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Oxford-AstraZeneca and Janssen / Johnson & Johnson... Two More COVID-19 Vaccines Approved by Canada

( Current upated information as of 25-Mar-2021 )
By Farheen Khan, (Hons)B.Sc. (Biochemistry) [Get Well Clinic]

 

It is now the month of March, and a few more vaccine candidates have marched into our COVID-19 vaccine toolkit. These include the newly approved Oxford-AstraZeneca and Janssen-Johnson & Johnson vaccines.  

Both vaccines are viral vector vaccines.1 More specifically, these vaccines contain a weakened, live adenovirus - a virus that causes the common cold.2 To develop these vaccines, scientists first removed all disease-causing and replication-related genes from the adenovirus.1,3–5 As the adenovirus can now no longer replicate or cause disease, it is harmless to the human body.1,3–5 

Next, scientists inserted the DNA, or genetic instructions, for the SARS-CoV-2 spike protein into the modified adenovirus.1

Now, you may be wondering, “why the spike protein?” This is because it is the spike protein of the SARS-CoV-2 virus that interacts with a specific receptor, the ACE-2 receptor, on the surface of our cells.6 Upon interaction, the virus is internalized into our cells, and proceeds to take over our cells’ machinery, repurposing them to create more copies of the virus. These infected cells then release millions of copies of the virus which then go on to infect other cells in our bodies, ultimately causing the COVID-19 disease.7

Once injected with the Oxford-AstraZeneca or Janssen-Johnson & Johnson vaccine, the adenovirus acts as a “viral vector,” or tool, to deliver the DNA of the SARS-CoV-2 spike proteins to the cells of the vaccinated individual.1,3–5 The adenovirus enters the cells, and inserts their genetic information, along with the spike protein DNA, into the vaccinated individual’s cells’ nuclei.1,3 Our cells’ machinery then transcribes this DNA into RNA in the nucleus of our cells.8 This RNA is then processed to become mature messenger RNA (mRNA).8 After this, the mRNA is transported to the cytoplasm of our cells (thus called messenger RNA), and is decoded and translated into the spike proteins, which are then presented on the surface of the vaccinated individual’s cells.8

 

Figure 1. The central dogma process includes DNA transcription into RNA (in nucleus), RNA processing to mRNA (in nucleus), and mRNA translation to protein product (in cytoplasm).

 

The presence of the spike proteins, and the adenovirus itself, then elicits an immune response as the individual’s body recognizes the protein and adenovirus as foreign substances.1–5 More specifically, the immune system produces antibodies against the protein and adenovirus, and executes other necessary immunogenic responses as well.9–11 Since only one protein of the virus would be created, rather than the whole virus itself, the vaccine cannot infect a vaccinated individual with COVID-19.1 

As a note, antibodies are large Y-shaped proteins that stick to the surface or part of a virus or bacteria, tagging it for attack by other elements of the immune system to ultimately neutralize the virus or bacteria.12 Antibodies are designed to bind to and attack one kind of virus or bacteria only.12 This means that an antibody that is for instance designed to destroy the Influenza A virus, cannot be used to attack the SARS-CoV-2 or EBOV viruses. 

As antibodies specific to the SARS-CoV-2 spike protein are produced upon administration of the Oxford-AstraZeneca or Janssen-Johnson & Johnson vaccine, if the SARS-CoV-2 virus does enter the vaccinated individual’s body at a later time, the antibodies produced post-vaccination will be able to recognize the spike proteins of the virus and thus bind to them.4,5,10,13 As a result, the virus will be unable to bind to the ACE-2 receptors on the surface of the individual’s cells, and therefore will not be internalized, rendering it incapable of taking over the cells’ machinery and replicating.10,13 In addition, the binding of the antibodies to the spike proteins present on the surface of the SARS-CoV-2 virus will also tag the virus for degradation by other elements of the immune system.10,13

 

Figure 2. The engineered adenoviral-vector containing the DNA for the SARS-CoV-2 spike protein is injected into an individual’s body. The DNA is transcribed into mRNA, which is then translated into a fragment or version of the SARS-CoV-2 spike protein in the cytoplasm of the individual’s cells. As the spikes are released from the individual’s cells, their immune system produces antibodies and releases T-cells to execute necessary immunogenic reactions. This image has been adapted from a Figure in The Washington Post’s “Your questions about coronavirus vaccines, answered” under “How does the Johnson & Johnson vaccine work?”.13

 

It is important to note that the adenovirus cannot replicate itself and does not have the necessary machinery to integrate into their hosts’ DNA. As such, an individual’s DNA will not be altered upon vaccination.1,3,11 Further, viral-vector vaccines tend to be less effective if the viral-vector in use is a virus that people may already have antibodies for.3,11 If this occurs, then the antibodies would overwhelm the adenovirus before it even gets the chance to deliver the spike protein DNA.3,11 As such, scientists at Oxford-AstraZeneca and Janssen-Johnson & Johnson have ensured to use adenoviruses that humans are unlikely to have encountered before.4,5 More specifically, the Oxford-AstraZeneca vaccine uses a modified version of a chimpanzee adenovirus, and the Janssen-Johnson & Johnson vaccine uses a recombinant, or modified, human adenovirus (adv26) - the same adenovirus that has been used in the company’s Ebola virus vaccine.4,5  

Now that we know how these viral-vector vaccines work, I would like to mention that this technology, unlike that of the mRNA vaccines, is not new.3,11 Research regarding adenoviral-vector vaccines date back to the 1990s.11 Adenoviruses were originally studied to be used in gene transfer therapy for diseases including cystic fibrosis.11,14 Though they seemed promising at first, it unfortunately did not work out as adenoviruses induce strong immune responses, causing them to be removed by our immune system fairly quickly, thus limiting their purpose in gene therapy.11,14 However, this very characteristic is what makes adenoviruses excellent candidates for vaccine development against infectious diseases.1,3,11 As such, scientists have worked on adenoviral-vector vaccines against a multitude of diseases including HIV, Zika and Tuberculosis.5,11  Further, adenoviral-vector vaccines were produced and distributed to West Africa and the Democratic Republic of the Congo during the Ebola outbreaks in the past decade.5,11,15 

Aside from the fact that these vaccines can induce strong immune responses and that they are a well-established technology, the Oxford-AstraZeneca and Janssen-Johnson & Johnson vaccines bring additional advantages over the Pfizer-BioNTech and Moderna vaccines.3 For instance, both adenoviral-vector vaccines can be stored in normal 2°C-8°C refrigerators for up to three to six months, making distribution of these vaccines easier.16,17 The Janssen-Johnson & Johnson vaccine also only requires one shot, while the others require two shots - something that can be of great help if we fall low in vaccination supply.17,18  For more comparisons between the Pfizer-BioNTech, Moderna, Oxford-AstraZeneca, and Janssen-Johnson & Johnson vaccines, please refer to Table 1 below. 

So, which vaccine is the best vaccine to take? They all are. Despite their differing overall efficacies, all vaccines have been approved for use in Canada, and are all 90-100% effective in preventing the worst outcomes: hospitalizations and death.19 It’s important that you get vaccinated with whichever vaccine is available to you as soon as possible to prevent the worst possible outcomes from COVID-19 infection. It is also important to remember that for the vaccination to be effective, we must combine the immunization strategy with continuous mask-wearing, hand-washing, and social distancing. We are multiple steps closer to potentially winning the battle against this life-changing virus than we were at the start of this year. We need to continue to remain cautious as everyone gets vaccinated so that we can ensure our success, and hopefully go back to the pre-COVID-19 times, when lockdowns, stay-at-home orders, and indoor capacity restrictions were not parts of our daily lives. 

