Frontiers in immunology
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Frontiers in immunology · Jan 2020
ReviewNeurotoxicity and Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy: Insights Into Mechanisms and Novel Therapies.
Chimeric antigen receptor T (CART) cell immunotherapy has been remarkably successful in treating certain relapsed/refractory hematological cancers. However, CART cell therapy is also associated with toxicities which present an obstacle to its wider adoption as a mainstay for cancer treatment. ⋯ New insights into the mechanisms of these toxicities have spurred novel treatment options. In this review, we summarize the available literature on the clinical manifestations, mechanisms, and treatments of CART-associated CRS and ICANS.
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Frontiers in immunology · Jan 2020
ReviewMitigating Coronavirus Induced Dysfunctional Immunity for At-Risk Populations in COVID-19: Trained Immunity, BCG and "New Old Friends".
The novel, highly contagious coronavirus SARS-CoV-2 spreads rapidly throughout the world, leading to a deadly pandemic of a predominantly respiratory illness called COVID-19. Safe and effective anti-SARS-CoV-2 vaccines are urgently needed. ⋯ Animal data from earlier coronavirus vaccine efforts indicate that elderly people, most at risk from severe COVID-19 disease, could be especially at risk from immunopathologic responses to novel coronavirus vaccines. Bacterial "new old friends" such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called "trained immunity." Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other "new old friends."
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Frontiers in immunology · Jan 2020
ReviewA 21st Century Evil: Immunopathology and New Therapies of COVID-19.
Coronavirus Disease 2019 (COVID-19) has been classified as a global threat, affecting millions of people and killing thousands. It is caused by the SARS-CoV-2 virus, which emerged at the end of 2019 in Wuhan, China, quickly spreading worldwide. COVID-19 is a disease with symptoms that range from fever and breathing difficulty to acute respiratory distress and death, critically affecting older patients and people with previous comorbidities. ⋯ The immune system of infected patients has been demonstrated to suffer important alterations, such as lymphopenia, exhausted lymphocytes, excessive amounts of inflammatory monocytes and macrophages, especially in the lungs, and cytokine storms, which may contribute to its severity and difficulty of establishing an effective treatment. Even though no specific treatment is currently available, several studies have been investigating potential therapeutic strategies, including the use of previously approved drugs and immunotherapy. In this context, this review addresses the interaction between SARS-CoV-2 and the patient's host immune system during infection, in addition to discussing the main immunopathological mechanisms involved in the development of the disease and potential new therapeutic approaches.
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Frontiers in immunology · Jan 2020
Could the Induction of Trained Immunity by β-Glucan Serve as a Defense Against COVID-19?
As the SARS-CoV-2 virus wreaks havoc on the populations, health care infrastructures and economies of nations around the world, finding ways to protect health care workers and bolster immune responses in the general population while we await an effective vaccine will be the difference between life and death for many people. Recent studies show that innate immune populations may possess a form of memory, termed Trained Immunity (TRIM), where innate immune cells undergo metabolic, mitochondrial, and epigenetic reprogramming following exposure to an initial stimulus that results in a memory phenotype of enhanced immune responses when exposed to a secondary, heterologous, stimulus. ⋯ We also evaluate the potential effects of β-glucan in relation to the immune dysregulation and cytokine storm observed in COVID-19. Ultimately, we hypothesize that the use of oral β-glucan in a prophylactic setting could be an effective way to boost immune responses and abrogate symptoms in COVID-19, though clinical trials are necessary to confirm the efficacy of this treatment and to further examine differential effects of β-glucan's from various sources.
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Frontiers in immunology · Jan 2020
Case ReportsLonger Duration of SARS-CoV-2 Infection in a Case of Mild COVID-19 With Weak Production of the Specific IgM and IgG Antibodies.
Background: The relationship between SARS-CoV-2-carrying time and specific antibody production has not yet been reported in re-admitted COVID-19 patients. We reported a case of mild COVID-19 with long virus-carrying time, weak production of virus-specific IgG and IgM antibodies, and recurrence of positive SARS-CoV-2 RNA in stool specimens after discharge. Case Presentation: A 27-year-old male was diagnosed as COVID-19 after returning to Meizhou from Wuhan. ⋯ The production of the IgM and IgG targeting SARS-CoV-2 in this very mild case was much lower than that in a severe case of COVID-19 during the same hospitalizing period, and the latter was used as a control. Conclusion: Mild COVID-19 patients could carry SARS-CoV-2 for a long time, which may be related to the weak production of the virus-specific IgG and IgM. Recurrence of positive SARS-CoV-2 RNA could occur in mild COVID-19 possibly due to intermittent virus shedding, so strict quarantine and health surveillance should be taken for all discharged COVID-19 patients to prevent a potential virus spread.