疫苗接种情况对新冠肺炎患者病情影响的临床研究

Effects of vaccination status on the disease severity of patients with coronavirus disease 2019

目的评价新型冠状病毒德尔塔变异株感染患者的新冠灭活疫苗接种情况对患者病情严重程度的影响。方法回顾分析2021年7月至9月扬州市新冠肺炎定点医院(苏北人民医院新区分院)收治的感染德尔塔变异株病毒且年龄≥18岁的704例新冠肺炎患者的临床资料,根据患者的临床特征,将轻型和普通型患者归为非重症组,重型和危重型患者归为重症组。根据新冠灭活疫苗接种情况,分为未接种组、接种1针组和接种2针组,评价疫苗接种情况对病情严重程度、抗体产生的影响,并分析导致重症新冠肺炎的影响因素。结果接种2针疫苗新冠肺炎患者的重症比例均明显低于接种1针组和未接种组〔3.02%(7/232)比9.48%(22/232)、15.83%(38/240),均P<0.05〕,而发病至就诊时间(d:1.97±1.66比2.66±2.70)、年龄(岁:45.3±12.2比63.6±17.0)、直接胆红素〔DBil(μmol/L):3.70±1.83比5.30±5.13〕、乳酸脱氢酶〔LDH(U/L):240.69±74.29比256.30±85.18〕、血肌酐〔SCr(μmol/L):63.38±19.86比70.23±25.43〕、白细胞介素-6〔IL-6(ng/L):7.32(1.54,17.40)比18.38(8.83,33.43)〕、肌酸激酶〔CK(U/L):66.00(43.00,99.75)比78.00(54.50,144.00)〕、D-二聚体〔mg/L:0.30(0.08,0.49)比0.41(0.23,0.69)〕均明显低于未接种组,血小板计数〔PLT(×10^(9)/L):176.69±60.25比149.25±59.07〕、白细胞计数〔WBC(×10^(9)/L):5.43±1.77比5.03±1.88〕、淋巴细胞计数〔LYM(×10^(9)/L):1.34±0.88比1.17±0.50〕均明显高于未接种组(均P<0.05)。接种2针组入院10 d免疫球蛋白G(IgG)滴度显著高于接种1针组和未接种组〔U/L:130.94(92.23,326.31)比113.18(17.62,136.20)、117.85(33.52,156.73),均P<0.05〕,入院16 d IgG滴度显著高于未接种组〔U/L:156.12(120.32,167.76)比126.52(61.34,149.57),P<0.05〕。重症组患者2针疫苗完全接种比例〔10.45%(7/67)比35.32%(225/637)〕、LYM(×10^(9)/L:1.09±0.32比1.25±0.56)、PLT(×10^(9)/L:138.55±68.03比166.93±59.70)均明显低于非重症组,而发病至就诊时间(d:3.01±2.99比2.25±2.09)、住院时间(d:28±18比16±6)、男性比例〔77.61%(52/67)比34.54%(220/637)〕、年龄(岁:69.13±12.63比52.28±16.53)、DBil〔μmol/L:4.20(3.18,6.65)比3.60(2.80,4.90)〕、LDH(U/L:310.61±98.33比238.19±72.14)、SCr(μmol/L:85.67±38.25比65.98±18.57)、C-反应蛋白〔CRP(μmol/L):28.12(11.32,42.23)比8.49(2.61,17.58)〕、IL-6〔ng/L:38.38(24.67,81.50)比11.40(4.60,22.07)〕、CK〔U/L:140.00(66.00,274.00)比72.80(53.00,111.00)〕、D-二聚体〔mg/L:0.46(0.29,0.67)比0.35(0.19,0.57)〕均明显高于非重症组(均P<0.05)。多因素回归分析显示,与未接种组相比,接种1针组和接种2针组发生重症的风险为0.430倍(P=0.010)。再将年龄纳入回归分析,与未接种组相比,接种2针组发生重症的风险为0.381倍〔优势比(OR)=0.381,95%可信区间(95%CI)为0.121~1.199〕,但差异无统计学意义(P>0.05);PLT为保护因素(OR=0.992,95%CI为0.986~0.998);年龄>60岁(OR=3.681,95%CI为1.637~8.278)、CK(OR=1.001,95%CI为1.000~1.001)、IL-6(OR=1.006,95%CI为1.002~1.010)、SCr(OR=1.020,95%CI为1.007~1.033)均为危险因素(均P<0.05)。结论针对德尔塔病毒感染,与未接种新冠疫苗患者相比,完全接种2针新冠灭活疫苗新冠肺炎患者的IL-6、SCr、CK和D-二聚体水平降低,PLT、LYM和IgG抗体滴度更高,发生重症比例降低,2针疫苗完全接种更具有保护作用。

