Phase I randomized, observer-blinded, placebo-controlled study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B.

Access to vaccines against SARS-CoV-2 virus was limited in poor countries during the COVID-19 pandemic. Therefore, a low-cost mRNA vaccine, PTX-COVID19-B, was produced and evaluated in a Phase 1 trial. PTX-COVID19-B encodes Spike protein D614G variant without the proline-proline (986-987) mutation present in other COVID-19 vaccines. The aim of the study was to evaluate safety, tolerability, and immunogenicity of PTX-COVID19-B vaccine in healthy seronegative adults 18-64 years old. The trial design was observer-blinded, randomized, placebo-controlled, and tested ascending doses of 16-µg, 40-µg, or 100-µg in a total of 60 subjects who received two intramuscular doses, 4 weeks apart. Participants were monitored for solicited and unsolicited adverse events after vaccination and were provided with a Diary Card and thermometer to report any reactogenicity during the trial. Blood samples were collected on baseline, days 8, 28, 42, 90, and 180 for serum analysis of total IgG anti-receptor binding domain (RBD)/Spike titers by ELISA, and neutralizing antibody titers by pseudovirus assay. Titers in BAU/mL were reported as geometric mean and 95% CI per cohort. After vaccination, few solicited adverse events were observed and were mild to moderate and self-resolved within 48 h. The most common solicited local and systemic adverse event was pain at the injection site, and headache, respectively. Seroconversion was observed in all vaccinated participants, who showed high antibody titers against RBD, Spike, and neutralizing activity against the Wuhan strain. Neutralizing antibody titers were also detected against Alpha, Beta, and Delta variants of concerns in a dose dependent manner. All tested doses of PTX-COVID19-B were safe, well-tolerated, and provided a strong immunogenicity response. The 40-µg dose showed fewer adverse reactions than the 100-µg dose, and therefore was selected for a Phase 2 trial, which is currently ongoing.Clinical Trial Registration number: NCT04765436 (21/02/2021). ( https://clinicaltrials.gov/ct2/show/NCT04765436 ).

Diminished Neutralization Capacity of SARS-CoV-2 Omicron BA.1 in Donor Plasma Collected from January to March 2021.

The 50% plaque reduction neutralization assay (PRNT50) has been previously used to assess the neutralization capacity of donor plasma against wild-type and variant of concern (VOC) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging data suggest that plasma with an anti-SARS-CoV-2 level of ≥2 × 104 binding antibody units/mL (BAU/mL) protects against SARS-CoV-2 Omicron BA.1 infection. Specimens were collected using a cross-sectional random sampling approach. For PRNT50 studies, 63 previously analyzed specimens by PRNT50 versus SARS-CoV-2 wild-type, Alpha, Beta, Gamma, and Delta were analyzed by PRNT50 versus Omicron BA.1. The 63 specimens plus 4,390 specimens (randomly sampled regardless of serological evidence of infection) were also tested using the Abbott SARS-CoV-2 IgG II Quant assay (anti-spike [S]; Abbott, Chicago, IL, USA; Abbott Quant assay). In the vaccinated group, the percentages of specimens with any measurable PRNT50 versus wild-type or VOC were wild type (21/25 [84%]), Alpha (19/25 [76%]), Beta (18/25 [72%]), Gamma (13/25 [52%]), Delta (19/25 [76%]), and Omicron BA.1 (9/25 [36%]). In the unvaccinated group, the percentages of specimens with any measurable PRNT50 versus wild type or VOC were wild-type SARS-CoV-2 (16/39 [41%]), Alpha (16/39 [41%]), Beta (10/39 [26%]), Gamma (9/39 [23%]), Delta (16/39 [41%]), and Omicron BA.1 (0/39) (Fisher's exact tests, vaccinated versus unvaccinated for each variant, P < 0.05). None of the 4,453 specimens tested by the Abbott Quant assay had a binding capacity of ≥2 × 104 BAU/mL. Vaccinated donors were more likely than unvaccinated donors to neutralize Omicron when assessed by a PRNT50 assay. IMPORTANCE SARS-CoV-2 Omicron emergence occurred in Canada during the period from November 2021 to January 2022. This study assessed the ability of donor plasma collected earlier (January to March 2021) to generate any neutralizing capacity against Omicron BA.1 SARS-CoV-2. Vaccinated individuals, regardless of infection status, were more likely to neutralize Omicron BA.1 than unvaccinated individuals. This study then used a semiquantitative binding antibody assay to screen a larger number of specimens (4,453) for individual specimens that might have high-titer neutralizing capacity against Omicron BA.1. None of the 4,453 specimens tested by the semiquantitative SARS-CoV-2 assay had a binding capacity suggestive of a high-titer neutralizing capacity against Omicron BA.1. These data do not imply that Canadians lacked immunity to Omicron BA.1 during the study period. Immunity to SARS-CoV-2 is complex, and there is still no wide consensus on correlation of protection to SARS-CoV-2.

