Unveiling a New Perspective on Distinguishing Omicron Breakthrough Cases and Postimmune COVID-19-Naive Individuals: Insights from Antibody Profiles.

In the situation of mass vaccination against COVID-19, few studies have reported on the early kinetics of specific antibodies (IgG/IgM/IgA) of vaccine breakthrough cases. There is still a lack of epidemiological evidence about the value of serological indicators in the auxiliary diagnosis of COVID-19 infection, especially when the nucleic acid results were undetectable. Omicron breakthrough cases post-inactivated vaccination (n = 456) and COVID-19-naive individuals with two doses of inactivated vaccination (n = 693) were enrolled. Blood samples were collected and tested for SARS-CoV-2 antibody levels based on the magnetic chemiluminescence enzyme immunoassay. Among Omicron breakthrough cases, the serum IgG antibody level was 36.34 Sample/CutOff (S/CO) (95% confidence interval [CI], 31.89 to 40.79) in the acute phase and 88.45 S/CO (95% CI, 82.79 to 94.12) in the recovery phase. Serum IgA can be detected in the first week post-symptom onset (PSO) and showed an almost linear increase within 5 weeks PSO. Compared with those of breakthrough cases, IgG and IgA titers of the postimmune group were much lower (4.70 S/CO and 0.46 S/CO, respectively). Multivariate regression showed that serum IgG and IgA levels in Omicron breakthrough cases were mainly affected by the weeks PSO (P < 0.001). Receiver operating characteristic ROC0 curve analysis showed that the area under the curve (AUC) was 0.744 and 0.806 when the cutoff values of IgA and IgG were 1 S/CO and 15 S/CO, respectively. Omicron breakthrough infection can lead to a further increase in IgG and IgA levels relative to those of the immunized population. When nucleic acid real-time PCR was negative, we would use the kinetics of IgG and IgA levels to distinguish the breakthrough cases from the immunized population. IMPORTANCE This study fills a gap in the epidemiological evidence by investigating the value of serological indicators, particularly IgG and IgA levels, in the auxiliary diagnosis of COVID-19 infections when nucleic acid results are undetectable. The findings reveal that among Omicron breakthrough cases, both IgG and IgA antibody levels exhibit significant changes. Serum IgG levels increase during the acute phase and rise further in the recovery phase. Serum IgA can be detected as early as the first week post-symptom onset (PSO), showing a consistent linear increase within 5 weeks PSO. Furthermore, receiver operating characteristic (ROC) curve analysis demonstrates the potential of IgG and IgA cutoff values as diagnostic markers. The study's conclusion underscores the importance of monitoring IgG and IgA kinetics in distinguishing Omicron breakthrough cases from vaccinated individuals. These findings contribute to the development of more accurate diagnostic approaches and help inform public health strategies during the ongoing COVID-19 pandemic.

Kinetics of SARS-CoV-2 neutralizing antibodies in Omicron breakthrough cases with inactivated vaccination: Role in inferring the history and duration of infection.

Background: The quantitative level and kinetics of neutralizing antibodies (NAbs) in individuals with Omicron breakthrough infections may differ from those of vaccinated individuals without infection. Therefore, we aimed to evaluate the difference in NAb levels to distinguish the breakthrough cases from the post-immunized population to identify early infected person in an outbreak epidemic when nasal and/or pharyngeal swab nucleic acid real-time PCR results were negative. Methods: We collected 1077 serum samples from 877 individuals, including 189 with Omicron BA.2 breakthrough infection and 688 post-immunized participants. NAb titers were detected using the surrogate virus neutralization test, and were log(2)-transformed to normalize prior to analysis using Student's unpaired t-tests. Geometric mean titers (GMT) were calculated with 95% confidence intervals (CI). Linear regression models were used to identify factors associated with NAb levels. We further conducted ROC curve analysis to evaluate the NAbs' ability to identify breakthrough infected individuals in the vaccinated population. Results: The breakthrough infection group had a consistently higher NAb levels than the post-immunized group according to time since the last vaccination. NAb titers in the breakthrough infection group were 6.4-fold higher than those in the post-immunized group (GMT: 40.72 AU/mL and 6.38 AU/mL, respectively; p<0.0001). In the breakthrough infection group, the NAbs in the convalescent phase were 10.9-fold higher than in the acute phase (GMT: 200.48 AU/mL and 18.46 AU/mL, respectively; p<0.0001). In addition, the time since infection, booster vaccination, and the time since last vaccination were associated with log(2)-transformed NAb levels in the breakthrough infection group. ROC curve analysis showed that ROC area was largest (0.728) when the cut-off value of log(2)-transformed NAb was 6, which indicated that NAb levels could identify breakthrough infected individuals in the vaccinated population. Conclusion: Our study demonstrates that the NAb titers of Omicron BA.2 variant breakthrough cases are higher than in the post-immunized group. The difference in NAb levels could be used to identify cases of breakthrough infection from the post-immunized population in an outbreak epidemic.

Impact of vaccination on kinetics of neutralizing antibodies against SARS-CoV-2 by serum live neutralization test based on a prospective cohort.

