Abstract
SARS-CoV2-induced direct cytopathic effects against type II pneumocytes are suspected to play a role in mediating and perpetuating lung damage. The aim of this study was to evaluate serum KL-6 behavior in COVID-19 patients to investigate its potential role in predicting clinical course. Sixty patients (median age IQR, 65 (52–69), 43 males), hospitalized for COVID-19 at Siena COVID Unit University Hospital, were prospectively enrolled. Twenty-six patients were selected (median age IQR, 63 (55–71), 16 males); all of them underwent follow-up evaluations, including clinical, radiological, functional, and serum KL-6 assessments, after 6 (t1) and 9 (t2) months from hospital discharge. At t0, KL-6 concentrations were significantly higher than those at t1 (760 (311–1218) vs. 309 (210–408) p = 0.0208) and t2 (760 (311–1218) vs 324 (279–458), p = 0.0365). At t0, KL-6 concentrations were increased in patients with fibrotic lung alterations than in non-fibrotic group (755 (370–1023) vs. 305 (225–608), p = 0.0225). Area under the receiver operating curve (AUROC) analysis showed that basal KL-6 levels showed good accuracy in discriminating patients with fibrotic sequelae radiologically documented (AUC 85%, p = 0.0404). KL-6 concentrations in patients with fibrotic involvement were significantly reduced at t1 (755 (370–1023) vs. 290 (197–521), p = 0.0366) and t2 (755 (370–1023) vs. 318 (173–435), p = 0.0490). Serum concentrations of KL-6 in hospitalized COVID-19 patients may contribute to identify severe patients requiring mechanical ventilation and to predict those who will develop pulmonary fibrotic sequelae in the follow-up.
Highlights
Krebs von den Lungen-6 (KL-6) is a serum high molecular weight glycoprotein, increased in many interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis and hypersensitivity pneumonitis [1,2,3]
Area under the receiver operating curve (AUROC) analysis showed that basal KL-6 had good accuracy in discriminating patients with high-resolution computed tomography (HRCT) evidence of fibrotic interstitial lung abnormalities
Serum concentrations of KL-6 at hospital admission were reported to be significantly increased in severe patients admitted to intensive care unit and requiring intubation with mechanical ventilation, but not in mild-moderate patients with less severe respiratory impairment [9]
Summary
Krebs von den Lungen-6 (KL-6) is a serum high molecular weight glycoprotein, increased in many interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis and hypersensitivity pneumonitis [1,2,3]. It is mainly produced by damaged or regenerating alveolar type II pneumocytes and its serum concentrations are regarded as biomarker of lung epithelial damage (reff). Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, KL-6 has been proposed as a prognostic marker for this disease [6,7,8,9]. The pathogenesis of COVID-19 (as the lung disease caused by SARS-CoV-2 is defined) is not entirely clear [10], it is postulated that elevated serum concentrations of proinflammatory cytokines and oxidative
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