We will conduct a clinical study in western Kenya and Burkina-Faso to determine if malaria affects the severity of COVID-19 or its duration. Some patients with COVID-19 also have malaria. We will determine if the treatment of malaria with pyronaridine-artesunate in these patients has an effect on COVID-19 severity or the immune response to COVID-19. Pyronaridine-artesunate is a highly effective malarial treatment that is being rolled out in Africa. In laboratory tests, pyronaridine-artesunate is able to kill viruses, including SARS-CoV-2, the Coronavirus that causes COVID-19. We will follow 708 patients of all ages with COVID-19 for 12 months (the ‘COVID-19 cohort study’). They will be enrolled from a population of approximately 4,720 patients who are being screened for COVID-19 (‘Screening study’). It is anticipated that about 1 in 5 of the 708 COVID-19 patients will also have malaria (about 142). They will be treated with either artemether-lumefantrine (the current standard malaria treatment) or artemether-lumefantrine. The assignment will be decided by chance (random). Hospitalisation, selfisolation and home-based care will follow national guidelines. All 708 COVID-19 patients will be seen again during home/clinic visits on days 1, 3, 7, 14, 21, 28, and 42 when swabs for COVID-19 tests and blood samples will be taken. They will then be seen again at 3, 6, and 12 months. The severity and duration of symptoms, the immune response, and the time that patients remain infectious (can spread the virus to others) will be compared between COVID-19 patients with malaria and without malaria, and between patients treated with artemether-lumefantrine and with pyronaridine-artesunate. Strict adherence to personal protection equipment (PPE) will be used to limit the transmission of the Coronavirus. The transport arrangements for patients and staff will follow national COVID-19 guidelines. Written informed consent/assent will be sought. Participants will potentially benefit from close observations. There is a potential benefit to society as the study will help to obtain a better understanding of the impact of COVID-19 on people’s health in malaria-endemic areas. The study is anticipated to start in October 2020 and finish approximately 18 months later in March 2022.

It is unknown whether malaria or malaria treatment affects COVID-19 severity, immune responses to SARS-CoV-2 virus, or viral loads and/or duration of shedding and therewith the onwards spread of SARS-COV-2. We will conduct an observational cohort study in 708 newly diagnosed COVID-19 patient of all ages in western Kenya and Burkina-Faso. They will be enrolled in hospitals with COVID-19 testing facilities from a source population screened for SARS-CoV-2 (N~4,720). Approximately 142 of the 708 COVID-19 patients are expected to be co-infected with malaria. They will be enrolled in the nested malaria treatment trial and randomized to receive 3-days of artemether-lumefantrine (the current standard of care) or pyronaridine-artesunate, a highly effective antimalarial with known antiviral properties against SARS-CoV-2 in-vitro, that is newly registered and being rolled out in Africa. Disease progression will be assessed and nasal swabs and blood samples taken during home/clinic visits on days 1, 3, 7, 14, 21, 28, and 42 and blood samples at 3, 6, and 12 months. Patients self-isolating will be phoned daily for the first 14 days to assess signs and symptoms. Hospitalisation, self-isolation and home-based care will follow national guidelines. The WHO clinical progression scale and FLU-PRO plus scales will be used to compare disease progression between COVID-19 patients with and without malaria, and by malaria. Other endpoints include seroconversion/reversion rates, chemokine/cytokine responses, T and B cell responses, viral load and duration of viral carriage. Infection prevention and control (IPC), including use of personal protection equipment (PPE), and measures for patient transport will follow national guidelines in each country. Written informed consent/assent will be sought. Participants will potentially benefit from close observations. Society may benefit from improved understanding of the impact of COVID-19 in malaria-endemic areas. The study is anticipated to start in October 2020 and last for approximately 18 months.