Objectives: The novel severe acute respiratory syndrome coronavirus 2 pandemic continues to spread globally without an effective treatment. In search of the cure, convalescent plasma (CP) containing ...protective antibodies from survivors of coronavirus disease 2019 (COVID-19) infection has shown potential benefit in a non-intensive care unit setting. We sought to evaluate the effectiveness of CP therapy for patients with COVID-19 on mechanical ventilation (MV) and/or acute respiratory distress syndrome (ARDS).
Methods: We conducted an open-label trial in a single center, Royal Hospital, in Oman. The study was conducted from 17 April to 20 June 2020. The trial included 94 participants with laboratory-confirmed COVID-19. The primary outcomes included extubation rates, discharges from the hospital and overall mortality, while secondary outcomes were the length of stay and improvement in respiratory and laboratory parameters. Analyses were performed using univariate statistics.
Results: The overall mean age of the cohort was 50.0+-15.0 years, and 90.4% (n = 85) were males. A total of 77.7% (n = 73) of patients received CP. Those on CP were associated with a higher extubation rate (35.6% vs. 76.2%; p < 0.001), higher extubation/home discharges rate (64.4% vs. 23.8%; p = 0.001), and tendency towards lower overall mortality (19.2% vs. 28.6%; p = 0.354; study power = 11.0%) when compared to COVID-19 patients that did not receive CP.
Conclusions: CP was associated with higher extubation/home discharges and a tendency towards lower overall mortality when compared to those that did not receive CP in COVID-19 patients on MV or in those with ARDS. Further studies are warranted to corroborate our findings.
Objectives: The novel severe acute respiratory syndrome coronavirus 2 pandemic continues to spread globally without an effective treatment. In search of the cure, convalescent plasma (CP) containing ...protective antibodies from survivors of coronavirus disease 2019 (COVID-19) infection has shown potential benefit in a non-intensive care unit setting. We sought to evaluate the effectiveness of CP therapy for patients with COVID-19 on mechanical ventilation (MV) and/or acute respiratory distress syndrome (ARDS).
Methods: We conducted an open-label trial in a single center, Royal Hospital, in Oman. The study was conducted from 17 April to 20 June 2020. The trial included 94 participants with laboratory-confirmed COVID-19. The primary outcomes included extubation rates, discharges from the hospital and overall mortality, while secondary outcomes were the length of stay and improvement in respiratory and laboratory parameters. Analyses were performed using univariate statistics.
Results: The overall mean age of the cohort was 50.0+-15.0 years, and 90.4% (n = 85) were males. A total of 77.7% (n = 73) of patients received CP. Those on CP were associated with a higher extubation rate (35.6% vs. 76.2%; p < 0.001), higher extubation/home discharges rate (64.4% vs. 23.8%; p = 0.001), and tendency towards lower overall mortality (19.2% vs. 28.6%; p = 0.354; study power = 11.0%) when compared to COVID-19 patients that did not receive CP.
Conclusions: CP was associated with higher extubation/home discharges and a tendency towards lower overall mortality when compared to those that did not receive CP in COVID-19 patients on MV or in those with ARDS. Further studies are warranted to corroborate our findings.
Leukocyte inflammatory responses require integrin cell-adhesion molecule signaling through spleen tyrosine kinase (Syk), a non-receptor kinase that binds directly to integrin β-chain cytoplasmic ...domains. Here, we developed a high-throughput screen to identify small molecule inhibitors of the Syk-integrin cytoplasmic domain interactions. Screening small molecule compound libraries identified the β-lactam antibiotics cefsulodin and ceftazidime, which inhibited integrin β-subunit cytoplasmic domain binding to the tandem SH2 domains of Syk (IC
range, 1.02-4.9 µM). Modeling suggested antagonist binding to Syk outside the pITAM binding site. Ceftazidime inhibited integrin signaling
Syk, including inhibition of adhesion-dependent upregulation of interleukin-1β and monocyte chemoattractant protein-1, but did not inhibit ITAM-dependent phosphorylation of Syk mediated by FcγRI signaling. Our results demonstrate a novel means to target Syk independent of its kinase and pITAM binding sites such that integrin signaling
this kinase is abrogated but ITAM-dependent signaling remains intact. As integrin signaling through Syk is essential for leukocyte activation, this may represent a novel approach to target inflammation.
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