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Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections is challenging with current serology assays and is further complicated by the marked decrease in routine viral testing practices as viral transmission increased during Omicron. Here, we provide proof-of-principle that high-avidity anti-nucleocapsid (N) antibodies detects reinfections after a single infection with higher specificity (85%; 95% confidence interval [95% CI], 80%-90%) compared to anti-N antibody levels (72%; 95% CI, 66%-79%) in a vaccinated cohort. This method could be used to retroactively investigate the epidemiology and incremental long-term health consequences of SARS-CoV-2 reinfections., Competing Interests: Potential conflicts of interest . B. A. R. has received honoraria for participation in live meetings from Sanofi Pasteur France and Canada related to pertussis and RSV, but not for this work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: We recently reported a near disappearance of B. pertussis and a decline in anti-B. pertussis antibodies during the peak implementation of Coronavirus disease 2019 (COVID-19) non-pharmaceutical interventions (NPI) in 2021 in British Columbia (BC), Canada. During 2021-2023, incidence of reported B. pertussis cases remained low in BC at < 1/100,000 population. This study determined how serological evidence of B. pertussis changed after the gradual relaxation of NPI between 2021-2023., Methods: Randomly selected blood samples from school staff 25-51 years old (n = 65) were collected yearly between 2021-2023 in the Vancouver metropolitan area, BC, Canada, and tested for anti-pertussis toxin (PT) IgG levels. Serological evidence of B. pertussis infection (thereafter "seroconversion") was defined as a quantifiable anti-PT IgG levels in subjects with anti-PT IgG levels below lower limit of quantification in the preceding year or a > 4-fold increase in anti-PT IgG levels between two subsequent years. Samples were also tested for anti-diphtheria toxoid (DT) IgG, and similar seroconversion criteria were applied to exclude seroconversion due to vaccination with tetanus-diphtheria-acellular-pertussis (Tdap)., Results: Three subjects met seroconversion criteria for anti-PT IgG between 2021 and 2022 and 9 between 2022 and 2023, yielding a seroconversion rate of 4.6 /100 person-years and 14.9/100 person-years, P = 0.127, respectively. None of the subjects met the criteria for vaccination with Tdap. The geometric mean concentration of anti-PT IgG showed a statistically significant decrease in 2022 compared with 2021, 4.8 IU/mL IU/ml (95 % confidence interval [CI], 3.8-5.9) vs. 6.4 IU/ml (95 % CI, 4.9-8.2; p = 0.001), followed by a statistically significant increase in 2023 compared with 2022 6.5 IU/ml (95 % CI, 4.9-8.5) vs. 4.8 IU/ml (95 % CI, 3.8-5.9; p = 0.0006), respectively., Discussion: Serological evidence of B. pertussis increased between 2022 and 2023 despite low reported cases, which suggests that B. pertussis circulation resumed after relaxing of COVID-19 NPI., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BA received honoraria for participation in live meetings from Sanofi Pasteur France and Canada related to pertussis and RSV., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To determine the SARS-CoV-2 seroprevalence among school workers within the Greater Vancouver area, British Columbia, Canada, after the first Omicron wave., Design: Cross-sectional study by online questionnaire, with blood serology testing., Setting: Three main school districts (Vancouver, Richmond and Delta) in the Vancouver metropolitan area., Participants: Active school staff enrolled from January to April 2022, with serology testing between 27 January and 8 April 2022. Seroprevalence estimates were compared with data obtained from Canadian blood donors weighted over the same sampling period, age, sex and postal code distribution., Primary and Secondary Outcomes: SARS-CoV-2 nucleocapsid antibody testing results adjusted for test sensitivity and specificity, and regional variation across school districts using Bayesian models., Results: Of 1850 school staff enrolled, 65.8% (1214/1845) reported close contact with a COVID-19 case outside the household. Of those close contacts, 51.5% (625/1214) were a student and 54.9% (666/1214) were a coworker. Cumulative incidence of COVID-19 positive testing by self-reported nucleic acid or rapid antigen testing since the beginning of the pandemic was 15.8% (291/1845). In a representative sample of 1620 school staff who completed serology testing (87.6%), the adjusted seroprevalence was 26.5% (95% CrI 23.9% to 29.3%), compared with 32.4% (95% CrI 30.6% to 34.5%) among 7164 blood donors., Conclusion: Despite frequent COVID-19 exposures reported, SARS-CoV-2 seroprevalence among school staff in this setting remained no greater than the community reference group. Results are consistent with the premise that many infections were acquired outside the school setting, even with Omicron., Competing Interests: Competing interests: CO'R is an employee of the Vancouver School District, but the latter was not involved in the design, analysis, interpretation of data or the drafting of this manuscript. LifeLabs played no role in the study other than providing a service for the collection of blood samples., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Health jurisdictions have seen a near-disappearance of respiratory syncytial virus (RSV) during the first year of the coronavirus disease 2019 (COVID-19) pandemic. Over this corresponding period, we report a reduction in RSV antibody levels and live virus neutralization in sera from women of childbearing age and infants between May to June 2020 and February to June 2021, in British Columbia (BC), Canada. This supports that antibody immunity against RSV is relatively short-lived and that maintaining optimal antibody levels in infants requires repeated maternal viral exposure. Waning immunity may explain the interseasonal resurgence of RSV cases observed in BC and other countries., Competing Interests: Potential conflicts of interest . All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. PML serves on the British Columbia RSV Immunoprophylaxis Program, a publicly funded program under the British Columbia Ministry of Health and Provincial Health Services Authority. Other authors declare no relevant conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

