Dataset Information

High-dimensional comparison of monocytes and T cells in post-COVID and idiopathic pulmonary fibrosis.

ABSTRACT:

Introduction

Up to 30% of hospitalized COVID-19 patients experience persistent sequelae, including pulmonary fibrosis (PF).

Methods

We examined COVID-19 survivors with impaired lung function and imaging worrisome for developing PF and found within six months, symptoms, restriction and PF improved in some (Early-Resolving COVID-PF), but persisted in others (Late-Resolving COVID-PF). To evaluate immune mechanisms associated with recovery versus persistent PF, we performed single-cell RNA-sequencing and multiplex immunostaining on peripheral blood mononuclear cells from patients with Early- and Late-Resolving COVID-PF and compared them to age-matched controls without respiratory disease.

Results and discussion

Our analysis showed circulating monocytes were significantly reduced in Late-Resolving COVID-PF patients compared to Early-Resolving COVID-PF and non-diseased controls. Monocyte abundance correlated with pulmonary function forced vital capacity and diffusion capacity. Differential expression analysis revealed MHC-II class molecules were upregulated on the CD8 T cells of Late-Resolving COVID-PF patients but downregulated in monocytes. To determine whether these immune signatures resembled other interstitial lung diseases, we analyzed samples from Idiopathic Pulmonary Fibrosis (IPF) patients. IPF patients had a similar marked decrease in monocyte HLA-DR protein expression compared to Late-Resolving COVID-PF patients. Our findings indicate decreased circulating monocytes are associated with decreased lung function and uniquely distinguish Late-Resolving COVID-PF from Early-Resolving COVID-PF, IPF, and non-diseased controls.

SUBMITTER: Bingham GC

PROVIDER: S-EPMC10824838 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

High-dimensional comparison of monocytes and T cells in post-COVID and idiopathic pulmonary fibrosis.

Bingham Grace C GC Muehling Lyndsey M LM Li Chaofan C Huang Yong Y Ma Shwu-Fan SF Abebayehu Daniel D Noth Imre I Sun Jie J Woodfolk Judith A JA Barker Thomas H TH Bonham Catherine A CA

Frontiers in immunology 20240116

<h4>Introduction</h4>Up to 30% of hospitalized COVID-19 patients experience persistent sequelae, including pulmonary fibrosis (PF).<h4>Methods</h4>We examined COVID-19 survivors with impaired lung function and imaging worrisome for developing PF and found within six months, symptoms, restriction and PF improved in some (Early-Resolving COVID-PF), but persisted in others (Late-Resolving COVID-PF). To evaluate immune mechanisms associated with recovery versus persistent PF, we performed single-cel ...[more]

PMID: 38292490

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Project description:BackgroundWe aimed to evaluate the image quality, feasibility, and diagnostic performance of three-dimensional ultrashort echo time magnetic resonance imaging (3D UTE-MRI) to assess idiopathic pulmonary fibrosis (IPF) compared with high-resolution computed tomography (HRCT) and half-Fourier single-shot turbo spin-echo (HASTE) MRI.MethodsA total of 36 patients with IPF (34 men; mean age: 62±8 years, age range: 43 to 78 years) were prospectively included and underwent HRCT and chest MRI on the same day. Chest MRI was performed with a free-breathing 3D spiral UTE pulse sequence and HASTE sequence on a 1.5 T MRI. Two radiologists independently evaluated the image quality of the HRCT, HASTE, and 3D UTE-MRI. They assessed the representative imaging features of IPF, including honeycombing, reticulation, traction bronchiectasis, and ground-glass opacities. Image quality of the 3D UTE-MRI, HASTE, and HRCT were assessed using a 5-point visual scoring method. Kappa and weighted kappa analysis were used to measure intra- and inter-observer and inter-method agreements. Sensitivity (SE), specificity (SP), and accuracy (AC) were used to assess the performance of 3D UTE-MRI for detecting image features of IPF and monitoring the extent of pulmonary fibrosis. Linear regressions and Bland-Altman plots were generated to assess the correlation and agreement between the assessment of the extent of pulmonary fibrosis made by the 2 observers.ResultsThe image quality of HRCT was higher than that of HASTE and UTE-MRI (HRCT vs. UTE-MRI vs. HASTE: 4.9±0.3 vs. 4.1±0.7 vs. 3.0±0.3; P<0.001). Interobserver agreement of HRCT, HASTE, and 3D UTE-MRI when assessing pulmonary fibrosis was substantial and excellent (HRCT: 0.727≤ κ ≤1, P<0.001; HASTE: 0.654≤ κ ≤1, P<0.001; 3D UTE-MRI: 0.719≤ κ ≤0.824, P<0.001). In addition, reticulation (SE: 97.1%; SP: 100%; AC: 97.2%; κ =0.654), honeycombing (SE: 83.3%; SP: 100%; AC: 86.1%; κ =0.625) patterns, and traction bronchiectasis (SE: 94.1%; SP: 100%; AC: 94.4%, κ =0.640) were also well-visualized on 3D UTE-MRI, which was significantly superior to HASTE. Compared with HRCT, the sensitivity of 3D UTE-MRI to detect signs of pulmonary fibrosis (n=35) was 97.2%. The interobserver agreement in elevation of the extent of pulmonary fibrosis with HRCT and 3D UTE-MRI was R2=0.84 (P<0.001) and R2=0.84 (P<0.001), respectively. The extent of pulmonary fibrosis assessed with 3D UTE-MRI [median =9, interquartile range (IQR): 6.25 to 10.00] was lower than that from HRCT (median =12, IQR: 9.25 to 13.00; U=320.00, P<0.001); however, they had a positive correlation (R=0.72, P<0.001).ConclusionsAs a radiation-free non-contrast enhanced imaging method, although the image quality of 3D UTE-MRI is inferior to that of HRCT, it has high reproducibility to identify the imaging features of IPF and evaluate the extent of pulmonary fibrosis.

