Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Kanth SM

PROVIDER: S-EPMC11293333 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Kanth Shreya M SM Huapaya Julio A JA Gairhe Salina S Wang Honghui H Tian Xin X Demirkale Cumhur Y CY Hou Chunyan C Ma Junfeng J Kuhns Douglas B DB Fink Danielle L DL Malayeri Ashkan A Turkbey Evrim E Harmon Stephanie A SA Chen Marcus Y MY Regenold David D Lynch Nicolas F NF Ramelli Sabrina S Li Willy W Krack Janell J Kuruppu Janaki J Lionakis Michail S MS Strich Jeffrey R JR Davey Richard R Childs Richard R Chertow Daniel S DS Kovacs Joseph A JA Parizi Parizad Torabi- PT Suffredini Anthony F AF

Cell reports. Medicine 20240708 7

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. Howeve ...[more]

PMID: 38981485

Similar Datasets

Project description:SARS-CoV2 infection results in clinically heterogeneous manifestations that are partially driven by complex longitudinal interactions with the immune system. The public health burden of mild COVID-19 is massive given the >100 million infected worldwide, but most research has focused on severe and fatal COVID-19. We recruited a mild COVID-19 cohort for multimodal immunophenotyping of single immune cells (scRNAseq, scATACseq, flow cytometry), serum proteins, virus-specific cellular and humoral immune responses, and clinical annotation from early acute infection to convalescence. Samples were acquired longitudinally from early acute infection before 15 days to >100 days post-symptom onset. Comparison to uninfected controls revealed marked immune activation consistent with acute response to viral infection at 15 days post-symptom onset with stronger inflammatory responses in older (>=40) compared to younger (<40) participants. Type I, II, and III interferon responses were most consistently upregulated in nearly all PBMC subsets. Plasmablasts were expanded in early infection with signatures of active IFNL and IFNG signaling, linking early inflammation and IFN responses to control of viral replication via antibodies. Longitudinal models of scRNAseq confirmed most inflammatory pathways decreased over time, including type I and II IFN signaling, as well as signaling by innate danger sensors (TLR, RIG-I) that detect viral replication. By contrast, genes with increasing expression over time were enriched for EMT and wound healing pathways. Most participants showed consistent decay of inflammatory signatures by convalescence at >d 30 post-symptom onset except those presenting with PASC. Despite similar virus-specific adaptive immune responses between post-acute sequelae PASC and recovered convalescent participants, PASC participants showed persistent serum cytokine and chemokine differences including elevated IL5, TNF, IL-12p70, and soluble CD28 at >30 d post-symptom onset. scRNAseq, scATACseq, and network analyses provided more signs of persistent inflammatory activation in multiple cell types, with multimodal evidence pointing to increased activity of innate cells (CD14 monocytes, DCs) and effector T cells (CD4 TEM, CD8 TEMRA). Cytokines at day 7 PSO were highly correlated with and predictive of both virus-specific IgG and neutralizing antibody titers. Integrative network analyses defined the most enriched ligand-receptor pathways across PBMC subsets including LTA/TNF , TNF, and IFNg in early infection, and these also showed signs of persistent activation in PASC. Common downstream targets of these pathways in PASC point to novel therapeutic targets and mechanistic hypotheses, including IL-1Ꞵ, AP-1, ZFP36/TTP, and CEBP/ꞵ. These findings revealed dynamics of immune activation and critical early signals correlated with adaptive immune responses. Serum protein signatures predicting antibody responses and correlating with PASC may provide opportunities for enhanced immunomonitoring and personalized treatment.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets