Symptom presentation among SARS-CoV-2 positive cases and the impact of COVID-19 vaccination; three prospective household cohorts

BACKGROUND: The symptom burden of Omicron BA.1 and BA.2 in the community and across paediatric and adult age-groups compared to earlier variants of SARS-CoV-2, and the impact of COVID-19 vaccination on the symptom burden is unclear. We aimed to systematically compare the symptom burden of the wild-type and Alpha variant infected individuals versus the Omicron BA.1 and BA.2 infected individuals, using European prospective household studies. METHODS: We combined data from three European prospective household studies conducted during the wild-type and Alpha period (April 2020 to April 2021) and the early Omicron BA.1 and BA.2 dominant period (January to March 2022). All three household transmission studies used similar protocols. Households were prospectively followed from detection of the first SARS-CoV-2 index case until at least day 21 including (repeated) PCR testing, paired serology and daily symptom reporting for all household members. To avoid possible index-case ascertainment bias, we restricted analyses to secondary household cases. Age-stratified SARS-CoV-2 symptom burden was compared for wild-type/Alpha versus Omicron infections and for primary versus primary plus booster series vaccinated adult cases. FINDINGS: In total 216 secondary cases from wild-type/Alpha, and 130 from the Omicron period were included. Unvaccinated children <12 years experienced more symptoms and higher maximum and cumulative severity scores during the Omicron compared to the wild-type/Alpha period (p=0.004, p=0.011 and p=0.075, respectively). In adults, disease duration and maximum and cumulative severity scores were reduced during the Omicron period. Overall, the odds ratios (OR) adjusted for age, gender and prior immunity, showed lower odds of loss of smell or taste during the Omicron period (OR:0.14; 95%CI 0.03-0.50), whereas sore throat (OR:2.23; 95%CI 1.03-4.81), fatigue (OR:2.00; 95%CI 0.98-4.14) and coughing (OR:1.85; 95%CI 0.92-3.78) were more frequent. Comparing primary versus primary plus booster vaccinated adult cases during the Omicron period no differences were observed in disease severity or duration (p[≥]0.12). INTERPRETATION: Upper respiratory tract symptoms are more common in SARS-CoV-2 infections during the Omicron period compared to wild-type/Alpha period, but loss of smell or taste is less frequent. In children, the Omicron variant causes higher symptom burden compared to the wild-type/Alpha. Adults experienced a lower symptom burden possibly due to prior vaccination. However, no significant differences in symptom severity between primary versus primary plus booster series vaccinated adults were observed.