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1. Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: International observational federated study based on electronic health records through the 4CE consortium.

Author

Moal B, Orieux A, Ferté T, Neuraz A, Brat GA, Avillach P, Bonzel CL, Cai T, Cho K, Cossin S, Griffier R, Hanauer DA, Haverkamp C, Ho YL, Hong C, Hutch MR, Klann JG, Le TT, Loh NHW, Luo Y, Makoudjou A, Morris M, Mowery DL, Olson KL, Patel LP, Samayamuthu MJ, Sanz Vidorreta FJ, Schriver ER, Schubert P, Verdy G, Visweswaran S, Wang X, Weber GM, Xia Z, Yuan W, Zhang HG, Zöller D, Kohane IS, Boyer A, and Jouhet V

Subjects
Humans, Young Adult, Aged, Adolescent, Adult, Middle Aged, SARS-CoV-2, Cohort Studies, Retrospective Studies, Electronic Health Records, Obesity complications, COVID-19 complications, COVID-19 epidemiology, Respiratory Distress Syndrome etiology, Respiratory Distress Syndrome complications
Abstract

Purpose: In young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population., Methods: A retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS., Results: Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%)., Conclusion: Trough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Moal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2023
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2. Changes in laboratory value improvement and mortality rates over the course of the pandemic: an international retrospective cohort study of hospitalised patients infected with SARS-CoV-2.

Author

Hong C, Zhang HG, L'Yi S, Weber G, Avillach P, Tan BWQ, Gutiérrez-Sacristán A, Bonzel CL, Palmer NP, Malovini A, Tibollo V, Luo Y, Hutch MR, Liu M, Bourgeois F, Bellazzi R, Chiovato L, Sanz Vidorreta FJ, Le TT, Wang X, Yuan W, Neuraz A, Benoit V, Moal B, Morris M, Hanauer DA, Maidlow S, Wagholikar K, Murphy S, Estiri H, Makoudjou A, Tippmann P, Klann J, Follett RW, Gehlenborg N, Omenn GS, Xia Z, Dagliati A, Visweswaran S, Patel LP, Mowery DL, Schriver ER, Samayamuthu MJ, Kavuluru R, Lozano-Zahonero S, Zöller D, Tan ALM, Tan BWL, Ngiam KY, Holmes JH, Schubert P, Cho K, Ho YL, Beaulieu-Jones BK, Pedrera-Jiménez M, García-Barrio N, Serrano-Balazote P, Kohane I, South A, Brat GA, and Cai T

Subjects
Hospitalization, Humans, Retrospective Studies, SARS-CoV-2, COVID-19, Pandemics
Abstract

Objective: To assess changes in international mortality rates and laboratory recovery rates during hospitalisation for patients hospitalised with SARS-CoV-2 between the first wave (1 March to 30 June 2020) and the second wave (1 July 2020 to 31 January 2021) of the COVID-19 pandemic., Design, Setting and Participants: This is a retrospective cohort study of 83 178 hospitalised patients admitted between 7 days before or 14 days after PCR-confirmed SARS-CoV-2 infection within the Consortium for Clinical Characterization of COVID-19 by Electronic Health Record, an international multihealthcare system collaborative of 288 hospitals in the USA and Europe. The laboratory recovery rates and mortality rates over time were compared between the two waves of the pandemic., Primary and Secondary Outcome Measures: The primary outcome was all-cause mortality rate within 28 days after hospitalisation stratified by predicted low, medium and high mortality risk at baseline. The secondary outcome was the average rate of change in laboratory values during the first week of hospitalisation., Results: Baseline Charlson Comorbidity Index and laboratory values at admission were not significantly different between the first and second waves. The improvement in laboratory values over time was faster in the second wave compared with the first. The average C reactive protein rate of change was -4.72 mg/dL vs -4.14 mg/dL per day (p=0.05). The mortality rates within each risk category significantly decreased over time, with the most substantial decrease in the high-risk group (42.3% in March-April 2020 vs 30.8% in November 2020 to January 2021, p<0.001) and a moderate decrease in the intermediate-risk group (21.5% in March-April 2020 vs 14.3% in November 2020 to January 2021, p<0.001)., Conclusions: Admission profiles of patients hospitalised with SARS-CoV-2 infection did not differ greatly between the first and second waves of the pandemic, but there were notable differences in laboratory improvement rates during hospitalisation. Mortality risks among patients with similar risk profiles decreased over the course of the pandemic. The improvement in laboratory values and mortality risk was consistent across multiple countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2022
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3. International Changes in COVID-19 Clinical Trajectories Across 315 Hospitals and 6 Countries: Retrospective Cohort Study.

Author

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, Kohane IS, Cai T, South AM, and Brat GA

Subjects
Adult, Aged, Female, Hospitalization, Hospitals, Humans, Male, Middle Aged, Retrospective Studies, SARS-CoV-2, COVID-19, Pandemics
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., (©Griffin M Weber, Harrison G Zhang, Sehi L'Yi, Clara-Lea Bonzel, Chuan Hong, Paul Avillach, Alba Gutiérrez-Sacristán, Nathan P Palmer, Amelia Li Min Tan, Xuan Wang, William Yuan, Nils Gehlenborg, Anna Alloni, Danilo F Amendola, Antonio Bellasi, Riccardo Bellazzi, Michele Beraghi, Mauro Bucalo, Luca Chiovato, Kelly Cho, Arianna Dagliati, Hossein Estiri, Robert W Follett, Noelia García Barrio, David A Hanauer, Darren W Henderson, Yuk-Lam Ho, John H Holmes, Meghan R Hutch, Ramakanth Kavuluru, Katie Kirchoff, Jeffrey G Klann, Ashok K Krishnamurthy, Trang T Le, Molei Liu, Ne Hooi Will Loh, Sara Lozano-Zahonero, Yuan Luo, Sarah Maidlow, Adeline Makoudjou, Alberto Malovini, Marcelo Roberto Martins, Bertrand Moal, Michele Morris, Danielle L Mowery, Shawn N Murphy, Antoine Neuraz, Kee Yuan Ngiam, Marina P Okoshi, Gilbert S Omenn, Lav P Patel, Miguel Pedrera Jiménez, Robson A Prudente, Malarkodi Jebathilagam Samayamuthu, Fernando J Sanz Vidorreta, Emily R Schriver, Petra Schubert, Pablo Serrano Balazote, Byorn WL Tan, Suzana E Tanni, Valentina Tibollo, Shyam Visweswaran, Kavishwar B Wagholikar, Zongqi Xia, Daniela Zöller, The Consortium For Clinical Characterization Of COVID-19 By EHR (4CE), Isaac S Kohane, Tianxi Cai, Andrew M South, Gabriel A Brat. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 11.10.2021.)

