SARS CoV 2 Infection Clinical Trial
Official title:
COVID-19 Transmission and Morbidity in Malawi
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.
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. ;