This article is presented by Spectrum, a point of care tool for infectious diseases.

SARS-CoV-2 Vaccines Approved in Canada to Prevent COVID-19

As of March 5th, 2021, 4 vaccines have been authorized for use by Health Canada to prevent COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These vaccines are produced by the companies Pfizer-BioNTech¹, Moderna², AstraZeneca³, and Janssen⁴. This is amazing news and a testament to the work and determination of scientists, clinicians, and public health experts.

Amongst the excitement about the public rollout of these vaccines, an important question is being asked by those looking to be vaccinated:

“Which vaccine should I get?”

This is a fair and valid question with a short answer and a long rationale.

In short, all 4 vaccines are great options barring any medical contraindications.

The reason for this answer is complicated. All clinical trials look at the efficacy of the vaccine against COVID-19. Efficacy as defined by the Centre for Disease Control and Prevention (CDC)’s Principles of Epidemiology in Public Health Practice Introduction to Applied Epidemiology and Biostatistics textbook focuses on how much the vaccine reduces the incidence of disease in a vaccinated group in comparison to that in an unvaccinated group under ideal conditions, such as in a randomized controlled trial.

However, comparison of the different clinical trials is not easy, nor will it provide a fair interpretation of results. The design of the COVID-19 vaccine trials including primary and secondary outcomes, demographics of participants, and the presence of viral variants were not the same across all the clinical trials. There are, however, a few important themes that can be drawn to help answer the question “which vaccine should I get?”

The World Health Organization (WHO), through the Vaccine and Immunization Devices Assessment Team (VAX), has created a guiding document for evaluation of the COVID-19 vaccines.⁵ This document discusses key parameters regarding safety, efficacy, immunogenicity, and duration of protection of the prospective COVID-19 vaccines in trials. This guidance is paramount to decision making regarding safety and efficacy of the vaccines in clinical trials and takes into consideration additional data collected after public vaccine rollout to look at real world effectiveness and monitor for any rare adverse events. A component of this guidance is that the proposed vaccine(s) must exceed 50% efficacy against COVID-19.5

The vaccine clinical trials focus on a primary outcome(s), or central study question(s), around efficacy of the vaccine against confirmed symptomatic COVID-19: a measurable, disease-oriented outcome.


COVID-19 Vaccine Studies’ Primary Efficacy Endpoints

Vaccine Primary Efficacy Outcome
Pfizer-BioNTech (BNT162b2 mRNA) Confirmed COVID-19 with onset at least 7 days after second dose in participants without evidence of SARS-CoV-2 infection up to 7 days after the second dose.
Moderna (mRNA-1273) Prevention of the first occurrence of symptomatic COVID-19 with onset at least 14 days after the second dose among participants who were seronegative (no measurable antibodies) at baseline.
Janssen (Ad26.COV2.S) Prevention of moderate to severe or critical COVID-19, confirmed by positive SARS-COV-2 viral RNA PCR test.
AstraZeneca (AZD1222) Prevention of symptomatic COVID-19 with at least 1 qualifying symptom and a positive SARS-COV-2 viral RNA PCR test (based on a combination of 4 smaller studies with varying qualifying symptoms).


Disease-Oriented Versus Patient-Oriented Outcomes⁶

These disease-oriented outcomes, although essential for telling an important part of the vaccine efficacy story, do not often focus on some of the vital patient-oriented outcomes such as need for hospitalization, ventilation and death. These patient-oriented outcomes will likely have the largest impact on population health.

Because of the impact of patient-oriented outcomes, scientists and clinicians look for this information within the clinical trials to determine how well all these vaccines will work to control some of the most devastating outcomes associated with COVID-19. With that in mind, all COVID-19 vaccines appear to significantly reduce risk of severe disease and death in clinical trials;⁷𝄒⁸ however, studies were not powered to evaluate these outcomes. Therefore, real-world effectiveness data is being followed closely.


Real-World Effectiveness of the COVID-19 Vaccines

Once vaccines have completed clinical trials and are authorized for use outside of a trial, we assess how the vaccines are working in the “real-world”; that is, we measure effectiveness. The CDC’s Principles of Epidemiology in Public Health Practice Introduction to Applied Epidemiology and Biostatistics textbook defines effectiveness as measuring the proportion of reduction in cases in vaccinated versus unvaccinated groups, but in a real-world setting using observational trials.

Two of the major real-world type studies that you may read about in the coming months are case-control and cohort studies. There are several other study designs and pharmacovigilance databases that will contribute to data regarding the safety and effectiveness of vaccines over time. Below we are going to briefly review how case-control and cohort studies can help us understand more about COVID-19 vaccine effectiveness.

Case-control studies studies look at the vaccination status of those diagnosed with COVID-19 (cases) compared to those who were not diagnosed with COVID-19 (controls). For an effective vaccine, we would expect cases to be less likely to have received a vaccine than controls. This would add confidence that the vaccine is working in the real-world setting.

