Laboratório de Virologia Molecular, Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, CCS, Bloco A, Sala 121 Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.
Laboratório de Biologia Integrativa, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901, Brazil.
Sci Rep. 2021 May 6;11(1):9658. doi: 10.1038/s41598-021-88944-8.
ACE2 and TMPRSS2 are key players on SARS-CoV-2 entry into host cells. However, it is still unclear whether expression levels of these factors could reflect disease severity. Here, a case-control study was conducted with 213 SARS-CoV-2 positive individuals where cases were defined as COVID-19 patients with respiratory distress requiring oxygen support (N = 38) and controls were those with mild to moderate symptoms of the disease who did not need oxygen therapy along the entire clinical course (N = 175). ACE2 and TMPRSS2 mRNA levels were evaluated in nasopharyngeal swab samples by RT-qPCR and logistic regression analyzes were applied to estimate associations with respiratory outcomes. ACE2 and TMPRSS2 levels positively correlated with age, which was also strongly associated with respiratory distress. Increased nasopharyngeal ACE2 levels showed a protective effect against this outcome (OR = 0.30; 95% CI 0.09-0.91), while TMPRSS2/ACE2 ratio was associated with risk (OR = 4.28; 95% CI 1.36-13.48). On stepwise regression, TMPRSS2/ACE2 ratio outperformed ACE2 to model COVID-19 severity. When nasopharyngeal swabs were compared to bronchoalveolar lavages in an independent cohort of COVID-19 patients under mechanical ventilation, similar expression levels of these genes were observed. These data suggest nasopharyngeal TMPRSS2/ACE2 as a promising candidate for further prediction models on COVID-19.
ACE2 和 TMPRSS2 是 SARS-CoV-2 进入宿主细胞的关键因素。然而，这些因素的表达水平是否能反映疾病的严重程度仍不清楚。在这里，我们进行了一项病例对照研究，共纳入了 213 例 SARS-CoV-2 阳性个体，其中病例定义为需要氧疗的 COVID-19 呼吸困难患者（N=38），对照组为整个临床过程中症状轻微至中度、无需氧疗的患者（N=175）。通过 RT-qPCR 检测鼻咽拭子样本中的 ACE2 和 TMPRSS2 mRNA 水平，并应用逻辑回归分析来评估与呼吸结局的关联。ACE2 和 TMPRSS2 水平与年龄呈正相关，年龄与呼吸窘迫也有很强的相关性。鼻咽 ACE2 水平升高对这种结果具有保护作用（OR=0.30；95%CI 0.09-0.91），而 TMPRSS2/ACE2 比值与风险相关（OR=4.28；95%CI 1.36-13.48）。在逐步回归中，TMPRSS2/ACE2 比值比 ACE2 更能预测 COVID-19 的严重程度。在一个接受机械通气的 COVID-19 患者的独立队列中，对鼻咽拭子和支气管肺泡灌洗液进行比较时，观察到这些基因的表达水平相似。这些数据表明，鼻咽 TMPRSS2/ACE2 是 COVID-19 进一步预测模型的一个有前途的候选物。
