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Severe acute respiratory syndrome coronavirus 2 is associated with a severe respiratory disease in China, that rapidly spread across continents. Since the beginning of the pandemic, available data suggested the asymptomatic transmission and patients were treated with specific drugs with efficacy and safety data not always satisfactory. The aim of this review is to describe the vaccines developed by three companies, Pfizer‐BioNTech, Moderna, and University of Oxford/AstraZeneca, in terms of both technological and pharmaceutical formulation, safety, efficacy, and immunogenicity. A critical analysis of Phases 1, 2, and 3 clinical trial results available was conducted, comparing the three vaccine candidates, underlining their similarities and differences. All candidates showed consistent efficacy and tolerability; although some differences can be noted, such as their technological formulation, temperature storage, which will be related to logistics and costs. Further studies will be necessary to evaluate long‐term effects and to assess the vaccine safety and efficacy in the general population., Highlights The rapid development of SARS‐CoV‐2 vaccines has been possible because in the last 20 years there have been rapid improvements in vaccine development in different scientific areas, such as molecular biology, genetic engineering, nano‐materials and lipid nanotechnology.The first three SARS‐CoV‐2 vaccines developed by Pfizer–BioNTech, Moderna and the University of Oxford/AstraZeneca are described, in terms of technology, pharmaceutical formulation, safety, efficacy and immunogenicity.The main detectable difference concerns the technological formulation, influencing logistics: two of these are mRNA‐based vaccines encapsulated in LNPs, whereas one is a DNA‐based vaccine encapsulated in viral vector.mRNA‐based vaccines have an advantage over DNA ones, because mRNA is directly translated in the cytoplasm form ribosomes once inside the cell.Technological and scientific advances allowed the encapsulation of mRNA into custom‐designed LNPs that mimic the structural features of a viral vector.Efficacy and safety studies of Pfizer–BioNTech, Moderna and the University of Oxford/AstraZeneca vaccines are reported, to report the massive pharmaceutical innovation brought.

Several pre-clinical and clinical trials show that exogenous pulmonary surfactant has clinical efficacy in inflammatory lung diseases, especially ARDS. By infecting type II alveolar cells, COVID-19 interferes with the production and secretion of the pulmonary surfactant and therefore causes an increase in surface tension, which in turn can lead to alveolar collapse. The use of the pulmonary surfactant seems to be promising as an additional therapy for the treatment of ARDS. COVID-19 causes lung damage and ARDS, so beneficial effects of surfactant therapy in COVID-19-associated ARDS patients are conceivable, especially when applied early in the treatment strategy against pulmonary failure. Because of the robust anti-inflammatory and lung protective efficacy and the current urgent need for lung-supportive therapy, the exogenous pulmonary surfactant could be a valid supportive treatment of COVID-19 pneumonia patients in intensive care units in addition to the current standard of ARDS treatment.

Highlights • Ozone therapy seems to have an immunological role within SARS-CoV-2 regimens, because of the modulation of cytokines and interferons, including the induction of gamma interferon. • Ozone exerts antiviral activity through the inhibition of viral replication and direct inactivation of viruses. • Ozone is an antiviral drug enhancer and is not an alternative to antiviral drugs. • The routes of ozone administration are direct intravenous, major autohaemotherapy and extravascular blood oxygenation-ozonation. • Combined treatment with involving ozone and antivirals demonstrated a reduction in inflammation and lung damage., The main objective of this narrative review is to describe the available evidence on the possible antiviral activity of ozone in patients with COVID-19 and its therapeutic applicability through hospital protocols. Amongst different possible therapies for SARS-CoV-2 pneumonia, ozone therapy seems to have an immunological role because of the modulation of cytokines and interferons, including the induction of gamma interferon. Some data suggest the possible role of ozone therapy in SARS, either as a monotherapy or, more realistically, as an adjunct to standard treatment regimens; therefore, there is increasing interest in the role of ozone therapy in COVID-19 treatment The PubMed and Scopus databases and the Italian Scientific Society of Oxygen Ozone Therapy website were used to identify articles focused on ozone therapy. The search was limited to articles published from January 2011 to July 2020. Of 280 articles found on ozone therapy, 13 were selected and narratively reviewed. Ozone exerts antiviral activity through the inhibition of viral replication and direct inactivation of viruses. Ozone is an antiviral drug enhancer and is not an alternative to antiviral drugs. Combined treatment with involving ozone and antivirals demonstrated a reduction in inflammation and lung damage. The routes of ozone administration are direct intravenous, major autohaemotherapy and extravascular blood oxygenation-ozonation. Systemic ozone therapy seems useful in controlling inflammation, stimulating immunity and as antiviral activity and providing protection from acute coronary syndromes and ischaemia reperfusion damage, thus suggesting a new methodology of immune therapy. Systemic ozone therapy in combination with antivirals in COVID-19-positive patients may be justified, helpful and synergic.

CoViD-19 pandemic heavily impacted most on-going research activities, causing delays and need of re-programming. EASY-NET (NET-2016-02364191) is a network project, started in April 2019, co-funded by the Italian Ministry of Health and the participating regions. Within the general project, centred on the evaluation of Audit and Feedback (AF) strategies in improving quality and equity in different health care contexts, the Piedmont region is responsible of the work package 3 (WP3) on specific oncology pathways and procedures. After a thorough evaluation of the impact of the CoViD-19 emergency on the WP3 activities, at the beginning of March 2020, the decision was to continue, with some adaptations, the audits already started, and to delay those in the early planning phase. The provisional availability of part of the time-persons involved in EASY-NET on one side, and the urgency of acquiring data on the management of the large number of CoViD-19 patients admitted to the study coordinator hospital on the other side, determined the personnel responsible of the WP3, in accordance with the hospital management, to invest these resources in monitoring the CoViD-19 hospitalized patients with both AF activity and research objectives. Besides periodic reports, a web site, with restricted access to the involved health care personnel, was developed to allow a direct and timely consultation of graphics describing the flow of the patients, their management, and outcomes. This experience was made possible thanks to a favourable combination of different factors: the presence within the hospital of a group of experienced epidemiologists in AF, the availability of extra resources, the strong support and collaboration by the hospital management and the readiness for authorisation by the Ethics Committee. We underline the need to provide a certain degree of flexibility in the long-term projects funded by the Ministry of Health, the extraordinary adaptability of the AF approach also to emergency situations and the possibility of combining audit activities and research objectives in the same project.