Hybrid Immunity
Humoral and cellular responses to SARS-CoV-2 vaccination in pediatric acute lymphoblastic leukemia patients
Tania Watts, University of Toronto
This study aims to characterize immunity to SARS-CoV-2 in pediatric acute lymphoblastic leukemia (ALL) patients six months or older on maintenance chemotherapy and post CAR-T therapy to evaluate vaccine immunogenicity. The goal is to understand whether children with ALL have lower SARS-CoV-2 vaccine-induced seroconversion rates and higher rates of breakthrough infections leading to severe outcomes.
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Determining the impact of hybrid immunity on the evolving landscape of host responses to SARS-CoV-2 in the Biobanque Québécoise de la COVID-19 (BQC19)
Madeleine Durand and Simon Rousseau, McGill University
The BQC19 is recruiting 500 new participants who are assigned to exposure groups according to whether or not they have been vaccinated and have had a prior infection with the goal of studying the impact of hybrid immunity on outcomes.
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SUrveying Prospective Population cOhorts for COVID19 pRevalence and ouTcomes in Canada (SUPPORT-Canada) – Hybrid Immunity Extension
Philip Awadalla, Canadian Partnership for Tomorrow’s Health (CanPath)
Using the third of participants from the COVID-19 in Long-Term Care study who have hybrid immunity (almost half infected with Omicron), this project will do additional blood collection from participants to better assess immune protection and longevity against evolving SARS-CoV-2 variants by vaccine type, additional vaccine doses, and hybrid immunity across variant lineages.
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COVID-19 Infection and Immunity in Residents of Long-term Care Facilities: Hybrid Immunity in Residents of Long-term Care Facilities
Andrew Costa and Dawn Bowdish, McMaster University
Using the third of participants from the COVID-19 in Long-Term Care study who have hybrid immunity (almost half infected with Omicron), this project will do additional blood collection from participants to better assess immune protection and longevity against evolving SARS-CoV-2 variants by vaccine type, additional vaccine doses, and hybrid immunity across variant lineages.
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Safety and immUnogenicity of Covid-19 vaCcines in systEmic immunE mediated inflammatory Diseases: Infections and Immunity (SUCCEED-II) – Hybrid Immunity Extension
Sasha Bernatsky, Research Institute of the McGill University Health Centre (RI-MUHC)
An extension of the SUCCEED study, this project will look at how vaccination and COVID-19 infection jointly affect hybrid immunity in adults who have autoimmune diseases such as rheumatoid arthritis, spondyloarthritis, inflammatory bowel disease, psoriasis, and other conditions.
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Immunogenicity of current SARS-CoV-2 vaccine schedules currently used in Canada – Hybrid immunity
Pascal Lavoie, University of British Columbia
This study, an extension of one focussing on education workers in Vancouver, aims to determine how immunity conferred by hybrid immunity differs from the immunity conferred by an infection alone, to compare re-infection rates between individuals with hybrid versus vaccine immunity; and to determine the long-term health impact of SARS-CoV-2 infections among school staff.
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Integrating longitudinal epidemiologic, virologic and immunologic analyses to understand COVID-19 immunity and infection outcomes in long term care – Hybrid immunity study extension
Marc Romney, University of British Columbia
This study will perform longitudinal characterizations of vaccine-induced immunity vs. hybrid immunity. It will quantify binding antibodies, virus neutralizing activity, as well as B cell and T cell responses against wild-type and Omicron spike proteins and explore features of B cells and T cells that determine antiviral activity and specificity.
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Characterization of humoral response in blood donors vaccinated against SARS-CoV-2 and then infected with variants of concern
Renée Bazin and Andrés Finzi, Héma-Québec
This study is evaluating the antibody response induced in participants vaccinated against SARS-CoV-2 and then infected with recently identified variants of concern to provide information on the type, duration of immunity and level of protection. Researchers are also studying the immunity induced by the new bivalent vaccines against SARS-CoV-2.
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Characterization of Hybrid Cellular and Humoral Immunity against SARS-CoV-2 and Evaluation of its Role in Protection from Infection and from Severe Illness
Michael Grant, Memorial Universty of Newfoundland
This study compares SARS-CoV-2 immunological and infectious outcomes between vaccinated individuals with 2 to 4 doses of a licensed vaccine, persons infected prior to vaccination who have now received 2 to 4 doses of a licensed vaccine, persons infected or re-infected with Omicron following 2 to 3 doses of a licensed vaccine, and persons infected at least twice with Omicron subvariants.
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Tania Watts
Tania Watts, PhD
Professor, Immunology, University of Toronto
Associate Chair Post Doctoral Program, Dept. of Immunology, Temerty Faculty of Medicine, University of Toronto
Key words
Immunity, Viruses, SARS-CoV-2, Influenza, T cells
Research interests
- Immunity to viruses
- T cells
Publications
- Law JC, Koh W, Budylowski P, Lin J, Yue F, Abe KT, et al. Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile. J Immunol. 2021;206:37-50. DOI: https://doi.org/10.4049/jimmunol.2001067
Humoral and cellular responses to SARS-CoV-2 vaccination in pediatric acute lymphoblastic leukemia patients
Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer, representing over one in four of all new diagnoses. Pediatric ALL patients are treated with multiagent chemotherapy followed by lower-intensity maintenance chemotherapy. Most patients are cured but 15 to 20% develop relapsed disease requiring additional therapy that may include chimeric antigen receptor T cell (CAR-T) therapy. Limited data from adults with hematological malignancies reveal lower SARS-CoV-2 vaccine-induced seroconversion rates and higher rates of breakthrough infections leading to severe outcomes, but there is little vaccine data in pediatric cancer populations.
