Humeral and cellular immune responses to SARS-CoV-2 vaccination in patients on peritoneal dialysis

Background Patients with chronic kidney disease are at high risk for coronavirus disease 2019. Little is known about immune response to severe acute respiratory syndrome coronavirus 2 vaccination in patients on peritoneal dialysis (PD). Method We prospectively enrolled 306 PD patients receiving two doses of vaccines (ChAdOx1-S: 283, mRNA-1273: 23) from July 2021 at a medical center. Humeral and cellular immune responses were assessed by anti-spike IgG concentration and blood T cell interferon-γ production 30 days after vaccination. Antibody > 0.8 U/mL and interferon-γ > 100 mIU/mL were defined as positive. Antibody was also measured in 604 non-dialysis volunteers (ChAdOx1-S: 244, mRNA-1273: 360) for comparison. Result PD patients had less adverse events after vaccinations than volunteers. After the first dose of vaccine, the median antibody concentrations were 8.5 U/mL and 50.4 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 66.6 U/mL and 195.3 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. And after the second dose of vaccine, the median antibody concentrations were 344.8 U/mL and 9941.0U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 620.3 U/mL and 3845.0 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. The median IFN-γ concentration was 182.8 mIU/mL in ChAdOx1-S group, which was substantially lower than the median concentration 476.8 mIU/mL in mRNA-1273 group of PD patients. Conclusions Both vaccines were safe and resulted in comparable antibody seroconversion in PD patients when compared with volunteers. However, mRNA-1273 vaccine induced significantly higher antibody and T cell response than ChAdOx1-S in PD patients. Booster doses are recommended for PD patients after two doses of ChAdOx1-S vaccination.

Humeral and cellular immune responses to SARS-CoV-2 vaccination in patients on peritoneal dialysis.

BACKGROUND: Patients with chronic kidney disease are at high risk for coronavirus disease 2019. Little is known about immune response to severe acute respiratory syndrome coronavirus 2 vaccination in patients on peritoneal dialysis (PD). METHOD: We prospectively enrolled 306 PD patients receiving two doses of vaccines (ChAdOx1-S: 283, mRNA-1273: 23) from July 2021 at a medical center. Humeral and cellular immune responses were assessed by anti-spike IgG concentration and blood T cell interferon-γ production 30 days after vaccination. Antibody ≥0.8 U/mL and interferon-γ ≥ 100 mIU/mL were defined as positive. Antibody was also measured in 604 non-dialysis volunteers (ChAdOx1-S: 244, mRNA-1273: 360) for comparison. RESULT: PD patients had less adverse events after vaccinations than volunteers. After the first dose of vaccine, the median antibody concentrations were 8.5 U/mL and 50.4 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 66.6 U/mL and 195.3 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. And after the second dose of vaccine, the median antibody concentrations were 344.8 U/mL and 9941.0 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 620.3 U/mL and 3845.0 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. The median IFN-γ concentration was 182.8 mIU/mL in ChAdOx1-S group, which was substantially lower than the median concentration 476.8 mIU/mL in mRNA-1273 group of PD patients. CONCLUSIONS: Both vaccines were safe and resulted in comparable antibody seroconversion in PD patients when compared with volunteers. However, mRNA-1273 vaccine induced significantly higher antibody and T cell response than ChAdOx1-S in PD patients. Booster doses are recommended for PD patients after two doses of ChAdOx1-S vaccination.

SARS-CoV-2 restructures host chromatin architecture.

Some viruses restructure host chromatin, influencing gene expression, with implications for disease outcome. Whether this occurs for SARS-CoV-2, the virus causing COVID-19, is largely unknown. Here we characterized the 3D genome and epigenome of human cells after SARS-CoV-2 infection, finding widespread host chromatin restructuring that features widespread compartment A weakening, A-B mixing, reduced intra-TAD contacts and decreased H3K27ac euchromatin modification levels. Such changes were not found following common-cold-virus HCoV-OC43 infection. Intriguingly, the cohesin complex was notably depleted from intra-TAD regions, indicating that SARS-CoV-2 disrupts cohesin loop extrusion. These altered 3D genome/epigenome structures correlated with transcriptional suppression of interferon response genes by the virus, while increased H3K4me3 was found in the promoters of pro-inflammatory genes highly induced during severe COVID-19. These findings show that SARS-CoV-2 acutely rewires host chromatin, facilitating future studies of the long-term epigenomic impacts of its infection.

