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Role of ACE1, ACE2, and CCR5-Δ32 Polymorphisms in the Transmission of SARS-CoV-2 to Intimate Contacts
1
Dipartimento di Medicina, Chirurgia e Farmacia, University of Sassari, Clinica Medica, Viale San Pietro 8, 07100 Sassari, Italy
2
Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
3
Dipartimento di Scienze Biomediche, University of Sassari, Viale San Pietro 43, 07100 Sassari, Italy
4
Sardinia Blue Zone Longevity Observatory, 08040 Santa Maria Navarrese, Italy
*
Author to whom correspondence should be addressed.
Biology 2025, 14(6), 587; https://doi.org/10.3390/biology14060587
Submission received: 7 April 2025
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Revised: 7 May 2025
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Accepted: 20 May 2025
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Published: 22 May 2025
(This article belongs to the Section Infection Biology)
Simple Summary
Some people seem to be resistant to infection by viruses that cause COVID-19, even after close and prolonged contact with someone who is infected. This study explores whether certain inherited genetic traits might explain this phenomenon. Researchers looked at 63 couples in Sardinia, where one partner had COVID-19 during the first wave of the pandemic, and the other either did or did not become infected despite sharing a bed. They focused on specific gene variants that may influence how easily a person becomes infected. The results showed that there were no major differences in these gene variants between the partners who became infected and those who did not. This suggests that resistance to the virus cannot be explained by these genes alone. Other factors (such as how an individual’s immune system works or environmental conditions) are likely to play an important role. Understanding why some people resist infection could help develop better ways to protect the public in future outbreaks.
Abstract
Background. Despite the high transmissibility of SARS-CoV-2, some individuals remain uninfected despite prolonged exposure to a high viral load, suggesting the involvement of an innate resistance mechanism, possibly underpinned by the host’s genetic factors. The angiotensin-converting enzyme-1 (ACE1), ACE2, and C-C Chemokine Receptor 5 (CCR5) polymorphisms have been shown to influence susceptibility to the infection. In this study, the role of ACE1, ACE2, and CCR5 gene polymorphisms in modulating susceptibility to SARS-CoV-2 infection within the context of intimate contact was evaluated. Methods. A cohort of heterosexual couples from Northern Sardinia, characterized by a homogenous genetic background, was recruited during the initial pandemic wave (March–June 2020). In each couple, one partner (index case) tested positive for SARS-CoV-2 by at least two consecutive independent molecular tests (real-time polymerase chain reaction: RT-PCR) on nasopharyngeal swabs. Bed-sharing partners of SARS-CoV-2 positive index cases, resistant and susceptible to the infection, were genotyped for ACE1 287 bp Alu repeat insertion/deletion (I/D) polymorphism, ACE2 G8790A (rs2285666) variant, and a 32-base pair deletion (Δ32) of CCR5. Resistant and susceptible partners to the infection were compared for polymorphisms. Results. Out of 63 couples, 30 partners acquired SARS-CoV-2 infection, while 33 remained uninfected despite intimate exposure. Clinical history was minimal for current or past illnesses. SARS-CoV-2-infected index spouses and partners who acquired the infection developed a mild disease, not requiring hospitalization. The observed distribution of ACE1 I/D and ACE2 G8790A genotypes was consistent with previously reported frequencies in Sardinia and across European populations. None of the study participants carried the CCR5-Δ32 variant. No statistically significant differences (p > 0.05) in the allelic or genotypic frequencies of these polymorphisms were observed between the infected and resistant partners. Conclusions. No differences in the distribution of ACE1, ACE2, and CCR5 polymorphisms between the two groups were detected. These findings suggest that resistance is likely multifactorial, involving a complex interplay of genetic, immunological, and environmental factors.
