The COVID-19 pandemic caused the shutdown of entire nations all over the world. In addition to mobility restrictions of people, the World Health Organization and the Governments have prescribed maintaining an inter-personal distance of 1.5 or 2 m (about 6 feet) from each other in order to minimize the risk of contagion through the droplets that we usually disseminate around us from nose and mouth. However, recently published studies support the hypothesis of virus transmission over a distance of 2 m from an infected person. Researchers have proved the higher aerosol and surface stability of SARS-COV-2 as compared with SARS-COV-1 (with the virus remaining viable and infectious in aerosol for hours) and that airborne transmission of SARS-CoV can occur besides close-distance contacts. Indeed, there is reasonable evidence about the possibility of SARS-COV-2 airborne transmission due to its persistence into aerosol droplets in a viable and infectious form. Based on the available knowledge and epidemiological observations, it is plausible that small particles containing the virus may diffuse in indoor environments covering distances up to 10 m from the emission sources, thus representing a kind of aerosol transmission. On-field studies carried out inside Wuhan Hospitals showed the presence of SARS-COV-2 RNA in air samples collected in the hospitals and also in the surroundings, leading to the conclusion that the airborne route has to be considered an important pathway for viral diffusion. Similar findings are reported in analyses concerning air samples collected at the Nebraska University Hospital. On March 16th, we have released a Position Paper emphasizing the airborne route as a possible additional factor for interpreting the anomalous COVID-19 outbreaks in northern Italy, ranked as one of the most polluted areas in Europe and characterized by high particulate matter (PM) concentrations. The available information on the SARS-COV-2 spreading supports the hypothesis of airborne diffusion of infected droplets from person to person at a distance greater than two meters (6 feet). The inter-personal distance of 2 m can be reasonably considered as an effective protection only if everybody wears face masks in daily life activities.

A number of nations were forced to declare a total shutdown due to COVID-19 infection, as extreme measure to cope with dramatic impact of the pandemic, with remarkable consequences both in terms of negative health outcomes and economic loses. However, in many countries a “Phase-2” is approaching and many activities will re-open soon, although with some differences depending on the severity of the outbreak experienced and SARS-COV-2 estimated diffusion in the general population. At the present, possible relapses of the epidemic cannot be excluded until effective vaccines or immunoprophylaxis with human recombinant antibodies will be properly set up and commercialized. COVD-19-related quarantines have triggered serious social challenges, so that decision makers are concerned about the risk of wasting all the sacrifices imposed to the people in these months of quarantine. The availability of possible early predictive indicators of future epidemic relapses would be very useful for public health purposes, and could potentially prevent the suspension of entire national economic systems. On 16 March, a Position Paper launched by the Italian Society of Environmental Medicine (SIMA) hypothesized for the first time a possible link between the dramatic impact of COVID-19 outbreak in Northern Italy and the high concentrations of particulate matter (PM₁₀ and PM_2.5) that characterize this area, along with its well-known specific climatic conditions. Thereafter, a survey carried out in the U.S. by the Harvard School of Public Health suggested a strong association between increases in particulate matter concentration and mortality rates due to COVID-19. The presence of SARS-COV-2 RNA on the particulate matter of Bergamo, which is not far from Milan and represents the epicenter of the Italian epidemic, seems to confirm (at least in case of atmospheric stability and high PM concentrations, as it usually occurs in Northern Italy) that the virus can create clusters with the particles and be carried and detected on PM₁₀. Although no assumptions can be made concerning the link between this first experimental finding and COVID-19 outbreak progression or severity, the presence of SARS-COV-2 RNA on PM₁₀ of outdoor air samples in any city of the world could represent a potential early indicator of COVID-19 diffusion. Searching for the viral genome on particulate matter could therefore be explored among the possible strategies for adopting all the necessary preventive measures before future epidemics start.

Epidemiological figures of the SARS-CoV-2 epidemic in Italy are higher than those observed in China. Our objective was to model the SARS-CoV-2 outbreak progression in Italian regions vs. Lombardy to assess the epidemic’s progression. Our setting was Italy, and especially Lombardy, which is experiencing a heavy burden of SARS-CoV-2 infections. The peak of new daily cases of the epidemic has been reached on the 29th, while was delayed in Central and Southern Italian regions compared to Northern ones. In our models, we estimated the basic reproduction number (R₀), which represents the average number of people that can be infected by a person who has already acquired the infection, both by fitting the exponential growth rate of the infection across a 1-month period and also by using day-by-day assessments based on single observations. We used the susceptible–exposed–infected–removed (SEIR) compartment model to predict the spreading of the pandemic in Italy. The two methods provide an agreement of values, although the first method based on exponential fit should provide a better estimation, being computed on the entire time series. Taking into account the growth rate of the infection across a 1-month period, each infected person in Lombardy has involved 4 other people (3.6 based on data of April 23rd) compared to a value of $R_0=2.68$ , as reported in the Chinese city of Wuhan. According to our model, Piedmont, Veneto, Emilia Romagna, Tuscany and Marche will reach an R₀ value of up to 3.5. The R₀ was 3.11 for Lazio and 3.14 for the Campania region, where the latter showed the highest value among the Southern Italian regions, followed by Apulia (3.11), Sicily (2.99), Abruzzo (3.0), Calabria (2.84), Basilicata (2.66), and Molise (2.6). The R₀ value is decreased in Lombardy and the Northern regions, while it is increased in Central and Southern regions. The expected peak of the SEIR model is set at the end of March, at a national level, with Southern Italian regions reaching the peak in the first days of April. Regarding the strengths and limitations of this study, our model is based on assumptions that might not exactly correspond to the evolution of the epidemic. What we know about the SARS-CoV-2 epidemic is based on Chinese data that seems to be different than those from Italy; Lombardy is experiencing an evolution of the epidemic that seems unique inside Italy and Europe, probably due to demographic and environmental factors.

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.