Kakugawa Tomoyuki, Doi Keiko, Ohteru Yuichi, Kakugawa Hiroyuki, Oishi Keiji, Kakugawa Masahiro, Hirano Tsunahiko, Mimura Yusuke, Matsunaga Kazuto
Department of Pulmonology and Gerontology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, 755-8505, Ube, Yamaguchi, Japan.
Department of Internal Medicine, Medical Corporation WADOKAI Hofu Rehabilitation Hospital, Hofu, Japan.
Immun Ageing. 2023 Aug 17;20(1):42. doi: 10.1186/s12979-023-00368-2.
Coronavirus disease 2019 (COVID-19) remains a threat to vulnerable populations such as long-term care facility (LTCF) residents, who are often older, severely frail, and have multiple comorbidities. Although associations have been investigated between COVID-19 mRNA vaccine immunogenicity, durability, and response to booster vaccination and chronological age, data on the association of clinical factors such as performance status, nutritional status, and underlying comorbidities other than chronological age are limited. Here, we evaluated the anti-spike IgG level and neutralizing activity against the wild-type virus and Delta and Omicron variants in the sera of LTCF residents, outpatients, and healthcare workers before the primary vaccination; at 8, 12, and 24 weeks after the primary vaccination; and approximately 3 months after the booster vaccination. This 48-week prospective longitudinal study was registered in the UMIN Clinical Trials Registry (Trial ID: UMIN000043558).
Of 114 infection-naïve participants (64 LTCF residents, 29 outpatients, and 21 healthcare workers), LTCF residents had substantially lower anti-spike IgG levels and neutralizing activity against the wild-type virus and Delta variant than outpatients and healthcare workers over 24 weeks after the primary vaccination. In LTCF residents, booster vaccination elicited neutralizing activity against the wild-type virus and Delta variant comparable to that in outpatients, whereas neutralizing activity against the Omicron variant was comparable to that in outpatients and healthcare workers. Multiple regression analyses showed that age was negatively correlated with anti-spike IgG levels and neutralizing activity against the wild-type virus and Delta variant after the primary vaccination. However, multivariate regression analysis revealed that poor performance status and hypoalbuminemia were more strongly associated with a lower humoral immune response than age, number of comorbidities, or sex after primary vaccination. Booster vaccination counteracted the negative effects of poor performance status and hypoalbuminemia on the humoral immune response.
LTCF residents exhibited suboptimal immune responses following primary vaccination. Although older age is significantly associated with a lower humoral immune response, poor performance status and hypoalbuminemia are more strongly associated with a lower humoral immune response after primary vaccination. Thus, booster vaccination is beneficial for older adults, especially those with a poor performance status and hypoalbuminemia.
2019冠状病毒病（COVID-19）仍然对长期护理机构（LTCF）居民等弱势群体构成威胁，这些居民通常年龄较大、极度虚弱且患有多种合并症。虽然已经研究了COVID-19 mRNA疫苗的免疫原性、持久性以及对加强免疫接种的反应与实际年龄之间的关联，但关于除实际年龄外的临床因素（如体能状态、营养状况和基础合并症）之间关联的数据有限。在此，我们评估了LTCF居民、门诊患者和医护人员在初次接种疫苗前；初次接种疫苗后8周、12周和24周；以及加强免疫接种后约3个月时血清中抗刺突蛋白IgG水平以及针对野生型病毒、德尔塔和奥密克戎变异株的中和活性。这项为期48周的前瞻性纵向研究已在日本大学医学情报网临床试验注册中心注册（试验编号：UMIN000043558）。
在114名未感染过的参与者（64名LTCF居民、29名门诊患者和21名医护人员）中，在初次接种疫苗后的24周内，LTCF居民针对野生型病毒和德尔塔变异株的抗刺突蛋白IgG水平和中和活性显著低于门诊患者和医护人员。在LTCF居民中，加强免疫接种引发的针对野生型病毒和德尔塔变异株的中和活性与门诊患者相当，而针对奥密克戎变异株的中和活性与门诊患者和医护人员相当。多元回归分析显示，年龄与初次接种疫苗后抗刺突蛋白IgG水平以及针对野生型病毒和德尔塔变异株的中和活性呈负相关。然而，多变量回归分析显示，在初次接种疫苗后，体能状态差和低白蛋白血症比年龄、合并症数量或性别与较低的体液免疫反应关联更强。加强免疫接种抵消了体能状态差和低白蛋白血症对体液免疫反应的负面影响。
LTCF居民在初次接种疫苗后表现出次优的免疫反应。虽然年龄较大与较低的体液免疫反应显著相关，但在初次接种疫苗后，体能状态差和低白蛋白血症与较低的体液免疫反应关联更强。因此，加强免疫接种对老年人有益，尤其是那些体能状态差和患有低白蛋白血症的老年人。
