ABSTRACT
Background: All donations at Canadian Blood Services (CBS) are screened for syphilis using a serology screening and confirmation test algorithm. Currently, syphilis repeat-reactive (RR) results lead to the indefinite deferral of CBS donors regardless of supplementary test results. We have previously described a temporal association of RR results with seasonal public health influenza vaccination campaigns that generally start in September and continue through winter. As of December 2020, there has also been an intensive COVID-19 public health vaccination campaign in Canada. Aims: To track temporal associations between RR, unconfirmed syphilis results among CBS blood donors and Canadian influenza and COVID-19 vaccination campaigns. Methods: All donations were tested on the PK 7300 instrument (Beckman Coulter;Brea, CA, USA) with the PK TP system test kit. Confirmatory laboratory testing was undertaken at reference laboratories using the Treponema pallidum particle agglutination (TP-PA) test. Syphilis RR results that did not confirm were obtained for CBS donations between September 2017 to January 2022. Data on donor influenza and COVID-19 vaccination histories, within 3 months of donation, were extracted. The temporal periodicity of unconfirmed syphilis RR results was graphed against vaccination data. Respiratory virus data were acquired from the Public Health Agency of Canada Respiratory Virus Detection Surveillance System. Results: Periodicity of RR, unconfirmed syphilis rates: September 2017-January 2022. Summary/Conclusions: We have previously noted a cyclical temporal trend in the number of RR, unconfirmed syphilis specimens with peaks corresponding to influenza vaccine campaigns or widespread community circulation of respiratory viruses. Although insufficient to establish a causal association, this analysis suggests that incidence of RR, unconfirmed syphilis results in Canadian blood donors may be variably influenced at different times of year by one or more of at least three factors: (1) influenza vaccination campaigns, (2) the COVID-19 vaccination campaign, and (3) circulation of respiratory viruses in the presence or absence of circulating seasonal influenza. Moreover, other mechanisms may affect these trends. For example, syphilis assays such as the PK TP test kit that detect IgM may be prone to false positive results that do not confirm either after influenza vaccine, COVID- 19 vaccination or during a respiratory virus season. (Table Presented).
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.
ABSTRACT
Background/Case Studies: Several commercial and laboratory-developed approaches are available to quantify the level of antibodies to the spike glycoprotein of SARSCoV- 2. Plaque reduction neutralization test (PRNT)50 titers can also be used to quantify the neutralizing capacity of anti- SARS-CoV-2 antibodies in plasma. Here we describe the ability of the Elecsys anti-SARS-CoV-2 S assay (Roche, Mississauga, ON, Canada) to quantitatively determine the level of total antibodies to SARS-CoV-2 spike glycoprotein receptor binding domain in plasma specimens previously assessed by PRNT50 as well as the GenScript SARS-CoV-2 Surrogate Virus Neutralization Test (sVNT) Kit (Piscataway, NJ). Study Design/Methods: Plasma specimens were collected from blood donors that self-identified with a COVID-19 diagnosis (either SARS-CoV-2-positive nucleic acid test [NAT], or risk factors and signs/symptoms of COVID-19 disease, ≥2 weeks after cessation of clinical symptoms). 18 specimens that were previously tested by both the sVNT assay as well as by PRNT50 (National Microbiology Laboratory, Winnipeg, MB, Canada) were included in this analysis. 40 plasma specimens collected prior to November 2019 were also included in the analysis as a negative control. Specimens were analyzed using the Elecsys anti-SARS-CoV-2 S assay on the Cobas e801 analyzer (Roche, Mississauga, ON, Canada). If individual specimens were analyzed multiple times during a run, the median result in Units/ml was calculated. If specimens were further analyzed between runs, then the median between runs was calculated as the result in Units/ml. Data was stored (Microsoft Excel;Redmond, WA) and statistically analyzed (GraphPad Prism 5;San Diego, CA). Results/Findings: Of the 40 pre-pandemic specimens analyzed, all were negative for anti-SARS-CoV-2 S antibodies (<0.8 U/ml) on the Elecsys anti-SARS-CoV-2 S assay. These specimens were not orthogonally tested by other assays. Results from the other specimens tested were: Elecsys anti-SARS-CoV-2 S assay (median 63 U/ml;range 1-456 U/ml), PRNT50 (median 1:60;range 0-1:640), sVNT (median 62% neutralizing capacity;range 16-87% neutralizing capacity), PRNT50 (median 1:80;range 0-1:640). There was no correlation between the Elecsys anti-SARS-CoV-2 S assay and sVNT assays (Spearman r=0.4, p=0.1, Gaussian approximation). There was a correlation between the Elecsys anti-SARS-CoV-2 S assay and PRNT50 (Spearman r=0.8, p<0.0001, Gaussian approximation). Conclusions: This preliminary data suggests that the Elecsys anti-SARS-CoV-2 S assay may be able to act as a proxy for the quantification of neutralizing capacity in plasma specimens from individuals who have been previously infected with SARS-CoV-2.