COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

ISARIC clinical characterisation group

doi:10.1007/s15010-021-01599-5

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

ISARIC clinical characterisation group

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Abstract

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.

Original language	English
Pages (from-to)	889-905
Number of pages	17
Journal	Infection
Volume	49
Issue number	5
DOIs	https://doi.org/10.1007/s15010-021-01599-5
Publication status	Published - 1 Oct 2021

Bibliographical note

Funding Information:
This work was supported by the Department for International Development and Wellcome Trust [215091/Z/18/Z]; the Bill and Melinda Gates Foundation [OPP1209135]. Country-specific support was provided by the Canadian Institutes of Health Research Coronavirus Rapid Research Funding Opportunity [OV2170359]; the Health Research Board Ireland [CTN Award 2014-012]; National Institute for Health Research (NIHR) [award CO-CIN-01]; the Medical Research Council (MRC) [grant MC_PC_19059]; the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford [award 200907]; NIHR HPRU in Respiratory Infections at Imperial College London with PHE [award 200927]; Liverpool Experimental Cancer Medicine Centre [grant reference C18616/A25153]; NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013]; EU Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) [FP7 project 602525]; National Institutes of Health (NIH) [UL1TR002240]; and NIHR Clinical Research Network infrastructure support. We acknowledge the generous support of all ISARIC Partners who have contributed data and expertise to this analysis, with or without dedicated funding. The views expressed are those of the authors and not necessarily those of the funders or institutions listed above.

Funding Information:
We are extremely grateful to the frontline clinical and research staff and volunteers, who collected this data in challenging circumstances, and the generosity of the patients and their families for their individual contributions in these difficult times. This work uses data provided by patients and collected by the health institutions and authorities in each country. In the UK, this study involves the National Health Service as part of their care and support #DataSavesLives. We also acknowledge the support of Jeremy J Farrar, Nahoko Shindo, Devika Dixit, Nipunie Rajapakse, Andrew Davison, Lyndsey Castle, Martha Buckley, Debbie Malden, Katherine Newell, Kwame O’Neill, Emmanuelle Denis, Claire Petersen, Scott Mullaney, Sue MacFarlane, Nicole Maziere, Julien Martinez, Oslem Dincarslan, Annette Lake and the Irish Critical Care Trials Group. We appreciate the strong collaboration of the WHO Clinical Data Platform Team, including Silvia Bertagnolio, Soe Soe Thwin, and Janet Diaz.

Funding Information:
M. Cheng declares grants from McGill Interdisciplinary Initiative in Infection and Immunity, and Canadian Institutes of Health Research; and personal fees from GEn1E Lifesciences (as a member of the scientific advisory board) and nplex biosciences (as a member of the scientific advisory board); M. Cummings and M. O'Donnell participated as investigators for completed and ongoing clinical trials evaluating the efficacy and safety of remdesivir (sponsored by Gilead Sciences) and convalescent plasma (sponsored by Amazon), in hospitalized patients with COVID-19—support for this work is paid to Columbia University; J. C. Holter declared grants from Research Council of Norway [grant 312780], and Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner, during the conduct of the study; A.Kimmoun declared personal fees (payment for lectures) from Baxter, Aguettant, Aspen; D. Kumar declared grants and personal fees from Roche, GSK and Merck, and personal fees from Pfizer and Sanofi; F.X. Lescure declared personal fees (payment for lectures) from Gilead, MSD; and travel/accommodation/meeting expenses from Astellas, Eumedica, MSD; A. Pesenti declared personal fees from Maquet, Novalung/Xenios, Baxter, and Boehringer Ingelheim; S. Shrapnel reported grants from Prince Charles Hospital Foundation during the conduct of the study, and concurrently performed data analytics for the COVID-19 Critical Care Consortium; R. Tedder reports grants from MRC/UKRI during the conduct of the study, and has a patent United Kingdom Patent Application No. 2014047.1 “SARS-CoV-2 antibody detection assay” issued; J. Troost declared personal fees from General Electric and Procter and Gamble.

