The effect of first-wave COVID-19 restrictions on HCV testing in Alberta, Canada: A trend analysis from 2019 to 2022.

Background: Prior to the COVID-19 pandemic, Alberta was on track to meet national HCV elimination targets by 2030. However, it is unclear how the pandemic has affected progress. Here, we aim to assess the impact of first-wave COVID-19 restrictions on Alberta HCV testing trends. Methods: HCV testing information was extracted from the provincial public health laboratory from 2019 to 2022. HCV antibody and RNA testing were categorized into (1) number ordered, (2) number positive, and (3) percent positivity, and stratified by HCV history status. Testing trends were evaluated across locations engaging high-risk individuals and priority demographics. An interrupted time-series analysis was used to identify average monthly testing rates before, during, and after first-wave COVID-19 restrictions. Results: Overall, HCV testing trends were significantly affected by COVID-19 restrictions in April 2020. Average monthly rates decreased by 98.39 antibody tests ordered per 100,000 among individuals without an HCV history and by 1.78 RNA tests ordered per 100,000 among those with an HCV history. While antibody and RNA testing trends started to rebound in the follow-up period relative to pre-restriction period, testing levels in the follow-up period remained below pre-restriction levels for all groups, except for addiction/recovery centres and emergency room/acute care facilities, which increased. Conclusions: If rates are to return to pre-restriction levels and elimination goals are to be met, more work is needed to engage individuals in HCV testing. As antibody testing rates are rebounding, reengaging those with a history of HCV for viral load monitoring and treatment should be prioritized.

Decreasing parvovirus B19 and hepatitis A nucleic acid test positivity rates in Canadian plasma donors following the initiation of COVID-19 restriction in March 2020.

BACKGROUND AND OBJECTIVES: In Canada, plasma sent for fractionation is tested for both parvovirus B19 (B19V) and hepatitis A virus (HAV). This study compared positivity rates of B19 and HAV nucleic acid tests (NATs) in Canadian plasma samples for the pre-COVID-19 restriction era (2015 to end of February 2020 [Q1] 2020) and the post-COVID-19 restriction era. MATERIALS AND METHODS: Pooled EDTA plasma specimens were tested within 24 months of blood draw using the Procleix Panther System (Grifols Diagnostic Solutions Inc, San Diego, CA, USA) for B19V and HAV detection. Reactive pools were resolved by individual specimen testing. RESULTS: Between 1 January 2015, and 31 March 2022, 3,928,619 specimens from Canadian plasma donors were tested for B19V. For the same period, 3,922,954 specimens were tested for HAV. To account for a lag in specimen testing for up to 24 months, the data were divided into: (1) a pre-pandemic period (1 January 2015-31 March 2020; B19V tested n = 2,412,701, B19V NAT-positive n = 240 [0.01%], HAV tested n = 2,407,036, HAV NAT-positive n = 26 [0.001%]); (2) a two-year mixed-impact period (1 April 2020-31 March 2022; B19V tested n = 968,250, B19V NAT-positive n = 14 [0.001%], HAV tested n = 968,250, HAV NAT-positive n = 2 [0.0002%]); and (3) a pandemic-impact period (1 April 2022-31 March, 2023; B19V tested n = 597,668, B19V NAT-positive n = 3 [0.0005%], HAV tested n = 597,668, HAV NAT-positive n = 1 [0.0002%]). CONCLUSION: The percentage of B19V- and HAV-positive donations was significantly reduced from the pre-pandemic period to the pandemic-impact period.

Determinants of SARS-CoV-2 IgG response and decay in Canadian healthcare workers: A prospective cohort study.

INTRODUCTION: Healthcare workers (HCWs) from an interprovincial Canadian cohort gave serial blood samples to identify factors associated with anti-receptor binding domain (anti-RBD) IgG response to the SARS-CoV-2 virus. METHODS: Members of the HCW cohort donated blood samples four months after their first SARS-CoV-2 immunization and again at 7, 10 and 13 months. Date and type of immunizations and dates of SARS-CoV-2 infection were collected at each of four contacts, together with information on immunologically-compromising conditions and current therapies. Blood samples were analyzed centrally for anti-RBD IgG and anti-nucleocapsid IgG (Abbott Architect, Abbott Diagnostics). Records of immunization and SARS-CoV-2 testing from public health agencies were used to assess the impact of reporting errors on estimates from the random-effects multivariable model fitted to the data. RESULTS: 2752 of 4567 vaccinated cohort participants agreed to donate at least one blood sample. Modelling of anti-RBD IgG titer from 8903 samples showed an increase in IgG with each vaccine dose and with first infection. A decrease in IgG titer was found with the number of months since vaccination or infection, with the sharpest decline after the third dose. An immunization regime that included mRNA1273 (Moderna) resulted in higher anti-RBD IgG. Participants reporting multiple sclerosis, rheumatoid arthritis or taking selective immunosuppressants, tumor necrosis factor inhibitors, calcineurin inhibitors and antineoplastic agents had lower anti-RBD IgG. Supplementary analyses showed higher anti-RBD IgG in those reporting side-effects of vaccination, no relation of anti-RBD IgG to obesity and lower titers in women immunized in early or mid-pregnancy. Sensitivity analysis results suggested no important bias in the self-report data. CONCLUSION: Creation of a prospective cohort was central to the credibility of results presented here. Serial serology assessments, with longitudinal analysis, provided effect estimates with enhanced accuracy and a clearer understanding of medical and other factors affecting response to vaccination.

