Effects of entecavir and tenofovir disoproxil fumarate on the incidence and severity of COVID-19 in patients with chronic hepatitis B

Background: Whether different anti-hepatitis B virus (HBV) drugs have different effects on COVID-19 is controversial. We aimed to evaluate the incidence of COVID-19 in chronic hepatitis B (CHB) patients receiving anti-HBV treatment, and to compare the impact of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on the severity of COVID-19.

Methods: CHB outpatients were enrolled from December 2022 to February 2023. Questionnaires were used to collect whether subjects were currently or previously had COVID-19 within the past 2 months, and the information of symptoms, duration, and severity if infected.

Results: Six hundred thirty CHB patients were enrolled, 64.3% (405/630) patients were currently or previously had COVID-19. No COVID-19 patient required hospitalization, intensive care unit admission, oxygen support or died. Majority of patients reported mild (32.8% [133/405]) and moderate (48.1% [195/405]) symptoms. After propensity score matching, 400 matched patients were obtained (ETV: 238; TDF: 162), among which the incidences of COVID-19 were comparable between ETV and TDF-treated patients (60.1% [143/238] vs. 64.2% [104/162], p = 0.468). The proportion of patients complicated with any symptom caused by COVID-19 were also similar (ETV vs. TDF: 90.9% [130/143] vs. 91.3% [95/104], p = 1.000). In addition, the severity of overall symptom was comparable between ETV and TDF-treated patients, in terms of proportion of patients complicated with severe symptom (9.8% vs. 8.7%, p = 0.989), symptom duration (4.3 vs. 4.3 days, p = 0.927), and symptom severity score (4.1 vs. 4.0, p = 0.758). Subgroup analysis supported these results.

Conclusions: During the current pandemic, the vast majority of CHB patients experienced non-severe COVID-19, and ETV and TDF did not affect COVID-19 severity differently.