Clinical trial NCT05973084: COVID-19 Transmission and Morbidity in Malawi
Official title: COVID-19 Transmission and Morbidity in Malawi
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: SARS CoV 2 Infection
SARS CoV 2 Vaccination
Keywords: Natural infection
Immune phenotypes
Innate immunity
SARS CoV 2 adaptive immunity
SARS CoV 2 antibody response
Vacinees
Household contacts
Malawi
Sub Saharan Africa
Lead sponsor: Boston University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Malaria Alert Center, Kamuzu University of Health Sciences
name: Burnet Institute
First posted: 2023-08-02
Enrollment: 1500
Sex: ALL
Minimum age (years): 5
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study 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.

Brief summary: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Risk of asymptomatic infection among contacts who acquire infection
timeFrame: up to 2 weeks
measure: Duration of neutralizing antibody (NAb) responses against two viruses
timeFrame: up to 15 months
measure: 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
timeFrame: baseline, 2 weeks
Secondary outcomes:
measure: Probably of infections in a household
timeFrame: up to 2 weeks
measure: Duration of COVID-19 symptoms, reinfection rates, and breakthrough infection rates
timeFrame: up to 15 months
measure: Change in activation status of monocytes and monocyte-derived macrophages (MDMs) with and without stimulation with TLR and RLR agonists in vitro
timeFrame: baseline, 2 weeks
measure: Change in cell activation markers among stimulated and unstimulated classical monocytes and MDMs
timeFrame: baseline, 2 weeks
measure: Change in concentrations of pro-inflammatory cytokines and chemokines produced by classic monocytes and MDMs
timeFrame: baseline, 2 weeks
measure: Change in expression of 770 host response genes in classical monocytes and MDMs
timeFrame: baseline, 2 weeks
measure: Antibody magnitude to 3 SARS-COV-2 antigens and 3 trimers
timeFrame: up to 12 months and 18 months, depending on the cohort
measure: NAb responses measured against 3 viruses and through a surrogate assay (sENAB)
timeFrame: up to 12 months, 15 months
measure: Fc-gamma receptors (FcγR) -II/III binding functional antibody activities
timeFrame: 1 month
measure: Duration of antibody-dependent cellular cytotoxicity (ADCC) responses
timeFrame: up to 12 months
measure: Magnitude of dimeric Immunoglobulin A (dIgA)
timeFrame: 1 month
measure: Frequencies of B (S-antigen specific and total) and plasma cells, and innate immunity parameters
timeFrame: up to 12 months, 15 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: BU School of Public Health, Global Health Department
state: Massachusetts
city: Blantyre
country: Malawi
facility: Health center
Study officials:
affiliation: BU School of Public Health, Department of Global Health
name: Clarissa Valim, MD ScD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kamuzu University of Health Sciences, Malaria Alert Center, Malawi
name: Don Mathanga, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: BU School of Public Health, Department of Global Health
name: Patricia Hibberd, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Burnet Institute, Australia
name: James Beeson, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References: