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All-cause mortality related to the SARS-CoV-2 infection has declined from the first wave to subsequent waves, probably through vaccination programs and the availability of effective antiviral therapies. Our study aimed to evaluate the impact of the SARS-CoV-2 vaccination on the prognosis of infected patients. Overall, we enrolled 545 subjects during the Delta variant wave and 276 ones during the Omicron variant wave. Data were collected concerning vaccination status, clinical parameters, comorbidities, lung involvement, laboratory parameters, and pharmacological treatment. Outcomes were admission to the intensive care unit (ICU) and 30-day all-cause mortality. Overall, the final sample included 821 patients with a mean age of 62 +/- 18 years [range 18-100], and 59% were men. Vaccinated patients during the Delta wave were 37% (over 3/4 with two doses), while during the Omicron wave they were 57%. Vaccinated patients were older (68 vs. 57 years), and 62% had at least one comorbidity Admission to the ICU was 20%, and the mortality rate at 30 days was 14%. ICU admissions were significantly higher during the Delta wave than during Omicron (OR 1.9, 95% CI 1.2-3.1), while all-cause mortality did not differ. Unvaccinated patients had a higher risk of ICU admission (OR 2.0, 95% CI 1.3-3.1) and 30-day all-cause mortality (OR 1.7, 95% CI 1.3-2.7). Results were consistent for both Delta and Omicron variants. Overall, vaccination with at least two doses was associated with a reduced need for ICU admission. Even one shot of the vaccine was associated with a significantly reduced 30-day mortality.

Systemic autoinflammatory diseases (SAIDs) are defined by recurrent febrile attacks associated with protean manifestations involving joints, the gastrointestinal tract, skin, and the central nervous system, combined with elevated inflammatory markers, and are caused by a dysregulation of the innate immune system. From a clinical standpoint, the most known SAIDs are familial Mediterranean fever (FMF); cryopyrin-associated periodic syndrome (CAPS); mevalonate kinase deficiency (MKD); and periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) syndrome. Current guidelines recommend the regular sequential administration of vaccines for all individuals with SAIDs. However, these patients have a much lower vaccination coverage rates in ‘real-world’ epidemiological studies than the general population. The main purpose of this review was to evaluate the scientific evidence available on both the efficacy and safety of vaccines in patients with SAIDs. From this analysis, neither serious adverse effects nor poorer antibody responses have been observed after vaccination in patients with SAIDs on treatment with biologic agents. More specifically, no new-onset immune-mediated complications have been observed following immunizations. Post-vaccination acute flares were significantly less frequent in FMF patients treated with colchicine alone than in those treated with both colchicine and canakinumab. Conversely, a decreased risk of SARS-CoV-2 infection has been proved for patients with FMF after vaccination with the mRNA-based BNT162b2 vaccine. Canakinumab did not appear to affect the ability to produce antibodies against non-live vaccines in patients with CAPS, especially if administered with a time lag from the vaccination. On the other hand, our analysis has shown that immunization against Streptococcus pneumoniae, specifically with the pneumococcal polysaccharide vaccine, was associated with a higher incidence of adverse reactions in CAPS patients. In addition, disease fla

COVID-19 is a novel disease with a broad range of clinical patterns. Several patients show dysbiosis in the intestinal tract, with evidence of reduced beneficial bacteria, such as Bifidobacteria and Lactobacilli. It is well established that human gut microbiota dysbiosis is associated with several clinical conditions, including respiratory tract diseases due to the gut-lung axis. This narrative review discusses the role of nutrients in the relationship between the gut microbiota and the immune response in SARS-CoV-2 infection. In particular, we will focus on the benefits offered by vitamins and micronutrients on different aspects of COVID-19 disease while also discussing which diets seem to provide the most advantages.

Remdesivir (RDV) has demonstrated clinical benefit in hospitalized COronaVIrus Disease (COVID)-19 patients. The objective of this brief report was to assess a possible correlation between RDV therapy and the variation in lymphocyte subpopulations. We retrospectively studied 43 hospitalized COVID-19 patients: 30 men and 13 women (mean age 69.3 ± 15 years); 9/43 had received RDV therapy. Six patients had no need for oxygen (severity group 0); 22 were on oxygen treatment with a fraction of inspired oxygen (FiO2) ≤ 50% (group 1); 7 on not-invasive ventilation (group 2); 3 on invasive mechanical ventilation (group 3); and 5 had died (group 4). Cytofluorimetric assessment of lymphocyte subpopulations showed substantial changes after RDV therapy: B lymphocytes and plasmablasts were significantly increased (p = 0.002 and p = 0.08, respectively). Cytotoxic T lymphocytes showed a robust reduction (p = 0.008). No changes were observed in CD4+-T cells and natural killers (NKs). There was a significant reduction in regulatory T cells (Tregs) (p = 0.02) and a significant increase in circulating monocytes (p = 0.03). Stratifying by disease severity, after RDV therapy, patients with severity 0–2 had significantly higher B lymphocyte and monocyte counts and lower memory and effector cytotoxic T cell counts. Instead, patients with severity 3–4 had significantly higher plasmablast and lower memory T cell counts. No significant differences for CD4+-T cells, Tregs, and NKs were observed. Our brief report showed substantial changes in the lymphocyte subpopulations analyzed between patients who did not receive RDV therapy and those after RDV treatment. Despite the small sample size, due to the retrospective nature of this brief report, the substantial changes in lymphocyte subpopulations reported could lead to speculation on the role of RDV treatment both on immune responses against the virus and on the possible downregulation of the cytokine storm observed in patients with more severe di

