Dataset Information

Fulminant lung fibrosis in non-resolvable COVID-19 requiring transplantation.

ABSTRACT:

Background

Coronavirus Disease 2019 (COVID-19) can lead to the development of acute respiratory distress syndrome (ARDS). In some patients with non-resolvable (NR) COVID-19, lung injury can progress rapidly to the point that lung transplantation is the only viable option for survival. This fatal progression of lung injury involves a rapid fibroproliferative response and takes on average 15 weeks from initial symptom presentation. Little is known about the mechanisms that lead to this fulminant lung fibrosis (FLF) in NR-COVID-19.

Methods

Using a pre-designed unbiased PCR array for fibrotic markers, we analyzed the fibrotic signature in a subset of NR-COVID-19 lungs. We compared the expression profile against control lungs (donor lungs discarded for transplantation), and explanted tissue from patients with idiopathic pulmonary fibrosis (IPF). Subsequently, RT-qPCR, Western blots and immunohistochemistry were conducted to validate and localize selected pro-fibrotic targets. A total of 23 NR-COVID-19 lungs were used for RT-qPCR validation.

Findings

We revealed a unique fibrotic gene signature in NR-COVID-19 that is dominated by a hyper-expression of pro-fibrotic genes, including collagens and periostin. Our results also show a significantly increased expression of Collagen Triple Helix Repeat Containing 1(CTHRC1) which co-localized in areas rich in alpha smooth muscle expression, denoting myofibroblasts. We also show a significant increase in cytokeratin (KRT) 5 and 8 expressing cells adjacent to fibroblastic areas and in areas of apparent epithelial bronchiolization.

Interpretation

Our studies may provide insights into potential cellular mechanisms that lead to a fulminant presentation of lung fibrosis in NR-COVID-19.

Funding

National Institute of Health (NIH) Grants R01HL154720, R01DK122796, R01DK109574, R01HL133900, and Department of Defense (DoD) Grant W81XWH2110032 to H.K.E. NIH Grants: R01HL138510 and R01HL157100, DoD Grant W81XWH-19-1-0007, and American Heart Association Grant: 18IPA34170220 to H.K.-Q. American Heart Association: 19CDA34660279, American Lung Association: CA-622265, Parker B. Francis Fellowship, 1UL1TR003167-01 and The Center for Clinical and Translational Sciences, McGovern Medical School to X.Y.

SUBMITTER: Jyothula SSK

PROVIDER: S-EPMC9667270 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Fulminant lung fibrosis in non-resolvable COVID-19 requiring transplantation.

Jyothula Soma S K SSK Peters Andrew A Liang Yafen Y Bi Weizhen W Shivshankar Pooja P Yau Simon S Garcha Puneet S PS Yuan Xiaoyi X Akkanti Bindu B Collum Scott S Wareing Nancy N Thandavarayan Rajarajan A RA Poli de Frias Fernando F Rosas Ivan O IO Zhao Bihong B Buja L Maximilian LM Eltzschig Holger K HK Huang Howard J HJ Karmouty-Quintana Harry H

EBioMedicine 20221111

<h4>Background</h4>Coronavirus Disease 2019 (COVID-19) can lead to the development of acute respiratory distress syndrome (ARDS). In some patients with non-resolvable (NR) COVID-19, lung injury can progress rapidly to the point that lung transplantation is the only viable option for survival. This fatal progression of lung injury involves a rapid fibroproliferative response and takes on average 15 weeks from initial symptom presentation. Little is known about the mechanisms that lead to this ful ...[more]

PMID: 36375315

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Dataset Information

Fulminant lung fibrosis in non-resolvable COVID-19 requiring transplantation.

Background

Methods

Findings

Interpretation

Funding

Publications

Fulminant lung fibrosis in non-resolvable COVID-19 requiring transplantation.

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