Involvement of the contact pathway in COVID-19 coagulopathy

Background: A novel acquired coagulopathy characterized by a severe procoagulant imbalance is common in COVID-19 patients and is associated with the clinical severity of the disease. Aim(s): Our study aims to elucidate the underlying mechanisms of coagulation activation in COVID-19 patients. Method(s): Symptomatic COVID-19 patients during Milan first wave were consecutively enrolled and stratified into 3 groups based on the intensity of care: Low, requiring only high-flow oxygen by nasal cannula;intermediate, requiring continuous positive airway pressure;high, requiring mechanical ventilation. Blood samples were tested for markers of activation of the intrinsic pathway (FXIa, FXIIa) together with its physiologic inhibitor (C1-inhibitor), of the extrinsic pathway (FVIIa), of global activation of the coagulation cascade (D-dimer, FDP, FM) and of fibrinolysis (plasminogen, t-PA, alpha2-antiplasmin, PAI-1). Result(s): 111 patients were included: 26 at low, 42 intermediate and 43 high care-intensity. Median age was 59 +/- 12 (34 patients >65 years);32 patients (29%) developed a venous thrombosis and 12 (11%) died (Table). Median D-dimer, FDP and FM plasma levels were higher in COVID-19 patients compared to controls, with a gradient of increase across the three care intensities, while all the fibrinolytic pathway parameters were in the normal range. Median plasma levels of FVIIa were lower in COVID-19 patients (27.5 mU/ml) than in controls (40.1 mU/ml) while median plasma levels of FXIIa and FXIa were higher in COVID-19 patients (11.2 and 11.3 mU/ml) than in controls (7.2 and 5.5 mU/ml), with a gradient of increase across the three care intensities. C1-inhibitor plasma levels were above the normal range in all the 3 COVID-19 patients' groups (Figure). Conclusion(s): Our study showed a prevalent activation of the contact pathway over the extrinsic pathway of the coagulation cascade in COVID-19 patients, which is proportional to the clinical severity of the infection, opening the possibility for targeted anticoagulant therapies. (Table Presented).

Impact assessment on air quality in Lombardy of the limitations for contrasting the diffusion of COVID-19

In this paper, ARPA Lombardy presents the simulation results and a preliminary impact assesment on air quality due to the introduction of limitation and social distancing rules for contrasting the diffusion of COVID-19 disease. A specific data flux and methodology have been developed on the base of the most recent emission inventory available for the Lombardy region and algorithms, ad hoc built up for the study, to estimate the primary emission variations of the main atmospheric pollutant, potentially affected by the anti-COVID rules. Two emission scenarios have been identified:”BAU”, defined as business as usual, and”COVID”, defined as the situation expected during the period. The main emission estimates on a daily base have been used as input in the chemical transport model FARM for evaluating the impact of lockdown on air quality in Lombardy. Simulated data have been also assimilated with measurements in 2020 and measured data in the three previous years 2017-2019. © 2020 HARMO. All rights reserved.