This study aims to characterize immunity to SARS-CoV-2 in pediatric ALL patients six months or older on maintenance chemotherapy, ALL patients six months or older post CAR-T therapy, and for comparison purposes, healthy individuals (controls) matched for age. Participants are patients from SickKids Hospital, Toronto, with blood samples collected at enrollment and four months later. We are recruiting fully vaccinated children (at least two-dose primary series) in each group who have vaccine-only or hybrid immunity to SARS-CoV-2.
We interview caregivers and review the child’s medical and vaccination records to establish their vaccination and infection history. Children receiving ALL treatment undergo frequent SARS-CoV-2 testing, so there are reliable records of prior infection.
The primary research outcome is evaluating vaccine immunogenicity. We are recruiting 30 ALL patients and 30 controls with vaccine-only immunity, as well as 30 ALL patients and 30 controls with hybrid immunity. We are also recruiting 10 CAR-T patients with vaccine-induced immunity and 10 with hybrid immunity. Our study size will allow for adjustments for factors such as time since vaccination and time since completion of intensive therapy.
Lessons learned from monitoring T cell responses to SARS-CoV-2 infection and vaccination
Madeleine Durand
Madeleine Durand, MD, MSc, FRCPC
Associate Clinical Professor, Faculté de médecine, Département de médecine, Université de Montréal
Affiliate Professor, École de santé publique – Département de médecine sociale et préventive, Université de Montréal
Researcher, Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM)
Internal medicine specialist, CHUM
Co-director, Biobanque québécoise de la COVID-19 (BQC19)
Co-lead, Clinical Care Management Core, CIHR HIV Clinical Trial Network
Contact info
madeleine.durand@gmail.com
514-890-8000, ext 84444
Key words
Epidemiology, Cohort, Internal medicine, COVID-19, HIV, Aging, Cardiovascular
Research interests
- Premature aging associated with the sustained activation of the immune system in chronic HIV infection
- Secondary use of health data to evaluate adverse drug effects
- Cohorts and biobanks
Publications
https://www.researchgate.net/profile/Madeleine-Durand
Simon Rousseau
Simon Rousseau, PhD
Associate Professor – Department of Medicine, Division of Experimental Medicine, McGill University
Meakins-Christie Laboratories at the Research Institute of the McGill University Health Centre
Co-director, Biobanque québécoise de la COVID-19 (BQC19)
Director, Biobanque du réseau en santé respiratoire du Québec
Contact info
Simon.rousseau@mcgill.ca
514-934-1934 ext. 76394
Key words
Intracellular signaling, MAPK, Infection, Inflammation, Lungs, Biobanking
Research interests
Systems biology of lung health and diseases
Publications
- Identification of COVID-19-relevant transcriptional regulatory networks and associated kinases as potential therapeutic targets (2021). Scientific reports 11 (1), 1-12. Su C., Rousseau S., Emad A.
- A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes’ interactions points to Neutrophil Extracellular Traps as mediators of thrombosis in COVID-19 (2021). PLoS Computational Biology 17(3): e1008810. Jun Ding, David Earl Hostallero, Mohamed Reda El Khili, Gregory Fonseca, Simon Milette, Nuzha Noorah, Myriam Guay-Belzile, Jonathan Spicer, Noriko Daneshtalab, Martin Sirois, Karine Tremblay, Amin Emad and Simon Rousseau. https://doi.org/10.1371/journal.pcbi.1008810
- Modeling consent in the time of COVID-19. Knoppers et al., Journal of Law and the Biosciences, 1–6. https://doi:10.1093/jlb/lsaa020
- The Biobanque québécoise de la COVID-19 (BQC19) – A case-control bioresource to prospectively study the clinical and biological determinants of COVID-19 clinical trajectories. Tremblay et al., PLoS ONE 16(5): e0245031. https://doi.org/10.1371/journal.pone.0245031
DETERMINING THE IMPACT OF HYBRID IMMUNITY ON THE EVOLVING LANDSCAPE OF HOST RESPONSES TO SARS-COV-2 IN THE BIOBANQUE QUÉBÉCOISE DE LA COVID-19 (BQC19)
Launched in April 2020, the Biobanque québécoise de la COVID-19 (Quebec COVID-19 Biobank) (BQC19) is a network of universities and hospitals in Quebec, led by Simon Rousseau (McGill University Health Centre) and Madeleine Durand (Centre hospitalier de l’Université de Montréal). The BCQ19 mission is to ensure that scientists have access to the biological materials and data necessary for their COVID-19 research efforts.
Since its inception, BQC19 has prospectively recruited and extensively characterized more than 5,000 participants (children and adults) infected with SARS-CoV-2 throughout every wave of infection in Quebec, representing a wide array of clinical manifestations of COVID-19 disease. Participants range from critically ill to asymptomatic, vaccinated or unvaccinated, those who experience post-COVID-19 conditions, people who were re-infected with SARS-CoV-2, as well as individuals who have never had a COVID-19 infection.
