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Innate immunology in COVID-19-a living review. Part II: dysregulated inflammation drives immunopathology. COVID-19中的先天免疫学--生动回顾。第二部分:炎症失调驱动免疫病理学。
Oxford open immunology Pub Date : 2020-12-08 eCollection Date: 2020-01-01 DOI: 10.1093/oxfimm/iqaa005
Patrícia R S Rodrigues, Aljawharah Alrubayyi, Ellie Pring, Valentina M T Bart, Ruth Jones, Clarissa Coveney, Fangfang Lu, Michael Tellier, Shayda Maleki-Toyserkani, Felix C Richter, D Oliver Scourfield, Ester Gea-Mallorquí, Luke C Davies
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引用次数: 0
A new immunology forum for a new age of immunology. 免疫学新时代的免疫学新论坛。
Oxford open immunology Pub Date : 2020-01-01 DOI: 10.1093/oxfimm/iqaa002
Daniel M Altmann
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引用次数: 0
Adaptive immunity to SARS-CoV-2. 对 SARS-CoV-2 的适应性免疫。
Oxford open immunology Pub Date : 2020-01-01 Epub Date: 2020-07-09 DOI: 10.1093/oxfimm/iqaa003
Daniel M Altmann
{"title":"Adaptive immunity to SARS-CoV-2.","authors":"Daniel M Altmann","doi":"10.1093/oxfimm/iqaa003","DOIUrl":"10.1093/oxfimm/iqaa003","url":null,"abstract":"<p><p>The majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 exposed individuals mount an antibody response within around 2-weeks and spike antigen-binding responses correlate well with functional virus neutralization. A minority makes little detectable antibody, generally those with either very mild/asymptomatic disease or those with severe/lethal infection. However, in general, antibody titre correlates with viral load and duration of exposure. There is evidence for cross-reactivity with the other human coronaviruses, though the functional impact of this is as yet unclear. Therapeutic use of neutralizing monoclonal antibodies offers potential for clinical use. While there is evidence for neutralizing antibody as a correlate of protection, some cases indicate the potential for full recovery in the absence of antibody. Studies of T-cell immunity following acute infection show CD4 and CD8 responses to epitopes across diverse viral antigens, possible cross-reactivity with epitopes from the common cold human coronaviruses and large-scale activation. However, in severe cases, there is evidence for T-cell lymphopaenia as well as expression of exhaustion markers. Analysis of serum biomarkers of disease severity implicates a hyperinflammatory contribution to pathogenesis, though this has not been mechanistically delineated beyond a likely role of raised IL-6, considered a therapeutic target. Despite rapid progress, there remain pressing unknowns. It seems likely that immune memory to SARS-CoV-2 may be relatively short lived, but this will need longitudinal investigation. Also, this is a disease of highly variable presentation and time course, with some progressing to protracted, chronic symptoms, which are not understood. The contribution of immunopathological mechanisms to tissue damage, whether in the lung, kidney, heart or blood vessels, is unclear. The immunology underlying the differential susceptibility between the very young and the very old is unresolved, a question with ramifications for vaccine roll-out. The greatest challenge relates to rapid generation, testing and manufacture of vaccines that are immunogenic, protective (at least from symptomatic disease) and safe-a challenge that looks achievable.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"1 1","pages":"iqaa003"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10770917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cholesterol-modifying drugs in COVID-19. COVID-19 中的胆固醇调节药物。
Oxford open immunology Pub Date : 2020-01-01 Epub Date: 2020-06-18 DOI: 10.1093/oxfimm/iqaa001
Nathalie M Schmidt, Peter A C Wing, Jane A McKeating, Mala K Maini
{"title":"Cholesterol-modifying drugs in COVID-19.","authors":"Nathalie M Schmidt, Peter A C Wing, Jane A McKeating, Mala K Maini","doi":"10.1093/oxfimm/iqaa001","DOIUrl":"10.1093/oxfimm/iqaa001","url":null,"abstract":"<p><p>Infection with severe acute respiratory syndrom coronavirus 2 (SARS-CoV-2) is more likely to lead to poor outcomes in the elderly and those with cardiovascular disease, obesity or metabolic syndrome. Here, we consider mechanisms by which dyslipidaemia and the use of cholesterol-modifying drugs could influence the virus-host relationship. Cholesterol is essential for the assembly, replication and infectivity of enveloped virus particles; we highlight several cholesterol-modifying drugs with the potential to alter the SARS-CoV-2 life cycle that could be tested in <i>in vitro</i> and <i>in vivo</i> models. Although cholesterol is an essential component of immune cell membranes, excess levels can dysregulate protective immunity and promote exaggerated pulmonary and systemic inflammatory responses. Statins block the production of multiple sterols, oxysterols and isoprenoids, resulting in a pleiotropic range of context-dependent effects on virus infectivity, immunity and inflammation. We highlight antiviral, immunomodulatory and anti-inflammatory effects of cholesterol-modifying drugs that merit further consideration in the management of SARS-CoV-2 infection.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"1 1","pages":"iqaa001"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9230131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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