International electronic health record-derived post-acute sequelae profiles of COVID-19 patients
Harrison G. Zhang
(1, 2)
,
Arianna Dagliati
(3)
,
Zahra Shakeri Hossein Abad
(1)
,
Xin Xiong
(4)
,
Clara-Lea Bonzel
(1)
,
Zongqi Xia
(5)
,
Bryce W. Q. Tan
(6)
,
Paul Avillach
(1)
,
Gabriel A. Brat
(1)
,
Chuan Hong
(1, 7)
,
Shyam Visweswaran
(5)
,
Lav P. Patel
(8)
,
Alba Gutierrez-Sacristan
(1)
,
David A. Hanauer
(9)
,
John H. Holmes
(10)
,
Malarkodi Jebathilagam Samayamuthu
(5)
,
Florence T. Bourgeois
(1)
,
Sehi l'Yi
(1)
,
Sarah E. Maidlow
(11)
,
Bertrand Moal
(12)
,
Shawn N. Murphy
(13)
,
Zachary H. Strasser
(13)
,
Antoine Neuraz
(14, 15)
,
Kee Yuan Ngiam
(16)
,
Ne Hooi Will Loh
(16)
,
Gilbert S. Omenn
(11)
,
Andrea Prunotto
(17)
,
Lauren A. Dalvin
(18)
,
Jeffrey G. Klann
(13)
,
Petra Schubert
(19)
,
Fernando J. Sanz Vidorreta
(20)
,
Vincent Benoit
(21)
,
Guillaume Verdy
(12)
,
Ramakanth Kavuluru
(22)
,
Hossein Estiri
(13)
,
Yuan Luo
(23)
,
Alberto Malovini
(24)
,
Valentina Tibollo
(24)
,
Riccardo Bellazzi
(3)
,
Kelly Cho
(19)
,
Yuk-Lam Ho
(19)
,
Amelia L. M. Tan
(1)
,
Byorn W. L. Tan
(6)
,
Nils Gehlenborg
(1)
,
Sara Lozano-Zahonero
(17)
,
Vianney Jouhet
(25, 12)
,
Luca Chiovato
(24)
,
Bruce J. Aronow
(26)
,
Emma M. S. Toh
(27)
,
Wei Gen Scott Wong
(16)
,
Sara Pizzimenti
(28)
,
Kavishwar B Wagholikar
(13)
,
Mauro Bucalo
(29)
,
Tianxi Cai
(1)
,
Andrew M. South
(30)
,
Isaac S. Kohane
(1)
,
Griffin M. Weber
(1)
1
HMS -
Harvard Medical School [Boston]
2 Columbia University [New York]
3 UNIPV - Università degli Studi di Pavia [Italia] = University of Pavia [Italy] = Université de Pavie [Italie]
4 Harvard T.H. Chan School of Public Health
5 PITT - University of Pittsburgh
6 NUH - National University Hospital [Singapore]
7 Duke University [Durham]
8 University of Kansas Medical Center [Kansas City, KS, USA]
9 University of Michigan Medical School [Ann Arbor]
10 University of Pennsylvania
11 University of Michigan [Ann Arbor]
12 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
13 Massachusetts General Hospital [Boston]
14 UPCité - Université Paris Cité
15 Service d'informatique médicale et biostatistiques [CHU Necker]
16 NUHS - National University Health System [Singapore]
17 Albert-Ludwigs-Universität Freiburg = University of Freiburg
18 Mayo Clinic [Rochester]
19 VA Boston Healthcare System
20 UCLA - University of California [Los Angeles]
21 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
22 UK - University of Kentucky
23 Northwestern University [Evanston]
24 IRCCS Pavia - ICS Maugeri - Istituti Clinici Scientifici Maugeri [Pavia]
25 BPH - Bordeaux population health
26 Cincinnati Children's Hospital Medical Center
27 NUS - National University of Singapore
28 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
29 BIOMERIS [Pavia]
30 Wake Forest School of Medicine [Winston-Salem]
2 Columbia University [New York]
3 UNIPV - Università degli Studi di Pavia [Italia] = University of Pavia [Italy] = Université de Pavie [Italie]
4 Harvard T.H. Chan School of Public Health
5 PITT - University of Pittsburgh
6 NUH - National University Hospital [Singapore]
7 Duke University [Durham]
8 University of Kansas Medical Center [Kansas City, KS, USA]
9 University of Michigan Medical School [Ann Arbor]
10 University of Pennsylvania
11 University of Michigan [Ann Arbor]
12 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
13 Massachusetts General Hospital [Boston]
14 UPCité - Université Paris Cité
15 Service d'informatique médicale et biostatistiques [CHU Necker]
16 NUHS - National University Health System [Singapore]
17 Albert-Ludwigs-Universität Freiburg = University of Freiburg
18 Mayo Clinic [Rochester]
19 VA Boston Healthcare System
20 UCLA - University of California [Los Angeles]
21 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
22 UK - University of Kentucky
23 Northwestern University [Evanston]
24 IRCCS Pavia - ICS Maugeri - Istituti Clinici Scientifici Maugeri [Pavia]
25 BPH - Bordeaux population health
26 Cincinnati Children's Hospital Medical Center
27 NUS - National University of Singapore
28 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
29 BIOMERIS [Pavia]
30 Wake Forest School of Medicine [Winston-Salem]
Résumé
The risk profiles of post-acute sequelae of COVID-19 (PASC) have not been well characterized in multi-national settings with appropriate controls. We leveraged electronic health record (EHR) data from 277 international hospitals representing 414,602 patients with COVID-19, 2.3 million control patients without COVID-19 in the inpatient and outpatient settings, and over 221 million diagnosis codes to systematically identify new-onset conditions enriched among patients with COVID-19 during the post-acute period. Compared to inpatient controls, inpatient COVID-19 cases were at significant risk for angina pectoris (RR 1.30, 95% CI 1.09-1.55), heart failure (RR 1.22, 95% CI 1.10-1.35), cognitive dysfunctions (RR 1.18, 95% CI 1.07-1.31), and fatigue (RR 1.18, 95% CI 1.07-1.30). Relative to outpatient controls, outpatient COVID-19 cases were at risk for pulmonary embolism (RR 2.10, 95% CI 1.58-2.76), venous embolism (RR 1.34, 95% CI 1.17-1.54), atrial fibrillation (RR 1.30, 95% CI 1.13-1.50), type 2 diabetes (RR 1.26, 95% CI 1.16-1.36) and vitamin D deficiency (RR 1.19, 95% CI 1.09-1.30). Outpatient COVID-19 cases were also at risk for loss of smell and taste (RR 2.42, 95% CI 1.90-3.06), inflammatory neuropathy (RR 1.66, 95% CI 1.21-2.27), and cognitive dysfunction (RR 1.18, 95% CI 1.04-1.33). The incidence of post-acute cardiovascular and pulmonary conditions decreased across time among inpatient cases while the incidence of cardiovascular, digestive, and metabolic conditions increased among outpatient cases. Our study, based on a federated international network, systematically identified robust conditions associated with PASC compared to control groups, underscoring the multifaceted cardiovascular and neurological phenotype profiles of PASC.
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