Cheung Ka Shing, Yan Vincent K C, Lam Lok Ka, Ye Xuxiao, Hung Ivan F N, Chan Esther W, Leung Wai K
Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Vaccines (Basel). 2023 Aug 8;11(8):1341. doi: 10.3390/vaccines11081341.
Antibiotics may increase the risk of COVID-19 among non-vaccinated subjects via probable gut dysbiosis. We aimed to investigate whether antibiotics also affect the clinical outcomes of COVID-19 vaccine recipients. This was a territory-wide cohort study of 3,821,302 COVID-19 vaccine recipients (aged ≥ 18 years) with ≥2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior COVID-19, prior gastrointestinal surgery, and immunocompromised status. The primary outcome was COVID-19 infection and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Exposure was pre-vaccination antibiotic use (within 180 days of first vaccine dose). Covariates included age, sex, Charlson Comorbidity Index, and concomitant medication use. Subjects were followed from the index date (first dose vaccination) until outcome occurrence, death, an additional dose of vaccination, or 15 November 2022. Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with antibiotic use. : Among 342,338 PS matched three-dose vaccine recipients (mean age: 57.4 years; male: 45.1%) with a median follow-up of 13.6 months (IQR: 9.2-16.3), antibiotics were associated with a higher risk of COVID-19 infection (aIRR: 1.16;95% CI: 1.14-1.19), hospitalization (aIRR: 1.75;95% CI: 1.65-1.86), and severe infection (aIRR: 1.60; 95% CI: 1.21-2.11). Notably, antibiotic use was associated with a higher risk of severe infection and death among CoronaVac recipients (aIRR: 1.62 95% CI: 1.18-2.22 and aIRR: 2.70, 95% CI: 1.54-4.73 for the two secondary outcomes, respectively), but not BNT162b2 recipients. Pre-vaccination use of antibiotics was associated with a higher risk of COVID-19 infection, hospitalization, and severe disease outcomes.
抗生素可能通过肠道菌群失调增加未接种疫苗人群感染新冠病毒的风险。我们旨在研究抗生素是否也会影响新冠疫苗接种者的临床结局。这是一项全地区队列研究，纳入了3,821,302名接种了≥2剂BNT162b2或科兴疫苗的18岁及以上新冠疫苗接种者。排除标准包括既往感染过新冠病毒、既往有胃肠道手术史以及免疫功能低下状态。主要结局是新冠病毒感染，次要结局包括与新冠相关的住院治疗和严重感染（综合重症监护病房入院、通气支持和/或死亡）。暴露因素为接种疫苗前使用抗生素（在第一剂疫苗接种前180天内）。协变量包括年龄、性别、查尔森合并症指数和同时使用的药物。研究对象从索引日期（第一剂疫苗接种）开始随访，直至结局发生、死亡、接种额外一剂疫苗或2022年11月15日。采用倾向评分（PS）匹配和泊松回归模型来估计使用抗生素情况下结局的调整发病率比（aIRR）。在342,338名PS匹配的三剂疫苗接种者中（平均年龄：57.4岁；男性：45.1%），中位随访时间为13.6个月（IQR：9.2 - 16.3），使用抗生素与新冠病毒感染风险较高相关（aIRR：1.16；95% CI：1.14 - 1.19）、住院风险较高相关（aIRR：1.75；95% CI：1.65 - 1.86）以及严重感染风险较高相关（aIRR：1.60；95% CI：1.21 - 2.11）。值得注意的是，在科兴疫苗接种者中，使用抗生素与严重感染和死亡风险较高相关（两个次要结局的aIRR分别为1.62，95% CI：1.18 - 2.22和aIRR：2.70，95% CI：1.54 - 4.73），但在BNT162b2疫苗接种者中并非如此。接种疫苗前使用抗生素与新冠病毒感染、住院和严重疾病结局的风险较高相关。
