Explaining the differential severity of COVID-19 between Indians in India and the UK

严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)是一种病毒感染；虽然许多人症状轻微，康复迅速，但其他人继续发展为严重冠状病毒病(新冠肺炎)，导致住院或死亡。许多研究表明，重度新冠肺炎在年龄较大、超重或有现有健康状况的人中更常见。在英国和美国等国家，新冠肺炎对包括印度在内的少数民族人口产生了更大的影响。一种解释是，这些危险因素在印度人口中的患病率高于大多数人口。相比之下，印度是全球新冠肺炎死亡人数最低的国家。这使得人们相信，严重的新冠肺炎在居住在印度的人中可能没有其他国家的印度人常见。对此有几个合理的解释；首先，居住在印度的人可能比居住在其他国家的印度人在环境中暴露在阳光下更多，这可能导致维生素D水平更高。其次，生活在印度的人可能因为更多地暴露在其他感染中而对新冠肺炎有更强的免疫力。这与社会经济地位有关，因为居住在卫生条件差的过度拥挤家庭的人可能比海外的印度人更有可能感染疾病。第三，与生活在高收入国家的印度人相比，居住在印度的人肥胖程度较低，既往疾病也较少。印度居民较低的体重指数可能是因为较低的卡路里摄入量或较多的体力活动--这两者都可能降低严重新冠肺炎的风险。虽然真正的生物差异可能解释了印度居民患严重新冠肺炎的风险较低，但也可能存在其他解释，如新冠肺炎数据质量和人口年龄结构的差异。例如，生活在印度的人可能因为对新冠肺炎病毒的耻辱而不太可能去医院感染这种病毒，或者他们更有可能死在家里而不是在医疗机构。这意味着印度对死因的捕捉可能不如其他国家，严重新冠肺炎患者的真实人数可能被低估了。到目前为止，还没有一项研究完全回答在印度和其他国家的印度人之间，新冠肺炎的严重程度是否真的不同。在这项研究中，我们将比较印度人、英国人和印度人患严重新冠肺炎的风险，并找出可能的解释。我们将进行两项大型研究。第一项研究将使用在英国的5040万印度人的匿名医疗记录和居住在印度城市和农村的22万人的采访数据。我们将首先比较曾经患有严重新冠肺炎的人口比例，严重新冠肺炎的定义是因新冠肺炎而去医院或死于新冠肺炎。然后，我们将探索严重新冠肺炎患病率的差异是否可以通过数据质量的差异、两个人群的年龄结构或关键风险因素的患病率差异来解释。我们的研究将解决新冠肺炎在印度是否被低估的关键问题，首先就新冠肺炎的症状采访曾入院的人，其次通过口头尸检的方法就家人的死亡采访人们。第二项研究将使用在印度进行的两项研究中收集的详细生物学和信息来深入研究新冠肺炎与既往感染或疫苗接种、肥胖、并存和维生素D之间的联系。我们预计研究的影响将包括制定考虑到世界各地印度人口的特定需求的新冠肺炎预防和管理策略，以及更深入地了解导致印度裔人群发生严重新冠肺炎的因素。

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral infection; while many people experience mild symptoms and recover quickly, others go on to develop severe coronavirus disease (COVID-19) resulting in hospitalisation or death. Many studies have shown that severe COVID-19 is more common in people who are older, overweight, or with existing health conditions. In countries such as the UK and USA, COVID-19 has had a greater impact on ethnic minority populations, including those of Indian ethnicity. One explanation is that the prevalence of these risk factors is higher in Indian populations than in the majority population. In contrast, India has the lowest number of COVID-19 deaths worldwide. This has led to the belief that severe COVID-19 may be less common in people residing in India than in Indian people in other countries. There are several plausible explanations for this; Firstly, people residing in India may have greater environmental exposure to sunlight than Indians residing in other countries, which may result in higher levels of vitamin D.Secondly, people living in India may have greater immunity to COVID-19 resulting from greater exposure to other infections. This is related to socioeconomic status as people living in overcrowded households with poor sanitation may be more likely to contract infections than Indian populations overseas. Thirdly, people residing in India may also be less obese and have fewer pre-existing conditions than Indian people living in higher-income countries. Lower BMI in Indian residents may result from lower calorie intake or higher physical activity - both of which may lower the risk of severe COVID-19. While it is possible that real biological differences may explain the lower risk of severe COVID-19 in Indian residents, there may be alternative explanations such as differences in the quality of COVID-19 data and age structure of the populations. For example, people living in India may be less likely to visit the hospital with COVID-19 due to stigma around the virus, or they may be more likely to die at home instead of in a medical facility. This means that the cause of death may be less well captured in India than in other countries, and the true number of people with severe COVID-19 may be underestimated. To date, no study has fully answered whether the severity of COVID-19 truly differs between Indian populations in India and in other countries. In this study, we will compare the risk of severe COVID-19 between Indians the UK and India and identify possible explanations. We will conduct two large studies. The first study will use the anonymised medical records of 50400,000 Indians in the UK and interview data from 220,000 people living in urban and rural India. We will first compare the proportion of the population who have ever had severe COVID-19, defined as either going to the hospital for or dying from COVID-19. We will then explore whether differences in the prevalence of severe COVID-19 can be explained by differences in data quality, the age structure of the two populations, or differences in the prevalence of key risk factors. Our study will address the key issue of whether COVID-19 is underestimated in India by firstly interviewing individuals ever admitted to hospital about COVID-19 symptom, and secondly, by interviewing people about deaths of their family members using a method known as a verbal autopsy. The second study will use detailed biological and information collected as part of two studies in India to conduct an in-depth examination of linked between COVID-19 and prior infections or vaccinations, obesity, co-morbidities, and vitamin D. We expect that the impacts of our research will include the development of COVID-19 prevention and management strategies which take into account the specific needs of Indian populations worldwide, and a deeper understanding of factors which lead to the development of severe COVID-19 in people of Indian origin.