DISCLAIMER: You may have heard on the news that several countries in the European Union suspended administration of the Oxford-AstraZeneca vaccine due to safety concerns.20–22 Out of approximately 20 million European residents who received their first dose of the Oxford-AstraZeneca vaccine, 30 individuals were reported to have developed blood clots.20 After conducting a review of the safety data, the European Union’s medicine regulator has since deemed the vaccine to be safe, and has even said that the benefits of the vaccine outweigh the risk of side effects.20,23 To put this into perspective, in the United States, 1 to 2 adults per 1000 are affected by venous thromboembolism (blood clots in the veins) each year, with higher risk in men, and individuals of older age.24,25 In fact, the World Health Organization even states that “venous thromboembolism is the third most common cardiovascular disease globally.”26 Furthermore, the incidence of venous thromboembolism associated with the COVID-19 disease is 21%, which further increases to 31% in ICU-related cases.27 As such, by vaccinating individuals, and thus reducing their risk of severe COVID-19 disease and complications, the overall risk of developing blood clots would actually be reduced. Thrombosis Canada also states, “there is no link between receiving this vaccine and the development of blood clots … vaccines of any type are not associated with the development of blood clots.”22 Finally, according to an interim analysis report regarding the U.S. Phase 3 trials published on March 22, 2021, “the data safety monitoring board conducted a specific review of thrombotic events, as well as cerebral venous sinus thrombosis (CVST) with the assistance of an independent neurologist … (and) found no increased risk of thrombosis or events characterised by thrombosis among the 21,583 participants receiving at least one dose of the vaccine.”28

 

TABLE 1. Table to Summarize the Similarities and Differences between the Two Vaccines*

 

 

Pfizer-BioNTech Vaccine

Moderna

Oxford-AstraZeneca

Janssen-Johnson & Johnson

Type of Vaccine

mRNA29

mRNA29

Non-replicating adenoviral vector30

Non-replicating adenoviral vector17,31

Shelf-life at Normal Refrigeration Temperatures (2°C-8°C)

5 days29

30 days29

6 months30

3 months17

Dosage Required

Two 0.3mL doses (30μg of mRNA each);

21 days apart29

Two 0.5mL doses (100μg of mRNA each);

28 days apart29

Two 0.5mL doses (5x1010 viral particles each);

12 weeks apart30,32

 

One 0.5mL dose (5x 1010 viral particles each)5

# of Phase 3 Trial Participants

> 43,00029

> 30,00029

> 17,00030

> 43,00017

Participants’ Age and Health Conditions

Age groups: 12-15 (100 participants only); 18-55; 65-85

Health Conditions: Healthy individuals with and without prior SARS-CoV-2 infection; Individuals with stable pre-existing disease; Individuals with stable, chronic HIV, HCV, and HBV infection29

Age: 18+;

Health Conditions: Healthy with no previous history of SARS-CoV-2 infection; Individuals with stable pre-existing medical conditions29

Age: 18-65;

Health Conditions: Healthy individuals; Individuals with stable pre-existing medical conditions33

Age: 18+;

Health Conditions: “Adults with and without comorbidities (most common comorbidities were obesity and hypertension) associated with increased risk of progression to severe COVID-19”5

Trial Design

Randomized, blinded, placebo-controlled29

Randomized, blinded, 1:1 placebo-controlled29

Randomized, blinded, placebo-controlled30

Randomized, blinded, placebo-controlled5,17

Placebo Used

Saline solution29

Saline solution29

Meningococcal vaccine or saline solution33

Saline solution5

Overall

Efficacy

95%

(>94% in individuals over the age of 65)29

94.1%29

54.9%-82.4%34**

66%17

When was Vaccine Efficacy Measured?

7 days after second dose

(day 28)29

14 days after second dose

(day 42) 29

At least 15 days after second dose (day varied) 34

14 days and 28 days after initial dose (day 14, 28)17

Observed Side Effects

Fatigue, Headache, Pain at Injection Site29

Fatigue, Muscle Aches, Headache, Pain, Redness at Injection Site29

Fatigue, Headache, Pain and Tenderness at Injection Site, Feverishness, Muscle Aches35

Fatigue, Headache, Pain at Injection Site, Muscle Aches36

How Long Will Participants Be Monitored?

2 years after second dose29

2 years after second dose29

2 years after second dose in U.S. trials37

2 years after vaccination5,17

*Note: These are initial clinical study trial data available by December 2020 in trials of less than 100,000 people, and short-term endpoints. The real-world results that are coming out in 2021 as over 100 million people are being vaccinated with COVID-19 vaccines likely will show even better results.

**Oxford-AstraZeneca conducted four randomized, controlled trials in Brazil, the U.K., and South Africa. As per their interim analysis (published in December 2020), trial participants were in one of two cohorts: the standard-dose cohort (receiving two doses with 5x1010 viral particles each) and the low-dose cohort (one dose with 2.5x1010 viral particles, and one dose with 5x1010 viral particles). For all cases, the doses were administered 28 days apart. The vaccine efficacy (VE) in the standard-dose cohort was 63.1%, while the VE in the low-dose cohort was 80.7%, with an overall VE of 66.7%. However, more recent data according to a pre-print posted in the Lancet on February 2021 showed that by increasing the dose interval from less than six weeks to 12 weeks or more, the VE also increased from 54.9% to 82.4% in the standard-dose cohort, suggesting that VE, in Oxford-AstraZeneca’s case, increases with longer interval periods between the two doses.34 Further, as per another interim analysis report regarding the U.S. Phase 3 trials published in March , 2021, the Oxford-AstraZeneca vaccine was 76-79% effective at preventing symptomatic COVID-19, 100% effective at preventing severe disease and hospitalization, and 80-85% effective in participants aged 65 years and over.28,44 The U.S. participants received two standard doses, four weeks apart, following the promising data in the Lancet pre-print.28,44

 

ADDITIONAL INFORMATION REGARDING RESULTS OBSERVED IN PHASE 3 CLINICAL TRIALS

Oxford-AstraZeneca executed their blinded, multi-centre, randomized, controlled Phase 3 trials with over 17,000 individuals in the UK, Brazil, and South Africa.30 Oxford-AstraZeneca then measured the efficacy of their vaccine candidate 28 days after trial participants received their first dose and found that the overall vaccine efficacy was 66.7% 30,32 While trial participants in South Africa and Brazil received two standard doses (~5x1010 viral particles each), participants in the UK received either two standard doses (~5x1010 viral particles each), or one half dose (~2.5x1010 viral particles) and one standard dose.33 While collecting participants’ blood samples and conducting clinical assessments for information regarding the vaccine’s safety and immunogenicity, weekly swabbing was also done “for detection of infection and assessment of vaccine efficacy against infection.”30 For reasons that are yet to be determined, Oxford-AstraZeneca found that the vaccine efficacy was higher in the cohort of participants who received one half dose and one standard dose compared to the cohort of participants who received two standard doses only.16 Further analysis in a preprint under review in the Lancet reported that “a single standard dose of vaccine provided 76% protection overall against symptomatic COVID-19 in the first 90 days after vaccination with protection not falling in this time frame.”27,32 Also, with a dosing interval of 12 weeks or more, vaccine efficacy reached 82.4% after a second dose, compared to a 54.9% efficacy when the two doses were given less than six weeks apart.34,38 In the cohort of participants who received two standard doses, 22 hospitalization cases were reported in the placebo group compared to two cases in the vaccine group. No deaths were observed in the vaccine group, but one case of death was reported in the placebo group.34 Overall, 332 symptomatic cases were reported in the analysis population of over 17,000 participants.30 As of February 2021, Oxford-AstraZeneca have extended their study to assess the effects of their vaccine on children aged 6-17, with approximately 300 trial participants.39 On March 25, 2021, AstraZeneca published a news release, reporting the outcomes as per an interim analysis regarding the U.S. Phase 3 trials. In these trials, “trial participants aged 18 years or over who are healthy or have medically stable chronic diseases and are at increased risk for being exposed to the SARS-CoV-2 virus” received either two standard doses of the Oxford-AstraZeneca vaccine or saline placebos, four weeks apart.44 According to the news release, the Oxford-AstraZeneca vaccine was 76% effective at preventing symptomatic COVID-19, 100% effective against severe or critical disease and hospitalization, and 85% effective in participants aged 65 years and over.44 The vaccine efficacy was also consistent across ethnicity and age.44 Out of the 32,449 participants, 141 symptomatic cases were reported, with no increased risk of thrombosis or events characterized by thrombosis.44

