Meng Zhang’s research while affiliated with Nanjing University of Chinese Medicine and other places

The rapid mutation of SARS-CoV-2 has led to multiple rounds of large-scale breakthrough infection and reinfection worldwide. However, the dynamic changes of humoral and cellular immunity responses to several subvariants after infection remain unclear. In our study, a 6-month longitudinal immune response evaluation was conducted on 118 sera and 50 PBMC samples from 49 healthy individuals who experienced BA.5/BF.7/XBB breakthrough infection or BA.5/BF.7-XBB reinfection. By studying antibody response, memory B cell, and IFN-γ secreting CD4⁺/CD8⁺ T cell response to several SARS-CoV-2 variants, we observed that each component of immune response exhibited distinct kinetics. Either BA.5/BF.7/XBB breakthrough infection or BA.5/BF.7-XBB reinfection induces relatively high level of binding and neutralizing antibody titers against Omicron subvariants at an early time point, which rapidly decreases over time. Most of the individuals at 6 months post-breakthrough infection completely lost their neutralizing activities against BQ.1.1, CH.1.1, BA.2.86, JN.1 and XBB subvariants. Individuals with BA.5/BF.7-XBB reinfection exhibit immune imprinting shifting and recall pre-existing BA.5/BF.7 neutralization antibodies. In the BA.5 breakthrough infection group, the frequency of BA.5 and XBB.1.16-RBD specific memory B cells, resting memory B cells, and intermediate memory B cells gradually increased over time. On the other hand, the frequency of IFN-γ secreting CD4⁺/CD8⁺ T cells induced by WT/BA.5/XBB.1.16 spike trimer remains stable over time. Overall, our research indicates that individuals with breakthrough infection have rapidly declining antibody levels but have a relatively stable cellular immunity that can provide some degree of protection from future exposure to new antigens.

This study aimed to investigate the prognostic value of a novel droplet digital polymerase chain reaction (DDPCR) assay in sepsis patients. In this prospective cohort study, univariable and multivariable Cox regressions were used to assess risk factors for 28-day mortality. We also monitored pathogen load together with clinical indicators in a subgroup of the cohort. A total of 107 sepsis patients with positive baseline DDPCR results were included. Detection of poly-microorganisms [adjusted hazard ratio (HR) = 3.19; 95% confidence interval (CI) = 1.34–7.62; P = 0.009], high Charlson Comorbidity Index (CCI) score (adjusted HR = 1.14; 95% CI = 1.01–1.29; P = 0.041), and Sequential Organ Failure Assessment (SOFA) score (adjusted HR = 1.18; 95% CI = 1.05–1.32; P = 0.005) at baseline were independent risk factors for 28-day mortality while initial pathogen load was not associated (adjusted HR = 1.17; 95% CI = 0.82–1.66; P = 0.385). Among 63 patients with serial DDPCR results, an increase in pathogen load at days 6–8 compared to baseline was a risk factor for 28-day mortality (P = 0.008). Also, pathogen load kinetics were significantly different between day-28 survivors and nonsurvivors (P = 0.022), with a decline overtime only in survivors and an increase from days 3 and 4 to days 6–8 in nonsurvivors. Using DDPCR technique, we found that poly-microorganisms detected and increased pathogen load a week after sepsis diagnosis were associated with poor prognosis. IMPORTANCE This prospective study was initiated to explore the prognostic implications of a novel multiplex PCR assay in sepsis. Notably, our study was the largest cohort of sepsis with droplet digital polymerase chain reaction pathogen monitoring to date, allowing for a comprehensive evaluation of the prognostic significance of both pathogen species and load. We found that detection of poly-microorganisms was an independent risk factors for 28-day mortality. Also, pathogen load increase 1 week after sepsis diagnosis was a risk factor for 28-day mortality, and differential pathogen load kinetics were identified between day-28 survivors and nonsurvivors. Overall, this study demonstrated that pathogen species and load were highly correlated with sepsis prognosis. Patients exhibiting conditions mentioned above face a more adverse prognosis, suggesting the potential need for an escalation of antimicrobial therapy. Registered at ClinicalTrials.gov (NCT05190861).

Data on reinfection in large Asian populations are limited. In this study, we aimd to evaluate the reinfections rate, disease severity and time interval between the infections in the symptomatic and asymptomatic population who are firstly infected with BA.2 Omicron Variant. We retrospectively included adult patients with COVID-19 discharged from four designated hospitals between April 27, 2021, and November 30, 2022, who were interviewed via telephone from January 29 to March 1, 2023. Univariable and multivariable analysis were used to explore risk factors associated with reinfection. A total of 16,558 patients were followed up, during the telephone survey of average 310.0 days, 1610 (9.72%) participants self-reported reinfection. The mean time range of reinfection was 257.9 days. Risk for reinfection were analyzed using multivariable logistic regression. Patients with severe first infection were at higher risk for reinfection (aORs, 2.50; P < 0.001). The male (aORs,0.82; P < 0.001), the elderly (aORs, 0.44; P < 0.001) and patients with fully vaccination (aORs, 0.67; P < 0.001) or booster (aORs, 0.63; P < 0.001) had the lower risk of reinfection. Patients over 60 years of age (aORs,9.02; P = 0.006) and in those with ≥2 comorbidities (aORs,11.51; P = 0.016). were at higher risk for severe reinfection. The number of clinical manifestations of reinfection increases in people with severe first infection (aORs, 2.82; P = 0.023). The overall reinfection rate was 9.72%, and the reinfection rate of Omicron-to-Omicron subvariants was 9.50% at one year. The severity of Omicron-Omicron reinfection decreased. Data from our clinical study may provide the clinical evidence and bolster response preparedness for future COVID-19 reinfection wave.