Published
2021
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4. Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortiumResearch in context

Author

Francesca Sperotto, Alba Gutiérrez-Sacristán, Simran Makwana, Xiudi Li, Valerie N. Rofeberg, Tianxi Cai, Florence T. Bourgeois, Gilbert S. Omenn, David A. Hanauer, Carlos Sáez, Clara-Lea Bonzel, Emily Bucholz, Audrey Dionne, Matthew D. Elias, Noelia García-Barrio, Tomás González González, Richard W. Issitt, Kate F. Kernan, Jessica Laird-Gion, Sarah E. Maidlow, Kenneth D. Mandl, Taha Mohseni Ahooyi, Cinta Moraleda, Michele Morris, Karyn L. Moshal, Miguel Pedrera-Jiménez, Mohsin A. Shah, Andrew M. South, Anastasia Spiridou, Deanne M. Taylor, Guillaume Verdy, Shyam Visweswaran, Xuan Wang, Zongqi Xia, Joany M. Zachariasse, Jane W. Newburger, Paul Avillach, James R. Aaron, Atif Adam, Giuseppe Agapito, Adem Albayrak, Giuseppe Albi, Mario Alessiani, Anna Alloni, Danilo F. Amendola, François Angoulvant, Li LLJ. Anthony, Bruce J. Aronow, Fatima Ashraf, Andrew Atz, Vidul Ayakulangara Panickan, Paula S. Azevedo, Rafael Badenes, James Balshi, Ashley Batugo, Brendin R. Beaulieu-Jones, Brett K. Beaulieu-Jones, Douglas S. Bell, Antonio Bellasi, Riccardo Bellazzi, Vincent Benoit, Michele Beraghi, José Luis Bernal-Sobrino, Mélodie Bernaux, Romain Bey, Surbhi Bhatnagar, Alvar Blanco-Martínez, Martin Boeker, John Booth, Silvano Bosari, Robert L. Bradford, Gabriel A. Brat, Stéphane Bréant, Nicholas W. Brown, Raffaele Bruno, William A. Bryant, Mauro Bucalo, Anita Burgun, Mario Cannataro, Aldo Carmona, Anna Maria Cattelan, Charlotte Caucheteux, Julien Champ, Jin Chen, Krista Y. Chen, Luca Chiovato, Lorenzo Chiudinelli, Kelly Cho, James J. Cimino, Tiago K. Colicchio, Sylvie Cormont, Sébastien Cossin, Jean B. Craig, Juan Luis Cruz-Bermúdez, Jaime Cruz-Rojo, Arianna Dagliati, Mohamad Daniar, Christel Daniel, Priyam Das, Batsal Devkota, Rui Duan, Julien Dubiel, Scott L. DuVall, Loic Esteve, Hossein Estiri, Shirley Fan, Robert W. Follett, Thomas Ganslandt, Lana X. Garmire, Nils Gehlenborg, Emily J. Getzen, Alon Geva, Rachel SJ. Goh, Tobias Gradinger, Alexandre Gramfort, Romain Griffier, Nicolas Griffon, Olivier Grisel, Pietro H. Guzzi, Larry Han, Christian Haverkamp, Derek Y. Hazard, Bing He, Darren W. Henderson, Martin Hilka, Yuk-Lam Ho, John H. Holmes, Jacqueline P. Honerlaw, Chuan Hong, Kenneth M. Huling, Meghan R. Hutch, Anne Sophie Jannot, Vianney Jouhet, Mundeep K. Kainth, Kernan F. Kate, Ramakanth Kavuluru, Mark S. Keller, Chris J. Kennedy, Daniel A. Key, Katie Kirchoff, Jeffrey G. Klann, Isaac S. Kohane, Ian D. Krantz, Detlef Kraska, Ashok K. Krishnamurthy, Sehi L'Yi, Judith Leblanc, Guillaume Lemaitre, Leslie Lenert, Damien Leprovost, Molei Liu, Ne Hooi Will Loh, Qi Long, Sara Lozano-Zahonero, Yuan Luo, Kristine E. Lynch, Sadiqa Mahmood, Adeline Makoudjou, Alberto Malovini, Chengsheng Mao, Anupama Maram, Monika Maripuri, Patricia Martel, Marcelo R. Martins, Jayson S. Marwaha, Aaron J. Masino, Maria Mazzitelli, Diego R. Mazzotti, Arthur Mensch, Marianna Milano, Marcos F. Minicucci, Bertrand Moal, Jason H. Moore, Jeffrey S. Morris, Sajad Mousavi, Danielle L. Mowery, Douglas A. Murad, Shawn N. Murphy, Thomas P. Naughton, Carlos Tadeu Breda Neto, Antoine Neuraz, Jane Newburger, Kee Yuan Ngiam, Wanjiku FM. Njoroge, James B. Norman, Jihad Obeid, Marina P. Okoshi, Karen L. Olson, Nina Orlova, Brian D. Ostasiewski, Nathan P. Palmer, Nicolas Paris, Lav P. Patel, Ashley C. Pfaff, Emily R. Pfaff, Danielle Pillion, Sara Pizzimenti, Tanu Priya, Hans U. Prokosch, Robson A. Prudente, Andrea Prunotto, Víctor Quirós-González, Rachel B. Ramoni, Maryna Raskin, Siegbert Rieg, Gustavo Roig-Domínguez, Pablo Rojo, Nekane Romero-Garcia, Paula Rubio-Mayo, Paolo Sacchi, Elisa Salamanca, Malarkodi Jebathilagam Samayamuthu, L. Nelson Sanchez-Pinto, Arnaud Sandrin, Nandhini Santhanam, Janaina C.C. Santos, Fernando J. Sanz Vidorreta, Maria Savino, Emily R. Schriver, Petra Schubert, Juergen Schuettler, Luigia Scudeller, Neil J. Sebire, Pablo Serrano-Balazote, Patricia Serre, Arnaud Serret-Larmande, Zahra Shakeri Hossein Abad, Domenick Silvio, Piotr Sliz, Jiyeon Son, Charles Sonday, Zachary H. Strasser, Amelia LM. Tan, Bryce W.Q. Tan, Byorn W.L. Tan, Suzana E. Tanni, Ana I. Terriza-Torres, Valentina Tibollo, Patric Tippmann, Emma MS. Toh, Carlo Torti, Enrico M. Trecarichi, Andrew K. Vallejos, Gael Varoquaux, Margaret E. Vella, Jill-Jênn Vie, Michele Vitacca, Kavishwar B. Wagholikar, Lemuel R. Waitman, Demian Wassermann, Griffin M. Weber, Martin Wolkewitz, Scott Wong, Xin Xiong, Ye Ye, Nadir Yehya, William Yuan, Janet J. Zahner, Alberto Zambelli, Harrison G. Zhang, Daniela Zöller, Valentina Zuccaro, and Chiara Zucco

