Association between Recent Antibiotic Use and Early Immunogenicity of Covid-19 Bnt162b2 Vaccine

ABSTRACT

Introduction: Gut microbiota have been shown to be associated with COVID- 19 and influenza vaccine immunogenicity. While antibiotic-induced gut microbiota perturbation leads to suboptimal antibody production among influenza vaccine recipients, little is known about the effect of preexposure antibiotics on COVID-19 vaccine immunogenicity. Aims & Methods: We aimed to determine whether recent antibiotics use impaired COVID-19 immunogenicity. This was a prospective cohort study recruiting adult BNT162b2 recipients from five vaccination centers in Hong Kong. Exclusion criteria included prior COVID-19 infection, history of gastrointestinal surgery, inflammatory bowel disease, immunocompromised status (post-organ transplantation, immunosuppressants, chemotherapy), cancer, hematological, rheumatological and autoimmune diseases. Subjects received two doses of BNT162b2 at three weeks apart. Blood samples were collected at three time-points (before vaccination, day 21 and 56after first dose), and were tested for neutralising antibody (NAb) against receptor-binding domain (RBD) of wild type SARS-CoV-2 virus using a one-step competitive chemiluminescence immunoassay. NAb seroconversion was defined as 15 AU/mL. Primary outcomes were seroconversion rates of NAb at day 21 and 56 after first dose of vaccine. Exposure was pre-vaccination antibiotic use, defined as ever use of any antibiotics (including 11 different classes) within 6 months before vaccination. The adjusted odds ratio (aOR) of seroconversion with antibiotic use was derived by multivariable logistic regression model by adjusting for age, sex, diabetes mellitus (DM), overweight (BMI >23 kg/m2for Asians), hypertension, raised LDL (>=3.4 mmol/L), moderate-to-severe hepatic steatosis (defined as controlled attenuated parameter >= 268 dB/M on transient elastography), smoking and alcohol. Result(s) Of 316 BNT162b2 recipients (100 [31.6%] male;median age 50.1 [IQR40.0-57.0] years), all and 284 (89.9%) had NAb level measured at day 21 and 56, respectively. There were 29 (9.2%) antibiotic users (median duration of use 7 [IQR7-13] days). There was no significant difference in baseline characteristics between antibiotic users and non-users. At day 21, there was a trend towards lower seroconversion rate among antibiotic users compared with non-users (82.8% vs 91.3%;p=0.135). Independent factors negatively associated with seroconversion after one dose of BNT162b2 were antibiotics use (aOR0.26, 95% CI0.08-0.96), age >60 years (aOR0.34, 95% CI0.13-0.95) and male sex (aOR0.14, 95% CI0.05-0.34). At day 56, there was no more significant difference in seroconversion rate between antibiotic users and non-users (96.6% vs 99.3%;p=0.149). Conclusion(s) Recent antibiotic use before BNT162b2 vaccination was associated with lower early seroconversion rate after a single dose of vaccine but not two doses of vaccine. Further research on the association between antibiotics, gut microbiota and COVID-19 early vaccine immunogenicity is warranted.