Frequently Asked Questions
Below you’ll find definitions and answers to the some of the most common questions about COVID-19.
We start with the basics, and answer questions about the virus and the disease itself. Next, we dive into SARS-CoV-2 testing and antibodies and what these mean for our immunity following an infection. We also take some time to breakdown exactly what serosurveillance and other population-based studies are and how their results, when allowed to inform the rollout of vaccines, will be critical to Canada’s response to the COVID-19 pandemic.
If you can’t find the answer to your question, feel free to contact us.
About the Virus and Disease
Figure 1.1. Rapidly spreading variants are being observed globally. Some mutations confer potential selective advantages to the virus, such as increased transmissibility or immune evasion. Photo Credit: Mariana Bego.
The name coronavirus is derived from the Latin corona, meaning “crown.” This refers to the characteristic “crown” shape of the virus’ protein spikes.
This coronavirus family has several members that can infect humans: four are potential causes of the common cold, while the others, SARS-CoV, MERS-CoV and SARS-CoV-2, have triggered dangerous epidemics. SARS-CoV-2 is a close relative to SARS-CoV, which was responsible for the severe acute respiratory syndrome (SARS) epidemic of 2002–2003, which infected over 8,000 people worldwide.
The morphology (shape) of coronavirus is depicted here with spike proteins (red) that form a corona (crown) around the virus. Additional proteins shown include envelope (yellow) and membrane (orange) proteins. Photo Credit: Alissa Eckert, MSMI, Dan Higgins, MAMS.
SARS-CoV-2 is the virus that causes the disease known as COVID-19.
Researchers are currently investigating this question. Research suggests prior coronavirus infections may result in the development of antibodies that fight against SARS-CoV-2, but these antibodies may not be strong enough to prevent COVID-19 infection. This is why people should get vaccinated, even if they had a previous SARS-CoV-2 infection.
Like with seasonal coronaviruses that cause the common cold, recovery from an initial infection of SARS-CoV-2 gives a degree of immunity and protection towards re-infection. However, some patients who have recovered from COVID-19 have caught the virus for a second time. The rise of variants increases the likelihood of catching a mutated form of the virus. This is why vaccination is important.
COVID-19 causes diverse degrees of illness, ranging from asymptomatic infection (no symptoms) to mild symptoms, to severe pneumonia, stroke, sepsis, organ failure, and even death. It is suggested that about 1 in 5 infected people will experience no symptoms, although this number is highly variable depending on the population studied.
It is important to differentiate between asymptomatic and pre-symptomatic infections. Someone who is asymptomatic never develops symptoms, from the time they acquire the virus to the time the infection has fully cleared. Pre-symptomatic refers to someone who will eventually develop symptoms (it generally takes 7-13 days after the initial exposure to SARS-CoV-2 to develop symptoms).
It should be noted that even in the absence of symptoms, people can still transmit the virus.
Infection with SARS-CoV-2 can result in a wide range of symptoms such as fever, chills and loss of taste or smell (right panel), or it may go completely unnoticed with no symptoms at all (asymptomatic, left panel). In both cases, infected individuals can go on to transmit the virus to others. Image credit: Kristin Davis
SARS-CoV-2 variants occur when there are changes or “mutations” in the original virus’ genetic code. These changes occur naturally over time as a by-product of replication. The World Health Organization (WHO) tracks variants of SARS-CoV-2 around the globe and designates them as variants of concern (VOCs) when they meet specific criteria demonstrating that they spread much faster, are better adept at infecting people and/or impact the effectiveness of vaccines and therapeutics.
Currently there are five VOCs: Alpha, Beta, Gamma, Delta, and Omicron. The Alpha variant, also known as the B.1.1.7 variant, was first identified in the United Kingdom where a mutation occurred in the receptor binding domain (RBD) of the spike protein. This resulted in a change of the genetic code, specifically, the amino acid asparagine (N) was replaced with tyrosine (Y) at location 501 (N501Y).
The Beta variant, also known as B.1.351 originated in South Africa, the Gamma variant, also known as P.1, originated in Brazil, the Delta variant, also known as B.1.617.2, originated in India and the newest variant entitled Omicron emerged in November 2021. Beta and Gamma variants also have the above N501Y mutation, but they have several others, like E484K. The Delta variant has a more diverse repertoire of mutations than other variants. It lacks the N501 mutation, has a different mutation in position 484 (E484Q), and has several other unique mutations (including P681R and L452R). The Omicron variant has over 30 mutations in the spike protein alone.
The WHO also tracks variants of interest (VOIs), defined as variants with mutations that could affect transmissibility, disease severity, and the effectiveness of immune responses and therapeutics. Currently, there are five VOIs: Eta (B.1.525), Iota (B.1.526), Kappa (B.1.617.1), Lambda (C.37), and Mu (B.1.621).
