More than three years have passed since the first case, and COVID-19 is still a health concern, with several open issues such as the lack of reliable predictors of a patient’s outcome. Osteopontin (OPN) is involved in inflammatory response to infection and in thrombosis driven by chronic inflammation, thus being a potential biomarker for COVID-19. The aim of the study was to evaluate OPN for predicting negative (death or need of ICU admission) or positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. We enrolled 133 hospitalized, moderate-to-severe COVID-19 patients in a prospective observational study between January and May 2021. Circulating OPN levels were measured by ELISA at admission and at day 7. The results showed a significant correlation between higher plasma concentrations of OPN at hospital admission and a worsening clinical condition. At multivariate analysis, after correction for demographic (age and gender) and variables of disease severity (NEWS2 and PiO2/FiO2), OPN measured at baseline predicted an adverse prognosis with an odds ratio of 1.01 (C.I. 1.0–1.01). At ROC curve analysis, baseline OPN levels higher than 437 ng/mL predicted a severe disease evolution with 53% sensitivity and 83% specificity (area under the curve 0.649, p = 0.011, likelihood ratio of 1.76, (95% confidence interval (CI): 1.35–2.28)). Our data show that OPN levels determined at the admission to hospital wards might represent a promising biomarker for early stratification of patients’ COVID-19 severity. Taken together, these results highlight the involvement of OPN in COVID-19 evolution, especially in dysregulated immune response conditions, and the possible use of OPN measurements as a prognostic tool in COVID-19.

Some studies suggested a high incidence of human herpesvirus (HHV) reactivation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To evaluate the prevalence of HHV reactivations in a population with various severity degrees of coronavirus disease 2019 (COVID-19), we analyzed 102 individuals and compared them with 51 SARS-CoV-2-negative subjects admitted in the same period (January–July 2022) for acute respiratory failure. Positivity was found in 76% of subjects for at least one HHV, and in 46% for ≥2 HHV. These proportions were more prevalent in SARS-CoV-2-positive than in negative patients (83% vs. 61%; 56% vs. 27%, respectively). The most common HHV was HHV-7 both in the whole population (51%) and in SARS-CoV-2-positive and -negative subjects (57% and 39%, respectively); human cytomegalovirus, herpes simplex virus-1, Epstein–Barr virus, and HHV-6 were more represented in SARS-CoV-2-positive individuals. No single or combined HHV reactivation was associated with the 60-day mortality rate. However, cytomegalovirus reactivation was an independent predictor of COVID-19 severity and longer hospitalizations, while the occurrence of ≥3 any HHV reactivations was independently associated with the aforementioned outcomes and ventilatory support need. Taken together, our data suggest that in patients with moderate-to-severe COVID-19, the diagnosis of HHV coinfections can add useful prognostic information.

Viral infections are a widely recognized cause of mortality. Recently it has been demonstrated that vitamin D plays an important immuno-modulatory role in both innate and adaptive immune responses against infections, by reducing excessive inflammation and enhancing defense mechanisms. Specifically, exacerbation of infections may cause sepsis, characterized by a dysregulated immune response with hyperinflammation and immune exhaustion. Vitamin D can modulate these processes through various mechanisms, such as enhancing antiviral protection, promoting anti-inflammatory responses, protecting endothelial barriers, and modulating T-cells. This has been demonstrated for various viral infections, including influenza viruses, respiratory syncytial virus, and severe acute respiratory syndrome coronavirus. Although vitamin D deficiency has been associated with increased susceptibility to viral infections and immune cells of infected patients are highly responsive to vitamin D, the clinical benefits of its supplementation to vitamin D-deficient infected individuals are uncertain and, most importantly, direct evidence linking vitamin D to viral sepsis specifically remains particularly limited, with most mechanistic inference extrapolated from non-septic viral infection and bacterial sepsis literature. Based on these assumptions, this review will outline the present understanding about vitamin D regulatory effects on immune system and the possible connection between its serum levels and viral infections, while also addressing controversial issues.