Longevity of SARS-CoV-2 immune responses in hemodialysis patients and protection against reinfection.

Patients with end stage kidney disease receiving in-center hemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, patients receiving ICHD frequently develop circulating antibodies to SARS-CoV-2, even with asymptomatic infection. Here, we investigated the durability and functionality of the immune responses to SARS-CoV-2 infection in patients receiving ICHD. Three hundred and fifty-six such patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection. Patients were regularly screened for nucleocapsid protein (anti-NP) and receptor binding domain (anti-RBD) antibodies, and those who became seronegative at six months were screened for SARS-CoV-2 specific T-cell responses. One hundred and twenty-nine (36.2%) patients had detectable antibody to anti-NP at time zero, of whom 127 also had detectable anti-RBD. Significantly, at six months, 71/111 (64.0%) and 99/116 (85.3%) remained anti-NP and anti-RBD seropositive, respectively. For patients who retained antibody, both anti-NP and anti-RBD levels were reduced significantly after six months. Eleven patients who were anti-NP seropositive at time zero, had no detectable antibody at six months; of whom eight were found to have SARS-CoV-2 antigen specific T cell responses. Independent of antibody status at six months, patients with baseline positive SARS-CoV-2 serology were significantly less likely to have PCR confirmed infection over the following six months. Thus, patients receiving ICHD mount durable immune responses six months post SARS-CoV-2 infection, with fewer than 3% of patients showing no evidence of humoral or cellular immunity.

HTLV seroprevalence in people using HIV pre-exposure prophylaxis in England.

OBJECTIVES: HTLV-1 is predominantly a sexually-transmitted infection but testing is not mentioned in HIV-PrEP guidelines. We ascertained HTLV-1/HTLV-2 seroprevalence amongst HIV-PrEP users in England. METHODS: An unlinked anonymous seroprevalence study. RESULTS: Amongst 2015 HIV-PrEP users, 95% were men, 76% of white ethnicity and 83% had been born in Europe. There were no HTLV-1/HTLV-2 seropositive cases (95% confidence interval 0% - 0.18%). CONCLUSIONS: There were no HTLV positive cases, likely reflecting the demographic of mostly white and European-born individuals. Similar studies are needed worldwide to inform public health recommendations for HIV-PrEP using populations, particularly in HTLV-endemic settings.

Comparison of immunogenicity and clinical effectiveness between BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines in people with end-stage kidney disease receiving haemodialysis: A prospective, observational cohort study.

Background: People with end-stage kidney disease, including people on haemodialysis, are susceptible to greater COVID-19 related morbidity and mortality. This study compares the immunogenicity and clinical effectiveness of BNT162B2 versus ChAdOx1 in haemodialysis patients. Methods: In this observational cohort study, 1021 patients were followed-up from time of vaccination until December 2021. All patients underwent weekly RT-PCR screening. Patients were assessed for nucleocapsid(anti-NP) and spike(anti-S) antibodies at timepoints after second(V2) and third(V3) vaccinations. 191 patients were investigated for T-cell responses. Vaccine effectiveness (VE) for prevention of infection, hospitalisation and mortality was evaluated using the formula VE=(1-adjustedHR)x100. Findings: 45.7% (467/1021) had evidence of prior infection. There was no difference in the proportion of infection-naïve patients who seroconverted by vaccine type, but median anti-S antibody titres were higher post-BNT162b2 compared with ChAdOx1; 462(152-1171) and 78(20-213) BAU/ml respectively, p<0.001.  Concomitant immunosuppressant use was a risk factor for non-response, OR 0.12[95% CI 0.05-0.25] p<0.001.  Post-V3 (all BNT162b2), median anti-S antibody titres remained higher in those receiving BNT162b2 versus ChAdOx1 as primary doses; 2756(187-1246) and 1250(439-2635) BAU/ml respectively, p=0.003.Anti-S antibodies waned over time. Hierarchical levels of anti-S post-V2 predicted risk of infection; patients with no/low anti-S being at highest risk. VE for preventing infection, hospitalisation and death was 53% (95% CI 6-75), 77% (95% CI 30-92) and 93% (95% CI 59-99) respectively, with no difference seen by vaccine type. Interpretation: Serum anti-S concentrations predict risk of breakthrough infection. Anti-S responses vary dependent upon clinical features, infection history and vaccine type. Monitoring of serological responses may enable individualised approaches to vaccine boosters in at risk populations. Funding: National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London.

