Novel Insight into Pulmonary Fibrosis and Long COVID

Kamp, Jan C.; Werlein, Christopher; Plucinski, Edith; Welte, Tobias; Lee, Peter; Tafforeau, Paul; Walsh, Claire; Schuppan, Detlef; Hoeper, Marius M.; Jonigk, Danny; Ackermann, Maximilian

doi:10.1164/rccm.202212-2314le

Cited by 9 publications

(8 citation statements)

References 6 publications

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“…In a subset of patients, however, fibrotic remodeling could be detected by light microscopy and confirmed by transmission electron microscopy analysis, in line with an increase in profibrotic macrophages and elevated concentrations of IL-1β in BAL fluid. These findings might warrant monitoring of pulmonary function in patients with PASC, given the reported profibrotic effect of SARS-CoV-2 infection ( 15 , 16 ).…”

Section: Discussionmentioning

confidence: 89%

Clinical, Imaging, and Histopathological Features of Pulmonary Sequelae after Mild COVID-19

Gagiannis

Hackenbroch

Bloch

et al. 2023

Am J Respir Crit Care Med

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Section: Discussionmentioning

confidence: 89%

Clinical, Imaging, and Histopathological Features of Pulmonary Sequelae after Mild COVID-19

Gagiannis

Hackenbroch

Bloch

et al. 2023

Am J Respir Crit Care Med

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“…Additionally, another study also found that the proportion of dyspnea was decreased, but the distance of 6MWD was increased within 1 year after symptom onset in COVID‐19 survivors. Mild abnormalities of PFT might not influence the performance of 6MWD 26 . DLco is an important measurement in evaluating the efficiency of gas exchange.…”

Section: Discussionmentioning

confidence: 99%

“…Mild abnormalities of PFT might not influence the performance of 6MWD. 26 DLco is an important measurement in evaluating the efficiency of gas exchange.…”

Section: Quality Of Life and Psychological Assessmentsmentioning

confidence: 99%

Two‐ and 3‐year outcomes in convalescent individuals with COVID‐19: A prospective cohort study

Yang,

Guan,

Yang

et al. 2024

Journal of Medical Virology

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As the long‐term consequences of coronavirus disease 2019 (COVID‐19) have not been defined, it is necessary to explore persistent symptoms, long‐term respiratory impairment, and impact on quality of life over time in COVID‐19 survivors. In this prospective cohort study, convalescent individuals diagnosed with COVID‐19 were followed‐up 2 and 3 years after discharge from hospital. Participants completed an in‐person interview to assess persistent symptoms and underwent blood tests, pulmonary function tests, chest high‐resolution computed tomography, and the 6‐min walking test. There were 762 patients at the 2‐year follow‐up and 613 patients at the 3‐year follow‐up. The mean age was 60 years and 415 (54.5%) were men. At 3 years, 39.80% of the participants had at least one symptom; most frequently, fatigue, difficulty sleeping, joint pain, shortness of breath, muscle aches, and cough. The participants experienced different degrees of pulmonary function impairment, with decreased carbon monoxide diffusion capacity being the main feature; results remained relatively stable over the 2–3 years. Multiple logistic regression analysis demonstrated that female sex and smoking were independently associated with impaired diffusion capacity. A subgroup analysis based on disease severity was performed, indicating that there was no difference in other parameters of lung function except forced vital capacity at 3‐year follow‐up. Persistent radiographic abnormalities, most commonly fibrotic‐like changes, were observed at both timepoints. At 3 years, patients had a significantly improved Mental Component Score compared with that at 2 years, with a lower percentage with anxiety. Our study indicated that symptoms and pulmonary abnormalities persisted in COVID‐19 survivors at 3 years. Further studies are warranted to explore the long‐term effects of COVID‐19 and develop appropriate rehabilitation strategies.