Retrospective Review of Prenatal Gonorrhea and Chlamydia Screening in Alberta: 2018-2022.

A retrospective 5-year province-wide evaluation of prenatal Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) screening in Alberta, Canada, was carried out to assess compliance with the provincial recommendations for universal prenatal screening as a prevention for neonatal ophthalmia. Screening generally improved across the province each year, 82.1% in 2018 and reaching 87.3% in 2022. Women in the age group under 25 years were the most likely to not have the recommended first-trimester screening and demonstrated the highest prevalence of GC and CT infections. The results of this investigation demonstrate that continued improvements are needed to achieve universal prenatal GC/CT screening in Alberta.

Molecular epidemiology of rotavirus among children in Western Canada: Dynamic changes in genotype prevalence in four consecutive seasons.

Rotavirus molecular surveillance remains important in the postvaccine era to monitor the changes in transmission patterns, identify vaccine-induced antigenic changes and discover potentially pathogenic vaccine-related strains. The Canadian province of Alberta introduced rotavirus vaccination into its provincial vaccination schedule in June 2015. To evaluate the impact of this program on stool rotavirus positivity rate, strain diversity, and seasonal trends, we analyzed a prospective cohort of children with acute gastroenteritis recruited between December 2014 and August 2018. We identified dynamic changes in rotavirus positivity and genotype trends during pre- and post-rotavirus vaccine introduction periods. Genotypes G9P[8], G1P[8], G2P[4], and G12P[8] predominated consecutively each season with overall lower rotavirus incidence rates in 2016 and 2017. The demographic and clinical features of rotavirus gastroenteritis were comparable among wild-type rotaviruses; however, children with G12P[8] infections were older (p < 0.001). Continued efforts to monitor changes in the molecular epidemiology of rotavirus using whole genome sequence characterization are needed to further understand the impact of the selection pressure of vaccination on rotavirus evolution.

The evolution of SARS-CoV-2 seroprevalence in Canada: a time-series study, 2020-2023.

BACKGROUND: During the first year of the COVID-19 pandemic, the proportion of reported cases of COVID-19 among Canadians was under 6%. Although high vaccine coverage was achieved in Canada by fall 2021, the Omicron variant caused unprecedented numbers of infections, overwhelming testing capacity and making it difficult to quantify the trajectory of population immunity. METHODS: Using a time-series approach and data from more than 900 000 samples collected by 7 research studies collaborating with the COVID-19 Immunity Task Force (CITF), we estimated trends in SARS-CoV-2 seroprevalence owing to infection and vaccination for the Canadian population over 3 intervals: prevaccination (March to November 2020), vaccine roll-out (December 2020 to November 2021), and the arrival of the Omicron variant (December 2021 to March 2023). We also estimated seroprevalence by geographical region and age. RESULTS: By November 2021, 9.0% (95% credible interval [CrI] 7.3%-11%) of people in Canada had humoral immunity to SARS-CoV-2 from an infection. Seroprevalence increased rapidly after the arrival of the Omicron variant - by Mar. 15, 2023, 76% (95% CrI 74%-79%) of the population had detectable antibodies from infections. The rapid rise in infection-induced antibodies occurred across Canada and was most pronounced in younger age groups and in the Western provinces: Manitoba, Saskatchewan, Alberta and British Columbia. INTERPRETATION: Data up to March 2023 indicate that most people in Canada had acquired antibodies against SARS-CoV-2 through natural infection and vaccination. However, given variations in population seropositivity by age and geography, the potential for waning antibody levels, and new variants that may escape immunity, public health policy and clinical decisions should be tailored to local patterns of population immunity.

Association of COVID-19 Government-Instituted Mask Mandates With Incidence of Mask Use Among Children in Alberta, Canada.

