Longitudinal analysis of the lung proteome reveals persistent repair months after mild to moderate COVID-19

In order to assess homeostatic mechanisms in the lung after COVID-19, changes in the protein signature of bronchoalveolar lavage from 45 patients with mild to moderate disease at three phases (acute, recovery, and convalescent) are evaluated over a year. During the acute phase, inflamed and uninflam...

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Published in:Cell reports. Medicine 2024-07, Vol.5 (7), p.101642, Article 101642
Main Authors: Kanth, Shreya M., Huapaya, Julio A., Gairhe, Salina, Wang, Honghui, Tian, Xin, Demirkale, Cumhur Y., Hou, Chunyan, Ma, Junfeng, Kuhns, Douglas B., Fink, Danielle L., Malayeri, Ashkan, Turkbey, Evrim, Harmon, Stephanie A., Chen, Marcus Y., Regenold, David, Lynch, Nicolas F., Ramelli, Sabrina, Li, Willy, Krack, Janell, Kuruppu, Janaki, Lionakis, Michail S., Strich, Jeffrey R., Davey, Richard, Childs, Richard, Chertow, Daniel S., Kovacs, Joseph A., Parizi, Parizad Torabi, Suffredini, Anthony F., Pastor, Gloria, Swaim, Doris, Sahagun, Seynt Jiro, Purdy, Julia, Chairez, Cheryl, Dee, Nicola, Curl, Kara, Rehm, Catherine, Santamaria, Ulisses, Caldararo, Rocco, Alsaaty, Sara
Format: Article
Language:English
Subjects:
COVID-19
data-independent acquisition mass spectrometry
longitudinal
lung repair
proteomics
proximal extension assay
SARS-CoV-2
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Summary:In order to assess homeostatic mechanisms in the lung after COVID-19, changes in the protein signature of bronchoalveolar lavage from 45 patients with mild to moderate disease at three phases (acute, recovery, and convalescent) are evaluated over a year. During the acute phase, inflamed and uninflamed phenotypes are characterized by the expression of tissue repair and host defense response molecules. With recovery, inflammatory and fibrogenic mediators decline and clinical symptoms abate. However, at 9 months, quantified radiographic abnormalities resolve in the majority of patients, and yet compared to healthy persons, all showed ongoing activation of cellular repair processes and depression of the renin-kallikrein-kinin, coagulation, and complement systems. This dissociation of prolonged reparative processes from symptom and radiographic resolution suggests that occult ongoing disruption of the lung proteome is underrecognized and may be relevant to recovery from other serious viral pneumonias. [Display omitted] •Host inflammatory proteins are downregulated by 3 months after symptom onset•Lung matrisome expression mirrors acute chest tomography abnormalities•Lavage SPP1 levels are predictive of post-COVID-19 interstitial lung disease•Persistent lung repair is occurring at 9 months post-COVID-19 Kanth et al. evaluate the lung lavage proteome in 45 persons with mild to moderate COVID-19 after acute symptom onset (40 days, mean), recovery (82 days), and convalescence (284 days). Despite clinical resolution at convalescence, the lung proteome does not normalize, suggesting an underrecognized prolongation of lung repair.
ISSN:2666-3791
2666-3791
DOI:10.1016/j.xcrm.2024.101642