More information about the Oxford-AstraZeneca vaccine and its Phase 3 trial can be found at: 

Janssen-Johnson & Johnson executed their blinded, randomized, controlled Phase 3 trials with over 43,000 individuals in the U.S., Latin America, and South Africa.17,40 Janssen-Johnson & Johnson then measured the efficacy of their vaccine candidate at two co-primary endpoints: 14 days post-vaccination, and 28 days post-vaccination.17 Trial participants were monitored daily and blood samples, saliva samples, and nasal swabs were collected.41 The efficacy of this vaccine varied geographically: 72% in the United States, 66% in Latin America, and 57% in South Africa.42 In all areas, there were no COVID-19 related hospitalization or death, 28 days post-vaccination.43 Further, the vaccine was 81.7% effective against severe forms of COVID-19 in South Africa, meaning that the Janssen-Johnson & Johnson vaccine can provide protection against serious disease caused by the South African SARS-CoV-2 variant.18 Overall, the vaccine was “85 percent effective in preventing severe disease across all regions studied.”43 468 symptomatic cases were reported after at least 14 days post-vaccination, and 261 symptomatic cases were reported at least 28 days post-vaccination in the analysis population of over 43,000 participants.18

More information about the Janssen-Johnson & Johnson vaccine and its Phase 3 trial can be found at: 

 

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E.; Saunders, C.; Sayed, A.; Schim van der Loeff, I.; Schmid, A. B.; Schofield, E.; Screaton, G.; Seddiqi, S.; Segireddy, R. R.; Senger, R.; Serrano, S.; Shah, R.; Shaik, I.; Sharpe, H. E.; Sharrocks, K.; Shaw, R.; Shea, A.; Shepherd, A.; Shepherd, J. G.; Shiham, F.; Sidhom, E.; Silk, S. E.; da Silva Moraes, A. C.; Silva-Junior, G.; Silva-Reyes, L.; Silveira, A. D.; Silveira, M. B. V.; Sinha, J.; Skelly, D. T.; Smith, D. C.; Smith, N.; Smith, H. E.; Smith, D. J.; Smith, C. C.; Soares, A.; Soares, T.; Solórzano, C.; Sorio, G. L.; Sorley, K.; Sosa-Rodriguez, T.; Souza, C. M. C. D. L.; Souza, B. S. D. F.; Souza, A. R.; Spencer, A. J.; Spina, F.; Spoors, L.; Stafford, L.; Stamford, I.; Starinskij, I.; Stein, R.; Steven, J.; Stockdale, L.; Stockwell, L. V.; Strickland, L. H.; Stuart, A. C.; Sturdy, A.; Sutton, N.; Szigeti, A.; Tahiri-Alaoui, A.; Tanner, R.; Taoushanis, C.; Tarr, A. W.; Taylor, K.; Taylor, U.; Taylor, I. J.; Taylor, J.; te Water Naude, R.; Themistocleous, Y.; Themistocleous, A.; Thomas, M.; Thomas, K.; Thomas, T. M.; Thombrayil, A.; Thompson, F.; Thompson, A.; Thompson, K.; Thompson, A.; Thomson, J.; Thornton-Jones, V.; Tighe, P. J.; Tinoco, L. A.; Tiongson, G.; Tladinyane, B.; Tomasicchio, M.; Tomic, A.; Tonks, S.; Towner, J.; Tran, N.; Tree, J.; Trillana, G.; Trinham, C.; Trivett, R.; Truby, A.; Tsheko, B. L.; Turabi, A.; Turner, R.; Turner, C.; Ulaszewska, M.; Underwood, B. R.; Varughese, R.; Verbart, D.; Verheul, M.; Vichos, I.; Vieira, T.; Waddington, C. S.; Walker, L.; Wallis, E.; Wand, M.; Warbick, D.; Wardell, T.; Warimwe, G.; Warren, S. C.; Watkins, B.; Watson, E.; Webb, S.; Webb-Bridges, A.; Webster, A.; Welch, J.; Wells, J.; West, A.; White, C.; White, R.; Williams, P.; Williams, R. L.; Winslow, R.; Woodyer, M.; Worth, A. T.; Wright, D.; Wroblewska, M.; Yao, A.; Zimmer, R.; Zizi, D.; Zuidewind, P. 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. The Lancet 2021, 397 (10269), 99–111. https://doi.org/10.1016/S0140-6736(20)32661-1.

(34)      Voysey, M.; Costa Clemens, S. A.; Madhi, S. A.; Weckx, L. Y.; Folegatti, P. M.; Aley, P. K.; Angus, B. J.; Baillie, V.; Barnabas, S. L.; Bhorat, Q. E.; Bibi, S.; Briner, C.; Cicconi, P.; Clutterbuck, E.; Collins, A. M.; Cutland, C.; Darton, T.; Dheda, K.; Douglas, A. D.; Duncan, C. J. A.; Emary, K. R. W.; Ewer, K.; Flaxman, A.; Fairlie, L.; Faust, S. N.; Feng, S.; Ferreira, D. M.; Finn, A.; Galiza, E.; Goodman, A. L.; Green, C. M.; Green, C. A.; Greenland, M.; Hill, C.; Hill, H. C.; Hirsch, I.; Izu, A.; Jenkin, D.; Kerridge, S.; Koen, A.; Kwatra, G.; Lazarus, R.; Libri, V.; Lillie, P. J.; Marchevsky, N. G.; Marshall, R. P.; Mendes, A. V. A.; Milan, E. P.; Minassian, A. M.; McGregor, A. C.; Farooq Mujadidi, Y.; Nana, A.; Payadachee, S. D.; Phillips, D. J.; Pittella, A.; Plested, E.; Pollock, K. M.; Ramasamy, M. N.; Robinson, H.; Schwarzbold, A. V.; Smith, A.; Song, R.; Snape, M. D.; Sprinz, E.; Sutherland, R. K.; Thomson, E. C.; Torok, M.; Toshner, M.; Turner, D. P. J.; Vekemans, J.; Villafana, T. L.; White, T.; Williams, C. J.; Hill, A. V. S.; Lambe, T.; Gilbert, S. C.; Pollard, A.; Group, O. C. V. T. Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 NCoV-19 (AZD1222) Vaccine; SSRN Scholarly Paper ID 3777268; Social Science Research Network: Rochester, NY, 2021. https://doi.org/10.2139/ssrn.3777268.

(35)      Information for UK recipients on COVID 19 Vaccine AstraZeneca https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-astrazeneca/information-for-uk-recipients-on-covid-19-vaccine-astrazeneca (accessed Mar 18, 2021).

(36) CDC. Information about Johnson & Johnson's Janssen COVID-19 Vaccine https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/janssen.html (accessed Mar 18, 2021).

(37)      Phase 3 Clinical Testing in the US of AstraZeneca COVID-19 Vaccine Candidate Begins https://www.nih.gov/news-events/news-releases/phase-3-clinical-testing-us-astrazeneca-covid-19-vaccine-candidate-begins (accessed Mar 18, 2021).

