Declining Levels of Neutralizing Antibodies to SARS-CoV-2 Omicron Variants Are Enhanced by Hybrid Immunity and Original/Omicron Bivalent Vaccination.

We determined neutralizing antibody levels to the ancestral Wuhan SARS-CoV-2 strain and three Omicron variants, namely BA.5, XBB.1.5, and EG.5, in a heavily vaccinated cohort of 178 adults 15-19 months after the initial vaccine series and prospectively after 4 months. Although all participants had detectable neutralizing antibodies to Wuhan, the proportion with detectable neutralizing antibodies to the Omicron variants was decreased, and the levels were lower. Individuals with hybrid immunity at the baseline visit and those receiving the Original/Omicron bivalent vaccine between the two sampling times demonstrated increased neutralizing antibodies to all strains. Both a higher baseline neutralizing antibody titer to Omicron BA.5 and hybrid immunity were associated with protection against a breakthrough SARS-CoV-2 infection during a 4-month period of follow up during the Omicron BA.5 wave. Neither were associated with protection from a breakthrough infection at 10 months follow up. Receipt of an Original/Omicron BA.4/5 vaccine was associated with protection from a breakthrough infection at both 4 and 10 months follow up. This work demonstrates neutralizing antibody escape with the emerging Omicron variants and supports the use of additional vaccine doses with components that match circulating SARS-CoV-2 variants. A threshold value for neutralizing antibodies for protection against reinfection cannot be determined.

Decentralized study of COVID Vaccine Antibody Response (STOPCoV): Results of a participant satisfaction survey.

The Covid-19 pandemic required many clinical trials to adopt a decentralized framework to continue research activities during lock down restrictions. The STOPCoV study was designed to assess the safety and efficacy of Covid-19 vaccines in those aged 70 and above compared to those aged 30-50 years of age. In this sub-study we aimed to determine participant satisfaction for the decentralized processes, accessing the study website and collecting and submitting study specimens. The satisfaction survey was based on a Likert scale developed by a team of three investigators. Overall, there were 42 questions for respondents to answer. The invitation to participate with a link to the survey was emailed to 1253 active participants near the mid-way point of the main STOPCoV trial (April 2022). The results were collated and answers were compared between the two age cohorts. Overall, 70% (83% older, 54% younger cohort, no difference by sex) responded to the survey. The overall feedback was positive with over 90% of respondents answering that the website was easy to use. Despite the age gap, both the older cohort and younger cohort reported ease of performing study activities through a personal electronic device. Only 30% of the participants had previously participated in a clinical trial, however over 90% agreed that they would be willing to participate in future clinical research. Some difficulties were noted in refreshing the browser whenever updates to the website were made. The feedback attained will be used to improve current processes and procedures of the STOPCoV trial as well as share learning experiences to inform future fully decentralized research studies.

Predictors of Breakthrough SARS-CoV-2 Infection after Vaccination.

The initial two-dose vaccine series and subsequent booster vaccine doses have been effective in modulating SARS-CoV-2 disease severity and death but do not completely prevent infection. The correlates of infection despite vaccination continue to be under investigation. In this prospective decentralized study (n = 1286) comparing antibody responses in an older- (≥70 years) to a younger-aged cohort (aged 30-50 years), we explored the correlates of breakthrough infection in 983 eligible subjects. Participants self-reported data on initial vaccine series, subsequent booster doses and COVID-19 infections in an online portal and provided self-collected dried blood spots for antibody testing by ELISA. Multivariable survival analysis explored the correlates of breakthrough infection. An association between higher antibody levels and protection from breakthrough infection observed during the Delta and Omicron BA.1/2 waves of infection no longer existed during the Omicron BA.4/5 wave. The older-aged cohort was less likely to have a breakthrough infection at all time-points. Receipt of an original/Omicron vaccine and the presence of hybrid immunity were associated with protection of infection during the later Omicron BA.4/5 and XBB waves. We were unable to determine a threshold antibody to define protection from infection or to guide vaccine booster schedules.

COVID-19 breakthrough infections in vaccinated participants of the Safety and Efficacy of Preventative COVID Vaccines sub-study.

