SARS-CoV-2 transmission was expected to have a devastating impact in sub-Saharan Africancountries. Instead, morbidity and mortality rates in nearly the whole region are an orderof magnitude lower than in Europe and the Americas. To identify what is differentrequires a better understanding of the underlying immunological substrate of thepopulation, and how these factors affect susceptibility to infection, progression ofsymptoms, 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.
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.
Inclusion Criteria Index Cases
1. Presents with symptoms of COVID-19 and has infection confirmed through RT-PCR or a
rapid antigen test;
2. 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;
3. Confirmed SARS-CoV-2 infection and share a household with 1 or more individuals of
eligible age;
4. Has not received a SARS-CoV-2 vaccine in the previous 3 months
5. Willingness to comply with study procedures and visits, and provides informed
consent.
Household Contacts of the Confirmed SARS-CoV-2 Case
1. 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;
2. Willingness to comply with study procedures and follow-up visits and provides
informed consent.
3. 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
1. Conditions that precludes from adherence to the visit schedule;
2. 50% or more of household members decline to participate.
3. Pregnancy at the enrollment visit
4. Long term use of cotrimoxazole prophylaxis
Household Contacts of the Confirmed SARS-CoV-2 Case
1. Conditions that preclude adherence to the visit schedule.
2. Participants with 2 consecutive negative SARS-CoV-2 RT-PCRs will be excluded from
visits after M1.
3. Pregnancy at the enrollment visit
4. Long term use of cotrimoxazole prophylaxis
Vaccinees
1. Conditions that preclude adherence to the visit schedule.
2. Pregnancy at the enrollment visit
3. Long term use of cotrimoxazole prophylaxis
BU School of Public Health, Global Health Department
Boston, Massachusetts, United States
Health center
Blantyre, Malawi
Clarissa Valim, MD ScD
(617) 414-1260
cvalim@bu.edu
Aditi S Kothari, BDS MDSc MPH
(617) 358-2441
aditi@bu.edu