Long-term exposure to air pollution and risk of venous thromboembolism in a large administrative cohort.

BACKGROUND: Venous thromboembolisms (VTE) are one of the most frequent cause among the cardiovascular diseases. Despite the association between long-term exposure to air pollution and cardiovascular outcomes have been widely explored in epidemiological literature, little is known about the air pollution related effects on VTE. We aimed to evaluate this association in a large administrative cohort in 15 years of follow-up. METHODS: Air pollution exposure (NO2, PM10 and PM2.5) was derived by land use regression models obtained by the ESCAPE framework. Administrative health databases were used to identify VTE cases. To estimate the association between air pollutant exposures and risk of hospitalizations for VTE (in total and divided in deep vein thrombosis (DVT) and pulmonary embolism (PE)), we used Cox regression models, considering individual, environmental (noise and green areas), and contextual characteristics. Finally, we considered potential effect modification for individual covariates and previous comorbidities. RESULTS: We identified 1,954 prevalent cases at baseline and 20,304 cases during the follow-up period. We found positive associations between PM2.5 exposures and DVT, PE and VTE with hazard ratios (HRs) up to 1.082 (95% confidence intervals: 0.992, 1.181), 1.136 (0.994, 1.298) and 1.074 (0.996, 1.158) respectively for 10 µg/m3 increases. The association was stronger in younger subjects (< 70 years old compared to > 70 years old) and among those who had cancer. CONCLUSION: The effect of pollutants on PE and VTE hospitalizations, although marginally non-significant, should be interpreted as suggestive of a health effect that deserves attention in future studies.

Spatial modes for transmission of chikungunya virus during a large chikungunya outbreak in Italy: a modeling analysis.

BACKGROUND: The spatial spread of many mosquito-borne diseases occurs by focal spread at the scale of a few hundred meters and over longer distances due to human mobility. The relative contributions of different spatial scales for transmission of chikungunya virus require definition to improve outbreak vector control recommendations. METHODS: We analyzed data from a large chikungunya outbreak mediated by the mosquito Aedes albopictus in the Lazio region, Italy, consisting of 414 reported human cases between June and November 2017. Using dates of symptom onset, geographic coordinates of residence, and information from epidemiological questionnaires, we reconstructed transmission chains related to that outbreak. RESULTS: Focal spread (within 1 km) accounted for 54.9% of all cases, 15.8% were transmitted at a local scale (1-15 km) and the remaining 29.3% were exported from the main areas of chikungunya circulation in Lazio to longer distances such as Rome and other geographical areas. Seventy percent of focal infections (corresponding to 38% of the total 414 cases) were transmitted within a distance of 200 m (the buffer distance adopted by the national guidelines for insecticide spraying). Two main epidemic clusters were identified, with a radius expanding at a rate of 300-600 m per month. The majority of exported cases resulted in either sporadic or no further transmission in the region. CONCLUSIONS: Evidence suggest that human mobility contributes to seeding a relevant number of secondary cases and new foci of transmission over several kilometers. Reactive vector control based on current guidelines might allow a significant number of secondary clusters in untreated areas, especially if the outbreak is not detected early. Existing policies and guidelines for control during outbreaks should recommend the prioritization of preventive measures in neighboring territories with known mobility flows to the main areas of transmission.

The Ebola virus disease outbreak in Tonkolili district, Sierra Leone: a retrospective analysis of the Viral Haemorrhagic Fever surveillance system, July 2014-June 2015.

