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

• Published in: Frontiers in immunology Vol. 14; p. 1308594
• Main Authors: Bingham, Grace C, Muehling, Lyndsey M, Li, Chaofan, Huang, Yong, Ma, Shwu-Fan, Abebayehu, Daniel, Noth, Imre, Sun, Jie, Woodfolk, Judith A, Barker, Thomas H, Bonham, Catherine A
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 16.01.2024
• Subjects: COVID – 19; idiopathic pulmonary fibrosis; Immunology; monocytes; peripheral blood mononuclear cells; pulmonary fibrosis; single cell RNA sequencing (scRNA); peripheral blood mononuclear cells; monocytes; idiopathic pulmonary fibrosis; COVID – 19; single cell RNA sequencing (scRNA); pulmonary fibrosis
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1308594

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