The Journal of immunology : official journal of the American Association of Immunologists
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Seasonal influenza and the current COVID-19 pandemic represent looming global health challenges. Efficacious and safe vaccines remain the frontline tools for mitigating both influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced diseases. This review will discuss the existing strategies for influenza vaccines and how these strategies have informed SARS-CoV-2 vaccines. It will also discuss new vaccine platforms and potential challenges for both viruses.
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Multicenter Study Observational Study
Repurposed Tocilizumab in Patients with Severe COVID-19.
The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable morbidity and mortality. Tocilizumab, an inhibitor of IL-6, has been widely repurposed as a treatment of severely ill patients without robust evidence supporting its use. In this study, we aimed to systematically describe the effectiveness of treatment and prevention of the cytokine storms in COVID-19 patients with tocilizumab. ⋯ After tocilizumab administration, abnormally elevated IL-6, C-reactive protein, fibrinogen, and activated partial thromboplastin time decreased. Tocilizumab may be of value in prolonging survival in patients with severe COVID-19, which provided a novel strategy for COVID-19-induced cytokine release syndrome. Our findings could inform bedside decisions until data from randomized, controlled clinical trials become available.
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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and has since become a global pandemic. Pathogen-specific Abs are typically a major predictor of protective immunity, yet human B cell and Ab responses during COVID-19 are not fully understood. In this study, we analyzed Ab-secreting cell and Ab responses in 20 hospitalized COVID-19 patients. ⋯ SARS-CoV-2-specific IgA, IgG, and IgM Ab levels positively correlated with SARS-CoV-2-neutralizing Ab titers, suggesting that SARS-CoV-2-specific Ab levels may reflect the titers of neutralizing Abs in COVID-19 patients during the acute phase of infection. Last, we showed that IL-6 and C-reactive protein serum concentrations were higher in patients who were hospitalized for longer, supporting the recent observations that IL-6 and C-reactive protein could be used as markers for COVID-19 severity. Altogether, this study constitutes a detailed description of clinical and immunological parameters in 20 COVID-19 patients, with a focus on B cell and Ab responses, and describes tools to study immune responses to SARS-CoV-2 infection and vaccination.
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Coronavirus disease of 2019 (COVID-19) is a highly contagious respiratory infection that is caused by the severe acute respiratory syndrome coronavirus 2. Although most people are immunocompetent to the virus, a small group fail to mount an effective antiviral response and develop chronic infections that trigger hyperinflammation. ⋯ Indeed, patients with severe COVID-19 show prominent complement activation in their lung, skin, and sera, and those individuals who were treated with complement inhibitors all recovered with no adverse reactions. These and other studies hint at complement's therapeutic potential in these sequalae, and thus, to support drug development, in this review, we provide a summary of COVID-19 and review complement's role in COVID-19 acute respiratory distress syndrome and coagulopathy.
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Over the first days of polymicrobial sepsis, there is robust activation of the innate immune system, causing the appearance of proinflammatory cytokines and chemokines, along with the appearance of extracellular histones, which are highly proinflammatory and prothrombotic. In the current study, we studied different innate immune responses in mice with knockout (KO) of complement protein 6 (C6). Polymorphonuclear neutrophils (PMNs) from these KO mice had defective innate immune responses, including defective expression of surface adhesion molecules, generation of superoxide anion, and appearance of reactive oxygen species and histone release after activation of PMNs, along with defective phagocytosis. ⋯ In addition, sepsis-induced cardiac dysfunction was attenuated in these KO mice. In a model of acute lung injury induced by LPS, C6-/- mice showed reduced PMN buildup and less lung epithelial/endothelial cell dysfunction (edema and hemorrhage). These data indicate that C6-/- mice have reduced innate immune responses that result in less organ injury and improved survival after polymicrobial sepsis.