COVID-19 Transmission and Morbidity in Malawi
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,500
- 试验地点
- 3
- 主要终点
- Change in frequencies of classical (CD14+CD16-) monocytes and markers of activation/inflammation with and without stimulation by by toll like receptor (TLR) and retinoic acid-inducible gene I (RIG-I) like receptors (RLR) ligands
研究概览
简要总结
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.
Study objectives
- Determine the risk and predictors of infection and disease among contacts of SARS-CoV-2 infection subjects in Malawi
- Determine whether innate immune responses lower the risk of SARS-CoV-2 infection and disease, and acquisition and duration of vaccine responses.
- Assess whether alterations in innate immune responses relevant to SARS-CoV-2 are associated with malaria or intestinal parasite infections.
- Assess the acquisition and longevity of antibodies (Ab) and cellular adaptive responses elicited by SARS-CoV-2 infection and vaccination.
- Assess whether malaria and intestinal parasite infections, chronic/mild undernutrition, and anemia mediate alterations in Ab and other adaptive cellular responses to SARS-CoV-2 through innate immune responses or a different unknown mechanism.
详细描述
The investigators hypothesize that malaria and intestinal parasitic diseases may result in enhanced or tolerogenic innate immune responses that decrease the risk of symptomatic COVID-19. On the other hand, these conditions and deficiency of micronutrients may decrease the acquisition and longevity of antibodies induced by natural infection and SARS-CoV-2 vaccines, increasing the risk of re-infection and breakthrough infections to vaccination.
To test these hypotheses, up to 200 symptomatic individuals (index cases)will be enrolled, their household contacts (anticipated ~700), and up to 600 vaccinees. The specific innate immune phenotypes that differentiate uninfected Malawians from Western controls (based on samples from blood banks) and whether those responses are protecting Malawians from infection and/or progression of disease will be assessed. Infected participants and vaccinees will be followed for up to 1.5 years to assess acquisition and longevity of Ab responses and memory B cells.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 5 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Index Cases
- •Presents with symptoms of COVID-19 and has infection confirmed through RT-PCR or a rapid antigen test;
- •Aged 5 years to 75 years and plans to live in Blantyre, in the catchment area of the target research health centers for the following 6 months;
- •Confirmed SARS-CoV-2 infection and share a household with 1 or more individuals of eligible age;
- •Has not received a SARS-CoV-2 vaccine in the previous 3 months
- •Willingness to comply with study procedures and visits, and provides informed consent.
- •Household Contacts of the Confirmed SARS-CoV-2 Case
- •Aged 5 years to 75 years and plans to live in Blantyre, in the catchment area of the target research health centers in the following 6 months;
- •Willingness to comply with study procedures and follow-up visits and provides informed consent.
- •Has not received a SARS-CoV-2 vaccine in the previous 3 months
- •1) Aged 18 years to 75 years; 2) Willingness to receive the primary regimen of the AZ and/or JJ vaccines 2) Not in the other 2 cohorts; 4) Willingness to comply with study procedures and follow-up visits and provides informed consent.
- •5) Has not received a prior dose of a SARS-CoV-2 vaccine
排除标准
- •Index Cases
- •Conditions that precludes from adherence to the visit schedule;
- •50% or more of household members decline to participate.
- •Pregnancy at the enrollment visit
- •Long term use of cotrimoxazole prophylaxis
- •Household Contacts of the Confirmed SARS-CoV-2 Case
- •Conditions that preclude adherence to the visit schedule.
- •Participants with 2 consecutive negative SARS-CoV-2 RT-PCRs will be excluded from visits after M
- •Pregnancy at the enrollment visit
- •Long term use of cotrimoxazole prophylaxis
- •Conditions that preclude adherence to the visit schedule.
- •Pregnancy at the enrollment visit
- •Long term use of cotrimoxazole prophylaxis
结局指标
主要结局
Change in frequencies of classical (CD14+CD16-) monocytes and markers of activation/inflammation with and without stimulation by by toll like receptor (TLR) and retinoic acid-inducible gene I (RIG-I) like receptors (RLR) ligands
时间窗: baseline, 2 weeks
Difference between measures obtained at 2 weeks and baseline in percentage positive. Percentage positive can range from 0 to 100. Change = Percentage positive at 2 weeks - Percentage positive at baseline
Risk of asymptomatic infection among contacts who acquire infection
时间窗: up to 2 weeks
Proportion of household members who acquire an asymptomatic (vs. symptomatic) infection among household contacts of an index case
Duration of neutralizing antibody (NAb) responses against two viruses
时间窗: up to 15 months
Among participants who develop neutralizing antibody responses, days to decay antibody levels to a 25% level from baseline. NAbs levels, defined as dilution of serum or plasma required to inhibit 50% of virus entry into a target cell lines (ID50) will be measured against the vaccine matched viruses and an additional predominant circulating variant of concern at the time participant samples are collected.
次要结局
- Duration of COVID-19 symptoms, reinfection rates, and breakthrough infection rates(up to 15 months)
- Change in concentrations of pro-inflammatory cytokines and chemokines produced by classic monocytes and MDMs(baseline, 2 weeks)
- Antibody magnitude to 3 SARS-COV-2 antigens and 3 trimers(up to 12 months and 18 months, depending on the cohort)
- Change in expression of 770 host response genes in classical monocytes and MDMs(baseline, 2 weeks)
- Fc-gamma receptors (FcγR) -II/III binding functional antibody activities(1 month)
- Magnitude of dimeric Immunoglobulin A (dIgA)(1 month)
- Frequencies of B (S-antigen specific and total) and plasma cells, and innate immunity parameters(up to 12 months, 15 months)
- Change in cell activation markers among stimulated and unstimulated classical monocytes and MDMs(baseline, 2 weeks)
- Probably of infections in a household(up to 2 weeks)
- Change in activation status of monocytes and monocyte-derived macrophages (MDMs) with and without stimulation with TLR and RLR agonists in vitro(baseline, 2 weeks)
- NAb responses measured against 3 viruses and through a surrogate assay (sENAB)(up to 12 months, 15 months)
- Duration of antibody-dependent cellular cytotoxicity (ADCC) responses(up to 12 months)