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

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.

Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial (preprint)

BackgroundPatients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate the safety and efficacy after two doses of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls. Methods539 study subjects (449 patients and 90 controls) were included in the clinical trial. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/chimeric antigen receptor T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection. FindingsAdverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72{middle dot}2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43{middle dot}4%) and CLL (63{middle dot}3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively. InterpretationThe results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. The rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups and/or subgroups to improve immunity. FundingKnut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, Swedish Research Council, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.