Antibody response to multiple antigens of SARS-CoV-2 in patients with diabetes: an observational cohort study.
Antibody response to multiple antigens of SARS-CoV-2 in patients with diabetes: an observational cohort study.
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DOI：
10.1007/s00125-020-05284-4
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发表时间：
2020-12
期刊：
影响因子：
8.2
通讯作者：
Piemonti L
中科院分区：
文献类型：
--
作者：
Lampasona V;Secchi M;Scavini M;Bazzigaluppi E;Brigatti C;Marzinotto I;Davalli A;Caretto A;Laurenzi A;Martinenghi S;Molinari C;Vitali G;Di Filippo L;Mercalli A;Melzi R;Tresoldi C;Rovere-Querini P;Landoni G;Ciceri F;Bosi E;Piemonti L
该研究的目的是表征糖尿病患者对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的体液反应。证明在高血糖的情况下产生适当的抗体反应的能力，对于理解与糖尿病患者中观察到的 2019 年冠状病毒病 (COVID-19) 肺炎的临床结果较差相关的机制以及未来预防 SARS-CoV-2 感染的疫苗接种活动的开展相关。我们通过液相荧光素酶免疫沉淀测定对抗体进行高度特异性和灵敏的测量，在我们机构前瞻性跟踪的 509 名确诊为 COVID-19 的患者中，对 SARS-CoV-2 多种抗原的 IgG、IgM 和 IgA 反应进行了表征。我们根据住院时或住院期间是否存在高血糖（即诊断或未诊断的糖尿病）分析临床结果和抗体滴度。在确诊的 COVID-19 患者中，139 名（27.3%）患有糖尿病：90 名（17.7%）在入院前诊断出糖尿病（合并糖尿病），而 49 名（9.6%）在入院时诊断出糖尿病（新诊断）。糖尿病与炎症生物标志物和高凝血病以及白细胞增多和中性粒细胞增多水平相关。即使在调整了年龄、性别和其他相关合并症后，糖尿病与死亡风险独立相关（HR 2.32 [95% CI 1.44, 3.75]，p= 0.001）。此外，无论糖尿病诊断如何，较高的血糖水平与死亡风险之间都存在很强的相关性（HR 1.14 × 1.1 mmol/l [95% CI 1.08, 1.21]，p< 0.001）。糖尿病患者针对 SARS-CoV-2 的体液反应是存在的，并且就时间和抗体滴度而言，与非糖尿病患者的体液反应可叠加，存在微小差异，并且不受血糖水平的影响。在测量的抗体反应中，针对 SARS-CoV-2 刺突受体结合域 (RBD) 的 IgG 阳性可预测生存率，无论是否存在糖尿病。在高血糖患者中观察到的 COVID-19 肺炎严重程度和死亡风险增加并不是针对 SARS-CoV-2 的体液反应受损的结果。 RBD IgG 阳性与显着的保护作用相关，因此我们对未来 SARs-COV-2 疫苗对糖尿病患者的功效持谨慎乐观态度。图文摘要 本文的在线版本 (10.1007/s00125-020-05284-4) 包含经过同行评审但未经编辑的补充材料，可供授权用户使用。
The aim of the study was to characterise the humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with diabetes. Demonstrating the ability to mount an appropriate antibody response in the presence of hyperglycaemia is relevant for the comprehension of mechanisms related to the observed worse clinical outcome of coronavirus disease 2019 (COVID-19) pneumonia in patients with diabetes and for the development of any future vaccination campaign to prevent SARS-CoV-2 infection. Using a highly specific and sensitive measurement of antibodies by fluid-phase luciferase immunoprecipitation assays, we characterised the IgG, IgM and IgA response against multiple antigens of SARS-CoV-2 in a cohort of 509 patients with documented diagnosis of COVID-19, prospectively followed at our institution. We analysed clinical outcomes and antibody titres according to the presence of hyperglycaemia, i.e., either diagnosed or undiagnosed diabetes, at the time of, or during, hospitalisation. Among patients with confirmed COVID-19, 139 (27.3%) had diabetes: 90 (17.7%) had diabetes diagnosed prior to the hospital admission (comorbid diabetes) while 49 (9.6%) had diabetes diagnosed at the time of admission (newly diagnosed). Diabetes was associated with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leucocytosis and neutrophilia. Diabetes was independently associated with risk of death (HR 2.32 [95% CI 1.44, 3.75], p = 0.001), even after adjustment for age, sex and other relevant comorbidities. Moreover, a strong association between higher glucose levels and risk of death was documented irrespective of diabetes diagnosis (HR 1.14 × 1.1 mmol/l [95% CI 1.08, 1.21], p < 0.001). The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable, as for timing and antibody titres, to that of non-diabetic patients, with marginal differences, and was not influenced by glucose levels. Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike receptor-binding domain (RBD) was predictive of survival rate, both in the presence or absence of diabetes. The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycaemia was not the result of an impaired humoral response against SARS-CoV-2. RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARs-COV-2 in people with diabetes. Graphical abstract The online version of this article (10.1007/s00125-020-05284-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
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DOI：
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