Efficacy and safety of Oral LL‐37 against the Omicron BA.5.1.3 variant of SARS‐COV‐2: A randomized trial

Abstract Recombinant LL‐37 Lactococcus lactis (Oral LL‐37) was designed to prevent progression of COVID‐19 by targeting virus envelope, however, effectiveness and safety of Oral LL‐37 in clinical application was unclear. A total of 238 adult inpatients, open‐labelled, randomized, placebo‐controlled, single‐center study was conducted to investigate the primary end points, including negative conversion time (NCT) of SARS‐CoV‐2 RNA and adverse events (AEs). As early as intervened on 6th day of case confirmed, Oral LL‐37 could significantly shorten NCT (LL‐37 9.80 ± 2.67 vs. placebo 14.04 ± 5.89, p < 0.01). For Oral LL‐37, as early as treated in 6 days, the adjusted hazard ratio (HR) for a primary event of nucleic acid negative outcome was 6.27‐fold higher than 7‐day‐later (HR: 6.276, 95% confidence interval [CI]: 3.631–10.848, p < 0.0001), and the adjusted HR of Oral LL‐37 within 6 days is higher than placebo (HR: 2.427 95% CI: 1.239–4.751, p = 0.0097). No severe AEs were observed during hospitalization and follow‐up investigation. This study shows that early intervention of Oral LL‐37 incredibly reduces NCT implying a potential for clearance of Omicron BA.5.1.3 without evident safety concerns.