COVID-19 Transmission and Morbidity in Malawi

NCT05973084 | Recruiting

• 2 other identifiers: H-425051R01AI164686-01A1
• Study Type: observational
• Target: 1,500
• Locations: 2 countries
• Sites: 2

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. 1.Determine the risk and predictors of infection and disease among contacts of SARS-CoV-2 infection subjects in Malawi
2. 2.Determine whether innate immune responses lower the risk of SARS-CoV-2 infection and disease, and acquisition and duration of vaccine responses.
3. 3.Assess whether alterations in innate immune responses relevant to SARS-CoV-2 are associated with malaria or intestinal parasite infections.
4. 4.Assess the acquisition and longevity of antibodies (Ab) and cellular adaptive responses elicited by SARS-CoV-2 infection and vaccination.
5. 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.

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

Outcome Measures

Primary Outcomes (3)

• 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

  up to 2 weeks

• 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.

  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

  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

  baseline, 2 weeks

Secondary Outcomes (12)

• Probably of infections in a household

  up to 2 weeks

• Duration of COVID-19 symptoms, reinfection rates, and breakthrough infection rates

  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

  baseline, 2 weeks

• Change in cell activation markers among stimulated and unstimulated classical monocytes and MDMs

  baseline, 2 weeks

• Change in concentrations of pro-inflammatory cytokines and chemokines produced by classic monocytes and MDMs

  baseline, 2 weeks

Study Arms (2)

Natural infection cohort

Up to 200 symptomatic subjects (index cases) will be enrolled when they seek diagnosis for their symptoms of COVID-19 and have their SARS-CoV-2 infection confirmed. All their household contacts (anticipated 700) aged 5-75 years who provide consent (participants) will be examined for infection through two consecutive SARS-CoV-2 RT-PCR. Blood will be drawn from all participants who provide consent. Venous Blood will be drawn at the first visit (so called W0). A second collection is planned for 15 days after the first visit, a third collection at three months after the first visit, and subsequent collections are planned at six, nine, and 15 months after the first visit. At the visits one month, nine months and 15 months after the first visit, capillary blood will be collected. A stool sample will be collected for diagnosis of intestinal parasites.

Vaccine cohort

Up to 600 subjects 18-75 years will be recruited when they attend a vaccination clinic at one of the study health centers in Blantyre to receive their 1st dose of the AstraZeneca (AZ) or the Johnson and Johnson (JJ) COVID-19 vaccines. Venous blood will be collected at that time. For AZ vaccinees, at their 2nd vaccine dose, about 90 days after the 1st dose, they will be given a stool sample container. JJ vaccinees will receive the stool sample container when they receive the first vaccine dose. Two weeks after completion of the primary regimen (2nd dose of the AZ \[M3.5\] and 1st dose of the JJ vaccines \[M0.5\]), venous blood draws will be repeated and stool containers will be collected. Subsequent visits/procedures will happen at one month thereafter (M4.5 for AZ and M1.5 for JJ), and 3, 6, 9, and 12 months after the primary regimen. Venous blood will be collected at the visit 1.5, 3, 6, and 12 months after the primary regimen and capillary blood will be collected at the other visits.

Eligibility Criteria

• Age: 5 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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
• \) 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.
• \) Has not received a prior dose of a SARS-CoV-2 vaccine

You may not qualify if:

• Conditions that precludes from adherence to the visit schedule;
• % 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

Sponsors & Collaborators

• Boston University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Malaria Alert Center, Kamuzu University of Health Sciences: collaborator
• Burnet Institute: collaborator

Study Sites (2)

BU School of Public Health, Global Health Department

Boston, Massachusetts, 02118, United States

ACTIVE NOT RECRUITING

Health center

Blantyre, Malawi

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peripheral Blood Mononuclear Cells (PBMC), Blood preserved in PAXgene solution, Nasopharyngeal Swab suspension and Plasma.

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Clarissa Valim, MD ScD

  BU School of Public Health, Department of Global Health

  PRINCIPAL INVESTIGATOR

• Don Mathanga, MBBS PhD

  Kamuzu University of Health Sciences, Malaria Alert Center, Malawi

  PRINCIPAL INVESTIGATOR

• Patricia Hibberd, MD PhD

  BU School of Public Health, Department of Global Health

  PRINCIPAL INVESTIGATOR

• James Beeson, MBBS PhD

  Burnet Institute, Australia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clarissa Valim, MD ScD

CONTACT

(617) 414-1260; cvalim@bu.edu

Aditi S Kothari, BDS MDSc MPH

CONTACT

(617) 358-2441; aditi@bu.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: August 2, 2023
• Study Start: January 17, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); MA (1)