2.1. Study Design and Participants
neutropenia, malignancy, HIV infection, diabetes mellitus, sepsis
NEUTROPENIA, HIV INFECTION, DISEASE, DIABETES MELLITUS, RECRUITMENT, COVID-19 INFECTION, SEPSIS
This was a double-blind, randomised, parallel-arm, placebo-controlled trial conducted in a university centre in Hong Kong. Subjects were recruited from a territory-wide, community-based recruitment initiative that reached the general population of Hong Kong from April 2021 to March 2022. Eligible subjects consisted of individuals aged ≥65 years and patients with diabetes mellitus who were naive to COVID-19 vaccination. Subjects were excluded if they had: a history of confirmed COVID-19 infection; active sepsis or active malignancy; underlying immunosuppressed state such as a prior organ or hematopoietic stem cell transplant; neutropenia with absolute neutrophil count (ANC) < 500 cells/μL at the time of study inclusion; HIV infection with CD4 < 200 cells/μL at the time of study inclusion; concomitant use of immunosuppressants or corticosteroids at a prednisolone-equivalent dose of ≥10 mg for more than three months; history or active infective endocarditis; been on peritoneal dialysis or haemodialysis; positive pregnancy test; or used prebiotics, probiotics, or antibiotics within one month prior to the study. Patients with diabetes mellitus should have had stable disease control and no changes in medications for ≥3 months. The study was approved by the Clinical Research Ethics Committee of the Chinese University of Hong Kong on 19 April 2021 (Ref. No. 2021.186). It was registered on ClinicalTrials.gov (identifier NCT04884776). This study was conducted according to the principles of the Declaration of Helsinki and ICH-GCP. All subjects provided informed consent.