Healthcare Practitioner COVID-19 Vaccine FAQs

COVID Vaccine-Specific Information

Vaccine Product Information

• Comirnaty™ COVID-19 Vaccine (Pfizer) - product monograph
• Pfizer-BioNTech - website
• SPIKEVAX™ (Moderna) - product monograph
• Moderna -  website
• COVISHIELD - product monograph
• Vaxzevria™ COVID-19 Vaccine (AstraZeneca) - product monograph
• Janssen COVID-19 Vaccine - product monograph

General Resources: 

• SK Drug Plan & Extended Benefits Branch - COVID-19 Immunization Program
• Saskatchewan Health Authority - Vaccine Info for HCPs
• Saskatchewan Health Authority- Vaccine Uptake Support
• eHealth COVID-19 Immunization Manual 
• Health Canada - COVID-19 page
• Health Canada - COVID-19 Vaccine page
• National Collaborating Centre for Infectious Diseases (NCCID) - home page
• Association of Medical Microbiology and Infectious Disease Canada - home page

Recommendations for Vaccine Use

• Health Canada - National Advisory Committee for Immunizations (NACI): Recommendations on the use of COVID-19 vaccine(s) 
• Public Health Agency of Canada (PHAC): COVID-19 Tool Kit for Health Care Providers
• Saskatchewan Health Authority: COVID-19 Vaccine Information
• The Society of Obstetricians and Gynaecologists of Canada (SOGC)- Statement on COVID-19 Vaccination in Pregnancy 
• Saskatchewan Cancer Agency - COVID-19 mRNA Vaccine in Adult Patients with Cancer
• The Canadian Network of MS Clinics - The CNMSC COVID-19 Recommendations

More Vaccine FAQs

• Saskatchewan Immunization Manual (SIM) Chapter 10 Biological Products provides links to the product monographs 
• For healthcare providers:
  • CanVax
  • Centre for Effective Practice

We were not able to find any information that suggests being on clozapine would be a contraindication to receiving the COVID-19 vaccine. However, the following information may be helpful for clinicians and patients on clozapine to consider:

• There is a single case report of increased clozapine levels and toxic effects in a patient on clozapine that received Comirnaty™ (Pfizer), but a causal relationship was neither determined nor ruled out. This would not be a reason to avoid vaccination, but may suggest increased monitoring for clozapine adverse effects following vaccination and clozapine drug level when indicated.⁽¹⁾
• There are several case studies indicate that COVID-19 infection can be associated with increased clozapine levels.^(2,3)  This may be attributed to infection-related inflammation inhibiting cytochrome P450 1A2 (CYP1A2), which then slows clozapine metabolism.⁽⁴⁾  This does not speak to any concern about giving a COVID-19 vaccine, but may explain the mechanism of increased drug levels.

Based on available information, and taking in to consideration the risk versus benefit, clozapine therapy would not be a contraindication to receiving the COVID-19 vaccine. It is important to ensure that the patient is aware of potential adverse effects, and monitor appropriately. 

References:

1. Thompson D, Delorme CM, White RF, Honer WG. Elevated clozapine levels and toxic effects after SARS-CoV-2 vaccination. J Psychiatry Neurosci. 2021 Mar 5;46(2):E210-E211. doi: 10.1503/jpn.210027. PMID: 33667055; PMCID: PMC8061735.
2. Cranshaw T, Harikumar T. COVID-19 infection may cause clozapine intoxication: case report and discussion. Schizophr Bull 2020;46:751.
3. Dotson S, Hartvigsen N, Wesner T, et al. . Clozapine toxicity in the setting of COVID-19. Psychosomatics 2020;61:577–8.
4. Clark SR, Warren NS, Kim G, et al. . Elevated clozapine levels associated with infection: a systematic review. Schizophr Res 2018;192:50–6.

May 20,2021

• Cases of Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT) have been reported following viral vector vaccines and usually occur between 4 and 28 days after receipt.
• Individuals should be monitored for symptoms -  such as persistent and severe headache, vision changes, seizures and other symptoms that resemble a stroke, such as weakness or numbness of the arms or legs, shortness of breath, abdominal or chest pain, swelling and redness in a limb and pallor and coldness in a limb, - for up to 42 days following a viral vector vaccine dose. If any of these symptoms present, individuals should seek immediate medical attention.
• The rate of VITT is estimated to be between 1 per 26,000 and 1 per 100,000 persons vaccinated with a first dose of Vaxzevria™ (AstraZeneca). As of May 12, 2021, PHAC has estimated the rate of VITT in Canada to be 1 in 83,000 doses administered, however, as investigations continue, this rate could be as high as 1 in 55,000.
• The frequency of VITT following a second dose of Vaxzevria™ (AstraZeneca) is currently reported as approximately 1 per 600,000 individuals vaccinated with a second dose but continues to evolve, based on vaccine safety surveillance data from the United Kingdom.