Subjects
Multisystem inflammatory syndrome, Paediatric inflammatory multisystem syndrome, COVID-19, SARS-CoV-2, Variants, Pediatrics, Medicine (General), R5-920
Abstract

Summary: Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES −1.18 years [95% CI −2.05, −0.32]), had fewer respiratory symptoms (RD −0.15 [95% CI −0.33, −0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD −0.35 [95% CI −0.64, −0.07]), lower lymphocyte count (ES −0.16 × 109/uL [95% CI −0.30, −0.01]), lower C-reactive protein (ES −28.5 mg/L [95% CI −46.3, −10.7]), and lower troponin (ES −0.14 ng/mL [95% CI −0.26, −0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES −1.6 years [95% CI −2.5, −0.8]), had less frequent SIRS (RD −0.18 [95% CI −0.30, −0.05]), lower lymphocyte count (ES −0.39 × 109/uL [95% CI −0.52, −0.25]), lower troponin (ES −0.16 ng/mL [95% CI −0.30, −0.01]) and less frequently received anticoagulation therapy (RD −0.19 [95% CI −0.37, −0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (−1.3 days [95% CI −2.3, −0.4]). Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding: None.

Published
2023
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5. Characterization of long COVID temporal sub-phenotypes by distributed representation learning from electronic health record data: a cohort studyResearch in Context

Author

Arianna Dagliati, Zachary H. Strasser, Zahra Shakeri Hossein Abad, Jeffrey G. Klann, Kavishwar B. Wagholikar, Rebecca Mesa, Shyam Visweswaran, Michele Morris, Yuan Luo, Darren W. Henderson, Malarkodi Jebathilagam Samayamuthu, Bryce W.Q. Tan, Guillame Verdy, Gilbert S. Omenn, Zongqi Xia, Riccardo Bellazzi, Shawn N. Murphy, John H. Holmes, Hossein Estiri, James R. Aaron, Giuseppe Agapito, Adem Albayrak, Giuseppe Albi, Mario Alessiani, Anna Alloni, Danilo F. Amendola, François Angoulvant, Li L.L.J. Anthony, Bruce J. Aronow, Fatima Ashraf, Andrew Atz, Paul Avillach, Paula S. Azevedo, James Balshi, Brett K. Beaulieu-Jones, Douglas S. Bell, Antonio Bellasi, Vincent Benoit, Michele Beraghi, José Luis Bernal-Sobrino, Mélodie Bernaux, Romain Bey, Surbhi Bhatnagar, Alvar Blanco-Martínez, Clara-Lea Bonzel, John Booth, Silvano Bosari, Florence T. Bourgeois, Robert L. Bradford, Gabriel A. Brat, Stéphane Bréant, Nicholas W. Brown, Raffaele Bruno, William A. Bryant, Mauro Bucalo, Emily Bucholz, Anita Burgun, Tianxi Cai, Mario Cannataro, Aldo Carmona, Charlotte Caucheteux, Julien Champ, Jin Chen, Krista Y. Chen, Luca Chiovato, Lorenzo Chiudinelli, Kelly Cho, James J. Cimino, Tiago K. Colicchio, Sylvie Cormont, Sébastien Cossin, Jean B. Craig, Juan Luis Cruz-Bermúdez, Jaime Cruz-Rojo, Mohamad Daniar, Christel Daniel, Priyam Das, Batsal Devkota, Audrey Dionne, Rui Duan, Julien Dubiel, Scott L. DuVall, Loic Esteve, Shirley Fan, Robert W. Follett, Thomas Ganslandt, Noelia García- Barrio, Lana X. Garmire, Nils Gehlenborg, Emily J. Getzen, Alon Geva, Tobias Gradinger, Alexandre Gramfort, Romain Griffier, Nicolas Griffon, Olivier Grisel, Alba Gutiérrez-Sacristán, Larry Han, David A. Hanauer, Christian Haverkamp, Derek Y. Hazard, Bing He, Martin Hilka, Yuk-Lam Ho, Chuan Hong, Kenneth M. Huling, Meghan R. Hutch, Richard W. Issitt, Anne Sophie Jannot, Vianney Jouhet, Ramakanth Kavuluru, Mark S. Keller, Chris J. Kennedy, Daniel A. Key, Katie Kirchoff, Isaac S. Kohane, Ian D. Krantz, Detlef Kraska, Ashok K. Krishnamurthy, Sehi L'Yi, Trang T. Le, Judith Leblanc, Guillaume Lemaitre, Leslie Lenert, Damien Leprovost, Molei Liu, Ne Hooi Will Loh, Qi Long, Sara Lozano-Zahonero, Kristine E. Lynch, Sadiqa Mahmood, Sarah E. Maidlow, Adeline Makoudjou, Alberto Malovini, Kenneth D. Mandl, Chengsheng Mao, Anupama Maram, Patricia Martel, Marcelo R. Martins, Jayson S. Marwaha, Aaron J. Masino, Maria Mazzitelli, Arthur Mensch, Marianna Milano, Marcos F. Minicucci, Bertrand Moal, Taha Mohseni Ahooyi, Jason H. Moore, Cinta Moraleda, Jeffrey S. Morris, Karyn L. Moshal, Sajad Mousavi, Danielle L. Mowery, Douglas A. Murad, Thomas P. Naughton, Carlos Tadeu Breda Neto, Antoine Neuraz, Jane Newburger, Kee Yuan Ngiam, Wanjiku F.M. Njoroge, James B. Norman, Jihad Obeid, Marina P. Okoshi, Karen L. Olson, Nina Orlova, Brian D. Ostasiewski, Nathan P. Palmer, Nicolas Paris, Lav P. Patel, Miguel Pedrera-Jiménez, Emily R. Pfaff, Ashley C. Pfaff, Danielle Pillion, Sara Pizzimenti, Hans U. Prokosch, Robson A. Prudente, Andrea Prunotto, Víctor Quirós-González, Rachel B. Ramoni, Maryna Raskin, Siegbert Rieg, Gustavo Roig-Domínguez, Pablo Rojo, Paula Rubio-Mayo, Paolo Sacchi, Carlos Sáez, Elisa Salamanca, L. Nelson Sanchez-Pinto, Arnaud Sandrin, Nandhini Santhanam, Janaina C.C. Santos, Fernando J. Sanz Vidorreta, Maria Savino, Emily R. Schriver, Petra Schubert, Juergen Schuettler, Luigia Scudeller, Neil J. Sebire, Pablo Serrano-Balazote, Patricia Serre, Arnaud Serret-Larmande, Mohsin Shah, Domenick Silvio, Piotr Sliz, Jiyeon Son, Charles Sonday, Andrew M. South, Anastasia Spiridou, Amelia L.M. Tan, Byorn W.L. Tan, Suzana E. Tanni, Deanne M. Taylor, Ana I. Terriza-Torres, Valentina Tibollo, Patric Tippmann, Emma M.S. Toh, Carlo Torti, Enrico M. Trecarichi, Yi-Ju Tseng, Andrew K. Vallejos, Gael Varoquaux, Margaret E. Vella, Guillaume Verdy, Jill-Jênn Vie, Michele Vitacca, Lemuel R. Waitman, Xuan Wang, Demian Wassermann, Griffin M. Weber, Martin Wolkewitz, Scott Wong, Xin Xiong, Ye Ye, Nadir Yehya, William Yuan, Alberto Zambelli, Harrison G. Zhang, Daniela Zo¨ller, Valentina Zuccaro, and Chiara Zucco

