Post-acute symptoms four months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study (preprint)

ABSTRACT

ObjectivesTo evaluate the effects of the Omicron variant on the post-acute symptoms, four months after infection with SARS-CoV-2. DesignA nationwide questionnaire study. SettingDenmark. Participants44,004 individuals aged 15 years or older with either a SARS-CoV-2 RT-PCR positive test result from the period of Delta dominance (July to November 2021), or a positive or negative RT-PCR test result from the period of Omicron dominance (December 2021 to January 2022). MethodsA questionnaire based cohort study with outcomes on post-acute physical, fatigue, cognitive, mental health symptoms, and new-onset general health problems, four months after testing. Risk differences (RDs) were estimated by comparing cases and controls during the Omicron period, cases during the Delta and Omicron periods, and vaccinated cases with two and three doses during the Omicron period, adjusted for age, sex, BMI, self-reported chronic diseases, Charlson comorbidity index, healthcare occupation and vaccination status. ResultsFour months after testing for SARS-CoV-2 during the Omicron period, cases experienced higher risk of 18 out of 26 post-acute symptoms and five out of five new-onset general health problems, compared to controls. Cases during the Omicron period experienced lower risks of 8 of the 18 symptoms and of all five new-onset general health problems, compared to Delta cases. The most prominent RDs estimated when comparing Omicron cases to controls were memory issues (RD=5.4%, 95% CI 4.8 to 6.1), post-exertional malaise (RD=5.3%, 95% CI 3.1 to 7.7), fatigue/exhaustion (RD=5.2%, 95% CI 3.7 to 6.9), substantial fatigue (RD=5.0%, 95% CI 2.7 to 7.5), and dyspnea (RD=4.8%, 95% CI 3.8 to 5.9). Compared to cases from the Delta period, Omicron cases reported reduced risks of post-acute altered/reduced sense of smell (dysosmia) (RD=-15.1%, 95% CI -17.0 to -12.9) and -taste (dysgeusia) (RD=-11.6%, 95% CI -13.6 to -9.7). Cases vaccinated with three doses prior to Omicron infection reported reduced risk of 13 of the 26 post-acute symptoms and of three of the five new-onset general health problems, compared to those vaccinated with two doses. ConclusionsA considerable amount of cases infected during the Omicron period experienced post-acute symptoms and new-onset health problems, four months after testing, although milder compared to Delta cases. During the Omicron period, a booster vaccination dose was associated with fewer post-acute symptoms and new-onset health problems, four months after infection, compared to two doses of COVID-19 vaccine.