COVID-19 vaccine antibody responses in community-dwelling adults to 48 weeks post primary vaccine series.

We report a decentralized prospective cohort study of self-reported adverse events and antibody responses to COVID vaccines derived from dried blood spots. Data are presented for 911 older (aged >70 years) and 375 younger (30-50 years) recruits to 48 weeks after the primary vaccine series. After a single vaccine, 83% younger and 45% older participants had overall seropositivity (p < 0.0001) increasing to 100/98% with the second dose, respectively (p = 0.084). A cancer diagnosis (p = 0.009), no mRNA-1273 vaccine doses (p <0 .0001), and older age (p <0 .0001) predicted lower responses. Antibody levels declined in both cohorts at 12 and 24 weeks increasing with booster doses. At 48 weeks, for participants with 3 vaccine doses, the median antibody levels were higher in the older cohort (p = 0.04) with any dose of mRNA-1273 (p <0 .0001) and with COVID infection (p <0 .001). The vaccines were well tolerated. Breakthrough COVID infections were uncommon (16% older cohort, 29% younger cohort; p < 0.0001) and mild.

Determining the Longitudinal Serologic Response to COVID-19 Vaccination in the Chronic Kidney Disease Population: A Clinical Research Protocol.

Background: People living with chronic kidney disease (CKD) have been disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic, including higher rates of infection, hospitalization, and death. Data on responsiveness to COVID-19 vaccination strategies and immunogenicity are limited, yet required to inform vaccination strategies in this at-risk population. Objective: The objective of this study is to characterize the longitudinal serologic response to COVID-19 vaccination. Design: This is a prospective observational cohort study. Setting: Participating outpatient kidney programs within Ontario and British Columbia. Patients: Up to 2500 participants with CKD G3b-5D receiving COVID-19 vaccination, including participants receiving dialysis and kidney transplant recipients (CKD G1T-5T). Measurements: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies (anti-spike, anti-receptor binding domain, anti-nucleocapsid) will be detected by ELISA (enzyme-linked immunosorbent assay) from serum or dried blood spot testing. In a subset of participants, neutralizing antibodies against novel variants of concern will be evaluated. Peripheral blood mononuclear cells will be collected for exploratory immune profiling of SARS-CoV-2 specific cellular immunity. Methods: Participants will be recruited prior to or following any COVID-19 vaccine dose and have blood sampled for serological testing at multiple timepoints: 1, 3, 6, 9, and 12 months post vaccination. When possible, samples will be collected prior to a dose or booster. Participants will remain in the study for at least 1 year following their last COVID-19 vaccine dose. Strengths and limitations: The adaptive design of this study allows for planned modification based on emerging evidence or rapid changes in public health policy surrounding vaccination. Limitations include incomplete earlier timepoints for blood collection due to rapid vaccination of the population. Conclusions: This large multicenter serologic study of participants living with kidney disease will generate data on the kinetics of SARS-CoV-2 immune response to vaccination across the spectrum of CKD, providing insights into the amplitude and duration of immunity conferred by COVID-19 vaccination and allowing for characterization of factors associated with immune response. The results of this study may be used to inform immunization guidelines and public health recommendations for the 4 million Canadians living with CKD.