Subjects
Post-acute sequelae of SARS-CoV-2, PASC, COVID-19, SARS-CoV-2, Electronic health records, Medicine (General), R5-920
Abstract

Summary: Background: Characterizing Post-Acute Sequelae of COVID (SARS-CoV-2 Infection), or PASC has been challenging due to the multitude of sub-phenotypes, temporal attributes, and definitions. Scalable characterization of PASC sub-phenotypes can enhance screening capacities, disease management, and treatment planning. Methods: We conducted a retrospective multi-centre observational cohort study, leveraging longitudinal electronic health record (EHR) data of 30,422 patients from three healthcare systems in the Consortium for the Clinical Characterization of COVID-19 by EHR (4CE). From the total cohort, we applied a deductive approach on 12,424 individuals with follow-up data and developed a distributed representation learning process for providing augmented definitions for PASC sub-phenotypes. Findings: Our framework characterized seven PASC sub-phenotypes. We estimated that on average 15.7% of the hospitalized COVID-19 patients were likely to suffer from at least one PASC symptom and almost 5.98%, on average, had multiple symptoms. Joint pain and dyspnea had the highest prevalence, with an average prevalence of 5.45% and 4.53%, respectively. Interpretation: We provided a scalable framework to every participating healthcare system for estimating PASC sub-phenotypes prevalence and temporal attributes, thus developing a unified model that characterizes augmented sub-phenotypes across the different systems. Funding: Authors are supported by National Institute of Allergy and Infectious Diseases, National Institute on Aging, National Center for Advancing Translational Sciences, National Medical Research Council, National Institute of Neurological Disorders and Stroke, European Union, National Institutes of Health, National Center for Advancing Translational Sciences.

Published
2023
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6. Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort studyResearch in context

Author

Byorn W.L. Tan, Bryce W.Q. Tan, Amelia L.M. Tan, Emily R. Schriver, Alba Gutiérrez-Sacristán, Priyam Das, William Yuan, Meghan R. Hutch, Noelia García Barrio, Miguel Pedrera Jimenez, Noor Abu-el-rub, Michele Morris, Bertrand Moal, Guillaume Verdy, Kelly Cho, Yuk-Lam Ho, Lav P. Patel, Arianna Dagliati, Antoine Neuraz, Jeffrey G. Klann, Andrew M. South, Shyam Visweswaran, David A. Hanauer, Sarah E. Maidlow, Mei Liu, Danielle L. Mowery, Ashley Batugo, Adeline Makoudjou, Patric Tippmann, Daniela Zöller, Gabriel A. Brat, Yuan Luo, Paul Avillach, Riccardo Bellazzi, Luca Chiovato, Alberto Malovini, Valentina Tibollo, Malarkodi Jebathilagam Samayamuthu, Pablo Serrano Balazote, Zongqi Xia, Ne Hooi Will Loh, Lorenzo Chiudinelli, Clara-Lea Bonzel, Chuan Hong, Harrison G. Zhang, Griffin M. Weber, Isaac S. Kohane, Tianxi Cai, Gilbert S. Omenn, John H. Holmes, Kee Yuan Ngiam, James R. Aaron, Giuseppe Agapito, Adem Albayrak, Giuseppe Albi, Mario Alessiani, Anna Alloni, Danilo F. Amendola, François Angoulvant, Li L.L.J. Anthony, Bruce J. Aronow, Fatima Ashraf, Andrew Atz, Vidul Ayakulangara Panickan, Paula S. Azevedo, James Balshi, Brett K. Beaulieu-Jones, Brendin R. Beaulieu-Jones, Douglas S. Bell, Antonio Bellasi, Vincent Benoit, Michele Beraghi, José Luis Bernal-Sobrino, Mélodie Bernaux, Romain Bey, Surbhi Bhatnagar, Alvar Blanco-Martínez, Martin Boeker, John Booth, Silvano Bosari, Florence T. Bourgeois, Robert L. Bradford, Stéphane Bréant, Nicholas W. Brown, Raffaele Bruno, William A. Bryant, Mauro Bucalo, Emily Bucholz, Anita Burgun, Mario Cannataro, Aldo Carmona, Anna Maria Cattelan, Charlotte Caucheteux, Julien Champ, Jin Chen, Krista Y. Chen, James J. Cimino, Tiago K. Colicchio, Sylvie Cormont, Sébastien Cossin, Jean B. Craig, Juan Luis Cruz-Bermúdez, Jaime Cruz-Rojo, Mohamad Daniar, Christel Daniel, Batsal Devkota, Audrey Dionne, Rui Duan, Julien Dubiel, Scott L. DuVall, Loic Esteve, Hossein Estiri, Shirley Fan, Robert W. Follett, Thomas Ganslandt, Noelia García-Barrio, Lana X. Garmire, Nils Gehlenborg, Emily J. Getzen, Alon Geva, Tomás González González, Tobias Gradinger, Alexandre Gramfort, Romain Griffier, Nicolas Griffon, Olivier Grisel, Pietro H. Guzzi, Larry Han, Christian Haverkamp, Derek Y. Hazard, Bing He, Darren W. Henderson, Martin Hilka, Jacqueline P. Honerlaw, Kenneth M. Huling, Richard W. Issitt, Anne Sophie Jannot, Vianney Jouhet, Ramakanth Kavuluru, Mark S. Keller, Chris J. Kennedy, Kate F. Kernan, Daniel A. Key, Katie Kirchoff, Ian D. Krantz, Detlef Kraska, Ashok K. Krishnamurthy, Sehi L'Yi, Trang T. Le, Judith Leblanc, Guillaume Lemaitre, Leslie Lenert, Damien Leprovost, Molei Liu, Qi Long, Sara Lozano-Zahonero, Kristine E. Lynch, Sadiqa Mahmood, Simran Makwana, Kenneth D. Mandl, Chengsheng Mao, Anupama Maram, Monika Maripuri, Patricia Martel, Marcelo R. Martins, Jayson S. Marwaha, Aaron J. Masino, Maria Mazzitelli, Diego R. Mazzotti, Arthur Mensch, Marianna Milano, Marcos F. Minicucci, Taha Mohseni Ahooyi, Jason H. Moore, Cinta Moraleda, Jeffrey S. Morris, Karyn L. Moshal, Sajad Mousavi, Douglas A. Murad, Shawn N. Murphy, Thomas P. Naughton, Carlos Tadeu Breda Neto, Jane Newburger, Wanjiku F.M. Njoroge, James B. Norman, Jihad Obeid, Marina P. Okoshi, Karen L. Olson, Nina Orlova, Brian D. Ostasiewski, Nathan P. Palmer, Nicolas Paris, Miguel Pedrera-Jiménez, Ashley C. Pfaff, Emily R. Pfaff, Danielle Pillion, Sara Pizzimenti, Tanu Priya, Hans U. Prokosch, Robson A. Prudente, Andrea Prunotto, Víctor Quirós-González, Rachel B. Ramoni, Maryna Raskin, Siegbert Rieg, Gustavo Roig-Domínguez, Pablo Rojo, Paula Rubio-Mayo, Paolo Sacchi, Carlos Sáez, Elisa Salamanca, L. Nelson Sanchez-Pinto, Arnaud Sandrin, Nandhini Santhanam, Janaina C.C. Santos, Fernando J. Sanz Vidorreta, Maria Savino, Petra Schubert, Juergen Schuettler, Luigia Scudeller, Neil J. Sebire, Pablo Serrano-Balazote, Patricia Serre, Arnaud Serret-Larmande, Mohsin Shah, Zahra Shakeri Hossein Abad, Domenick Silvio, Piotr Sliz, Jiyeon Son, Charles Sonday, Francesca Sperotto, Anastasia Spiridou, Zachary H. Strasser, Suzana E. Tanni, Deanne M. Taylor, Ana I. Terriza-Torres, Emma M.S. Toh, Carlo Torti, Enrico M. Trecarichi, Andrew K. Vallejos, Gael Varoquaux, Margaret E. Vella, Jill-Jênn Vie, Michele Vitacca, Kavishwar B. Wagholikar, Lemuel R. Waitman, Xuan Wang, Demian Wassermann, Martin Wolkewitz, Scott Wong, Xin Xiong, Ye Ye, Nadir Yehya, Joany M. Zachariasse, Janet J. Zahner, Alberto Zambelli, Valentina Zuccaro, and Chiara Zucco