In Sierra Leone, the Ebola virus disease (EVD) outbreak occurred with substantial differences between districts with someone even not affected. To monitor the epidemic, a community event-based surveillance system was set up, collecting data into the Viral Haemorrhagic Fever (VHF) database. We analysed the VHF database of Tonkolili district to describe the epidemiology of the EVD outbreak during July 2014-June 2015 (data availability). Multivariable analysis was used to identify risk factors for EVD, fatal EVD and barriers to healthcare access, by comparing EVD-positive vs. EVD-negative cases. Key-performance indicators for EVD response were also measured. Overall, 454 EVD-positive cases were reported. At multivariable analysis, the odds of EVD was higher among those reporting contacts with an EVD-positive/suspected case (odds ratio (OR) 2.47; 95% confidence interval (CI) 2.44-2.50; P < 0.01) and those attending funeral (OR 1.02; 95% CI 1.01-1.04; P < 0.01). EVD cases from Kunike chiefdom had a lower odds of death (OR 0.22; 95% CI 0.08-0.44; P < 0.01) and were also more likely to be hospitalised (OR 2.34; 95% CI 1.23-4.57; P < 0.05). Only 25.1% of alerts were generated within 1 day from symptom onset. EVD preparedness and response plans for Tonkolili should include social-mobilisation activities targeting Ebola/knowledge-attitudes-practice during funeral attendance, to avoid contact with suspected cases and to increase awareness on EVD symptoms, in order to reduce delays between symptom onset to alert generation and consequently improve the outbreak-response promptness.

Transmission dynamics of the ongoing chikungunya outbreak in Central Italy: from coastal areas to the metropolitan city of Rome, 2017.

A large chikungunya outbreak is ongoing in Italy, with a main cluster in the Anzio coastal municipality. With preliminary epidemiological data, and a transmission model using mosquito abundance and biting rates, we estimated the basic reproduction number R0 at 2.07 (95% credible interval: 1.47-2.59) and the first case importation between 21 May and 18 June 2017. Outbreak risk was higher in coastal/rural sites than urban ones. Novel transmission foci could occur up to mid-November.

Meat intake and non-Hodgkin lymphoma: a meta-analysis of observational studies.

PURPOSE: High intake of meat has been inconsistently associated with increased risk of non-Hodgkin lymphoma (NHL). We carried out a meta-analysis to summarize the evidence of published observational studies reporting association between red meat and processed meat intake and NHL risk. METHODS: Analytical studies reporting relative risks with 95 % confidence intervals (95 % CI) for the association between intake of red and/or processed meat and NHL or major histological subtypes were eligible. We conducted random-effects meta-analysis comparing lowest and highest intake categories and dose-response meta-analysis when risk estimates and intake levels were available for more than three exposure classes. RESULTS: Fourteen studies (four cohort and ten case-control) were included in the meta-analysis, involving a total of 10,121 NHL cases. The overall relative risks of NHL for the highest versus the lowest category of consumption were 1.14 (95 % CI 1.03, 1.26) for red meat and 1.06 (95 % CI 0.98, 1.15) for processed meat. Significant associations were present when the analysis was restricted to case-control studies but not when restricted to cohort studies. No significant associations were found for major NHL etiological subtypes. Dose-response meta-analysis could be based only on eight studies that provided sufficient data, and compared to no meat consumption, the overall NHL relative risk increased nonlinearly with increased daily intake of red meat. CONCLUSION: The observed positive association between red meat consumption and NHL is mainly supported by the effect estimates coming from case-control studies and is affected by multiple sources of heterogeneity. This meta-analysis provided mixed and inconclusive evidences on the supposed relationship between red and processed meat consumption and NHL.

Is swimming in recreational water associated with the occurrence of respiratory illness? A systematic review and meta-analysis.

This study represents the first systematic review and meta-analysis conducted to assess the association between swimming in recreational water and the occurrence of respiratory illness. Most studies focus their attention on gastrointestinal illnesses occurring after exposure to microbial polluted water. Fourteen independent studies that included 50,117 patients with significant heterogeneity (I(2) = 95.3%) were reviewed. The meta-analysis reports that people exposed to recreational water (swimmers/bathers) present a higher risk of respiratory illness compared to non-swimmers/non-bathers [relative risk (RR) = 1.63 (confidence interval at 95% [95% CI]: 1.34-1.98)]. This percentage increases if adjusted RR by age and gender [RR = 2.24 (95% CI: 1.81-2.78)] are considered. A clear association between swimming in recreational water and the occurrence of respiratory illness was found. The surveillance of water quality monitoring systems is crucial not only for gastrointestinal illness, but also for respiratory ones.