Reference: 

Note: while mixed vaccine regimens and Vaxzevria™ (AstraZeneca) are still authorized, some jurisdictions do not recognize these regimens. Those planning to travel must confirm with their planned destination what vaccines and/or regimens are considered valid, and may need to consider receiving two doses of the same mRNA product (i.e. receive two Comirnaty™ [Pfizer] doses or two SPIKEVAX™ [Moderna] doses). See “Who can receive 3rd and 4th doses” tab.

Saskatchewan is adopting the following strategy for vaccine to use as 2nd dose:

• Anyone who received Vaxzevria™ (AstraZeneca) or COVISHIELD for their first dose is eligible to receive Vaxzevria™ (AstraZeneca), Comirnaty™ (Pfizer) or SPIKEVAX™ (Moderna) for the 2nd dose, as preferred, unless contraindicated.
• mRNA vaccines (Comirnaty™ [Pfizer] or SPIKEVAX™ [Moderna]) are considered interchangeable. Anyone who received an mRNA vaccine for the 1st dose should take whichever of these two vaccines is available to them for their 2nd dose, rather than waiting for the same brand of vaccine. This will provide residents with more options to be immunized sooner.
• Currently there are limited data regarding safety and efficacy of interchangeability of COVID-19 vaccines. For a review of the current available evidence and to support informed decision making, refer to NACI Interchangeability of Authorized COVID-19 Vaccines Rapid Response full report or summary. 
  
  

  Minimum Intervals Between COVID-19 Vaccine Doses
  Vaccine Brand 1st Dose	Vaccine Brand 2nd Dose	Interval*
  Comirnaty™ (Pfizer)	Comirnaty™ (Pfizer)	Minimum 28 days^
  SPIKEVAX™ (Moderna)	SPIKEVAX™ (Moderna)	Minimum 28 days†
  Comirnaty™ (Pfizer)	SPIKEVAX™ (Moderna)	Minimum 28 days
  SPIKEVAX™ (Moderna)	Comirnaty™ (Pfizer)	Minimum 28 days
  Vaxzevria™ (AstraZeneca)	Vaxzevria™ (AstraZeneca)	Minimum 28 days
  Vaxzevria™ (AstraZeneca)	Comirnaty™ (Pfizer)	Minimum 28 days
  Vaxzevria™ (AstraZeneca)	SPIKEVAX™ (Moderna)	Minimum 28 days

  ^{*Previous information suggested 8-12 weeks between doses is optimal; however, with the Delta variant circulating in Saskatchewan, it's recommended that all residents receive second dose vaccinations as soon as eligible.
  ^21 days is the minimum interval authorized by Health Canada;19 days is included in NACI recommendations based on the per-protocol design for the Comirnaty™ (Pfizer) clinical trial that was 19-23 days. The province is adopting a 28 day interval for all vaccines. 
  †28 days is the minimum interval authorized by Health Canada; 21 days is included in NACI recommendations based on the majority of participants in the SPIKEVAX™ (Moderna) clinical trial received the second dose 21 to 42 days after the first, as per the pre-defined window.}

References

• NACI Rapid Response Interchangeability of Authorized COVID-19 Vaccines full report or summary
• Ministry of Health: COVID-19 Update for June 1
• DPEBB: Pharmacy FAQs on COVID-19 Vaccine Eligibility, updated Jun 22, 2021
• Saskatchewan COVID-19 update, June 21, 2021

• The Saskatchewan Ministry of Health has authorized additional doses for those who wish to complete a schedule acceptable for international travel in situations where their current completed immunization series is not approved by the country/agency/venue they intend to visit.
  • These doses are not mandatory and are not considered booster doses.
  • Consider necessity to travel and COVID-19 vaccine requirements at destination(s) –jurisdictions may recognize the individual’s current COVID-19 vaccination history.
  • See Table below for eligible combinations.
  • Doses should be separated by at least 28 days from the most recent  COVID-19 immunization; additional intervals from other vaccines may apply.
  • Currently, NACI has no recommendations for more than two doses.
  • There are preliminary data on the safety of third COVID-19 doses, mainly in the context of giving booster doses to immunocompromised patients. Results from a larger Comirnaty™ (Pfizer) study of a booster dose in healthy adults are still forthcoming. It is expected that individuals may experience mild to moderate symptoms (e.g., fever, chills, aches and pains at the injection site) after additional COVID-19 vaccine doses.

