Characteristics of SARS-CoV-2 vaccine breakthrough infections among Chinese travelers entering China via Chengdu city
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摘要:
目的 了解新冠病毒疫苗突破感染者感染特征及其预后情况,为新冠肺炎疫情防控提供参考。 方法 选择 2020年12月10日 — 2021年7月7日由成都市入境的38例中国籍新型冠状病毒(新冠病毒)感染者为研究对象,将其中14例有国产新冠病毒灭活疫苗接种史且基因分型明确的感染者作为疫苗突破感染组,将其中24例无新冠病毒疫苗接种史的感染者作为自然感染组,比较2组感染者确诊时核酸Ct值,IgM、IgG以及总抗体滴度等感染特征,入院时首次淋巴细胞计数,CD3+、CD4+、CD8+计数等临床指标及核酸转阴时间、住院时长等预后情况方面差异。 结果 确诊时,疫苗突破感染组感染者新冠病毒核酸N基因Ct值(26.8 ± 4.1)、ORF1ab基因Ct值(29.4 ± 4.5)均明显高于自然感染组(22.4 ± 7.4)、(24.8 ± 6.9)(t = 2.376、2.228,均P < 0.05),IgM、IgG、总抗体滴度P50(P25,P75)分别为0.9(0.3,11.6)、4.5(1.7,7.6)、31.9(4.6,916.4),也均明显高于自然感染组0.040(0.027,0.096)、0.006(0.003,0.052)、0.015(0.010,0.038)(均P < 0.05)。疫苗突破感染组入院时首次淋巴细胞计数,CD3+CD4+计数、CD3+CD8+计数、CD3+计数等指标均明显高于自然感染组(均P < 0.05);嗜酸性细胞数、中性粒细胞百分比均低于自然感染组(均P < 0.05)。2组感染者从确诊时核酸阳性至核酸转阴间隔时间及住院时长差异均无统计学意义(t = 1.106、1.889,均P > 0.05),但疫苗突破感染组住院时长 < 20 d的比例明显高于自然感染组(P < 0.05)。 结论 接种新冠病毒疫苗有助于降低疫苗突破感染者体内的病毒载量,可增强感染者机体T细胞免疫反应,对感染者预后产生积极影响。 Abstract:Objective To investigate the characteristics and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infections for providing a reference for coronavirus disease 19 (COVID-19) epidemic prevention and control. Methods We collected the information on 38 SARS-CoV-2 infections laboratory-confirmed among Chinese travelers entering China via Chengdu city, Sichuan province during the period from December 10, 2020 to July 7, 2021 and divided the infections into a vaccine breakthrough group (14 male cases ever receiving domestic inactivated COVID-19 vaccine and with confirmed genotype of SARS-CoV-2 strains inducing the infections) and a natural infection group (18 male and 6 female cases reporting no COVID-19 vaccination history). Comparison analyses were conducted to examine differences between the two groups in epidemiological characteristics, clinical/laboratory indicators and treatment outcomes. Results The participants arrived at Chengdu from 15 foreign countries during December 10, 2020 – July 7, 2021 and were diagnosed with SARS-CoV-2 infection within the period of December 11, 2020 – July 12, 2021; all the participants reported no history of SARS-CoV-2 infection/nucleic acid positive before entering China. In the vaccine breakthrough group, 9 participants had two doses of COVID-19 vaccine by separate inoculations with the interval of 56 days, 3 had two doses in one inoculation and only 2 had one dose; the interval from the last vaccination to the confirmation of SARS-CoV-2 infection ranged 8 – 173 days, with a median of 100 days. No statistically significant between-group differences were observed in the distribution of age (35.0 ± 7.7 vs. 35.8 ± 10.9 years), Pangolin-based genotyping of SARS-CoV-2 strains isolated, and the time of