Ecological correlation between diabetes hospitalizations and fine particulate matter in Italian provinces.

BACKGROUND: Exposure to particulate matter has been associated with increased risk of cardiovascular and respiratory diseases. We evaluated the ecological correlation between standardized hospital discharges with diabetes in Italian provinces and fine particulate matter (PM2.5) adjusting for common risk factors, socioeconomic factors and differences in hospitalization appropriateness. METHODS: We used cross sectional data aggregated at the province level and available from official institutional databases for years 2008-2010. Covariates included prevalence of adult overweight, obese, smokers, physically inactive, education and income (as average gross domestic product per person, GDP). We reduced the number of covariates to a smaller number of factors for the subsequent statistical model by extracting meaningful components using principal component analysis (PCA). Log-linear multiple regression analysis was used to model diabetes hospital discharges with PCA components and PM2.5 levels and hospitalization appropriateness for men and women. RESULTS: The first PCA components for both men and women were characterized by larger loadings of risk factors (obesity, overweight, physical inactivity, cigarette smoking) and lower socioeconomic factors (educational level and mean GDP). Diabetes hospitalization increases with the first PCA component and decreases with the index of hospitalization appropriateness. In fully adjusted models, diabetes hospitalizations increase with increasing annual PM2.5 concentrations, with a rise of 3.5 % (1.3 %-5.6 %) for men and of 4.0 % (1.5 %-6.4 %) for women per unit of PM2.5 increase. CONCLUSIONS: We found a significant ecological relationship between sex and age standardised hospital discharge with diabetes as principle diagnosis and mean annual PM2.5 concentrations in Italian provinces, once that covariates have been accounted for. The relationship was robust to different means of estimating PM2.5 exposure. A large portion of the variance of diabetes hospitalizations was linked to differences of hospital care appropriateness between Italian regions and this variable should routinely be included in ecological analyses of hospitalizations.

Microbiological safety of glasses dispensed at 3D movie theatres.

Recent popularity of three-dimensional movies raised some concern about microbiological safety of glasses dispensed into movie theatres. In this study, we analysed the level of microbiological contamination on them before and after use and between theatres adopting manual and automatic sanitation systems. The manual sanitation system was more effective in reducing the total mesophilic count levels compared with the automatic system (P < 0.05), but no differences were found for coagulase-positive staphylococci levels (P = 0.22). No differences were found for mould and yeast between before and after levels (P = 0.21) and between sanitation systems (P = 0.44). We conclude that more evidences are needed to support microbiological risk evaluation.

Factors influencing persistence of Legionella pneumophila serogroup 1 in laboratory cocultures.

BACKGROUND: Risk for infections from Legionella pneumophila for immunocompromised individuals increases greatly when this species is present within the biofilm of the water distribution systems of hospitals or other health facilities. Multiplication and persistence of Legionella may dependent also upon planktonic growth in alternative to sessile growth. Here we compared the persistence of L. pneumophila serogroup 1 in experimental planktonic co-cultures subsided with iron, Pseudomonas aeruginosa and other non Legionella bacteria (quantified as Heterotrophic Plate Count, HPC at 37°C), isolated from drinking water sources of a large hospital. RESULTS: Concentrations of L. pneumophila showed a decreasing pattern with incubation time in all co-cultures, the degree of reduction depending on the experimental treatment. In co-cultures with added P. aeruginosa, no L. pneumophila was detectable already after 4 days of incubation. In contrast in co-cultures without P. aeruginosa, HPC but not iron were significant factors in explaining the pattern of L. pneumophila, although the HPC effect was different according to the incubation time (HPC x time interaction, p < 0.01). CONCLUSIONS: Our results highlight the need of controlling for both HPC and metal constituents of the water systems of buildings used by individuals at particular risk to the effects of Legionella exposure.

Association between air pollution and emergency room admission for eye diseases in Rome, Italy: A time-series analysis.

