Predictive symptoms for COVID-19 in the community: REACT-1 study of over 1 million people
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Abstract
Rapid detection, isolation, and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and investigated whether predictive symptoms differ between the B.1.1.7 (Alpha) lineage (predominating as of April 2021 in the US, UK, and elsewhere) and wild type.
Methods and findings
We obtained throat and nose swabs with valid SARS-CoV-2 PCR test results from 1,147,370 volunteers aged 5 years and above (6,450 positive cases) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This study involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%–27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR-positive samples with N-gene cycle threshold value < 34 ( N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least 1 symptom identified 7 symptoms as jointly and positively predictive of PCR positivity in rounds 2–7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss, and muscle aches. The resulting model (rounds 2–7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same 7 symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although when comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. The main limitations of our study are (i) potential participation bias despite random sampling of named individuals from the National Health Service register and weighting designed to achieve a representative sample of the population of England and (ii) the necessary reliance on self-reported symptoms, which may be prone to recall bias and may therefore lead to biased estimates of symptom prevalence in England.
Conclusions
Where testing capacity is limited, it is important to use tests in the most efficient way possible. We identified a set of 7 symptoms that, when considered together, maximize detection of COVID-19 in the community, including infection with the B.1.1.7 lineage.
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SciScore for 10.1101/2021.02.10.21251480: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization 17 In our stability selection, LASSO models are refitted on 1,000 random subsamples of the data, with a representative proportion of negative and positive tests retained in each subsample. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of our study include that the participants, though randomly selected from the community, may not be fully representative and therefore results may not be directly applicable to …
SciScore for 10.1101/2021.02.10.21251480: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization 17 In our stability selection, LASSO models are refitted on 1,000 random subsamples of the data, with a representative proportion of negative and positive tests retained in each subsample. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of our study include that the participants, though randomly selected from the community, may not be fully representative and therefore results may not be directly applicable to the whole population. However, our sampling procedure, which provided approximately equal numbers of participants in all 315 lower tier local authority areas in England, ensured wide geographical coverage and captured the socio-demographic and ethnic diversity of the population of England. In addition, self-administered questionnaires are subject to possible recall and other biases and therefore may not give an accurate representation of the symptom profiles among the population as a whole. Also, as sampling in each round was cross-sectional, some individuals may have been infected (and had symptoms) more than one week before the swab was obtained, but were no longer symptomatic at the time of the study. Our models with stably selected symptoms have the advantage of increasing the yield of positive tests leading to greater numbers of infected people being required to self-isolate, and therefore reducing the pool of infection in the community. However, this may increase the need to support individuals who may be economically disadvantaged by having to self-isolate. Also, since a high proportion of community infections are non-symptomatic, the majority of infected individuals would still go undetected. Thus, at the same time as widening the availability of testing among symptomatic people, co...
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.
Results from scite Reference Check: We found no unreliable references.
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