Jiménez-Gil Karina, Cerón-Albarrán Jorge Alberto, Gonzalez-Fernandez Melissa Daniella, Sevilla-Montoya Rosalba, Hidalgo-Bravo Alberto, Angeles-Martínez Javier, Montes-Herrera Daniel, Villavicencio-Carrisoza Oscar, García-Romero Carmen Selene, Muñoz-Medina José Esteban, Monroy-Muñoz Irma Eloisa
Reproductive and Perinatal Health Research Department, National Institute of Perinatology, Mexico City 11000, Mexico.
Genomics Medicine Department, National Institute of Rehabilitation, Mexico City 14610, Mexico.
Microorganisms. 2024 Dec 12;12(12):2560. doi: 10.3390/microorganisms12122560.
The persistence of qPCR positivity for SARS-CoV-2 in individuals who recovered from COVID-19 raised several questions regarding viral transmission, with a special interest in healthcare professionals who may pose a risk of transmitting SARS-CoV-2. This issue highlights the necessity for identifying the genetic risk factors associated with persistent SARS-CoV-2 infection. A promising target for achieving this goal is the angiotensin-converting enzyme 2 () gene, which has been associated with clinical characteristics of COVID-19 infection, such as severity. The analysis of samples from the first wave of the COVID-19 pandemic represents the initial response of the immune human system against this new virus, without the effect of vaccination or the presence of multiple strains. The aim of this study was to analyze the association of genetic variants in with persistent SARS-CoV-2 infection. We conducted a case-control study, including 151 healthcare workers who tested positive for SARS-CoV-2 by qPCR during the first wave of the COVID-19 pandemic, and who were followed up until their results were negative. was sequenced through Sanger sequencing. The sequence was compared against a reference sequence and variants identified. Four variants were associated with persistent SARS-CoV-2 qPCR positivity. Three of the variants with an effect on the resulting protein were associated with increased risk of persistent SARS-CoV-2 qPCR positivity, NG_012575.2:g.35481 C>T, NG_012575.2:g.35483 G>T and NG_012575.2:g.35498 G>T. On the other hand, the rs2285666 (NG_012575.2:g.14934 G>A) was associated with a higher risk for persistent SARS-CoV-2 qPCR positivity in women and rs4646150 (NG_012575.2:g.25701 G>A) in men. The NG_012575.2:g.35498 G>T variant represents an amino acid change with a possibly harmful effect on ACE2 function. Our results suggest that variants might be useful for identifying the population at higher risk for developing persistent SARS-CoV-2-positive qPCR results. This knowledge can be helpful for designing health policies for protecting healthcare professionals and, in consequence, users of health services.
新冠病毒感染康复者中SARS-CoV-2的qPCR检测持续呈阳性，引发了有关病毒传播的几个问题，尤其引起了对可能构成SARS-CoV-2传播风险的医护人员的关注。这个问题凸显了识别与SARS-CoV-2持续感染相关的遗传风险因素的必要性。实现这一目标的一个有前景的靶点是血管紧张素转换酶2（ACE2）基因，它与新冠病毒感染的临床特征（如严重程度）有关。对新冠疫情第一波期间样本的分析代表了人类免疫系统对这种新病毒的初始反应，没有疫苗接种的影响或多种毒株的存在。本研究的目的是分析ACE2基因变异与SARS-CoV-2持续感染之间的关联。我们进行了一项病例对照研究，纳入了151名医护人员，他们在新冠疫情第一波期间通过qPCR检测SARS-CoV-2呈阳性，并接受随访直至检测结果转为阴性。通过桑格测序对ACE2进行测序。将序列与参考序列进行比较并确定变异。四个ACE2变异与SARS-CoV-2的qPCR持续阳性有关。其中三个对所产生蛋白质有影响的变异与SARS-CoV-2的qPCR持续阳性风险增加有关，即NG_012575.2:g.35481 C>T、NG_012575.2:g.35483 G>T和NG_012575.2:g.35498 G>T。另一方面，rs2285666（NG_012575.2:g.14934 G>A）与女性SARS-CoV-2的qPCR持续阳性风险较高有关，而rs4646150（NG_012575.2:g.25701 G>A）与男性有关。NG_012575.2:g.35498 G>T变异代表一种氨基酸变化，可能对ACE2功能产生有害影响。我们的结果表明，ACE2变异可能有助于识别SARS-CoV-2 qPCR检测结果持续呈阳性风险较高的人群。这一知识有助于制定保护医护人员以及卫生服务使用者的卫生政策。
