CARDINNATE: Variation in innate immune activation and cardiovascular disease risk as drivers of COVID19 outcome in South Asians in UK and India

CARDINNATE：先天免疫激活和心血管疾病风险的变化是英国和印度南亚人 COVID19 结果的驱动因素

• 批准号: MR/V040162/1
• 负责人: Adrian Hayday
• 金额: $ 128.76万
• 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: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV040162%2F1
• 关键词: CARDINNATE; Variation; innate; immune; activation

While COVID-19 causes minor illness in most people, some individuals develop more severe disease requiring admission to hospital including intensive care. People of South Asian heritage admitted with severe COVID-19 in the UK have a higher death rate than those of other ethnic backgrounds even after adjusting for their age or socioeconomic status. However, death rates for South Asians with COVID-19 appear to be much lower in India than the UK. This is very surprising given that the health service in India is less comprehensive than the national health service and in India the average socioeconomic conditions are significantly lower than the UK. This unexpected disparity between countries suggests that factors beyond socioeconomic conditions per se are important in determining whether people survive severe COVID-19. Our understanding of immune priming and activation leads us to propose that biological factors that regulate how the body responds to infection may be very important. The body's immune system is vital in fighting infection. We know that severe COVID-19 is associated with profound abnormalities of the immune response. Furthermore, severe COVID-19 is accompanied by life-threatening problems with heart and blood vessel function. We propose that differences in immune response and how this impacts on heart and blood vessel function may contribute to the effects of COVID-19 on South Asians in the UK and India. One possibility is that the immune system of people in India is better trained to respond to infection because of continued exposure to a variety of infections and environmental factors that are uncommon in the UK. A poorer immune response to infection in South Asians in the UK combined with their high underlying rates of diabetes and heart disease may result in worse disease and life threatening complications when they get COVID-19. Such biological factors may therefore account for the disproportionate effects of COVID-19 in South Asians in UK.We have put together an expert interdisciplinary team of scientists and medical doctors from the UK and India who have outstanding experience in infectious diseases, immunology, heart and blood vessel disorders, and intensive care. Our team will work together to drill down into the problem and prove exactly why COVID-19 affects South Asians in different countries in different ways. We aim to rapidly identify information that allows us to develop new prevention steps, more targeted monitoring, and hopefully new treatments to improve the outcome of COVID-19 in both India and the UK.

虽然 COVID-19 在大多数人中引起轻微疾病，但有些人会出现更严重的疾病，需要入院治疗，包括重症监护。即使在调整了年龄或社会经济地位后，在英国入院的患有严重 COVID-19 的南亚裔人的死亡率仍高于其他种族背景的人。然而，印度南亚人感染 COVID-19 的死亡率似乎比英国低得多。这是非常令人惊讶的，因为印度的医疗服务不如国家医疗服务全面，而且印度的平均社会经济条件明显低于英国。国家之间这种意想不到的差异表明，社会经济条件本身以外的因素对于决定人们能否在严重的 COVID-19 中生存下来很重要。我们对免疫启动和激活的理解使我们提出，调节身体如何应对感染的生物因素可能非常重要。身体的免疫系统对于抵抗感染至关重要。我们知道，严重的 COVID-19 与免疫反应的严重异常有关。此外，严重的 COVID-19 还伴有危及生命的心脏和血管功能问题。我们认为，免疫反应的差异及其对心脏和血管功能的影响可能会导致 COVID-19 对英国和印度的南亚人产生影响。一种可能性是，印度人的免疫系统受到了更好的训练，能够更好地应对感染，因为他们持续接触各种感染和环境因素，而这在英国并不常见。英国的南亚人对感染的免疫反应较差，加上糖尿病和心脏病的潜在发病率较高，当他们感染 COVID-19 时，可能会导致更严重的疾病和危及生命的并发症。因此，这些生物因素可能是COVID-19对英国南亚人造成不成比例影响的原因。我们组建了一支由来自英国和印度的科学家和医生组成的跨学科专家团队，他们在传染病、免疫学、心脏和血管疾病以及重症监护方面拥有杰出的经验。我们的团队将共同努力深入研究这个问题，并证明为什么 COVID-19 以不同的方式影响不同国家的南亚人。我们的目标是快速识别信息，使我们能够制定新的预防措施、更有针对性的监测，并希望采用新的治疗方法来改善印度和英国的 COVID-19 治疗结果。

项目成果

Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19.

• DOI: 10.1073/pnas.2201541119
• 发表时间: 2022-08-23
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1

SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care.

• DOI: 10.1038/s41467-021-23494-1
• 发表时间: 2021-06-07
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Gutmann C;Takov K;Burnap SA;Singh B;Ali H;Theofilatos K;Reed E;Hasman M;Nabeebaccus A;Fish M;McPhail MJ;O'Gallagher K;Schmidt LE;Cassel C;Rienks M;Yin X;Auzinger G;Napoli S;Mujib SF;Trovato F;Sanderson B;Merrick B;Niazi U;Saqi M;Dimitrakopoulou K;Fernández-Leiro R;Braun S;Kronstein-Wiedemann R;Doores KJ;Edgeworth JD;Shah AM;Bornstein SR;Tonn T;Hayday AC;Giacca M;Shankar-Hari M;Mayr M
• 通讯作者: Mayr M

Association of cardiometabolic microRNAs with COVID-19 severity and mortality.

• DOI: 10.1093/cvr/cvab338
• 发表时间: 2022-01-29
• 期刊: Cardiovascular research
• 影响因子: 10.8
• 作者: Gutmann C;Khamina K;Theofilatos K;Diendorfer AB;Burnap SA;Nabeebaccus A;Fish M;McPhail MJW;O'Gallagher K;Schmidt LE;Cassel C;Auzinger G;Napoli S;Mujib SF;Trovato F;Sanderson B;Merrick B;Roy R;Edgeworth JD;Shah AM;Hayday AC;Traby L;Hackl M;Eichinger S;Shankar-Hari M;Mayr M
• 通讯作者: Mayr M

Anti-type I interferon antibodies as a cause of severe COVID-19.

• DOI: 10.12703/r-01-0000010
• 发表时间: 2022-01-01
• 期刊: Faculty reviews
• 作者: Fajgenbaum, David C;Hayday, Adrian C;Zanoni, Ivan
• 通讯作者: Zanoni, Ivan

Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer.

• DOI: 10.1158/2767-9764.crc-22-0298
• 发表时间: 2022-11-17
• 期刊: Cancer research communications
• 作者: McKenzie DR;Graham R;Lechmere T;Domingo-Vila C;Alaguthurai T;Arman C;Pollock E;Gousis C;Kakkassery H;Carpenter E;Kurshan A;Vidler J;Kulasekararaj A;Patten P;North BV;Tree T;Doores KJ;Hayday AC;Irshad S
• 通讯作者: Irshad S