系统性自身免疫性肌病：针对 SARS-CoV-2 的灭活病毒疫苗的前瞻性 4 期对照试验。
Systemic autoimmune myopathies: a prospective phase 4 controlled trial of an inactivated virus vaccine against SARS-CoV-2.
机构信息
Division of Rheumatology.
Central Laboratory Division.
出版信息
Rheumatology (Oxford). 2022 Aug 3;61(8):3351-3361. doi: 10.1093/rheumatology/keab773.
OBJECTIVES
To evaluate immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in systemic autoimmune myopathies (SAMs) and the possible influence of baseline disease parameters, comorbidities and therapy on immune response.
METHODS
This prospective controlled study included 53 patients with SAMs and 106 non-immunocompromised control group (CTRL). All participants received two doses of the Sinovac-CoronaVac vaccine (28-day interval). Immunogenicity was assessed by anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC), anti-S1/S2 IgG geometric mean titre (GMT), factor increase GMT (FI-GMT), neutralizing antibodies (NAb) positivity, and median neutralizing activity after each vaccine dose (D0 and D28) and six weeks after the second dose (D69). Participants with pre-vaccination positive IgG serology and/or NAb and those with RT-PCR confirmed COVID-19 during the protocol were excluded from immunogenicity analysis.
RESULTS
Patients and CTRL had comparable sex (P>0.99) and age (P=0.90). Immunogenicity of 37 patients and 79 CTRL-naïve participants revealed at D69, a moderate but significantly lower SC (64.9% vs 91.1%, P<0.001), GMT [7.9 (95%CI 4.7-13.2) vs 24.7 (95%CI 30.0-30.5) UA/ml, P<0.001] and frequency of NAb (51.4% vs 77.2%, P<0.001) in SAMs compared with CTRL. Median neutralizing activity was comparable in both groups [57.2% (interquartile range (IQR) 43.4-83.4) vs 63.0% (IQR 40.3-80.7), P=0.808]. Immunosuppressives were less frequently used among NAb+ patients vs NAb- patients (73.7% vs 100%, P=0.046). Type of SAMs, disease status, other drugs or comorbidities did not influence immunogenicity. Vaccine-related adverse events were mild with similar frequencies in patients and CTRL (P>0.05).
CONCLUSION
Sinovac-CoronaVac is safe and has a moderate short-term immunogenicity in SAMs, but reduced compared with CTRL. We further identified that immunosuppression is associated with diminished NAb positivity.
TRIAL REGISTRATION
COVID-19 CoronaVac in Patients With Autoimmune Rheumatic Diseases and HIV/AIDS (CoronavRheum), http://clinicaltrials.gov/ct2/show/NCT04754698.
目的
评估 SARS-CoV-2 灭活疫苗在系统性自身免疫性肌病（SAMs）中的免疫原性和安全性，以及基线疾病参数、合并症和治疗对免疫反应的可能影响。
方法
本前瞻性对照研究纳入了 53 例 SAMs 患者和 106 例非免疫抑制对照组（CTRL）。所有参与者均接受了两剂科兴疫苗（间隔 28 天）。通过抗 SARS-CoV-2 S1/S2 IgG 血清转化率（SC）、抗 S1/S2 IgG 几何平均滴度（GMT）、因子增加 GMT（FI-GMT）、中和抗体（NAb）阳性率以及每剂疫苗后的中位数中和活性（D0 和 D28）以及第二次接种后 6 周（D69）来评估免疫原性。在方案期间，排除了具有预接种 IgG 血清学阳性和/或 NAb 的参与者和经 RT-PCR 确诊 COVID-19 的参与者。
结果
患者和 CTRL 的性别（P>0.99）和年龄（P=0.90）具有可比性。在 D69 时，对 37 例患者和 79 例 CTRL-初治患者进行了免疫原性分析，结果显示 SAMs 患者的 SC（64.9% vs 91.1%，P<0.001）、GMT [7.9（95%CI 4.7-13.2）vs 24.7（95%CI 30.0-30.5）UA/ml，P<0.001]和 NAb 频率（51.4% vs 77.2%，P<0.001）均显著低于 CTRL。两组的中位数中和活性相当[57.2%（四分位距（IQR）43.4-83.4）vs 63.0%（IQR 40.3-80.7），P=0.808]。与 NAb-患者相比，NAb+患者的免疫抑制剂使用频率较低（73.7% vs 100%，P=0.046）。SAMs 类型、疾病状态、其他药物或合并症均未影响免疫原性。疫苗相关不良事件在患者和 CTRL 中发生率相似，且均为轻度（P>0.05）。
结论
科兴疫苗在 SAMs 中安全且具有短期中度免疫原性，但与 CTRL 相比有所降低。我们进一步发现，免疫抑制与 NAb 阳性率降低有关。
试验注册
COVID-19 CoronaVac 在自身免疫性风湿病和 HIV/AIDS 患者中的研究（CoronavRheum），http://clinicaltrials.gov/ct2/show/NCT04754698。
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