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.

Recently, the world has been dealing with a devastating global pandemic coronavirus infection, with more than 12 million infected worldwide and over 300,000 deaths as of May 15th 2020, related to a novel coronavirus (2019-nCoV), characterized by a spherical morphology and identified through next-generation sequencing. Although the respiratory tract is the primary portal of entry of SARS-CoV-2, gastrointestinal involvement associated with nausea, vomiting and diarrhoea may also occur. No drug or vaccine has been approved due to the absence of evidence deriving from rigorous clinical trials. Increasing interest has been highlighted on the possible preventative role and adjunct treatment of lactoferrin, glycoprotein of human secretions part of a non-specific defensive system, known to play a crucial role against microbial and viral infections and exerting anti-inflammatory effects on different mucosal surfaces and able to regulate iron metabolism. In this review, analysing lactoferrin properties, we propose designing a clinical trial to evaluate and verify its effect using a dual combination treatment with local, solubilized intranasal spray formulation and oral administration. Lactoferrin could counteract the coronavirus infection and inflammation, acting either as natural barrier of both respiratory and intestinal mucosa or reverting the iron disorders related to the viral colonization.

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.

Retinoids have numerous applications in inflammatory, dyskeratotic, and oncohematology diseases. Retinoids have now reached the fourth generation, progressively reducing toxicity whilst increasing their efficacy. Trifarotene is a new fourth-generation retinoid with a selective action on RAR-γ. In this review, we reported the trials—both concluded and in progress—including the use of trifarotene in dermatological diseases. Studies were identified by searching electronic databases (MEDLINE, EMBASE, PubMed, Cochrane, Trials.gov) from 2012 to today and reference lists of respective articles. Only articles published in English language were included. Randomized trials evaluating trifarotene tolerability, safety, and efficacy in congenital ichthyosis and acne have demonstrated great results and mild side effects, leading to the approval by the FDA of trifarotene for the treatment of lamellar ichthyosis in 2014, and of acne vulgaris in October 2019. No high-quality randomized clinical trials have evaluated the treatment of primary cutaneous lymphomas with trifarotene. Finally, we are hypothesizing future perspectives in the treatment of non-melanoma skin cancers, fungal infections, photoaging, and hand-foot skin reactions with trifarotene.

Psoriasis and psoriatic arthritis are multifactorial chronic disorders whose etiopathogenesis essentially derives from the alteration of several signalling pathways and the co‐occurrence of genetic, epigenetic and non‐genetic susceptibility factors that altogether affect the functional and structural property of the skin. Although shared and differential susceptibility genes and molecular pathways are known to contribute to the onset of pathological phenotypes, further research is needed to dissect the molecular causes of psoriatic disease and its progression towards Psoriatic Arthritis. This review will therefore be addressed to explore differences and similarities in the etiopathogenesis and progression of both disorders, with a particular focus on genes involved in the maintenance of the skin structure and integrity (keratins and collagens), modulation of patterns of recognition (through Toll‐like receptors and dectin‐1) and immuno‐inflammatory response (by NLRP3‐dependent inflammasome) to microbial pathogens. In addition, special emphasis will be given to the contribution of epigenetic elements (methylation pattern, non‐coding RNAs, chromatin modifiers and 3D genome organization) to the etiopathogenesis and progression of psoriasis and psoriatic arthritis. The evidence discussed in this review highlights how the knowledge of patients' clinical and (epi)genomic make‐up could be helpful for improving the available therapeutic strategies for psoriasis and psoriatic arthritis treatment.