The SARS-CoV-2 Omicron variant has spread rapidly and has been the dominant variant since 2022. The course of acute infection, in a vaccinated population, with Omicron is milder compared with earlier variants. However, little is known about how the occurrence of long-term symptoms after Omicron infection compared with other variants is modulated by previous infections and/or vaccinations.

Participants of the DigiHero study provided information about their SARS-CoV-2 infections, vaccinations, and symptoms 12 or more weeks after infection (post-COVID-19 condition - PCC).

Participants infected with wildtype SARS-CoV-2 had the highest PCC risk (adjusted odds ratio [aOR] 6.44, 95% confidence interval (CI): 5.49; 7.56), followed by participants infected with Alpha and Delta compared with the reference group (individuals infected with Omicron having received three or more vaccinations). Among those infected with a specific variant, the number of preceding vaccinations was not associated with a risk reduction for PCC, whereas previous infection was strongly associated with a lower PCC risk (aOR 0.14, 95% CI 0.07; 0.25).

While infection with Omicron is less likely to result in PCC compared with previous variants, lack of protection by vaccination suggests a substantial challenge for the healthcare system during the early endemic period. In the midterm, the protective effects of previous infections can reduce the burden of PCC.