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Dalbavancin is a novel, long-acting lipoglycopeptide characterized by a long elimination half-life coupled with excellent in vitro activity against multidrug-resistant Gram-positives. Although it is currently approved only for the treatment of acute bacterial skin and skin structure infections, an ever-growing amount of evidence supports the efficacy of dalbavancin as a long-term therapy in osteomyelitis, prosthetic joint infections, endocarditis, and bloodstream infections. This article provides a critical reappraisal of real-world use of dalbavancin for off-label indications. A search strategy using specific keywords (dalba-vancin, osteomyelitis, endocarditis, long-term suppressive therapy, bloodstream infection, pharmacokinetic/pharmacodynamic profile) until April 2021 was performed on the PubMed-MEDLINE database. As for other novel antibiotics, a conundrum between approved indications and potential innovative therapeutic uses has emerged for dalbavancin as well. The promising efficacy in challenging scenarios (i.e., osteomyelitis, endocarditis, prosthetic joint infections), coupled with the unique pharmacokinetic/pharmacodynamic properties, makes dalbavancin a valuable alternative to daily in-hospital intravenous or outpatient antimicrobial regimens in the treatment of long-term Gram-positive infections. This makes dalbavancin valuable in the current COVID-19 scenario, in which hospitalization and territorial medicine empowerment are unavoidable. Keywords: dalbavancin, osteomyelitis, endocarditis, long-term suppressive therapy, PK/PD properties, COVID-19

The outbreak of 2019 novel coronavirus disease (Covid-19) caused by SARS-CoV-2 has spread rapidly, inducing a progressive growth in infected patients number. Social isolation (lockdown) has been assessed to prevent and control virus diffusion, leading to a worldwide financial and political crisis. Currently, SARS-CoV-2 RNA detection in nasopharyngeal swab takes place by real-time PCR (RT-qPCR). However, molecular tests can give some false-negative results. In this context, serological assays can be useful to detect IgG/IgM antibodies, to assess the degree of immunization, to trace the contacts, and to support the decision to re-admit people at work. A lot of serological diagnostic kits have been proposed on the market but validation studies have not been published for many of them. The aim of our work was to compare and to evaluate different assays analytical performances (two different immunochromatographic cards, an immunofluorescence chromatographic card, and a chemiluminescence-automated immunoassay) on 43 positive samples with RT-qPCR-confirmed SARS-CoV-2 infection and 40 negative control subjects. Our data display excellent IgG/IgM specificities for all the immunocromatographic card tests (100% IgG and 100% IgM) and for the chemiluminescence-automated assay (100% IgG and 94% IgM); IgG/IgM sensitivities are moderately lower for all methods, probably due to the assay viral antigen’s nature and/or to the detection time of nasopharyngeal swab RT-qPCR, with respect to symptoms onset. Given that sensitivities (around 94% and 84% for IgG and IgM, respectively) implicate false-negative cases and given the lack of effective vaccines or treatments, the only currently available procedure to reduce SARS-CoV-2 transmission is to identify and isolate persons who are contagious. For this reason, we would like to submit a flowchart in which serological tests, integrated with nasopharyngeal swab RT-qPCR, are included to help social and work activities implementation after the pandemic acute phase and to overcome lockdown.

SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro , asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo . These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients.

The aim of this study was to evaluate the role of baseline lymphocyte subset counts in predicting the outcome and severity of COVID-19 patients. Hospitalized patients confirmed to be infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were included and classified according to in-hospital mortality (survivors/nonsurvivors) and the maximal oxygen support/ventilation supply required (nonsevere/severe). Demographics, clinical and laboratory data, and peripheral blood lymphocyte subsets were retrospectively analyzed. Overall, 160 patients were retrospectively included in the study. T-lymphocyte subset (total CD3+, CD3+ CD4+, CD3+ CD8+, CD3+ CD4+ CD8+ double positive [DP] and CD3+ CD4− CD8− double negative [DN]) absolute counts were decreased in nonsurvivors and in patients with severe disease compared to survivors and nonsevere patients (p < 0.001). Multivariable logistic regression analysis showed that absolute counts of CD3+ T-lymphocytes < 524 cells/µl, CD3+ CD4+ < 369 cells/µl, and the number of T-lymphocyte subsets below the cutoff (T-lymphocyte subset index [TLSI]) were independent predictors of in-hospital mortality. Baseline T-lymphocyte subset counts and TLSI were also predictive of disease severity (CD3+  < 733 cells/µl; CD3+ CD4+ < 426 cells/µl; CD3+ CD8+ < 262 cells/µl; CD3+ DP < 4.5 cells/µl; CD3+ DN < 18.5 cells/µl). The evaluation of peripheral T-lymphocyte absolute counts in the early stages of COVID-19 might represent a useful tool for identifying patients at increased risk of unfavorable outcomes.

