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.

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.

Cross-Canada Variability in Blood Donor SARS-CoV-2 Seroprevalence by Social Determinants of Health.

We compared the seroprevalence of SARS-CoV-2 anti-nucleocapsid antibodies in blood donors across Canadian regions in 2021. The seroprevalence was the highest in Alberta and the Prairies, and it was so low in Atlantic Canada that few correlates were observed. Being male and of young age were predictive of seropositivity. Racialization was associated with higher seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. Living in a materially deprived neighborhood predicted higher seroprevalence, but it was more linear across quintiles in Alberta and the Prairies, whereas in British Columbia and Ontario, the most affluent 60% were similarly low and the most deprived 40% similarly elevated. Living in a more socially deprived neighborhood (more single individuals and one parent families) was associated with lower seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. These data show striking variability in SARS-CoV-2 seroprevalence across regions by social determinants of health. IMPORTANCE Canadian blood donors are a healthy adult population that shows clear disparities associated with racialization and material deprivation. This underscores the pervasiveness of the socioeconomic gradient on SARS-CoV-2 infections in Canada. We identify regional differences in the relationship between SARS-CoV-2 seroprevalence and social determinants of health. Cross-Canada studies, such as ours, are rare because health information is under provincial jurisdiction and is not available in sufficient detail in national data sets, whereas other national seroprevalence studies have insufficient sample sizes for regional comparisons. Ours is the largest seroprevalence study in Canada. An important strength of our study is the interpretation input from a public health team that represented multiple Canadian provinces. Our blood donor seroprevalence study has informed Canadian public health policy at national and provincial levels since the start of the SARS-CoV-2 pandemic.

Seropositivity and risk factors for SARS-CoV-2 infection in a South Asian community in Ontario: a cross-sectional analysis of a prospective cohort study.

BACKGROUND: Early in the COVID-19 pandemic, the South Asian community in the Greater Toronto Area (GTA) was identified as having risk factors for exposure and specific barriers to accessing testing and reliable health information, rendering them particularly vulnerable to SARS-CoV-2 infection. We sought to investigate the burden of SARS-CoV-2 infection among South Asian people in the GTA, and to characterize the demographic characteristics, risk perceptions and trusted sources of health information in this group. METHODS: We conducted a cross-sectional analysis from the baseline assessment of participants in a prospective cohort study. Participants from the GTA were enrolled from Apr. 14 to July 28, 2021. Seropositivity for antispike and antinucleocapsid antibodies was determined from dried blood spots, and estimates of seropositivity were age and sex standardized to the South Asian population in Ontario. Demographic characteristics, risk perceptions and sources of COVID-19 information were collected via questionnaire and reported descriptively. RESULTS: Among the 916 South Asian participants enrolled (mean age 41 yr), the age- and sex-standardized seropositivity was 23.6% (95% confidence interval 20.8%-26.4%). Of the 693 respondents to the questionnaire, 228 (32.9%) identified as essential workers, and 125 (19.1%) reported living in a multigenerational household. A total of 288 (49.4%) perceived that they were at high COVID-19 risk owing to their geographic location, and 149 (34.3%) owing to their type of employment. The top 3 most trusted sources of information related to COVID-19 included health care providers and public health, traditional media sources and social media. INTERPRETATION: By the third wave of the COVID-19 pandemic, about one-quarter of a sample of South Asian individuals in Ontario had serologic evidence of prior SARS-CoV-2 infection. Insight into factors that put certain populations at risk can help future pandemic planning and disease control efforts.

Différences d'immunogénicité des vaccins anti-SRAS-CoV-2 mRNA-1273 (Moderna) et BNT162b2 (Pfizer-BioNTech) chez les patients dialysés.

