COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study
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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.
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SciScore for 10.1101/2020.10.26.20219519: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was approved by the World Health Organization Ethics Review Committee (RPC571 and RPC572).
Consent: Informed consent was obtained where required by local ethics committees.Randomization To display heterogeneity between countries on the same scale as the fixed effects, we plotted median odds ratios (MOR), which quantify variation between countries by comparing odds of an outcome between randomly chosen persons in different clusters who share covariates [19]. Blinding not detected. Power Analysis not detected. Sex as a biological variable We tested for differences between female and male patients using Wilcoxon rank-sum tests for continuous variables and … SciScore for 10.1101/2020.10.26.20219519: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was approved by the World Health Organization Ethics Review Committee (RPC571 and RPC572).
Consent: Informed consent was obtained where required by local ethics committees.Randomization To display heterogeneity between countries on the same scale as the fixed effects, we plotted median odds ratios (MOR), which quantify variation between countries by comparing odds of an outcome between randomly chosen persons in different clusters who share covariates [19]. Blinding not detected. Power Analysis not detected. Sex as a biological variable We tested for differences between female and male patients using Wilcoxon rank-sum tests for continuous variables and chi-square tests for categorical variables. Table 2: Resources
Software and Algorithms Sentences Resources Investigators from 41 countries used Research Electronic Data Capture (REDCap, version 8.11.11, Vanderbilt University, Nashville, Tenn.) to contribute their data to a central database hosted by the University of Oxford. REDCapsuggested: (REDCap, RRID:SCR_003445)Analyses were performed using R (version 4.0.3, R Foundation for Statistical Computing, Vienna, Austria) with packages including binom, Epi, ggplot2, lme4, sjstats, tableone, and tidyverse. ggplot2suggested: (ggplot2, RRID:SCR_014601)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:However, the study has several limitations. Firstly, almost 80% of patients were recruited in a single country. Moreover, less than 1% of patients were recruited from low- or lower-middle-income countries. Secondly, the cohort overwhelmingly includes older adults, with only 1.8% of the cohort aged 18 years or younger. Thirdly, our analysis includes only patients who were hospitalized with COVID-19 and who had a laboratory-confirmed diagnosis. This patient population is more likely to be severely unwell and more likely to exhibit symptoms typically associated with COVID-19 than people who were managed in the community or whose disease has not been recognized. Accordingly, the reporting of ‘typical’ COVID-19 symptoms in this cohort is likely to be an overestimate of the population prevalence. Symptoms are subjective and cannot be externally verified. Some differences for children may reflect that symptoms could only be recorded if a caregiver recognised the symptom or the child had the appropriate vocabulary to describe it. Similarly, some symptoms may be under-reported in elderly patients if there are difficulties in communication, for example due to delirium. As such, the generalizability of estimates of our symptom prevalence is limited. Similarly, there is a shortage of studies conducted outside of high-income countries: a recent scoping review of clinical characteristics of COVID-19 identified no large cohorts in non-high-income countries except China [8]. The absence of a...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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