Rheumatology Unit, University of Modena and Reggio Emilia, School of Medicine, Modena, Italy; Rheumatology Clinic 'Madonna dello Scoglio' Cotronei, Crotone, Italy.
MASVE Interdepartmental Hepatology Center, Department of Experimental and clinical Medicine, University of Florence Center, Center for Research and Innovation CRIA-MASVE, Firenze, Italy.
J Autoimmun. 2022 Jul;131:102866. doi: 10.1016/j.jaut.2022.102866. Epub 2022 Jul 11.
Autoimmune systemic diseases (ASD) show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed at evaluating the seroconversion elicited by COVID-19 vaccine over the entire vaccination cycle including the booster dose. Among 478 unselected ASD patients originally evaluated at the end of the first vaccination cycle (time 1), 344 individuals were re-evaluated after a 6-month period (time 2), and 244 after the booster vaccine dose (time 3). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was assessed by measuring serum IgG-neutralizing antibody (NAb) on samples obtained at the three time points in both patients and 502 age-matched controls. In the 244 ASD group that received booster vaccine and monitored over the entire follow-up, the mean serum NAb levels (time 1, 2, and 3: 696.8 ± 52.68, 370.8 ± 41.92, and 1527 ± 74.16SD BAU/mL, respectively; p < 0.0001) were constantly lower compared to controls (p < 0.0001), but they significantly increased after the booster dose compared to the first two measurements (p < 0.0001). The percentage of patients with absent/suboptimal response to vaccine significantly decreased after the booster dose compared to the first and second evaluations (time 1, 2, and 3: from 28.2% to 46.3%, and to 7.8%, respectively; p < 0.0001). Of note, the percentage of patients with absent/suboptimal response after the booster dose was significantly higher compared to controls (19/244, 7.8% vs 1/502, 0.2%; p < 0.0001). Similarly, treatment with immune-modifiers increased the percentage of patients exhibiting absent/suboptimal response (16/122, 13.1% vs 3/122, 2.46%; p = 0.0031). Overall, the above findings indicate the usefulness of booster vaccine administration in ASD patients. Moreover, the persistence of a significantly higher percentage of individuals without effective seroconversion (7.8%), even after the booster dose, warrants for careful monitoring of NAb levels in all ASD patients to identify those with increased risk of infection. In this particularly frail patients' setting, tailored vaccination and/or therapeutic strategy are highly advisable.
自身免疫性系统性疾病（ASD）对 COVID-19 疫苗的免疫原性受损。我们的前瞻性观察性多中心研究旨在评估 COVID-19 疫苗在整个接种周期（包括加强针）中的血清转化。在最初接种第一针疫苗后（时间 1）对 478 名未经选择的 ASD 患者进行评估，其中 344 名患者在 6 个月后（时间 2）接受了重新评估，244 名患者在接种加强针后（时间 3）接受了评估。在三个时间点分别测量了患者和 502 名年龄匹配的对照组的血清 IgG 中和抗体（NAb），评估了 mRNA COVID-19 疫苗（BNT162b2 和 mRNA-1273）的免疫原性。在接受加强针并在整个随访过程中监测的 244 名 ASD 组中，平均血清 NAb 水平（时间 1、2 和 3：分别为 696.8 ± 52.68、370.8 ± 41.92 和 1527 ± 74.16SD BAU/mL；p < 0.0001）明显低于对照组（p < 0.0001），但与前两次测量相比，加强针后明显升高（p < 0.0001）。与第一和第二次评估相比（时间 1、2 和 3：从 28.2%降至 46.3%，再降至 7.8%；p < 0.0001），疫苗无应答或应答不足的患者比例在加强针后显著降低。值得注意的是，与对照组相比（244 名患者中有 19 名，7.8% vs 502 名中有 1 名，0.2%；p < 0.0001），加强针后无应答或应答不足的患者比例明显更高。同样，免疫调节剂的治疗增加了无应答或应答不足的患者比例（122 名患者中有 16 名，13.1% vs 122 名患者中有 3 名，2.46%；p = 0.0031）。综上所述，上述结果表明，ASD 患者接种加强针是有用的。此外，即使在加强针后，仍有相当高比例的个体未能有效产生血清转化（7.8%），这需要对所有 ASD 患者的 NAb 水平进行仔细监测，以识别那些感染风险增加的患者。在这种特别脆弱的患者环境中，强烈建议量身定制疫苗接种和/或治疗策略。
