SFlt-1 and CA 15.3 are indicators of endothelial damage and pulmonary fibrosis in SARS-CoV-2 infection

Marilena Greco,Fernando Sicuro,Giambattista Lobreglio,Salvatore Suppressa,Carmelo Catanese,Roberta Assunta Lazzari

doi:10.1038/s41598-021-99470-y

Marilena Greco, Fernando Sicuro + Show 4 more

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https://doi.org/10.1038/s41598-021-99470-y

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Journal: Scientific Reports	Publication Date: Oct 7, 2021
Citations: 13	License type: open-access

Affiliation: Ospedale Vito Fazzi

Abstract

COVID-19 pandemic led to a worldwide increase of hospitalizations for interstitial pneumonia with thrombosis complications, endothelial injury and multiorgan disease. Common CT findings include lung bilateral infiltrates, bilateral ground-glass opacities and/or consolidation whilst no current laboratory parameter consents rapidly evaluation of COVID-19 risk and disease severity. In the present work we investigated the association of sFLT-1 and CA 15.3 with endothelial damage and pulmonary fibrosis. Serum sFlt-1 has been associated with endothelial injury and sepsis severity, CA 15.3 seems an alternative marker for KL-6 for fibrotic lung diseases and pulmonary interstitial damage. We analysed 262 SARS-CoV-2 patients with differing levels of clinical severity; we found an association of serum sFlt-1 (ROC AUC 0.902, decision threshold > 90.3 pg/mL, p < 0.001 Sens. 83.9% and Spec. 86.7%) with presence, extent and severity of the disease. Moreover, CA 15.3 appeared significantly increased in COVID-19 severe lung fibrosis (ICU vs NON-ICU patients 42.6 ± 3.3 vs 25.7 ± 1.5 U/mL, p < 0.0001) and was associated with lung damage severity grade (ROC AUC 0.958, decision threshold > 24.8 U/mL, p < 0.0001, Sens. 88.4% and Spec. 91.8%). In conclusion, serum levels of sFlt-1 and CA 15.3 appeared useful tools for categorizing COVID-19 clinical stage and may represent a valid aid for clinicians to better personalise treatment.

Highlights

COVID-19 pandemic led to a worldwide increase of hospitalizations for interstitial pneumonia with thrombosis complications, endothelial injury and multiorgan disease
We investigated and analysed the data regarding serum level of sFlt-1, previously described as a serum marker of endothelial dysfunction during bacterial sepsis and CA 15.3, analog of KL-6, for pulmonary fibrosis, in 262 patients affected by SARS-CoV-2 infection (Table 1)
Serum sFlt-1 showed an association with SARS-CoV-2 infection status with a decisive threshold value for positive patients > 90.3 pg/mL, as resulting from the receiver operating characteristic (ROC) curve (AUC 0.902 with p < 0.001, Sensitivity 83.9%, Specificity 86.7%; Fig. 1)

Summary

Introduction

COVID-19 pandemic led to a worldwide increase of hospitalizations for interstitial pneumonia with thrombosis complications, endothelial injury and multiorgan disease. Serum sFlt-1 has been associated with endothelial injury and sepsis severity, CA 15.3 seems an alternative marker for KL-6 for fibrotic lung diseases and pulmonary interstitial damage. We analysed 262 SARS-CoV-2 patients with differing levels of clinical severity; we found an association of serum sFlt-1 The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19) pandemic, has led to a rapid and extensive worldwide increase in hospitalisations for interstitial pneumonia, with several complications such as thrombosis, endothelial injury and multiorgan disease. Increase of Red Cell Distribution Width (RDW) has been associated with disease severity in hospitalised adults with SARS-CoV-2 infection, previously published RDW thresholds of ≥ 14.5% (RDW-CV) or ≥ 47 fL (RDW-SD) have been associated to increased risk of d eath[7,8,9]

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