Subjects
COVID-19, Acute kidney injury, SARS-CoV-2, Chronic kidney disease, Electronic health records, Medicine (General), R5-920
Abstract

Summary: Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings: Advanced age (HR 2.77, 95%CI 2.53–3.04, p

Published
2023
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7. Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: International observational federated study based on electronic health records through the 4CE consortium

Author

Moal, Bertrand, Orieux, Arthur, Ferté, Thomas, Neuraz, Antoine, Brat, Gabriel A, Avillach, Paul, Bonzel, Clara-Lea, Cai, Tianxi, Cho, Kelly, Cossin, Sébastien, Griffier, Romain, Hanauer, David A, Haverkamp, Christian, Ho, Yuk-Lam, Hong, Chuan, Hutch, Meghan R, Klann, Jeffrey G, Le, Trang T, Loh, Ne Hooi Will, Luo, Yuan, Makoudjou, Adeline, Morris, Michele, Mowery, Danielle L, Olson, Karen L, Patel, Lav P, Samayamuthu, Malarkodi J, Sanz Vidorreta, Fernando J, Schriver, Emily R, Schubert, Petra, Verdy, Guillaume, Visweswaran, Shyam, Wang, Xuan, Weber, Griffin M, Xia, Zongqi, Yuan, William, Zhang, Harrison G, Zöller, Daniela, Kohane, Isaac S, Consortium for Clinical Characterization of COVID-19 by EHR (4CE), Boyer, Alexandre, Jouhet, Vianney, and Chen, Robert Jeenchen

Subjects
Adult, Adolescent, General Science & Technology, Consortium for Clinical Characterization of COVID-19 by EHR, Cohort Studies, Young Adult, Rare Diseases, Clinical Research, Humans, Electronic Health Records, Obesity, Aetiology, Lung, Acute Respiratory Distress Syndrome, Retrospective Studies, Aged, Respiratory Distress Syndrome, SARS-CoV-2, Prevention, COVID-19, Middle Aged, Infectious Diseases, Emerging Infectious Diseases, Good Health and Well Being, Patient Safety, 2.4 Surveillance and distribution
Abstract

PurposeIn young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population.MethodsA retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS.ResultsAmong the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%).ConclusionTrough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

Published
2023

8. Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: International observational federated study based on electronic health records through the 4CE consortium

Author

Bertrand, Moal, Arthur, Orieux, Thomas, Ferté, Antoine, Neuraz, Gabriel A, Brat, Paul, Avillach, Clara-Lea, Bonzel, Tianxi, Cai, Kelly, Cho, Sébastien, Cossin, Romain, Griffier, David A, Hanauer, Christian, Haverkamp, Yuk-Lam, Ho, Chuan, Hong, Meghan R, Hutch, Jeffrey G, Klann, Trang T, Le, Ne Hooi Will, Loh, Yuan, Luo, Adeline, Makoudjou, Michele, Morris, Danielle L, Mowery, Karen L, Olson, Lav P, Patel, Malarkodi J, Samayamuthu, Fernando J, Sanz Vidorreta, Emily R, Schriver, Petra, Schubert, Guillaume, Verdy, Shyam, Visweswaran, Xuan, Wang, Griffin M, Weber, Zongqi, Xia, William, Yuan, Harrison G, Zhang, Daniela, Zöller, Isaac S, Kohane, Alexandre, Boyer, and Vianney, Jouhet

Subjects
Adult, Respiratory Distress Syndrome, Multidisciplinary, Adolescent, SARS-CoV-2, COVID-19, Middle Aged, Cohort Studies, Young Adult, Humans, Electronic Health Records, Obesity, Aged, Retrospective Studies
Abstract

Purpose In young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population. Methods A retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS. Results Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%). Conclusion Trough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

