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Observational Study
. 2022 Feb 21;23(1):37.
doi: 10.1186/s12931-022-01955-5.

Elevated plasma levels of epithelial and endothelial cell markers in COVID-19 survivors with reduced lung diffusing capacity six months after hospital discharge

Oriol Sibila #  1   2   3 , Lídia Perea #  4   5 , Núria Albacar  6   4   5 , Jorge Moisés  6   4   5 , Tamara Cruz  4   5 , Núria Mendoza  4   5 , Belen Solarat  6   4   5 , Gemma Lledó  4   7 , Gerard Espinosa  4   7 , Joan Albert Barberà  6   4   5 , Joan Ramon Badia  6   4   5 , Alvar Agustí  6   4   5 , Jacobo Sellarés  6   4   5 , Rosa Faner  4   5
Affiliations
Observational Study

Elevated plasma levels of epithelial and endothelial cell markers in COVID-19 survivors with reduced lung diffusing capacity six months after hospital discharge

Oriol Sibila et al. Respir Res. .

Abstract

Background: Some COVID-19 survivors present lung function abnormalities during follow-up, particularly reduced carbon monoxide lung diffusing capacity (DLCO). To investigate risk factors and underlying pathophysiology, we compared the clinical characteristics and levels of circulating pulmonary epithelial and endothelial markers in COVID-19 survivors with normal or reduced DLCO 6 months after discharge.

Methods: Prospective, observational study. Clinical characteristics during hospitalization, and spirometry, DLCO and plasma levels of epithelial (surfactant protein (SP) A (SP-A), SP-D, Club cell secretory protein-16 (CC16) and secretory leukocyte protease inhibitor (SLPI)), and endothelial (soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and Angiopoietin-2) 6 months after hospital discharge were determined in 215 COVID-19 survivors.

Results: DLCO was < 80% ref. in 125 (58%) of patients, who were older, more frequently smokers, had hypertension, suffered more severe COVID-19 during hospitalization and refer persistent dyspnoea 6 months after discharge. Multivariate regression analysis showed that age ≥ 60 years and severity score of the acute episode ≥ 6 were independent risk factors of reduced DLCO 6 months after discharge. Levels of epithelial (SP-A, SP-D and SLPI) and endothelial (sICAM-1 and angiopoietin-2) markers were higher in patients with reduced DLCO, particularly in those with DLCO ≤ 50% ref. Circulating SP-A levels were associated with the occurrence of acute respiratory distress syndrome (ARDS), organizing pneumonia and pulmonary embolisms during hospitalization.

Conclusions: Reduced DLCO is common in COVID-19 survivors 6 months after hospital discharge, especially in those older than 60 years with very severe acute disease. In these individuals, elevated levels of epithelial and endothelial markers suggest persistent lung damage.

Keywords: DLCO; Endothelial markers; Epithelial markers; Post-COVID; Sequelae.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study flow-chart
Fig. 2
Fig. 2
Proportion of patients with abnormal pulmonary values (< 80% ref.). Values of FEV1, FVC or DLCO at 6-months after hospital discharge. For further explanations, see text
Fig. 3
Fig. 3
Association between epithelial and endothelial markers and the grades of DLCO alteration. a Levels of surfactant proteins (SP) A, SP-D and secretory leukocyte protease inhibitor (SLPI) as epithelial markers and b intercellular adhesion molecule 1 (sICAM-1) and Angiopoietin-2 as endothelial markers significantly increased in patients with the most abnormal DLCO (≤ 50%). Kruskal–Wallis tests are applied, and the adjusted P-values are obtained by Dunn’s test correction
Fig. 4
Fig. 4
Association between epithelial markers and clinical severity during hospitalization. Surfactant protein (SP) A levels according to a the severity scale, b acute distress respiratory syndrome (ARDS), c the development of organizing pneumonia and d pulmonary embolism. Kruskal–Wallis test or Mann–Whitney test are applied, as appropriate. The adjusted P-values are obtained by Dunn’s test correction
See this image and copyright information in PMC

References

    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5. - DOI - PMC - PubMed
    1. Osuchowski MF, Winkler MS, Skirecki T, Cajander S, Shankar-Hari M, Lachmann G, et al. The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Lancet Respir Med. 2021;9(6):622–642. doi: 10.1016/S2213-2600(21)00218-6. - DOI - PMC - PubMed
    1. Mo X, Jian W, Su Z, Chen M, Peng H, Peng P, et al. Abnormal pulmonary function in COVID-19 patients at time of hospital discharge. Eur Respir J. 2020;55(6):2001217. doi: 10.1183/13993003.01217-2020. - DOI - PMC - PubMed
    1. Sibila O, Albacar N, Perea L, Faner R, Torralba Y, Hernandez-Gonzalez F, et al. Lung function sequelae in COVID-19 patients 3 months after hospital discharge. Arch Bronconeumol. 2021;57:59–61. doi: 10.1016/j.arbres.2021.01.036. - DOI - PMC - PubMed
    1. Qin W, Chen S, Zhang Y, Dong F, Zhang Z, Hu B, et al. Diffusion capacity abnormalities for carbon monoxide in patients with COVID-19 at three-month follow-up. Eur Respir J. 2021;58:2003677. doi: 10.1183/13993003.03677-2020. - DOI - PMC - PubMed

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