Erika Zecca

Research into effective predictive markers and therapeutic interventions for COVID-19 remains of considerable interest. Vitamin D may be relevant, especially in frail populations in whom deficiency is more prevalent. In this prospective observational cohort study, 139 patients with moderate-to-severe COVID-19 who were hospitalized during the third wave of the pandemic in Italy were enrolled. Plasma vitamin D concentrations (both 25-hydroxyvitamin D-25(OH)D and 1,25-dihydroxyvitamin D-1,25(OH)₂D) together with parathyroid hormone levels were measured using a chemiluminescent assay validated for clinical use on automated laboratory platforms. Plasma vitamin D levels were below the sufficiency threshold. Notably, 25(OH)D concentrations were significantly lower in patients who experienced a negative outcome (11.10 [8.80–16.20] vs. 15.25 [9.90–24.80] ng/mL, p = 0.0450) and significantly higher in patients with rapid clinical recovery (15.25 [10.70–24.80] vs. 13.30 [7.47–19.60] ng/mL, p = 0.0446) compared with all other patients. Through multivariable logistic regression analysis, higher 25(OH)D levels at the time of hospitalization were confirmed as an independent predictor of favorable outcome. A plasma 25(OH)D concentration above 11.10 ng/mL predicted favorable disease resolution, with a positive likelihood ratio of 1.40 (IQR: 1.05–1.87). In conclusion, our findings support plasma vitamin D levels as an independent predictor of clinical outcomes in patients hospitalized with COVID-19 pneumonia.

As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63–1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70–1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19.

SARS-CoV-2 is the etiological agent of COVID-19, an extremely heterogenous disease that can cause severe respiratory failure and critical illness. To date, reliable biomarkers allowing for early patient stratification according to disease severity are still lacking. Calcitonin gene-related peptide (CGRP) is a vasoactive neuropeptide involved in lung pathophysiology and immune modulation and is poorly investigated in the COVID-19 context. In this observational, prospective cohort study, we investigated the correlation between CGRP and clinical disease evolution in hospitalized moderate to severe COVID-19 patients. Between January and May 2021 (Italian third pandemic wave), 135 consecutive SARS-CoV-2 patients were diagnosed as being eligible for the study. Plasma CGRP level evaluation and routine laboratory tests were performed on blood samples collected at baseline and after 7 days of hospitalization. At baseline, the majority our patients had a moderate to severe clinical presentation, and higher plasma CGRP levels predicted a higher risk of in-hospital negative evolution (odds-ratio OR 2.84 [IQR 1.07–7.51]) and were correlated with pulmonary intravascular coagulopathy (OR 2.92 [IQR 1.19–7.17]). Finally, plasma CGRP levels were also correlated with plasma IP10 levels. Our data support a possible crosstalk between the lung and the neuroimmune axis, highlighting a crucial role for plasma CGRP in sustaining COVID-19-related hyperinflammation.

Vaccines are the most effective means to prevent the potentially deadly effects of SARS-CoV-2 infection, but not all vaccinated individuals gain the same degree of protection. Patients undergoing chronic immunosuppressive therapy due to autoimmune diseases or liver transplants, for example, may show impaired anti-SARS-CoV-2 antibody response after vaccination. We performed a prospective observational study with parallel arms, aiming to (a) evaluate seroconversion after anti-SARS-CoV-2 mRNA vaccine administration in different subgroups of patients receiving immunosuppressive treatment for rheumatological or autoimmune diseases or to prevent organ rejection after liver transplantation and (b) identify negative predictors of IgG anti-SARS-CoV-2 development. Out of 437 eligible patients, 183 individuals were enrolled at the Rheumatology and Hepatology Tertiary Units of “Maggiore della Carità” University Hospital in Novara: of those, 52 were healthy subjects, while among the remaining 131 patients, 30 had a diagnosis of spondyloarthritis, 25 had autoimmune hepatitis, 10 were liver transplantation recipients, 23 suffered from connective tissue diseases (including 10 cases that overlapped with other diseases), 40 were treated for rheumatoid arthritis, and 5 had vasculitis. Moreover, all patients were receiving chronic immunosuppressive therapy. The immunogenicity of mRNA COVID-19 vaccines was evaluated by measuring IgG anti-SARS-CoV-2 antibody titers before vaccination and after 10, 30, and 90 days since the first dose administration. Of the selected cohort of patients, 24.0% did not develop any detectable anti-SARS-CoV-2 IgG after a complete mRNA-based two doses primary vaccination cycle. At univariate analysis, independent predictors of an absent antibody response to vaccine were a history of liver transplantation (OR 11.5, 95% CI 2.5–53.7, p = 0.0018), the presence of a comorbid active neoplasia (OR 26.4, 95% CI 2.8–252.4, p = 0.0045), and an ongoing immunosuppressive treatment with mycophenolate (MMF) (OR 14.0, 95% CI 3.6–54.9, p = 0.0002) or with calcineurin inhibitors (OR 17.5, 95% CI 3.1–99.0, p = 0.0012). At multivariate analysis, only treatment with MMF (OR 24.8, 95% CI 5.9–103.2, p < 0.0001) and active neoplasia (OR 33.2, 95% CI 5.4–204.1, p = 0.0002) were independent predictors of seroconversion failure. These findings suggest that MMF dose reduction or suspension may be required to optimize vaccine response in these patients.