Published
2023

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

Author

Weber, Griffin M, Zhang, Harrison G, L'Yi, Sehi, Bonzel, Clara-Lea, Hong, Chuan, Avillach, Paul, Gutiérrez-Sacristán, Alba, Palmer, Nathan P, Tan, Amelia Li Min, Wang, Xuan, Yuan, William, Gehlenborg, Nils, Alloni, Anna, Amendola, Danilo F, Bellasi, Antonio, Bellazzi, Riccardo, Beraghi, Michele, Bucalo, Mauro, Chiovato, Luca, Cho, Kelly, Dagliati, Arianna, Estiri, Hossein, Follett, Robert W, García Barrio, Noelia, Hanauer, David A, Henderson, Darren W, Ho, Yuk-Lam, Holmes, John H, Hutch, Meghan R, Kavuluru, Ramakanth, Kirchoff, Katie, Klann, Jeffrey G, Krishnamurthy, Ashok K, Le, Trang T, Liu, Molei, Loh, Ne Hooi Will, Lozano-Zahonero, Sara, Luo, Yuan, Maidlow, Sarah, Makoudjou, Adeline, Malovini, Alberto, Martins, Marcelo Roberto, Moal, Bertrand, Morris, Michele, Mowery, Danielle L, Murphy, Shawn N, Neuraz, Antoine, Ngiam, Kee Yuan, Okoshi, Marina P, Omenn, Gilbert S, Patel, Lav P, Pedrera Jiménez, Miguel, Prudente, Robson A, Samayamuthu, Malarkodi Jebathilagam, Sanz Vidorreta, Fernando J, Schriver, Emily R, Schubert, Petra, Serrano Balazote, Pablo, Tan, Byorn WL, Tanni, Suzana E, Tibollo, Valentina, Visweswaran, Shyam, Wagholikar, Kavishwar B, Xia, Zongqi, Zöller, Daniela, Kohane, Isaac S, Cai, Tianxi, South, Andrew M, and Brat, Gabriel A

Subjects
Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, SARS-CoV-2, COVID-19, Health Informatics, Retrospective cohort study, Middle Aged, Corrigenda and Addenda, Hospitals, Hospitalization, Family medicine, medicine, Humans, Female, business, Pandemics, Aged, Retrospective Studies
Abstract

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.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.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.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.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.

Published
2021

10. Multinational characterization of neurological phenotypes in patients hospitalized with COVID-19

Author

Le, Trang, Gutiérrez-Sacristán, Alba, Son, Jiyeon, Hong, Chuan, South, Andrew, Beaulieu-Jones, Brett, Loh, Ne Hooi Will, Luo, Yuan, Morris, Michele, Ngiam, Kee Yuan, Patel, Lav, Samayamuthu, Malarkodi, Schriver, Emily, Tan, Amelia, Moore, Jason, Cai, Tianxi, Omenn, Gilbert, Avillach, Paul, Kohane, Isaac, Visweswaran, Shyam, Mowery, Danielle, Xia, Zongqi, Aaron, James, Agapito, Giuseppe, Albayrak, Adem, Alessiani, Mario, Amendola, Danilo, Angoulvant, François, Anthony, Li, Aronow, Bruce, Atz, Andrew, Balshi, James, Bell, Douglas, Bellasi, Antonio, Bellazzi, Riccardo, Benoit, Vincent, Beraghi, Michele, Bernal Sobrino, José Luis, Bernaux, Mélodie, Bey, Romain, Blanco Martínez, Alvar, Boeker, Martin, Bonzel, Clara-Lea, Booth, John, Bosari, Silvano, Bourgeois, Florence, Bradford, Robert, Brat, Gabriel, Bréant, Stéphane, Brown, Nicholas, Bryant, William, Bucalo, Mauro, Burgun, Anita, Cannataro, Mario, Carmona, Aldo, Caucheteux, Charlotte, Champ, Julien, Chen, Krista, Chen, Jin, Chiovato, Luca, Chiudinelli, Lorenzo, Cimino, James, Colicchio, Tiago, Cormont, Sylvie, Cossin, Sébastien, Craig, Jean, Cruz Bermúdez, Juan Luis, Cruz Rojo, Jaime, Dagliati, Arianna, Daniar, Mohamad, Daniel, Christel, Davoudi, Anahita, Devkota, Batsal, Dubiel, Julien, Esteve, Loic, Fan, Shirley, Follett, Robert, Gaiolla, Paula, Ganslandt, Thomas, García Barrio, Noelia, Garmire, Lana, Gehlenborg, Nils, Geva, Alon, Gradinger, Tobias, Gramfort, Alexandre, Griffier, Romain, Griffon, Nicolas, Grisel, Olivier, Hanauer, David, Haverkamp, Christian, He, Bing, Henderson, Darren, Hilka, Martin, Holmes, John, Horki, Petar, Huling, Kenneth, Hutch, Meghan, Issitt, Richard, Jannot, Anne Sophie, Jouhet, Vianney, Kavuluru, Ramakanth, Keller, Mark, Kirchoff, Katie, Klann, Jeffrey, Krantz, Ian, Kraska, Detlef, Krishnamurthy, Ashok, L’yi, Sehi, Leblanc, Judith, Leite, Andressa, Lemaitre, Guillaume, Lenert, Leslie, Leprovost, Damien, Liu, Molei, Lozano-Zahonero, Sarah, Lynch, Kristine, Mahmood, Sadiqa, Maidlow, Sarah, Makoudjou