Eye diseases impose a significant burden on health services due to high case numbers. However, exposure to outdoor air pollution is seldom mentioned as potential harmful factor. We conducted a time-series analysis in Rome, Italy, to estimate the association between daily mean concentration of NO2, PM10 and PM2.5 and daily number of emergency room (ER) admissions for a selected cluster of eye diseases from 2006 to 2016. We used Poisson regression adjusted for time trend, population decrease during summer vacations and holidays, day of week, apparent temperature (hot and cold) and daily concentration of nine pollen species. We observed 581,868 ER admissions during the study period. 44.74% of cases were observed in subjects with less than 20 years, 19.50% in 51-65 age category and 13.4% among children (0-14 years). No differences between sexes were recorded. Mean values of pollutant concentrations were 54.75, 31.01 and 18.14 µg/m3 for NO2, PM10 and PM2.5 respectively. The air temperature ranged from -1 °C to 32.5 °C, with a mean value of 16 °C (SD = 6.88). The apparent temperature spaced from -3.58 °C to 34.08 °C (mean = 15.61 °C, SD = 8.5). The highest percent risk increases for 10 µg/m3 increases of the three pollutants were observed at lag0-1 day (1.3%, 0.63-1.98 for PM2.5; 1.03%, 0.56-1.51 for PM10 and 0.6%, 0.13-1.07 for NO2). Risk increased significantly also at lag0 and lag0-5 day for each pollutant. Secondary analyses showed higher effects in the elderly compared to younger subjects. No differences emerged between sexes. The dose response analysis suggested of possible effects on ER admission risk also at low-level concentrations of PM2.5. A strong confounding effect of pollen was not detected. RESULTS: of this study are coherent with previous analyses. Speculation can be done about the biological mechanisms that link air pollution to eye damage.

Estimating the potential risk of transmission of arboviruses in the Americas and Europe: a modelling study.

BACKGROUND: Estimates of the spatiotemporal distribution of different mosquito vector species and the associated risk of transmission of arboviruses are key to design adequate policies for preventing local outbreaks and reducing the number of human infections in endemic areas. In this study, we quantified the abundance of Aedes albopictus and Aedes aegypti and the local transmission potential for three arboviral infections at an unprecedented spatiotemporal resolution in areas where no entomological surveillance is available. METHODS: We developed a computational model to quantify the daily abundance of Aedes mosquitoes, leveraging temperature and precipitation records. The model was calibrated on mosquito surveillance data collected in 115 locations in Europe and the Americas between 2007 and 2018. Model estimates were used to quantify the reproduction number of dengue virus, Zika virus, and chikungunya in Europe and the Americas, at a high spatial resolution. FINDINGS: In areas colonised by both Aedes species, A aegypti was estimated to be the main vector for the transmission of dengue virus, Zika virus, and chikungunya, being associated with a higher estimate of R0 when compared with A albopictus. Our estimates highlighted that these arboviruses were endemic in tropical and subtropical countries, with the highest risks of transmission found in central America, Venezuela, Colombia, and central-east Brazil. A non-negligible potential risk of transmission was also estimated for Florida, Texas, and Arizona (USA). The broader ecological niche of A albopictus could contribute to the emergence of chikungunya outbreaks and clusters of dengue autochthonous cases in temperate areas of the Americas, as well as in mediterranean Europe (in particular, in Italy, southern France, and Spain). INTERPRETATION: Our results provide a comprehensive overview of the transmission potential of arboviral diseases in Europe and the Americas, highlighting areas where surveillance and mosquito control capacities should be prioritised. FUNDING: EU and Ministero dell'Università e della Ricerca, Italy (Piano Nazionale di Ripresa e Resilienza Extended Partnership initiative on Emerging Infectious Diseases); EU (Horizon 2020); Ministero dell'Università e della Ricerca, Italy (Progetti di ricerca di Rilevante Interesse Nazionale programme); Brazilian National Council of Science, Technology and Innovation; Ministry of Health, Brazil; and Foundation of Research for Minas Gerais, Brazil.

