MALCOV - Malaria as a Risk Factor for COVID-19
To assess whether malaria infection affects the clinical course of COVID-19 in Kenya and Burkina Faso.
Screening study (cross-sectional survey source population)
• To determine if malaria infection is predictive of the prevalence of SARS-CoV-2, adjusted for other risk factors of SARS-CoV-2 infection
COVID-19 cohort study
• To determine if malaria infection affects COVID-19 severity
Nested malaria treatment trial
• To determine if pyronaridine-artesunate compared to artemether-lumefantrine reduces early SARS-CoV-2 viral shedding
While in resource-rich countries, knowledge about the risk factors for severe COVID-19 is rapidly evolving, less is known about risk factors in malaria-endemic countries. It is unknown whether malaria worsens COVID-19, affects the acquisition of protective antibodies against the SARS-CoV-2 virus, or contributes to its onwards spread by resulting in higher viral loads and longer duration of viral shedding. The relationship may be complex, as chronic malaria may result in a hypo-responsive immune system, which, in some instances, could be protective if it dampens some of the potentially fatal excessive immune responses associated with ‘cytokine storms’ seen in some patients with severe COVID-19. It is also unknown if the effective treatment of malaria changes any of these potential associations. Evidence is accumulating that the antimalarial chloroquine, which has antiviral properties against SARS-CoV-2 in the laboratory, may not be as effective for the treatment of COVID-19 as was anticipated. Treatment with chloroquine may also have unintended consequences as it is known to reduce the effectiveness of vaccination against the viral disease rabies. It remains to be determined if chloroquine, or related antimalarial compounds such as pyronaridine, have a positive, negative, or no negligible effect on the immune response to COVID-19
The overarching goal of this study is to assess if malaria alters the severity and duration of COVID-19 among a predominantly outpatient population with SARS-CoV-2 infection to inform public health control strategies. We propose to enrol a prospective COVID-19 cohort study among confirmed COVID-19 cases selected from a source population consisting of all suspected cases tested for SARS-CoV-2. We will conduct a nested malaria treatment trial among the COVID-19 cohort study participants who are co-infected with malaria at enrolment.
- Kenya - As of writing (July 24, 2020), there are 16,601 COVID-19 cases in Kenya. The study will be conducted in western Kenya, where malaria transmission is perennial, and the year-round all-age prevalence (mRDT-positivity) in rural areas in Siaya County is 29% (range 25-40%). Recruitment will be from a series of public and private hospitals and clinics that conduct screening for COVID-19 cases in counties encompassing the previous Nyanza and Western Provinces in western Kenya. The precise location will depend on the local transmission dynamics of SARS-CoV-2.The fieldwork will be conducted as part of the ongoing collaboration between KEMRI, CDC, and LSTM in malaria-endemic counties western Kenya.
- Burkina Faso - As of writing (July 24, 2020), there are 1,075 COVID-19 cases in Burkina Faso. In Burkina, malaria transmission is seasonal, reaching a peak in October/ November of 30% RDT positivity in all ages. The study will be conducted in hospitals designated for care and treatment of COVID-19 cases in Ouagadougou (currently three hospitals) and, if sample size requirements dictate, Bobo Dioulasso. The work will be coordinated by the Groupe de Recherche Action en Santé, Ouagadougou.
We will conduct an 18-month clinical study in multiple sites in Kenya and Burkina-Faso to determine if malaria or the type of antimalarial drugs affect COVID-19 disease progression. The study consists of a cohort of approximately 708 patient of all ages with newly diagnosed COVID-19 (the ‘COVID-19 cohort study’). They will be enrolled from a population of approximately 4,720 participants across ages who will be screened for COVID-19. It is anticipated that approximately 142 (20%) of the 708 cohort participants will also be co-infected with malaria and require antimalarial treatment. These 142 participants co-infected with malaria will be enrolled in a ‘nested malaria treatment trial’ if they have mild disease and are able to take oral medication. They will be randomised to receive either a standard 3-day treatment course of artemether-lumefantrine (the current first-line treatment) or pyronaridine-artesunate, a new highly effective antimalarial combination that is rapidly being rolled out in Kenya and Burkina-Faso. All COVID-19 patients without malaria will be treated as per the national guidelines, which includes either self-isolation or hospitalisation in treatment or isolation wards. All cohort patients will be followed for 28 days and nasal swabs and blood samples taken on days 1, 3, 7, 14, 21 and 28. Subject to funding, additional samples will be taken at 6 weeks, and at 3, 6, and 12 months to determine the duration of the protective antibody responses to the SARS-CoV-2 virus. The severity and duration of symptoms, the immunological response, and the time the patients remain infectious will be compared between COVID-19 patients with and without malaria co-infection, and by malaria treatment arm. Results will also be compared by age group, gender, and other known risk factors. To limit the transmission of SARS-CoV-2, strict adherence to personal protection equipment (PPE) use, and patient transport will be followed as per national guidelines. Written informed consent/assent will be sought.
- Cross-sectional comparison of the proportion of participants with SARS-CoV-2 in the source population among participants with and without malaria infection expressed as the prevalence ratio for COVID-19 (95% CI)
- Cohort: Comparison of the severity of COVID-19 by day-28 in cases with and without malaria using a severity index score
- Malaria treatment cohort- Incidence of SARS-CoV-2 clearance (defined as the proportion of participants with a negative nasal swab) on Day 7 after the start of treatment