Contexte: Les personnes atteintes d'insuffisance rénale chronique (IRC) ont été touchées de façon disproportionnée par la pandémie de COVID-19 ayant notamment présenté des taux plus élevés d'infection, d'hospitalisation et de décès. Les données sur la réactivité aux stratégies de vaccination de la COVID-19 et à l'immunogénicité sont limitées, mais elles sont nécessaires pour développer des stratégies de vaccination dans cette population à risque. Objectif: Caractériser la réponse sérologique longitudinale à la vaccination contre la COVID-19. Conception: Étude de cohorte observationnelle prospective. Cadre: Les programmes ambulatoires de santé rénale participants en Ontario et en Colombie-Britannique. Sujets: Jusqu'à 2 500 personnes atteintes d'IRC G3B-5D recevant un vaccin contre la COVID-19, y compris des patients suivant des traitements de dialyse et des receveurs d'une greffe rénale (IRC G1T-5T). Mesures: Les anticorps IgG anti-SARS-CoV-2 (anti-spike, anti-domaine de liaison au récepteur, anti-nucléocapside) seront détectés par ELISA à partir du sérum ou de taches de sang séché. Un sous-groupe de sujets participera également à l'évaluation d'anticorps neutralisants dirigés contre les nouveaux variants préoccupants. Des cellules mononuclées de sang périphérique seront prélevées pour établir un profil immunitaire exploratoire de l'immunité cellulaire spécifique au SARS-CoV-2. Méthodologie: Les sujets seront recrutés avant ou après toute dose du vaccin contre la COVID-19 et se soumettront à des prélèvements sanguins pour les tests sérologiques à 1, 3, 6, 9 et 12 mois post-vaccination. Lorsque possible, des échantillons seront prélevés avant l'administration d'une dose ou d'un rappel. Les sujets demeureront dans l'étude pendant au moins un an après leur dernière dose de vaccin contre la COVID-19. Points forts et limites: La conception adaptative de l'étude permet d'apporter des modifications planifiées fondées sur de nouvelles données ou des changements rapides dans les politiques de santé publique entourant la vaccination. Les résultats sont limités par l'absence de certains prélèvements sanguins antérieurs (point temporels) en raison de la vaccination rapide de la population. Conclusion: Cette vaste étude sérologique multicentrique menée auprès de personnes atteintes de néphropathie fournira des données sur la cinétique de la réponse immunitaire à la vaccination contre le SARS-CoV-2 dans l'ensemble du spectre de l'IRC. Elle fournira des informations sur l'amplitude et la durée de l'immunité conférée par la vaccination contre la COVID-19 et permettra de caractériser les facteurs associés à la réponse immunitaire. Ces résultats serviront à orienter les recommandations de santé publique et les lignes directrices en matière d'immunisation pour les quatre millions de Canadiens et Canadiennes qui vivent avec l'IRC.

Incidence of SARS-CoV-2 Infection Among People Experiencing Homelessness in Toronto, Canada.