Importance: To help prevent the spread of SARS-CoV-2, government-instituted nonpharmaceutical interventions (eg, social distancing, mask use, isolating), a provincewide government-instituted mask mandate occurred on December 8, 2020, in Alberta, Canada, although some local jurisdictions implemented an earlier mask mandate. There remains a limited understanding of the association between government-implemented public health measures and individual health behaviors of children. Objective: To examine the association between government mask mandates and mask use among children in Alberta, Canada. Design, Setting, and Participants: A cohort of children from Alberta, Canada, was recruited to examine longitudinal SARS-CoV-2 serologic factors. Parents were prospectively asked about their child's mask use in public places every 3 months (5-point Likert scale: never to always) from August 14, 2020, to June 24, 2022. A multivariable logistic generalized estimating equation was used to examine government mandatory masking mandates and child mask use. Child mask use was operationalized into a single composite dichotomous outcome by grouping parents who reported their child often or always wore a mask vs those who reported their child never, rarely, or occasionally wore a mask. Exposures: The primary exposure variable was the government masking mandate (began on different dates in 2020). The secondary exposure variable was government private indoor and outdoor gathering restrictions. Main Outcomes and Measures: The primary outcome was parent report of child mask use. Results: A total of 939 children participated (467 female [49.7%]; mean [SD] age, 10.61 [1.6] years). The odds of parents' report of child mask use (often or always) was 18.3 times higher (95% CI, 5.7-58.6; P < .001; risk ratio, 1.7; 95% CI, 1.5-1.8; P < .001) with the mask mandate on compared with the mask mandate off. There was no significant change in mask use over the course of the mask mandate due to time. In contrast, each day with the mask mandate off was associated with a 1.6% decrease in mask use (odds ratio, 0.98; 95% CI, 0.98-0.99; P < .001). Conclusions and Relevance: The results of this study suggest that government-mandated mask use and providing the public with up-to-date health information (eg, case counts) is associated with increased parent-reported child mask use, while increasing time without a mask mandate is associated with decreased mask use.

Evaluation and comparison of risk-based and universal prenatal HCV screening programs in Alberta, Canada.

BACKGROUND & AIMS: Canadian clinical practice guidelines currently recommend risk-based screening for HCV in pregnant individuals. However, no provinces or territories have ever compared the effectiveness of risk-based vs. universal screening for the prenatal diagnosis of HCV. We aimed to evaluate and compare HCV screening programs after implementing a universal population-level pilot program among prenatal patients in Alberta, Canada. METHODS: The Alberta Prenatal Screening Program for Select Communicable Diseases was amended to include universal HCV antibody screening. Cohorts of pregnant individuals screened for HCV through risk-based or universal programs were generated over 1-year periods. HCV screening rates and prevalence were analyzed and compared between cohorts to evaluate the effectiveness of screening methods. Social and demographic risk factors for HCV-positive individuals were compared between screening cohorts to identify which populations may be overlooked with risk-based guidelines. RESULTS: HCV antibody screening rates were 11.9% and 99.9% among pregnant individuals in the risk-based and universal cohorts, respectively. HCV prevalence among the cohorts was 0.07% and 0.11% (difference = 0.04%, p = 0.032), with an average of 21 additional HCV-positive pregnant individuals identified annually with universal screening. HCV-positive pregnant patients diagnosed through universal screening were more likely to engage in high-risk sexual behaviours/sex work compared to those diagnosed through risk-based screening (47.6% vs. 12.5%, respectively p = 0.035), suggesting that these high-risk cases are being missed by risk-based screening. CONCLUSIONS: Universal HCV screening diagnoses significantly higher numbers of pregnant individuals infected with HCV compared to risk-based screening. Universal HCV screening or amending risk-based guidelines to incorporate more proxy variables for risk factors should be considered to improve prenatal HCV screening guidelines in Canada and help achieve HCV elimination in the next decade. IMPACT AND IMPLICATIONS: HCV is a bloodborne pathogen that can cause severe liver disease and be vertically transmitted from a mother to her baby during pregnancy. Pregnant individuals in Alberta are currently only tested for HCV if they disclose engaging in activities that put them at risk of acquiring the infection (risk-based screening). Using a population-wide universal prenatal HCV screening program, our work shows that testing based on patient disclosed risk alone leads to the significant underdiagnosis of HCV in pregnant individuals and suggests individuals engaging in sex work or risky sexual behaviours are being overlooked by the current risk-based program. Our outcomes represent the first province-wide study to evaluate and compare prenatal HCV risk-based and universal screening programs in Canada and provide evidence to support the update of prenatal HCV screening policies across the country and in similar jurisdictions.

