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

新型SARS-CoV-2和古老的结核分枝杆菌(M.tb)代表着突发公共卫生事件的碰撞，与这些传染病病原体的混合感染可能给英国和国际带来灾难性的后果。新冠肺炎存在巨大的潜力叠加M.tb感染，导致联合感染并加剧。这在惰性、潜伏性结核病感染(LTBI)中可能更重要，这种感染通常通过主动、持续的免疫得到很好的控制。例如，在有症状的新冠肺炎病中，SARS-CoV-2会导致显著的淋巴细胞减少。由于抗原特异性T细胞反应对结核分枝杆菌的控制和LTBI的诊断至关重要，这可能会有严重的后遗症。此外，初步研究表明，结核病感染和疾病增加了新冠肺炎的易感性和疾病严重性。然而，这种关系没有得到很好的描述--自然地，目前文献中的观点多于数据。目前还没有关于SARS-CoV-2对下呼吸道感染发展为活动性肺结核(ATB)的影响的数据，也没有关于结核分枝杆菌和SARS-CoV-2混合感染的免疫病理学方面的实验数据。为了回答这些未知的问题，我们将解决以下假设和目标：假设：SARS-CoV-2感染损害了结核分枝杆菌的免疫控制，导致LTBI向ATB的进展，混淆了LTBI诊断和限制了结核病控制程序的实施。目的：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。[目的]研究新冠肺炎在肺结核合并肺损伤患者中的发生率及其对疾病严重程度和结核病控制服务提供的影响

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