We are supplementing our research work with a nine-month project to study hybrid immunity. We are recruiting 500 new participants who are assigned to exposure groups according to whether or not they have been vaccinated and whether or not they have had a prior infection with the goal of studying the impact of hybrid immunity on outcomes. These groups are further subdivided according to the number of doses and type of vaccine they receive, which SARS-CoV-2 variant caused their infection, the number of reinfections they’ve had, and the delays between infections and vaccinations.
To understand the impact of hybrid immunity on disease outcomes and immunity, we are comprehensively characterising the molecular profile of blood samples from each participant and comparing each group described above to capture changes in exposure categories over time. The clinical outcomes of interest will be COVID-19 infection or re-infection and its severity.
Michael Grant
Michael Grant, PhD
Professor of Immunology, Memorial University of Newfoundland
Associate Dean, BioMedical Sciences
Contact information
mgrant@mun.ca
Key words
CD8, T cell, CTL, NK cell, ADCC, HIV, CMV, Aging, Immune senescence
Research Interests
- Immunology of viral infection
- Aging of the immune system
- Regulation of NK cells
CHARACTERIZATION OF HYBRID CELLULAR AND HUMORAL IMMUNITY AGAINST SARS-COV-2 AND EVALUATION OF ITS ROLE IN PROTECTION FROM INFECTION AND FROM SEVERE ILLNESS
The primary cohort for this study consists of more than 200 adults (18 to 80 years old), who were either infected with SARS-CoV-2, vaccinated against SARS-CoV-2 with an approved vaccine regimen, or both infected and vaccinated.
We began recruiting participants in July 2020, so there are 57 people in the study who were infected with SARS-CoV-2 during early waves of the pandemic prior to the availability of vaccines. We collected post-infection blood samples from these individuals at enrollment. We collected pre-vaccination samples from virtually all subsequent recruits. For all participants, we continue to collect samples over the course of their COVID-19 vaccinations and COVID-19 infections.
We have been measuring antibody levels against SARS-CoV-2 spike proteins (Wuhan, Delta, and Omicron) to assess infection and vaccination-induced immunity and measure antibody levels against SARS-CoV-2 nucleoprotein to monitor incident infection. At each visit, study participants complete questionnaires and update their vaccination history as well as report duration and severity of any symptoms related to a positive COVID-19 PCR test or self-administered COVID-19 rapid antigen test.
We are comparing SARS-CoV-2 immunological and infectious outcomes between our participant groups, which include vaccinated individuals with 2 to 4 doses of a licensed vaccine, persons infected prior to vaccination who have now received 2 to 4 doses of a licensed vaccine, persons infected or re-infected with Omicron following 2 to 3 doses of a licensed vaccine, and persons infected at least twice with Omicron subvariants. We are comparing the strength of immune responses and their breadth and selectivity of recognition for early through recent SARS-CoV-2 variants. Sequence, timing, and SARS-CoV-2 variant are all expected to influence the nature of induced immunity.
Hybrid immunity protects against cell-to-cell spread of SARS-CoV-2
Andrew Costa
Andrew Costa
Associate Professor and Schlegel Chair in Clinical Epidemiology & Aging, McMaster University
Contact info
acosta@mcmaster.ca
Key words
Long-term care, Nursing homes, Epidemiology
Research interests
- Use of health information (‘big data’) to target, develop, and evaluate models of care in home and community care, emergency departments, hospitals, and long-term care (https://bdg.mcmaster.ca/)
- Digital tools for health care, including caregivers (https://www.yourcareplus.ca)
- Data platforms
- Integrated care
Publications
- Costa AP, Manis D, Jones A, Stall N, Brown KA, et al. Risk factors for outbreaks of SARS-CoV-2 infection at retirement homes in Ontario, Canada: A population-level cohort study. (pre-print). CMAJ. In press.
- Stall NM, Zipursky JS, Rangrej J, Jones A, Costa AP, Hillmer MP, Brown K. Assessment of Psychotropic Drug Prescribing Among Nursing Home Residents in Ontario, Canada, During the COVID-19 Pandemic. JAMA Intern Med. doi:10.1001/jamainternmed.2021.0224
- Pitre T, Jones A, Su J, Helmeczi W, Xu G, Lee C, Shamsuddin A, Mir A, MacGregor S, Duong M, Ho T, Beauchamp MK, Costa AP, Kruisselbrink R; COREG Investigators. Inflammatory biomarkers as independent prognosticators of 28-day mortality for COVID-19 patients admitted to general medicine or ICU wards: a retrospective cohort study. Intern Emerg Med. 2021 Jan 26:1–10. doi: 10.1007/s11739-021-02637-8.
- Brown KA, Jones A, Daneman N, Chan AK, Schwartz KL, Garber GE, Costa AP, Stall NM. Association Between Nursing Home Crowding and COVID-19 Infection and Mortality in Ontario, Canada. JAMA Intern Med. 2021 Feb 1;181(2):229-236. doi: 10.1001/jamainternmed.2020.6466. PMID: 33165560; PMCID: PMC7653540.