Retrospective testing for the presence of monkeypox virus in a high-risk population from February-June 2022 in Alberta, Canada.

Background: A multi-country outbreak of monkeypox virus (MPXV) infections was identified by the World Health Organization in May 2022. The western Canadian province of Alberta identified its first case of MPXV in a returning traveller on June 2, 2022. We undertook a retrospective testing exercise to evaluate whether MPXV may have been circulating in the province earlier. Methods: Skin (genital and non-genital) and mucosal lesion swabs submitted for herpes simplex virus (HSV)/varicella zoster virus (VZV)/syphilis testing from male patients attending sexually-transmitted infection clinics across the province of Alberta from January 28 to May 30, 2022 were retrieved from storage. The population tested was selected based on the epidemiology of the current 2022 multi-country MPXV outbreak. Samples underwent viral nucleic acid extraction and testing for the presence of Orthopoxvirus DNA using a commercial real-time polymerase chain reaction (PCR) kit. Results: A total of 392 samples (representing 341 unique individuals of median age 31 years) were retrieved. Of them, 349 (89.0%) samples were submitted for HSV/VZV/syphilis testing, 13 (3.3%) for HSV/VZV only, and 30 (7.7%) for syphilis PCR only. None of the 392 samples tested were found to be positive for Orthopoxvirus DNA. Conclusions: The results of this study indicate that circulation of MPXV in a higher-risk population in Alberta, prior to the first case, was less likely. We recommend that other provinces/territories review their local epidemiology, context and resources prior to conducting similar studies.

Historique: En mai 2022, l'Organisation mondiale de la Santé a déclaré une flambée multinationale d'infection par le virus de la variole simienne (MPXV). Le 2 juin 2022, la province de l'Alberta, dans l'Ouest canadien, a recensé son premier cas de MPXV chez un voyageur de retour de l'étranger. Les chercheurs ont entrepris un exercice de dépistage rétrospectif pour évaluer la possibilité que le MPXV ait circulé auparavant dans la province. Méthodologie: Les chercheurs ont extrait de l'entreposage les écouvillons des lésions cutanées (génitales et non génitales) et muqueuses soumis en vue de dépister le virus herpès simplex (VHS), le virus varicelle-zona (VZV) et le virus de la syphilis des patients de sexe masculin qui avaient fréquenté les cliniques d'infections transmises sexuellement de la province de l'Alberta entre le 28 janvier et le 30 mai 2022. Ils ont sélectionné la population soumise au dépistage en fonction de l'épidémiologie de la flambée multinationale de MPXV en 2022. Les écouvillons ont été soumis à l'extraction et au test des acides nucléiques viraux pour dépister la présence d'ADN de l'Orthopoxvirus au moyen d'un test commercial d'amplification en chaîne par polymérase (PCR). RÉsultats: Les chercheurs ont extrait un total de 392 échantillons (représentant 341 personnes uniques d'un âge médian de 31 ans). De ce nombre, 349 (89,0 %) avaient été soumis au test PCR du VHS, du VZV et de la syphilis, 13 (3,3 %), du VHS et du VZV seulement et 30 (7,7 %), de la syphilis seulement. Aucun des 392 échantillons n'a donné de résultat positif à l'ADN de l'Orthopoxvirus. Conclusions: D'après les résultats de la présente étude, il est peu probable que le MPXV ait circulé dans la population plus vulnérable de l'Alberta avant la détection du premier cas. Les chercheurs recommandent que les autres provinces et territoires examinent leur épidémiologie locale, le contexte et les ressources avant de procéder à des études de ce type.

Canadian SARS-CoV-2 serological survey using antenatal serum samples: a retrospective seroprevalence study.