Cohort studies follow participants over time, both those who have and have not had a COVID-19 vaccine. Over this period of follow-up, we are looking to see if an individual participant develops the disease. An effective vaccine would result in fewer diagnoses of COVID-19 in those who were vaccinated compared to those who were not vaccinated. Cohort studies can be prospective (looking forward and starting in real time) or retrospective (looking at data that is being collected in real-time with outcomes in the past).

Below we will briefly review a retrospective cohort study utilizing data collected from the national vaccination campaign in Israel focusing on vaccination in health care workers (Israel has also provided further data regarding its nationwide vaccination campaign).


A Retrospective Cohort Study of Vaccine Effectiveness in Healthcare Workers¹⁰

In December 2020, the Israeli government began vaccinations with the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). The national immunization campaign prioritized all healthcare workers (HCW), except those previously documented to have been infected with SARS-CoV-2, as eligible for vaccination. A retrospective cohort study of 9019 vaccine eligible HCW comparing vaccinated versus unvaccinated individuals was conducted. All positive SARS-CoV-2 tests (by PCR) in HCW or community members were recorded as positive for infection. All PCR positive individuals responded to a contact tracing questionnaire and questions regarding symptoms.

  • Of the eligible staff, 7214 (79%) received 1 dose and 6037 (66%) received the complete 2 dose series.
  • A total of 170 SARS-CoV-2 infections among HCWs was documented between December 19th, 2020 to January 24th, 2021.


COVID-19 Infection and Rate Reduction Related Outcomes

Outcome Unvaccinated 1-14 days after 1st dose 15-28 days after 1st dose
Infection rates for SARS-CoV2 7.4/10 000 person-days 5.5/10 000 person-days 3/10 000 person-days
Adjusted rate reduction in infection - 30% (CI 2-50) 75% (CI 72-84)
Symptomatic COVID-19 rate 5/ 10 000 person-days 2.8/ 10 000 person-days 1.2/ 10 000 person-days
Adjusted rate reduction of COVID-19 disease - 47% (CI 17-66) 85% (CI 71-92)

Bottom-line: Vaccination, as described above, appears to be associated with a reduction in SARS-CoV-2 infection and symptomatic COVID-19 rates following administration of the first vaccine dose, with a greater reduction as more time elapses after vaccination.


Pharmacovigilance and Post-Market Monitoring

The Public Health Agency of Canada closely follows all reported adverse events following COVID-19 vaccinations and provides a report on the Health Infobase website. The Canadian Adverse Events Following Immunizations Surveillance system (CAEFISS) is where all adverse events following immunizations are tracked and categorized in Canada according to severity, in order to keep the public informed on this topic. Countries and regions around the world have different monitoring and reporting systems, for example, in the United States, this information is housed in the Vaccines Adverse Events Reporting system (VAERS) database.

It is important to note that all reports of adverse events received by Health Canada are included in this report regardless of whether they have been linked to the vaccine. Any serious adverse events are reviewed further to determine the need to reassess the safety of the vaccine. The current reports do not suggest any unusual adverse events for any of the COVID-19 vaccines.

When adverse events are reported that require further review and investigation, Health Canada issues a communication through the Recalls and Safety Alerts portal. This was recently done on March 11th, 2021 when Health Canada provided an update on the adverse events reported in Europe following vaccination with the AstraZeneca COVID-19 vaccine noting “at this time, there is no indication that the vaccine caused these [thromboembolic] events.” An updated statement was added to the Health Canada website on March 18th 2021.

The widespread administration of the COVID-19 vaccines worldwide and continued monitoring by Health Canada of all authorized COVID-19 vaccines is another reason to be confident in the rigorous process of assessing safety and efficacy of these vaccines.

Back to the Question: “Which Vaccine Should I get?”

If an individual has had an allergic reaction to a component of the vaccine or has a history of severe allergic reactions, it is always best to speak with a healthcare provider to determine the risk of a reaction following administration of any of the COVID-19 vaccines authorized in Canada.

Otherwise, all 4 COVID-19 vaccines offer great protection against severe disease and death based on clinical trials and real-world data and exceed the 50% efficacy against COVID-19 proposed by the WHO guidance discussed above.5 Also, there is no reason to assume that effectiveness of these vaccines will vary significantly from the proven efficacy in the clinical trial setting. This is the reason why you may be hearing:

“The best vaccine is the one offered to you.”

As we obtain more data from population-based studies regarding effectiveness, immunogenicity, tolerability and length of protection, we will be able to provide more details.


