Among seven coronaviruses that infect humans, three (SARS-CoV, MERS-CoV, and the newly identified SARS-CoV-2) are associated with a severe, life-threatening respiratory infection and multiorgan failure. We previously proposed that the cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) is a potent inhibitor of HCoV-NL63. Next, we demonstrated the broad-spectrum antiviral activity of the compound, as it inhibited all low pathogenic human coronaviruses (HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1). Here, using in vitro and ex vivo model of human airway epithelium, we show that HTCC effectively blocks MERS-CoV and SARS-CoV-2 infection. We also confirmed the mechanism of action for these two viruses, showing that the polymer blocks the virus entry to the host cell by interaction with the S protein. IMPORTANCE The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the health care measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of previously developed by us HTCC compound, which may be used as a potential inhibitor of currently circulating highly pathogenic coronaviruses – SARS-CoV-2 and MERS-CoV.
38The beginning of 2020 brought us information about the novel coronavirus emerging in China. 39Rapid research resulted in the characterization of the pathogen, which appeared to be a member 40 of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus 41 escaped the healthcare measures and rapidly spread in China and later globally, officially 42 causing a pandemic and global crisis in March 2020. At present, different scenarios are being 43 written to contain the virus, but the development of novel anticoronavirals for all highly 44 pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity 45 of previously developed by us HTCC compound (N-(2-hydroxypropyl)-3-trimethylammonium 46 chitosan chloride), which may be used as potential inhibitor of currently circulating highly 47
Background In Poland, the clinical characteristics and outcomes of patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) remain unknown. This study aimed to answer these unknowns by analyzing data collected from high-volume ECMO centers willing to participate in this project. Methods This retrospective, multicenter cohort study was completed between March 1, 2020, and May 31, 2021 (15 months). Data from all patients treated with ECMO for COVID-19 were analyzed. Pre-ECMO laboratory and treatment data were compared between non-survivors and survivors. Independent predictors for death in the intensive care unit (ICU) were identified. Results There were 171 patients admitted to participating centers requiring ECMO for refractory hypoxemia due to COVID-19 during the defined time period. A total of 158 patients (mean age: 46.3 ± 9.8 years) were analyzed, and 13 patients were still requiring ECMO at the end of the observation period. Most patients (88%) were treated after October 1, 2020, 77.8% were transferred to ECMO centers from another facility, and 31% were transferred on extracorporeal life support. The mean duration of ECMO therapy was 18.0 ± 13.5 days. The crude ICU mortality rate was 74.1%. In the group of 41 survivors, 37 patients were successfully weaned from ECMO support and four patients underwent a successful lung transplant. In-hospital death was independently associated with pre-ECMO lactate level (OR 2.10 per 1 mmol/L, p = 0.017) and BMI (OR 1.47 per 5 kg/m2, p = 0.050). Conclusions The ICU mortality rate among patients requiring ECMO for COVID-19 in Poland was high. In-hospital death was independently associated with increased pre-ECMO lactate levels and BMI.
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