^{*Vaxzevria™ (AstraZeneca) is available through Public Health and may be given to individuals who have contraindications to mRNA vaccines.}

Reference: 

Ministry of Health Directives to Provide Additional COVID-19 Vaccine Doses

• All COVID-19 vaccines are to be injected intramuscularly and the deltoid is the preferred site.
• There may be instances when the deltoid sites cannot be used or are inaccessible. Examples may include individuals with:
  • Poor lymphatic circulation
    • These may include individuals with local lymphedema, upper limb amputation, axillary lymph node removal (which sometimes accompanies mastectomy), lymphangioma, arteriovenous (A-V) fistula
  • Poor muscle mass
  • Active cutaneous conditions (e.g. psoriasis plaques, inflammation, scars on the injection site)
  • Pain at the injection site
• If only one deltoid is affected, use the other deltoid.
• If both deltoid sites are unsuitable for IM injection, the vastus lateralis is an alternative site.
  • Landmarking
    • With the individual in the seated position, visually divide the length of the muscle from the greater trochanter of the femur to the lateral border of the kneecap into thirds.
    • Visually divide the width of the outer thigh in two with a horizontal line.
    • The injection site is in the middle third, just above the horizontal line.
  • Needle length
    • Needle length for IM injections is based on age, muscle mass and amount of subcutaneous tissue. For both deltoid and vastus lateralis:
      • 18 years and older: 1” to 1.5” (1” most common)
      • 5 to ≤ 17 years old: 1” (1.5” for heavier children)
• Dorsogluteal is NOT an acceptable alternative site.
  • This injection site is not used for active immunization because it is less immunogenic for vaccines.

References

• NACI Recommendations on the use of COVID-19 Vaccines
• Saskatchewan Immunization Manual: Chapter 8 Administration of Biological Products
• BC Centre for Disease Control: Communicable Disease Control; Chapter 2: Immunization; Appendix B –Administration of Biological Products

Approval for the vaccines is following the usual processes to ensure safety and efficacy. The process could be expedited because:

• more resources were made available
• resources / work were shifted from other projects to focus on the vaccine
• global agencies have been working together and sharing data
• trials were undertaken in areas with high risk of COVID-19 infection so it didn't take long to accrue data

• The two mRNA vaccines have been shown to be ~95% effective beginning one week (Comirnaty™ [Pfizer]) to two weeks (SPIKEVAX™ [Moderna]) after the 2^nd dose. Note: The stated effectiveness of both of these vaccines are for the dominant strains of the virus and do not yet account for the variants that have popped up since.
  • Individuals may not be optimally protected until 1-2 weeks after receiving the second dose.  
  • Maximum duration of immunity is not yet known; data continue to be collected.
• Vaxzevria™ (AstraZeneca) and COVISHIELD have demonstrated an average efficacy of ~62% effective in those 18-64 years of age. 
  • The protection offered by the first dose of the viral vector vaccine is comparable to the efficacy observed after the second dose, with protection lasting until the second dose is administered (up to 12 weeks later).
  • Maximum duration of immunity is not yet known; data continue to be collected.
• The Janssen COVID-19 vaccine had a 72% efficacy in preventing COVID infections after 28 days in the company’s U.S. trials. Note: The efficacy dropped to 66% when averaging in results from other global trials, including a South African study that factored in more transmissible variants of the COVID virus.

Short-term adverse effects are similar to those experienced with other vaccines and no safety concerns have been identified. Long-term adverse effects are not known, though most adverse effects of vaccines appear fairly soon after the dose.

In clinical trials of mRNA vaccines, some adverse events, including fever, are more frequent after the second dose; this was not the case with Vaxzevria™ (AstraZeneca).

Viral vector-based vaccines use a harmless virus, such as an adenovirus, as a delivery system. This “vector” virus is not the virus that causes COVID-19. Adenoviruses are among the viruses that can cause the common cold. There are many different types of adenoviruses, and many have been used as delivery systems for other vector-based vaccines for decades.

When a person is given the vaccine, the vector virus contained within the vaccine produces the SARS-CoV-2 spike protein. This protein is found on the surface of the virus that causes COVID-19. This protein will not make you sick. It does its job and goes away. Just like with a natural infection, when the immune cells in the body are exposed to parts of the virus in a vaccine, antibodies are developed and immune cells are primed to respond to prevent infection. 

Canada has authorized 2 manufacturers of the ChAdOx1-S vaccine:

• AstraZeneca (brand name Vaxzevria™ COVID-19 Vaccine)
• Verity Pharmaceuticals and Serum Institute of India (SII) in collaboration with  AstraZeneca (brand name COVISHIELD)

Vaxzevria™ COVID-19 Vaccine (manufactured by AstraZeneca) and COVISHIELD (manufactured by Serum Institute of India) are ChAdOx1-S recombinant vaccines developed by AstraZeneca and Oxford University. Health Canada has reviewed the manufacturing information for these vaccines and found them to be comparable.

Unfortunately, at this time, the duration of protection after receiving one or both doses is unknown. The vaccine clinical trials have only provided us with short-term data; data continue to be collected.