(38)      Wise, J. Covid-19: New Data on Oxford AstraZeneca Vaccine Backs 12 Week Dosing Interval. BMJ 2021, 372, n326. https://doi.org/10.1136/bmj.n326.

(39)      Oxford coronavirus vaccine childrens study - FAQs https://www.research.ox.ac.uk/Article/2021-02-15-oxford-coronavirus-vaccine-childrens-study-faqs (accessed Mar 18, 2021).

(40)      Johnson & Johnson Initiates Pivotal Global Phase 3 Clinical Trial of Janssen’s COVID-19 Vaccine Candidate | Johnson & Johnson https://www.jnj.com/johnson-johnson-initiates-pivotal-global-phase-3-clinical-trial-of-janssens-covid-19-vaccine-candidate (accessed Mar 18, 2021).

(41)      About Our ENSEMBLE Studies https://www.jnj.com/coronavirus/about-phase-3-study-of-our-covid-19-vaccine-candidate (accessed Mar 18, 2021).

(42)      Janssen Investigational COVID-19 Vaccine: Interim Analysis of Phase 3 Clinical Data Released https://www.nih.gov/news-events/news-releases/janssen-investigational-covid-19-vaccine-interim-analysis-phase-3-clinical-data-released (accessed Mar 18, 2021).

(43)      Johnson & Johnson COVID-19 Vaccine Authorized by U.S. FDA For Emergency Use | Johnson & Johnson https://www.jnj.com/johnson-johnson-covid-19-vaccine-authorized-by-u-s-fda-for-emergency-usefirst-single-shot-vaccine-in-fight-against-global-pandemic (accessed Mar 17, 2021).

(44)    AZD1222 US Phase III primary analysis confirms safety and efficacy , https://www.astrazeneca.com/media-centre/press-releases/2021/azd1222-us-phase-iii-primary-analysis-confirms-safety-and-efficacy.html (accessed Mar 25, 2021).

 

 

 

 

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2021: A SHOT at a Better Year

How the COVID-19 mRNA Vaccines Work

Farheen Khan, (Hons)B.Sc. (Biochemistry) [Get Well Clinic]

 

The year 2020 will forever be remembered as the year of COVID-19, social distancing, cancelled plans, and more. Luckily, it is coming to an end (finally) with promising results from Pfizer/BioNTech and Moderna regarding the availability of COVID-19 vaccines by early 2021. These vaccines are one type of many different vaccine systems being developed and produced for protection against COVID19.

Both vaccines are messenger RNA (mRNA) vaccines.1,2 Before going on to further explain how these vaccines work, I’d like to first assure that the mRNA engineered for the Pfizer and Moderna vaccines will not integrate into and remain in our DNA forever. Here’s why:

If we look at the central dogma process, our DNA (genetic material) is transcribed into RNA in the nucleus of our cells.3 This RNA is then processed to become mature mRNA. After, this mRNA is transported to the cytoplasm of our cells (thus called messenger RNA), where it is decoded and translated into corresponding proteins.3

 

Figure 1. The central dogma process includes DNA transcription into RNA (in nucleus), RNA processing to mRNA (in nucleus), and mRNA translation to protein product (in cytoplasm).

When someone is injected with the mRNA in the Pfizer or Moderna vaccines, the mRNA travels encapsulated in lipid nanoparticles to the cytoplasm of the individual’s cells.4,5 The mRNA then serves as genetic instructions for the cells and is translated to create the engineered protein of interest. In this case, the protein of interest is a version or part of the SARS-CoV-2 spike protein.4,5

Now, you may be wondering, “why the spike protein?” This is because it is the spike protein of the virus that interacts with a specific receptor, the ACE-2 receptor, on the surface of our cells.6 Upon interaction, the virus is internalized into our cells, and proceeds to take over our cells’ machinery, repurposing them to create more copies of the virus. These infected cells then release millions of copies of the virus which then go on to infect other cells in our bodies, ultimately causing the COVID-19 disease.7

The presence of this version or fragment of the spike protein then elicits an immune response as the individual’s body recognizes the protein as a foreign substance.8 More specifically, the immune system produces antibodies against the protein and executes other necessary immunogenic responses as well.5,9 Since only one protein of the virus would be created, the vaccine would not infect a vaccinated individual with COVID-19.10 

As a note, antibodies are large Y-shaped proteins that stick to the surface or part of a virus or bacteria, tagging it for attack by other elements of the immune system to ultimately neutralize the virus or bacteria.11 Antibodies are designed to bind to and attack one kind of virus or bacteria only.11 This means that an antibody that is for instance designed to destroy the common cold virus, cannot be used to attack the SARS-CoV-2 or Influenza A viruses. 

As antibodies specific to the SARS-CoV-2 spike protein are produced upon administration of the Pfizer or Moderna vaccine, if the SARS-CoV-2 virus does enter the vaccinated individual’s body at a later time, the antibodies produced post-vaccination will be able to recognize the spike proteins of the virus and thus bind to them.12 As a result, the virus will be unable to bind to the ACE-2 receptors on the surface of the individual’s cells, and therefore will not be internalized, rendering it incapable of taking over the cells’ machinery and replicating.12 In addition, the binding of the antibodies to the spike proteins present on the surface of the SARS-CoV-2 virus will also tag the virus for degradation by other elements of the immune system.12

 

Figure 2. The engineered mRNA is injected into an individual’s body in a lipid nanoparticle. The mRNA is then translated into a fragment or version of the SARS-CoV-2 spike protein in the cytoplasm of the individual’s cells. As the spikes are released from the individual’s cells, their immune system produces antibodies and releases T-cells to execute necessary immunogenic reactions. This image has been adapted from a Figure in an article in The Washington Post: “What you need to know about the AstraZeneca, Moderna and Pfizer vaccines”.12

While the injected mRNA remains in vaccinated individuals’ bodies just long enough to be translated, the resulting protein stick around long enough to induce the production of antibodies. After, both the mRNA and protein are degraded.8

Now that we know how the mRNA vaccines work, it is important to note that this is new technology. Before 2020, mRNA vaccines have never been authorized to be used for humans due to their unknown short- and long-term effects.8 

Further, due to the fragility of mRNA, mRNA vaccines must be kept at very low temperatures to prevent degradation.13 The Pfizer vaccine needs to be stored at -70°C during transportation, at which it will last for up to 10 days.14 In ultra-low-temperature freezers, the vaccine’s shelf life extends to six months, but in refrigeration units commonly available in hospitals (2°C-8°C), the Pfizer vaccine can only last for up to five days.14 On the other hand, the Moderna vaccine can last up to six months at -20°C (equivalent to a regular freezer), and in refrigeration units (2°C-8°C), the Moderna vaccine remains stable for 30 days.15

In addition, both vaccines require two doses to be administered.2,16 For the Pfizer vaccine, patients would receive their second dose 21 days after the first dose (30μg each), whereas for the Moderna vaccine, patients would receive their second dose 28 days after the first dose (an additional week later; 100μg each).2,16

 

Table 1. Similarities and Differences Between Two COVID-19 mRNA Vaccines

 

Pfizer Vaccine

Moderna Vaccine

Type of Vaccine

mRNA

mRNA

Shelf-life at Normal Refrigeration Temperatures (2°C-8°C)

5 days

30 days

mRNA Dosage Required

Two 30μg doses, 21 days apart

Two 100μg doses, 28 days apart

# of Phase 3 Trial Participants

> 43,000

> 30,000

Participants’ Age and Health Conditions

Age groups: 12-15 (100 participants only); 18-55; 65-85

Health Conditions: Healthy individuals with and without prior SARS-CoV-2 infection; Individuals with stable pre-existing disease; Individuals with stable, chronic HIV, HCV, and HBV infection

Age: 18+

Health Conditions: Healthy with no previous history of SARS-CoV-2 infection; Individuals with stable pre-existing medical conditions

Trial Design

Randomized, blinded, placebo-controlled

Randomized, blinded, 1:1 placebo-controlled

Placebo Used

Saline solution

Saline solution

Efficacy

95%

(>94% in individuals over the age of 65)

94.1%

When was Vaccine Efficacy Measured?

