations in the cohort between the first and second waves. (B) The intensity rate of hospitalizations over time by country.
Figure 3
Figure 3
(A) Prevalence of demographic subgroups in the first and second waves for the entire cohort and estimated absolute risk for severe COVID-19 by demographic subgroup. (B) Country-level demographics of all patients by wave. Error bars indicate 95% CIs. *Significant difference by nonoverlapping 95% CIs.
Figure 4
Figure 4
(A) Absolute risk for severe COVID-19 in the first and second waves. (B) Relative risk of severe COVID-19 in the second compared to the first wave stratified by country. Error bars indicate 95% CIs.
Figure 5
Figure 5
Standardized mean laboratory values (A) and corresponding laboratory testing rates (B) among all patients and those with severe disease in the first and second waves. Error bars indicate 95% CIs.
Figure 6
Figure 6
Laboratory testing rates across hospitalization days in each country. Error bars indicate 95% CIs. Laboratory data for creatinine were unavailable for health care systems in Germany. NA: Not Available.
See this image and copyright information in PMC

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