Immune responses following 3rd and 4th doses of heterologous and homologous COVID-19 vaccines in kidney transplant recipients.

Background: Solid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. In this study, we report on immune responses to 3rd- (V3) and 4th- (V4) doses of heterologous and homologous vaccines in a kidney transplant population. Methods: We undertook a single centre cohort study of 724 kidney transplant recipients prospectively screened for serological responses following 3 primary doses of a SARS-CoV2 vaccine. 322 patients were sampled post-V4 for anti-spike (anti-S), with 69 undergoing assessment of SARS-CoV-2 T-cell responses. All vaccine doses were received post-transplant, only mRNA vaccines were used for V3 and V4 dosing. All participants had serological testing performed post-V2 and at least once prior to their first dose of vaccine. Findings: 586/724 (80.9%) patients were infection-naïve post-V3; 141/2586 (24.1%) remained seronegative at 31 (21-51) days post-V3. Timing of vaccination in relation to transplantation, OR: 0.28 (0.15-0.54), p=0.0001; immunosuppression burden, OR: 0.22 (0.13-0.37), p<0.0001, and a diagnosis of diabetes, OR: 0.49 (0.32-0.75), p=0.001, remained independent risk factors for non-seroconversion. Seropositive patients post-V3 had greater anti-S if primed with BNT162b2 compared with ChAdOx1, p=0.001.Post-V4, 45/239 (18.8%) infection-naïve patients remained seronegative. De novo seroconversion post-V4 occurred in 15/60 (25.0%) patients. There was no difference in anti-S post-V4 by vaccine combination, p=0.50. T-cell responses were poor, with only 11/54 (20.4%) infection-naive patients having detectable T-cell responses post-V4, with no difference seen by vaccine type. Interpretation: A significant proportion of transplant recipients remain seronegative following 3- and 4- doses of SARS-CoV-2 vaccines, with poor T-cell responses, and are likely to have inadequate protection against infection. As such alternative strategies are required to provide protection to this vulnerable group. Funding: MW/PK received study support from Oxford Immunotec.

Comparison of the ADVIA Centaur and Abbott AxSYM immunoassay systems for a routine diagnostic virology laboratory.

BACKGROUND: Routine diagnostic laboratories are confronted with an ever-increasing workload with limited resources. Automation has provided some solutions to these challenges particularly high through put analysers such as the Abbott AxSYM. OBJECTIVE: The aim of the present study was to compare the performance of two automated immunoassay systems in a diagnostic virology laboratory. Samples previously tested using the Abbott AxSYM were tested with a recently introduced immunoassay analyser, the Bayer ADVIA Centaur, for six virology analytes: HBsAg, anti-HBc total, anti-HBc IgM, anti-HBs, anti-HCV and anti-HIV1/O/2. STUDY DESIGN: This study was a retrospective analysis of stored serum samples previously tested on the Abbott AxSYM. Samples giving discrepant results were tested by other alternative immunoassays and re-tested on the Abbott AxSYM in the same freeze-thaw cycle. RESULTS: Although the sensitivities of the two automated immunoassays were similar there was improved specificity demonstrated for anti-HIV and anti-HCV when using the ADVIA Centaur assays. The low background signals allowed resolution of samples previously shown to have indeterminate results for anti-HIV antibody in the AxSYM assay. In addition, samples shown to have Abbott AxSYM anti-HCV results that could not be confirmed by RIBA and HCV molecular methods were shown to be negative by the ADVIA Centaur assay.