Symptom evolution in individuals with ongoing symptomatic COVID-19 and post-COVID-19 syndrome after SARS-CoV-2 vaccination versus influenza vaccination

Background: COVID-19 symptoms may persist beyond acute SARS-CoV-2 infection, as ongoing symptomatic COVID-19 [OSC] (symptom duration 4–12 weeks) and post-COVID syndrome [PCS] (symptom duration ≥12 weeks). Vaccination against SARS-CoV-2 decreases OSC/PCS in individuals subsequently infected with SARS-CoV-2 post-vaccination. Whether vaccination against SARS-CoV-2, or any other vaccinations (such as against influenza) affects symptoms in individuals already experiencing OSC/PCS, more than natural symptom evolution, is unknown. Method: Using data from the ZOE COVID Symptom Study app, two comparative analyses were carried out, both in prospectively-reporting individuals with OSC/PCS: A) symptoms in individuals receiving first vaccination against SARS-CoV-2, compared with unvaccinated individuals, matched for age, sex, BMI and week of test (n=1679 in each group); B) symptoms in individuals receiving vaccination against influenza, compared with unvaccinated individuals, matched for age, sex, BMI, week of test and number of SARS-CoV-2 vaccinations (n=692 in each group). In both analyses, vaccination date (or equivalent time from start of symptoms in the unvaccinated group) was considered as the index time, and symptom evolution was measured by comparing symptoms during the second week before and second week after vaccination. Symptoms were considered by prevalence and burden over the considered periods; all results were adjusted for multiple comparisons. Results: After first vaccination against SARS-CoV-2, many symptoms in individuals with OSC/PCS improved more rapidly than natural history resolution, including the commonly reported symptoms of fatigue (p<0.0001, β=-−0.9 [95% CI: −1.86; −0.67]) and myalgia (p<0.001, β=−0.3 [95% CI: −0.50; −0.12]). No symptom worsened after vaccination. In contrast, there was no improvement in OSC/PCS symptoms beyond natural history resolution after vaccination against influenza. Conclusion: In individuals with OSC/PCS, symptom resolution improved after vaccination against SARS-CoV-2; this was not observed, however, after other vaccinations.