Introduction: The emergence of SARS-CoV-2 Omicron subvariants characterized by increased transmissibility and immune escape has raised concerns about the efficacy of current treatments. This systematic review and meta-analysis evaluated pharmacological and non-pharmacological interventions in Omicron-infected non-hospitalized patients, focusing on key clinical outcomes such as hospitalization, respiratory failure, ICU admission, and 30-day mortality. Methods: Searches were performed in MEDLINE, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov (last update: 13 July 2025). Eligible studies reported outcomes on antiviral agents, monoclonal antibodies, adjunctive therapies, or telemedicine. Random-effects meta-analyses were conducted when appropriate, with heterogeneity assessed by I2. Publication bias was evaluated via funnel plots and Egger’s test. Subgroup analyses explored sources of heterogeneity. Results: Eighty-eight studies were included. Meta-analyses, comparing treatment vs. no treatment, revealed that nirmatrelvir/ritonavir reduced hospitalization by 52% (RR 0.48, 95% CI 0.36–0.63) and all-cause mortality by 84% (RR 0.16, 95% CI 0.11–0.24). Remdesivir reduced hospitalization by 70% (RR 0.30, 95% CI 0.19–0.47) and respiratory failure by 89% (RR 0.11, 95% CI 0.03–0.44). Sotrovimab decreased hospitalization (RR 0.71, 95% CI 0.54–0.93) and mortality (RR 0.34, 95% CI 0.19–0.61). Molnupiravir modestly reduced hospitalization (RR 0.80, 95% CI 0.70–0.91) and respiratory failure (RR 0.45, 95% CI 0.27–0.77). Conclusions: Nirmatrelvir/ritonavir and remdesivir remain important for reducing severe outcomes, while sotrovimab retains partial efficacy. Rapid access to antivirals remains an important factor in mitigating SARS-CoV-2’s burden.

Background Influenza‐like syndromes (ILS), characterized by fever, cough, myalgia, and fatigue, present significant challenges in clinical management. Paracetamol (acetaminophen), known for its antipyretic and analgesic properties, is widely used to alleviate these symptoms. This article reports the results of an expert consensus on the efficacy, safety, and appropriate use of paracetamol in managing ILS, particularly in vulnerable populations. Methods A Delphi methodology was employed to gather expert opinions from 72 healthcare professionals, including general practitioners (GPs) and infectious disease specialists. The panelists rated 27 statements on a 5‐point Likert scale, with a consensus threshold set at 66%. Statements covered the efficacy, safety, drug interactions, and patient communication related to paracetamol use in ILS. Results were presented in aggregate form, with specific attention to areas of consensus and divergence. Results The panel reached consensus on 26 out of 27 statements. Paracetamol was unanimously recognized as the preferred treatment for ILS due to its effective symptom control and minimal risk of drug interactions. It was deemed safer for fragile populations, including the elderly and those with multiple comorbidities. Concerns regarding hepatotoxicity were noted mainly in cases of overdose; however, rare cases have been reported even at therapeutic doses in patients with pre‐existing liver disease, where alternative antipyretics may sometimes be considered. Divergence occurred in opinions on the potential immunosuppressive effects of nonsteroidal anti‐inflammatory drugs and the associated risk of bacterial superinfections. Conclusions Paracetamol is a safer and more suitable option for managing ILS. This work highlights the need for further research on its frequent use in specific populations and emphasizes the importance of patient education on appropriate dosing to improve medication safety and compliance.

Background Coronaviruses (CoV) are a large family of viruses that are common in humans and many animal species. Animal coronaviruses rarely infect humans with the exceptions of the Middle East respiratory syndrome ( MERS-CoV ), the severe acute respiratory syndrome corona virus (SARS-CoV), and now SARS-CoV-2, which is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19). Several studies suggested that genetic variants in the ACE2 gene may influence the host susceptibility or resistance to SARS-CoV-2 infection according to the functional role of ACE2 in human pathophysiology. However, many of these studies have been conducted in silico based on epidemiological and population data. We therefore investigated the occurrence of ACE2 variants in a cohort of 131 Italian unrelated individuals clinically diagnosed with COVID-19 and in an Italian control population, to evaluate a possible allelic association with COVID-19, by direct DNA analysis. Methods As a pilot study, we analyzed, by whole-exome sequencing, genetic variants of ACE2 gene in 131 DNA samples of COVID-19 patients hospitalized at Tor Vergata University Hospital and at Bambino Gesù Children’s Hospital, Rome. We used a large control group consisting of 1000 individuals (500 males and 500 females). Results We identified three different germline variants: one intronic c.439+4G>A and two missense c.1888G>C p.(Asp630His) and c.2158A>G p.(Asn720Asp) in a total of 131 patients with a similar frequency in male and female. Thus far, only the c.1888G>C p.(Asp630His) variant shows a statistically different frequency compared to the ethnically matched populations. Therefore, further studies are needed in larger cohorts, since it was found only in one heterozygous COVID-19 patient. Conclusions Our results suggest that there is no strong evidence, in our cohort, of consistent association of ACE2 variants with COVID-19 severity. We might speculate that rare susceptibility/resistant alleles could be located in the non-coding regions of the ACE2 gene, known to play a role in regulation of the gene activity.