CONTEXTE: Les différences d'immunogénicité entre les vaccins anti-SRAS-CoV-2 à ARNm n'ont pas été bien caractérisées chez les patients hémodialysés. Nous avons comparé la réponse sérologique chez les patients sous hémodialyse après la vaccination contre le SRAS-CoV-2 au moyen des vaccins BNT162b2 (Pfizer-BioNTech) et mRNA-1273 (Moderna). MÉTHODES: Nous avons procédé à une étude de cohorte observationnelle et prospective dans 2 centres universitaires de Toronto, au Canada, du 2 février au 20 juillet 2021, et avons inclus 129 et 95 patients qui ont reçu respectivement les vaccins anti-SRAS-CoV-2 BNT162b2 et mRNA-1273. Nous avons mesuré les taux d'anticorps IgG dirigés contre la protéine S (anti-S), contre le domaine de liaison au récepteur (ou RBD, pour receptor-binding domain [anti-RBD]) et contre la protéine de la nucléocapside (anti-N) du SRAS-CoV-2 6­7) puis 12 semaines après la deuxième dose de vaccin et nous avons comparé ces taux aux taux médians d'anticorps présents dans le sérum de 211 témoins convalescents qui avaient déjà contracté le SRAS-CoV-2. RÉSULTATS: Six à 7 semaines après la deuxième dose de vaccin, nous avons constaté que 51 patients sur 70 (73 %) ayant reçu le BNT162b2 et 83 patients sur 87 (95 %) ayant reçu le mRNA-1273, ont obtenu des taux équivalents à ceux du sérum de convalescents pour ce qui est de l'anticorps anti-S (p < 0,001). Chez ceux qui ont reçu le BNT162b2, 35 sur 70 (50 %) ont atteint le taux du sérum de convalescents pour l'anti-RBD, contre 69 sur 87 (79 %) de ceux qui ont reçu le mRNA-1273 (p < 0,001). Douze semaines après la deuxième dose, les taux d'anti-S et d'anti-RBD étaient significativement moindres chez les patients ayant reçu le BNT162b2 que chez ceux qui avaient reçu le mRNA-1273. Pour l'anti-S, 70 patients sur 122 (57,4 %) ayant reçu le BNT162b2 ont maintenu un taux équivalent à celui du sérum de convalescents, contre 68 sur 71 (96 %) de ceux qui avaient reçu le mRNA-1273 (p < 0,001). Pour l'anti-RBD, 47 patients sur 122 (38,5 %) ayant reçu le BNT162b2 ont maintenu des taux anti-RBD équivalant à celui du sérum de convalescents, contre 45 sur 71 (63 %) de ceux qui avaient reçu le mRNA-1273 (p = 0,002). INTERPRÉTATION: Chez les patients hémodialysés, le mRNA-1273 a généré une réponse humorale plus forte que le BNT162b2. Étant donné le déclin rapide de l'immunogénicité à 12 semaines chez les patients ayant reçu le BNT162b2, une troisième dose est recommandée chez les patients hémodialysés dans le cadre d'une première série, ce qui concorde avec les recommandations concernant d'autres populations vulnérables.

Does a humoral correlate of protection exist for SARS-CoV-2? A systematic review.

BACKGROUND: A correlate of protection (CoP) is an immunological marker associated with protection against infection. Despite an urgent need, a CoP for SARS-CoV-2 is currently undefined. OBJECTIVES: Our objective was to review the evidence for a humoral correlate of protection for SARS-CoV-2, including variants of concern. METHODS: We searched OVID MEDLINE, EMBASE, Global Health, Biosis Previews and Scopus to January 4, 2022 and pre-prints (using NIH iSearch COVID-19 portfolio) to December 31, 2021, for studies describing SARS-CoV-2 re-infection or breakthrough infection with associated antibody measures. Two reviewers independently extracted study data and performed quality assessment. RESULTS: Twenty-five studies were included in our systematic review. Two studies examined the correlation of antibody levels to VE, and reported values from 48.5% to 94.2%. Similarly, several studies found an inverse relationship between antibody levels and infection incidence, risk, or viral load, suggesting that both humoral immunity and other immune components contribute to protection. However, individual level data suggest infection can still occur in the presence of high levels of antibodies. Two studies estimated a quantitative CoP: for Ancestral SARS-CoV-2, these included 154 (95% confidence interval (CI) 42, 559) anti-S binding antibody units/mL (BAU/mL), and 28.6% (95% CI 19.2, 29.2%) of the mean convalescent antibody level following infection. One study reported a CoP for the Alpha (B.1.1.7) variant of concern of 171 (95% CI 57, 519) BAU/mL. No studies have yet reported an Omicron-specific CoP. CONCLUSIONS: Our review suggests that a SARS-CoV-2 CoP is likely relative, where higher antibody levels decrease the risk of infection, but do not eliminate it completely. More work is urgently needed in this area to establish a SARS-CoV-2 CoP and guide policy as the pandemic continues.

