Sibylle Mellinghoff

Objective Preventing severe COVID‐19 remains a priority globally, particularly in the immunocompromised population. As shown in healthy individuals, immunity against SARS‐CoV‐2 can be yielded by previous infection, vaccination, or both (hybrid immunity). The objective of this observation study was to investigate hybrid immunity in patients with chronic lymphocytic leukemia (CLL). Methods/Results Blood samples of six patients with CLL were collected 55 days after fourth COVID‐19 vaccination. All patients had a SARS‐CoV‐2 infection within 12 months before the second booster (fourth vaccination). SARS‐CoV‐2 spike receptor binding domain (RBD)‐specific IgG antibodies were detectable in 6/6 (100.0%) CLL patients after four compared to 4/6 (66.7%) after three vaccinations. The median number of SARS‐CoV‐2 spike‐specific T cells after repeated booster vaccination plus infection was 166 spot‐forming cells (SFC) per million peripheral blood mononuclear cells. Overall, 5/5 (100%) studied patients showed a detectable increase in T cell activity. Conclusion Our data reveal an increase of cellular and humoral immune response in CLL patients after fourth COVID‐19 vaccination combined with SARS‐CoV‐2 infection, even in those undergoing B cell‐depleting treatment. Patients with prior vaccination failure now show a specific IgG response. Future research should explore the duration and effectiveness of hybrid immunity considering various factors like past infection and vaccination rates, types and numbers of doses, and emerging variants.