Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Humoral and cellular immunity of two-dose inactivated COVID-19 vaccination in Chinese children: A prospective cohort study.

Children are the high-risk group for COVID-19, and in need of vaccination. However, humoral and cellular immune responses of COVID-19 vaccine remain unclear in vaccinated children. To establish the rational immunization strategy of inactivated COVID-19 vaccine for children, the immunogenicity of either one dose or two doses of the vaccine in children was evaluated. A prospective cohort study of 322 children receiving inactivated COVID-19 vaccine was established in China. The baseline was conducted after 28 days of the first dose, and the follow-up was conducted after 28 days of the second dose. The median titers of receptor binding domain (RBD)-IgG, and neutralizing antibody (NAb) against prototype strain and Omicron variant after the second dose increased significantly compared to those after the first dose (first dose: 70.0, [interquartile range, 30.0-151.0] vs. second dose: 1261.0 [636.0-2060.0] for RBD-IgG; 2.5 [2.5-18.6] vs. 252.0 [138.6-462.1] for NAb against prototype strain; 2.5 [2.5-2.5] vs. 15.0 [7.8-26.5] for NAb against Omicron variant, all p < 0.05). The flow cytometry results showed that the first dose elicited SARS-CoV-2 specific cellular immunity, while the second dose strengthened SARS-CoV-2 specific IL-2+ or TNF-α+  monofunctional, IFN-γ+ TNF-α+  bifunctional, and IFN-γ- IL-2+ TNF-α+ multifunctional CD4+ T cell responses (p < 0.05). Moreover, SARS-CoV-2 specific memory T cells were generated after the first vaccination, including the central memory T cells and effector memory T cells. The present findings provide scientific evidence for the vaccination strategy of the inactive vaccines among children against COVID-19 pandemic.

Long-term outcomes of COVID-19 convalescents: An 18.5-month longitudinal study in Wuhan.

OBJECTIVES: This study aimed to describe the full scope of long-term outcomes and the ongoing pathophysiological alterations among COVID-19 survivors. METHODS: We established a longitudinal cohort of 208 COVID-19 convalescents and followed them at 3.3 (interquartile range [IQR]: 1.3, 4.4, visit 1), 9.2 (IQR: 9.0, 9.6, visit 2), and 18.5 (IQR: 18.2, 19.1, visit 3) months after infection, respectively. Serial changes in multiple physical and psychological outcomes were comprehensively characterized. We, in addition, explored the potential risk factors of SARS-CoV-2 antibody response and sequelae symptoms. RESULTS: We observed continuous improvement of sequelae symptoms, lung function, chest computed tomography (CT), 6-minute walk test, and the Borg dyspnea scale, whereas sequelae symptoms (at least one) and abnormal chest CT patterns still existed in 45.2% and about 30% of participants at 18.5 months, respectively. Anxiety and depression disorders were alleviated for the convalescents, although depression status was sustained for a longer duration. CONCLUSIONS: Most COVID-19 convalescents had an overall improved physical and psychological health status, whereas sequelae symptoms, residual lesions on lung function, exercise impairment, and mental health disorders were still observed in a small proportion of participants at 18.5 months after infection. Implementing appropriate preventive and management strategies for the ever-growing COVID-19 population is warranted.

One-year mortality and consequences of COVID-19 in cancer patients: A cohort study.

The 1-year mortality and health consequences of COVID-19 in cancer patients are relatively underexplored. In this multicenter cohort study, 166 COVID-19 patients with cancer were compared with 498 non-cancer COVID-19 patients and 498 non-COVID cancer patients. The 1-year all-cause mortality and hospital mortality rates in Cancer COVID-19 Cohort (30% and 20%) were significantly higher than those in COVID-19 Cohort (9% and 8%, both P < .001) and Cancer Cohort (16% and 2%, both P < 0.001). The 12-month all-cause post-discharge mortality rate in survival discharged Cancer COVID-19 Cohort (8%) was higher than that in COVID-19 Cohort (0.4%, P < .001) but similar to that in Cancer Cohort (15%, P = .084). The incidence of sequelae in Cancer COVID-19 Cohort (23%, 26/114) is similar to that in COVID-19 Cohort (30%, 130/432, P = .13). The 1-year all-cause mortality was high among patients with hematologic malignancies (59%), followed by those who have nasopharyngeal, brain, and skin tumors (45%), digestive system neoplasm (43%), and lung cancers (32%). The rate was moderate among patients with genitourinary (14%), female genital (13%), breast (11%), and thyroid tumors (0). COVID-19 patients with cancer showed a high rate of in-hospital mortality and 1-year all-cause mortality, but the 12-month all-cause post-discharge mortality rate in survival discharged cancer COVID-19 patients was similar to that in Cancer Cohort. Comparing to COVID-19 Cohort, risk stratification showed that hematologic, nasopharyngeal, brain, digestive system, and lung tumors were high risk (44% vs 9%, P < 0.001), while genitourinary, female genital, breast, and thyroid tumors had moderate risk (10% vs 9%, P = .85) in COVID-19 Cancer Cohort. Different tumor subtypes had different effects on COVID-19. But if cancer patients with COVID-19 manage to survive their COVID-19 infections, then long-term mortality appears to be similar to the cancer patients without COVID-19, and their long-term clinical sequelae were similar to the COVID-19 patients without cancer.

Collagen-tussah silk fibroin hybrid scaffolds loaded with bone mesenchymal stem cells promote skin wound repair in rats.