- Jones A, Watts AG, Khan SU, Forsyth J, Brown KA, Costa AP, Bogoch II, Stall NM. Impact of a Public Policy Restricting Staff Mobility Between Nursing Homes in Ontario, Canada During the COVID-19 Pandemic. J Am Med Dir Assoc. 2021 Mar;22(3):494-497. doi: 10.1016/j.jamda.2021.01.068. Epub 2021 Jan 26. PMID: 33516671.
- Stall NM, Jones A, Brown KA, Rochon PA, Costa AP*. For-profit long-term care homes and the risk of COVID-19 outbreaks and resident deaths. CMAJ. 2020. August 17, 2020 192 (33) E946-E955 / Stall NM, Jones A, Brown KA, Rochon PA, Costa AP*. Risque d’eclosions de COVID-19 et de deces de residents dans les foyers de soins de longue duree a but lucrative. CMAJ. 2020 Nov 30;192(48):E1662-E1672.
Dawn Bowdish
Dawn Bowdish
Professor, McMaster University
Canada Research Chair in Aging & Immunity, McMaster University
Contact info
bowdish@mcmaster.ca
Key words
Long-term care, Frailty, Vaccination, Immunology, Antibodies, Cellular immunity
Research interests
- Immunosenescence
- Respiratory infections
- Microbiome
- Innate immunity
- Inflammation
Publications
- Characteristics of anti-SARS-CoV-2 antibodies in recovered COVID-19 subjects. Authors: Angela Huynh, Donald M. Arnold, James W. Smith, Jane C. Moore, Ali Zhang, Zain Chagla, Bart J. Harvey, Hannah D. Stacey, Jann C. Ang, RumiClare, Nikola Ivetic, Vasudhevan T. Chetty, Dawn M.E. Bowdish, Matthew S. Miller, John G. Kelton, Ishac Nazy. Accepted for publication in Viruses
COVID-19 INFECTION AND IMMUNITY IN RESIDENTS OF LONG-TERM CARE FACILITIES: HYBRID IMMUNITY IN RESIDENTS OF LONG-TERM CARE FACILITIES
In Canada, as elsewhere in the world, residents of nursing homes and retirement homes have been one of the most adversely affected groups of people during the COVID-19 pandemic.
Our initial study, COVID-19 in Long-term Care, is an open enrollment cohort study of residents in 25 nursing homes and retirement homes in Ontario. We have been following residents who have provided blood samples (dried blood sample and/or venous blood draw) at multiple time points to determine their SARS-CoV-2 antibody levels, neutralizing capacity, and cellular immunity.
Currently, our study has an enrollment of more than 900 people. Our data includes participants’ individual vaccination history, including vaccine dose, type, and intervals between shots. Any PCR-confirmed infections are also collected from participants’ electronic medical records. Infections are also determined by seropositivity for anti-nucleocapsid IgG antibodies at blood collection points. The scale of our longitudinal biosample collection is unique in Canada and internationally.
A third of our participants have hybrid immunity, with almost half infected with Omicron and a quarter with multiple past infections. We are extending our study through to winter 2023 and will do additional blood collection from participants at three-month intervals. This will enhance our capacity to assess immune protection and longevity against evolving SARS-CoV-2 variants by vaccine type, additional vaccine doses, and hybrid immunity across variant lineages.
In the Omicron era, the degree to which hybrid immunity is protective is less clear. Our investigations of hybrid immunity will determine whether there are immune mechanisms associated with susceptibility or resistance to repeat infection in this vulnerable population.
Philip Awadalla
Philip Awadalla, PhD
Professor, Department of Molecular Genetics, Faculty of Medicine, University of Toronto
Professor, Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto
Adjunct Professor, CHUM, Department of Medicine, Faculty of Medicine, University of Montreal
Director, Computational Biology, Ontario Institute for Cancer Research
Senior Investigator, Ontario Institute for Cancer Research
National Scientific Director, Canadian Partnership for Tomorrow’s Health (CanPath)
Executive Scientific Director, Ontario Health Study
Principal Investigator and Director, Genome Canada Canadian Data Integration Centre
Key words
Canadian Partnership for Tomorrow’s Health (CanPath), SUPPORT-Canada, Ontario Health Study, Serology, Immunity, COVID-prevalence, Genomics
Research interests
- Genomics
- Early Cancer Detection
- Quantitative and population genetics
- Precision medicine
- Cancer diagnostic markers development
- Big data and Machine Intelligence
Publications
- CPHA Webinar – CanPath COVID-19 Questionnaire Results: A Preliminary Analysis
- Ouellette TW, Shaw J, Awadalla P. Using image-based haplotype alignments to map global adaptation of SARS-CoV-2. 2021. Biorxiv (and in review)
SURVEYING PROSPECTIVE POPULATION COHORTS FOR COVID19 PREVALENCE AND OUTCOMES IN CANADA (SUPPORT-CANADA) – HYBRID IMMUNITY EXTENSION
As SARS-CoV-2 variants have continued to emerge, there is a pressing need to better understand the extent to which both viral- and vaccine-induced antibodies may decline over time. Understanding how changing antibody levels in people who are vaccinated, or who have past infection history, or who have both (hybrid immunity), correlate with infection rates and disease severity will allow for tailored recommendations regarding COVID-19 vaccine distribution and preventative behaviours.