Importance: People experiencing homelessness are at high risk of SARS-CoV-2 infection. Incident infection rates have yet to be established in these communities and are needed to inform infection prevention guidance and related interventions. Objective: To quantify the SARS-CoV-2 incident infection rate among people experiencing homelessness in Toronto, Canada, in 2021 and 2022 and to assess factors associated with incident infection. Design, Setting, and Participants: This prospective cohort study was conducted among individuals aged 16 years and older who were randomly selected between June and September 2021 from 61 homeless shelters, temporary distancing hotels, and encampments in Toronto, Canada. Exposures: Self-reported housing characteristics, such as number sharing living space. Main Outcomes and Measures: Prevalence of prior SARS-CoV-2 infection in summer 2021, defined as self-reported or polymerase chain reaction (PCR)- or serology-confirmed evidence of infection at or before the baseline interview, and SARS-CoV-2 incident infection, defined as self-reported or PCR- or serology-confirmed infection among participants without history of infection at baseline. Factors associated with infection were assessed using modified Poisson regression with generalized estimating equations. Results: The 736 participants (415 of whom did not have SARS-CoV-2 infection at baseline and were included in the primary analysis) had a mean (SD) age of 46.1 (14.6) years; 486 (66.0%) self-identified as male. Of these, 224 (30.4% [95% CI, 27.4%-34.0%]) had a history of SARS-CoV-2 infection by summer 2021. Of the remaining 415 participants with follow-up, 124 experienced infection within 6 months, representing an incident infection rate of 29.9% (95% CI, 25.7%-34.4%), or 5.8% (95% CI, 4.8%-6.8%) per person-month. Report after onset of the SARS-CoV-2 Omicron variant was associated with incident infection, with an adjusted rate ratio (aRR) of 6.28 (95% CI, 3.94-9.99). Other factors associated with incident infection included recent immigration to Canada (aRR, 2.74 [95% CI, 1.64-4.58]) and alcohol consumption over the past interval (aRR, 1.67 [95% CI, 1.12-2.48]). Self-reported housing characteristics were not significantly associated with incident infection. Conclusions and Relevance: In this longitudinal study of people experiencing homelessness in Toronto, SARS-CoV-2 incident infection rates were high in 2021 and 2022, particularly once the Omicron variant became dominant in the region. Increased focus on homelessness prevention is needed to more effectively and equitably protect these communities.

Protection from Omicron Infection in Residents of Nursing and Retirement Homes in Ontario, Canada.

OBJECTIVES: To identify factors that contribute to protection from infection with the Omicron variant of SARS-CoV-2 in older adults in nursing and retirement homes. DESIGN: Longitudinal cohort study with retrospective analysis of infection risk. SETTING AND PARTICIPANTS: 997 residents of nursing and retirement homes from Ontario, Canada, in the COVID in LTC study. METHODS: Residents with 3 messenger RNA (mRNA) dose vaccinations were included in the study. SARS-CoV-2 infection was determined by positive nasopharyngeal polymerase chain reaction test and/or circulating antinucleocapsid IgG antibodies. Cumulative probability of Omicron infection after recent COVID-19 was assessed by log-rank test of Kaplan-Meier curves. Cox regression was used to assess risk of Omicron infection by age, sex, mRNA vaccine combination, whether individuals received a fourth dose, as well as recent COVID-19. RESULTS: In total, 171 residents (17.2%) had a presumed Omicron variant SARS-CoV-2 infection between December 15, 2021 (local start of the first Omicron wave) and May 3, 2022. Risk of Omicron infection was not different by age [hazard ratio (95% confidence interval) 1.01 (0.99‒1.02)], or in women compared with men [0.97 (0.70‒1.34)], but infection risk decreased 47% with 3 vaccine doses of mRNA-1273 (Moderna) compared with BNT162b2 (Pfizer) [0.53 (0.31-0.90)], 81% with any fourth mRNA vaccine dose [0.19 (0.12‒0.30)], and 48% with SARS-CoV-2 infection in the 3 months prior to beginning of the Omicron wave [0.52, (0.27‒0.99)]. CONCLUSIONS AND IMPLICATIONS: Vaccine type (ie, mRNA-1273/Spikevax vs BNT162b2/Cominarty), any fourth vaccine dose, and hybrid immunity from recent COVID-19, were protective against infection with the Omicron variant. These data emphasize the importance of vaccine type, and number of vaccine doses, in maintenance of protective immunity and reduction of risk of Omicron variant breakthrough infection. These findings promote continued public health efforts to support vaccination programs and monitor vaccine immunogenicity in older adults.

