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

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 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 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, 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 short illness. In individuals with long illness, baseline symptomatic ( 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.