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: 10467335
• 负责人: James Beeson
• 金额: $ 66.11万
• 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/10467335
• 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; Attenuated; B-Lymphocytes; COVID-19 mortality; 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; Interferons; Intestinal parasite; Lead; Longevity; Malaria; Malawi; Malnutrition; Memory B-Lymphocyte; Morbidity - disease rate; Natural Immunity; Parasitic infection; Participant; Pathogenesis; Phenotype; Policies; Population; Predisposition; Regimen; Risk; SARS coronavirus; 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; base; booster vaccine; comorbidity; coronavirus disease; cost effective; cytokine; design; high risk; immune activation; improved; indexing; infection risk; macrophage; malaria infection; malarial anemia; monocyte; mortality; pandemic disease; pathogen; programs; 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.

项目总结