Evolution of anti-SARS-CoV-2 spike protein titers after two-dose of COVID-19 vaccination among people living with HIV.

Background: A community COVID-19 outbreak caused by the B.1.1.7 SARS-CoV-2 variant occurred in Taiwan in May 2021. High-risk populations such as people living with HIV (PLWH) were recommended to receive two doses of COVID-19 vaccines. While SARS-CoV-2 vaccines have demonstrated promising results in general population, real-world information on the serological responses remains limited among PLWH. Methods: PLWH receiving the first dose of SARS-CoV-2 vaccine from 2020 to 2021 were enrolled. Determinations of anti-SARS-CoV-2 spike IgG titers were performed every one to three months, the third dose of the SARS-CoV-2 vaccine or confirmed SARS-CoV-2 infection. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from analysis. Results: A total of 1189 PLWH were enrolled: 829 (69.7%) receiving two doses of the AZD1222 vaccine, 232 (19.5%) of the mRNA-1273 vaccine, and 128 (10.8%) of the BNT162b2 vaccine. At all time-points, PLWH receiving two doses of mRNA vaccines had consistently higher antibody levels than those receiving the AZD1222 vaccine (p <0.001 for all time-point comparisons). Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/mL within 12 weeks, included type 2 diabetes mellitus (DM) (adjusted odds ratio [aOR], 2.24; 95% CI, 1.25-4), a CD4 T cell count <200 cells/mm3 upon receipt of the first dose of vaccination (aOR, 3.43; 95% CI, 1.31-9) and two homologous AZD1222 vaccinations (aOR, 16.85; 95%CI, 10.13-28). For those receiving two doses of mRNA vaccines, factors associated with failure to achieve an anti-spike IgG titer >899 BAU/mL within 12 weeks were a CD4 T cell count <200 cells/mm3 on first-dose vaccination (aOR, 3.95; 95% CI, 1.08-14.42) and dual BNT162b2 vaccination (aOR, 4.21; 95% CI, 2.57-6.89). Conclusions: Two doses of homologous mRNA vaccination achieved significantly higher serological responses than vaccination with AZD1222 among PLWH. Those with CD4 T cell counts <200 cells/mm3 and DM had consistently lower serological responses.

Hepatitis C microelimination among people living with HIV in Taiwan.

To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39-7.12%) in 2018 to 2.09% (95% CI, 1.60-2.77%) in 2021 (decline by 66.4% [95% CI, 55.4-74.7%]); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44-32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14-17.44) (decline by 53.2% [95% CI, 27.3-70.6%]). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.

Reactivity of human antisera to codon optimized SARS-CoV2 viral proteins expressed in Escherichia coli.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV2 virus continues to pose a serious threat to public health worldwide. The development of rapid diagnostic kits can assist the Tzu Chi Foundation in supporting global volunteers working to provide relief during the current pandemic. MATERIALS AND METHODS: In this study, nucleotide sequences derived from publicly available viral genome data for several domains of the SARS-CoV2 spike and nucleocapsid (N) proteins were chemically synthesized, with codon optimization for Escherichia coli protein expression. No actual viral particles were involved in these experiments. The synthesized sequences were cloned into an E. coli expression system based on pQE80L, and expressed viral proteins were subsequently purified using Ni-affinity chromatography. Western blotting was conducted using human antiviral sera to assess the response of codon-modified viral proteins to COVID-19 patient sera. RESULTS: N protein was expressed in amounts large enough to support large-scale production. The N-terminal domain, receptor-binding domain (RBD), Region 3, and the S2 domain were expressed in small but sufficient amounts for experiments. Immunoblotting results showed that anti-N IgG and anti-N IgM antibodies were detected in most patient sera, but only 60% of samples reacted with the recombinant RBD and S2 domain expressed by E. coli. CONCLUSION: The results indicated that codon-optimized SARS-CoV2 viral proteins can be expressed in E. coli and purified for rapid antibody detection kit preparation, with the codon-optimized N protein, RBD, and S2 protein demonstrating the most potential.