4 Useful Resources

1. Public Health Agency of Canada COVID-19 Main Page

2. Centre for Effective Practice COVID-19 Vaccines:COVID-19 Vaccines Tools

3. Centre for Disease Control’s Ensuring Vaccines Work

4. Unambiguous Science: summarizing evidence-based information for the COVID-19 vaccines


Biographies

Dr. Mira Maximos (PharmD) completed an Honours Specialization in Health Sciences and Major in Physiology at Western University & Bachelor of Science in Pharmacy at the University of Waterloo. She then completed a hospital pharmacy residency at London Health Sciences Centre concomitantly with a Master of Science in Pharmacy and went on to pursue a Doctor of Pharmacy degree at the University of Waterloo. Dr. Maximos works at Woodstock Hospital in Ontario as the Antimicrobial Stewardship Pharmacy Lead, with @Spectrum as the Knowledge Mobilization pharmacist, and the Centre of Excellence in Women’s Health as a Research Associate, on contract. She has been involved in research in different areas from medication taking behaviours, to medication safety and knowledge translation. Dr. Maximos lectures at the University of Waterloo in areas such as drug induced disease and infectious diseases in the elderly. Like Dr. Sankar and Dr. Gauthier, she participates in the COVID-19 Resource Canada Q&A town halls as a clinician-scientist. You can follow her on Twitter @miramaximos.

Dr. Krishana Sankar completed her PhD from the Faculty of Medicine at the University of Toronto where she specialized in cellular & molecular biology and used bioengineering with the aim of improving islet transplantation for type 1 diabetes. She is currently the science communication lead for COVID-19 Resources Canada and Advisory committee member for ScienceUpFirst. Dr. Sankar is passionate about countering misinformation and has been dispelling misconceptions around healthcare issues for several years. Since the COVID-19 pandemic was declared in March 2020, she has been sharing accurate scientific information with her communities. You can follow her on Twitter @KrishanaSankar.

Dr.Kimberley Gauthier is a research fellow at The Hospital for Sick Children in Toronto where she studies embryogenesis, tissue development, and lipids in Drosophila (fruit flies). She completed her PhD in Cell Biology at McGill University where she specialized in cell signaling, protein trafficking, genetics, and model organism (C. elegans) development. Since January 2021, she has been volunteering alongside scientists and clinicians from COVID-19 Resources Canada as a science communicator for COVID-19 vaccine Q&A town halls hosted for the public. You can follow her on Twitter @thekimgauthier.

Corri Levine is a graduate student at the University of Texas Medical Branch where she is completing her PhD in Human Pathophysiology and Translational Medicine and a Master’s in Public Health. Ms. Levine’s research focuses on therapeutics for emerging viruses such as ebolavirus and most recently has been involved in coordinating clinical research efforts for COVID-19. Ms. Levine is heavily involved in public health outreach including volunteering at local COVID-19 vaccination clinics and educating the community about the vaccines. You can follow her on Twitter @CBLevineMS.

Sabina Vohra-Miller has an MSc in Clinical Pharmacology from the University of Toronto. She is the founder of Unambiguous Science and the co-founder of the South Asian Health Network. She is the Vice-Chair of the board at Lymphoma Canada and sits on the Dean’s Advisory Committee at the Dalla Lana School of Public Health. Sabina’s passions include both science education, especially countering vaccine mis- and dis-information, as well as promoting and advocating for health equity and access to healthcare. You can follow her on Twitter @SabiVM.



Conflicts of Interest

  • Mira Maximos is employed with Spectrum Mobile Health as a Knowledge Mobilization pharmacist
  • Krishana Sankar declares no conflicts of interest
  • Kimberley Gauthier declares no conflicts of interest
  • Corri Levine declares no conflicts of interest
  • Sabina Vohra-Miller declares no conflicts of interest

This blog post is for information/educational purposes only, and does not substitute professional medical advice. Also please note that opinions are those of the authors and do not necessarily reflect that of their employers.



References:

1 Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577

2 Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2020;384(5):403-416. doi:10.1056/NEJMoa2035389

3 Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet (London, England). 2021;397(10269):99-111. doi:10.1016/S0140-6736(20)32661-1

4 National Institute of Health. Janssen Investigational COVID-19 Vaccine: Interim Analysis of Phase 3 Clinical Data Released. NIH News Release. Published 2021. Accessed March 12, 2021.

5 World Health Organization. Considerations for Evaluation of COVID-19 Vaccines: Points to consider for manufacturers of COVID19 vaccines. Vaccine and Immunization Devices Assessment Team (VAX). Published 2020. Accessed March 11, 2021.

6 Farley Library Research Guides. Evidence-Based Practice and Information Mastery: POEMs and DOEs. Evidence Based Practice and Information Mastery. Published 2021. Accessed March 11, 2021.

7 The Centre for Effective Practice. Types of COVID-19 Vaccines. Published 2021. Accessed March 5, 2021.

8 Public Health Agency of Canada. COVID-19 Vaccines and Treatments Portal. Published 2021. Accessed March 5, 2021.

9 Centre for Disease Control. Evaluating COVID-19 Vaccine Effectiveness in the Real World. Published 2021. Accessed March 12, 2021.

10 Amit S, Regev-Yochay G, Afek A, Kreiss Y, Leshem E. Early rate reductions of SARS-CoV-2 infection and COVID-19 in BNT162b2 vaccine recipients. Lancet (London, England). 2021;397(10277):875-877. doi:10.1016/S0140-6736(21)00448-7