Publisher Copyright:
© 2021, The Author(s).

Keywords

COVID-19
Case definition
Diagnosis
SARS-CoV-2
Symptoms

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s15010-021-01599-5

Cite this

@article{de748e8570104a95a79caee2dd16737e,

title = "COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study",

abstract = "Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: {\textquoteleft}Typical{\textquoteright} symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.",

keywords = "COVID-19, Case definition, Diagnosis, SARS-CoV-2, Symptoms",

author = "{ISARIC clinical characterisation group} and Abdukahil, {Sheryl Ann} and Ryuzo Abe and Laurent Abel and Lara Absil and Andrew Acker and Shingo Adachi and Elisabeth Adam and Diana Adri{\~a}o and Kate Ainscough and Hssain, {Ali Ait} and Tamlihat, {Younes Ait} and Takako Akimoto and Tala Al-Dabbous and Abdulrahman Al-Fares and {Al Qasim}, Eman and Razi Alalqam and Beatrice Alex and K{\'e}vin Alexandre and Huda Alfoudri and Alidjnou, {Kazali Enagnon} and Jeffrey Aliudin and Clotilde Allavena and Nathalie Allou and Jo{\~a}o Alves and Rita Alves and Maria Amaral and Heidi Ammerlaan and Phoebe Ampaw and Roberto Andini and Claire Andrejak and Andrea Angheben and Fran{\c c}ois Angoulvant and S{\'e}verine Ansart and Massimo Antonelli and {De Brito}, {Carlos Alexandre Antunes} and Yaseen Arabi and Irene Aragao and Antonio Arcadipane and Lukas Arenz and Arlet, {Jean Beno{\^i}t} and Christel Arnold-Day and Lovkesh Arora and Elise Artaud-Macari and Angel Asensio and Assie, {Jean Baptiste} and Meera Chand and Jake Dunning and Samreen Ijaz and Tedder, {Richard S.} and Maria Zambon",

note = "Funding Information: This work was supported by the Department for International Development and Wellcome Trust [215091/Z/18/Z]; the Bill and Melinda Gates Foundation [OPP1209135]. Country-specific support was provided by the Canadian Institutes of Health Research Coronavirus Rapid Research Funding Opportunity [OV2170359]; the Health Research Board Ireland [CTN Award 2014-012]; National Institute for Health Research (NIHR) [award CO-CIN-01]; the Medical Research Council (MRC) [grant MC_PC_19059]; the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford [award 200907]; NIHR HPRU in Respiratory Infections at Imperial College London with PHE [award 200927]; Liverpool Experimental Cancer Medicine Centre [grant reference C18616/A25153]; NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013]; EU Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) [FP7 project 602525]; National Institutes of Health (NIH) [UL1TR002240]; and NIHR Clinical Research Network infrastructure support. We acknowledge the generous support of all ISARIC Partners who have contributed data and expertise to this analysis, with or without dedicated funding. The views expressed are those of the authors and not necessarily those of the funders or institutions listed above. Funding Information: We are extremely grateful to the frontline clinical and research staff and volunteers, who collected this data in challenging circumstances, and the generosity of the patients and their families for their individual contributions in these difficult times. This work uses data provided by patients and collected by the health institutions and authorities in each country. In the UK, this study involves the National Health Service as part of their care and support #DataSavesLives. We also acknowledge the support of Jeremy J Farrar, Nahoko Shindo, Devika Dixit, Nipunie Rajapakse, Andrew Davison, Lyndsey Castle, Martha Buckley, Debbie Malden, Katherine Newell, Kwame O{\textquoteright}Neill, Emmanuelle Denis, Claire Petersen, Scott Mullaney, Sue MacFarlane, Nicole Maziere, Julien Martinez, Oslem Dincarslan, Annette Lake and the Irish Critical Care Trials Group. We appreciate the strong collaboration of the WHO Clinical Data Platform Team, including Silvia Bertagnolio, Soe Soe Thwin, and Janet Diaz. Funding Information: M. Cheng declares grants from McGill Interdisciplinary Initiative in Infection and Immunity, and Canadian Institutes of Health Research; and personal fees from GEn1E Lifesciences (as a member of the scientific advisory board) and nplex biosciences (as a member of the scientific advisory board); M. Cummings and M. O'Donnell participated as investigators for completed and ongoing clinical trials evaluating the efficacy and safety of remdesivir (sponsored by Gilead Sciences) and convalescent plasma (sponsored by Amazon), in hospitalized patients with COVID-19—support for this work is paid to Columbia University; J. C. Holter declared grants from Research Council of Norway [grant 312780], and Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner, during the conduct of the study; A.Kimmoun declared personal fees (payment for lectures) from Baxter, Aguettant, Aspen; D. Kumar declared grants and personal fees from Roche, GSK and Merck, and personal fees from Pfizer and Sanofi; F.X. Lescure declared personal fees (payment for lectures) from Gilead, MSD; and travel/accommodation/meeting expenses from Astellas, Eumedica, MSD; A. Pesenti declared personal fees from Maquet, Novalung/Xenios, Baxter, and Boehringer Ingelheim; S. Shrapnel reported grants from Prince Charles Hospital Foundation during the conduct of the study, and concurrently performed data analytics for the COVID-19 Critical Care Consortium; R. Tedder reports grants from MRC/UKRI during the conduct of the study, and has a patent United Kingdom Patent Application No. 2014047.1 “SARS-CoV-2 antibody detection assay” issued; J. Troost declared personal fees from General Electric and Procter and Gamble. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = oct,

