COVID-19 Transmission and Morbidity in Malawi
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age5-75
SponsorBoston University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial population
This study will take place in Blantyre, in one or all of the following health centers and their catchment areas: Bangwe, Chileka, Chilomoni, and Mpemba. These health centers were chosen because transmission of SARS-CoV-2 and malaria were recorded in their catchment area in the past two years. If needed, to reach the recruitment target, different health services in Blantyre may be considered for this research.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
1,500 Participants
are grouped into 2 trial groupsGroup A: Natural infection cohort
Group B: Vaccine cohort
Trial outcomes
Primary outcomes
1
Risk of asymptomatic infection among contacts who acquire infection
Proportion of household members who acquire an asymptomatic (vs. symptomatic) infection among household contacts of an index case
Time frame
up to 2 weeks2
Duration of neutralizing antibody (NAb) responses against two viruses
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.
Time frame
up to 15 months3
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
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
Time frame
baseline, 2 weeksSecondary outcomes
1
Probably of infections in a household
Estimated probability of infection among household contacts of an index case
Time frame
up to 2 weeks2
Duration of COVID-19 symptoms, reinfection rates, and breakthrough infection rates
Days to resolve symptoms in each symptomatic episode and number of confirmed SARS-CoV-2 infection through RT-PCR after a first infection or vaccination
Time frame
up to 15 months3
Change in activation status of monocytes and monocyte-derived macrophages (MDMs) with and without stimulation with TLR and RLR agonists in vitro
Percentage positive of activation markers (CD169, CD86, and CD80) will be quantified by flow cytometry and can range from 0 to 100 of percent positive cells. Change = Percentage positive of CD169, CD86, and CD80 at 2 weeks - Percentage positive at baseline
Time frame
baseline, 2 weeks4
Change in cell activation markers among stimulated and unstimulated classical monocytes and MDMs
Difference between measures obtained at 2 weeks and baseline in percentage positive of CD169, CD86 and CD80 expression will be measured quantified through flow cytometry. Change = Percentage positive of CD169, CD86, and CD80 at 2 weeks - Percentage positive at baseline
Time frame
baseline, 2 weeksSponsors and contacts
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Boston University
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator
Kamuzu University of Health Sciences
Collaborator
Burnet Institute
Collaborator
Source ClinicalTrials.gov