ABSTRACT
Background: People with HIV (PWH) older than age 55 have an enhanced risk of complications from SARS-CoV-2 infection. It is unclear whether COVID-19 vaccines with a booster are as durable in terms of immunogenicity in this cohort or whether these vaccines can destabilize HIV reservoirs. Method(s): We prospectively studied 91 PWH on cART aged 55 or over (n=91) and 23 age-matched individuals without HIV (control group, CG) who received three doses of COVID-19 vaccines (D1-D3) over 48 weeks. Participants received combinations of BNT162b2, mRNA-1273, and ChAdOx1. Of PWH, 42 were immune responders (IR), 20 were non-responders (INR), and 3 had a low-level viremia (LLV). Total and neutralizing Abs to SARS-CoV-2 spike (S) and RBD in sera and saliva, frequency of anti-RBD/NTD memory B cells (spectral flow cytometry), S-specific T cell immunity (IFN-g, IL-2 ELISpot) and HIV reservoirs in peripheral CD4+ T cells (IPDA) were measured. Result(s): No significant differences in vaccine regimens or dosing intervals were observed between PWH and CG. Vaccines elicited equally strong anti-S IgG in PWH vs CG in serum and saliva, and RBD IgG in serum. Serum Abs peaked at 4w after D3. Week 48 serum IgG in PWH vs CG were 916 vs 919 BAU/ mL for S (p=0.624) and 706 vs 752 for RBD (p=0.198), respectively. Week 48 median saliva S IgG: 48.1% AUC of the positive control in PWH vs 95.9% for CG (p=0.384). S IgA: 3.83 vs 20.5 in PWH vs CG (p=0.039). Median neutralizing titers post-D2 were significantly lower in PWH than in CG (NT50 82.9 vs 535, p< 0.001). However, after D3, at 48w, PWH had similar titers as CG: 309 vs 269 (p=0.745), mirroring an increase in RBD/NTD-specific B cells in PWH. Anti-S T cell cytokine responses were stronger in IR PWH after D2 and D3 than in CG. Week 48 S IL-2 responses: median 135 SFC/106 PBMC vs 43.8 (p< 0.001), but only 12.5 in INR (p=0.001 vs IR). COVID-19 vaccines did not affect the size of HIV reservoir in PWH (change in median frequency of intact proviruses from baseline: 95.0 vs 90.9, p=0.952), except in three LLV PWH (mean increase 93.7% at 48w). Conclusion(s): PWH aged 55 and over show diminished neutralizing Ab responses to SARS-CoV-2 with two vaccine doses which are 'rescued' after a booster. PWH have lower S-specific IgA in saliva after vaccination which may affect protection. Enhanced S-specific T cell immunity in PWH suggests Th1 imprinting from preexistent HIV infection. COVID-19 vaccines did not destabilize the HIV reservoir in most PWH but may pose potential risk in unsuppressed viremia.
ABSTRACT
Background: Hemodialysis (HD) patients have high mortality from COVID-19 and immunity following vaccination remains uncertain. This study evaluated SARS-CoV-2 antibody response in HD patients following BNT162b2 COVID-19 vaccination compared to health care workers (HCW) and convalescent serum. Methods: This single centre observational cohort study enrolled 142 HD patients and 35 HCW receiving the BNT162b2 vaccine. SARS-CoV-2 IgG antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD), and nucleocapsid protein (anti-NP) were measured in 66 HD patients receiving one vaccine dose, 76 HD patients receiving two vaccine doses, and 35 HCW receiving two vaccine doses. Results: In HD patients receiving a single BNT162b2 dose, seroconversion occurred in 53/66 (80%) for anti-spike and 35/66 (55%) for anti-RBD by 28 days post dose, but only 15/66 (23%) and 4/66 (6%), respectively attained a robust response defined as reaching the median level of anti-spike and anti-RBD in convalescent serum. In patients receiving two doses of BNT162b2 vaccine, seroconversion occurred in 69/72 (96%) for anti-spike and 63/72 (88%) for anti-RBD by 2 weeks following the second dose while 52/72 (72%) and 43/72 (60%) reached median convalescent serum levels of anti-spike and anti-RBD. In HCW, 35/35 (100%) exceeded median levels of anti-spike and anti-RBD in convalescent serum 2-4 weeks post second dose. Conclusions: This study found poor immunogenicity 28 days following a single dose of BNT162b2 vaccine in HD patients, supporting adherence to recommended vaccination schedules, and avoiding delay of the second dose in this population.
ABSTRACT
Background/Case Studies: Multiple assays to detect SARS-COV-2 antibodies are available but no gold standard exists. Due to many factors including waning antibodies and differences in test designs, discordance between SARS-CoV-2 serology assays is common. Given these limitations we used multiple assays and methodological approaches to estimate SARS-COV-2 seroprevalence during the first COVID-19 wave in Canada. Study Design/Methods: This serial cross-sectional study was conducted using residual plasma from healthy blood donors between April-September 2020. Qualitative (Table Presented) assessment of SARS-CoV-2 IgG antibodies was based on four assays: Abbott Architect SARS-Cov-2 IgG assay (target nucleocapsid) (Abbott-NP) and three in-house IgG ELISA assays (target spike glycoprotein (Spike), spike receptor binding domain (RBD), and nucleocapsid (NP)) based on thresholds set by the manufacture or 3-standarddeviations from the negative mean. We compared seroprevalence rates by multiple composite reference standards (CRS) and by a series of Bayesian Latent Class Models (BLCM) (using uninformative, weakly and informative priors). Using the BLCM we estimated assay characteristics, bimonthly to evaluate changes over time. Results/Findings: In total, 8999 blood samples were tested. The Abbott-NP assay consistently estimated seroprevalence to be lower than the ELISA-based assays. A priori, choosing a combination of 2 assays resulted in a range of seroprevalence estimates that ranged from 0.2% to 0.5% in April to 0.4% to 1.5% in September. From 16 possible diagnostic phenotypes, 13 were observed, only 33 samples (0.4%) were positive by all four assays. BLCM with non-informative priors provided the best model fit and predicted seroprevalence increased from 0.7% (95% CrI;0.6, 0.8%) in April/May to 1.0% (0.8, 1.1%) in June/ July to 1.5% (1.3, 1.8) in August/September. Assay characteristics varied considerably over time. Overall RBD had the highest sensitivity 82.2% (69.3, 92.9%) with a specificity of 99.6% (99.4, 99.7%). In contrast the sensitivity of the Abbott-NP assay was the lowest and waned from 63.2% (41.4, 83.1%) in April/May to 33.9% (19.7, 53.1%) by August/September. Conclusions: Regardless of the analytical method we found at the end of the first COVID-19 wave, SARSCoV- 2 seroprevalence among a healthy population of blood donors was low (<2%). While the sensitivity of all assays waned, the rates did vary. We found significant limitations to using a single assay to estimate SARSCoV- 2 seroprevalence in a low prevalence setting, such as healthy Canadian blood donors during the first wave of the COVID-19 pandemic.