day = "1",

doi = "10.1007/s15010-021-01599-5",

language = "English",

volume = "49",

pages = "889--905",

journal = "Infection",

issn = "0300-8126",

publisher = "Urban und Vogel",

number = "5",

}

TY - JOUR

T1 - COVID-19 symptoms at hospital admission vary with age and sex

T2 - results from the ISARIC prospective multinational observational study

AU - ISARIC clinical characterisation group

AU - Abdukahil, Sheryl Ann

AU - Abe, Ryuzo

AU - Abel, Laurent

AU - Absil, Lara

AU - Acker, Andrew

AU - Adachi, Shingo

AU - Adam, Elisabeth

AU - Adrião, Diana

AU - Ainscough, Kate

AU - Hssain, Ali Ait

AU - Tamlihat, Younes Ait

AU - Akimoto, Takako

AU - Al-Dabbous, Tala

AU - Al-Fares, Abdulrahman

AU - Al Qasim, Eman

AU - Alalqam, Razi

AU - Alex, Beatrice

AU - Alexandre, Kévin

AU - Alfoudri, Huda

AU - Alidjnou, Kazali Enagnon

AU - Aliudin, Jeffrey

AU - Allavena, Clotilde

AU - Allou, Nathalie

AU - Alves, João

AU - Alves, Rita

AU - Amaral, Maria

AU - Ammerlaan, Heidi

AU - Ampaw, Phoebe

AU - Andini, Roberto

AU - Andrejak, Claire

AU - Angheben, Andrea

AU - Angoulvant, François

AU - Ansart, Séverine

AU - Antonelli, Massimo

AU - De Brito, Carlos Alexandre Antunes

AU - Arabi, Yaseen

AU - Aragao, Irene

AU - Arcadipane, Antonio

AU - Arenz, Lukas

AU - Arlet, Jean Benoît

AU - Arnold-Day, Christel

AU - Arora, Lovkesh

AU - Artaud-Macari, Elise

AU - Asensio, Angel

AU - Assie, Jean Baptiste

AU - Chand, Meera

AU - Dunning, Jake

AU - Ijaz, Samreen

AU - Tedder, Richard S.

