1 BACKGROUND

Type 2 diabetes (T2D) is associated with an increased risk of infection-related morbidity and mortality.¹ Accordingly, coronavirus disease 2019 (COVID-19) results in increased hospitalization rates and illness severity in people with T2D.² Moreover, poor glycaemic control worsens patients’ prognosis with COVID-19, raising the risk of mechanical ventilation, shock, and multiple organ failure necessitating ICU treatment.³ Thus, the absolute burden of infection attributable to poor glycaemic control in this population would be substantial. This association may be explained by the degree of poor glycaemic control, which may be correlated to the worsening of cell-mediated immunity.³ Although a normal humoral response against severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been evidenced in T2D patients,⁴ previous studies have shown that dysregulation of the cellular immune response, especially T lymphocytes, might be highly involved in the pathological process of COVID-19.⁵ Although no significant difference was observed in total lymphocyte count or lymphopenia incidence between patients with T2D and those without diabetes, distinguishable differences in the subpopulations of lymphocytes have been observed.⁷ The sustained decrease in total T cells and Th and Tc subsets and NK subsets were all more remarkable in people with T2D than in those without diabetes.⁶ Therefore, T2D may hamper the immune responses after vaccination against SARS-CoV2.

Previous studies have shown that individuals with diabetes had a consistently lower immunological response to the hepatitis B vaccine,⁷ while less consistent results were noted for influenza and varicella-zoster vaccines.⁸ In this context, evaluating SARS-CoV-2 vaccine efficacy is critical to reducing the morbidity and mortality associated with COVID-19 in this vulnerable population. Testing vaccines that prevent infection with SARS-CoV-2 in T2D populations with poorly controlled glycaemia, therefore, is important because increased incidences of illness and death from COVID-19 have been associated with hyperglycaemia. Two doses of 30 μg BNT162b (Pfizer-BioNtech) elicited similar binding-antibody responses in people with or without T2D.⁹ However, there are no data on neutralizing antibodies and cell-mediated response to BNT162b vaccine in T2D patients, nor data on the immunological vaccine responses related to glycaemic control.¹⁰ The aim of the present study, therefore, was to evaluate cell-mediated response to the COVID-19 vaccine with regard to diabetic status and glycaemic control.

中文翻译：

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血糖控制不佳是否会影响 2 型糖尿病患者 COVID-19 疫苗接种的免疫原性：CAVEAT 研究

1 背景

2 型糖尿病 (T2D) 与感染相关发病率和死亡率的风险增加有关。¹因此，2019 年冠状病毒病 (COVID-19) 导致 T2D 患者的住院率和疾病严重程度增加。²此外，血糖控制不佳会恶化 COVID-19 患者的预后，增加机械通气、休克和需要 ICU 治疗的多器官衰竭的风险。³因此，在该人群中，由于血糖控制不佳导致的感染绝对负担将是巨大的。这种关联可以通过血糖控制不佳的程度来解释，这可能与细胞介导免疫的恶化有关。³尽管已在 T2D 患者中证实对严重急性呼吸综合征冠状病毒 (SARS-CoV-2) 的正常体液反应，但之前的⁴项研究表明，细胞免疫反应的失调，尤其是 T 淋巴细胞，可能与病理过程高度相关COVID-19 的。⁵尽管 T2D 患者和非糖尿病患者的总淋巴细胞计数或淋巴细胞减少发生率没有显着差异，但已观察到淋巴细胞亚群的显着差异。⁷ T2D 患者的总 T 细胞和 Th 和 Tc 亚群和 NK 亚群的持续减少都比没有糖尿病的人更显着。⁶因此，T2D 可能会阻碍 SARS-CoV2 疫苗接种后的免疫反应。

先前的研究表明，糖尿病患者对乙型肝炎疫苗的免疫反应始终较低，⁷而流感和水痘带状疱疹疫苗的结果则不太一致。⁸在这种情况下，评估 SARS-CoV-2 疫苗的功效对于降低这一弱势人群中与 COVID-19 相关的发病率和死亡率至关重要。因此，在血糖控制不佳的 T2D 人群中测试预防 SARS-CoV-2 感染的疫苗非常重要，因为 COVID-19 导致的疾病和死亡发病率增加与高血糖有关。两剂 30 μg BNT162b (Pfizer-BioNtech) 在患有或未患有 T2D 的人中引发了相似的结合抗体反应。⁹然而，没有关于 T2D 患者对 BNT162b 疫苗的中和抗体和细胞介导反应的数据，也没有关于与血糖控制相关的免疫疫苗反应的数据。¹⁰因此，本研究的目的是评估细胞介导的对 COVID-19 疫苗的糖尿病状态和血糖控制反应。