Therapeutic BCG vaccine protects against long COVID: The BATTLE randomized clinical trial

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine Pub Date : 2024-11-19 DOI:10.1111/joim.20033

Mehrsa Jalalizadeh, Keini Buosi, Cristiane F. Giacomelli, Patricia A.F. Leme, Karen L. Ferrari, Franciele A.V. Dionato, Wandrey R.S. Brito, Natália S. Brunetti, Aline R. Maia, Joseane Morari, Ana C. Pagliarone, Alessandro S. Farias, Licio A. Velloso, Maria A.F. Queiroz, Antonio C.R. Vallinoto, Marcio C. Bajgelman, Leonardo O. Reis

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引用次数: 0

Abstract

Background

Bacillus Calmette–Guérin (BCG) injected during the COVID-19 convalescence period was safe and enhanced recovery from anosmia and dysgeusia in the acute phase.

Objectives

To report the long-term results of the BATTLE trial, BCG vaccine in adults with mild COVID-19.

Methods

Design: Double-blind, placebo-controlled, randomized (1:1) clinical trial. Intervention: BCG intradermal vaccine and placebo. Patients: A total of 157 BCG and 142 placebo recipients participated in the 6-month follow-up, and 97 BCG and 95 placebo recipients participated in the 12-month follow-up. Measurements: Long COVID symptoms and mechanistic analyses.

Results

BCG reduced hearing problems at 6 months (odds ratio [OR] = 0.26) and sleeping, concentration, memory, and vision problems at 12 months (OR = 0.45, 0.36, 0.38, and 0.36, respectively). Sensitivity analyses confirmed that long COVID-19 symptoms were reduced at the 6- and 12-month follow-ups (p = 0.010 and 0.031, respectively). BCG's crossover interaction paradoxically increased hair loss in women and decreased it in men at 6 months (p = 0.032). BCG immunomodulation is likely mediated through inhibition of Fas ligand expression in the blood and increased induction of IL6, IL10, interferon-induced transmembrane protein 3, and angiotensin-converting enzyme 2 in cultured human macrophages.

Conclusion

Long-term follow-up of the BATTLE trial participants revealed that BCG protects against long COVID development if administered within the COVID-19 convalescence period. The response to BCG was subject-specific, including a paradoxical crossover interaction based on sex. Limitations: Not tested for previous mycobacterial exposure; loss to follow-up, particularly at 12 months.

Abstract Image

查看原文本刊更多论文

治疗性卡介苗可预防长效 COVID：BATTLE 随机临床试验。

背景：在COVID-19康复期注射卡介苗（Bacillus Calmette-Guérin，BCG）是安全的，并能促进急性期嗅觉障碍和发音障碍的恢复：报告BATTLE试验（卡介苗用于轻度COVID-19成人患者）的长期结果：方法：设计：双盲、安慰剂对照、随机（1:1）临床试验：卡介苗皮内接种和安慰剂：共有157名卡介苗接种者和142名安慰剂接种者参加了6个月的随访，97名卡介苗接种者和95名安慰剂接种者参加了12个月的随访：测量：长期COVID症状和机理分析：结果：卡介苗减少了6个月时的听力问题（几率比[OR] = 0.26）和12个月时的睡眠、注意力、记忆力和视力问题（OR = 0.45、0.36、0.38和0.36）。敏感性分析证实，在 6 个月和 12 个月的随访中，COVID-19 长症状有所减轻（p = 0.010 和 0.031）。卡介苗的交叉作用矛盾地增加了女性的脱发，而在 6 个月时减少了男性的脱发（p = 0.032）。卡介苗的免疫调节作用可能是通过抑制血液中 Fas 配体的表达和增加培养的人巨噬细胞中 IL6、IL10、干扰素诱导跨膜蛋白 3 和血管紧张素转换酶 2 的诱导来实现的：对 BATTLE 试验参与者的长期随访表明，如果在 COVID-19 康复期内接种卡介苗，卡介苗可防止 COVID 长期发展。对卡介苗的反应是受试者特异性的，包括基于性别的矛盾交叉相互作用：局限性：未检测既往是否接触过分枝杆菌；随访损失，尤其是12个月的随访损失。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Internal Medicine 医学-医学：内科

CiteScore

22.00

自引率

0.90%

发文量

176

审稿时长

4-8 weeks

期刊介绍： JIM – The Journal of Internal Medicine, in continuous publication since 1863, is an international, peer-reviewed scientific journal. It publishes original work in clinical science, spanning from bench to bedside, encompassing a wide range of internal medicine and its subspecialties. JIM showcases original articles, reviews, brief reports, and research letters in the field of internal medicine.