Uncomplicated malaria as a risk factor for COVID-19 duration and severity in western Kenya and Burkina Faso (MALCOV):...

The relationship between malaria and COVID-19 varies across different clinical scenarios; historical malaria exposure might protect against severe COVID-19, whereas co-infection in hospitalised patients with severe disease might increase mortality. Interactions between non-severe malaria and COVID-19 remain poorly understood. We conducted a cohort study among COVID-19 patients of all ages in western Kenya and Burkina Faso to assess the effects of acute, uncomplicated Plasmodium falciparum malaria co-infection on COVID-19 outcomes in ambulatory patients.

Participants with laboratory-confirmed SARS-CoV-2 infection (positive rapid antigen test or reverse transcription quantitative real-time PCR [RT-qPCR]) were tested for malaria by rapid antigen tests with confirmatory microscopy. Patients with COVID-19 and malaria co-infection received artemether-lumefantrine or pyronaridine-artesunate. COVID-19 symptom course was assessed daily using FLU-PRO Plus (a validated patient-reported outcome instrument) until day 14. Viral load was measured by RT-qPCR on days 0, 3, 7, 14, and 28. The primary endpoint was time to symptom resolution on the FLU-PRO Plus. Analyses were adjusted for country, age, disease severity, and viral load.

Between Jan 8, 2021 and Jan 24, 2022, we screened 5161 participants and recruited 756 with COVID-19. 742 participants with valid malaria tests were enrolled, of which 151 (20%) had malaria co-infection and the remaining 591 (80%) did not have malaria. Patients with malaria were younger (49 [32%] aged <15 years) than those without malaria (35 [6%]; p<0·0001). Time to symptom resolution was similar between those with malaria (median 9 days [IQR 5-13]) and those without (10 days [IQR 6-13]; adjusted hazard ratio [aHR] 1·14 [95% CI 0·91-1·42]; p=0·26). Three (2%) patients with malaria and nine (2%) without malaria were hospitalised; two (1%) with malaria and three (1%) without malaria died, four from acute respiratory distress syndrome and one (in the no malaria group) from perforated peptic ulcer complicated by anaemia. Participants with malaria more frequently reported moderate-to-severe symptoms at enrolment (68% vs 60%; p=0·074), but overall symptom duration was similar (adjusted incidence rate ratio 0·95 [95% CI 0·86-1·05]; p=0·31). Previous malaria exposure significantly modified outcomes, with patients with malaria co-infection and previous exposure having faster symptom clearance than those without previous exposure (p_interaction=0·042). SARS-CoV-2 clearance was slower in the malaria group by day 7 (aHR 0·69 [95% CI 0·51-0·94]; p=0·017) but was similar between groups by day 28 (adjusted risk ratio 0·99 [95% CI 0·79-1·24]; p=0·95).

This study shows that acute uncomplicated malaria co-infection does not adversely affect COVID-19 progression when appropriately treated. Moreover, serological evidence confirms that previous lifelong malaria exposure might provide some protection, with exposed individuals having faster symptom resolution.

Gates Foundation.

For the French translation of the abstract see Supplementary Materials section.