Symptoms before and after COVID-19: a population and case-control study using prospective data

Abstract

Background: Some individuals experience prolonged illness after acute coronavirus disease 2019 (COVID-19). We assessed whether pre-infection symptoms affected post-acute COVID illness duration.

Methods: Survival analysis was performed in adults (n=23 452) with community-managed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prospectively self-logging data through the ZOE COVID Symptom Study app, at least weekly, from 8 weeks before to 12 weeks after COVID-19 onset, conditioned on presence versus absence of baseline symptoms (4-8 weeks before COVID-19). A case-control study was performed in 1350 individuals with long illness (≥8 weeks, including 906 individuals (67.1%) with illness ≥12 weeks), matched 1:1 (for age, sex, body mass index, testing week, prior infection, vaccination, smoking, index of multiple deprivation) with 1350 individuals with short illness (<4 weeks). Baseline symptoms were compared between the two groups, and against post-COVID symptoms.

Results: Individuals reporting baseline symptoms had longer COVID-related symptom duration (median 15 days versus 10 days for individuals without baseline symptoms) with baseline fatigue nearly doubling duration. Two-thirds (910 (67.4%) of 1350) of individuals with long illness were asymptomatic beforehand. However, 440 (32.6%) had baseline symptoms, versus 255 (18.9%) of 1350 individuals with short illness (p<0.0001). Baseline symptoms doubled the odds ratio for long illness (2.14, 95% CI 1.78-2.57). Prior comorbidities were more common in individuals with long versus short illness. In individuals with long illness, baseline symptomatic (versus asymptomatic) individuals were more likely to be female, younger, and have prior comorbidities; and baseline and post-acute symptoms, and symptom burden, correlated strongly.

Conclusions: Individuals experiencing symptoms before COVID-19 had longer illness duration and increased odds of long illness. However, many individuals with long illness were well before SARS-CoV-2 infection.

FIGURE 1

Flowchart for study participant selection. LFAT: lateral flow antigen test; MH: mental health; COVID-19: coronavirus disease 2019. ^#: at least one health report logged weekly from 8 weeks before to 12 weeks after commencement of COVID-19; ^¶: body mass index (BMI) <15 kg·m⁻² or BMI >55 kg·m⁻²; age >100 years or age <18 years; no possibility to extract index of multiple deprivation.

FIGURE 2

Symptom prevalence during the baseline period in individuals with long illness versus short illness (descriptive data only, unadjusted for comorbidities, week of testing, prior infection, vaccination status, smoking or index of multiple deprivation).

FIGURE 3

Odds ratios from conditional logistic regression of individual symptoms in individuals with long illness versus short illness (reference group), according to baseline symptom reporting. Model 1: no adjustment; model 2: additionally adjusted for any comorbidity reported at registration; model 3: additionally adjusted for prior mental health diagnosis. Circle size represents baseline symptom prevalence in individuals with short versus long illness duration. Odds ratios are shown as dots with 95% confidence intervals as lines: results in red are significant after adjustment for multiple comparisons.

FIGURE 4

Concordance of symptoms between baseline and post-COVID (coronavirus disease 2019) periods, in individuals with short versus long illness (n=1350 in each group).

FIGURE 5

Odds ratios of symptom concordance (i.e. present in the post-COVID (coronavirus disease 2019) period, if reported at baseline (reference period)) in individuals with long illness. Model 1: adjusted for age, sex, body mass index (BMI), vaccination number, prior infection, week of testing, smoking and index of multiple deprivation; model 2: additionally adjusted for comorbidities reported at registration; model 3: additionally adjusted for prior mental health diagnosis. Circle size refers to symptom prevalence during baseline and post-COVID periods. Symptoms are ordered by decreasing prevalence at baseline. Odds ratios are shown as dots with 95% CI as lines; results in red are significant after adjustment for multiple comparisons.

FIGURE 6

Symptom prevalence by sex in individuals with short and long illness duration, considered during a, c) baseline and b, d) post-COVID (coronavirus disease 2019) periods.

FIGURE 7

Symptom prevalence in individuals with long illness according to baseline symptom reporting (any symptom reported versus no symptom); odds ratios of each individual symptom in the post-COVID (coronavirus disease 2019) period according to baseline symptom reporting (any reported symptom versus no symptom). Red lines indicate significantly increased odds. Symptoms are ordered by decreasing prevalence at baseline.