Neutralization against Omicron variant in transplant recipients after three doses of mRNA vaccine.

The SARS-CoV-2 virus Omicron variant has now supplanted wild-type virus as the dominant circulating strain globally. Three doses of mRNA COVID-19 vaccine are recommended for transplant recipients as their primary vaccine series. However, the immunogenicity of mRNA vaccines as they specifically relate to the Omicron variant are not well studied. We analyzed Omicron-specific neutralization in transplant recipients after three-doses of mRNA-1273 vaccine. Neutralization was determined using a SARS-CoV-2 spike pseudotyped lentivirus assay with constructs for Omicron and Delta variants. A total of 60 transplant patients (kidney, kidney-pancreas, lung, heart, liver) were analyzed 1 month and 3 months after completion of three doses of mRNA-1273. At 1 month, 11/60 (18.3%) patients had detectable neutralizing antibody responses to Omicron (log10 ID50 of 2.38 [range 1.34-3.57]). At 3 months, 8/51 (15.7%) were positive (median log10 ID50 [1.68; range 1.12-3.61; approximate fivefold reduction over time]). The proportion of positive patients was lower for Omicron versus wild-type, and Omicron vs. Delta (p < .001). No demographic variables were found to be significantly associated with Omicron response. Many patients with a positive anti-RBD response still had undetectable Omicron-specific neutralizing antibody. In conclusion, three doses of mRNA vaccine results in poor neutralizing responses against the Omicron variant in transplant patients.

Genome screening, reporting, and genetic counseling for healthy populations.

Rapid advancements of genome sequencing (GS) technologies have enhanced our understanding of the relationship between genes and human disease. To incorporate genomic information into the practice of medicine, new processes for the analysis, reporting, and communication of GS data are needed. Blood samples were collected from adults with a PCR-confirmed SARS-CoV-2 (COVID-19) diagnosis (target N = 1500). GS was performed. Data were filtered and analyzed using custom pipelines and gene panels. We developed unique patient-facing materials, including an online intake survey, group counseling presentation, and consultation letters in addition to a comprehensive GS report. The final report includes results generated from GS data: (1) monogenic disease risks; (2) carrier status; (3) pharmacogenomic variants; (4) polygenic risk scores for common conditions; (5) HLA genotype; (6) genetic ancestry; (7) blood group; and, (8) COVID-19 viral lineage. Participants complete pre-test genetic counseling and confirm preferences for secondary findings before receiving results. Counseling and referrals are initiated for clinically significant findings. We developed a genetic counseling, reporting, and return of results framework that integrates GS information across multiple areas of human health, presenting possibilities for the clinical application of comprehensive GS data in healthy individuals.

Omicron BA.4/5 neutralization and T-cell responses in organ transplant recipients after Booster mRNA vaccine: a Multicenter Cohort Study.

BACKGROUND: In solid organ transplant (SOT) recipients, the primary vaccination series against COVID-19 is three doses followed by boosters. We determined whether a fourth dose booster induced Omicron BA.4/5 neutralizing antibodies and T-cells in a large multicenter cohort study. METHODS: Serum was collected 4-6 weeks post third and fourth dose of mRNA vaccine in 222 SOT recipients. Neutralizing antibodies (nAb) were measured using a pseudovirus neutralization assay targeting the Omicron BA.4/5 spike protein. A subset underwent T-cell testing. RESULTS: Median age of the cohort was 63 years (IQR 50-68) with 61.7% men. BA.4/5 nAb detection increased from 26.6%(59/222) post third dose to 53.6%(119/222) post fourth dose (p<0.0001). In patients with breakthrough infection prior to fourth dose (n=27), nAb were detected in 77.8% and median nAb titers were significantly higher compared to those with four vaccine doses alone (p<0.0001). Factors associated with a low BA.4/5 neutralization response after fourth dose were older age (OR 0.96, 95%CI 0.94-0.99), mycophenolate use (OR 0.39, 95%CI 0.20-0.77) and prednisone use (OR 0.34, 95%CI 0.18-0.63), and vaccine type (OR 0.72, 95%CI 0.51-0.99) while breakthrough infection prior to fourth dose (OR 3.6, 95%CI 1.3-9.9) was associated with a greater nAb response. Polyfunctional BA.4/5-specific CD4+ T-cells significantly increased after four doses and were identified in 76.9% of patients at a median frequency of 213 per 106 cells (IQR 98-650). CONCLUSION: In summary, a booster significantly increases BA.4/5-specific neutralization and polyfunctional CD4+ T-cell responses, suggesting protection from severe disease even with new Omicron variants. However, SOT recipients that are older, on mycophenolate and prednisone need further preventative strategies.