Assessment of population infection with SARS-CoV-2 in Ontario, Canada, March to June 2020.

BackgroundSerosurveys for SARS-CoV-2 aim to estimate the proportion of the population that has been infected.AimThis observational study assesses the seroprevalence of SARS-CoV-2 antibodies in Ontario, Canada during the first pandemic wave.MethodsUsing an orthogonal approach, we tested 8,902 residual specimens from the Public Health Ontario laboratory over three time periods during March-June 2020 and stratified results by age group, sex and region. We adjusted for antibody test sensitivity/specificity and compared with reported PCR-confirmed COVID-19 cases.ResultsAdjusted seroprevalence was 0.5% (95% confidence interval (CI): 0.1-1.5) from 27 March-30 April, 1.5% (95% CI: 0.7-2.2) from 26-31 May, and 1.1% (95% CI: 0.8-1.3) from 5-30 June 2020. Adjusted estimates were highest in individuals aged ≥ 60 years in March-April (1.3%; 95% CI: 0.2-4.6), in those aged 20-59 years in May (2.1%; 95% CI: 0.8-3.4) and in those aged ≥ 60 years in June (1.6%; 95% CI: 1.1-2.1). Regional seroprevalence varied, and was highest for Toronto in March-April (0.9%; 95% CI: 0.1-3.1), for Toronto in May (3.2%; 95% CI: 1.0-5.3) and for Toronto (1.5%; 95% CI: 0.9-2.1) and Central East in June (1.5%; 95% CI: 1.0-2.0). We estimate that COVID-19 cases detected by PCR in Ontario underestimated SARS-CoV-2 infections by a factor of 4.9.ConclusionsOur results indicate low population seroprevalence in Ontario, suggesting that public health measures were effective at limiting the spread of SARS-CoV-2 during the first pandemic wave.

SARS-CoV-2 antibodies in Ontario health care workers during and after the first wave of the pandemic: a cohort study.

BACKGROUND: Health care workers have a critical role in the pandemic response to COVID-19 and may be at increased risk of infection. The objective of this study was to assess the seroprevalence of SARS-CoV-2 immunoglobulin G (IgG) antibodies among health care workers during and after the first wave of the pandemic. METHODS: We conducted a prospective multicentre cohort study involving health care workers in Ontario, Canada, to detect IgG antibodies against SARS-CoV-2. Blood samples and self-reported questionnaires were obtained at enrolment, at 6 weeks and at 12 weeks. A community hospital, tertiary care pediatric hospital and a combined adult-pediatric academic health centre enrolled participants from Apr. 1 to Nov. 13, 2020. Predictors of seropositivity were evaluated using a multivariable logistic regression, adjusted for clustering by hospital site. RESULTS: Among the 1062 health care workers participating, the median age was 40 years, and 834 (78.5%) were female. Overall, 57 (5.4%) were seropositive at any time point (2.5% when participants with prior infection confirmed by polymerase chain reaction testing were excluded). Seroprevalence was higher among those who had a known unprotected exposure to a patient with COVID-19 (p < 0.001) and those who had been contacted by public health because of a nonhospital exposure (p = 0.003). Providing direct care to patients with COVID-19 or working on a unit with a COVID-19 outbreak was not associated with higher seroprevalence. In multivariable logistic regression, presence of symptomatic contacts in the household was the strongest predictor of seropositivity (adjusted odds ratio 7.15, 95% confidence interval 5.42-9.41). INTERPRETATION: Health care workers exposed to household risk factors were more likely to be seropositive than those not exposed, highlighting the need to emphasize the importance of public health measures both inside and outside of the hospital.