SARS-CoV-2 anti-spike antibody concentrations and angiotensin converting enzyme-2 (ACE-2) inhibition have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. We tested the correlation of these measures among vaccinated participants, and examined subgroups based on duration since vaccination and vaccine dosing intervals. We analyzed 120 samples from two-dose mRNA vaccinees without previous COVID-19. We calculated Spearman correlation coefficients between wild-type viral neutralizing antibody titers and: anti-spike (total and IgG), anti-receptor-binding-domain (RBD), and anti-N-terminal-domain (NTD) antibodies; and ACE-2 binding by RBD. We performed three secondary analyses, dichotomizing samples by the first vaccination-to-blood collection interval, second vaccination-to-blood collection interval, and by the vaccine dosing interval (all groups divided by the median), and compared correlation coefficients (Fisher's Z test). Of 120 participants, 63 (53%) were women, 91 (76%) and 29 (24%) received BNT162b2 and mRNA-1273 vaccines, respectively. Overall, live viral neutralization was correlated with anti-spike total antibody (correlation coefficient = 0.80), anti-spike IgG (0.63), anti-RBD IgG (0.62), anti-NTD IgG (0.64), and RBD ACE2 binding (0.65). Samples with long (>158 days) first vaccination-to-blood collection and long (>71 days) second vaccination-to-blood collection intervals demonstrated higher correlation coefficients, compared with short groups. When comparing cases divided by short (≤39 days) versus long vaccine dosing intervals, only correlation with RBD-ACE-2 binding inhibition was higher in the long group. Among COVID-negative mRNA vaccinees, anti-spike antibody and ACE-2 inhibition concentrations are correlated with live viral neutralizing antibody titers. Correlation was stronger among samples collected at later durations from vaccination. IMPORTANCE Live viral neutralizing antibody titers are an accepted measure of immunity; however, testing procedures are labor-intensive. COVID-19 antibody and angiotensin converting enzyme-2 (ACE-2) levels have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. Using samples from 120 two-dose mRNA vaccinees without previous COVID-19, we found that live viral neutralization was correlated with COVID-19 antibody and ACE2 binding levels. When grouping samples by the time interval between vaccination and sample blood collection, samples collected over 158 days after the first vaccine and over 71 days from the second vaccine demonstrated stronger correlation between live viral neutralization titers and both antibody and ACE2 levels, in comparison to those collected earlier.

