Elevated ANG2/ACE2 and immune responses associated with Plasmodium falciparum and SARS-CoV-2 coinfection in Cameroon

Abstract

Malaria and COVID-19 co-infections pose a major clinical challenge, as overlapping symptoms can lead to misdiagnosis and delays in treatment. Emerging evidence suggests that SARS-CoV-2 may influence malaria pathogenesis through dysregulation of the renin-angiotensin system. This study assessed clinical, biochemical, and immunological alterations associated with single and dual infections. A total of 96 participants aged 15-64 years were enrolled and classified into four groups: COVID-19 (n = 28), malaria (n = 28), co-infection (n = 16), and healthy controls (n = 24). Blood and nasopharyngeal samples were tested using rapid diagnostic tests, microscopy, and RT-PCR. Disease severity biomarkers were quantified using spectrophotometry and ELISA. Statistical analyses were performed in GraphPad Prism version 9.0, with significance set at p < 0.05. Co-infected participants exhibited significantly elevated biochemical markers (ALT, AST, urea, creatinine, and erythropoietin) compared to all other groups. Co-infection also triggered robust increases in IFN-γ and IL-1β, whereas malaria alone was associated with higher IL-6, IL-4, and IL-10, and COVID-19 alone was associated with elevated IL-2 and TNF-α. ANG2 levels were highest in both COVID-19 and co-infected groups, while ACE2 was markedly elevated in COVID-19 (p < 0.01). Correlation analyses revealed distinct biomarker networks driven by parasitaemia and viral load, implicating pathways linked to inflammation, erythropoiesis, and endothelial dysfunction. Notably, ACE2 demonstrated strong discriminatory power for predicting disease severity, with AUCs of 0.77 for malaria and 0.85 for COVID-19. These findings underscore the diagnostic and prognostic value of vascular and immune biomarkers for early risk stratification, particularly in malaria-COVID-19 co-infection, and may guide improved clinical management in co-endemic regions.