Cellular and Humoral Responses to Recombinant and Inactivated SARS-CoV-2 Vaccines in CKD Patients: An Observational Study.

BACKGROUND: It remains unclear what B cell and humoral responses are mounted by chronic kidney disease (CKD) patients in response to recombinant and inactivated SARS-CoV-2 vaccines. In this study, we aimed to explore the cellular and humoral responses, and the safety of recombinant and inactivated SARS-CoV-2 vaccines in CKD patients. METHODS: 79 CKD and 420 non-CKD individuals, who completed a full course of vaccination, were enrolled in the study. Adverse events (AEs) were collected via a questionnaire. Cellular and humoral responses were detected at 1, 3, and 6 months, including IgG antibody against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (anti-RBD-IgG), neutralizing antibodies (NAbs), the positive rate of NAbs and anti-RBD-IgG, RBD-atypical memory B cells (MBCs) (CD3 - CD19 + RBD + CD21 - CD27-), RBD-activated MBCs (CD3 - CD19 + RBD + CD21 - CD27+), RBD-resting MBCs (CD3 - CD19 + RBD + CD21 + CD27+), and RBD-intermediate MBCs (CD3 - CD19 + RBD + CD21 + CD27-). RESULTS: We found no differences in the positivity rates of NAbs (70.89% vs. 79.49%, p = 0.212) and anti-RBD IgG (72.15% vs. 83.33%, p = 0.092) between the CKD and control groups. A total of 22 CKD individuals completed the full follow-up (1, 3, and 6 months). Significant and sustained declines were found at 3 months in anti-RBD IgG (26.64 BAU/mL vs. 9.08 BAU/mL, p < 0.001) and NAbs (161.60 IU/mL vs. 68.45 IU/mL p < 0.001), and at 6 months in anti-RBD IgG (9.08 BAU/mL vs. 5.40 BAU/mL, p = 0.064) and NAbs (68.45 IU/mL vs. 51.03 IU/mL, p = 0.001). Significant differences were identified in MBC subgroups between CKD patients and healthy controls, including RBD-specific atypical MBCs (60.5% vs. 17.9%, p < 0.001), RBD-specific activated MBCs (36.3% vs. 14.8%, p < 0.001), RBD-specific intermediate MBCs (1.24% vs. 42.6%, p < 0.001), and resting MBCs (1.34% vs. 22.4%, p < 0.001). Most AEs in CKD patients were mild (grade 1 and 2) and self-limiting. One patient with CKD presented with a recurrence of nephrotic syndrome after vaccination. CONCLUSIONS: The recombinant and inactivated SARS-CoV-2 vaccine was well-tolerated and showed a good response in the CKD cohort. Our study also revealed differences in MBC subtypes after SARS-CoV-2 vaccination between CKD patients and healthy controls.

Impaired antibody responses were observed in patients with type 2 diabetes mellitus after receiving the inactivated COVID-19 vaccines.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have been reported to be more susceptible to 2019 novel coronavirus (2019-nCoV) and more likely to develop severe pneumonia. However, the safety and immunological responses of T2DM patients after receiving the inactivated vaccines are not quite definite. Therefore, we aimed to explore the safety, antibody responses, and B-cell immunity of T2DM patients who were vaccinated with inactivated coronavirus disease 2019 (COVID-19) vaccines. METHODS: Eighty-nine patients with T2DM and 100 healthy controls (HCs) were enrolled, all of whom had received two doses of full-course inactivated vaccines. At 21-105 days after full-course vaccines: first, the safety of the vaccines was assessed by questionnaires; second, the titers of anti-receptor binding domain IgG (anti-RBD-IgG) and neutralizing antibodies (NAbs) were measured; third, we detected the frequency of RBD-specific memory B cells (RBD-specific MBCs) to explore the cellular immunity of T2DM patients. RESULTS: The overall incidence of adverse events was similar between T2DM patients and HCs, and no serious adverse events were recorded in either group. Compared with HCs, significantly lower titers of anti-RBD-IgG (p = 0.004) and NAbs (p = 0.013) were observed in T2DM patients. Moreover, the frequency of RBD-specific MBCs was lower in T2DM patients than in HCs (p = 0.027). Among the 89 T2DM patients, individuals with lower body mass index (BMI) had higher antibody titers (anti-RBD-IgG: p = 0.009; NAbs: p = 0.084). Furthermore, we found that sex, BMI, and days after vaccination were correlated with antibody titers. CONCLUSIONS: Inactivated COVID-19 vaccines were safe in patients with T2DM, but the antibody responses and memory B-cell responses were significantly decreased compared to HCs. TRIAL REGISTRATION NUMBER AND DATE: NCT05043246. September 14, 2021. (Clinical Trials.gov).

Salivary orosomucoid 1 as a biomarker of hepatitis B associated hepatocellular carcinoma.

Saliva is rich in proteins, DNA, RNA and microorganisms, and can be regarded as a biomarker library. In order to explore a noninvasive and simple means of early screening for liver cancer, proteomics was used to screen salivary markers of hepatitis B associated liver cancer. We used mass spectrometry coupled isobaric tags for relative and absolute quantitation (iTRAQ)-technology to identify differentially expressed proteins (DEPs). Western blot, immunohistochemistry and enzyme linked immunosorbent assay were used to detect marker expression of in tissues and saliva. Statistical analysis was used to analyze the diagnostic efficacy of the markers was analyzed through statistical analyses. By comparing the hepatocellular carcinoma (HCC) group with non-HCC groups, we screened out 152 salivary DEPs. We found orosomucoid 1(ORM1) had significantly higher expression in saliva of HCC patients compared with non-HCC groups (p < 0.001) and the expression of ORM1 in liver cancer tissues was significantly higher than that in adjacent normal tissues (p < 0.001). The combination of salivary ORM1 and alpha-fetoprotein (AFP) showed reasonable specificities and sensitivities for detecting HCC. In a word, salivary ORM1 as a new biomarker of hepatitis B associated hepatocellular carcinoma, combination of salivary ORM1 and AFP as an improved diagnostic tool for hepatocellular carcinoma.