BACKGROUND: Insufficient data on the rate and distribution of SARS-CoV-2 infection in Canada has presented a substantial challenge to the public health response to the COVID-19 pandemic. Our objective was to assess SARS-CoV-2 seroprevalence in a representative sample of pregnant people throughout Canada, across multiple time points over 2 years of the pandemic, to describe the seroprevalence and show the ability of this process to provide prevalence estimates. METHODS: This Canadian retrospective serological surveillance study used existing serological prenatal samples across 10 provinces over multiple time periods: Feb. 3-21, 2020; Aug. 24-Sept. 11, 2020; Nov. 16-Dec. 4, 2020; Nov. 15-Dec. 3, 2021; and results from the province of British Columbia during a period in which the SARS-CoV-2 B.1.1.529 (Omicron) variant was predominant, from Nov. 15, 2021, to June 11, 2022. Age and postal code administrative data allowed for comparison with concurrent polymerase chain reactivity (PCR)-positive results collected by Statistics Canada and the Canadian Surveillance of COVID-19 in Pregnancy (CANCOVID-Preg) project. RESULTS: Seropositivity in antenatal serum as early as February 2020 indicates SARS-CoV-2 transmission before the World Health Organization's declaration of the pandemic. Seroprevalence in our sample of pregnant people was 1.84 to 8.90 times higher than the recorded concurrent PCR-positive prevalence recorded among females aged 20-49 years in November-December 2020. Overall seropositivity in our sample of pregnant people was low at the end of 2020, increasing to 15% in 1 province by the end of 2021. Seroprevalence among pregnant people in BC during the Omicron period increased from 5.8% to 43% from November 2021 to June 2022. INTERPRETATION: These results indicate widespread vulnerability to SARS-CoV-2 infection before vaccine availability in Canada. During the time periods sampled, public health tracking systems were under-reporting infections, and seroprevalence results during the Omicron period indicate extensive community spread of SARS-CoV-2 infection.

A longitudinal seroepidemiology study to evaluate antibody response to SARS-CoV-2 virus infection and vaccination in children in Calgary, Canada from July 2020 to April 2022: Alberta COVID-19 Childhood Cohort (AB3C) Study.

BACKGROUND: Measurement of SARS-CoV-2 antibody seropositivity is important to accurately understand exposure to infection and/or vaccination in specific populations. This study aimed to estimate the serologic response to SARS-CoV-2 virus infection and vaccination in children in Calgary, Alberta over a two-year period. METHODS: Children with or without prior SARS-CoV-2 infections, were enrolled in Calgary, Canada in 2020. Venous blood was sampled 4 times from July 2020 to April 2022 for SARS-CoV-2 nucleocapsid and spike antibodies. Demographic and clinical information was obtained including SARS-CoV-2 testing results and vaccination records. RESULTS: 1035 children were enrolled and 88.9% completed all 4 visits; median age 9 years (IQR: 5,13); 519 (50.1%) female; and 815 (78.7%) Caucasian. Before enrolment, 118 (11.4%) had confirmed or probable SARS-CoV-2. By April 2022, 39.5% of previously uninfected participants had a SARS-CoV-2 infection. Nucleocapsid antibody seropositivity declined to 16.4% of all infected children after more than 200 days post diagnosis. Spike antibodies remained elevated in 93.6% of unvaccinated infected children after more than 200 days post diagnosis. By April 2022, 408 (95.6%) children 12 years and older had received 2 or more vaccine doses, and 241 (61.6%) 5 to 11 year-old children had received 2 vaccine doses. At that time, all 685 vaccinated children had spike antibodies, compared with 94/176 (53.4%) of unvaccinated children. CONCLUSIONS: In our population, after the first peak of Omicron variant infections and introduction of COVID-19 vaccines for children, all vaccinated children, but just over one-half of unvaccinated children, had SARS-CoV-2 spike antibodies indicating infection and/or vaccination, highlighting the benefit of vaccination. It is not yet known whether a high proportion of seropositivity at the present time predicts sustained population-level protection against future SARS-CoV-2 transmission, infection or severe COVID-19 outcomes in children.

Prevalence of syphilis coinfection in hepatitis C virus positive prenatal patients from Alberta during a pilot routine screening program.

BACKGROUND: Alberta routinely screens pregnant patients for select communicable diseases. Hepatitis C virus (HCV) was added to the prenatal screening panel as part of a provincial pilot program in February 2020. This retrospective cross-sectional study aimed to characterize the prevalence of syphilis coinfections in prenatal patients infected with HCV following implementation of the pilot program.METHODS: Routine prenatal HCV and syphilis testing data were extracted from the Public Health Laboratory Information System over a 21-month period. HCV positivity was defined as HCV enzyme immunoassay (EIA) reactive with detected HCV ribonucleic acid (RNA) following molecular confirmation, and positive results were examined for syphilis coinfections. All patients reactive on a syphilis EIA and confirmatory Treponema pallidum particle agglutination (TPPA) or follow-up rapid plasma reagin (RPR) test were considered positive for syphilis. Descriptive statistics for coinfected patients were analyzed. RESULTS: Eighty-seven prenatal patients were identified to be positive for HCV. Of those, 19 (21.8%) were reactive on the syphilis EIA and 17 (19.5%) had confirmed infections with the TPPA or RPR tests. For HCV/syphilis coinfected patients, the majority resided in metropolitan regions (64.6%), were from the lowest income quintile neighbourhoods (47.1%) and had previously tested positive for HCV (82.4%) and syphilis (64.6%) at the public health laboratory. CONCLUSIONS: The prevalence of syphilis coinfections in prenatal patients infected with HCV is high in Alberta. HCV/syphilis coinfection prevalence should be further investigated in other jurisdictions and prenatal cohorts to better understand testing and treatment options for prevention of congenital transmission.

