Role of the oral microbiome & mucosal immunity in COVID-19 disease: diagnostic/prognostic utility in South Asian populations

口腔微生物组的作用

• 批准号: MR/V040170/1
• 负责人: Stephen Challacombe
• 金额: $ 55.78万
• 依托单位: King's College London
• 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%2FV040170%2F1
• 关键词: Role; oral; microbiome; mucosal; immunity

COVID-19 primarily infects lungs, mouth and nose, which are all mucosae (linings of body cavities) and all part of the mucosal immune system which protects mucosal surfaces and is distinct from systemic immunity. In spite of it being the primary target of the coronavirus (SARS-CoV2), its role in disease resistance, susceptibility or severity is unknown. In the UK, South Asian origin patients have a higher mortality from SARS-CoV2 infection than most ethnic groups, even after adjusting for co-morbidities, age, social gradient factors. In India, similarly adjusted mortality rates are lower than in the UK. Our hypothesis is that mucosal immunity, as reflected in the mouth nose and lungs (oral cavity/oropharynx), plays a critical role in susceptibility to, and severity of COVID-19 and explains differences in mortality between similar populations in the UK and India. We will compare mucosal and concurrent systemic immunity to reveal biomarkers for risk of disease progression which can be applied clinically so as to indicate prognosis and initiate early treatment.COVID-19 has an initial phase of about one week when extremely high viral counts can be found in saliva and minor salivary glands, which appear to be major sites of SARS-CoV2 replication. The next phase is of increased production of non-specific immune factors (innate immunity) and especially of the products of cells (cytokines) some of which protect and others damage. It is known that 'T'-cells and cytokines are altered in both systemic and mucosal immunity to viral diseases but mucosal responses have not been much explored in relation to COVID-19. Mucosal surfaces have their own normal fungal, bacterial and viral flora (the microbiome) which protects against unwanted pathogens. Recent years have seen great increases in our understanding of the oral microbiome in health and disease. The oral microbiome is closely related to both lung and nose microbiomes and there is evidence that upsetting the normal balance of host microbes may be a factor in COVID-19 severity. This study will therefore examine and compare the oral microbiome in two South Asian populationsProposed Methodology: In this prospective longitudinal study, healthy controls and SARS-CoV2-positive patients of South Indian origin diagnosed to have mild or severe symptomatic disease or who have recovered from COVID will be recruited in the UK and India. Blood and saliva samples will be collected longitudinally for up to 90 days from infected individuals. The cell factors (cytokines), and different types of T cells (lymphocytes) as well as anti-SARS-CoV2 antibodies will be determined in saliva and compared with those in blood. The bacteria, fungi and viruses present in saliva (salivary microbiome) will be analysed by new molecular techniques and compared in the two populations in relation to the development of immunity and disease. We will be able to examine the development of antibodies in the mouth (reflecting those in the nose and lung), comparing those who develop mild or severe disease. We will look at the influence of pre-existing mouth disease in susceptibility to COVID. The immune responses and the oral flora will thus be correlated with COVID-19 severity as well as both COVID and non-COVID mouth disease and enable the identification of host, viral or bacterial factors which affect the susceptibility and severity of COVID in South Asian populations in the UK and India. Identification of these factors will not only reveal differences in the UK and India but will also have direct and applicable clinical benefit to both populations and others.There are ongoing close collaborations between London, Chennai and Bangalore which should facilitate the early commencement of these studies. In London, Chennai and Bangalore, samples of blood and saliva will be taken from patients who are also part of a partner proposal (KCL-SIMS), thus enabling saving on costs of the research.

COVID-19主要感染肺、口和鼻，这些都是粘膜（体腔的衬里），也是保护粘膜表面的粘膜免疫系统的所有部分，与全身免疫不同。尽管它是冠状病毒（SARS-CoV 2）的主要靶标，但其在疾病抵抗力，易感性或严重性中的作用尚不清楚。在英国，南亚裔患者的SARS-CoV 2感染死亡率高于大多数种族群体，即使在调整了合并症、年龄、社会梯度因素后。在印度，类似调整后的死亡率低于英国。我们的假设是，反映在口鼻和肺（口腔/口咽）中的粘膜免疫在COVID-19的易感性和严重程度中起着关键作用，并解释了英国和印度相似人群之间死亡率的差异。我们将比较粘膜和并发的全身免疫，以揭示疾病进展风险的生物标志物，这些生物标志物可以应用于临床，以指示预后并开始早期治疗。COVID-19的初始阶段约为一周，此时可以在唾液和小唾液腺中发现极高的病毒计数，这似乎是SARS-CoV 2复制的主要部位。下一个阶段是非特异性免疫因子（先天免疫）的产生增加，特别是细胞产物（细胞因子）的产生增加，其中一些细胞具有保护作用，而另一些细胞则具有破坏作用。已知“T”细胞和细胞因子在对病毒性疾病的全身和粘膜免疫中均发生改变，但尚未对与COVID-19相关的粘膜反应进行过多探索。粘膜表面有其自身的正常真菌、细菌和病毒植物群（微生物组），其保护免受不想要的病原体的侵害。近年来，我们对健康和疾病中的口腔微生物组的了解大大增加。口腔微生物组与肺和鼻微生物组密切相关，有证据表明，破坏宿主微生物的正常平衡可能是COVID-19严重程度的一个因素。因此，这项研究将检查和比较两个南亚人群的口腔微生物组。建议的方法：在这项前瞻性纵向研究中，将在英国和印度招募健康对照和SARS-CoV 2阳性患者，这些患者被诊断为患有轻度或重度症状性疾病或已从COVID中康复。血液和唾液样本将从感染个体纵向收集长达90天。将在唾液中测定细胞因子（细胞因子）和不同类型的T细胞（淋巴细胞）以及抗SARS-CoV 2抗体，并与血液中的细胞因子进行比较。唾液中存在的细菌，真菌和病毒（唾液微生物组）将通过新的分子技术进行分析，并在两个人群中比较免疫力和疾病的发展。我们将能够检查口腔中抗体的发展（反映在鼻子和肺部），比较那些发展为轻度或严重疾病的人。我们将研究先前存在的口腔疾病对COVID易感性的影响。因此，免疫反应和口腔植物群将与COVID-19严重程度以及COVID和非COVID口腔疾病相关，并能够识别影响英国和印度南亚人群COVID易感性和严重程度的宿主、病毒或细菌因素。这些因素的识别不仅将揭示在英国和印度的差异，但也将有直接和适用的临床效益，两个人口和others.There是正在进行的密切合作之间的伦敦，钦奈和班加罗尔，这应该有利于这些研究的早日开始。在伦敦、钦奈和班加罗尔，将从也是合作伙伴提案（KCL-SIMS）一部分的患者身上采集血液和唾液样本，从而节省研究费用。

项目成果

Implications in the quantitation of SARS-CoV2 copies in concurrent nasopharyngeal swabs, whole mouth fluid and respiratory droplets

对同步鼻咽拭子、全口腔液和呼吸道飞沫中 SARS-CoV2 拷贝定量的影响

• DOI: 10.1101/2021.01.03.21249157
• 发表时间: 2021
• 作者: Kannian P

Mucosal immunity and antibody anergy in COVID-exposed Covishield vaccinees

接触过 Covishield 疫苗接种者的粘膜免疫和抗体无反应性

• DOI: 10.1101/2022.09.06.22279625
• 发表时间: 2022
• 作者: Kannian P