Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA, USA.
Department of Pediatrics, University of California, San Francisco, CA, USA.
Nat Commun. 2024 Oct 29;15(1):9339. doi: 10.1038/s41467-024-53566-x.
Secondary bacterial pneumonia (2°BP) is associated with significant morbidity following respiratory viral infection, yet remains incompletely understood. In a prospective cohort of 112 critically ill adults intubated for COVID-19, we comparatively assess longitudinal airway microbiome dynamics and the pulmonary transcriptome of patients who developed 2°BP versus controls who did not. We find that 2°BP is significantly associated with both mortality and corticosteroid treatment. The pulmonary microbiome in 2°BP is characterized by increased bacterial RNA mass and dominance of culture-confirmed pathogens, detectable days prior to 2°BP clinical diagnosis, and frequently also present in nasal swabs. Assessment of the pulmonary transcriptome reveals suppressed TNFα signaling in patients with 2°BP, and sensitivity analyses suggest this finding is mediated by corticosteroid treatment. Further, we find that increased bacterial RNA mass correlates with reduced expression of innate and adaptive immunity genes in both 2°BP patients and controls. Taken together, our findings provide fresh insights into the microbial dynamics and host immune features of COVID-19-associated 2°BP, and suggest that suppressed immune signaling, potentially mediated by corticosteroid treatment, permits expansion of opportunistic bacterial pathogens.
继发性细菌性肺炎（2°BP）与呼吸道病毒感染后出现的严重发病率有关，但仍未完全了解。在一项针对 112 例因 COVID-19 而接受气管插管的危重症成年人的前瞻性队列研究中，我们比较评估了发生 2°BP 的患者与未发生 2°BP 的对照组的纵向气道微生物组动态和肺部转录组。我们发现，2°BP 与死亡率和皮质类固醇治疗显著相关。2°BP 的肺部微生物组以细菌 RNA 质量增加和培养确认的病原体优势为特征，在 2°BP 临床诊断前几天即可检测到，并且经常也存在于鼻拭子中。对肺部转录组的评估表明，2°BP 患者的 TNFα 信号受到抑制，敏感性分析表明，这一发现是由皮质类固醇治疗介导的。此外，我们发现，2°BP 患者和对照组中，细菌 RNA 质量的增加与先天和适应性免疫基因的表达降低相关。综上所述，我们的研究结果为 COVID-19 相关 2°BP 的微生物动态和宿主免疫特征提供了新的见解，并表明受抑制的免疫信号（可能由皮质类固醇治疗介导）允许机会性细菌病原体的扩张。