This study demonstrates the efficacy of collagen/tussah silk fibroin (Col/TSF) hybrid scaffolds loaded with bone mesenchymal stem cells (BMSCs) in skin repair. Collagen (Col) and tussah silk fibroin (TSF) were extracted from bovine tendons and tussah cocoons, respectively. Col/TSF scaffolds were obtained using a freeze-drying method and were characterised using fourier transform infrared spectroscopy, scanning electron microscopy, porosity, water retention, thermal stability, and biocompatibility. The results revealed that addition of TSF to scaffolds could enhance their moisturising ability and cell infiltration. The antibacterial properties of Col/TSF scaffolds loaded with antibiotics were also excellent. BMSCs cultured in contact with developed Col/TSF scaffolds showed increased cell adhesion, viability, and differentiation. An in vivo study on rats showed that the Col/TSF scaffold seeded with BMSCs was more conducive to wound healing compared to the Col/TSF scaffold alone. The present study suggests that Col/TSF scaffold seeded with BMSCs could be a promising candidate for skin tissue engineering, due to its excellent skin affinity, good air and water permeability, and improved wound healing potential.

Effect of Anoectochilus roxburghii flavonoids extract on H2O2 - Induced oxidative stress in LO2 cells and D-gal induced aging mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus roxburghii (A. roxburghii) is a popular folk medicine in many Asian countries, which has been used traditionally for treatment of some diseases such as diabetes, tumors, hyperlipemia, and hepatitis. The ethanol extract from A. roxburghii was recently shown to exert better ability to scavenge free radicals in vitro and possess antioxidant on natural aging mice in vivo. AIM OF THE STUDY: This study is to characterize the chemical composition, and investigate the protective effect of the A. roxburghii flavonoids extract (ARF) against hydrogen peroxide (H2O2)-induced oxidative stress in LO2 cells in vitro and D-galactose (D-gal)-induced aging mice model in vivo, and explore the underlying mechanisms. MATERIALS AND METHODS: The chemical components of the flavonoids extract fromA. roxburghii were detected by ultraperformance lipid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). H2O2 was used to establish an oxidative stress model in LO2 cells. Cytotoxic and protective effects of ARF on the LO2 cells were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Moreover, the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) in cell supernatants were measured by commercial reagent kits. Kun-Ming mice were induced to aging with D-gal (400 mg/kg, BW) by subcutaneous injection for 58 days. From the 28th day to the 58th day of D-gal treatment, ARF (122.5, 245 and 490 mg/kg, BW) and vitamin E (100 mg/kg, BW) were orally administrated to aging mice once a day for consecutive 30 days. After 25 days of the treatment with ARF, learning and memory were assessed using Morris Water Maze (MWM). At the end of the test period, the animals were euthanized by cervical dislocation, and the levels of SOD, GSH-PX, and MDA in serum, liver homogenates and brain homogenates were measured. The levels of monoamine oxidase (MAO) and acetylcholinesterase (AchE) were determined in brain homogenates. Skin and liver histopathological morphology were observed by H&E staining. Furthermore, antioxidant-related gene expression levels in the liver were carried out by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Nine flavonoids were identified in the extracts of A. roxburghii. In vitro assay, a high concentration of ARF (>612.5 µg/ml) reduced the survival rate and had toxic effects on LO2 cells. In addition, ARF (245 µg/ml, 490 µg/ml) and Vitamin C (200 µg/ml) markedly inhibited generations of MDA and increased activities of SOD, GSH-PX in H2O2-induced LO2 cells supernatants. In vivo assay, ARF (122.5 mg/kg, 245 mg/kg and 490 mg/kg) and Vitamin E (100 mg/kg) not only ameliorated learning and memory ability but also improved skin and liver pathological alterations. Strikingly, ARF significantly decreased MDA and MAO levels, markedly enhanced antioxidant enzyme (SOD and GSH-PX) activities. Further, compared to the D-gal group, ARF could obviously up-regulate glutathione peroxidase-1 (GPx-1) and glutathione peroxidase-4 (GPx-4) mRNA levels. CONCLUSIONS: These findings suggested that ARF protects LO2 cells against H2O2-induced oxidative stress and exerts the potent anti-aging effects in D-gal aging mice model, which may be related to the inhibition of oxidative stress. Flavonoid compounds may contribute to the anti-oxidative capability and modulating aging.

Low-dose tubacin promotes BMSCs proliferation and morphological changes through the ERK pathway.

Histone deacetylase 6 (HDAC6) plays critical roles in many cellular processes related to cancer, but its epigenetic regulation in bone marrow stromal stem cells (BMSCs) remains unexplored. This study investigated the beneficial effects of Tubulin Acetylation Inducer (tubacin), a novel specific HDAC6 inhibitor, on the proliferation and migration of BMSCs. A low concentration of tubacin promoted BMSC commitment and enhanced proliferation of BMSCs. Atomic force microscopy results showed that tubacin induced morphological changes and enhanced the mechanical properties of BMSCs. Furthermore, low tubacin concentrations significantly upregulated protein expression of acetylated α-tubulin, VCAM-1, and ICAM-1, which could be suppressed by an ERK inhibitor. Protein chip analysis showed that there were significant changes in the expression levels of 49 cytokines after tubacin treatment, which participate in inflammatory responses and cell activation, proliferation, and differentiation. Our findings suggest that the protective effects of tubacin on BMSCs involve HDAC6 inhibition by activating the ERK pathway.