SUPPORT-Canada is a CITF-funded initiative that uses the Canadian Partnership for Tomorrow’s Health (CanPath)—a national population health research platform that follows the health of 330,000 Canadians—to capture critical short-and long-term COVID-19 clinical features from Canadians.
This new study involves collecting blood samples at an additional time point from approximately 3,000 SUPPORT-Canada participants to assess levels of protection conferred through prior vaccination, infection, or hybrid immunity. Our main objectives are to:
- Estimate the effectiveness of vaccination/infection/hybrid immunity against SARS-CoV-2 infection and severe outcomes by variant of concern;
- Estimate whether previous infection offers protection against emerging Omicron variants;
- Determine if post-vaccination antibody levels vary between vaccinated Canadians infected by Omicron and those who were uninfected, or those infected by earlier variants, and determine the rate at which antibody concentrations wane over time;
- Determine if post-vaccination antibody levels correlate with immune protection and the duration of protection.
Our study will support Canada’s COVID-19 vaccination schedule by informing whether, when, or for whom a booster might be necessary, and will enable the integration of infection- and vaccination-induced immunity into vaccine strategies.
Sasha Bernatsky
Sasha Bernatsky, MD, PhD
Professor of Medicine, McGill University
Senior Clinical Investigator, Research Institute of the McGill University Health Centre
Nominate Principal Investigator, CAnadian Network for Advanced Interdisciplinary Methods (CANAIM)
Contact info
Jennifer Lee (RIMUHC)
jennifer.lee@rimuhc.ca
Key words
Drug/device safety and effectiveness, Epidemiology, Autoimmunity, Rheumatic disease
Research interests
- Drug/device safety and effectiveness research
- Patient-centred outcomes research and evaluation
- Rheumatic disease outcomes
- Pharmacoepidemiology
- Administrative data/deep data analytics
Publications
- Bérard A, Sheehy O, Zhao JP, Vinet E, Quach C, Kassai B, Bernatsky S. Available medications used as potential therapeutics for COVID-19: What are the known safety profiles in pregnancy. PLoS One. 2021 May 19;16(5):e0251746. doi: 10.1371/journal.pone.0251746. PMID: 34010282; PMCID: PMC8133446.
- Hazlewood GS, Pardo Pardo J, Barnabe C, Schieir O, Barber CEH, Bernatsky S, Colmegna I, Hitchon C, Loeb M, Mertz D, Proulx L, Richards DP, Scuccimarri R, Tugwell P, Schünemann HJ, Mirza RD, Zhou AL, Nikolic RPA, Thomas M, Chase H, Ejaredar M, Nieuwlaat R. Canadian Rheumatology Association Recommendation for the Use of COVID-19 Vaccination for Patients With Autoimmune Rheumatic Diseases. J Rheumatol. 2021 May 15:jrheum.210288. doi: 10.3899/jrheum.210288. Epub ahead of print. PMID: 33993119.
- Mendel A, Bernatsky S, Askanase A, Bae SC, Clarke AE, Costedoat-Chalumeau N, Gladman DD, Gordon C, Hanly J, Jacobsen S, Kalunian K, Mak A, Mosca M, Pons-Estel BA, Ruiz-Irastorza G, Urowitz M, Vinet É. Hydroxychloroquine shortages among patients with systemic lupus erythematosus during the COVID-19 pandemic: experience of the Systemic Lupus International Collaborating Clinics. Ann Rheum Dis. 2021 Feb;80(2):1-2. doi: 10.1136/annrheumdis-2020-218164. Epub 2020 Jun 25. PMID: 32586918.
- Mendel A, Bernatsky S, Thorne JC, Lacaille D, Johnson SR, Vinet É. Hydroxychloroquine shortages during the COVID-19 pandemic. Ann Rheum Dis. 2020 May 20:annrheumdis-2020-217835. doi: 10.1136/annrheumdis-2020-217835. Epub ahead of print. PMID: 32434820.
- Zhao N, Liu Y, Smargiassi A, Bernatsky S. Tracking the origin of early COVID-19 cases in Canada. Int J Infect Dis. 2020 Jul;96:506-508. doi: 10.1016/j.ijid.2020.05.046. Epub 2020 May 17. PMID: 32425633; PMCID: PMC7231484.
SAFETY AND IMMUNOGENICITY OF COVID-19 VACCINES IN SYSTEMIC IMMUNE MEDIATED INFLAMMATORY DISEASES: INFECTIONS AND IMMUNITY (SUCCEED-II) – HYBRID IMMUNITY EXTENSION
Launched in 2021, the SUCCEED study follows adults 18 years and older who have autoimmune diseases such as rheumatoid arthritis, spondyloarthritis, inflammatory bowel disease, psoriasis, and other conditions (e.g. systemic lupus) to learn about their immune response to COVID-19 vaccines. We are extending the study (SUCCEED-II) to look at how vaccination and COVID-19 infection jointly affect hybrid immunity. People with autoimmune diseases often have to take immunosuppressive drugs, so they may be at risk not only for SARS-CoV-2 infection, but also possibly for poorer responses to COVID-19 vaccines.
