Evaluation of anti-nucleocapsid level variation to assess SARS-CoV-2 seroprevalence in a vaccinated population.

BACKGROUND: Serosurveys have been key to public health decision-making since the beginning of the SARS-CoV-2 pandemic. However, several studies have uncovered that vaccination blunts the anti-nucleocapsid (N) response to a subsequent infection, which hinders the ability of serologic assays (including commercial ones) to detect recent infections. We therefore developed a new analytical approach to increase the sensitivity of detection of infection in vaccinated individuals. METHODS: Two samples were obtained from 248 SARS-CoV-2-positive (PCR-confirmed), vaccinated donors: one before the infection (reference sample) and one after (test sample). All samples were tested using an in-house, anti-N enzyme-linked immunosorbent assay (ELISA) which had a sensitivity of 98.1% before the mass vaccination campaign. Instead of applying a seropositivity threshold based on a single absorbance value (i.e. conventional approach), seropositivity was determined based on the ratio between the anti-N absorbance of the test and reference samples. RESULTS: The sensitivity of the new approach to detect infection in vaccinated individuals was 95.2% using a cut-off of 1.5 for the anti-N ratio, whereas that of the conventional approach was 63.3%. CONCLUSION: The new analytical approach described herein captured a significantly greater proportion of vaccinated individuals with a known history of SARS-CoV-2 infection than the conventional approach used in most serosurveys.

Cohort profile: A Québec-based plasma donor biobank to study COVID-19 immunity (PlasCoV).

PURPOSE: The long-term humoral immunity to COVID-19 is not well understood owing to the continuous emergence of new variants of concern, the evolving vaccine-induced and infection-induced immunity, and the limited duration of follow-up in previous studies. As the sole blood service in Québec (Canada), Héma-Québec established a COVID-19-focused biobank ('PlasCoV') in April 2021. PARTICIPANTS: As of January 2022, the biobank included 86 483 plasma samples from 15 502 regular donors (age range=18-84 years, females=49.7%), for an average of 5.6 donations per donor. Nearly two-thirds (65.6%) of biobank donors made at least two donations, with many donors having provided samples prevaccination and postvaccination (3061 (19.7%)) or preinfection and postinfection (131 (0.8%)), thus allowing for longitudinal studies on vaccine-induced and infection-induced immunity. FINDINGS TO DATE: A study that used PlasCoV samples revealed that previously infected individuals who received a single dose of the BNT162b2 COVID-19 vaccine exhibited the strongest immune response. By contrast, SARS-CoV-2-naïve individuals required two vaccine doses to produce a maximal immune response. Furthermore, the results of a four-phase seroprevalence study indicated that the antinucleocapsid (N) response wanes rapidly, so that up to one-third of previously infected donors were seronegative for anti-N. FUTURE PLANS: Donations from individuals who consented to participate before 1 October 2022 will be collected up until 31 March 2023. This plasma biobank will facilitate the conduct of longitudinal studies on COVID-19 immunity, thus helping to provide valuable insights into the anti-SARS-CoV-2 immune response and its persistence, and the effects of vaccination and variants on the specificity of the anti-SARS-CoV-2 immune response.

Active seeking of post-donation information to minimize a potential threat to transfusion safety: A pilot programme in the context of the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: Early in the pandemic, the transmissibility of coronavirus disease-19 (COVID-19) by transfusion was unknown. We piloted a systematic, post-donation outreach programme to contact blood donors and inquired about symptoms post-donation. MATERIALS AND METHODS: Persons who donated on on May 1 and 2, 2020 were contacted 3 days post-donation, by phone to assess COVID-19-related symptoms. Half of the donors were administered a short questionnaire, consisting of only three questions. Others were questioned using a longer, more specific questionnaire. If symptoms were reported, products were quarantined until donors were contacted again by a trained nurse who more thoroughly assessed the likelihood of COVID-19. Blood products were withdrawn if symptoms indicative of COVID-19 were identified. RESULTS: Of 654 donors, 609 (93.1%) were successfully contacted. Of 310 donors who answered the short questionnaire and 299 who answered the long questionnaire, 19 (6.1%) and 8 (2.7%) had one or more symptoms, respectively. Based on the nurses' assessment, two donations (0.3%) had to be withdrawn. CONCLUSION: These results suggest that actively seeking post-donation information might be feasible to mitigate emerging, unqualified transfusion risks.