7 days after second dose

(day 28)

14 days after second dose

(day 42)

Observed Side Effects*

Fatigue, Headache

Fatigue, Muscle Aches, Stiff Joints, Headache, Pain, Redness at Injection Site

How Long Will Participants Be Monitored?

2 years after second dose

2 years after second dose

*For more details on the observed frequency and severity of the side effects, please read the section titled “Additional Information Regarding Results Observed in the Phase 3 Clinical Trials” below.

 

It is important to note that peer-reviewed articles with the data above have not yet been published but will be soon. Most of the up-to-date information at the moment can only be retrieved from Pfizer and Moderna’s press releases. 

Finally, though the vaccines do sound promising, there still remains a lot to learn:

  1. Although the vaccines seem effective at the moment, how effective will they be in the long term? By continuously monitoring trial participants, Moderna and Pfizer will get a better idea of how long the immunity resulting from the vaccines will last. Will the vaccine provide immunity for decades like the measles vaccine, or will people need to get frequent boosters?17
  2. Both vaccines prevent the COVID-19 disease effectively. However, it is unknown if both vaccines also prevent infection (replication of the virus). If they do, transmission and asymptomatic spread can be blocked as well.18
  3. The safety profile for both vaccines is promising and generally tolerable according to the most recent data. Trial participants still need to be monitored for months and years to determine long-term side effects.17 Though we do not know the long-term side effects of the vaccine just yet, we do know that COVID-19 itself can have long-term effects including fatigue and lung damage.19

It has definitely been one long year, but the fact that we are ending 2020 with two promising and effective vaccine candidates is no less than exciting. Both the Pfizer and Moderna vaccines have surpassed the minimum threshold set by the Food and Drug Administration (FDA) for consideration of an emergency approval.2,20 Nonetheless, in the meantime, it is important for all of us to continue to stay educated, socially distanced (even when the vaccines do come out as not everyone will be able to get immunized at once), healthy, and safe until the vaccines are ready for distribution and administration. 

 

ADDITIONAL INFORMATION REGARDING RESULTS OBSERVED IN THE PHASE 3 CLINICAL TRIALS

 

Pfizer executed their randomized, blinded, placebo-controlled Phase 3 trials with over 43,000 participants.1,21 Pfizer then measured the efficacy of the vaccine 28 days after trial participants received their first dose (seven days after receiving their second dose).21 The vaccine was found to be 95% effective as from the 170 positive confirmed cases that were evaluated, 162 were observed in the placebo group.1 This was measured in participants over the age of 18 both with and without prior SARS-CoV-2 infection.1 Pfizer has also submitted solicited safety data on approximately 100 children, aged 12-15 in their request to the FDA for Emergency Use Authorization.20 As Pfizer mentioned in their press release on Wednesday November 18th, 2020, “this efficacy was consistent across age, gender, race and ethnicity demographics; observed efficacy in adults over 65 years of age was over 94% ... There were 10 severe cases of COVID-19 observed in the trial, with nine of the cases occurring in the placebo group … To date, the Data Monitoring Committee for the study has not reported any serious safety concerns related to the vaccine … The only Grade 3 (severe) solicited adverse events greater than or equal to 2% in frequency after the first or second dose were fatigue at 3.8% and headache at 2.0% following dose 2. Consistent with earlier shared results, older adults tended to report fewer and milder solicited adverse events following vaccination.”1 Trial participants have been followed for at least two months after receiving the second dose. Pfizer plans to monitor participants’ health for two years after receiving the second dosage of the vaccine candidate or placebo.20

 More information about the Pfizer vaccine and its Phase 3 trial can be found at: 

Moderna executed their randomized, blinded, 1:1 placebo-controlled study Phase 3 trials with more than 30,000 participants.2,22 Moderna then measured the efficacy of the vaccine 42 days after trial participants received their first dose (14 days after receiving their second dose).2 The vaccine was found to be 94.1% effective; from the 196 positive confirmed cases that were evaluated, 185 were observed in the placebo group.2 30 severe cases were confirmed, of which all occurred in the placebo group as well.2 One COVID-19-related death was reported, however, this too occurred in the placebo group.2 According to Moderna’s press release from November 30th, 2020, “efficacy was consistent across age, race and ethnicity and gender demographics.”2 This was measured in healthy participants over the age of 18 who either had no previous history of COVID-19 or had stable pre-existing medical conditions at time of screening, putting them at higher risk of severe COVID-19.23 Moderna’s Phase 3 trial also assessed approximately 7000 participants over the age of 65 and observed similar “binding- and neutralizing-antibody responses similar to those observed and reported among vaccine recipients between the age of 18 and 55 and above the “median of a panel of controls who had donated convalescent serum” (serum from individuals who had recently recovered from COVID-19).24 According to Moderna’s press release from November 16, 2020, the vaccine “did not report any significant safety concerns … The majority of adverse events were mild or moderate in severity. Grade 3 (severe) events greater than or equal to 2% in frequency after the first dose included injection site pain (2.7%), and after the second dose included fatigue (9.7%), myalgia [muscle aches] (8.9%), arthralgia [joint stiffness] (5.2%), headache (4.5%), pain (4.1%), and erythema/redness at the infection site (2.0%). These solicited adverse events were generally short-lived.”25 According to Moderna’s Phase 3 study overview, “trial participants will be asked to return to the study site three more times over approximately a year. Participants will have one final visit to the study site approximately two years from the date of their second injection.”23

More information about the Moderna vaccine and its Phase 3 trial can be found at: 

 

REFERENCES: 