How habitat factors affect an Aedes mosquitoes driven outbreak at temperate latitudes: The case of the Chikungunya virus in Italy.

BACKGROUND: Outbreaks of Aedes-borne diseases in temperate areas are not frequent, and limited in number of cases. We investigate the associations between habitat factors and temperature on individuals' risk of chikungunya (CHIKV) in a non-endemic area by spatially analyzing the data from the 2017 Italian outbreak. METHODOLOGY/PRINCIPAL FINDINGS: We adopted a case-control study design to analyze the association between land-cover variables, temperature, and human population density with CHIKV cases. The observational unit was the area, at different scales, surrounding the residence of each CHIKV notified case. The statistical analysis was conducted considering the whole dataset and separately for the resort town of Anzio and the metropolitan city of Rome, which were the two main foci of the outbreak. In Rome, a higher probability for the occurrence of CHIKV cases is associated with lower temperature (OR = 0.72; 95% CI: 0.61-0.85) and with cells with higher vegetation coverage and human population density (OR = 1.03; 95% CI: 1.00-1.05). In Anzio, CHIKV case occurrence was positively associated with human population density (OR = 1.03; 95% CI: 1.00-1.06) but not with habitat factors or temperature. CONCLUSION/SIGNIFICANCE: Using temperature, human population density and vegetation coverage data as drives for CHIKV transmission, our estimates could be instrumental in assessing spatial heterogeneity in the risk of experiencing arboviral diseases in non-endemic temperate areas.

Reporting delays of chikungunya cases during the 2017 outbreak in Lazio region, Italy.

BACKGROUND: Emerging arboviral diseases in Europe pose a challenge due to difficulties in detecting and diagnosing cases during the initial circulation of the pathogen. Early outbreak detection enables public health authorities to take effective actions to reduce disease transmission. Quantification of the reporting delays of cases is vital to plan and assess surveillance and control strategies. Here, we provide estimates of reporting delays during an emerging arboviral outbreak and indications on how delays may have impacted onward transmission. METHODOLOGY/PRINCIPAL FINDINGS: Using descriptive statistics and Kaplan-Meyer curves we analyzed case reporting delays (the period between the date of symptom onset and the date of notification to the public health authorities) during the 2017 Italian chikungunya outbreak. We further investigated the effect of outbreak detection on reporting delays by means of a Cox proportional hazard model. We estimated that the overall median reporting delay was 15.5 days, but this was reduced to 8 days after the notification of the first case. Cases with symptom onset after outbreak detection had about a 3.5 times higher reporting rate, however only 3.6% were notified within 24h from symptom onset. Remarkably, we found that 45.9% of identified cases developed symptoms before the detection of the outbreak. CONCLUSIONS/SIGNIFICANCE: These results suggest that efforts should be undertaken to improve the early detection and identification of arboviral cases, as well as the management of vector species to mitigate the impact of long reporting delays.

A survey of visually induced symptoms and associated factors in spectators of three dimensional stereoscopic movies.

BACKGROUND: The increasing popularity of commercial movies showing three dimensional (3D) computer generated images has raised concern about image safety and possible side effects on population health.This study aims to (1) quantify the occurrence of visually induced symptoms suffered by the spectators during and after viewing a commercial 3D movie and (2) to assess individual and environmental factors associated to those symptoms. METHODS: A cross-sectional survey was carried out using a paper based, self administered questionnaire. The questionnaire includes individual and movie characteristics and selected visually induced symptoms (tired eyes, double vision, headache, dizziness, nausea and palpitations). Symptoms were queried at 3 different times: during, right after and after 2 hours from the movie. RESULTS: We collected 953 questionnaires. In our sample, 539 (60.4%) individuals reported 1 or more symptoms during the movie, 392 (43.2%) right after and 139 (15.3%) at 2 hours from the movie. The most frequently reported symptoms were tired eyes (during the movie by 34.8%, right after by 24.0%, after 2 hours by 5.7% of individuals) and headache (during the movie by 13.7%, right after by 16.8%, after 2 hours by 8.3% of individuals). Individual history for frequent headache was associated with tired eyes (OR = 1.34, 95%CI = 1.01-1.79), double vision (OR = 1.96; 95%CI = 1.13-3.41), headache (OR = 2.09; 95%CI = 1.41-3.10) during the movie and of headache after the movie (OR = 1.64; 95%CI = 1.16-2.32). Individual susceptibility to car sickness, dizziness, anxiety level, movie show time, animation 3D movie were also associated to several other symptoms. CONCLUSIONS: The high occurrence of visually induced symptoms resulting from this survey suggests the need of raising public awareness on possible discomfort that susceptible individuals may suffer during and after the vision of 3D movies.