We prospectively studied SARS-CoV-2 transmission at schools in an era of variants of concern, offering all close contacts serial viral asymptomatic testing up to 14 days. From the 69 primary cases detected in schools, 392 close contacts were identified and offered asymptomatic testing. A total of 229 (58%) were close school contacts, and of these, 3 tested positive (1.3%), 2 of which were detected through asymptomatic testing. This is in contrast to the 117 household contacts, where 43 (37%) went on to become secondary cases. Routine asymptomatic testing of close contacts should be examined in the context of local testing rates, preventive measures, programmatic costs, and health impacts of asymptomatic transmission. IMPORTANCE There is concern that schools may be a setting where asymptomatic infections might result in significant "silent" transmission of SARS-CoV-2, particularly after the emergence of more transmissible variants of concern. After the programmatic implementation of a strategy of asymptomatic testing of close COVID-19 contacts as part of contact tracing in the school setting, the majority of the secondary cases were still found to have occurred in home or social contacts. However, for the 6.2% of secondary cases that occurred in close school contacts, the majority were detected through asymptomatic testing. The potential added yield of this approach needs to be considered within the overall setting, including consideration of the local epidemiology, ongoing goals of case and contact management, additional costs, logistical challenges for families, and possible health impacts of asymptomatic transmission.

The optimal dosing interval for severe acute respiratory syndrome coronavirus 2 vaccines remains controversial. In this prospective study, we compared serology results of paramedics vaccinated with mRNA vaccines at the recommended short (17-28 days) vs long (42-49 days) interval. We found that a long dosing interval resulted in higher spike, receptor binding domain, and spike N terminal domain antibody concentrations., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Immunization against Bordetella pertussis during pregnancy reduces morbidity from severe pertussis in young infants via trans-placental transfer of anti-B. pertussis Immunoglobulin G (IgG). Studies have reported a near disappearance of respiratory pathogens including B. pertussis following implementation of mitigation strategies to control Coronavirus disease 2019 (COVID-19). We explored how immunity against B. pertussis changed in women of childbearing-age through the COVID-19 pandemic., Methods: Paired blood samples from females of childbearing-age collected at the beginning (May-June 2020) and nearly one year into the COVID-19 pandemic (February-May 2021) in British Columbia (BC), Canada were tested for anti-B. pertussis IgG levels. To ascertain whether early-pandemic IgG levels in 2020 reflected levels in pregnant women early in gestation, 1st trimester sera collected from age-matched healthy pregnant women in 2018 and 2019 were tested for anti-B. pertussis IgG. Levels were compared by t tests. P-value of 0.05 was assigned and statistical significance was set as p < 0.016 using Bonferroni correction., Results: Annual provincial B. pertussis incidences per 100,000 in BC in 2020 (3/100,000) and 2021 (<1/100,000) approximated the lowest levels since 1990. In 2021 vs. 2020, anti-pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) IgG levels declined in women of childbearing-age: 6.8 IU/ml (95 %CI, 4.2-10.9) vs. 8.4 IU/ml (5.1-13.9; p = 0.004); 18.8 IU/ml (10.9-32.2) vs. 23.6 IU/ml (13.2-42.1; p < 0.001); and 37.1 IU/ml (18.1-75.9) vs. 47.2 IU/ml (24.8-89.9; p = 0.092), respectively. Although all values were slightly higher, anti-PT, FHA and PRN IgG levels in women of childbearing age did not significantly differ in 2020 compared with early-gestation pregnant women in 2018-2019, 8.4 IU/ml (95% CI, 5.1-13.9) vs. 5.4 IU/ml (95% CI, 3.8-7.7; p = 0.166), 23.6 IU/ml (95% CI, 13.2-42.1) vs. 20.1 IU/ml (95% CI, 13.4-30.2; p = 0.656), and 47.2 IU/ml (24.8-89.9) vs. 17.3 IU/ml (95% CI, 10.5-28.7; p = 0.021), respectively., Discussion: B. pertussis infections should be closely monitored during the relaxing of mitigation measures for COVID-19., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