nucleic acid negative conversion from the first positive detection (t = 1.106, P > 0.05). Compared to the participants of natural infection, the participants with vaccine breakthrough infection had following significantly higher indicators: Ct value for N gene (26.8 ± 4.1 vs. 22.4 ± 7.4) and ORF1ab gene (29.4 ± 4.5 vs. 24.8 ± 6.9) of SARS-CoV-2 (t = 2.376 and t = 2.228, both P < 0.05); 50th percentile (P50), (25th percentile [P25], 75th percentile [P75]) of immunoglobulin M (IgM) antibody titer (0.9 [0.3, 11.6] vs. 0.040 [0.027, 0.096]); P50 (P25, P75) of immunoglobulin G (IgG) antibody titer (4.5 [1.7, 7.6] vs. 0.006 [0.003, 0.052]); total antibody titer (31.9 [4.6, 916.4] vs. 0.015 [0.010, 0.038]) (P < 0.05 for all); and the counts of lymphocyte, CD3+ T lymphocyte, CD3+/CD4+ T lymphocyte, CD3+/CD8+T lymphocyte detected at the time of hospital admission (all P < 0.05). While the participants of vaccine breakthrough infection had significantly lower peripheral blood eosinophil count and neutrophil percentage than those of the participants with natural infection (both P < 0.05). Although there was no significant between-group difference in the duration of hospitalization (t = 1.889, P > 0.05), the proportion of the participants being hospitalized less than 20 days was significantly higher for the vaccine breakthrough group than that for the natural infection group. Conclusion For COVID-19 vaccine breakthrough infections, the vaccination helps to reduce viral load and may enhance the vaccinees′ T-cell immune response and exert a positive impact on vaccinees′ outcome of the infection treatment. 1) (刘竹为本文并列第一作者) -
表 1 疫苗突破感染组与自然感染组确诊时核酸Ct值及抗体滴度
项目 疫苗突破感染组(n = 14) 自然感染组(n = 24) t/Z 值 P 值 Ct 值 a N基因 26.8 ± 4.1 22.4 ± 7.4 2.376 < 0.05 ORF 1ab基因 29.4 ± 4.5 24.8 ± 6.9 2.228 < 0.05 抗体滴度 b IgG 4.5(1.7, 7.6) 0.006(0.003,0.052) 3.822 < 0.001 IgM 0.9(0.3,11.6) 0.040(0.027,0.096) 3.946 < 0.001 总抗体 31.9(4.6,916.4) 0.015(0.010,0.038) 3.649 < 0.001 注:a 采用 $\bar x \pm s$ 描述;b 采用 P50(P25,P75)描述。 表 2 疫苗突破感染组与自然感染组入院时临床指标比较
临床指标 疫苗突破感染组(n = 14) 自然感染组(n = 24) t/Z 值 P 值 CD3+CD4+计数 b(cells/uL) 863(570,1284) 593(492,664) 2.239 0.025 CD3+CD8+计数 b(cells/uL) 499(329,675) 293(228,417) 2.663 0.007 CD3+计数 b(cells/uL) 1345(1021,2125) 945(737,1154) 2.618 0.008 红细胞计数 b(1012/L) 5.24(4.86,5.52) 4.70(4.40,5.03) 2.527 0.01 淋巴细胞百分比 b(%) 22.1(15.7,25.9) 16.0(13.2,20.9) 2.542 0.01 淋巴细胞计数 b(cells/ul) 2072(1541,2807) 1336(1058,1743) 3.026 0.002 嗜酸性细胞数 a(109/L) 0.04 ± 0.02 0.07 ± 0.07 2.175 0.036 嗜碱性细胞百分比 b(%) 0.5(0.4,0.7) 0.3(0.2,0.5) 2.497 0.012 嗜碱性细胞数 b(109/L) 0.04(0.02,0.06) 0.02(0.01,0.04) 2.642 0.009 中性粒细胞百分比 b(%) 56.8(52.9,62.2) 64.3(55.9,69.0) 2.164 0.029 注:a 采用 $\bar x \pm s$ 描述;b 采用 P50(P25,P75)描述。 -
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