(1)        Pfizer and BioNTech Conclude Phase 3 Study of COVID-19 Vaccine Candidate, Meeting All Primary Efficacy Endpoints | Pfizer https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine (accessed Dec 2, 2020).
(2)        Moderna Announces Primary Efficacy Analysis in Phase 3 COVE Study for Its COVID-19 Vaccine Candidate and Filing Today with U.S. FDA for Emergency Use Authorization | Moderna, Inc. https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-primary-efficacy-analysis-phase-3-cove-study/ (accessed Dec 2, 2020).
(3)        The Central Dogma | Protocol https://www.jove.com/science-education/10798/the-central-dogma (accessed Dec 2, 2020).
(4)        Mulligan, M. J.; Lyke, K. E.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Neuzil, K.; Raabe, V.; Bailey, R.; Swanson, K. A.; Li, P.; Koury, K.; Kalina, W.; Cooper, D.; Fontes-Garfias, C.; Shi, P.-Y.; Türeci, Ö.; Tompkins, K. R.; Walsh, E. E.; Frenck, R.; Falsey, A. R.; Dormitzer, P. R.; Gruber, W. C.; Şahin, U.; Jansen, K. U. Phase I/II Study of COVID-19 RNA Vaccine BNT162b1 in Adults. Nature 2020, 586 (7830), 589–593. https://doi.org/10.1038/s41586-020-2639-4.
(5)        Jackson, L. A.; Anderson, E. J.; Rouphael, N. G.; Roberts, P. C.; Makhene, M.; Coler, R. N.; McCullough, M. P.; Chappell, J. D.; Denison, M. R.; Stevens, L. J.; Pruijssers, A. J.; McDermott, A.; Flach, B.; Doria-Rose, N. A.; Corbett, K. S.; Morabito, K. M.; O’Dell, S.; Schmidt, S. D.; Swanson, P. A.; Padilla, M.; Mascola, J. R.; Neuzil, K. M.; Bennett, H.; Sun, W.; Peters, E.; Makowski, M.; Albert, J.; Cross, K.; Buchanan, W.; Pikaart-Tautges, R.; Ledgerwood, J. E.; Graham, B. S.; Beigel, J. H. An MRNA Vaccine against SARS-CoV-2 — Preliminary Report. N. Engl. J. Med. 2020, 383 (20), 1920–1931. https://doi.org/10.1056/NEJMoa2022483.
(6)        Yan, R.; Zhang, Y.; Li, Y.; Xia, L.; Guo, Y.; Zhou, Q. Structural Basis for the Recognition of SARS-CoV-2 by Full-Length Human ACE2. Science 2020, 367 (6485), 1444–1448. https://doi.org/10.1126/science.abb2762.
(7)        Cevik, M.; Kuppalli, K.; Kindrachuk, J.; Peiris, M. Virology, Transmission, and Pathogenesis of SARS-CoV-2. BMJ 2020, 371. https://doi.org/10.1136/bmj.m3862.
(8)        CDC. Coronavirus Disease 2019 (COVID-19) https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html (accessed Dec 2, 2020).
(9)        Walsh, E. E.; Frenck, R. W.; Falsey, A. R.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Neuzil, K.; Mulligan, M. J.; Bailey, R.; Swanson, K. A.; Li, P.; Koury, K.; Kalina, W.; Cooper, D.; Fontes-Garfias, C.; Shi, P.-Y.; Türeci, Ö.; Tompkins, K. R.; Lyke, K. E.; Raabe, V.; Dormitzer, P. R.; Jansen, K. U.; Şahin, U.; Gruber, W. C. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N. Engl. J. Med. 2020, 0 (0), null. https://doi.org/10.1056/NEJMoa2027906.
(10)      Abbasi, J. COVID-19 and MRNA Vaccines—First Large Test for a New Approach. JAMA 2020, 324 (12), 1125. https://doi.org/10.1001/jama.2020.16866.
(11)      July 17, T. G.-A. M. E.; 2020. What are antibodies? https://www.livescience.com/antibodies.html (accessed Dec 2, 2020).
(12)      What you need to know about the AstraZeneca, Moderna and Pfizer vaccines https://www.washingtonpost.com/health/2020/11/17/covid-vaccines-what-you-need-to-know/ (accessed Dec 2, 2020).
(13)      Why Does Pfizer’s COVID-19 Vaccine Need To Be Kept Colder Than Antarctica? https://www.npr.org/sections/health-shots/2020/11/17/935563377/why-does-pfizers-covid-19-vaccine-need-to-be-kept-colder-than-antarctica (accessed Dec 2, 2020).
(14)      COVID-19 Vaccine U.S. Distribution Fact Sheet | Pfizer https://www.pfizer.com/news/hot-topics/covid_19_vaccine_u_s_distribution_fact_sheet (accessed Dec 2, 2020).
(15)      Moderna Announces Longer Shelf Life for its COVID-19 Vaccine Candidate at Refrigerated Temperatures | Moderna, Inc. https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-longer-shelf-life-its-covid-19-vaccine/ (accessed Dec 2, 2020).
(16)      Pfizer and BioNTech Choose Lead mRNA Vaccine Candidate Against COVID-19 and Commence Pivotal Phase 2/3 Global Study | Pfizer https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-choose-lead-mrna-vaccine-candidate-0 (accessed Dec 2, 2020).
(17)      What We Know and What We Don’t About the Moderna and Pfizer COVID-19 Vaccines https://www.kqed.org/science/1971077/what-we-know-and-what-we-dont-about-the-moderna-and-pfizer-covid-19-vaccines (accessed Dec 2, 2020).
(18)      MedCram - Medical Lectures Explained CLEARLY. Coronavirus Update 117: Moderna vs. Pfizer COVID 19 Vaccine (MRNA Vaccines); 2020.
(19)      Marshall, M. The Lasting Misery of Coronavirus Long-Haulers. Nature 2020, 585 (7825), 339–341. https://doi.org/10.1038/d41586-020-02598-6.
(20)      Pfizer and BioNTech to Submit Emergency Use Authorization Request Today to the U.S. FDA for COVID-19 Vaccine | Pfizer https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-submit-emergency-use-authorization (accessed Dec 2, 2020).
(21)      Coronavirus COVID-19 Scientific Research and Resources | Pfizer https://www.pfizer.com/science/coronavirus (accessed Dec 3, 2020).
(22)      MRNA-1273-P301-Protocol.Pdf.
(23)      Moderna’s Fully Enrolled Phase 3 COVE Study of mRNA-1273 | Moderna, Inc. https://www.modernatx.com/cove-study (accessed Dec 2, 2020).
(24)      Anderson, E. J.; Rouphael, N. G.; Widge, A. T.; Jackson, L. A.; Roberts, P. C.; Makhene, M.; Chappell, J. D.; Denison, M. R.; Stevens, L. J.; Pruijssers, A. J.; McDermott, A. B.; Flach, B.; Lin, B. C.; Doria-Rose, N. A.; O’Dell, S.; Schmidt, S. D.; Corbett, K. S.; Swanson, P. A.; Padilla, M.; Neuzil, K. M.; Bennett, H.; Leav, B.; Makowski, M.; Albert, J.; Cross, K.; Edara, V. V.; Floyd, K.; Suthar, M. S.; Martinez, D. R.; Baric, R.; Buchanan, W.; Luke, C. J.; Phadke, V. K.; Rostad, C. A.; Ledgerwood, J. E.; Graham, B. S.; Beigel, J. H. Safety and Immunogenicity of SARS-CoV-2 MRNA-1273 Vaccine in Older Adults. N. Engl. J. Med. 2020, 0 (0), null. https://doi.org/10.1056/NEJMoa2028436.
(25)      Moderna’s COVID-19 Vaccine Candidate Meets its Primary Efficacy Endpoint in the First Interim Analysis of the Phase 3 COVE Study | Moderna, Inc. https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy/ (accessed Dec 2, 2020).

 

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How to Prevent Getting Cancer

Newer HPV Vaccine prevents 90% of cervical cancers, anal cancers, and genital warts!

Gardasil-9 is better than original Gardasil.

 

 

Cancer is a scary word. We all know someone, a friend, family member, or co-worker who developed cancer. They go through difficult treatments like surgery, chemotherapy and radiation. Sometimes they die. We all fear getting cancer some day in our life. When you feel a little sensation in your body, do you often wonder if you might have cancer? Many people always end up going to family doctors and asking if they have cancer. It is a top reason why people request unnecessary imaging and tests, just to reassure themselves that they don't have cancer. We also always get asked questions about what kind of foods, or supplements to take to prevent getting cancer. Why wait until you have cancer to treat it, when you can prevent getting cancer in the first place?

 

What if we told you that there was a vaccine that prevents 90% of cervical cancers, anal cancers, and genital warts? Would you want to prevent getting cancer and avoid going through all that stress and anxiety in the first place? Gardasil-9 is an HPV vaccine that does just that! 90% on anything, even a school exam, is worth it!

 

Gardasil-9 has been shown to prevent approximately 90% of cervical cancers in women. It also prevents anal cancers in men. It also prevents ugly genital warts in men and women. Research has shown that it is HPV (human papilloma virus) infects human skin and mucosa and causes cellular changes which lead to cancer. Gardasil 9 trains the body's immune system to recognize and kill the top 9 strains of HPV (human papilloma virus 6, 11, 16, 18, 31, 33, 45, 52 and 58) that cause cervical cancer and genital warts. If your body can fight off the infection and kill the virus, then your body heals and doesn't develop cancer. Gardasil 9 is available at your family doctor's office, such as Get Well Clinic (416-508-5691).