AU - Zambon, Maria

N1 - Funding Information: This work was supported by the Department for International Development and Wellcome Trust [215091/Z/18/Z]; the Bill and Melinda Gates Foundation [OPP1209135]. Country-specific support was provided by the Canadian Institutes of Health Research Coronavirus Rapid Research Funding Opportunity [OV2170359]; the Health Research Board Ireland [CTN Award 2014-012]; National Institute for Health Research (NIHR) [award CO-CIN-01]; the Medical Research Council (MRC) [grant MC_PC_19059]; the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford [award 200907]; NIHR HPRU in Respiratory Infections at Imperial College London with PHE [award 200927]; Liverpool Experimental Cancer Medicine Centre [grant reference C18616/A25153]; NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013]; EU Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) [FP7 project 602525]; National Institutes of Health (NIH) [UL1TR002240]; and NIHR Clinical Research Network infrastructure support. We acknowledge the generous support of all ISARIC Partners who have contributed data and expertise to this analysis, with or without dedicated funding. The views expressed are those of the authors and not necessarily those of the funders or institutions listed above. Funding Information: We are extremely grateful to the frontline clinical and research staff and volunteers, who collected this data in challenging circumstances, and the generosity of the patients and their families for their individual contributions in these difficult times. This work uses data provided by patients and collected by the health institutions and authorities in each country. In the UK, this study involves the National Health Service as part of their care and support #DataSavesLives. We also acknowledge the support of Jeremy J Farrar, Nahoko Shindo, Devika Dixit, Nipunie Rajapakse, Andrew Davison, Lyndsey Castle, Martha Buckley, Debbie Malden, Katherine Newell, Kwame O’Neill, Emmanuelle Denis, Claire Petersen, Scott Mullaney, Sue MacFarlane, Nicole Maziere, Julien Martinez, Oslem Dincarslan, Annette Lake and the Irish Critical Care Trials Group. We appreciate the strong collaboration of the WHO Clinical Data Platform Team, including Silvia Bertagnolio, Soe Soe Thwin, and Janet Diaz. Funding Information: M. Cheng declares grants from McGill Interdisciplinary Initiative in Infection and Immunity, and Canadian Institutes of Health Research; and personal fees from GEn1E Lifesciences (as a member of the scientific advisory board) and nplex biosciences (as a member of the scientific advisory board); M. Cummings and M. O'Donnell participated as investigators for completed and ongoing clinical trials evaluating the efficacy and safety of remdesivir (sponsored by Gilead Sciences) and convalescent plasma (sponsored by Amazon), in hospitalized patients with COVID-19—support for this work is paid to Columbia University; J. C. Holter declared grants from Research Council of Norway [grant 312780], and Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner, during the conduct of the study; A.Kimmoun declared personal fees (payment for lectures) from Baxter, Aguettant, Aspen; D. Kumar declared grants and personal fees from Roche, GSK and Merck, and personal fees from Pfizer and Sanofi; F.X. Lescure declared personal fees (payment for lectures) from Gilead, MSD; and travel/accommodation/meeting expenses from Astellas, Eumedica, MSD; A. Pesenti declared personal fees from Maquet, Novalung/Xenios, Baxter, and Boehringer Ingelheim; S. Shrapnel reported grants from Prince Charles Hospital Foundation during the conduct of the study, and concurrently performed data analytics for the COVID-19 Critical Care Consortium; R. Tedder reports grants from MRC/UKRI during the conduct of the study, and has a patent United Kingdom Patent Application No. 2014047.1 “SARS-CoV-2 antibody detection assay” issued; J. Troost declared personal fees from General Electric and Procter and Gamble. Publisher Copyright: © 2021, The Author(s).

PY - 2021/10/1

Y1 - 2021/10/1

N2 - Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.

AB - Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.

KW - COVID-19

KW - Case definition

KW - Diagnosis

KW - SARS-CoV-2

KW - Symptoms

UR - http://www.scopus.com/inward/record.url?scp=85109024314&partnerID=8YFLogxK

U2 - 10.1007/s15010-021-01599-5

DO - 10.1007/s15010-021-01599-5

M3 - Article

AN - SCOPUS:85109024314

SN - 0300-8126

VL - 49

SP - 889

EP - 905

JO - Infection

JF - Infection

IS - 5

ER -

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Abstract

Bibliographical note

Keywords

UN SDGs

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