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.

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.

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.