Sulaiman Imran, Chung Matthew, Angel Luis, Tsay Jun-Chieh J, Wu Benjamin G, Yeung Stephen T, Krolikowski Kelsey, Li Yonghua, Duerr Ralf, Schluger Rosemary, Thannickal Sara A, Koide Akiko, Rafeq Samaan, Barnett Clea, Postelnicu Radu, Wang Chang, Banakis Stephanie, Perez-Perez Lizzette, Jour George, Shen Guomiao, Meyn Peter, Carpenito Joseph, Liu Xiuxiu, Ji Kun, Collazo Destiny, Labarbiera Anthony, Amoroso Nancy, Brosnahan Shari, Mukherjee Vikramjit, Kaufman David, Bakker Jan, Lubinsky Anthony, Pradhan Deepak, Sterman Daniel H, Weiden Michael, Hegu Adriana, Evans Laura, Uyeki Timothy M, Clemente Jose C, De Wit Emmie, Schmidt Ann Marie, Shopsin Bo, Desvignes Ludovic, Wang Chan, Li Huilin, Zhang Bin, Forst Christian V, Koide Shohei, Stapleford Kenneth A, Khanna Kamal M, Ghedin Elodie, Segal Leopoldo N
medRxiv. 2021 Feb 26:2021.02.23.21252221. doi: 10.1101/2021.02.23.21252221.
Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.
新冠病毒病（COVID-19）合并呼吸衰竭患者的死亡率很高，且目前尚无已知的可预测临床结局的下呼吸道生物标志物。我们调查了细菌性呼吸道感染和病毒载量是否与不良临床结局及宿主免疫状态相关。我们获取了589例需要机械通气的COVID-19危重症患者的细菌和真菌培养数据。在接受支气管镜检查的部分患者中，我们还对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒载量进行了定量分析，通过宏基因组和宏转录组分析对下呼吸道微生物群进行了分析，并对宿主免疫反应进行了分析。我们发现，医院获得性呼吸道病原体的分离与死亡结局无关。然而，临床结局不佳与下呼吸道微生物群中口腔共生菌（ ）的富集有关，而高SARS-CoV-2病毒载量、抗SARS-CoV-2抗体反应不佳以及下呼吸道独特的宿主转录组谱最能预测死亡率。总体而言，这些数据支持以下假设：1）病毒感染程度决定了重症COVID-19的死亡率，因此2）应优先考虑针对病毒复制和宿主对SARS-CoV-2反应的临床管理策略。
