The role of chronic diseases, environmental and genetic influences on the infection with SARS-CoV-2: boosters, effect modifiers or mediators?

最近发现的“严重急性呼吸综合征冠状病毒2型”（SARS-CoV-2）病毒是新冠病毒的病原体。COVID-19的病程通常较轻，但会导致大量病例住院甚至死亡，这可能取决于先前存在的疾病和遗传易感性。环境空气污染是心脏代谢、呼吸和神经疾病的主要环境风险因素，也与COVID-19疾病的传播和严重程度有重大关系。COVGENAIR的目的是评估慢性疾病、环境因素和遗传易感性及其相互作用对SARS-CoV-2感染严重程度的影响。具体而言，我们将调查：(a)不同年龄和风险群体中SARS-CoV-2感染的患病率和症状，(b)解开环境暴露与SARS-CoV-2感染之间的关联，(c)确定人群中可能特别容易感染SARS-CoV-2病毒的易感亚组，以及(d)调查SARS-CoV-2感染的长期健康影响。该建议基于三项综合表型纵向队列研究获得的数据，这些研究均可追溯到20多年前，参与者年龄在20至95岁之间，包括对COVID-19大流行前的既往亚临床疾病表现、暴露史、生活方式因素和基因分型的广泛评估。在该提案中，我们将通过问卷调查和抗体测试收集关于SARS-CoV-2感染的数据，并邀请受试者进行重新检查，以评估COVID-19最常见的后果，如嗅觉丧失和持续呼吸问题。阐明可能增加SARS-CoV-2感染风险的环境和分子途径，以确定易感受试者，并确定COVID-19后对呼吸、心脏代谢和神经系统的长期健康结果，是管理COVID-19大流行带来的公共卫生挑战的重要步骤。具体来说，了解基因构成的影响，以及空气污染和已有疾病对不同年龄组感染反应的相互作用，将有助于更好地了解潜在的分子途径，以及高危个体的可变性和发病机制。

The recently discovered virus “Severe Acute Respiratory Syndrome CoronaVirus 2” (SARS-CoV-2) is the pathogenic agent of COVID-19. The disease course of COVID-19 is often mild, but leads in a substantial number of cases to hospitalization and even death, which is likely depending on pre-existing conditions and genetic predisposition. Ambient air pollution is a major environmental risk factor for cardio-metabolic, respiratory and neurological diseases, and also has been implicated to significantly contribute to COVID-19 disease spread and severity. It is the objective of COVGENAIR to assess the role of chronic diseases, environmental factors and genetic predisposition and their interplay on the severity of SARS-CoV-2 infections. In particular, we will investigate: (a) the prevalence of SARS-CoV-2 infections and symptoms within different age and risk groups, (b) disentangle the association between environmental exposures and SARS-CoV-2 infections, (c) identify susceptible subgroups in the population who might be particularly vulnerable for an infection with the SARS-CoV-2 virus, and (d) investigate the long-term health effects of an infection with SARS-CoV-2. This proposal is based on data obtained from three comprehensively phenotyped longitudinal cohort studies, all reaching back more than 20 years with participants now being 20 to 95 years old, comprising an extensive assessment of previous subclinical disease manifestations, exposure history, lifestyle factors and genotyping before the COVID-19 pandemic. Within the proposal, we will collect data on SARS-CoV-2 infections by questionnaire and antibody tests and invite subjects for re-examination to assess the most common consequences of COVID-19, such as loss of smell and persistent respiratory problems. Elucidating the environmental and molecular pathways which could increase the risk of a SARS-CoV-2 infection to identify susceptible subjects and determining the long-term post-COVID-19 health outcomes on the respiratory, cardiometabolic and neurological system are important steps in managing the public health challenges of the COVID-19 pandemic. Specifically, understanding the influence of our genetic make-up and the interplay with air pollution and pre-existing conditions on the response to an infection in different age groups would help to better understand the underlying molecular pathways as well as the variability and pathogenesis in at-risk individuals.