What if you wanted to take your chances with cancer, how likely could you get HPV infection? 7 out of 10 people (who are sexually active) will get an HPV infection in their lifetime (75%). What if you are not "sexually active?" Think again, you don't need to be "sexually active" to get infected with HPV. (https://www.ncbi.nlm.nih.gov/pubmed/2256864)

What if you didn't have a cervix? Well, you can still be protected against 90% of anal cancers and genital warts! The HPV vaccine is also for boys and men, especially if you love your current or future partner!

There is another older version of HPV vaccine, called Gardasil that is available in Ontario, and given to all Gr 7 and 8 students in the schools. As you can tell from the number, it only covers 4 strains of HPV (2 strains which cause cervical cancer, and 2 strains that cause genital warts). It only prevents 70% of cervical cancers. Would you 70% or 90% on a school exam? In order to boost your protection up to 90%, we recommend students be re-immunized with the newer Gardasil-9 at Get Well Clinic. Grade 7 boys in Ontario only started getting Gardasil in 2015 (but this was the original 4-strain version only).

Other countries are starting to recongize the importance of preventing cancer with vaccines. Hong Kong had introduced Gardasil 9 in 2016, and many Chinese students were travelling to the territory for this vaccine. Mainland China recently approved Cervarix and original Gardasil (another HPV vaccine) in 2016/2017. However, Cervarix and original Gardasil only covers 2 strains of HPV (16, 18), and therefore is only offers 70% protection for cervical cancer, but no protection against the other strains that cause genital warts.

Gardasil-9 is better than original Gardasil.

Get 90% Protected from cervical cancer and genital warts!

 

Even if you get the HPV vaccine, women should still see their family doctor regularly for PAP test's (Women's Health Exam) to check for early signs of cervical abnormalities that may develop in to cancer. Getting the vaccine does NOT mean you can skip the PAP tests.

 

Gardasil-9 is a vaccine that is injected in to the shoulder muscle. There are 2 or 3 shots needed over a span of 6 months, depending of your age. Gardasil 9 is officially indicated for girls/women from 9 yr old to 45 yrs old, and for boys/men from 9 yrs old to 26 yrs old. It has been recommended by the Canadian NACI guidelines for any age and any gender. It is safe for older men and women, however, the research studies only studied the vaccine in the indicated age groups. Your doctor may still recommend it for you depending on your specific situation.

It is better to get it earlier than later. Getting the HPV vaccine earlier means you get protected sooner and more effectively, before you are exposed to all the strains of HPV in your lifetime.

If you got original Gardasil or Cervarix, you can still get Gardasil-9 safely and boost your immunity to 90%.

 

Get your HPV vaccine today at Get Well Clinic! Contact us to make an appointment. 416.508.5691.

 

References:

http://www.arhp.org/publications-and-resources/clinical-proceedings/Managing-HPV/Impact
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC145302/
https://www.ncbi.nlm.nih.gov/pubmed/2256864
http://www.gardasil.ca/what-is-gardasil.html

 

 

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Mental Health and Exercise

By Nadia Butt [Get Well Clinic]

 

Defining mental illness and mental health

Mental illness is when the brain is not working the way it should, and as a result, it affects how a person behaves, thinks and feels. Mental illness often disrupts a person’s ability to function in society and interact with others (American Psychiatric Association, 2018). There is a collection of different types of mental illnesses such as depression, anxiety, bipolar disorder, schizophrenia and post-traumatic stress disorder.  Individuals with mental illness may experience sadness, extreme feelings of worry, anger and/or mood changes (Lobo & Agius, 2012).  However, since mental illnesses are on a spectrum, the severity of symptoms vary between individuals (Lobo & Agius, 2012). 

Figure 1. Mental Health Continuum Model (Every Moment Counts, n.d.)

Mental health is a state of well-being that everyone has. Good mental health often involves you having a sense of purpose, enjoying life and having the ability to cope with the stresses of life (World Health Organization, 2012). Even if you do not have a mental illness, throughout your life, you will experience strains from life events that affect your happiness and may cause stress, burnout, anxiety, or other negative feelings (Canadian Mental Health Association, 2020).  Therefore, your mental health status changes throughout your life.  Since mental health lies on a spectrum, you do not only experience the two extremes of good or bad mental health – there’s everything in between as well (Canadian Mental Health Association, n.d.).  Additionally, if your mental health is significantly suffering or you are experiencing poor mental health for a significant amount of time, you can eventually acquire a mental illness (Franken et al., 2018). This can be explained through the mental health continuum model (refer to figure 1), which consists of having mental health and mental illness at two endpoints (Franken et al., 2018).  In this model, an individual can lie at one point of the continuum and later on move positions depending on if their mental health improves or deteriorates (Franken et al., 2018).  

It is important to note that mental health is not just a lack of mental illness – you can have bad mental health without a mental illness (Westerhof & Keyes, 2010). Similarly, if you have a mental illness, it does not mean you cannot achieve good mental health (Westerhof & Keyes, 2010). Someone with mental illness can live a healthy life. Moreover, it is important to remember that mental health concerns are health problems, just like arthritis and diabetes. Thus, mental health problems are just as concerning as physical health problems.   

Introduction

Every year, one in five people living in Canada will be affected by a mental illness (Mental Health Commission of Canada, 2013). By the age of 40, one in two people will be affected by a mental illness (Mental Health Commission of Canada, 2013). Mental illness is so prominent in our population because no one is immune to it. COVID-19 has only made matters worse, as many more Canadians are facing serious mental health problems, which can lead to more people experiencing mental illnesses. An astounding 50% of Canadians feel that their mental health is worsening throughout the pandemic (Angus Reid Institute, 2020). So, what is something you can do to help improve your mental health? Exercise. 

Regardless of mental health status, you should exercise

We all know that exercise is beneficial. You hear it all the time. That you should exercise because it’s “good for you.” But can exercise really help you?   Well, a large-scale study which consisted of 1.2 million people found that exercise significantly helps to improve mental health. The study found a 43.2% reduction in the number of poor mental health days experienced by individuals who exercise regularly than those who do not exercise (Chekroud et al., 2018). Therefore, if you are doing “okay,” exercise can help improve your mental health. Likewise, if you are doing “good” you should still exercise, as exercise can prevent future mental health problems. This is because happy” hormones are created and released in our brain during exercise, such as endorphins. Endorphins help us feel good and alleviate pain and stress (Orlova et al., 2008). Additionally, dopamine, norepinephrine, and serotonin are other “happy” hormones released in the brain during exercise; they play an important role in regulating mood (Lin & Kuo, 2013). Contrastingly, exercise not only increases “happy” hormones but also reduces stress hormones, such as cortisol (Exercising to Relax, 2020). In fact, mental health medications often work by regulating the activity of these hormones in the brain (Dfarhud et al., 2014; Dremencov et al., 2009). Thus, regardless of your mental health status, you should exercise as it helps you achieve and preserve good mental health.

Exercise not only helps mental health but can also help prevent the development of mental illnesses. For instance, individuals who exercise are 17% less likely to develop depression (Schuch et al., 2018). Exercise even reduces the likelihood of depression for individuals with high genetic risk for this disease (Choi et al., 2019). Similarly, another study found that rigorous exercise protects individuals from certain anxiety disorders and post-traumatic stress disorders (Schuch et al., 2019). To further explore the benefits of exercise on mental illness, three mental health disorders – anxiety, PTSD and depression – will be discussed.

Exercise helps those who have mental illnesses 

Anxiety

Exercise has been proven to help those who have anxiety by being a form of exposure therapy (DeBoer et al., 2012). This is because anxiety disorders and moderate-intensity exercises share similar symptoms (Broman-Fulks & Storey, 2008). Your body tenses, you sweat, your heart races and your respiratory rate increases when you feel anxious and when you exercise. Therefore, exercising can expose individuals to anxiety symptoms in a manner that is safe, which allows individuals to become less sensitive to these symptoms (DeBoer et al., 2012). This is because individuals learn to link these symptoms with feelings of excitement and enjoyment, rather than danger. Consequently, individuals with anxiety and who exercise are less likely to panic when experiencing these linked symptoms, helping them recover from anxiety disorders (DeBoer et al., 2012).