Impact of Omicron BA.1 infection on BA.4/5 immunity in transplant recipients.

Mutations in the spike protein of SARS-CoV-2 have allowed Omicron subvariants to escape neutralizing antibodies. The degree to which this occurs in transplant recipients is poorly understood. We measured BA.4/5 cross-neutralizing responses in 75 mostly vaccinated transplant recipients who recovered from BA.1 infection. Sera were collected at 1 and 6 months post-BA.1 infection, and a lentivirus pseudovirus neutralization assay was performed using spike constructs corresponding to BA.1 and BA.4/5. Uninfected immunized transplant recipients and health care worker controls were used for comparison. Following BA.1 infection, the proportion of transplant recipients with neutralizing antibody responses was 88.0% (66/75) against BA.1 and 69.3% (52/75) against BA.4/5 (P = .005). The neutralization level against BA.4/5 was approximately 17-fold lower than that against BA.1 (IQR 10.6- to 45.1-fold lower, P < .0001). BA.4/5 responses declined over time and by ≥0.5 log10 (approximately 3-fold) in almost half of the patients by 6 months. BA.4/5-neutralizing antibody titers in transplant recipients with breakthrough BA.1 infection were similar to those in immunized health care workers but significantly lower than those in uninfected triple-vaccinated transplant recipients. These results provide evidence that transplant recipients are at ongoing risk for BA.4/5 infection despite vaccination and prior Omicron strain infection, and additional mitigation strategies may be required to prevent severe disease in this cohort.

Humoral Responses in the Omicron Era Following 3-Dose SARS-CoV-2 Vaccine Series in Kidney Transplant Recipients.

Kidney transplant recipients (KTRs) have a diminished response to SARS-CoV-2 vaccination compared with immunocompetent individuals. Deeper understanding of antibody responses in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron. Methods: We profiled antibody responses in KTRs pre- and at 1 and 3 mo post-third-dose SARS-CoV-2 mRNA-based vaccine. Binding antibody levels were determined by ELISA. Neutralization against wild type, Beta, Delta, and Omicron (BA.1) variants was determined using a SARS-CoV-2 spike-pseudotyped lentivirus assay. Results: Forty-four KTRs were analyzed at 1 and 3 mo (n = 26) post-third dose. At 1 mo, the proportion of participants with a robust antibody response had increased significantly from baseline, but Omicron-specific neutralizing antibodies were detected in just 45% of KTRs. Median binding antibody levels declined at 3 mo, but the proportion of KTRs with a robust antibody response was unchanged; 38.5% KTRs maintained Omicron-specific neutralization at 3 mo. No clinical variables were significantly associated with Omicron-neutralizing antibodies, but antireceptor binding domain titers appeared to identify those with Omicron-specific neutralizing capacity. Conclusions: Over 50% of KTRs lack Omicron-specific neutralization capacity 1 mo post-third mRNA-vaccine dose. Antibody levels of responders were well preserved at 3 mo. Anti receptor binding domain antibody titers may identify patients with a detectable Omicron-neutralizing antibody response.

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.

