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COVID Lung Proteome Provides Recovery, Convalescence Clues

NEW YORK – A team led by investigators at the US National Heart, Lung, and Blood Institute has spelled out the lung proteome patterns that accompany SARS-CoV-2 infection, along with the shifting protein profiles found in the lungs in the months following an infection.

The findings appeared in Cell Reports Medicine on Monday.

"In contrast to healthy persons, the post-COVID-19 lung proteome revealed persistent elevations of proteins associated with tissue repair and activation of proteostasis up to [nine] months after symptom onset," first and corresponding author Shreya Kanth, a critical care medicine researcher at the National Institutes of Health, and her colleagues wrote in their paper.

For their analyses, the researchers relied on three different approaches to profile proteomic patterns in bronchoalveolar lavage lung samples collected over time — during acute, recovery, and convalescent stages of SARS-CoV-2 infection — from 45 individuals with PCR-confirmed COVID-19.

Along with mass spectrometry profiles on lung samples from 29 individuals, they incorporated Olink proximal extension assay data for 39 participants and Meso Scale Discovery- and Luminex-based targeted immunoassay data on 31 of the individuals. They also considered targeted immunoassay data on blood plasma samples for 23 individuals.

"To the best of our knowledge, this is the first comprehensive study investigating the evolution of the lung proteome over the course of [nine] months in patients who have recovered from mild-to-moderate COVID-19," the authors explained.

The team's analyses highlighted divergent phenotypes found during the acute stage of SARS-CoV-2 infection, uncovering lung protein profiles that distinguished COVID-19 cases with inflamed or uninflamed features.

In a recovery period spanning about six to 12 weeks after infection, the team saw waning inflammatory protein activity and declining levels of proteins involved in an extracellular matrix remodeling process known as fibrogenesis as symptoms subsided.

Over a longer convalescent period stretching out to up to 13 months after the initial infection, on the other hand, the researchers saw lung protein patterns that converged on pathways involved in immune activity, proteostasis protein dynamics, and cellular repair processes, even in individuals with seemingly healthy lungs based on post-infection imaging.

"Overall, with the resolution of clinical signs and symptoms, the lung proteome after SARS-CoV-2 infection still shows evidence of ongoing repair and resolution of the host defense response despite differences in the initial host clinical presentation," the authors explained. "Given the absence of protracted pulmonary dysfunction in our patients, these findings reflect a timeline of biological processes occurring in a coordinated post-COVID-19 response."

When the investigators focused on a handful of participants who went on to develop interstitial lung abnormalities in convalescence, meanwhile, they narrowed in on a potential protein marker called SPP1 on the surface of macrophage immune cells that turned up at higher-than-usual levels in bronchoalveolar lavage samples collected earlier on in the recovery process.

"[O]ur findings suggest that SPP1 levels in [bronchoalveolar lavage] early in the post-acute illness phase may serve as a potential marker for the subsequent risk of developing fibrosis," the authors reported, but noted that "[l]arger prospective cohort studies are needed to confirm these observations."