Post-traumatic stress disorder

Exercise helps individuals who suffer from post-traumatic stress disorder (PTSD). A study revealed that individuals who exercise experience fewer PTSD symptoms than those who do not exercise (Fetzner & Asmundson, 2015). Specifically, studies have shown that individuals who undergo exposure therapy–a popular treatment option–and exercise have higher levels of brain-derived neurotrophic factor (BDNF) than those who only participate in exposure therapy (Powers et al., 2015). BDNF is a protein that is important to reduce conditioned fear experienced by those with trauma (Powers et al., 2015). Thus, it is best for individuals recovering from PTSD to combine exercise with other treatment options. Moreover, individuals with PTSD greatly benefit from focusing on their body and how they feel while exercising. This mindfulness helps their nervous system become “unstuck,” allowing their body to depart out of the immobilization stress response caused by PTSD (Smith et al., 2020; Williamson et al., 2015). 

Depression

Exercise is found to reduce depressive symptoms and, in some cases, can be just as beneficial as antidepressants and psychotherapies (Blumenthal et al., 2012). Interestingly, a study found that depressed individuals who exercise regularly are less likely to have depressive symptoms in the long-term than those who are taking antidepressants (Craft & Perna, 2004). So how does exercise helps to combat depression? One reason is that exercise helps the growth of new neurons by increasing the release of proteins called neurotrophic factors (Gujral et al., 2017). Consequently, this neuronal growth increases neuron connections, particularly in the region of the brain called the hippocampus (Gujral et al., 2017).  The hippocampus is responsible for regulating mood, and as a result, the increased activity of neurons in this brain region helps relieve depression (Gujral et al., 2017). Evidently, individuals who are depressed experience hippocampal atrophy, and consequently have abnormally small hippocampi (Gujral et al., 2017). Thus, exercise prevents brain atrophy and can increase the hippocampus size through neuronal growth (Gujral et al., 2017).

What should you do?

Studies have shown that aerobic exercise is the best type of exercise to help manage mental illnesses and improve mental health (Chekroud et al., 2018). Aerobic exercise includes running, biking, hiking, jumping rope, swimming and dancing.  Also, group activities like fitness classes and team sports can improve your mental health by providing you with opportunities for social interactions (Chekroud et al., 2018). During the pandemic, you should consider exercising with others virtually. Furthermore, the Canadian Physical Activity Guidelines and the Canadian Society for Exercise Professionals recommends that adults between the age of 18-64 should exercise 30-60 minutes a day for a total of 150 minutes of exercise a week.

If you or a loved one is struggling with mental health, here are some resources available to you

  • Get Well Clinic has a mental health program that integrates medical assessments, medications, psychotherapy and counselling to help you get better. You can contact our mental health coordinator or ask your family doctor to refer you.
  • 211 Ontario: Call 211 or the toll-free number at 1-877-330-3213 to receive information about mental health resources available to you.
  • BounceBack: Call the toll-free number at 1-866-345-0224 to participate in a free cognitive behavioural therapy (CBT) based program to support your mental health. The program is available for individuals who are at least 15 years old.
  • Good2Talk: Call the toll-free number at 1-866-925-5454 or text good2talkon to 686868 if you’re aged 17 to 25 and need someone to talk to.

 

References:
 

American Psychiatric Association. (2018, August). What Is Mental Illness? https://www.psychiatry.org/patients-families/what-is-mental-illness.

Angus Reid Institute. (2020). Worry, gratitude & boredom: As Covid-19 affects mental, financial health, who fares better; who is worse? http://angusreid.org/covid19-mental-health/avenue for the treatment of anxiety disorders. Expert review of neurotherapeutics, 12(8), 1011–11022. https://doi.org/10.1586/ern.12.73

Blumenthal, J. A., Smith, P. J., & Hoffman, B. M. (2012). Opinion And Evidence. ACSM's Health & Fitness Journal,16(4), 14-21.https://doi.org/10.1249/01.fit.0000416000.09526.eb

Broman-Fulks, J. J., & Storey, K. M. (2008). Evaluation of a brief aerobic exercise intervention for high anxiety sensitivity. Anxiety, Stress & Coping, 21(2), 117-128. https://doi.org/10.1080/10615800701762675

Canadian Mental Health Association. (2020, January 13). Mental health: What is it, really? CMHA National. https://cmha.ca/blogs/mental-health-what-is-it-really.

Canadian Mental Health Association. (n.d.). What's the difference between mental health and mental illness? What's the difference between mental health and mental illness? | Here to Help. https://www.heretohelp.bc.ca/q-and-a/whats-the-difference-between-mental-health-and-mental-illness.

Chekroud, S. R., Gueorguieva, R., Zheutlin, A. B., Paulus, M., Krumholz, H. M., Krystal, J. H., & Chekroud, A. M. (2018). Association between physical exercise and mental health in 1·2 million individuals in the USA between 2011 and 2015: a cross-sectional study. The Lancet Psychiatry, 5(9), 739–746. https://doi.org/10.1016/s2215-0366(18)30227-x

Choi, K. W., Zheutlin, A. B., Karlson, R. A., Wang, M. J., Dunn, E. C., Stein, M. B., … Smoller, J. W. (2019). Physical activity offsets genetic risk for incident depression assessed via electronic health records in a biobank cohort study. Depression and Anxiety, 37(2), 106–114. https://doi.org/10.1002/da.22967

Craft, L. L., & Perna, F. M. (2004). The Benefits of Exercise for the Clinically Depressed. The Primary Care Companion to The Journal of Clinical Psychiatry, 06(03), 104-111.  https://doi.org/10.4088/pcc.v06n0301

DeBoer, L. B., Powers, M. B., Utschig, A. C., Otto, M. W., & Smits, J. A. (2012). Exploring exercise as an avenue for the treatment of anxiety disorders. Expert Rev Neurother. 2012 Aug;12(8):1011-22. doi: 10.1586/ern.12.73. PMID: 23002943; PMCID: PMC3501262.

Dfarhud, D., Malmir, M., & Khanahmadi, M. (2014). Happiness & Health: The Biological Factors-Diamond, A., McIntyre, C., & Smits, J. A. (2015). Exercise Augmentation of Exposure Therapy for PTSD: Rationale and Pilot Efficacy Data. Cognitive behaviour therapy, 44(4), 314–327. https://doi.org/10.1080/16506073.2015.1012740

Dremencov, E., Mansari, M., & Blier, P. (2009). Brain Norepinephrine System as a Target for Antidepressant and Mood Stabilizing Medications. Current Drug Targets, 10(11), 1061-1068. https://doi.org/10.2174/138945009789735165

Every Moment Counts. (n.d.). Mental Health Continuum [Figure]. https://everymomentcounts.org/view.php?nav_id=33

Exercising to relax. (2020, July 7). https://www.health.harvard.edu/staying-healthy/exercising-to-relax

Fetzner, M. G., & Asmundson, G. J. (2015). Aerobic Exercise Reduces Symptoms of in PTSD accelerates physiological aging. Frontiers in psychology, 5, 1571. https://doi.org/10.3389/fpsyg.2014.01571

Franken, K., Lamers, S., Ten Klooster, P. M., Bohlmeijer, E. T., & Westerhof, G. J. (2018). Validation of the Mental Health Continuum-Short Form and the dual continua model of well-being and psychopathology in an adult mental health setting. Journal of clinical psychology, 74(12), 2187–2202. https://doi.org/10.1002/jclp.22659

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