What's in a number? The value of titers as routine proof of immunity for medical students.

OBJECTIVES: To assess the guideline concordance of medical school requirements for students' proof-of-immunity in the United States (US) and Canada. METHODS: National guidelines for healthcare worker proof-of-immunity to measles, mumps, rubella, and varicella were compared to admission requirements for 62 US and 17 Canadian medical schools. RESULTS: All surveyed schools accepted at least one recommended form of proof-of-immunity, however, contrary to national guidelines, 16% of surveyed US schools asked for a serologic titer, and only 73-79% US schools accepted vaccination as the sole proof-of-immunity. CONCLUSIONS: The requirement of numerical, non-standardized serologic testing highlights an oversight in medical school admissions documentation. The requirement for quantitative values to demonstrate immunity is not practical from a laboratory standpoint, and is not needed to show individual immunity to these vaccine-preventable diseases. Until a more standardized process is adopted, laboratories will need to provide clear documentation and direction for quantitative titer requests.

Label-free impedimetric immunosensor for point-of-care detection of COVID-19 antibodies.

The COVID-19 pandemic has posed enormous challenges for existing diagnostic tools to detect and monitor pathogens. Therefore, there is a need to develop point-of-care (POC) devices to perform fast, accurate, and accessible diagnostic methods to detect infections and monitor immune responses. Devices most amenable to miniaturization and suitable for POC applications are biosensors based on electrochemical detection. We have developed an impedimetric immunosensor based on an interdigitated microelectrode array (IMA) to detect and monitor SARS-CoV-2 antibodies in human serum. Conjugation chemistry was applied to functionalize and covalently immobilize the spike protein (S-protein) of SARS-CoV-2 on the surface of the IMA to serve as the recognition layer and specifically bind anti-spike antibodies. Antibodies bound to the S-proteins in the recognition layer result in an increase in capacitance and a consequent change in the impedance of the system. The impedimetric immunosensor is label-free and uses non-Faradaic impedance with low nonperturbing AC voltage for detection. The sensitivity of a capacitive immunosensor can be enhanced by simply tuning the ionic strength of the sample solution. The device exhibits an LOD of 0.4 BAU/ml, as determined from the standard curve using WHO IS for anti-SARS-CoV-2 immunoglobulins; this LOD is similar to the corresponding LODs reported for all validated and established commercial assays, which range from 0.41 to 4.81 BAU/ml. The proof-of-concept biosensor has been demonstrated to detect anti-spike antibodies in sera from patients infected with COVID-19 within 1 h. Photolithographically microfabricated interdigitated microelectrode array sensor chips & label-free impedimetric detection of COVID-19 antibody.

Faradaic Impedimetric Immunosensor for Label-Free Point-of-Care Detection of COVID-19 Antibodies Using Gold-Interdigitated Electrode Array.

Label-free electrochemical biosensors have many desirable characteristics in terms of miniaturization, scalability, digitization, and other attributes associated with point-of-care (POC) applications. In the era of COVID-19 and pandemic preparedness, further development of such biosensors will be immensely beneficial for rapid testing and disease management. Label-free electrochemical biosensors often employ [Fe(CN)6]-3/4 redox probes to detect low-concentration target analytes as they dramatically enhance sensitivity. However, such Faradaic-based sensors are reported to experience baseline signal drift, which compromises the performance of these devices. Here, we describe the use of a mecaptohexanoic (MHA) self-assembled monolayer (SAM) modified Au-interdigitated electrode arrays (IDA) to investigate the origin of the baseline signal drift, developed a protocol to resolve the issue, and presented insights into the underlying mechanism on the working of label-free electrochemical biosensors. Using this protocol, we demonstrate the application of MHA SAM-modified Au-IDA for POC analysis of human serum samples. We describe the use of a label-free electrochemical biosensor based on covalently conjugated SARS-CoV-2 spike protein for POC detection of COVID-19 antibodies. The test requires a short incubation time (10 min), and has a sensitivity of 35.4/decade (35.4%/10 ng mL-1) and LOD of 21 ng/mL. Negligible cross reactivity to seasonal human coronavirus or other endogenous antibodies was observed. Our studies also show that Faradaic biosensors are ~17 times more sensitive than non-Faradaic biosensors. We believe the work presented here contributes to the fundamental understanding of the underlying mechanisms of baseline signal drift and will be applicable to future development of electrochemical biosensors for POC applications.

