COVID-19 Transmission and Morbidity in Malawi
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: SARS CoV 2 Infection, SARS CoV 2 Vaccination. Basic parameters: 5 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Malawi
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
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 1. Determine the risk and predictors of infection and disease among contacts of SARS-CoV-2 infection subjects in Malawi 2. Determine whether innate immune responses lower the risk of SARS-CoV-2 infection and disease, and acquisition and duration of vaccine responses. 3. Assess whether alterations in innate immune responses relevant to SARS-CoV-2 are associated with malaria or intestinal parasite infections. 4. Assess the acquisition and longevity of antibodies (Ab) and cellular adaptive responses elicited by SARS-CoV-2 infection and vaccination. 5. 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.
Detailed description
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.
Primary outcome measures
- Risk of asymptomatic infection among contacts who acquire infection [Time frame: up to 2 weeks]
- Duration of neutralizing antibody (NAb) responses against two viruses [Time frame: up to 15 months]
- 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 [Time frame: baseline, 2 weeks]
Secondary outcome measures (12)
- Probably of infections in a household [Time frame: up to 2 weeks]
- Duration of COVID-19 symptoms, reinfection rates, and breakthrough infection rates [Time frame: up to 15 months]
- Change in activation status of monocytes and monocyte-derived macrophages (MDMs) with and without stimulation with TLR and RLR agonists in vitro [Time frame: baseline, 2 weeks]
- Change in cell activation markers among stimulated and unstimulated classical monocytes and MDMs [Time frame: baseline, 2 weeks]
- Change in concentrations of pro-inflammatory cytokines and chemokines produced by classic monocytes and MDMs [Time frame: baseline, 2 weeks]
- Change in expression of 770 host response genes in classical monocytes and MDMs [Time frame: baseline, 2 weeks]
- Antibody magnitude to 3 SARS-COV-2 antigens and 3 trimers [Time frame: up to 12 months and 18 months, depending on the cohort]
- NAb responses measured against 3 viruses and through a surrogate assay (sENAB) [Time frame: up to 12 months, 15 months]
- Fc-gamma receptors (FcγR) -II/III binding functional antibody activities [Time frame: 1 month]
- Duration of antibody-dependent cellular cytotoxicity (ADCC) responses [Time frame: up to 12 months]
- Magnitude of dimeric Immunoglobulin A (dIgA) [Time frame: 1 month]
- Frequencies of B (S-antigen specific and total) and plasma cells, and innate immunity parameters [Time frame: up to 12 months, 15 months]
Eligibility criteria
Inclusion Criteria 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
Vaccinees
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
Exclusion Criteria 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 M1.
- Pregnancy at the enrollment visit
- Long term use of cotrimoxazole prophylaxis
Vaccinees
- Conditions that preclude adherence to the visit schedule.
- Pregnancy at the enrollment visit
- Long term use of cotrimoxazole prophylaxis
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
United States · 1 center
- BU School of Public Health, Global Health Department — Boston
Malawi · 1 center
- Health center — Blantyre
Identifiers
NCT: NCT05973084 · H-42505 · 1R01AI164686-01A1