Consistent neutralization of circulating omicron sub-variants by hybrid immunity up to 6 months after booster vaccination.

The current COVID-19 vaccination program requires frequent booster vaccination to maintain sufficient neutralization levels against immune evasive SARS-CoV-2 variants. However, prior studies found more potent and durable immune response in convalescing individuals, raising the possibility of less frequent booster vaccination for them. Here, we conducted a longitudinal immunological study based on two prospective cohorts of booster vaccinated convalescing COVID-19 patients or healthcare workers (HCW) without COVID-19 history in Xiangyang, China. Comparing to 1-month post-boosting, pseudovirus neutralization titers (pVNT50) of ancestral Wuhan-Hu-1 and circulating omicron sub-variants BA.5, BF.7, BA.4.6, BA.2.75, and BA.2.75.2 spikes were stable or even increased in convalescing samples at 6-month post-boosting, when HCW samples showed substantial drop of neutralization titers across the spectrum. Variant-to-Wuhan-Hu-1 pVNT50 ratios showed no significant variation during the 17 months from pre-vaccination to 6-month post-boosting in convalescing individuals, indicating that the high durability of hybrid immunity was likely sustained by continuously improving neutralization potency that compensated immune decay. Our data provide mechanistic insight into prior epidemiological findings that vaccine-elicited humoral immune response was more durable in convalescing individuals than those without SARS-CoV-2 infection, and suggest further research into potential extension of boosting intervals for convalescing individuals.

SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection.

The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life. Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang, China at 1-year after diagnosis. Among them, chemiluminescence immunoassay-based screening showed 99% (95% CI, 98-100%) seroprevalence 10-12 months after infection, comparing to 0.8% (95% CI, 0.7-0.9%) in the general population. Total anti-receptor-binding domain (RBD) antibodies remained stable since discharge, while anti-RBD IgG and neutralization levels decreased over time. A predictive model estimates 17% (95% CI, 11-24%) and 87% (95% CI, 80-92%) participants were still 50% protected against detectable and severe re-infection of WT SARS-CoV-2, respectively, while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced. All non-severe patients showed normal chest CT and 21% reported COVID-19-related symptoms. In contrast, 53% severe patients had abnormal chest CT, decreased pulmonary function or cardiac involvement and 79% were still symptomatic. Our findings suggest long-lasting immune protection after SARS-CoV-2 infection, while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.

A verification of the application of the non-derivatized mass spectrometry method in newborns screening of metabolic disorders.

It is required that the clinical screening of metabolic disorders in newborns meet International Organization for Standardization 15189-2012 approval. The new tandem mass spectrometry (MS/MS) based screening system and its companion reagent should be independently authenticated before their implementation in clinical diagnosis laboratories.Linearity, stability, accuracy, and precision evaluations were carried out to verify the performance of the Waters ACQUITY TQD MS/MS system with the NeoBase non-derivatized MS/MS PerkinElmer kit for detecting amino acids and acylcarnitine in newborns with metabolic disorders.Statistically, the correlation coefficient (R) of 0.9982 to 0.9999 indicates good linearity. The measurements at the beginning and end of the reagent storage procedure were taken for stability verification. No significant difference was detected between the 2 periods. The amino acid exhibited a degree of bias in the range of 0% to 14.17%, with acylcarnitine's being was in the range of 0% to 14.84%; they consequently passed the quality assessment requirements for clinical laboratories of the China National Centre. The amino acids' within-run, between-run, and day-to-day run precision were 1.19% to 7.68%, 1.63% to 5.01%, and 4.77% to 12.48%, respectively, while the total imprecision was 5.55% to 13.33%. Acylcarnitine's within-run, between-run, and day-to-day run precision was 1.2% to 8.43%, 0.19% to 9.60%, and 2.33% to 10.74%, respectively, while it's total imprecision was 6.57% to 13.99%. The manufacturer declared that the total imprecision of the tests, using Multiple Reaction Monitoring, should be less than or equal to 25% of the coefficient of variation for the kit's high and low-quality control levels.The performance of the non-derivatized MS/MS screening system in detecting the amino acids and acylcarnitines passed the test's requirements. It was maintained in accordance with the routine clinical chemical detection system.

p53, Bcl-2 and cox-2 are involved in berberine hydrochloride-induced apoptosis of HeLa229 cells.

The present study aimed to investigate the effects of berberine hydrochloride on the proliferation and apoptosis of HeLa229 human cervical cancer cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to examine the cytotoxicity of berberine hydrochloride against HeLa229 cells. The effects of berberine hydrochloride on the apoptosis of HeLa229 cells was detected by immunofluorescence and flow cytometry, and the mRNA expression levels of p53, B­cell lymphoma 2 (Bcl­2) and cyclooxygenase­2 (cox­2) were analyzed by reverse transcription-quantitative polymerase chain reaction. Berberine hydrochloride inhibited the proliferation of HeLa229 cells in a dose­dependent manner; minimum cell viability (3.61%) was detected following treatment with 215.164 µmol/l berberine hydrochloride and the half maximal inhibitory concentration value was 42.93 µmol/l following treatment for 72 h. In addition, berberine hydrochloride induced apoptosis in HeLa229 cells in a dose­ and time­dependent manner. Berberine hydrochloride upregulated the mRNA expression levels of p53, and downregulated mRNA expression levels of Bcl­2 and cox­2, in a dose­dependent manner. In conclusion, berberine hydrochloride inhibited the proliferation and induced apoptosis of HeLa229 cells, potentially via the upregulation of p53 and the downregulation of Bcl­2 and cox­2 mRNA expression levels.