TB and COVID-19 coinfection: Investigating the clinical and biological interactions between Mycobacterium tuberculosis and SARS-CoV-2

结核病和 COVID-19 双重感染：研究结核分枝杆菌和 SARS-CoV-2 之间的临床和生物学相互作用

• 批准号: MR/W015374/1
• 负责人: Matthew O'Shea
• 金额: $ 40.6万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW015374%2F1
• 关键词: TB; COVID; 19; coinfection; Investigating

The novel SARS-CoV-2 and ancient Mycobacterium tuberculosis (M.tb) represent a collision of the public health emergencies and coinfection with these infectious pathogens could have disastrous consequences for the UK and internationally.There is significant potential for COVID-19 to superimpose on M.tb infections, resulting in coinfections that co-exacerbate. This may potentially be more important in indolent, latent tuberculosis infections (LTBI), which are typically well-controlled by active, ongoing immunity. For instance, SARS-CoV-2 causes marked lymphopenia in symptomatic COVID-19 disease. Since antigen-specific T-cell responses are crucial for the control of M.tb and in LTBI diagnostics, this may have serious sequelae. Moreover, preliminary studies suggest that TB infection and disease increase susceptibility and disease severity in COVID-19. However, this relationship is poorly characterised - naturally, there is currently more opinion in the literature than data. There are no data about the influence of SARS-CoV-2 on the progression of LTBI to active TB (ATB) and no experimental data surrounding immunopathological aspects of M.tb and SARS-CoV-2 coinfection.To answer these unknowns we will address the following hypothesis and objectives:Hypothesis "SARS-CoV-2 infection impairs immune control of M.tb, leading to progression of LTBI to ATB, confounding LTBI diagnostics and limiting TB control programme delivery"Objectives:1. To determine the effects of SARS-CoV-2 on immune control of M.tb in TB infection, disease and diagnostics2. To study the incidence of COVID-19 among patients with ATB and LTBI, and its impact on disease severity and provision of TB control services

新型 SARS-CoV-2 和古老的结核分枝杆菌 (M.tb) 代表了突发公共卫生事件的碰撞，这些传染性病原体的双重感染可能会给英国和国际造成灾难性后果。COVID-19 很可能叠加结核分枝杆菌感染，导致双重感染同时加剧。这对于惰性、潜伏性结核感染（LTBI）可能更为重要，这种感染通常可以通过主动、持续的免疫力得到很好的控制。例如，SARS-CoV-2 会导致有症状的 COVID-19 疾病出现明显的淋巴细胞减少。由于抗原特异性 T 细胞反应对于 M.tb 的控制和 LTBI 诊断至关重要，因此这可能会产生严重的后遗症。此外，初步研究表明，结核病感染和疾病会增加 COVID-19 的易感性和疾病严重程度。然而，这种关系的描述很差——自然地，目前文献中的观点多于数据。没有关于 SARS-CoV-2 对 LTBI 进展为活动性结核病 (ATB) 的影响的数据，也没有关于 M.tb 和 SARS-CoV-2 共感染的免疫病理学方面的实验数据。为了回答这些未知因素，我们将提出以下假设和目标：假设“SARS-CoV-2 感染损害 M.tb 的免疫控制，导致 LTBI 进展为 ATB，混淆 LTBI 诊断和限制结核病控制计划的实施”目标：1．确定 SARS-CoV-2 在结核感染、疾病和诊断中对结核分枝杆菌免疫控制的影响2。研究 ATB 和 LTBI 患者中 COVID-19 的发病率及其对疾病严重程度和结核病控制服务提供的影响