Unisabana Center of Translational Science, Universidad de La Sabana, Campus Puente del Común, KM 7.5 Autopista Norte de Bogotá, Chia, Colombia.
Bioscience Ph.D., Engineering Faculty, Universidad de La Sabana, Chia, Colombia.
Sci Rep. 2024 Nov 12;14(1):27637. doi: 10.1038/s41598-024-78992-1.
Patients with COVID-19 under invasive mechanical ventilation are at higher risk of developing ventilator-associated pneumonia (VAP), associated with increased healthcare costs, and unfavorable prognosis. The underlying mechanisms of this phenomenon have not been thoroughly dissected. Therefore, this study attempted to bridge this gap by performing a lung microbiota analysis and evaluating the host immune responses that could drive the development of VAP. In this prospective cohort study, mechanically ventilated patients with confirmed SARS-CoV-2 infection were enrolled. Nasal swabs (NS), endotracheal aspirates (ETA), and blood samples were collected initially within 12 h of intubation and again at 72 h post-intubation. Plasma samples underwent cytokine and metabolomic analyses, while NS and ETA samples were sequenced for lung microbiome examination. The cohort was categorized based on the development of VAP. Data analysis was conducted using RStudio version 4.3.1. In a study of 36 COVID-19 patients on mechanical ventilation, significant differences were found in the nasal and pulmonary microbiome, notably in Staphylococcus and Enterobacteriaceae, linked to VAP. Patients with VAP showed a higher SARS-CoV-2 viral load in respiratory samples, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1β, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. Metabolomic analysis revealed changes in 22 metabolites in non-VAP patients and 27 in VAP patients, highlighting D-Maltose-Lactose, Histidinyl-Glycine, and various phosphatidylcholines, indicating a metabolic predisposition to VAP. This study reveals a critical link between respiratory microbiome alterations and ventilator-associated pneumonia in COVID-19 patients with higher SARS-CoV-2 viral loads in respiratory samples, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1β, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. These findings provide novel insights into the underlying mechanisms of VAP, with potential implications for management and prevention.
COVID-19 患者接受有创机械通气治疗后，发生呼吸机相关性肺炎（VAP）的风险较高，这与医疗成本增加和预后不良有关。但这一现象的潜在机制尚未被彻底剖析。因此，本研究试图通过进行肺部微生物组分析并评估可能导致 VAP 发生的宿主免疫反应来填补这一空白。在这项前瞻性队列研究中，纳入了确诊为 SARS-CoV-2 感染且接受有创机械通气治疗的患者。在插管后 12 小时内以及再次插管后 72 小时，采集鼻拭子（NS）、气管内吸出物（ETA）和血样。对血浆样本进行细胞因子和代谢组学分析，同时对 NS 和 ETA 样本进行测序以进行肺部微生物组检查。根据 VAP 的发生情况对队列进行分类。数据分析使用 RStudio 版本 4.3.1 进行。在一项对 36 名 COVID-19 机械通气患者的研究中，在鼻腔和肺部微生物组中发现了显著差异，尤其是葡萄球菌属和肠杆菌科，这与 VAP 相关。发生 VAP 的患者在呼吸道样本中显示出更高的 SARS-CoV-2 病毒载量、更高水平的中和抗体和更低水平的炎症细胞因子，包括 IFN-δ、IL-1β、IL-12p70、IL-18、IL-6、TNF-α和 CCL4。代谢组学分析显示，非 VAP 患者中有 22 种代谢物发生变化，VAP 患者中有 27 种代谢物发生变化，其中包括 D-麦芽糖乳糖、组氨酰-甘氨酸和各种磷脂酰胆碱，表明存在发生 VAP 的代谢倾向。这项研究揭示了 COVID-19 患者中呼吸微生物组改变与呼吸机相关性肺炎之间的关键联系，这些患者的呼吸道样本中 SARS-CoV-2 病毒载量较高、中和抗体水平升高、炎症细胞因子（包括 IFN-δ、IL-1β、IL-12p70、IL-18、IL-6、TNF-α和 CCL4）水平降低。这些发现为 VAP 的潜在机制提供了新的见解，可能对管理和预防具有重要意义。
