ACE2 Polymorphisms rs2285666 and rs147311723 Are Clinically Relevant Variants in SARS-CoV-2 and Mycobacterium tuberculosis Co-infection.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells primarily through the angiotensin-converting enzyme 2 (ACE2) receptor. Genetic variation in the ACE2 gene may influence host inflammatory responses and clinical outcomes during COVID-19. Tuberculosis (TB) on the other hand increases the level of ACE2 expression through interferon stimulation. The objective of this study was to investigate the association between specific single-nucleotide polymorphism (SNP) in the ACE2 gene and their impact on susceptibility to and severity of SARS-CoV-2 and Mycobacterium tuberculosis Co-infection. Methods: This retrospective cross-sectional study included 120 symptomatic individuals recruited between September 2020 and December 2023 from four hospitals in Yaounde, Cameroon. Participants were classified into four groups: COVID-19, TB, TB/COVID-19 co-infection, and infection-negative controls. Diagnoses were confirmed using RT-PCR and standard microbiological methods. Serum biochemical markers and cytokines were quantified, and genotyping of ACE2 polymorphisms was performed using TaqMan assays. Results: Statistical analysis showed a significant association between ACE2 expression and inflammatory or biochemical markers, particularly for rs147311723. Several ACE2 polymorphisms (rs6632677, rs147311723, rs4646140, rs2285666, and rs4646142) were significantly associated with increased pro-inflammatory cytokine levels. Selected biochemical parameters demonstrated suggestive associations with ACE2 variants, including creatinine (rs147311723, p = 0.0522), AST (rs2285666, p = 0.0536), and ALT (rs4646142, p = 0.0582), indicating potential renal and hepatic involvement. Principal component analysis identified distinct immunometabolic profiles across patient groups, with co-infected individuals exhibiting heightened inflammatory and metabolic perturbations. Conclusions: These findings suggest that ACE2 genetic variability is associated with modulation of inflammatory responses and may contribute to organ-specific dysfunction in COVID-19 and TB across different populations. This highlights the potential role of host genetics in shaping disease severity and underscore the need for larger studies to validate these associations in diverse populations. Keywords: ACE2 polymorphisms; COVID-19; tuberculosis; co-infection; cytokines; biomarkers; genetic susceptibility;