Utilization of the Abbott SARS-CoV-2 IgG II Quant Assay To Identify High-Titer Anti-SARS-CoV-2 Neutralizing Plasma against Wild-Type and Variant SARS-CoV-2 Viruses.

There is evidence that COVID-19 convalescent plasma may improve outcomes of patients with impaired immune systems; however, more clinical trials are required. Although we have previously used a 50% plaque reduction/neutralization titer (PRNT50) assay to qualify convalescent plasma for clinical trials and virus-like particle (VLP) assays to validate PRNT50 methodologies, these approaches are time-consuming and expensive. Here, we characterized the ability of the Abbott severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG II Quant assay to identify high- and low-titer plasma for wild-type and variant (Alpha, Beta, Gamma, and Delta) SARS-CoV-2 characterized by both VLP assays and PRNT50. Plasma specimens previously tested in wild-type, Alpha, Beta, Gamma, and Delta VLP neutralization assays were selected based on availability. Selected specimens were evaluated by the Abbott SARS-CoV-2 IgG II Quant assay [Abbott anti-Spike (S); Abbott, Chicago, IL], and values in units per milliliter were converted to binding antibody units (BAU) per milliliter. Sixty-three specimens were available for analysis. Abbott SARS-CoV-2 IgG II Quant assay values in BAU per milliliter were significantly different between high- and low-titer specimens for wild-type (Mann-Whitney U = 42, P < 0.0001), Alpha (Mann-Whitney U = 38, P < 0.0001), Beta (Mann-Whitney U = 29, P < 0.0001), Gamma (Mann-Whitney U = 0, P < 0.0001), and Delta (Mann-Whitney U = 42, P < 0.0001). A conservative approach using the highest 95% confidence interval (CI) values from wild-type and variant of concern (VOC) SARS-CoV-2 experiments would identify a potential Abbott SARS-CoV-2 IgG II Quant assay cutoff of ≥7.1 × 103 BAU/mL. IMPORTANCE The United States Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the use of COVID-19 convalescent plasma (CCP) to treat hospitalized patients with COVID-19 in August 2020. However, by 4 February 2021, the FDA had revised the convalescent plasma EUA. This revision limited the authorization for high-titer COVID-19 convalescent plasma and restricted patient groups to hospitalized patients with COVID-19 early in their disease course or hospitalized patients with impaired humoral immunity. Traditionally our group utilized 50% plaque reduction/neutralization titer (PRNT50) assays to qualify CCP in Canada. Since that time, the Abbott SARS-CoV-2 IgG II Quant assay (Abbott, Chicago IL) was developed for the qualitative and quantitative determination of IgG against the SARS-CoV-2. Here, we characterized the ability of the Abbott SARS-CoV-2 IgG II Quant assay to identify high- and low-titer plasma for wild-type and variant (Alpha, Beta, Gamma, and Delta) SARS-CoV-2.

Third dose corrects waning immunity to SARS-CoV-2 mRNA vaccines in immunocompromised patients with immune-mediated inflammatory diseases

Immunocompromised patients treated with immunosuppressive drugs are at increased risk of adverse outcomes following SARS-CoV-2 infection.1 There is limited information on the effect of immunomodulatory therapies on the quality of SARS-CoV-2 vaccine-induced immunity in these populations.2 In a cohort of patients with immune-mediated inflammatory diseases (IMIDs) not treated with B-cell depleting agents or corticosteroids, we recently demonstrated that antibody levels and T cell responses showed greater waning by 3 months following the second dose of SARS-CoV-2 mRNA vaccine compared with healthy controls, emphasising the need for third doses of the vaccine.3 Here, we investigated immune responses in uninfected patients with IMID following a third dose of the Pfizer/BioNTech BNT162b2 or Moderna mRNA-1273 mRNA vaccine. NS, non-significant;RBD, receptor binding domain;FPR, false positive rate;PBMC, peripheral blood mononuclear cells;DMSO, dimethyl sulfoxide;SQRT, square root. Competing interests VP has no personal financial ties with any pharmaceutical company but has received honoraria for speaker and/or advisory board member roles from AbbVie, Almirall, Celgene, Janssen, Kyowa Kirin, LEO Pharma, Novartis, Pfizer, Sanofi, UCB and Union Therapeutics.

