COVID Transmission and Morbidity in Malawi (COVID-TMM)

马拉维的新冠病毒传播和发病率 (COVID-TMM)

• 批准号: 10597697
• 负责人: James Beeson
• 金额: $ 61.89万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10597697
• 关键词: 2019-nCoV; Acute; Adult; Affect; Africa South of the Sahara; African; Age Distribution; American; Americas; Anemia; Antibodies; Antibody Response; Antibody-mediated protection; Antiviral Response; B-Lymphocytes; COVID-19 mortality; COVID-19 susceptibility; COVID-19 vaccination; COVID-19 vaccine; Cells; Childhood; Chronic; Collaborations; Communicable Diseases; Country; Data; Disease; Disease Progression; Effectiveness; Enrollment; Epidemiology; Europe; Exhibits; Exposure to; Frequencies; Health; Helminthiasis; High Prevalence; Household; Immune; Immunity; Immunization Programs; Immunologics; Impairment; Individual; Infection; Inflammatory; Innate Immune Response; Innate Immune System; Interferon Type I; Intestinal parasite; Longevity; Macrophage; Malaria; Malawi; Malnutrition; Memory B-Lymphocyte; Morbidity - disease rate; Natural Immunity; Parasitic infection; Participant; Pathogenesis; Phenotype; Policies; Population; Predisposition; Regimen; Risk; SARS-CoV-2 B.1.617.2; SARS-CoV-2 immunity; SARS-CoV-2 infection; SARS-CoV-2 transmission; Social Behavior; Symptoms; Testing; Time; Training; Universities; Vaccination; Vaccinee; Vaccines; Viral; Viremia; Virus; Work; adaptive immune response; assault; booster vaccine; chemokine; comorbidity; coronavirus disease; cost effective; cytokine; design; high risk; immune activation; improved; indexing; infection risk; malaria infection; monocyte; mortality; pandemic disease; pathogen; programs; progression risk; respiratory virus; response; seroconversion; serosurvey; transmission process; vaccination outcome; vaccine hesitancy

PROJECT SUMMARY SARS-CoV-2 transmission was expected to have a devastating impact in sub-Saharan African countries. Instead, morbidity and mortality rates in nearly the whole region are an order of magnitude lower than in Europe and the Americas. To identify what is different requires a better understanding of the underlying immunological substrate of the population, and how these factors affect susceptibility to infection, progression of symptoms, transmission, and responses to SARS-CoV-2 vaccination. These populations are assaulted by many infectious diseases, including malaria. Exposure to these pathogens can produce long-lasting changes in the innate immune system, which may confer decreased susceptibility to heterologous infections. By generating rapid responses to the virus, the innate immune system can decrease the susceptibility to SARS-CoV-2 infection and the risk of progression from infection to disease. On the other hand, malaria infections and helminthiasis can impair the acquisition and longevity of antibody (Ab)- induced immunity through several mechanisms, including tolerogenic innate immune responses. In addition to malaria, other co-morbidities, e.g., anemia and chronic undernutrition, are likely to affect Ab-mediated immunity. We hypothesize that malaria and helminthiasis affect morbidity of SARS-CoV-2 in sub-Saharan Africa. Compared to Western populations, both uninfected and infected-but-asymptomatic subjects will have enhanced innate immune phenotypes. Most infections will be asymptomatic. Once infected, though, malaria, infections with intestinal parasites, anemia, and mild undernutrition will decrease the acquisition and longevity of Ab responses, increasing the risk of re-infection. These comorbidities will also reduce longevity of Ab responses elicited by the Astrazeneca vaccine. To test these hypotheses, we will enroll 200 symptomatic individuals (index cases), their household contacts, and 300 vaccinees. We will assess the specific innate immune phenotypes that differentiate uninfected Malawians from Western controls and whether those responses are protecting Malawians from infection and/or progression of disease. We will follow infected participants and vaccinees for 1.5 years to assess acquisition and longevity of Ab responses and memory B cells. The work will be supported by a platform established on the basis of long-term collaborations with the Ministry of Health and the University of Malawi. As global vaccination campaigns launch, data to optimize vaccination in sub-Saharan countries are urgently needed. Identifying groups at high risk of infection and disease and understanding the susceptibility of the local population will help to define optimal vaccination policies to control transmission. Identifying “hypo- responders” and those whose Ab responses wane more quickly will help to optimize vaccination regimen. In summary, data generated by this study will improve our general understanding of SARS-CoV-2 transmission and pathogenesis and will allow regional vaccination programs to be designed for maximum effectiveness.

项目摘要 预计SARS-CoV-2的传播将对撒哈拉以南非洲国家产生破坏性影响。 相反，几乎整个地区的发病率和死亡率都比欧洲低一个数量级 和美洲。要确定什么是不同的，需要更好地了解潜在的免疫学 人群的基质，以及这些因素如何影响感染的易感性，症状的进展， 传播和对SARS-CoV-2疫苗接种的反应。 这些人口受到包括疟疾在内的许多传染病的侵袭。暴露于这些 病原体可以在先天免疫系统中产生持久的变化，这可能会降低 对异源感染的易感性。通过对病毒产生快速反应，先天免疫系统 可以降低对SARS-CoV-2感染的易感性和从感染发展为疾病的风险。 另一方面，疟疾感染和蠕虫病会损害抗体（Ab）的获得和寿命- 通过几种机制诱导免疫，包括致耐受性先天免疫应答。除了 疟疾、其他合并症，例如，贫血和慢性营养不良，可能会影响抗体介导的免疫。 我们假设疟疾和蠕虫病影响撒哈拉以南非洲SARS-CoV-2的发病率。 与西方人群相比，未感染者和感染但无症状的受试者都将增强 先天免疫表型大多数感染将是无症状的。一旦感染了疟疾， 肠道寄生虫、贫血和轻度营养不良将降低Ab应答的获得和寿命， 增加了再次感染的风险。这些合并症还将减少由免疫抑制剂引起的Ab应答的寿命。 阿斯利康疫苗。为了检验这些假设，我们将招募200名有症状的个体（索引病例）， 家庭接触者和300名疫苗接种者。我们将评估特异性先天免疫表型， 未受感染的马拉维人免受西方控制，以及这些反应是否保护马拉维人免受 感染和/或疾病进展。我们将对受感染的参与者和疫苗接种者进行为期1.5年的跟踪调查， 抗体应答和记忆B细胞的获得和寿命。这项工作将得到一个平台的支持 在与马拉维卫生部和马拉维大学长期合作的基础上建立的。 随着全球疫苗接种运动的启动，优化撒哈拉以南国家疫苗接种的数据如下： 迫切需要。确定感染和疾病的高风险群体，并了解 当地人口将有助于确定控制传播的最佳疫苗接种政策。识别“hypo- 应答者”和抗体应答下降更快的人将有助于优化疫苗接种方案。在 总之，这项研究产生的数据将提高我们对SARS-CoV-2传播的总体理解 和发病机制，并将允许区域疫苗接种计划的设计，以最大限度地发挥效力。