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Antiviral Res ; 202: 105311, 2022 06.
Article in English | MEDLINE | ID: covidwho-1773103


Nelfinavir is an HIV protease inhibitor that has been widely prescribed as a component of highly active antiretroviral therapy, and has been reported to exert in vitro antiviral activity against SARS-CoV-2. We here assessed the effect of Nelfinavir in a SARS-CoV-2 infection model in hamsters. Despite the fact that Nelfinavir, [50 mg/kg twice daily (BID) for four consecutive days], did not reduce viral RNA load and infectious virus titres in the lung of infected animals, treatment resulted in a substantial improvement of SARS-CoV-2-induced lung pathology. This was accompanied by a dense infiltration of neutrophils in the lung interstitium which was similarly observed in non-infected hamsters. Nelfinavir resulted also in a marked increase in activated neutrophils in the blood, as observed in non-infected animals. Although Nelfinavir treatment did not alter the expression of chemoattractant receptors or adhesion molecules on human neutrophils, in vitro migration of human neutrophils to the major human neutrophil attractant CXCL8 was augmented by this protease inhibitor. Nelfinavir appears to induce an immunomodulatory effect associated with increasing neutrophil number and functionality, which may be linked to the marked improvement in SARS-CoV-2 lung pathology independent of its lack of antiviral activity. Since Nelfinavir is no longer used for the treatment of HIV, we studied the effect of two other HIV protease inhibitors, namely the combination Lopinavir/Ritonavir (Kaletra™) in this model. This combination resulted in a similar protective effect as Nelfinavir against SARS-CoV2 induced lung pathology in hamsters.

COVID-19 , HIV Infections , HIV Protease Inhibitors , Animals , COVID-19/drug therapy , Cricetinae , HIV Infections/drug therapy , HIV Protease Inhibitors/pharmacology , HIV Protease Inhibitors/therapeutic use , Lopinavir/pharmacology , Lopinavir/therapeutic use , Lung , Mesocricetus , Nelfinavir/pharmacology , Nelfinavir/therapeutic use , RNA, Viral , Ritonavir/therapeutic use , SARS-CoV-2
Semin Thromb Hemost ; 47(4): 362-371, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1203471


BACKGROUND: Venous thromboembolism (VTE) is a frequent complication of COVID-19, so that the importance of adequate in-hospital thromboprophylaxis in patients hospitalized with COVID-19 is well established. However, the incidence of VTE after discharge and whether postdischarge thromboprophylaxis is beneficial and safe are unclear. In this prospective observational single-center study, we report the incidence of VTE 6 weeks after hospitalization and the use of postdischarge thromboprophylaxis. METHODS: Patients hospitalized with confirmed COVID-19 were invited to a multidisciplinary follow-up clinic 6 weeks after discharge. D-dimer and C-reactive protein were measured, and all patients were screened for deep vein thrombosis with venous duplex-ultrasound. Additionally, selected high-risk patients received computed tomography pulmonary angiogram or ventilation-perfusion (V/Q) scan to screen for incidental pulmonary embolism. RESULTS: Of 485 consecutive patients hospitalized from March through June 2020, 146 patients were analyzed, of which 39% had been admitted to the intensive care unit (ICU). Postdischarge thromboprophylaxis was prescribed in 28% of patients, but was used more frequently after ICU stay (61%) and in patients with higher maximal D-dimer and C-reactive protein levels during hospitalization. Six weeks after discharge, elevated D-dimer values were present in 32% of ward and 42% of ICU patients. Only one asymptomatic deep vein thrombosis (0.7%) and one symptomatic pulmonary embolism (0.7%) were diagnosed with systematic screening. No bleedings were reported. CONCLUSION: In patients who had been hospitalized with COVID-19, systematic screening for VTE 6 weeks after discharge revealed a low incidence of VTE. A strategy of selectively providing postdischarge thromboprophylaxis in high-risk patients seems safe and potentially effective.

C-Reactive Protein/metabolism , COVID-19 , Fibrin Fibrinogen Degradation Products/metabolism , Patient Discharge , SARS-CoV-2/metabolism , Venous Thromboembolism , COVID-19/blood , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Pulmonary Embolism/blood , Pulmonary Embolism/etiology , Pulmonary Embolism/mortality , Pulmonary Embolism/prevention & control , Venous Thromboembolism/blood , Venous Thromboembolism/etiology , Venous Thromboembolism/mortality , Venous Thromboembolism/prevention & control , Venous Thrombosis/blood , Venous Thrombosis/etiology , Venous Thrombosis/mortality , Venous Thrombosis/prevention & control