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BackgroundFor SARS-CoV-2 and other respiratory viruses, the nasal epithelium is a key portal for infection. Therefore, the nose is an important target of prophylactic and therapeutic interventions against these viruses. We developed a nasal spray (AM-301, a medical device marketed as Bentrio) to protect against infection by SARS-CoV-2 and potentially other viruses. Aims of the studyTo test the safety and efficacy of AM-301 against SARS-CoV-2 infection. MethodsAM-301 was tested on an in vitro 3D model of primary human nasal airway epithelium. Safety was assessed in assays for tight junction integrity, cytotoxicity and cilia beating frequency. Efficacy against SARS-CoV-2 infection was evaluated in prophylaxis and infection mitigation assays. ResultsAM-301 did not have any detrimental effect on the nasal epithelium. Prophylactic treatment with AM-301 reduced viral titer significantly vs. controls over 4 days, reaching a maximum reduction of 99%. When treatment with AM-301 was started 24 or 30 h after infection, epithelia that received the formulation had a 12- or 14-fold lower titer than controls. ConclusionAM-301 was found to be safe in vitro, and it significantly decelerated viral titer growth in experimental models of prophylaxis and mitigation. Its physical (non-pharmaceutical) mechanism of action, safety and efficacy pave the way for further investigation of its possible use against a broad spectrum of viruses, allergens and pollutants.
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In previous communications, we have hypothesized the possibility that SARS-CoV-2 virus could be present on particulate matter (PM) during the spreading of the infection, consistently with evidence already available for other viruses. Here, we present the first results of the analyses that we have performed on 34 PM10 samples of outdoor/airborne PM10 from an industrial site of Bergamo Province, collected with two different air samplers over a continuous 3-weeks period, from February 21st to March 13th. We can confirm to have reasonably demonstrated the presence of SARS-CoV-2 viral RNA by detecting highly specific RtDR gene on 8 filters in two parallel PCR analyses. This is the first preliminary evidence that SARS-CoV-2 RNA can be present on outdoor particulate matter, thus suggesting that, in conditions of atmospheric stability and high concentrations of PM, SARS-CoV-2 could create clusters with outdoor PM and, by reducing their diffusion coefficient, enhance the persistence of the virus in the atmosphere. Further confirmations of this preliminary evidence are ongoing, and should include real-time assessment about the vitality of the SARS-CoV-2 as well as its virulence when adsorbed on particulate matter. At the present, no assumptions can be made concerning the correlation between the presence of the virus on PM and COVID-19 outbreak progression. Other issues to be specifically addressed are the average concentrations of PM eventually required for a potential boost effect of the contagion (in case it is confirmed that PM might act as a carrier for the viral droplet nuclei), or even the theoretic possibility of immunization consequent to minimal dose exposures at lower thresholds of PM.
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BackgroundAn epidemic model based only on respiratory droplets and close contact could not fully explain the regional differences in the spread of the recent severe acute respiratory syndrome COVID-19 in Italy, which was fast and dramatic only in Lombardy and Po Valley. On March 16th 2020, we presented a Position Paper proposing a research hypothesis concerning the association between higher mortality rates due to COVID-19 observed in Northern Italy and the peaks of particulate matter concentrations, frequently exceeding the legal limit of 50 {micro}g/m3 as PM10 daily average MethodsTo assess environmental factors related to the spread of the COVID-19 in Italy from February 24th to March 13th (the date when the lockdown has been imposed over Italy), official daily data relevant to ambient PM10 levels were collected from all Italian Provinces between February 9th and February 29th, taking into account the average time (estimated in 17 days) elapsed between the initial infection and the recorded COVID positivity. In addition to the number of exceedances of PM10 daily limit value, we considered also population data and daily travelling information per each Province. ResultsPM10 daily limit value exceedances appear to be a significant predictor (p < .001) of infection in univariate analyses. Less polluted Provinces had a median of 0.03 infection cases over 1000 residents, while most polluted Provinces had a median of 0.26 cases over 1000 residents. Thirty-nine out of 41 Northern Italian Provinces resulted in the category with highest PM10 levels, while 62 out of 66 Southern Provinces presented low PM10 concentrations (p< 0.001). In Milan, the average growth rate before the lockdown was significantly higher than Rome (0.34 vs. 0.27 per day, with a doubling time of 2.0 days vs. 2.6), suggesting a basic reproductive number R0>6.0, comparable with the highest values estimated for China.