Tchendjou, Adeline, Malovini, Alberto, Mandl, Kenneth, Mao, Chengsheng, Maram, Anupama, Martel, Patricia, Masino, Aaron, Matheny, Michael, Maulhardt, Thomas, Mazzitelli, Maria, Mcduffie, Michael, Mensch, Arthur, Ashraf, Fatima, Milano, Marianna, Minicucci, Marcos, Moal, Bertrand, Moraleda, Cinta, Morris, Jeffrey, Moshal, Karyn, Mousavi, Sajad, Murad, Douglas, Murphy, Shawn, Naughton, Thomas, Neuraz, Antoine, Norman, James, Obeid, Jihad, Okoshi, Marina, Olson, Karen, Orlova, Nina, Ostasiewski, Brian, Palmer, Nathan, Paris, Nicolas, Pedrera Jimenez, Miguel, Pfaff, Emily, Pillion, Danielle, Prokosch, Hans, Prudente, Robson, Quirós González, Víctor, Ramoni, Rachel, Raskin, Maryna, Rieg, Siegbert, Roig Domínguez, Gustavo, Rojo, Pablo, Sáez, Carlos, Salamanca, Elisa, Sandrin, Arnaud, Santos, Janaina, Savino, Maria, Schuettler, Juergen, Scudeller, Luigia, Sebire, Neil, Balazote, Pablo Serrano, Serre, Patricia, Serret-Larmande, Arnaud, Shakeri, Zahra, Silvio, Domenick, Sliz, Piotr, Sonday, Charles, Spiridou, Anastasia, Tan, Bryce, Tan, Byorn, Tanni, Suzana, Taylor, Deanne, Terriza-Torres, Ana, Tibollo, Valentina, Tippmann, Patric, Torti, Carlo, Trecarichi, Enrico, Tseng, Yi-Ju, Vallejos, Andrew, Varoquaux, Gael, Vella, Margaret, Vie, Jill-Jênn, Vitacca, Michele, Wagholikar, Kavishwar, Waitman, Lemuel, Wassermann, Demian, Weber, Griffin, William, Yuan, Yehya, Nadir, Zambelli, Alberto, Zhang, Harrison, Zoeller, Daniela, Zucco, Chiara, Unité d'informatique médicale, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), AS is funded by National Institutes of Health (NIH) National Heart Lung, and Blood Institute (NHLBI) K23HL148394 and L40HL148910, and NIH-National Center for Advancing Translational Sciences (NCATS) UL1TR001420. JM is funded by NIH-National Institute of Allergy and Infectious Disease (NIAD) AI11679. LP is funded by NCATS Clinical and Translational Science Award (CTSA) Number UL1TR002366. GO is funded by NIH National Institute of Environmental Health Sciences (NIEHS) P30ES017885 and National Cancer Institute (NCI) U24CA210967. SV is funded by NIH-National Library of Medicine (NLM) R01LM012095 and NCATS UL1TR001857. DM is funded by NCATS CTSA Number UL1-TR001878. ZX is funded by NIH National Institute of Neurological Disorders and Stroke (NINDS) R01NS098023., Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Cancer Institute, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), University of Pennsylvania Perelman School of Medicine, Harvard Medical School, University of Pittsburgh, Wake Forest School of Medicine, National University Health Systems, Northwestern University, University of Kansas Medical Center, University of Pennsylvania Health System, University of Michigan, University of Kentucky, University Magna Graecia of Catanzaro, INC., Lombardia Region Health System, Universidade Estadual Paulista (UNESP), Assistance Publique-Hôpitaux de Paris, Tan Tock Seng Hospital, University of Cincinnati, Medical University of South Carolina, St. Luke’s University Health Network, David Geffen School of Medicine at UCLA, ASST Papa Giovanni XXIII, University of Pavia, APHP Greater Paris University Hospital, ASST Pavia, Hospital Universitario, University of Freiburg, Informatics and Virtual Environments (DRIVE), IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, University of North Carolina, BIOMERIS (BIOMedical Research Informatics Solutions), CEA, LIRMM, Boston Children’s Hospital, Istituti Clinici Scientifici Maugeri SpA SB IRCCS, University of Alabama at Birmingham, Bordeaux University Hospital/ERIAS-Inserm U1219 BPH, Children’s Hospital of Philadelphia, Inria Centre de Paris, Heidelberg University, and Pain Medicine Boston Children’s Hospital, University of Michigan Medical School, MSHI Medical University of South Carolina, Massachusetts General Hospital, The Children’s Hospital of Philadelphia, University Hospital, Clevy.io, Harvard T.H. Chan School of Public Health, VA Salt Lake City Health Care System, Veterans Affairs Medical Center, PSL Université Paris, School of Biomedical Informatics, Great Ormond Street Hospital for Children, University of Erlangen-Nürnberg, Office of Research and Development, Universitat Politècnica de València, Nurse Department of FMB-Medicine School of Botucatu, FAU Erlangen-Nürnberg, National University Hospital, Chang Gung University, Medical College of Wisconsin, McGill University, Inria Lille, ICS S Maugeri IRCCS, University of Missouri, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), and Université Paris Cité (UPC)

