COVID-19 vaccination alters NK cell dynamics and transiently reduces HBsAg titers among patients with chronic hepatitis B

Abstract

Background and aims: COVID-19 vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on HBsAg titer and host immunity in chronic hepatitis B (CHB) patients. Method: Consecutive CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of natural killer (NK) cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Results: Vaccinated CHB patients (n = 2,329) had significantly lower HBsAg levels 1–30 days post-vaccination compared to baseline (median, −21.4 IU/ml from baseline), but the levels reverted to baseline by 91–180 days (median, −3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: −0.06, −0.39, and −0.04 log10 IU/ml/year in pre-vaccination period, days 1–30, and days 31–90, respectively). In contrast, unvaccinated patients (n = 468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, −13.1% from baseline; p < 0.001). The decrease in the frequency of NKG2A+ NK cells was observed in the CD56dimCD16+ NK cell population regardless of type of COVID-19 vaccine. Conclusion: COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer, which may be attributed to a decrease in the frequency of NKG2A+ NK cells.