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Case Reports
. 2021 Oct;49(5):889-905.
doi: 10.1007/s15010-021-01599-5. Epub 2021 Jun 25.

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

ISARIC Clinical Characterisation Group
Collaborators
Case Reports

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

ISARIC Clinical Characterisation Group. Infection. 2021 Oct.

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.

Keywords: COVID-19; Case definition; Diagnosis; SARS-CoV-2; Symptoms.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Flow of participants in this analysis. ISARIC Core and ISARIC Rapid represent data collected internationally via two sets of case report forms; ISARIC 4C and COVID-19 CCC data were collected on separate databases using aligned case report forms; Non-REDCap data were submitted from additional sites and were collected with different case report forms. 4C, Coronavirus Clinical Characterisation Consortium; CCC, Critical Care Consortium; ISARIC, International Severe Acute Respiratory and emerging Infection Consortium; REDCap, Research Electronic Data Capture; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2.
Fig. 2
Fig. 2
Age-specific prevalence of symptoms at hospital admission. Dark blue bars show symptom present, maroon bars show symptom absent, pale grey bars show missing data
Fig. 3
Fig. 3
Proportions meeting clinical criteria at hospital admission stratified by 10-year age band. Black boxes show the proportion of individuals, with error bars showing 95% confidence intervals calculated using the Clopper–Pearson method. The size of each box is inversely proportional to the variance, so larger boxes indicate greater certainty. Grey boxes with 95% confidence intervals show the proportions in the sensitivity analysis excluding patients recruited in the United Kingdom. In panel A, the three symptoms are from the list of fever, cough, fatigue, headache, myalgia, sore throat, rhinorrhoea, shortness of breath, nausea and vomiting, diarrhoea, and confusion; in panel B the two symptoms are from the list fever, myalgia, headache, and sore throat. Patients with missing data for cough, fever or shortness of breath are excluded from all four plots
Fig. 4
Fig. 4
Odds of symptoms among patients admitted to hospital with COVID-19, stratified by age and sex. Each plot is the result of a logistic regression with a symptom as an outcome. Fixed effects of age in ten-year bands (baseline group 50–60 years) and sex are shown in black boxes with 95% confidence intervals. The size of each square is inversely proportional to the variance of the log odds ratio, so larger boxes indicate greater certainty. Clustering by country is included as a random intercept and heterogeneity is depicted by circles showing the median odds ratio
Fig. 5
Fig. 5
Age- and sex-specific odds of meeting clinical definitions among patients admitted to hospital with COVID-19, stratified by age and sex. Each plot is the result of a logistic regression with a composite group of symptoms as an outcome. Fixed effects of age in ten-year bands (baseline group 50–60 years) and sex are shown in black boxes with 95% confidence intervals. The size of each square is inversely proportional to the variance of the log odds ratio, so larger boxes indicate greater certainty. Clustering by country is included as a random intercept and heterogeneity is depicted by circles showing the median odds ratio. In panel A, the three symptoms are from the list of fever, cough, fatigue, headache, myalgia, sore throat, rhinorrhoea, shortness of breath, nausea and vomiting, diarrhoea, and confusion; in panel B the two symptoms are from the list fever, myalgia, headache, and sore throat. Patients with missing data for cough, fever or shortness of breath are excluded from all four plots
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