How much the vaccine contributes to the induction and development of neutralizing antibodies (NAbs) of breakthrough cases relative to those unvaccinated-infected cases is not fully understood. We conducted a prospective cohort study and collected serum samples from 576 individuals who were diagnosed with SARS-CoV-2 Delta strain infection, including 245 breakthrough cases and 331 unvaccinated-infected cases. NAbs were analysed by live virus microneutralization test and transformation of NAb titre. NAbs titres against SARS-CoV-2 ancestral and Delta variant in breakthrough cases were 7.8-fold and 4.0-fold higher than in unvaccinated-infected cases, respectively. NAbs titres in breakthrough cases peaked at the second week after onset/infection. However, the NAbs titres in the unvaccinated-infected cases reached their highest levels during the third week. Compared to those with higher levels of NAbs, those with lower levels of NAbs had no difference in viral clearance duration time (P>0.05), did exhibit higher viral load at the beginning of infection/maximum viral load of infection. NAb levels were statistically higher in the moderate cases than in the mild cases (P<0.0001). Notably, in breakthrough cases, NAb levels were highest longer than 4 months after vaccination (Delta strain: 53,118.2 U/mL), and lowest in breakthrough cases shorter than 1 month (Delta strain: 7551.2 U/mL). Cross-neutralization against the ancestral strain and the current circulating isolate (Omicron BA.5) was significantly lower than against the Delta variant in both breakthrough cases and unvaccinated-infected cases. Our study demonstrated that vaccination could induce immune responses more rapidly and greater which could be effective in controlling SARS-CoV-2.

Safety and Immunogenicity of Pertussis Vaccine Immunization during Pregnancy: A Meta-Analysis of Randomized Clinical Trials.

The objective of this meta-analysis is to assess the safety and immunogenicity of maternal pertussis vaccination based on randomized clinical trials. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Internet, and Wan Fang Database were searched from inception up to the 8th of October 2021, using a protocol registered on PROSPERO with no. 42021287717, and a meta-analysis was conducted. We measured pooled geometric mean concentrations (GMCs) for IgG antibodies against pertussis and the incidence of serious adverse events (SAEs). We identified a total of 522 publications, and after a strict screening, we found that 6 RCTs were eligible for our meta-analysis. GMCs were determined with a standardized mean difference (SMD), and the pooled SMD of anti-PT, anti-FHA, and anti-PRN IgG from cord blood were 0.91 (95% CI: 0.58, 1.24), 1.03 (95% CI: (0.70, 1.35)), and 1.55(95% CI: 1.22, 1.88), respectively. The pooled OR of SAEs of women and infants did not show a statistical difference; the pooled ORs were 1.26 (95% CI: 0.78, 2.05); P = 0.35) and 0.61 (95% CI: 0.37, 1.01); p = 0.053), respectively. Infants of immunized women have significantly higher transplacental antibodies for protection against pertussis disease during the first 2 months of life.

Racial/Ethnic Disparities and Survival in Pediatrics with Gliomas Based on the Surveillance, Epidemiology, and End Results Database in the United States.

BACKGROUND: Gliomas are the most common type of primary central nervous system tumor for both children and adults. However, the influence of racial/ethnic disparities on the survival of children with gliomas has not been fully evaluated yet. METHODS: Baseline characteristics of patients, including sex, year of diagnosis, surgery, grade, radiation, histology, and races, were collected. Univariate and multivariate analyses for overall survival (OS) were performed using Cox proportional hazards regression model. Survival curves were plotted using Kaplan-Meier methods. RESULTS: A total of 4400 childhood patients were enrolled, including 2516 non-Hispanic whites (NHWs), 1050 Hispanic whites (HWs), 519 blacks, 282 Asians or Pacific Islanders (APIs), and 33 American Indian/Alaska Natives. NHWs had the longest overall survival (OS), whereas blacks had the shortest OS (P = 0.003). Stratified by histologic type, OS of children with astrocytoma was better among NHWs and HWs than among blacks and APIs (P = 0.004). OS of children with ependymoma was better among NHWs and APIs than among HWs and blacks (P = 0.008). However, no significant difference was observed in OS for children with medulloblastoma (P = 0.854). CONCLUSIONS: Survival outcomes varied significantly by race/ethnicity among childhood gliomas. Better management of childhood gliomas is warranted to close the survival gap between race/ethnicity.

Risk and protective factors of co-morbid depression in patients with type 2 diabetes mellitus: a meta analysis.

The aim from this paper is to identify the main influencing factors of co-morbid depression among T2DM (Type 2 Diabetes Mellitus) patients and to provide reliable evidence for relative researches. A systematic review and meta-analysis of risk factors for co-morbid depression in T2DM was performed on all retrieved studies through an observational research of network database. Data were analyzed by Review Manager 5.3 from the extracted results, the heterogeneity index of the studies was determined using Chi-squared I2 tests and on the basis of heterogeneity, a fixed or random effect model was used to estimates the pooled effect of each influencing factor. Fourteen observational studies containing total of 82,239,298 cases that have been identified. Diabetic complications (OR = 2.91; 95%CI, 1.76-4.82, p < 0.0001), insulin use (OR = 1.71; 95%CI, 1.18-2.48, p = 0.005), education status (OR = 1.91; 95%CI, 1.30-2.81, p = 0.001) were confirmed as risk factors, while regular exercising (OR = 0.51; 95%CI, 0.27-0.96, p = 0.04), gender (OR = 0.56; 95%CI, 0.47-0.65, p < 0.0001), marital status (OR = 0.53; 95%CI, 0.34-0.83, p = 0.005), current social status (OR = 0.64; 95%CI, 0.47-0.88, p = 0.006) were confirmed as protective factors of co-morbid depression in the patients with T2DM. Subgroup analysis claimed age (≥60 years) was a risk factor and smoking was protective factor for co-morbid depression in the patients with T2DM. Being female, have diabetic complications, insulin use, education level less than secondary are risk factors. However, doing regular exercise, being married and on work are protective factors of co-morbid depression in patients with T2DM. As to the other influencing factors should be further studied.