Objectives
The risk of Post-COVID-19 condition (PCC) under hybrid immunity remains unclear.
Methods
Using data from the German National Cohort (NAKO Gesundheitsstudie), we investigated risk factors for self-reported post-infection symptoms (any PCC is defined as having at least one symptom, and high symptom burden PCC as having nine or more symptoms).
Results
Sixty percent of 109,707 participants reported at least one previous SARS-CoV-2 infection; 35% reported having had any symptoms 4–12 months after infection; among them 23% reported nine or more symptoms. Individuals, who did not develop PCC after their first infection, had a strongly reduced risk for PCC after their second infection (50%) and a temporary risk reduction, which waned over 9 months after the preceding infection. The risk of developing PCC strongly depended on the virus variant. Within variants, there was no effect of the number of preceding vaccinations, apart from a strong protection by the fourth vaccination compared to three vaccinations for the Omicron variant (odds ratio = 0.52; 95% confidence interval 0.45–0.61).
Conclusions
Previous infections without PCC and a fourth vaccination were associated with a lower risk of PCC after a new infection, indicating diminished risk under hybrid immunity. The two components of risk reduction after a preceding infection suggest different immunological mechanisms.