While mRNA vaccines are highly efficacious against short-term COVID-19, long-term immunogenicity is less clear. We compared humoral immunogenicity between BNT162b2 and mRNA-1273 vaccines 6 months after the first vaccine dose, examining the wild-type strain and multiple Delta-variant lineages. Using samples from a prospective observational cohort study of adult paramedics, we included COVID-19-negative participants who received two BNT162b2 or mRNA-1273 vaccines, and provided a blood sample 170 to 190 days post first vaccine dose. We compared wild-type spike IgG concentrations using the Mann-Whitney U test. We also compared secondary outcomes of: receptor binding domain (RBD) wild-type antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to spike proteins from the wild-type strain and five Delta-variant lineages. We included 571 adults: 475 BNT162b2 (83%) and 96 mRNA-1273 (17%) vaccinees, with a mean age of 39 (SD = 10) and 43 (SD = 10) years, respectively. Spike IgG antibody concentrations were significantly higher ( P  < 0.0001) for those who received mRNA-1273 (GM 601 BAU/mL [GSD 2.05]) versus BNT162b2 (GM 375 BAU/mL [GSD 2.33) vaccines. Results of RBD antibody comparisons ( P  < 0.0001), and inhibition of ACE-2 binding to the wild-type strain and all tested Delta lineages (all P  < 0.0001), were consistent. Adults who received two doses of mRNA-1273 vaccines demonstrated improved wild-type and Delta variant-specific humoral immunity outcomes at 6 months compared with those who received two doses of the BNT162b2 vaccine. IMPORTANCE The BNT162b2 and mRNA-1273 mRNA SARS-CoV-2 vaccines have demonstrated high efficacy for preventing short-term COVID-19. However, comparative long-term effectiveness is unclear, especially pertaining to the Delta variant. We tested virus-specific antibody responses 6 months after the first vaccine dose and compared individuals who received the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines. We found that individuals who received the mRNA-1273 vaccine demonstrated superior serological markers at 6 months in comparison with those who received the BNT162b2 vaccine.

Background: The purpose of this study was to explore factors associated with COVID-19 vaccine intentions among school staff as high vaccine uptake is essential to ensure schools return to normal activities., Methods: Staff (e.g., teachers, administrators, student support workers) from three urban school districts in the Greater Vancouver Area of British Columbia, Canada completed a survey between February and June 2021 ( n = 2,393) on COVID-19 vaccine intentions and perceptions (i.e., acceptance of routine vaccines, benefits and risks of vaccination, susceptibility to, and severity of COVID-19, recommendation by authority figures, information mistrust and conspiracy beliefs) as part of a COVID-19 seroprevalence study. Confirmatory factor analysis followed by multiple logistic regression models adjusting for relevant covariates were used to identify vaccine perceptions uniquely associated with (a) intention to get the COVID-19 vaccine ( intention ), and (b) intention to get vaccinated right away ( urgency )., Results: In total, 95.4% of participants of the seroprevalence study completed the vaccine questionnaire, corresponding to 17.7% of the target population. Vaccine intention was associated with staff who valued expert recommendations (AOR = 10.5, 95% CI = 7.39-14.90) accepted routine vaccines (AOR = 1.94, 95% CI = 1.26-2.98) and perceived higher benefits (AOR = 1.29, 95% CI = 1.01-1.65) and lower safety risks of vaccination (AOR = 0.40, 95% CI = 0.29-0.54). Comparable associations were found with vaccine urgency . Perceived susceptibility to the COVID-19 virus was uniquely associated with vaccine urgency (AOR = 1.30, 95% CI = 1.05-1.61). A significant interaction effect ( p = 0.01) revealed that staff who expressed mistrust in COVID-19 information intended to get vaccinated only if they also perceived high benefits of vaccination., Conclusions: Education about the risks and benefits of COVID-19 vaccines from a trusted source had the strongest relationship with vaccine intentions among this occupational group. Notably, those who expressed mistrust in information still intended to get vaccinated if they also perceived strong benefits of the vaccine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Watts, Hutchison, Bettinger, Gadermann, Oberle, Oberlander, Goldfarb, Lavoie and Mâsse.)