HCV reflex testing: A single-sample, low-contamination method that improves the diagnostic efficiency of HCV testing among patients in Alberta, Canada.

BACKGROUND: Hepatitis C virus (HCV) can be cured with antiviral treatments. Diagnosis normally requires two blood samples, one for serology screening and one for molecular confirmation. This multi-step process creates barriers in patient care and decreases testing for hard-to-reach populations. We used the cobas® 6800 to detect HCV RNA after antibody testing to investigate whether a single-sample reflex testing method is effective and efficient for diagnosing HCV-positive patients. METHODS: HCV RNA-positive clinical samples (n = 152) were interchangeably loaded on the ARCHITECT i2000SR with negative samples (n = 152) in a checkerboard fashion, tested for HCV antibodies using fixed probes, and directly transferred to the cobas 6800 for molecular testing. Contamination rates, sensitivity, and specificity were determined by comparing Abbott m2000 and cobas 6800 viral loads. After implementing reflex testing, clinical data over a 6-month period were analyzed for diagnostic efficiency. RESULTS: Contamination was present in 5 of 152 pairs (3.29%) after reflex testing. Sensitivity and specificity were 99.3% (95% CI 95.1% to 99.9%) and 100% (95% CI 97.5% to 100%), respectively, using the cobas 6800 assay after serotesting. Approximately 97% of clinical patients received a conclusive test result with the reflex-testing algorithm. For HCV-positive patients, mean diagnostic turnaround times were significantly lower using reflex testing versus the two-sample method (4 versus 39 days; p < 0.0001). CONCLUSIONS: HCV reflex testing demonstrated low levels of contamination without compromising the integrity of the molecular assay. Implementation in clinical laboratories would increase the efficiency of diagnosis and decrease steps in the continuum of care for patients.

HISTORIQUE: Il est possible de vaincre le virus de l'hépatite C (VHC) par des traitements antirétroviraux. Pour poser un diagnostic, il faut normalement deux prélèvements de sang : l'un pour le dépistage sérologique et l'autre pour la confirmation moléculaire. Ce processus en plusieurs étapes crée des obstacles dans les soins aux patients et limite le dépistage auprès des populations difficiles à atteindre. Les auteurs ont utilisé la plateforme cobasMD 6800 pour déceler l'ARN du VHC après des tests de détection des anticorps et pour explorer si une méthode de dépistage réflexe à échantillon unique est efficace et efficiente lors du diagnostic des patients positifs au VHC. MÉTHODOLOGIE : Les chercheurs ont placé les échantillons cliniques positifs à l'ARN du VHC (n = 152) en échiquier avec des échantillons négatifs (n = 152) dans l'analyseur ARCHITECT i2000SR, ont dépisté les anticorps du VHC à l'aide de sondes fixes, puis ont transféré les échantillons directement sur la plateforme cobas 6800 en vue du test moléculaire. Ils ont établi les taux de contamination, la sensibilité et la spécificité en comparant les charges virales des plateformes Abbott m2000 et cobas 6800. Après le dépistage réflexe, ils ont analysé les données cliniques sur une période de six mois pour en établir l'efficience diagnostique. RÉSULTATS : Les chercheurs ont constaté une contamination dans cinq des 152 paires (3,29 %) après le dépistage réflexe. Après l'examen sérologique, ils ont obtenu une sensibilité de 99,3 % (IC à 95 %, de 95,1 % à 99,9 %) et une spécificité de 100 % (IC à 95 %, de 97,5 % à 100 %) au moyen de la plateforme cobas 6800. Environ 97 % des patients cliniques ont reçu un test concluant selon l'algorithme du dépistage réflexe. Chez les patients positifs au VHC, le délai diagnostique moyen était considérablement plus court après le dépistage réflexe qu'après la méthode à deux échantillons (quatre jours plutôt que 39; p < 0,0001). CONCLUSIONS : Le dépistage réflexe du VHC a démontré de faibles taux de contamination sans compromettre l'intégrité du dosage moléculaire. Son adoption en laboratoire clinique accroîtrait l'efficience du diagnostic et réduirait le nombre d'étapes dans le continuum des soins aux patients.

Evaluation of the performance of multiple immunoassay diagnostic platforms on the National Microbiology Laboratory SARS-CoV-2 National Serology Panel.

