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

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.

CA 15-3 prognostic biomarker in SARS-CoV-2 pneumonia

“…Our results indicate that CA 15-3 is elevated in patients with worse prognosis, correlates with severity measured on the WHO Scale, is higher in those requiring intensive care, and is also higher in patients who die. Similar results have been published recently, in which higher levels of CA 15-3 have been observed in patients admitted to intensive care compared with those admitted to the ward, and it has been correlated with the degree of fibrosis measured with the computer tomography 19 . Unlike this study, in our study, CA 15-3 was measured at the time of admission, relating to severity and the possibility of worsening health status and risk of death, especially among those requiring intensive care.…”

“…MUC1 and CA 15-3 are also markers of pulmonary fibrotic processes 42 , and their elevation is related to a greater degree of pulmonary involvement and a worse prognosis 43 . In our study, patients who required oxygen therapy at discharge exhibited a higher level of CA 15-3 upon admission, which could be related to greater pulmonary damage and fibrosis 19 , 23 .…”

“…The KL-6 is a prognostic marker of interstitial lung disease 14 , 15 , and CA 15-3 is an alternative marker for KL-6 16 . Studies have shown an elevation of KL-6 and CA 15-3 markers in patients with SARS-CoV-2 pneumonia 17 – 19 . Unlike KL-6, CA 15-3 is more measurable in clinical practice because it is used as a tumor marker.…”

Changes of Tumor Markers in Patients with Breast Cancer during Postoperative Adjuvant Chemotherapy

“…The expression of CEA correlates with age [ 26 ], smoking [ 27 ], glucose and lipid metabolism disorders [ 28 , 29 ], and the chronic inflammatory state of the body [ 30 ]. However, CA153 was also significantly increased in diseases such as renal impairment in type 2 diabetes [ 31 ], interstitial lung disease [ 32 ], idiopathic inflammatory myositis [ 33 ], sarcoidosis [ 34 ], and SARS-CoV-2 infection [ 35 ]. Adjuvant chemotherapy can aggravate blood glucose and blood lipid metabolic disorders while killing potential tumors [ 36 , 37 ], leaving the body in a state of chronic inflammation.…”

Vascular Endothelial Growth Factor Receptor, fms-Like Tyrosine Kinase-1 (Flt-1), as a Novel Binding Partner for SARS-CoV-2 Spike Receptor-Binding Domain

“…It has been reported in the literature that increased sFlt-1/PlGF ratio in COVID-19 is a novel link to angiotensin II-mediated endothelial dysfunction (21). In addition, many studies (16,22,23) have reported that Covid positive patients with high sFlt-1 levels have extensive endothelial damage characterized by thrombotic complications, and a poor prognosis. Since sFlt-1 contains regions with sequence identities with spike-RBD, as reported in Figure 1D, we compared the 3D structures of these two proteins to verify whether their structural similarity could provoke the cross-reactivity of antibodies specific for each protein for the other one as shown in Figure 1.…”