Short-term effects of particulate matter on cardiovascular morbidity in Italy: a national analysis.

AIMS: We aimed at investigating the relationship between particulate matter (PM) and daily admissions for cardiovascular diseases (CVDs) at national level in Italy. METHODS AND RESULTS: Daily numbers of cardiovascular hospitalizations were collected for all 8084 municipalities of Italy, in the period 2013-2015. A satellite-based spatiotemporal model was used to estimate daily PM10 (inhalable particles) and PM2.5 (fine particles) concentrations at 1-km2 resolution. Multivariate Poisson regression models were fit to estimate the association between daily PM and cardiovascular admissions. Flexible functions were estimated to explore the shape of the associations at low PM concentrations, also in non-urban areas. We analysed 2 154 810 acute hospitalizations for CVDs (25% stroke, 24% ischaemic heart diseases, 22% heart failure, and 5% atrial fibrillation). Relative increases of total cardiovascular admissions, per 10 µg/m3 variation in PM10 and PM2.5 at lag 0-5 (average of last 6 days since admission), were 0.55% (95% confidence intervals: 0.32%, 0.77%) and 0.97% (0.67%, 1.27%), respectively. The corresponding estimates for heart failure were 1.70% (1.28%, 2.13%) and 2.66% (2.09%, 3.23%). We estimated significant effects of PM10 and PM2.5 also on ischaemic heart diseases, myocardial infarction, atrial fibrillation, and ischaemic stroke. Associations were similar between less and more urbanized areas, and persisted even at low concentrations, e.g. below WHO guidelines. CONCLUSION: PM was robustly associated with peaks in daily cardiovascular admissions, especially for heart failure, both in large cities and in less urbanized areas of Italy. Current WHO Air Quality Guidelines for PM10 and PM2.5 are not sufficient to protect public health.

Diversity predicts stability and resource use efficiency in natural phytoplankton communities.

The relationship between species diversity and ecosystem functioning has been debated for decades, especially in relation to the "macroscopic" realm (higher plants and metazoans). Although there is emerging consensus that diversity enhances productivity and stability in communities of higher organisms; however, we still do not know whether these relationships apply also for communities of unicellular organisms, such as phytoplankton, which contribute approximately 50% to the global primary production. We show here that phytoplankton resource use, and thus carbon fixation, is directly linked to the diversity of phytoplankton communities. Datasets from freshwater and brackish habitats show that diversity is the best predictor for resource use efficiency of phytoplankton communities across considerable environmental gradients. Furthermore, we show that the diversity requirement for stable ecosystem functioning scales with the nutrient level (total phosphorus), as evidenced by the opposing effects of diversity (negative) and resource level (positive) on the variability of both resource use and community composition. Our analyses of large-scale observational data are consistent with experimental and model studies demonstrating causal effects of microbial diversity on functional properties at the system level. Our findings point at potential linkages between eutrophication and pollution-mediated loss of phytoplankton diversity. Factors reducing phytoplankton diversity may have direct detrimental effects on the amount and predictability of aquatic primary production.

A global association between Covid-19 cases and airborne particulate matter at regional level.