The SUCCEED study is recruiting approximately 2,000 participants with these diseases and 250 who do not have these diseases (for control purposes) with investigators in Montreal (Inés Colmegna), Quebec City (Paul R. Fortin), Sherbrooke (Gilles Boire, Sophie Roux and Hugues Allard-Chamard), Toronto (Vinod Chandran, Anne-Claude Gingras, Tania Watts, and others), Hamilton (Dawn Bowdish and Maggie Larche), Winnipeg (Carol Hitchon and others), Calgary (Gil Kaplan and others), and Vancouver (Antonio Avina-Zubieta and Diane Lacaille).
We are collecting detailed information on both timing and type of vaccination and any SARS-CoV-2 infections. Participants do finger-prick blood tests at home at different time points over the study, and samples are tested for antibodies to the SARS-CoV-2 virus. Information about COVID-19 symptoms and testing is also collected, and some participants provide saliva samples to detect if they may have COVID-19 even without symptoms. A new addition is the use of special tests to see if antibodies that participants produce are effective at neutralizing COVID-19 virus in the lab.
COVID-19 vaccination has helped people who take immunosuppressive medications feel safe again, but more information is needed as we move forward into a ‘new normal’ with the possibility of yearly vaccination.
SAFETY AND IMMUNOGENICITY OF COVID-19 VACCINES IN SYSTEMIC IMMUNE MEDIATED INFLAMMATORY DISEASES: INFECTIONS AND IMMUNITY (SUCCEED-II) – HYBRID IMMUNITY EXTENSION
Marc Romney
Marc Romney, MD, FRCPC, DTM&H
Clinical Professor, University of British Columbia
Head, Medical Microbiology and Virology, St. Paul’s Hospital/Providence Health Care
Contact info
mromney@providencehealth.bc.ca
Publications
https://pubmed.ncbi.nlm.nih.gov/?term=romney+mg
DECONSTRUCTING HYBRID IMMUNE RESPONSES TO SARS-COV-2 IN OLDER ADULTS AND PEOPLE LIVING WITH HIV
Our project, which began in 2020 and is co-led by Drs. Marc Romney, Zabrina Brumme and Mark Brockman, is a longitudinal cohort study of 274 adults from key population groups relevant to COVID-19 vaccine and hybrid immunity studies. This includes older adults and long-term care residents, people living with HIV, and a control group consisting mainly of healthcare workers. For each participant, we have already collected baseline data (pre-vaccine) as well as blood samples after the first, second and third COVID-19 vaccine dose.
Our study will perform longitudinal characterizations of vaccine-induced immunity vs. hybrid immunity. Overall, 43% of the cohort has experienced SARS-CoV-2 infection, including 26% during the Omicron wave. We will quantify binding antibodies, virus neutralizing activity, as well as B cell and T cell responses against wild-type SARS-CoV-2 and Omicron spike proteins. We will also explore features of B cells and T cells that determine their antiviral activity and specificity, which may be used to develop new diagnostic tests to assess immune function in vaccinated and infected individuals.
We will apply multivariable analyses adjusting for age, health and vaccine-related factors when evaluating immune measures. Associations with symptom severity will also be explored. Importantly, many of our participants (e.g. healthcare workers and long-term care residents) have remained eligible for PCR testing throughout the pandemic.
We remain in contact with study participants and staff from long-term care sites which allows us to obtain additional clinical information and samples as needed through individual follow-up.
DECONSTRUCTING HYBRID IMMUNE RESPONSES TO SARS-COV-2 IN OLDER ADULTS AND PEOPLE LIVING WITH HIV
Pascal Lavoie
Pascal Lavoie
Associate Professor, University of British Columbia
Neonatologist, BC Women’s Hospital
Clinician-Scientist, BC Children’s Hospital Research Institute
Contact info
604-875-2135
Key words
Human immunology, Pediatric, Health, Cohort studies
Research interests
- Development of the human, neonatal immune system
- Immunity to common respiratory infections in infants
- Neonatal sepsis biomarkers
- COVID-19 immunity and viral transmission in schools
- Population immunity and cross-reactivity to SARS-CoV-2
Publications
https://pubmed.ncbi.nlm.nih.gov/?term=lavoie%20PM%20and%20covid&sort=date
LONG-TERM IMPACT OF COVID-19 INFECTION AND IMMUNITY IN EDUCATION WORKERS
This study is an extension of our study started in spring 2021 of education workers from three main school districts in the Vancouver metropolitan area. More than 85% of study participants have received at least three doses of a COVID-19 vaccine. We have collected blood samples at two time points; the second one is the baseline for the extension study. School districts have expressed an interest in continuing the study and are helping to facilitate our work.
The main objectives of the extension study are to:
- determine how the immunity of individuals who were infected after three doses of vaccines (hybrid immunity) differ from the immunity conferred by an infection alone;
- compare re-infection rates between individuals with hybrid versus vaccine immunity; and
- determine the long-term health impact of SARS-CoV-2 infections among school staff.
Using the baseline sample, we will measure participants’ serum antibody levels against recent Omicron variants, viral neutralization and other factors.