Subjects
Male, Epidemiology, Cross-sectional study, Disease, Severity of Illness Index, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Child, Prevalence, MESH: COVID-19, 030212 general & internal medicine, Young adult, Child, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Multidisciplinary, MESH: Infant, Newborn, Middle Aged, MESH: Infant, 3. Good health, Neurology, MESH: Young Adult, Child, Preschool, Medicine, Female, Encephalitis, Adult, MESH: Pandemics, medicine.medical_specialty, Adolescent, Science, Myelitis, MESH: Nervous System Diseases, Article, Young Adult, 03 medical and health sciences, Medical research, MESH: Cross-Sectional Studies, MESH: Severity of Illness Index, Internal medicine, Severity of illness, medicine, Humans, Pandemics, MESH: Prevalence, Aged, MESH: Adolescent, MESH: Humans, business.industry, MESH: Child, Preschool, Infant, Newborn, COVID-19, Infant, MESH: Adult, medicine.disease, MESH: Male, Confidence interval, Cross-Sectional Studies, Relative risk, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Nervous System Diseases, business, MESH: Female, Neurological disorders, 030217 neurology & neurosurgery
Abstract

Made available in DSpace on 2022-04-29T08:35:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Division of Intramural Research, National Institute of Allergy and Infectious Diseases Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases National Institute of Allergy and Infectious Diseases National Center for Advancing Translational Sciences National Heart, Lung, and Blood Institute National Institute of Environmental Health Sciences U.S. National Library of Medicine National Institute of Neurological Disorders and Stroke Division of Cancer Prevention, National Cancer Institute Neurological complications worsen outcomes in COVID-19. To define the prevalence of neurological conditions among hospitalized patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test in geographically diverse multinational populations during early pandemic, we used electronic health records (EHR) from 338 participating hospitals across 6 countries and 3 continents (January–September 2020) for a cross-sectional analysis. We assessed the frequency of International Classification of Disease code of neurological conditions by countries, healthcare systems, time before and after admission for COVID-19 and COVID-19 severity. Among 35,177 hospitalized patients with SARS-CoV-2 infection, there was an increase in the proportion with disorders of consciousness (5.8%, 95% confidence interval [CI] 3.7–7.8%, pFDR < 0.001) and unspecified disorders of the brain (8.1%, 5.7–10.5%, pFDR < 0.001) when compared to the pre-admission proportion. During hospitalization, the relative risk of disorders of consciousness (22%, 19–25%), cerebrovascular diseases (24%, 13–35%), nontraumatic intracranial hemorrhage (34%, 20–50%), encephalitis and/or myelitis (37%, 17–60%) and myopathy (72%, 67–77%) were higher for patients with severe COVID-19 when compared to those who never experienced severe COVID-19. Leveraging a multinational network to capture standardized EHR data, we highlighted the increased prevalence of central and peripheral neurological phenotypes in patients hospitalized with COVID-19, particularly among those with severe disease. Department of Biostatistics Epidemiology and Informatics University of Pennsylvania Perelman School of Medicine Department of Biomedical Informatics Harvard Medical School Department of Neurology University of Pittsburgh, Biomedical Science Tower 3, Suite 7014, 3501 5th Avenue Department of Pediatrics Wake Forest School of Medicine Department of Critical Care National University Health Systems Department of Preventive Medicine Northwestern University Department of Biomedical Informatics University of Pittsburgh Department of Surgery National University Health Systems Department of Internal Medicine University of Kansas Medical Center Data Analytics Center University of Pennsylvania Health System Department of Computational Medicine and Bioinformatics University of Michigan Department of Biomedical Informatics University of Kentucky Department of Legal Economic and Social Sciences University Magna Graecia of Catanzaro Health Catalyst INC. Department of Surgery ASST Pavia Lombardia Region Health System Clinical Research Unit of Botucatu Medical School São Paulo State University Pediatric Emergency Department Hôpital Necker-Enfants Malades Assistance Publique-Hôpitaux de Paris National Center for Infectious Diseases Tan Tock Seng Hospital Departments of Biomedical Informatics Pediatrics Cincinnati Children’s Hospital Medical Center University of Cincinnati Department of Pediatrics Medical University of South Carolina Department of Surgery St. Luke’s University Health Network Department of Medicine David Geffen School of Medicine at UCLA UOC Ricerca Innovazione e Brand Reputation ASST Papa Giovanni XXIII Department of Electrical Computer and Biomedical Engineering University of Pavia IT Department Innovation & Data APHP Greater Paris University Hospital I.T. Department ASST Pavia Health Informatics Hospital Universitario, 12 de Octubre Strategy and Transformation Department APHP Greater Paris University Hospital Faculty of Medicine and Medical Center University of Freiburg Digital Research Informatics and Virtual Environments (DRIVE), Great Ormond Street Hospital for Children Scientific Direction IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano North Carolina Translational and Clinical Sciences (NC TraCS) Institute University of North Carolina BIOMERIS (BIOMedical Research Informatics Solutions) Department of Biomedical Informatics HEGP APHP Greater Paris University Hospital Department of Medical and Surgical Sciences Data Analytics Research Center University Magna Graecia of Catanzaro Department of Anesthesia St. Luke’s University Health Network Université Paris-Saclay Inria CEA INRIA Sophia-Antipolis–ZENITH Team LIRMM Computational Health Informatics Program Boston Children’s Hospital Department of Internal Medicine University of Kentucky Unit of Internal Medicine and Endocrinology Istituti Clinici Scientifici Maugeri SpA SB IRCCS Department of Internal Medicine and Therapeutics University of Pavia Informatics Institute University of Alabama at Birmingham IAM Unit Bordeaux University Hospital/ERIAS-Inserm U1219 BPH Biomedical Informatics Center Medical University of South Carolina Clinical Research Informatics Boston Children’s Hospital Department of Biomedical and Health Informatics Children’s Hospital of Philadelphia SED/SIERRA Inria Centre de Paris Health Information Technology & Services University of Michigan Internal Medicine Department Botucatu Medical School São Paulo State University Heinrich-Lanz-Center for Digital Health University Medicine Mannheim Heidelberg University Department of Anesthesiology Critical Care and Pain Medicine Boston Children’s Hospital Department of Learning Health Sciences University of Michigan Medical School MSHI Medical University of South Carolina Department of Medicine Massachusetts General Hospital Division of Human Genetics Department of Pediatrics The Children’s Hospital of Philadelphia Center for Medical Information and Communication Technology University Hospital Renaissance Computing Institute/Department of Computer Science University of North Carolina Clinical Research Unit Saint Antoine Hospital APHP Greater Paris University Hospital Clevy.io Department of Biostatistics Harvard T.H. Chan School of Public Health VA Informatics and Computing Infrastructure VA Salt Lake City Health Care System MICHR Informatics University of Michigan Laboratory of Informatics and Systems Engineering for Clinical Research Istituti Clinici Scientifici Maugeri SpA SB IRCCS Harvard Catalyst Harvard Medical School Clinical Research Unit Paris Saclay APHP Greater Paris University Hospital Department of Anesthesiology and Critical Care Children’s Hospital of Philadelphia VA Informatics and Computing Infrastructure Tennessee Valley Healthcare System Veterans Affairs Medical Center École Normale Supérieure PSL Université Paris BIG-ARC The University of Texas Health Science Center at Houston School of Biomedical Informatics Pediatric Infectious Disease Department Hospital Universitario, 12 de Octubre Department of Infectious Diseases Great Ormond Street Hospital for Children Department of Neurology Massachusetts General Hospital Internal Medicine Department of Botucatu Medical School São Paulo State University Department of Pediatrics Boston Children’s Hospital Center for Biomedical Informatics Wake Forest School of Medicine Department of Medical Informatics University of Erlangen-Nürnberg Department of Veterans Affairs Office of Research and Development Biomedical Data Science Lab ITACA Institute Universitat Politècnica de València Nurse Department of FMB-Medicine School of Botucatu Management Engineering ASST Pavia Lombardia Region Health System Department of Anesthesiology University Hospital Erlangen FAU Erlangen-Nürnberg Critical Care Medicine Department of Medicine St. Luke’s University Health Network Department of Medicine National University Hospital Department of Information Management Chang Gung University Clinical & Translational Science Institute Medical College of Wisconsin Montréal Neurological Institute McGill University SequeL Inria Lille Respiratory Department ICS S Maugeri IRCCS Department of Health Management and Informatics University of Missouri Department of Oncology ASST Papa Giovanni XXIII Clinical Research Unit of Botucatu Medical School São Paulo State University Internal Medicine Department Botucatu Medical School São Paulo State University Internal Medicine Department of Botucatu Medical School São Paulo State University Division of Intramural Research, National Institute of Allergy and Infectious Diseases: AI11679 Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases: AI11679 National Institute of Allergy and Infectious Diseases: AI11679 National Center for Advancing Translational Sciences: CTSA Award #UL1TR001878 National Center for Advancing Translational Sciences: CTSA Award #UL1TR002366 National Heart, Lung, and Blood Institute: K23HL148394 National Institute of Environmental Health Sciences: P30ES017885 U.S. National Library of Medicine: R01LM012095 National Institute of Neurological Disorders and Stroke: R01NS098023 Division of Cancer Prevention, National Cancer Institute: U24CA210967 National Center for Advancing Translational Sciences: UL1TR001420 National Center for Advancing Translational Sciences: UL1TR001857

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2021

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