Objective To evaluate the effect of 2019 novel coronavirus inactivated vaccine on the disease severity of patients with Delta variant of coronavirus disease 2019.Methods A retrospective analysis was performed on 704 patients with coronavirus disease 2019 infected with Delta variant who were older than 18 years old and admitted in the coronavirus disease 2019 designated hospital of Yangzhou(Subei Hospital New Area Branch)from July 2021 to September 2021.They were divided into severe(severe,critical)group and non-severe(light,ordinary)group according to the clinical characteristics of patients.According to the vaccination status,they were divided into 0-dose group,1-dose group and 2-dose group.We evaluated the effects of vaccination on the severity of the disease and the production of antibodies,and analyzed the influencing factors leading to the severe group of coronavirus disease 2019.Results The proportion of severe group in the 2-dose vaccinated group was significantly lower than that in the 1-dose vaccinated group and 0-dose vaccinated group[3.02%(7/232)vs.9.48%(22/232),15.83%(38/240),P<0.05].The time from onset to admission(day:1.97±1.66 vs.2.66±2.70),age(years:45.3±12.2 vs.63.6±17.0),direct bilirubin[DBil(μmol/L):3.70±1.83 vs.5.30±5.13],lactate dehydrogenase[LDH(U/L):240.69±74.29 vs.256.30±85.18],creatinine[SCr(μmol/L):63.38±19.86 vs.70.23±25.43],interleukin-6[IL-6(ng/L):7.32(1.54,17.40)vs.18.38(8.83,33.43)],creatine kinase[CK(U/L):66.00(43.00,99.75)vs.78.00(54.50,144.00)]and D-dimer[mg/L:0.30(0.08,0.49)vs.0.41(0.23,0.69)]of patients in the 2-dose group were significantly lower than those in the 0-dose group(all P<0.05),while platelet[PLT(×10^(9)/L):176.69±60.25 vs.149.25±59.07],white blood cell count[WBC(×10^(9)/L):5.43±1.77 vs.5.03±1.88]and lymphocyte[LYM(×10^(9)/L):1.34±0.88 vs.1.17±0.50]were significantly higher than those in the 0-dose group(all P<0.05).The titer of immunoglobulin G(IgG)in the 2-dose group was significantly higher than those in the 1-dose group and 0-dose group on the 10th day after admission[U/L:130.94(92.23,326.31),113.18(17.62,136.20),117.85(33.52,156.73),both P<0.05],and higher than 0-dose group on the 16th day[U/L:156.12(120.32,167.76)vs.126.52(61.34,149.57),P<0.05].The proportion of complete 2-dose vaccination[10.45%(7/67)vs.35.32%(225/637)],LYM(×10^(9)/L:1.09±0.32 vs.1.25±0.56)and PLT(×10^(9)/L:138.55±68.03 vs.166.93±59.70)in the severe group were significantly lower than those in the non-severe group(P<0.05),while the time from onset to admission(day:3.01±2.99 vs.2.25±2.09),the length of hospital stay(day:28±18 vs.16±6),male proportion[77.61%(52/67)vs.34.54%(220/637)],age(years:69.13±12.63 vs.52.28±16.53),DBil[μmol/L:4.20(3.18,6.65)vs.3.60(2.80,4.90)],LDH(U/L:310.61±98.33 vs.238.19±72.14),SCr(μmol/L:85.67±38.25 vs.65.98±18.57),C-reactive protein[CRP(μmol/L):28.12(11.32,42.23)vs.8.49(2.61,17.58)],IL-6[ng/L:38.38(24.67,81.50)vs.11.40(4.60,22.07)],CK[U/L:140.00(66.00,274.00)vs.72.80(53.00,11.00)]and the D-dimer[mg/L:0.46(0.29,0.67)vs.0.35(0.19,0.57)]in the severe group were significantly higher than those in the non-severe group(all P<0.05).Multivariate regression analysis showed that the odds ratio(OR)of severe group was 0.430(P=0.010)in the 1-dose group and the 2-dose group compared with the 0-dose group.However,the risk of severe group was 0.381-fold in the 2-dose group compared with the 0-dose group[OR=0.381,95%confidence interval(95%CI)was 0.121-1.199]which was not statistically significant,when the age was included in the regression analysis(P>0.05).PLT(OR=0.992,95%CI was 0.986-0.998)were protective factors,but older than 60 years old(OR=3.681,95%CI was 1.637-8.278),CK(OR=1.001,95%CI was 1.000-1.001),IL-6(OR=1.006,95%CI was 1.002-1.010),SCr(OR=1.020,95%CI was 1.007-1.033)were risk factors for severe group(all P<0.05).Conclusions Compared with the 0-dose vaccinated patients,the coronavirus disease 2019 patients infected with delta variant and fully vaccinated with 2-dose 2019 novel coronavirus inactivated vaccine had lower level of IL-6,SCr,CK and D-dimer,and higher PLT,LYM and IgG titer,who were not easy to develop into the severe condition.