Objectives: Few studies reported COVID-19 cases in schools during the 2020/21 academic year in a setting of uninterrupted in-person schooling. The main objective was to determine the SARS-CoV-2 seroprevalence among school staff in Vancouver public schools., Design: Cumulative incident COVID-19 cases among all students and school staff based on public health data, with an embedded cross-sectional serosurvey among a school staff sample that was compared to period, age, sex and geographical location-weighted data from blood donors., Setting: Vancouver School District (British Columbia, Canada) from kindergarten to grade 12., Participants: Active school staff enrolled from 3 February to 23 April 2021 with serology testing from 10 February to 15 May 2021., Main Outcome Measures: SARS-CoV-2 seroprevalence among school staff, based on spike (S)-based (unvaccinated staff) or N-based serology testing (vaccinated staff)., Results: Public health data showed the cumulative incidence of COVID-19 among students attending in-person was 9.8 per 1000 students (n=47 280), and 13 per 1000 among school staff (n=7071). In a representative sample of 1689 school staff, 78.2% had classroom responsibilities, and spent a median of 17.6 hours in class per week (IQR: 5.0-25 hours). Although 21.5% (363/1686) of surveyed staff self-reported close contact with a COVID-19 case outside of their household (16.5% contacts were school-based), 5 cases likely acquired the infection at school based on viral testing. Sensitivity/Specificity-adjusted seroprevalence in 1556/1689 staff (92.1%) was 2.3% (95% CI: 1.6% to 3.2%), comparable to a sex, age, date and residency area-weighted seroprevalence of 2.6% (95% CI: 2.2% to 3.1%) among 5417 blood donors., Conclusion: Seroprevalence among staff was comparable to a reference group of blood donors from the same community. These data show that in-person schooling could be safely maintained during the 2020/21 school year with mitigation measures, in a large school district in Vancouver, Canada., Competing Interests: Competing interests: CO'R is an employee of the Vancouver School District, but the District was not involved in the design, analysis, interpretation of the data or the drafting of this manuscript; MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines. All funds have been paid to his institute, and he has not received any personal payments; the authors declare no relevant conflicts of interest. LifeLabs and Dynacare played no role in the study other than providing a service for the collection of blood samples., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