Among those in the study who have received at least three doses of a COVID-19 vaccine, 274 developed hybrid immunity, and 1,107 received three doses of vaccine but were never infected by the virus.
We are following all eligible individuals from the hybrid and vaccine immunity groups for one year, asking them to complete questionnaires to report SARS-CoV-2 infections (symptoms, hospitalization, dates of viral testing). Participants are also asked to provide a third blood sample in early 2023 to validate their self-reported infection data and estimate undetected infections. We will also determine the long-term health impact of infection through a mental and physical health questionnaire.
Results: LONG-TERM IMPACT OF COVID-19 INFECTION AND IMMUNITY IN EDUCATION WORKERS
Renée Bazin
Renée Bazin, PhD
Scientific Director, Medical Affairs and Innovation at Héma-Québec
Associate Professor at the University of Laval
Key words
Scientific Director, Medical Affairs and Innovation at Héma-Québec
Research interests
– Monoclonal antibodies
– Plasma immunoglobulins
– COVID convalescent plasma
– Humoral immunity against SARS-CoV-2
Publications
– Cognasse F et al.; Biomedical Excellence for Safer Transfusion (BEST) Collaborative. 2022. Assessment of the soluble proteins HMGB1, CD40L and CD62P during various platelet preparation processes and the storage of platelet concentrates: The BEST collaborative study. Transfusion Dec 1. Doi:10.1111/trf17200. Online ahead of print.
– Amri N et al. 2022. Blood endothelial-cell extracellular vesicles as potential biomarkers for the selection of plasma in COVID-19 convalescent plasma therapy. Cells 11(19):3122.
– Tauzin A et al. 2022. A boost with SARS-CoV-2 BNT162b2 mRNA vaccine elicits strong humoral responses independently of the interval between the two first doses. Cell Reports. 41(4):111554.
– Tauzin A et al. 2022. Humoral immune responses against SARS-CoV-2 Spike variants after mRNA vaccination in solid organ transplant recipients. iScience 25(9):104990.
– Laumaea AE et al. 2022. COVID-19 vaccine humoral response in frequent platelet donors with plateletpheresis-associated lymphopenia. Transfusion 62(9):1779-1790.
– Trépanier P et al.; Biomedical Excellence for Safer Transfusion Collaborative. 2022. Multicenter evaluation of the IL-3-pSTAT5 assay to assess the potency of cryopreserved stem cells from cord blood units: The BEST Collaborative study. Transfusion 62(8):1595-1601.
– Burnouf T et al.; ISBT COVID-19 Convalescent Plasma Working Group. 2022. Production and Quality Assurance of Human Polyclonal Hyperimmune Immunoglobulins Against SARS-CoV-2. Transfus Med Rev 36(3): 125-132.
– Al-Riyami AZ et al.; ISBT COVID-19 Convalescent Plasma Working Group. 2022. International Society of Blood Transfusion survey of experiences of blood banks and transfusion services during the COVID-19 pandemic. Vox Sang 117(6):822-830.
– Lewin A et al. 2022. Seroprevalence of SARS-CoV-2 antibodies among blood donors in Québec: an update from a serial cross-sectional study. Can J Public Health 113(3):385-393.
– Tauzin A et al. 2022. Evolution of Anti-RBD IgG Avidity following SARS-CoV-2 Infection. Viruses 14(3):532.
– Amri N et al. 2022. Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells. Pharmaceuticals 15(3):365.
– Chatterjee D et al. 2022. SARS-CoV-2 Omicron Spike recognition by plasma from individuals receiving BNT162b2 mRNA vaccination with a 16-week interval between doses. Cell Rep 38(9):110429.
– Simard C et al. 2022. Standardization of a flow cytometry SARS-CoV-2 serologic test. Cytotechnology 74(1):99-103.
– Bégin P et al. 2022. Author Correction: Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial. Nat Med 28(1):212.
– Bégin P et al.; CONCOR-1 Study Group, Arnold DM. 2022. Reply to: Concerns about estimating relative risk of death associated with convalescent plasma for COVID-19. Nat Med 28(1):53-58.
– Tauzin A et al. 2022. Strong humoral immune responses against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a 16-week interval between doses. Cell Host Microbe 30(1):97-109.e5
CHARACTERIZATION OF HUMORAL RESPONSE IN BLOOD DONORS VACCINATED AGAINST SARS-COV-2 AND THEN INFECTED WITH VARIANTS OF CONCERN
Following its emergence in late 2019, SARS-CoV-2, the virus that causes COVID-19, spread rapidly around the world. Vaccines were quickly developed against the virus, and now a significant portion of the world’s population is vaccinated. However, although these vaccines have been very effective in protecting against severe forms of the disease caused by several variants of concern (such as the Omicron variant), they are not very effective in limiting disease transmission. Thus, SARS-CoV-2 continues to circulate, including among vaccinated individuals. In addition, humoral responses (i.e., responses that lead to the production of antibodies to the virus) elicited by vaccination decline quite rapidly over time and new doses of vaccine may need to be administered regularly. It is well documented that vaccination of previously infected individuals results in a stronger and more durable immune response (so-called hybrid immunity) than in individuals who are vaccinated but have not been infected. However, the effects of infection with a SARS-CoV-2 variant (e.g. Omicron) in vaccinated individuals still need to be characterized.
