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Investigating the potential of clinical variables and ace2/tmprss2 genetic variants as a biomarkers for COVID-19 and malaria co-infection in Cameroon

Tchoupe Kamoua, E. B.; Kameni, M. N.; Eric, M. B.; Taya, J. B.; Kamdem, S. D.; Numfor Nkah, L.; Ama Moor, V.; Tepa, A.; Neba, F. R.; Afum-Adjei Awuah, A.; Humphrey Amuasi, J.; Masumbe Netongo, P.

2025-08-05 genetic and genomic medicine
10.1101/2025.08.01.25332654 medRxiv
Show abstract

Malaria and COVID-19 dual infections can worsen the severity of both diseases and lead to misdiagnosis due to overlapping symptoms. It is reported that SARS-CoV-2 may affect malaria progression through the renin-angiotensin system. A total of 96 participants aged 15 to 64 years were retained and divided into four groups: COVID-19 (28), malaria (28), co-infection (16), and controls (24). Blood and nasopharyngeal samples were tested for both diseases using RDT and RT-PCR. Disease severity markers were assessed using spectrophotometry and ELISA while genetic variations in ace2 and tmprss2 genes were analyzed using qPCR. Data were analyzed using GraphPad Prism version 9.0. Statistical significance was set at p<0.05. Significant increases in biochemical markers (ALT, AST, urea, creatinine, and erythropoietin) were observed in the co-infected group compared to others groups. While inflammatory cytokines (IL-4, IL6, and IL-10) levels were higher in malaria cohort, the ACE2 biomarker showed strong discriminatory capacity for predicting disease severity, with AUCs of 0.77 for malaria and 0.85 for COVID-19. Additionally, ACE2 genetic mutations correlated with higher vascular markers (ANG2 and ACE2). This research explored the role of single nucleotide polymorphisms (SNPs) in ace2/tmprss2 in malaria and COVID-19 co-infection severity.

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