COVID-19 is a viral pandemic caused by the new coronavirus SARS-CoV-2, an enveloped positive stranded RNA virus. The mechanisms of innate immunity, considered as the first line of antiviral defense, is essential towards viruses. A significant role in host defense of the lung, nasal and oral cavities is played by Human epididymis secretory protein 4 (HE4) HE4 has been demonstrated to be serum inflammatory biomarker and to show a role in natural immunity at the level of oral cavity, nasopharynx and respiratory tract with both antimicrobial/antiviral and anti-inflammatory activity. Several biomarkers like IL-6, presepsin (PSP), procalcitonin (PCT), CRP, D-Dimer have showed a good function as predictor factors for the clinical evolution of COVID-19 patients (mild, severe and critical). The aim of this study was to correlate the blood levels of CRP, IL-6, PSP, PCT, D-Dimer with He4, to identify the predictive values of these biomarkers for the evolution of the disease and to evaluate the possible role of HE4 in the defense mechanisms of innate immunity at the level of oral cavity, nasopharynx and respiratory tract. Of 134 patients admitted at COVID hospital of Policlinico—University of Bari, 86 (58 men age 67.6 ± 12.4 and 28 women age 65.7 ± 15.4) fulfilled the inclusion criteria: in particular, 80 patients (93%) showed prodromal symptoms (smell and/or taste dysfunctions) and other typical clinical manifestations and 19 died (13 men age 73.4 ± 7.7 and 6 women age 74.8 ± 6.7). 48 patients were excluded because 13 finished chemotherapy and 6 radiotherapy recently, 5 presented suspected breast carcinoma, 5 suspected lung carcinoma, 6 suspected ovarian carcinoma or ovary cyst, 1 cystic fibrosis, 3 renal fibrosis and 9 were affected by autoimmune diseases in treatment with monoclonal antibodies. The venous sample was taken for each patient on the admission and during the hospital stay. For each patient, six measurements relating to considered parameters were performed. Significant correlations between He4 and IL-6 levels (r = 0.797), between He4 and PSP (r = 0.621), between He4 and PCT (r = 0.447), between He4 and D-Dimer (r = 0.367), between He4 and RCP (r = 0.327) have been found. ROC curves analysis showed an excellent accuracy for He4 (AUC = 0.92) and IL-6 (AUC = 0.91), a very good accuracy for PSP (AUC = 0.81), a good accuracy for PCT (AUC = 0.701) and D-Dimer (AUC = 0.721) and sufficient accuracy for RCP (AUC = 0.616). These results demonstrated the important correlation between He4, IL6 and PSP, an excellent accuracy of He4 and IL6 and showed a probable role of He4 in the innate immunity in particularly at the level of oral cavity, nasopharynx and respiratory tract. Besides He4 together with IL6 might be involved in the onset of smell and/or taste disorders and it might be used as innovative biomarker to monitor clinical evolution of COVID-19 because He4 could indicate a multi-organ involvement.

Objectives: The aim of this observational study was to evaluate whether the presence of periapical inflammatory cysts (PIC) is accompanied by a state of vitamin D (25OHD) 25(OH)D insufficiency or deficiency and biochemical variations in biomarkers of bone metabolism such as osteocalcin (OC), isoenzyme of bone alkaline phosphatase (BALP), and C-terminal telopeptide of type 1 collagen (CTX). Methods: A total of 56 patients (group P), 36 males and 20 females, of which 42 had one cyst (group P1) and 14 had multiple periapical cysts (group P2), alongside 56 healthy subjects (group H) were recruited. Rx-OPT and clinical evaluation were used to evaluate the presence of PIC. At the first visit, all subjects underwent venous sampling (group P and H) to measure bone biomarkers by the chemiluminescence method. The Mann–Whitney test was used to compare the different biomarkers in the H vs. P, H vs. P1, H vs. P2, and P1 vs. P2 groups. The Mann–Whitney test was used to compare biomarker levels between the study groups. ROC curves were used to search for the concentration of the different biomarkers in which the best sensitivity and specificity were found. Results: 25OHD and CTX showed a difference between H vs. P, H vs. P1, H vs. P2, and P1 vs. P1 groups (p < 0.05). The study of the ROC curves with a comparison between concentrations in the H vs. P group showed the best sensitivity and specificity for 25OHD at a concentration <19 ng/mL, highlighting a picture of 25OHD deficiency. Conclusions: The presence of apical cysts could be indicative of a vitamin D deficiency that should be appropriately treated. The findings suggest that vitamin D deficiency, given its role in bone metabolism and mineralisation, may contribute to a biological environment that favours the development or persistence of periapical cystic lesions.