COVID-19 恢复期患者卡介苗疫苗的随机临床试验：临床演变、不良事件和体液免疫反应。
Randomized clinical trial of BCG vaccine in patients with convalescent COVID-19: Clinical evolution, adverse events, and humoral immune response.
机构信息
Department of UroScience, School of Medical Sciences, State University of Campinas-UNICAMP, Campinas, Brazil.
Brigham and Women's Center for Surgery and Public Health, Harvard Medical School, Boston, Massachusetts, USA.
出版信息
J Intern Med. 2022 Oct;292(4):654-666. doi: 10.1111/joim.13523. Epub 2022 Jun 3.
BACKGROUND
The Bacillus Calmette-Guérin (BCG) vaccine may confer cross-protection against viral diseases in adults. This study evaluated BCG vaccine cross-protection in adults with convalescent coronavirus disease 2019 (COVID-19).
METHOD
This was a multicenter, prospective, randomized, placebo-controlled, double-blind phase III study (ClinicalTrials.gov: NCT04369794).
SETTING
University Community Health Center and Municipal Outpatient Center in South America.
PATIENTS
a total of 378 adult patients with convalescent COVID-19 were included.
INTERVENTION
single intradermal BCG vaccine (n = 183) and placebo (n = 195).
MEASUREMENTS
the primary outcome was clinical evolution. Other outcomes included adverse events and humoral immune responses for up to 6 months.
RESULTS
A significantly higher proportion of BCG patients with anosmia and ageusia recovered at the 6-week follow-up visit than placebo (anosmia: 83.1% vs. 68.7% healed, p = 0.043, number needed to treat [NNT] = 6.9; ageusia: 81.2% vs. 63.4% healed, p = 0.032, NNT = 5.6). BCG also prevented the appearance of ageusia in the following weeks: seven in 113 (6.2%) BCG recipients versus 19 in 126 (15.1%) placebos, p = 0.036, NNT = 11.2. BCG did not induce any severe or systemic adverse effects. The most common and expected adverse effects were local vaccine lesions, erythema (n = 152; 86.4%), and papules (n = 111; 63.1%). Anti-severe acute respiratory syndrome coronavirus 2 humoral response measured by N protein immunoglobulin G titer and seroneutralization by interacting with the angiotensin-converting enzyme 2 receptor suggest that the serum of BCG-injected patients may neutralize the virus at lower specificity; however, the results were not statistically significant.
CONCLUSION
BCG vaccine is safe and offers cross-protection against COVID-19 with potential humoral response modulation.
LIMITATIONS
No severely ill patients were included.
背景
卡介苗（BCG）疫苗可能为成人提供针对病毒疾病的交叉保护。本研究评估了恢复期 2019 年冠状病毒病（COVID-19）成人的 BCG 疫苗交叉保护作用。
方法
这是一项多中心、前瞻性、随机、安慰剂对照、双盲 III 期研究（ClinicalTrials.gov：NCT04369794）。
地点
南美洲的大学社区卫生中心和市门诊中心。
患者
共纳入 378 例恢复期 COVID-19 成年患者。
干预措施
单次皮内 BCG 疫苗（n=183）和安慰剂（n=195）。
测量
主要结局是临床转归。其他结局包括 6 个月内的不良事件和体液免疫反应。
结果
在 6 周随访时，BCG 组嗅觉丧失和味觉丧失患者的恢复比例显著高于安慰剂组（嗅觉丧失：83.1%比 68.7%治愈，p=0.043，需要治疗的人数[NNT]为 6.9；味觉丧失：81.2%比 63.4%治愈，p=0.032，NNT 为 5.6）。BCG 还预防了以下几周味觉丧失的发生：BCG 组 113 例中有 7 例（6.2%），安慰剂组 126 例中有 19 例（15.1%），p=0.036，NNT 为 11.2。BCG 不会引起任何严重或全身性不良反应。最常见和预期的不良反应是局部疫苗损伤、红斑（n=152；86.4%）和丘疹（n=111；63.1%）。通过 N 蛋白免疫球蛋白 G 滴度和与血管紧张素转换酶 2 受体相互作用的血清中和来衡量针对严重急性呼吸综合征冠状病毒 2 的体液免疫反应表明，注射 BCG 的患者的血清可能以较低的特异性中和病毒；然而，结果没有统计学意义。
结论
BCG 疫苗安全，并对 COVID-19 提供交叉保护作用，可能调节体液免疫反应。
局限性
未纳入重症患者。
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