BACKGROUND: The rate of breakthrough infection in vaccinated Ontarians during the Omicron wave is unknown. METHODS: Active participants of the Safety and Efficacy of Preventative COVID Vaccines (STOPCoV) study (892 ≥age 70 years and 369 aged 30-50 years) were invited to participate in a sub-study evaluating breakthrough COVID-19 infection. Self-administered rapid antigen tests (RAT) were reported twice weekly and symptom questionnaires weekly for 6 weeks. The primary outcome was the proportion reporting a positive RAT. RESULTS: A total of 806 e-consented, and 727 (90%) completed ≥1 RAT, with total 7,116 RATs completed between January 28 and March 29, 2022. Twenty out of twenty-five participants with a positive RAT had a booster vaccine prior to the positive test. All cases were mild, none requiring hospitalization. Nineteen had positive dried blood spot analysis for IgG antibody to the receptor binding domain (RBD) prior to the positive RAT. The mean normalized IgG ratio to RBD was 1.22 (SD 0.29) for younger and 0.98 (SD 0.44) for older participants, values similar to corresponding ratios for those without positive RATs and those in the main cohort. One hundred and five participants reported one and 96 reported ≥2 possible COVID-19 symptoms despite negative RATs. The false negative RAT was low (4% to 6.6 %) compared with subsequent positive nucleoprotein antibody. CONCLUSIONS: Positive RAT for COVID-19 was infrequent (3.4%). We were unable to determine a protective antibody level against breakthrough infection. Our findings can inform public health COVID-19 restrictions guidelines. Our decentralized study provides a model for rapid institution of new questions during a pandemic.

HISTORIQUE: On ne connaît pas le taux d'infections postvaccinales pendant la vague Omicron chez les Ontariens vaccinés. MÉTHODOLOGIE: Les participants actifs de l'étude Safety and Efficacy of Preventative COVID Vaccines (STOPCoV; 892 de 79 ans ou plus et 369 de 30 à 50 ans) ont été invités à prendre part à une sous-étude évaluant les infections postvaccinales causées par la COVID-19. Les résultats des tests d'antigène rapides (TAR) autoadministrés ont été transmis deux fois par semaine et le questionnaire sur les symptômes, toutes les semaines pendant six semaines. Les résultats primaires correspondaient à la proportion ayant déclaré des TAR positifs. RÉSULTATS: Au total, 806 ont consenti par voie électronique et 727 (90 %) ont effectué au moins un TAR, pour un total de 7 116 TAR effectués entre le 28 janvier et le 29 mars 2022. Ainsi, 21 des 25 participants ayant obtenu un résultat positif au TAR avaient reçu une dose de rappel auparavant. Tous les cas étaient légers, et aucun n'a dû être hospitalisé. Dix-neuf ont obtenu une analyse des gouttes de sang séché positives aux anticorps des IgG du domaine de liaison des récepteurs (RBD) avant le résultat positif du TAR. L'écart-type moyen du ratio d'IgG normalisé au RBD était de 1,22 (ÉT = 0,29) pour les participants plus jeunes, et de 0,98 (ÉT = 0,44) chez les participants plus âgés, les valeurs étaient semblables aux ratios correspondants pour ceux dont le TAR n'était pas positif et ceux de la cohorte principale. Au total, 105 participants ont déclaré un symptôme possible de COVID-19 et 96 en ont déclaré au moins deux, malgré des résultats négatifs au TAR. Le taux de TAR faussement négatifs était faible (4 % à 6,6 %) par rapport à l'anticorps nucléoprotéique positif subséquent. CONCLUSIONS: Les résultats positifs des TAR à la COVID-19 étaient peu courants (3,4 %). Les chercheurs n'ont pas été en mesure de déterminer le taux d'anticorps protecteurs contre l'infection postvaccinale. Ces résultats peuvent éclairer les directives sur les restrictions sanitaires liées à la COVID-19. La présente étude décentralisée fournit un modèle pour l'adoption rapide de nouvelles questions pendant une pandémie.