A New Pharmacological Approach Based on Remdesivir Aerosolized Administration on SARS-CoV-2 Pulmonary Inflammation: A Possible and Rational Therapeutic Application

The new zoonotic coronavirus (SARS-CoV-2) responsible for coronavirus disease (COVID-19) is a new strain of coronavirus not previously seen in humans and which appears to come from bat species. It originated in Wuhan, Hubei Province, China, and spread rapidly throughout the world, causing over 5,569,679 global cases and 351,866 deaths in almost every country in the world, including Europe, particularly Italy. In general, based on existing data published to date, 80.9% of patients infected with the virus develop mild infection; 13.8% severe pneumonia; 4.7% respiratory failure, septic shock or multi-organ failure; 3% of these cases are fatal. Critical patients have been shown to develop acute respiratory distress syndrome (ARDS) and hospitalization in intensive care units. The average age of patients admitted to hospital is 57–79 years, with one third half with an un- derlying disease. Asymptomatic infections have also been described, but their frequency is not known. SARS- CoV-2 transmission is mainly airborne from one person to another via droplets. The data available so far seem to indicate that SARS-CoV-2 is capable of producing an excessive immune reaction in the host. The virus attacks type II pneumocytes in the lower bronchi through the binding of the Spike protein (S protein) to viral receptors, of which the angiotensin 2 conversion enzyme (ACE2) receptor is the most important. ACE2 receptor is widely expressed in numerous tissues, including the oropharynx and conjunctiva, but mostly distributed in ciliated bronchial epithelial cells and type II pneumocytes in the lower bronchi. The arrival of SARS-CoV-2 in the lungs causes severe primary interstitial viral pneumonia that can lead to the “cytokine storm syndrome”, a deadly uncontrolled systemic inflammatory response triggered by the activation of interleukin 6 (IL-6), whose effect is extensive lung tissue damage and disseminated intravascular coagulation (DIC), that are life-threatening for patients with COVID-19. In the absence of a therapy of proven efficacy, current management consists of off-label or compassionate use therapies based on antivirals, antiparasitic agents in both oral and parenteral formulation, anti-inflammatory drugs, oxygen therapy and heparin support and convalescent plasma. Like most respiratory viruses can function and replicate at low temperatures (i.e. 34–35 °C) and assuming viral thermolability of SARS- CoV-2, local instillation or aerosol of antiviral (i.e. remdesivir) in humid heat vaporization (40°–41 °C) in the first phase of infection (phenotype I, before admission), both in asymptomatic but nasopharyngeal swab positive patients, together with antiseptic-antiviral oral gargles and povidone-iodine eye drops for conjunctiva (0,8–5% conjunctival congestion), would attack the virus directly through the receptors to which it binds, significantly decreasing viral replication, risk of evolution to phenotypes IV and V, reducing hospitalization and therefore death

Psoriatic uveitis is not an exploded myth

Psoriatic uveitis, a distinct clinical entity quoted for 7% to 25% in psoriatic ophthalmic patients with spondyloarthritis, and for 25.,% +/- 2,3 in meta-analysis of rheumatic patients with a prevalence of HLA-B27 quoted as for 40%-50%, is often misdiagnosed. The model proposed by Conti & Coll. [Clinical Dermatology 2017;5(1):30-36]merits also to drive attention of Dermatologist, Radiologist, General Practitioner to submit those psoriatic patients to an ophthalmological screening

Improving visual activity using Gabor patch technology in Stargardt disease: a retrospective study

Gabor patch technology is a non-invasive, patient-specific treatment based on visual stimulation and facilitation of neural connections responsible for vision. The treatment improved BCVA in Stargardt patients. Mean BCVA, for the 10 eyes, has raised from 0.81 (+- 0.17) logMar to 0.49 (+-0.07) logMar. Mean ETDRS’ chart lines improvement has been 3.18 +-2.05. This improvement appears to be retained for at least 12 months after treatment, consistent with the disease progression

New insight into systemic mastocytosis mediated by cytokines IL-1 beta and IL-33: Potential inhibitory effect of IL-37

Systemic mastocytosis in various forms is characterized by mast cell (MC) infiltration of the bone marrow and other internal organs. The most common form is the indolent one with life expectancy similar to the normal population, while the systemic aggressive myeloproliferative type presents serious damage to various organs and is associated with mature and immature atypical mast cells. In systemic mastocytosis patients, MCs could be activated with consequent severe anaphylactic reactions, along with other symptoms. MCs, which are reactive to a variety of external factors such as allergens or other inflammatory or physical stimuli, derive from pluripotent cellular progenitor CD34(+) which leaves the bone marrow as CD34(+)/CD17(+) for implantation in the tissues where they reach maturation. MCs participate in the innate and adaptive immune system where they play a role in host defense. Activation of MCs occurs through the binding of IgE to Fc epsilon RI receptor, and initiates the phosphorylation and activation of the p38 tyrosine MAP kinase. After various reactions there is a subsequent translation and generation of pro-inflammatory cytokines which are strongly linked to allergic inflammation and mastocytosis. Human cytokine interleukin-37 (IL-37), a unique IL-1 beta family member, has strong protective and anti-inflammatory properties, influencing cellular metabolism. We investigated the effect of IL-37 on inflammation in mastocytosis and report that the hematopoietic expression of IL-37 can reduce the inflammatory state in this disease. IL-37 limits excessive inflammation, which suggests that IL-37 may be beneficial to the metabolic and inflammatory process and is a candidate as a potential new therapeutic agent