Overall, 102,473 (16%) of the 638,125 people invited participated: 33,281 (20%) of the 162,957 people who had a positive test, and 69,192 (15%) of the 475,168 invited following only negative tests. We excluded 6,235 participants who had only negative tests recorded but self-reported they had tested positive. Therefore, the study cohort comprised 96,238 participants. Their median age at baseline was 45 (IQR 31-56) years, 39% were male, 91% white, 30% had at least one pre-existing health condition and 16% at least two; and 4% had received at least one COVID-19 vaccination dose prior to their index test (Table 1).
SYMPTOMS DURING ACUTE INFECTION
Among the 33,281 participants who had a positive test, 31,486 (95%) were symptomatic at the time of infection; 1,208 (4%) had one symptom, 1,999 (6%) had two, 2,493 (8%) had three, and 25,786 (82%) had more than three. Overall, 83% reported fatigue at the time of acute infection, 64% headache, 63% change in taste, 63% myalgia, 60% change in smell, 54% cough, 52% fever, 45% breathlessness, 41% loss of appetite, 38% joint pain, 31% sore throat, 23% diarrhea, 21% chest pain, 20% runny nose, 15% abdominal pain, 13% confusion, 13% hoarse voice, 9% hair loss, 8% ear pain, 2% reduced consciousness, and 0.3% seizures. Of those who reported symptom duration, 7,259 (23%) reported <1 week, 13,710 (44%) 1-4 weeks, and 10,489 (33%) >4 weeks.
Of the 96,238 participants, all had at least 6 months follow-up; 19,491 (20%) completed questionnaires at 12 months follow-up and 809 (1%) at eighteen months. At their most recent follow-up, 1,856 (6%) of the 31,486 people who had had symptomatic infections reported that they had not recovered and 13,350 (42%) that they had only partially recovered. Among the 1,342 people whose infection required hospitalization, the figures were 217 (16%) and 797 (59%) respectively and among the 30,096 managed in the community, they were 1,639 (5%) and 12,553 (42%) respectively.
For the 3,941 with serial questionnaire data there was little change in the overall breakdown; at their first follow-up, 316 (8%) had not recovered and 1,866 (47%) had only partially recovered, compared to 324 (8%) and 1,806 (46%) respectively at their most recent follow-up. However, there was some cross-over between groups; 1,453 (37%) remained fully recovered, 1,372 (35%) remained partially recovered, and 175 (4%) continued to report no recovery, while 494 (13%) reported delayed recovery (improvement over time), and 447 (11%) reported relapse (deterioration over time).
Of the 21,525 people with ongoing symptoms following symptomatic infection, the most common were tiredness, headache and muscle aches/weakness (Table 2). However, symptoms were also common among people never infected. Compared with the latter, people who had previous symptomatic infection were significantly more likely to report 24 of the 26 symptoms at follow-up after adjusting for potential confounders (Table 3). After changes in smell and taste, the largest effect sizes were observed for cardiovascular symptoms (breathlessness, chest pain and palpitations) and confusion (Table 3). People with previous symptomatic infection were also more likely to have multiple (³3) symptoms than people never infected (14,236 (45%) vs 19,613 (31%)). There was weak evidence of clustering of musculoskeletal and neuropsychological symptoms following previous symptomatic infection (Supplementary Figure 1).
Routine data were available until January 2022 providing a median (IQR) of 6 (5-8) months follow-up. People who had previous symptomatic infection were not at significantly increased risk of all-cause hospitalization (fully adjusted HR 1.01, 95% CI 0.97-1.05, p=0.575), ICU admission (fully adjusted HR 1.21, 95% CI 0.86-1.71, p=0.268) or all-cause mortality (fully adjusted HR 0.63, 95% CI 0.38-1.02, p=0.061). However, they had a median EQ-5D score of 75 (IQR 60-89) at latest questionnaire follow-up compared with 80 (IQR 63-90) for people never infected (p<0.001). Similarly, people who had had symptomatic infection were significantly more likely to report impaired mobility, housework/chores, working/studying, washing/dressing, exercise/sport, hobbies and relationships after adjusting for potential confounders (Table 4). Asymptomatic SARS-CoV-2 infection was not associated with increased risk of current symptoms, impaired daily activities, reduced quality of life, hospitalization, ICU admission or death.
FACTORS ASSOCIATED WITH OUTCOMES
Following previous symptomatic infection, lack of complete recovery was associated with more severe (hospitalized) initial infection, older age, female sex, deprivation, white ethnicity, and pre-existing health conditions, including respiratory disease and depression (Table 5). Compared to unvaccinated people, people vaccinated prior to symptomatic infection were less likely to report persistent change in smell (HR 0.58, 0.44-0.75), change in taste (HR 0.60, 95% CI 0.46-0.78), problems hearing (HR 0.62, 95% CI 0.45-0.85), poor appetite (HR 0.73, 95% CI 0.53-0.99), balance problems (HR 0.75, 95% CI 0.56-0.99), confusion/difficulty concentrating (HR 0.76, 95% CI 0.61-0.94), and anxiety/depression (HR 0.78, 95% CI 0.65-0.94) at their latest follow-up after adjustment for potential confounders.