Systemic and mucosal adaptive immunity to SARS-CoV-2 during the Omicron wave in patients with chronic lymphocytic leukemia

Patients with chronic lymphocytic leukemia (CLL) were at high risk early in the COVID-19 pandemic. The Omicron SARS-CoV-2 variant is considered less aggressive, but a significant fatality rate was recently reported from CLL register studies. Here we report on Omicron hybrid immunity in CLL after vaccinations against SARS-CoV-2 followed by disease. Post-infection systemic and mucosal immunity against SARS-CoV-2 were analyzed in patients with CLL (n = 38) during the Omicron BA.1/BA.2 time-period. Most patients (30/38, 79%) had received 3 to 4 vaccine doses, yet median anti-Spike antibody titers were 0 U/mL (range 0–6,528) at the onset of infection. Significantly elevated serum antibody levels were observed post-infection (p = 0.0027 vs baseline) to a median of 3,145 U/mL (range 0->25 000) which correlated with inhibition of Spike-ACE2 binding. Low convalescent IgA responses were noted in both saliva and serum in patients with ongoing BTKi/BCL-2i therapy compared with early-stage untreated patients (p = 0.010; p = 0.051). Post-Omicron CD4 + and CD8 + T cell responses were observed at levels similar to those of healthy donors. Forty-seven percent of the patients required hospitalization but there was only one possibly related death. Broad immunity was observed in patients with CLL following Omicron infection. Impaired mucosal immunity during BTKi therapy requires further studies.