This retrospective study analyzed SARS-CoV-2 Omicron variability since its emergence, focusing on immunocompromised (IPs) and non-immunocompromised adult people (NIPs). Phylogenetic analysis identified at least five major Omicron lineage groups circulating in Central Italy, from December 2021 to December 2023: (a) BA.1 (34.0%), (b) BA.2 + BA.4 (25.8%), (c) BA.5 + BF (10.8%), (d) BQ + BE + EF (9.2%), and (e) Recombinants (20.2%). The BA.2 + BA.4 lineages were more common in IPs compared to NIPs (30.9% vs. 17.8%, respectively; p = 0.011); conversely, Recombinants were less prevalent in IPs than in NIPs (16.0% vs. 27.1%, respectively; p = 0.018). High-abundant single nucleotide polymorphisms (SNPs; prevalence ≥ 40%) and non-synonymous SNPs (prevalence ≥ 20%) increased during the emergence of new variants, rising from BA.1 to Recombinants (54 to 92, and 43 to 70, respectively, both p < 0.001). Evaluating the genetic variability, 109 SNPs were identified as being involved in significant positive or negative associations in pairs (phi > 0.70, p < 0.001), with 19 SNPs associated in 3 distinct clusters (bootstrap > 0.96). Multivariate regression analysis showed that hospitalization was positively associated with one specific cluster, including S686R and A694S in Spike and L221F in Nucleocapsid (AOR: 2.74 [95% CI: 1.13–6.64, p = 0.025]), and with increased age (AOR:1.03 [95% CI: 1.00–1.06], p = 0.028). Conversely, negative associations with hospitalization were observed for female gender and previous vaccination status (AORs: 0.34 [95% CI: 0.14–0.83], p = 0.017 and 0.19 (95% CI: 0.06–0.63, p = 0.006, respectively). Interestingly, the S686R SNP located in a furin cleavage site suggests its potential pathogenetic role. The results show how Omicron genetic diversification significantly influences disease severity and hospitalization, together with age, sex, and vaccination status as key factors.

Lactoferrin (Lf) is a cationic glycoprotein synthetized by exocrine glands and is present in all human secretions. It is also secreted by neutrophils in infection and inflammation sites. This glycoprotein possesses antimicrobial activity due to its capability to chelate two ferric ions per molecule, as well as to interact with bacterial and viral anionic surface components. The cationic features of Lf bind to cells, protecting the host from bacterial and viral injuries. Its anti-inflammatory activity is mediated by the ability to enter inside the nucleus of host cells, thus inhibiting the synthesis of proinflammatory cytokine genes. In particular, Lf down-regulates the synthesis of IL-6, which is involved in iron homeostasis disorders and leads to intracellular iron overload, favoring viral replication and infection. The well-known antiviral activity of Lf has been demonstrated against DNA, RNA, and enveloped and naked viruses and, therefore, Lf could be efficient in counteracting also SARS-CoV-2 infection. For this purpose, we performed in vitro assays, proving that Lf exerts an antiviral activity against SARS-COV-2 through direct attachment to both SARS-CoV-2 and cell surface components. This activity varied according to concentration (100/500 μg/ml), multiplicity of infection (0.1/0.01), and cell type (Vero E6/Caco-2 cells). Interestingly, the in silico results strongly supported the hypothesis of a direct recognition between Lf and the spike S glycoprotein, which can thus hinder viral entry into the cells. These in vitro observations led us to speculate a potential supplementary role of Lf in the management of COVID-19 patients.

Lactoferrin (Lf), a multifunctional cationic glycoprotein synthesized by exocrine glands and neutrophils, possesses an in vitro antiviral activity against SARS-CoV-2. Thus, we conducted an in vivo preliminary study to investigate the antiviral effect of oral and intranasal liposomal bovine Lf (bLf) in asymptomatic and mild-to-moderate COVID-19 patients. From April 2020 to June 2020, a total of 92 mild-to-moderate (67/92) and asymptomatic (25/92) COVID-19 patients were recruited and divided into three groups. Thirty-two patients (14 hospitalized and 18 in home-based isolation) received only oral and intranasal liposomal bLf; 32 hospitalized patients were treated only with standard of care (SOC) treatment; and 28, in home-based isolation, did not take any medication. Furthermore, 32 COVID-19 negative, untreated, healthy subjects were added for ancillary analysis. Liposomal bLf-treated COVID-19 patients obtained an earlier and significant (p < 0.0001) SARS-CoV-2 RNA negative conversion compared to the SOC-treated and untreated COVID-19 patients (14.25 vs. 27.13 vs. 32.61 days, respectively). Liposomal bLf-treated COVID-19 patients showed fast clinical symptoms recovery compared to the SOC-treated COVID-19 patients. In bLf-treated patients, a significant decrease in serum ferritin, IL-6, and D-dimers levels was observed. No adverse events were reported. These observations led us to speculate a potential role of bLf in the management of mild-to-moderate and asymptomatic COVID-19 patients.