Symptoms After COVID-19 Vaccination in Patients with Post-Acute Sequelae of SARS-CoV-2

From April 23 to July 27, 2021, an online survey was sent to 6987 individuals who previously tested positive for SARS-CoV-2 infection (RT-PCR test) at the outpatient testing center of the Geneva University Hospitals, Switzerland. The survey inquired about post-acute sequelae of SARS-CoV-2 and vaccination status. At the time of the study, the public health recommendations in Switzerland were for previously infected individuals to preferably receive one dose of vaccination only. Data was collected using REDCap v11.0.3 and analyzed using Stata, version 15.1 (StataCorp). The outcome of persistence of symptoms was defined as having any of the following: fatigue, difficulty concentrating or memory loss, loss of or change in smell, loss of or change in taste, shortness of breath, and headache. These six cardinal symptoms were chosen to characterize persistent symptoms post-SARS-CoV-2 based on previous studies. Overall, 2094 participants answered the survey (response rate 29.9%). Of symptomatic participants, n = 1596 reported their symptoms developed after SARS-CoV-2 infection and that their comorbidities, when applicable, pre-dated the infection (characteristics in Table 1 ). Proportions of vaccinated participants included in our study were 47.1% (26.6% one dose, 20.5% two doses), compared to 65.3% of 228 asymptomatic participants (17.5% one dose, 47.8% two doses), and 69.0% of eligible adults in the general population by the end of July 2021 (18.8% one dose, 50.2% two doses). Following vaccination, symptoms disappeared (30.8%) or improved (4.7%) in 35.5% of cases, were stable in 28.7% of cases, and worsened in 3.3% of cases. Symptoms’ evolution was reported as other in 29.0% of cases and 2.6% preferred not to answer. Symptoms’ improvement or worsening occurred within 5 days post-vaccination in 69.6% and 82.3% of cases respectively. Vaccination (one or two doses) was associated with a decreased prevalence of the six cardinal post-SARS-CoV-2 symptoms (adjusted odds ratio, aOR 0.72; 0.56–0.92). Vaccination with 2 doses was associated with a decreased prevalence of dyspnea (aOR 0.34; 0.14–0.82) and change in taste (0.38; 0.18–0.83) as well as a decreased prevalence of any one symptom (aOR 0.60; 0.43–0.83) (details in Fig. 1 ). Associations between vaccination and the post-acute sequelae of SARS-CoV-2 infection, stratified by age groups and sex ( n = 1596). Post-acute sequelae of SARS-CoV-2 were defined as the presence of fatigue, difficulty concentrating or memory loss, loss of or change in smell, loss of or change in taste, shortness of breath, and headache. These six cardinal symptoms were chosen to characterize persistent symptoms in long-COVID patients based on previous studies on the prevalence of symptoms more than 6 months after an infection. Participants answering (“Prefer not to answer”) were not included in this analysis ( n = 8). Participants reporting never having symptoms were not included in this analysis of post-acute sequelae of SARS-CoV-2. Participants received the COVID-19 vaccine (mRNA-1273) of Moderna in 60.7% of cases, and the Comirnaty® (BNT162b2) vaccine of Pfizer/BioNTech in 38.5% of cases. Participants answered the survey on average 250.3 ± 72.1 days from their infection (257.8 ± 70.9 days for vaccinated versus 243.2 ± 72.5 days for non-vaccinated) and on average 40.3 ± 29.2 days after vaccination (range from 0 to 183 days, median 37 days, IQR 19–57). OR: odds ratios; CI: confidence interval. Odds ratios were adjusted for time for infection, age, sex, smoking, and the following comorbidities present prior to the infection: overweight or obese, hypertension, respiratory disease, cardiovascular disease, diabetes, migraine, tension headache, sleeping disorder, anxiety, depression, hypothyroidism, anemia, and chronic fatigue.