Variant-specific symptoms of COVID-19 in a study of 1,542,510 adults in England

Abstract

Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study monitored the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell or taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and effects on daily activities will become increasingly important.

Fig. 1. Study population flow-chart.

Variant prevalence data in bottom panel is from GISAID.

Fig. 2. Comparison of ORs for swab positivity based on presence or absence of any of 26 symptoms surveyed in N = 1,542,510 participants across five variant-phases of REACT-1.

ORs are derived from logistic regression models with swab positive (1/0) as the outcome variable, adjusted for age, sex and vaccination status. Error bars show 95% confidence intervals. ORs are higher for BA.2 than BA.1 for all symptoms. Fever and cough have the highest ORs for BA.2 and BA.1, while loss or change of smell or taste have the highest ORs in all previous variants.

Fig. 3. Results of LASSO stability selection proportions with swab positive/negative as the binary outcome variable and each of 26 symptoms as predictors, for five SARS-CoV-2 variants in England.

Age, sex and, where appropriate, vaccination status are forced into the models as unpenalised variables; regression coefficients for the symptoms are constrained to be positive. The selection proportion indicates the proportion of LASSO models, trained on subsamples of the data, in which each symptom was selected as a predictor.

Fig. 4. ORs for infection with BA.2 vs BA.1 among swab-positive respondents.

ORs are derived from (i) logistic regression models with BA.2 vs BA.1 as the binary outcome variable, and presence or absence of any of 26 symptoms as explanatory variables, adjusted for age group, sex, round and vaccination status, among N = 5598 swab-positive individuals with either BA.2 or BA.1 in rounds 17–19 (5 January to 31 March 2022); and (ii) conditional logistic regression models with BA.2 vs BA.1 as the outcome variable among 1510 swab-positive individuals with either the BA.2 or BA.1 variant in rounds 17–19, matched 1:1 on age (±5 years), sex, vaccination status and round. In left panel, bars show 95% confidence intervals, and symptoms are ordered by mean OR across both models. Right panel directly plots the ORs from the two models for comparison. In both analyses, infection with BA.2 (vs BA.1) is positively associated with chest pain, severe fatigue, runny nose, muscle aches, sneezing, fever, chills, tiredness, blocked nose and headache; in unmatched analysis, infection with BA.2 is further associated with sore eyes, appetite loss and new persistent cough.

Fig. 5. Results of linear regression models with N-gene Ct values as the outcome variable and symptoms as individual predictors, adjusted for age, sex and, where appropriate, vaccination status, among N = 10,709 swab-positive respondents in rounds 17–19 (5 January to 31 March 2022).

Error bars show 95% confidence intervals. Fever, chills, and sore throat are the symptoms with the strongest negative association with Ct value, each associated with approximately a tenfold increase in viral load.