Purpose: The pandemic diffusion of Coronavirus Disease 2019 (COVID-19) has highlighted significant genderrelated differences in disease severity. Despite several hypotheses being proposed, how the genetic background of COVID-19 patients might impact clinical outcomes remains largely unknown. Methods: We collected blood samples from 192 COVID-19 patients (115 men, 77 women, mean age 67 +/- 19 years) admitted between March and June 2020 at two different hospital centers in Italy, and determined the allelic distribution of nine Single Nucleotide Polymorphisms (SNPs), located at the 3 ' Regulatory Region (3 ' RR)-1 in the immunoglobulin (Ig) heavy chain locus, including *1 and *2 alleles of polymorphic hs1.2 enhancer region. Results: In COVID-19 patients, the genotyped SNPs exhibited strong Linkage Disequilibrium and produced 7 specific haplotypes, associated to different degrees of disease severity, including the occurrence of pneumonia. Additionally, the allele *2, which comprises a DNA binding site for the Estrogen receptor alpha (ER alpha) in the polymorphic enhancer hs1.2 of 3 ' RR-1, was significantly enriched in women with a less severe disease. Conclusions: These findings document genetic variants associated to individual clinical severity of COVID-19 disease. Most specifically, a novel genetic protective factor was identified that might explain the sex-related differences in immune response to Sars-COV-2 infection in humans.

Objectives: Auto-inflammatory Diseases (AIDs) are agroup of diseases with a strong genetic component, inducing an inappropriate activation of innate immunity.The patients with pediatric onset will face the transitionalcare (TC) from a pediatrician to an adult care setting, during the critical phase of the adolescence. That implies arisk of failure and drop out, due to the different approach ofpediatrician compared to the adult doctor. To describe themodel of TC for AIDs from a paediatric to adult centre of twohospitals in Rome, and to pointing out the different stepsemerged from specific experiences. Methods: In November 2020, a Board of paediatriciansand internists discussed their experience to identify “hot topics” for a successful management of TC. Results: The Board agreed on the optimal time for thetransition (12-18 years). Specific elements to be consideredare the reached level of emotional and intellectual matu-rity, and the clinical stability of the disease. Conclusions: The TC of patients with chronic AIDs, re-quires a strong cooperation to define the adequate follow-up, and to guarantee the compliance to the treatment. Thismodel allows us to investigate AIDs complex cases requiring a long period of observations.

Gut microbiota (GM) comprises more than one thousand microorganisms between bacterial species, viruses, fungi, and protozoa and represents the main actor of a wide net of molecular interactions, involving, among others, the endocrine system, immune responses, and metabolism. GM influences many endocrine functions, such as adrenal steroidogenesis, thyroid function, sexual hormones, IGF-1 pathway and peptides, produced in the gastrointestinal system. It is fundamental in glycaemic control and obesity, while also exerting an important function in modulating the immune system and associated inflammatory disease. The result of this crosstalk in gut mucosa is the formation of the intestinal immunological niche. Visceral adipose tissue (VAT) produces about 600 different peptides and it is involved in lipid and glucose metabolism, and some immune reactions, through several adipokines. GM and VAT interact in a bidirectional fashion: while gut dysbiosis can modify VAT adipokines and hormone secretion, VAT hyperpla-sia modifies GM composition. Acquired or genetic factors leading to gut dysbiosis or increasing VAT (i.e., Western diet) induce a pro-inflammatory condition, which plays a pivotal role in the development of dysmetabolic and immunologic conditions, such as diabetes mellitus. Diabetes is associated with specific patterns of GM alterations, an abun-dance or reduction of GM species involved in controlling mucosal barrier status, glycaemic levels and exerting a pro-or anti-inflammatory activity. All these factors could ex-plain the higher incidence of several inflammatory conditions in Western countries; fur-thermore, besides the specific alterations observed in diabetes, this paradigm could repre-sent a common pathway acting in many metabolic conditions and could pave the way to new, interesting therapeutic approaches.

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Vaccinations are among the most effective medical procedures and have had an incredible impact on almost everyone’s life. One of the populations that can benefit the most from them are elderly people. Unfortunately, in this group, vaccines are less effective than in other groups, due to immunosenescence. The immune system ages like the whole body and becomes less effective in responding to infections and vaccinations. At the same time, immunosenescence also favors an inflammatory microenvironment, which is linked to many conditions typical of the geriatrics population. The microbiota is one of the key actors in modulating the immune response and, in this review, we discuss the current evidence on the role of microbiota in regulating the immune response to vaccines, particularly in elderly people.

We have evaluated long-term retention rate of anakinra in adult onset Still disease and predictive factors for treatment response. The risk of losing anakinra efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of anakinra withdrawal.