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“…An evolving body of evidence demonstrates heightened levels of plasma monocyte/macrophage‐related markers associated with proinflammation and fibrosis in COVID-19 convalescents ( 86 ). In concordance with our observed upregulation of gene expression related to pulmonary symptoms/fibrosis, these cell types could engage in sustaining the fibrotic process that may fuel pulmonary sequelae.…”

Section: Discussionmentioning

confidence: 99%

“…In concordance with our observed upregulation of gene expression related to pulmonary symptoms/fibrosis, these cell types could engage in sustaining the fibrotic process that may fuel pulmonary sequelae. Findings of fibrosing phenotypes in the lungs of post-COVID-19 patients have been demonstrated via histopathologic analysis ( 86 ). Examination of the lungs after 7 days of hospitalization revealed an increase in VEGFA and fibrotic pathology akin to organizing pneumonia ( 87 ).…”

Section: Discussionmentioning

confidence: 99%

Single‐cell RNA sequencing reveals characteristics of myeloid cells in post-acute sequelae of SARS-CoV-2 patients with persistent respiratory symptoms

Yoon,

Dean,

Jiyarom

et al. 2024

Front. Immunol.

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BackgroundAlthough our understanding of the immunopathology and subsequent risk and severity of COVID-19 disease is evolving, a detailed account of immune responses that contribute to the long-term consequences of pulmonary complications in COVID-19 infection remains unclear. Few studies have detailed the immune and cytokine profiles associated with post-acute sequelae of SARS-CoV-2 infection (PASC) with persistent pulmonary symptoms. The dysregulation of the immune system that drives pulmonary sequelae in COVID-19 survivors and PASC sufferers remains largely unknown.ResultsTo characterize the immunological features of pulmonary PASC (PPASC), we performed droplet-based single-cell RNA sequencing (scRNA-seq) to study the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from a participant naïve to SARS-CoV-2 (Control) (n=1) and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC) (n=2). After integrating scRNA-seq data with a naïve participant from a published dataset, 11 distinct cell populations were identified based on the expression of canonical markers. The proportion of myeloid-lineage cells ([MLCs]; CD14+/CD16+monocytes, and dendritic cells) was increased in PPASC (n=2) compared to controls (n=2). MLCs from PPASC displayed up-regulation of genes associated with pulmonary symptoms/fibrosis, while glycolysis metabolism-related genes were downregulated. Similarly, pathway analysis showed that fibrosis-related (VEGF, WNT, and SMAD) and cell death pathways were up-regulated, but immune pathways were down-regulated in PPASC. Further comparison of PPASC with scRNA-seq data with Severe COVID-19 (n=4) data demonstrated enrichment of fibrotic transcriptional signatures. In PPASC, we observed interactive VEGF ligand-receptor pairs among MLCs, and network modules in CD14+ (cluster 4) and CD16+ (Cluster 5) monocytes displayed a significant enrichment for biological pathways linked to adverse COVID-19 outcomes, fibrosis, and angiogenesis. Further analysis revealed a distinct metabolic alteration in MLCs with a down-regulation of glycolysis/gluconeogenesis in PPASC compared to SARS-CoV-2 naïve samples.ConclusionAnalysis of a small scRNA-seq dataset demonstrated alterations in the immune response and cellular landscape in PPASC. The presence of elevated MLC levels and their corresponding gene signatures associated with fibrosis, immune response suppression, and altered metabolic states suggests a potential role in PPASC development.

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Novel Insight into Pulmonary Fibrosis and Long COVID

Cited by 9 publications

References 6 publications

Clinical, Imaging, and Histopathological Features of Pulmonary Sequelae after Mild COVID-19

Clinical, Imaging, and Histopathological Features of Pulmonary Sequelae after Mild COVID-19

Two‐ and 3‐year outcomes in convalescent individuals with COVID‐19: A prospective cohort study

Single‐cell RNA sequencing reveals characteristics of myeloid cells in post-acute sequelae of SARS-CoV-2 patients with persistent respiratory symptoms

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