BACKGROUND: Serological assays designed to detect SARS-CoV-2 antibodies are being used in serological surveys and other specialized applications. As a result, and to ensure that the outcomes of serological testing meet high quality standards, evaluations are required to assess the performance of these assays and the proficiency of laboratories performing them. METHODS: A panel of 60 plasma/serum samples from blood donors who had reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections and 21 SARS-CoV-2 negative samples were secured and distributed to interested laboratories within Canada (n = 30) and the United States (n = 1). Participating laboratories were asked to provide details on the diagnostic assays used, the platforms the assays were performed on, and the results obtained for each panel sample. Laboratories were blinded with respect to the expected outcomes. RESULTS: The performance of the different assays evaluated was excellent, with the high-throughput platforms of Roche, Ortho, and Siemens demonstrating 100% sensitivity. Most other high-throughput platforms had sensitivities of >93%, with the exception of the IgG assay using the Abbott ARCHITECT which had an average sensitivity of only 87%. The majority of the high-throughput platforms also demonstrated very good specificities (>97%). CONCLUSION: This proficiency study demonstrates that most of the SARS-CoV-2 serological assays utilized by provincial public health or hospital laboratories in Canada have acceptable sensitivity and excellent specificity.

HISTORIQUE: Les dosages sérologiques conçus pour dépister les anticorps anti-SRAS-CoV-2 sont utilisés dans les études sérologiques et d'autres applications spécialisées. Par conséquent, et pour s'assurer que leurs résultats respectent des normes de qualité, il faut procéder à des évaluations de leur performance et de la compétence des laboratoires à les effectuer. MÉTHODOLOGIE: Les chercheurs ont obtenu une batterie de 60 prélèvements de plasma et de sérum chez des donneurs dont l'amplification en chaîne par polymérase après transcription inverse (RT-PCR) avait confirmé des infections par le SRAS-CoV-2 et de 21 prélèvements dont les résultats étaient négatifs au SRAS-CoV-2 et les ont distribués aux laboratoires intéressés du Canada (n = 30) et des États-Unis (n = 1). Ils ont invité les laboratoires participants à fournir de l'information détaillée sur les dosages diagnostiques utilisés, les plateformes sur lesquelles les dosages étaient exécutés et les résultats obtenus pour chaque échantillon. Les chercheurs ont demandé aux laboratoires participants de fournir de l'information détaillée sur les dosages diagnostiques utilisés, les plateformes sur lesquelles les dosages ont été effectués, et les résultats obtenus à l'égard de chaque échantillon. Les laboratoires ont mené les études à l'insu des résultats escomptés. RÉSULTATS: Les divers dosages avaient une excellente exécution, les plateformes à haut débit de Roche, d'Ortho et de Siemens démontrant une sensibilité de 100 %. La plupart des autres plateformes à haut débit avaient des sensibilités de plus de 93 %, à l'exception des dosages des IgG faisant appel à l'analyseur ARCHITECT d'Abbott, dont la sensibilité moyenne était de seulement 87 %. La majorité des plateformes à haut débit avaient également une très bonne spécificité (plus de 97 %). CONCLUSION: La présente étude de compétence démontre que la plupart des dosages sérologiques du SRAS-CoV-2 évalués dans des laboratoires sanitaires provinciaux ou les laboratoires hospitaliers du Canada possèdent une sensibilité acceptable et une excellente spécificité.

Comparison of SARS-CoV-2 spike antibody quantitative titer reporting using the World Health Organization International Standard Units by four commercial assays.

The accurate measurement of serological response to SARS-CoV-2 vaccination is needed to correlate responses with effective protective immunity. The World Health Organization (WHO) has created an international standard to allow harmonization of immune response assessment to an arbitrary unit across different commercial assays; however, the accuracy of reporting of SARS-CoV-2 spike antibody titers in international standard units (BAU or IU/mL) from commercial assays is not well studied. Here, we report the performance comparison of four quantitative commercial assays testing for SARS-CoV-2 spike immunoglobins using the WHO's international standard. Sera, EDTA-plasma and heparinized plasma collected from individuals who are vaccine naïve or received BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna) or ChAdOx1-S (Oxford-AstraZeneca) were tested using Abbott Architect AdviseDx SARS-CoV-2 IgG II, DiaSorin LIAISON SARS-CoV-2 TrimericS IgG, Roche Elecsys Anti-SARS-CoV-2 S and GenScript cPass SARS-CoV-2 surrogate virus neutralization assays. The sensitivities ranged from 90% to 100%, and specificities from 88% to 100%. These four assays had excellent agreement (0.79-0.93) and correlation (0.87-0.97); however, Passing-Bablok regression analysis indicated that data generated by these assays were not comparable. Our data suggests that natural SARS-CoV-2 infection elicited a greater antibody response compared to vaccines, evident by a significantly higher neutralizing antibody titer in unvaccinated individuals who seroconverted.