■以前的感染和疫苗接种已经产生了预先存在的免疫力,在机体免疫反应方面与原发感染不同,再次感染时可能导致不同的疾病严重程度和预后。
■这项回顾性队列研究的目的是研究免疫突破对COVID-19患者疾病进展和预后的影响。
■于2020年1月至2022年11月对成都公共卫生临床医学中心1513例COVID-19患者进行回顾性队列研究。将所有患者分为无免疫组(原发感染和未接种疫苗,n=1102)和免疫突破组(以前的感染或疫苗接种,n=411)。免疫突破组进一步分为天然免疫亚组(n=73),获得性免疫亚组(n=322)和混合免疫亚组(n=16)。通过方差分析比较两组之间或三个亚组之间的临床和结局数据以及T淋巴细胞亚群和抗体水平的差异。t检验和卡方检验,采用单因素分析和logistic回归分析评估T淋巴细胞亚群和抗体水平与COVID-19患者病情进展和预后的关系。
■总临界率和总死亡率分别为2.11%和0.53%,分别。免疫突破率为27.16%。在无免疫组中,临界率和死亡率都较高,冠状病毒阴性转化时间长于免疫突破组。两组的临界率和冠状病毒转阴时间差异均有统计学意义(3.72%vs.0.24%,14.17vs.11.90天,所有p<0.001)。此外,在无豁免权组中,尽管入院时淋巴细胞计数和T亚群较高,入院后第1周至第4周,均持续显著下降,且均显著低于免疫突破组(均p<0.01)。从入院到入院后第4周,总抗体水平和特异性免疫球蛋白G(IgG)水平逐渐升高,并始终明显低于免疫突破组(均p<0.001)。此外,在自然免疫亚组中,入院时淋巴细胞计数和T亚群最高,入院时的总抗体水平和特异性IgG水平最低。然后,从入院到入院后1个月,所有这些指标均显着下降,并且在三个亚组中最低(总抗体:从546.07到158.89,IgG:从6.00到3.95)(均p<0.001)。混合免疫亚组的人其次是获得性免疫亚组的人。而这两个亚组的淋巴细胞计数和T亚群以及获得性免疫亚组的总抗体水平(从830.84到1008.21)和特异性IgG水平(从6.23到7.51)逐渐增加,混合免疫亚组的总抗体水平(从1100.82到908.58)和特异性IgG水平(从7.14到6.58)逐渐下降。此外,T淋巴细胞亚群和抗体水平与疾病严重程度呈负相干,预后和冠状病毒阴性转化时间。总抗体,特异性IgM和IgG水平对预测重症COVID-19患者和死亡COVID-19患者具有良好的实用性。
■在COVID-19患者中,以前的感染或疫苗接种导致的免疫突破,可以通过加快宿主细胞和体液免疫以加速病毒清除来减缓疾病进展并增强预后,特别是在接种过疫苗和以前感染过的人中。
■中国临床试验注册中心ChiCTR2000034563。
Previous infections and vaccinations have produced preexisting immunity, which differs from primary infection in the organism immune response and may lead to different disease severities and prognoses when reinfected.
The purpose of this retrospective cohort study was to investigate the impact of immune breakthroughs on disease progression and prognosis in patients with COVID-19.
A retrospective cohort study was conducted on 1513 COVID-19 patients in Chengdu Public Health Clinical Medical Center from January 2020 to November 2022. All patients were divided into the no immunity group (primary infection and unvaccinated, n=1102) and the immune breakthrough group (previous infection or vaccination, n=411). The immune breakthrough group was further divided into the natural immunity subgroup (n=73), the acquired immunity subgroup (n=322) and the mixed immunity subgroup (n=16). The differences in clinical and outcome data and T lymphocyte subsets and antibody levels between two groups or between three subgroups were compared by ANOVA, t test and chi-square test, and the relationship between T lymphocyte subsets and antibody levels and the disease progression and prognosis of COVID-19 patients was assessed by univariate analysis and logistic regression analysis.
The total critical rate and the total mortality rate were 2.11% and 0.53%, respectively. The immune breakthrough rate was 27.16%. In the no immunity group, the critical rate and the mortality rate were all higher, and the coronavirus negative conversion time was longer than those in the immune breakthrough group. The differences in the critical rate and the coronavirus negative conversion time between the two groups were all statistically significant (3.72% vs. 0.24%, 14.17 vs. 11.90 days, all p<0.001). In addition, in the no immunity group, although lymphocyte counts and T subsets at admission were higher, all of them decreased consistently and significantly and were significantly lower than those in the immune breakthrough group at the same time from the first week to the fourth week after admission (all p<0.01). The total antibody levels and specific Immunoglobulin G (IgG) levels increased gradually and were always significantly lower than those in the immune breakthrough group at the same time from admission to the fourth week after admission (all p<0.001). Moreover, in the natural immunity subgroup, lymphocyte counts and T subsets at admission were the highest, and total antibody levels and specific IgG levels at admission were the lowest. Then, all of them decreased significantly and were the lowest among the three subgroups at the same time from admission to one month after admission (total antibody: from 546.07 to 158.89, IgG: from 6.00 to 3.95) (all p<0.001). Those in the mixed immunity subgroup were followed by those in the acquired immunity subgroup. While lymphocyte counts and T subsets in these two subgroups and total antibody levels (from 830.84 to 1008.21) and specific IgG levels (from 6.23 to 7.51) in the acquired immunity subgroup increased gradually, total antibody levels (from 1100.82 to 908.58) and specific IgG levels (from 7.14 to 6.58) in the mixed immunity subgroup decreased gradually. Furthermore, T lymphocyte subsets and antibody levels were negatively related to disease severity, prognosis and coronavirus negative conversion time. The total antibody, specific IgM and IgG levels showed good utility for predicting critical COVID-19 patients and dead COVID-19 patients.
Among patients with COVID-19 patients, immune breakthroughs resulting from previous infection or vaccination, could decelerate disease progression and enhance prognosis by expediting host cellular and humoral immunity to accelerate virus clearance, especially in individuals who have been vaccinated and previously infected.
Chinese Clinical Trial Register ChiCTR2000034563.