Seroprevalence of SARS-CoV-2 antibodies among blood donors in Québec: an update from a serial cross-sectional study.

OBJECTIVES: We previously estimated the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies following the first pandemic wave at 2.23% in Québec, Canada. Following the much bigger second wave in fall 2020 and early 2021, we estimated the seroprevalence of anti-SARS-CoV-2 in Québec during the first months of 2021. METHODS: Blood samples from regular, asymptomatic (for ≥ 14 days) donors were collected between January 25, 2021 and March 11, 2021. Anti-SARS-CoV-2 seropositivity was assessed using an enzyme-linked immunosorbent assay that captures antibodies directed against the receptor binding domain of the SARS-CoV-2 spike (and hence cannot discriminate between infection- and vaccine-induced seropositivity). Seroprevalence estimates were adjusted for regional distribution, age, and sex. RESULTS: Samples from 7924 eligible donors were analyzed, including 620 (7.8%) vaccinated donors and 7046 (88.9%) unvaccinated donors (vaccination status unknown for 258 (3.3%) donors). Overall, median age was 51 years; 46.4% of donors were female. The adjusted seroprevalence was 10.5% (95% CI = 9.7-11.3) in the unvaccinated population and 14.7% (95% CI = 13.8-15.6) in the overall population. Seroprevalence gradually decreased with age and was higher among donors who self-identified as having a racial/ethnic background other than white, both in the overall and in the unvaccinated populations. CONCLUSION: The seroprevalence of SARS-CoV-2 antibodies significantly increased in Québec since spring 2020, with younger persons and ethnic minorities being disproportionately affected. When compared with the cumulative incidence rate reported by public health authorities (i.e., 3.3% as of March 11, 2021), these results suggest that a substantial proportion of infections remain undetected despite improvements in access to COVID-19 testing.

RéSUMé: OBJECTIFS: Lors d'une première étude, nous avons estimé la séroprévalence des anticorps contre le syndrome respiratoire aigu sévère coronavirus 2 (SRAS-CoV-2) après la première vague pandémique à 2,23 % au Québec, Canada. Cette seconde étude estime la séroprévalence de l'anti-SRAS-CoV-2 au Québec lors de la deuxième vague pandémique. MéTHODES: Des échantillons de donneurs de sang asymptomatiques (≥ 14 jours) ont été prélevés entre le 25 janvier et le 11 mars 2021. La séropositivité a été évaluée à l'aide d'un dosage immuno-enzymatique qui capture les anticorps dirigés contre la protéine Spike du récepteur de domaine de liaison du SARS-CoV-2 (et ne peut donc distinguer l'immunité induite par l'infection et la vaccination). La séroprévalence a été ajustée en fonction de l'âge et du sexe par région. RéSULTATS: Des échantillons de 7 924 donneurs ont été analysés, dont 620 (7,8 %) étaient vaccinés et 7 046 (88,9 %) étaient non vaccinés (statut vaccinal inconnu pour 258 (3,3 %) donneurs). Dans l'ensemble, l'âge médian était de 51 ans et 46,4 % des donneurs étaient des femmes. La séroprévalence ajustée était de 10,5 % (IC 95 % = 9,7 à 11,3) dans la population non vaccinée et de 14,7 % (IC 95 % = 13,8 à 15,6) dans la population globale. La séroprévalence diminuait progressivement avec l'âge et était plus élevée chez les donneurs d'origine ethnique autre que blanche. CONCLUSION: La séroprévalence anti-SRAS-CoV-2 a considérablement augmenté au Québec depuis le printemps 2020, les personnes plus jeunes et les minorités ethniques étant plus touchées. Comparés au taux d'incidence cumulatif signalé par la santé publique (c.-à-d. 3,3 % au 11 mars 2021), ces résultats suggèrent qu'une proportion importante d'infections reste non détectée.