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

SARS-CoV2 (CoV2) primarily infects respiratory mucosae, yet the role of mucosal immunity is not known. UK South Asian (SA) patients have a higher mortality from CoV2 infection than most ethnic groups, whereas in India similarly adjusted mortality rates are lower than in the UK. We hypothesise that mucosal immunity plays a role in susceptibility to and severity of COVID-19 and explains these differences. Minor salivary glands appear to be major sites of CoV2 replication leading to extremely high viral counts in saliva and upregulated production of cytokines. Mucosal surfaces have their own microbiome which protects against pathogens and oral, lung & nasal microbiomes are closely related. Microbiome dysbiosis may be a factor in COVID-19 severity. This study will therefore compare the oral microbiome, salivary innate and specific mucosal antibody responses longitudinally among CoV2-positive SA patients in India and the UK and determine their diagnostic and prognostic utility.Healthy controls and CoV2-positive patients of SA origin with asymptomatic or symptomatic disease or who are COVID recovered will be recruited in the UK and India. Blood and stimulated whole mouth saliva (SWMF) samples will be collected longitudinally for up to 90 days from infected individuals. Cytokines, T cell phenotypes and IgA & IgG anti-CoV2 antibodies will be determined in SWMF and compared with those in blood. The SWMF microbiome will be analysed by shotgun metagenomics and the metabolome by using NMR. The influence of pre-existing mouth disease in susceptibility to COVID will be determined. Identification of these factors should result in direct and applicable clinical benefit to SA populations and others. Ongoing collaborations between London and Chennai will facilitate commencement of these studies. In London, samples will be taken from patients who are also part of a partner proposal (KCL-SIMS), enabling saving on research costs.