In this study, we are prospectively evaluating the humoral response induced in participants vaccinated against SARS-CoV-2 and then infected with recently identified variants of concern (e.g. Omicron, BA.4/5). Several parameters of the humoral response are being measured, including the level of antibodies produced and their capacity (neutralization, recognition of the spikes of different variants, etc.), according to age and sex of participants. Our results will provide information on the type, duration of immunity, and level of protection for these individuals. We are also studying the immunity induced by the new bivalent vaccines against emerging SARS-CoV-2. Our data will contribute to the development of future vaccine strategies.
Andrés Finzi
Andrés Finzi, PhD
Canada Research Chair on Retroviral Entry, Member of The College of the Royal Society of Canada
Associate Professor, Faculty of Medicine
Université de Montréal
Centre de recherche du CHUM (CRCHUM)
Key words
HIV-1, Envelope glycoproteins, SARS-CoV-2, Spike, Humoral responses, Fc-mediated effector functions
Research interests
Dr. Finzi is an expert in HIV replication and antibody effector functions. His work identified new evasion mechanisms put in place by HIV to avoid immune responses. Dr. Finzi is also interested in the conformational landscape of the SARS-CoV-2 Spike, particularly on how it affects immune responses. His work has significant translational implications on the development of new therapeutic strategies to fight HIV and SARS-CoV-2.
Publications
– Prévost J, Gasser R, Beaudoin-Bussières G, Richard J, Duerr R, Laumaea A, et al. Cross-sectional evaluation of humoral responses against SARS-CoV-2 Spike. Cell Rep Med. 2020;1(7):100126. DOI: https://doi.org/10.1016/j.xcrm.2020.100126
– Perreault J, Tremblay T, Fournier MJ, Drouin M, Beaudoin-Bussières G, Prévost J, et al. Waning of SARS-CoV-2 RBD antibodies in longitudinal convalescent plasma samples within 4 months after symptom onset. Blood. 2020;136(22):2588-2591. DOI: https://doi.org/10.1182/blood.2020008367
– Beaudoin-Bussières G, Laumaea A, Anand SP, Prévost J, Gasser R, Goyette G, et al. Decline of humoral Responses against SARS-CoV-2 spike in convalescent individuals. mBio. 2020;11(5):e02590-20. DOI: https://doi.org/10.1128/mbio.02590-20
– Anand SP, Chen Y, Prévost J, Gasser R, Beaudoin-Bussières G, Abrams CF, et al. Interaction of human ACE2 to membrane-bound SARS-CoV-1 and SARS-CoV-2 S glycoproteins. Viruses. 2020;12(10):1104. DOI: https://doi.org/10.3390/v12101104
– Ding S, Laumaea A, Benlarbi M, Beaudoin-Bussières G, Gasser R, Medjahed H, et al. Antibody binding to SARS-CoV-2 S glycoprotein correlates with but does not predict neutralization. Viruses. 2020;12(11):1214. DOI: https://doi.org/10.3390/v12111214
– Lu M, Uchil PD, Li W, Zheng D, Terry DS, Gorman J, et al. Real-time conformational dynamics of SARS-CoV-2 spikes on virus particles. Cell Host Microbe. 2020;28(6):880-891. DOI: https://doi.org/10.1016/j.chom.2020.11.001
– Anand SP, Prévost J, Richard J, Perreault J, Tremblay T, Drouin M, et al. High-throughput detection of antibodies targeting the SARS-CoV-2 Spike in longitudinal convalescent plasma samples. Transfusion (in press). DOI: https://doi.org/10.1101/2020.10.20.346783
– Therrien C, Serhir B, Bélanger-Collard, Skrzypczak, Skank DK, Renaud C, et al. Multicenter evaluation of the clinical performance and the neutralizing antibody activity prediction properties of ten high throughput serological assays used in clinical laboratories. J Clin Microbiol. 2020;.02511-20. DOI: https://doi.org/10.1128/JCM.02511-20
– Gasser R, Cloutier M, Prévost J, Fink C, Ducas R, Ding S, et al. Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2. Cell Rep. 2021;10:108790. DOI: https://doi.org/10.1016/j.celrep.2021.108790
– Rébillard RM, Charabati M, Grasmuck C, Filali-Mouhim A, Tastet O, Brassard N, et al. Identification of SARS-CoV-2-specific immune alterations in acutely ill patients. medRxiv preprint. 2020. DOI: https://doi.org/10.1101/2020.12.21.20248642.
– Anand SP, Prévost J, Nayrac M, Beaudoin-Bussières G, Benlarbi M, Gasser R, et al. Longitudinal analysis of humoral immunity against SARS-CoV-2 Spike in convalescent individuals up to 8 months post-symptom onset. bioRxiv preprint. 2021. DOI: https://doi.org/10.1101/2021.01.25.428097.
– Papenburg J, Cheng MP, Corsini R, Caya C, Mendoza E, Manguiat K, et al. Evaluation of a commercial culture-free neutralization antibody detection kit for severe acute respiratory syndrome-related coronavirus-2 and comparison with an anti-RBD ELISA assay. medRxiv preprint. 2021. DOI: https://doi.org/10.1101/2021.01.23.21250325.