Evidences of an association between air pollution and Covid-19 infections are mixed and inconclusive. We conducted an ecological analysis at regional scale of long-term exposure to air-borne particle matter and spread of Covid-19 cases during the first wave of epidemics. Global air pollution and climate data were calculated from satellite earth observation data assimilated into numerical models at 10 km resolution. Main outcome was defined as the cumulative number of cases of Covid-19 in the 14 days following the date when > 10 cumulative cases were reported. Negative binomial mixed effect models were applied to estimate the associations between the outcome and long-term exposure to air pollution at the regional level (PM10, PM2.5), after adjusting for relevant regional and country level covariates and spatial correlation. In total we collected 237,749 Covid-19 cases from 730 regions, 63 countries and 5 continents at May 30, 2020. A 10 µg/m3 increase of pollution level was associated with 8.1% (95% CI 5.4%, 10.5%) and 11.5% (95% CI 7.8%, 14.9%) increases in the number of cases in a 14 days window, for PM2.5 and PM10 respectively. We found an association between Covid-19 cases and air pollution suggestive of a possible causal link among particulate matter levels and incidence of COVID-19.

Real-life use of tocilizumab with or without corticosteroid in hospitalized patients with moderate-to-severe COVID-19 pneumonia: A retrospective cohort study.

OBJECTIVE: To evaluate the effectiveness of Tocilizumab (with or without corticosteroids) in a real-life context among moderate-to-severe COVID-19 patients hospitalized at the Infectious Diseases ward of two hospitals in Lazio region, Italy, during the first wave of SARS-CoV-2 pandemic. METHOD: We conducted a retrospective cohort study among moderate-to-severe COVID-19 pneumonia to assess the influence of tocilizumab (with or without corticosteroids) on: 1) primary composite outcome: risk for death/invasive mechanical ventilation/ICU-transfer at 14 days from hospital admission; 2) secondary outcome: COVID-related death only. Both outcomes were also assessed at 28 days and restricted to baseline more severe cases. We also evaluated the safety of tocilizumab. RESULTS: Overall, 412 patients were recruited, being affected by mild (6.8%), moderate (66.3%) or severe (26.9%) COVID-19 at baseline. The median participant' age was 63 years, 56.5% were men, the sum of comorbidities was 1.34 (±1.44), and the median time from symptom onset to hospital admission was 7 [3-10] days. Patients were subdivided in 4 treatment groups: standard of care (SoC) only (n = 172), SoC plus corticosteroid (n = 65), SoC plus tocilizumab (n = 50), SoC plus tocilizumab and corticosteroid (n = 125). Twenty-six (6.3%) patients underwent intubation, and 37 (9%) COVID-related deaths were recorded. After adjusting for several factors, multivariate analysis showed that tocilizumab (with or without corticosteroids) was associated to improved primary and secondary outcomes at 14 days, and at 28-days only when tocilizumab administered without corticosteroid. Among more severe cases the protective effect of tocilizumab (± corticosteroids) was observed at both time-points. No safety concerns were recorded. CONCLUSION: Although contrasting results from randomized clinical trials to date, in our experience tocilizumab was a safe and efficacious therapeutic option for patients with moderate-to-severe COVID-19 pneumonia. Its efficacy was improved by the concomitant administration of corticosteroids in patients affected by severe-COVID-19 pneumonia at baseline.

Differential induction of type I and III interferon genes in the upper respiratory tract of patients with coronavirus disease 2019 (COVID-19).

The natural course of type I and III interferon (IFN) response in the respiratory tract of COVID-19 patients needs to be better defined. We showed that type I/III IFNs, IFN-regulatory factor 7 (IRF7), and IFN stimulated genes (ISGs), are highly expressed in the oropharyngeal cells of SARS-CoV-2 positive patients compared to healthy controls. Notably, the subgroup of critically-ill patients that required invasive mechanical ventilation had a general decrease in expression of IFN/ISG genes. Heterogeneous patterns of IFN-I/III response in the respiratory tract of COVID-19 patients may be associated to COVID-19 severity.