Comparative performance data for multiplex SARS-CoV-2 serological assays from a large panel of dried blood spot specimens.

The extent of the COVID-19 pandemic will be better understood through serosurveys and SARS-CoV-2 antibody testing. Dried blood spot (DBS) samples will play a central role in large scale serosurveillance by simplifying biological specimen collection and transportation, especially in Canada. Direct comparative performance data on multiplex SARS-CoV-2 assays resulting from identical DBS samples are currently lacking. In our study, we aimed to provide performance data for the BioPlex 2200 SARS-CoV-2 IgG (Bio-Rad), V-PLEX SARS-CoV-2 Panel 2 IgG (MSD), and Elecsys Anti-SARS-CoV-2 (Roche) commercial assays, as well as for two highly scalable in-house assays (University of Ottawa and Mount Sinai Hospital protocols) to assess their suitability for DBS-based SARS-CoV-2 DBS serosurveillance. These assays were evaluated against identical panels of DBS samples collected from convalescent COVID-19 patients (n = 97) and individuals undergoing routine sexually transmitted and bloodborne infection (STBBI) testing prior to the COVID-19 pandemic (n = 90). Our findings suggest that several assays are suitable for serosurveillance (sensitivity >97% and specificity >98%). In contrast to other reports, we did not observe an improvement in performance using multiple antigen consensus-based rules to establish overall seropositivity. This may be due to our DBS panel which consisted of samples collected from convalescent COVID-19 patients with significant anti-spike, -receptor binding domain (RBD), and -nucleocapsid antibody titers. This study demonstrates that biological specimens collected as DBS coupled with one of several readily available assays are useful for large-scale COVID-19 serosurveillance.

Ku-gaa-gii pimitizi-win, the COVID-19 cohort study of people experiencing homelessness in Toronto, Canada: a study protocol

Introduction Initial reports suggest people experiencing homelessness (PEH) are at high risk for SARS-CoV-2 infection and associated morbidity and mortality. However, there have been few longitudinal evaluations of the spread and impact of COVID-19 among PEH. This study will estimate the prevalence and incidence of COVID-19 infections in a cohort of PEH followed prospectively in Toronto, Canada. It will also examine associations between individual-level and shelter-level characteristics with COVID-19 infection, adverse health outcomes related to infection and vaccination. Finally, the data will be used to develop and parameterise a mathematical model to characterise SARS-CoV-2 transmission dynamics, and the transmission impact of interventions serving PEH. Design, methods and analysis Ku-gaa-gii pimitizi-win will follow a random sample of PEH from across Toronto (Canada) for 12 months. 736 participants were enrolled between June and September 2021, and will be followed up at 3-month intervals. At each interval, specimens (saliva, capillary blood) will be collected to determine active SARS-CoV-2 infection and serologic evidence of past infection and/or vaccination, and a detailed survey will gather self-reported information, including a detailed housing history. To examine the association between individual-level and shelter-level characteristics on COVID-19-related infection, adverse outcomes, and vaccination, shelter and healthcare administrative data will be linked to participant study data. Healthcare administrative data will also be used to examine long-term (up to 5 years) COVID-19-related outcomes among participants. Ethics and dissemination Ethical approval was obtained from the Unity Health Toronto and University of Toronto Health Sciences Research Ethics Boards (# 20-272). Ku-gaa-gii pimitizi-win was designed in collaboration with community and service provider partners and people having lived experience of homelessness. Findings will be reported to groups supporting Ku-gaa-gii pimitizi-win, Indigenous and other community partners and service providers, funding bodies, public health agencies and all levels of government to inform policy and public health programs.