Reliable biomarkers allowing early patients’ stratification for the risk of adverse outcomes in COVID-19 are lacking. Gas6, together with its tyrosine kinase receptors named TAM, is involved in the regulation of immune homeostasis, fibrosis, and thrombosis. Our aim was to evaluate whether Gas6, sAxl, and sMerTK could represent early predictors of disease evolution either towards a negative (death or need of ICU admission) or a positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. To this purpose, between January and May 2021 (corresponding to third pandemic wave in Italy), 139 consecutive SARS-CoV-2 positive patients were enrolled in a prospective observational study. Plasma levels of these molecules were measured by ELISA at the time of hospitalization and after 7 and 14 days. We observed that higher plasma Gas6 concentrations at hospital admission were associated with a worsening in clinical conditions while lower sMerTK concentrations at baseline and after 7 days of hospitalization were associated with a more favorable outcome. At multivariate analysis, after correction for demographic and COVID-19 severity variables (NEWS2 and PiO₂/FiO₂), only Gas6 measured at baseline predicted an adverse prognosis with an odds ratio of 1.03 (C.I. 1.01-10.5). At ROC curve analysis, baseline Gas6 levels higher than 58.0 ng/ml predicted a severe disease evolution with 53.3% sensitivity and 77.6% specificity (area under the curve 0.653, , likelihood ratio of 2.38, IQR: 1.46-3.87). Taken together, these results support the hypothesis that a dysregulation in the Gas6/TAM axis could play a relevant role in modulating the course of COVID-19 and suggest that plasma Gas6 may represent a promising prognostic laboratory parameter for this condition.

Background. SARS-CoV-2 is responsible for COVID-19, a clinically heterogeneous disease, ranging from being completely asymptomatic to life-threating manifestations. An unmet clinical need is the identification at disease onset or during its course of reliable biomarkers allowing patients’ stratification according to disease severity. In this observational prospective cohort study, patients’ immunologic and laboratory signatures were analyzed to identify independent predictors of unfavorable (either death or intensive care unit admission need) or favorable (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. Methods. Between January and May 2021 (third wave of the pandemic), we enrolled 139 consecutive SARS-CoV-2 positive patients hospitalized in Northern Italy to study their immunological and laboratory signatures. Multiplex cytokine, chemokine, and growth factor analysis, along with routine laboratory tests, were performed at baseline and after 7 days of hospital stay. Results. According to their baseline characteristics, the majority of our patients experienced a moderate to severe illness. At multivariate analysis, the only independent predictors of disease evolution were the serum concentrations of IP-10 (at baseline) and of C-reactive protein (CRP) after 7 days of hospitalization. Receiver-operating characteristic (ROC) curve analysis confirmed that baseline and at 7 days predict a worsening in clinical conditions (87% sensitivity, 66% specificity, area under the curve (AUC) 0.772, and 83% sensitivity, 73% specificity, AUC 0.826, , respectively). Conclusions. According to our results, baseline IP-10 and CRP after 7 days of hospitalization could be useful in driving clinical decisions tailored to the expected disease trajectory in hospitalized COVID-19 patients.

Red blood cell distribution width (RDW) has been studied as a prognostic biomarker for different chronic inflammatory diseases. In this paper we aim to evaluate its potential role in the prediction of early relapse in patients affected by polymyalgia rheumatica (PMR). We revised retrospectively clinical records of patients who received a diagnosis of PMR, according to 2012 ACR/EULAR classification criteria, for whom baseline clinical and laboratory data were available. The baseline RDW variation coefficient was correlated to the risk of relapse, in the first 6 months of the disease. We identified 44 patients [females 15 (34.0%)/males 29 (66.0%); median age 80 (72-83)], 9 of whom had an early relapse. These patients showed a larger median RDW than patients who did not relapse [13.7 (13.5-14.9)% vs 13.5 (12.7-14.2)%; p=0.04). The two groups were comparable for all the other clinical and laboratory parameters considered. Interestingly, patients in the higher half of the RDW distribution showed a shorter relapse-free survival (p<0.03). In a stepwise logistic regression, RDW (p=0.01) predicted the risk of relapse at 6 months, while age, gender, CRP, ESR, Hb, MCV and prednisone dose did not fit the model. Our results show that RDW is an independent biomarker of early relapse, making this parameter a potentially promising predictive marker in PMR.

Staphylococcus condimenti (S. condimenti) is a coagulase-negative bacterium, generally regarded as not pathogenic. Indeed, S. condimenti owes its name to having been isolated from starter cultures of fermented sausage, as well as from fish and soy sauces. To the best of our knowledge, only two cases of human infection caused by this bacterium have been reported. Here, we present a case of meningitis by S. condimenti in a 65-year-old woman who was brought to hospital after having been found unconscious at home. At her arrival, she had a Glasgow coma scale = 3, fever, and hypoxic–normocapnic respiratory failure. Examination of her cerebrospinal fluid showed a slightly increased white blood cell count, normal glucose and protein concentrations. Paired cultures on blood and liquor samples yielded S. condimenti. Targeted antibiotic treatment with ceftriaxone led to a complete recovery. This unique case expands our knowledge on S. condimenti as a pathogenic bacterium.