SARS-CoV-2 seroprevalence studies may be complicated by vaccination efforts. It is important to characterize the ability of serology methods to correctly distinguish prior infection from postvaccination seroreactivity. We report the performance of the Meso Scale Discovery (MSD) V-PLEX COVID-19 Coronavirus Panel 2 IgG assay. Using serum samples from a prospective cohort of paramedics, we calculated the performance of the V-PLEX nucleocapsid ("N") assay to classify prior SARS-CoV-2 infections, defined as a (i) history of a positive SARS-CoV-2 PCR test or (ii) positive serology results using the Roche Elecsys total nucleocapsid anti-SARS-Cov-2 assay. We calculated sensitivity and specificity at the optimal threshold (defined by the highest Youden index). We compared subgroups based on vaccination status, and between models that excluded prior infections 3 to 12 months before sample collection. Of 1119 participants, 914 (81.7%) were vaccinated and 60 (5.4%) had evidence of a preceding SARS-CoV-2 infection. Overall and within vaccinated and unvaccinated subgroups, the optimal thresholds were 828 AU/mL, 827 AU/mL, and 1324 AU/mL; with sensitivities of 0.95 (95% CI: 0.94 to 0.96), 0.95 (0.94 to 0.96), 0.94 (0.92 to 0.96) and specificities of 0.88 (0.86 to 0.90), 0.87 (0.85 to 0.89), and 0.94 (0.89 to 0.98), respectively. N-assay specificity was significantly better in unvaccinated (versus vaccinated) individuals ( P = 0.005). Overall optimal thresholds based on the AUC values were higher for samples from unvaccinated participants, especially when examining infections within the preceding 9 months (5855 versus 1704 AU/mL). Overall, V-PLEX nucleocapsid assay cutoff values were higher among unvaccinated individuals. Specificity was also significantly higher among unvaccinated individuals. Different thresholds were required to achieve optimal test performance, especially for detecting SARS-CoV-2 infections within the preceding 9 months. IMPORTANCE Among a cohort of adult paramedics in Canada, we investigated the performance of nucleocapsid (N) antibody detection (measured with a V-PLEX assay) to identify previous COVID-19 infections and compared differences among vaccinated and unvaccinated. Our data indicate that vaccinated and unvaccinated groups require different thresholds to achieve optimal test performance, especially for detecting COVID-19 within the preceding 9 months. Overall, specificity was significantly higher among unvaccinated, compared to vaccinated individuals.

Preexisting cross-reactivity to SARS-CoV-2 occurs in the absence of prior viral exposure. However, this has been difficult to quantify at the population level due to a lack of reliably defined seroreactivity thresholds. Using an orthogonal antibody testing approach, we estimated that about 0.6% of nontriaged adults from the greater Vancouver, Canada, area between May 17 and June 19, 2020, showed clear evidence of a prior SARS-CoV-2 infection, after adjusting for false-positive and false-negative test results. Using a highly sensitive multiplex assay and positive/negative thresholds established in infants in whom maternal antibodies have waned, we determined that more than 90% of uninfected adults showed antibody reactivity against the spike protein, receptor-binding domain (RBD), N-terminal domain (NTD), or the nucleocapsid (N) protein from SARS-CoV-2. This seroreactivity was evenly distributed across age and sex, correlated with circulating coronaviruses' reactivity, and was partially outcompeted by soluble circulating coronaviruses' spike. Using a custom SARS-CoV-2 peptide mapping array, we found that this antibody reactivity broadly mapped to spike and to conserved nonstructural viral proteins. We conclude that most adults display preexisting antibody cross-reactivity against SARS-CoV-2, which further supports investigation of how this may impact the clinical severity of COVID-19 or SARS-CoV-2 vaccine responses.

Studies have linked respiratory syncytial virus (RSV) antibody-mediated phagocytosis and complement deposition to severe RSV infection in humans. This study shows waning of these antibody functions in women of childbearing age in 2020-2021 during the implementation of COVID-19 mitigation measures, in absence of RSV circulation. These functions could be explored as correlates of protection against severe RSV disease. [ABSTRACT FROM AUTHOR]

Nucleocapsid serological assay sensitivity to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among vaccinees and for Omicron cases is unclear. In this prospective study, the Elecsys nucleocapsid assay was 89% sensitive in identifying SARS-CoV-2 infections 14–607 days pre–blood collection. Sensitivity was similar when comparing by vaccination status, and in Omicron (vs pre-Omicron) cases. [ABSTRACT FROM AUTHOR]

The optimal dosing interval for severe acute respiratory syndrome coronavirus 2 vaccines remains controversial. In this prospective study, we compared serology results of paramedics vaccinated with mRNA vaccines at the recommended short (17–28 days) vs long (42–49 days) interval. We found that a long dosing interval resulted in higher spike, receptor binding domain, and spike N terminal domain antibody concentrations. [ABSTRACT FROM AUTHOR]