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.

<b><i>Background:</i></b> Specific drugs and/or immunotherapies are widely used to treat allergies, but drug-induced adverse effects recently led to explore new additional strategies. We studied whether a probiotic preparation (iPROB®; Anallergo SpA, Florence, Italy) is effective in allergic patients and the mechanisms underlying clinical outcomes. <b><i>Methods:</i></b> Eligible patients (<i>n</i> = 28), all suffering from allergic rhinitis with/without bronchial asthma, were consecutively recruited at the Allergology Medical Unit (Novara, Italy) and treated with this probiotic. From each patient, we collected blood and stool samples at the baseline, after 60 days of probiotic supplementation, and after 60 days from probiotic discontinuation. In each blood sample, the percentage of hematopoietic stem cells, eosinophils, and basophils was measured by FACS. To analyze stool microbiota composition, genomic DNA was extracted, bacterial 16S DNA libraries sequenced by Illumina platform (Miseq), and raw sequences processed. Generated data were statistically analyzed. <b><i>Results:</i></b> Probiotic-treated patients showed a significant decrease in Average Rhinitis Total Symptom Score (<i>d</i> = −10.5714), and Visual Analog Scale (<i>d</i> = −2.00) clinical indices, as well as important improvements in quality of life. In whole blood, a significant reduction in the percentage of activated eosinophils and basophils was determined, and this effect persisted after specific cell stimulation. Consistently, the serum levels of IL-4 and IL-5 decreased after probiotic treatment, suggesting a reduction in the Th2 cytokine profile. In addition, microbiome genomic analysis (<i>n</i> = 6) showed an increase in microbiome biodiversity, which positively correlates with clinical and cellular data. <b><i>Conclusion:</i></b> Present study suggests that iPROB® preparation has clinical/biological properties to be a valid add-on supplementation in allergic patients with asthma and rhinitis.

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.