Project description:IntroductionPulmonary fibrosis is an irreversible condition that may be caused by known (including viral triggers such as SARS-CoV-2) and unknown insults. The latter group includes idiopathic pulmonary fibrosis (IPF), which is a chronic, progressive fibrosing interstitial pneumonia of unknown cause. The longer the insult acts on lung tissue, the lower the probability of a complete resolution of the damage. An emerging clinical entity post-COVID-19 is pulmonary fibrosis (PCPF), which shares many pathological, clinical, and immunological features with IPF. The fibrotic response in both diseases-IPF and PCPF-is orchestrated in part by the immune system. An important role regarding the inhibitory or stimulatory effects on immune responses is exerted by the immune checkpoints (ICs). The aim of the present study was to analyse the similarities and differences between CD4+, CD8+, and NK cells in the peripheral blood of patients affected by fibrotic disease, IPF, and PCPF compared with sarcoidosis patients and healthy controls. The second aim was to evaluate the expression and co-expression of PD-1 and TIGIT on CD4, CD8, and NK cells from our patient cohort.MethodsOne hundred and fifteen patients affected by IPF, PCPF, and sarcoidosis at the rare pulmonary disease centre of the University of Siena were enrolled. Forty-eight patients had an IPF diagnosis, 55 had PCPF, and 12 had sarcoidosis. Further, ten healthy controls were enrolled. PCPF patients were included between 6 and 9 months following hospital discharge for COVID-19. The peripheral blood samples were collected, and through flow cytometric analysis, we analysed the expression of CD4, CD8, NK cells, PD-1, and TIGIT.ResultsThe results show a greater depletion of CD4 and NK cells in IPF patients compared to other groups (p = 0.003), in contrast with CD8 cells (p < 001). Correlation analysis demonstrated an indirect correlation between CD4 and CD8 cells in IPF and sarcoidosis patients (p < 0.001 = -0.87 and p = 0.042; r = -0.6, respectively). Conversely, PCPF patients revealed a direct correlation between CD4 and CD8 cells (p < 0.001; r = 0.90) accentuating an immune response restoration. The expression of PD-1 and TIGIT was abundant on T and NK cell subsets of the two lung fibrotic groups, IPF and PCPF. Analogously, the co-expression of PD-1 and TIGIT on the surfaces of CD4 and CD8 were increased in such diseases. Conclusions: Our study shines a spotlight on the immune responses involved in the development of pulmonary fibrosis, idiopathic and secondary to SARS-CoV-2 infection. We observed a significant imbalance not only in CD4, CD8, and NK blood percentages in IPF and PCPF patients but also in their functional phenotypes evaluated through the expression of ICs.

Project description:BackgroundAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is well known as a life-threatening condition during its clinical course. However, the clinical features and prognosis in AE of unclassifiable idiopathic interstitial pneumonia (AE-UCIIP) remain to be elucidated. The aim of this study was to clarify the clinical features and prognosis of AE-UCIIP compared with those of AE-IPF.MethodsIn 187 patients with UCIIP or IPF, 64 patients with AE-UCIIP or AE-IPF, who were diagnosed and treated at our hospital, were retrospectively evaluated.ResultsA total of 24 patients with AE-UCIIP were significantly older (p = 0.011), included more women (p < 0.001) and never-smokers (p < 0.001), and showed fewer lung lesions on high-resolution computed tomography (p = 0.006) than 40 patients with AE-IPF. Incidence of AE-UCIIP was 10.29%/year and was significantly higher than in AE-IPF (Gray's test, p = 0.008). Prognosis of AE-UCIIP was as poor as that of AE-IPF (log-rank, p = 0.681). Percent-predicted forced vital capacity (%FVC) [hazard ratio (HR) 0.934, p = 0.045], and GAP stage within 12 months before AE (HR 3.530, p = 0.023), and partial pressure arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio at AE (HR 0.998, p = 0.016) were significant prognostic factors. Finally, commencement of long-duration (⩾12 h) direct hemoperfusion with a polymyxin B-immobilised fibre column (PMX-DHP) within 2 days after admission significantly improved survival (log-rank, p = 0.038) and was a significant prognostic factor (HR 0.175, p = 0.0039) in AE-UCIIP. Long-duration PMX-DHP showed favourable treatment effects even in the combined group of patients with AE-UCIIP or AE-IPF (log-rank p = 0.002; HR 0.328, p = 0.006).ConclusionsPatients with AE-UCIIP were older and included more women and never-smokers than those with AE-IPF. Prognosis of AE-UCIIP was as poor as that of AE-IPF. The reviews of this paper are available via the supplemental material section.

Dataset Information

High-dimensional comparison of monocytes and T cells in post-COVID and idiopathic pulmonary fibrosis.

Introduction

Methods

Results and discussion

Publications

High-dimensional comparison of monocytes and T cells in post-COVID and idiopathic pulmonary fibrosis.

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