Evaluation of the SARS-CoV-2 Antibody Response to the BNT162b2 Vaccine in Patients Undergoing Hemodialysis.

Importance: Patients undergoing hemodialysis have a high mortality rate associated with COVID-19, and this patient population often has a poor response to vaccinations. Randomized clinical trials for COVID-19 vaccines included few patients with kidney disease; therefore, vaccine immunogenicity is uncertain in this population. Objective: To evaluate the SARS-CoV-2 antibody response in patients undergoing chronic hemodialysis following 1 vs 2 doses of BNT162b2 COVID-19 vaccination compared with health care workers serving as controls and convalescent serum. Design, Setting, and Participants: A prospective, single-center cohort study was conducted between February 2 and April 17, 2021, in Toronto, Ontario, Canada. Participants included 142 patients receiving in-center hemodialysis and 35 health care worker controls. Exposures: BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. Main Outcomes and Measures: SARS-CoV-2 IgG antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD), and nucleocapsid protein (anti-NP). Results: Among the 142 participants undergoing maintenance hemodialysis, 94 (66%) were men; median age was 72 (interquartile range, 62-79) years. SARS-CoV-2 IgG antibodies were measured in 66 patients receiving 1 vaccine dose following a public health policy change, 76 patients receiving 2 vaccine doses, and 35 health care workers receiving 2 vaccine doses. Detectable anti-NP suggestive of natural SARS-CoV-2 infection was detected in 15 of 142 (11%) patients at baseline, and only 3 patients had prior COVID-19 confirmed by reverse transcriptase polymerase chain reaction testing. Two additional patients contracted COVID-19 after receiving 2 doses of vaccine. In 66 patients receiving a single BNT162b2 dose, seroconversion occurred in 53 (80%) for anti-spike and 36 (55%) for anti-RBD by 28 days postdose, but a robust response, defined by reaching the median levels of antibodies in convalescent serum from COVID-19 survivors, was noted in only 15 patients (23%) for anti-spike and 4 (6%) for anti-RBD in convalescent serum from COVID-19 survivors. In patients receiving 2 doses of BNT162b2 vaccine, seroconversion occurred in 69 of 72 (96%) for anti-spike and 63 of 72 (88%) for anti-RBD by 2 weeks following the second dose and median convalescent serum levels were reached in 52 of 72 patients (72%) for anti-spike and 43 of 72 (60%) for anti-RBD. In contrast, all 35 health care workers exceeded the median level of anti-spike and anti-RBD found in convalescent serum 2 to 4 weeks after the second dose. Conclusions and Relevance: This study suggests poor immunogenicity 28 days following a single dose of BNT162b2 vaccine in the hemodialysis population, supporting adherence to recommended vaccination schedules and avoiding delay of the second dose in these at-risk individuals.

SARS-CoV-2 Seroprevalence Survey Estimates Are Affected by Anti-Nucleocapsid Antibody Decline.

We analyzed 21 676 residual specimens from Ontario, Canada collected March-August 2020 to investigate the effect of antibody decline on SARS-CoV-2 seroprevalence estimates. Testing specimens orthogonally using Abbott (anti-nucleocapsid) and Ortho (anti-spike) assays, seroprevalence estimates were 0.4%-1.4%, despite ongoing disease activity. The geometric mean concentration (GMC) of antibody-positive specimens decreased over time (P = .015), and GMC of antibody-negative specimens increased over time (P = .0018). Association between the 2 tests decreased each month (P < .001), suggesting anti-nucleocapsid antibody decline. Lowering Abbott antibody index cutoff from 1.4 to 0.7 resulted in a 16% increase in positive specimens.