Experts are still analyzing data to understand the extent of the severity of disease and potential long-term implications from infection with the Omicron variant. This includes characterizing disease severity in infected individuals vaccinated with one, two, three, or four doses compared to those not yet vaccinated. Currently, population-level disease appears less severe with Omicron compared to Delta (Public Health Ontario). Reports worldwide have described infection with Omicron to be mild to moderate in most cases6-8. Nevertheless, people who are older, with underlying health conditions, or are immunosuppressed may have a higher risk of more severe disease, including life-threatening illness9, 10. Likewise, the impact on healthcare systems will be significant due to the sheer number of cases and increased transmissibility of the new variant.
Symptoms from an infection with Omicron are like those previously reported for COVID-19: fever, cough, sore throat, tiredness, and headache being the most common. Individuals with COVID-19-like symptoms should self-isolate.
Yes, the Omicron variant has been associated with an increased risk of reinfection, that is, new infections with SARS-CoV-2 in previously recovered individuals. This is due to the substantial number of new genetic mutations found in Omicron compared to previous strains, including the Delta variant that was widely circulating in the third and fourth viral waves. Reports show a series of at least 36 mutations in the virus’ spike protein, about half being in the receptor-binding domain (RBD), compared to the original strain of the virus (11). These have been linked to increased transmissibility and immune evasion, meaning that the antibodies made from previous infection or vaccination don’t recognize Omicron (12-15). Since the new variant ‘looks’ very different, antibodies may not be able to respond to it.
The name coronavirus is derived from the Latin corona, meaning “crown.” This refers to the characteristic “crown” shape of the virus’ protein spikes.
This coronavirus family has several members that can infect humans: four are potential causes of the common cold, while the others, SARS-CoV, MERS-CoV and SARS-CoV-2, have triggered dangerous epidemics. SARS-CoV-2 is a close relative to SARS-CoV, which was responsible for the severe acute respiratory syndrome (SARS) epidemic of 2002–2003, which infected over 8,000 people worldwide.
The morphology (shape) of coronavirus is depicted here with spike proteins (red) that form a corona (crown) around the virus. Additional proteins shown include envelope (yellow) and membrane (orange) proteins. Photo Credit: Alissa Eckert, MSMI, Dan Higgins, MAMS.
SARS-CoV-2 is the virus that causes the disease known as COVID-19.
Researchers are currently investigating this question. Research suggests prior coronavirus infections may result in the development of antibodies that fight against SARS-CoV-2, but these antibodies may not be strong enough to prevent COVID-19 infection. This is why people should get vaccinated, even if they had a previous SARS-CoV-2 infection.
Like with seasonal coronaviruses that cause the common cold, recovery from an initial infection of SARS-CoV-2 gives a degree of immunity and protection towards re-infection. However, some patients who have recovered from COVID-19 have caught the virus for a second time. The rise of variants increases the likelihood of catching a mutated form of the virus. This is why vaccination is important.
COVID-19 causes diverse degrees of illness, ranging from asymptomatic infection (no symptoms) to mild symptoms, to severe pneumonia, stroke, sepsis, organ failure, and even death. It is suggested that about 1 in 5 infected people will experience no symptoms, although this number is highly variable depending on the population studied.
It is important to differentiate between asymptomatic and pre-symptomatic infections. Someone who is asymptomatic never develops symptoms, from the time they acquire the virus to the time the infection has fully cleared. Pre-symptomatic refers to someone who will eventually develop symptoms (it generally takes 7-13 days after the initial exposure to SARS-CoV-2 to develop symptoms).
It should be noted that even in the absence of symptoms, people can still transmit the virus.
Infection with SARS-CoV-2 can result in a wide range of symptoms such as fever, chills and loss of taste or smell (right panel), or it may go completely unnoticed with no symptoms at all (asymptomatic, left panel). In both cases, infected individuals can go on to transmit the virus to others. Image credit: Kristin Davis
SARS-CoV-2 variants occur when there are changes or “mutations” in the original virus’ genetic code. These changes occur naturally over time as a by-product of replication. The World Health Organization (WHO) tracks variants of SARS-CoV-2 around the globe and designates them as variants of concern (VOCs) when they meet specific criteria demonstrating that they spread much faster, are better adept at infecting people and/or impact the effectiveness of vaccines and therapeutics.
Currently there are five VOCs: Alpha, Beta, Gamma, Delta, and Omicron. The Alpha variant, also known as the B.1.1.7 variant, was first identified in the United Kingdom where a mutation occurred in the receptor binding domain (RBD) of the spike protein. This resulted in a change of the genetic code, specifically, the amino acid asparagine (N) was replaced with tyrosine (Y) at location 501 (N501Y).
The Beta variant, also known as B.1.351 originated in South Africa, the Gamma variant, also known as P.1, originated in Brazil, the Delta variant, also known as B.1.617.2, originated in India and the newest variant entitled Omicron emerged in November 2021. Beta and Gamma variants also have the above N501Y mutation, but they have several others, like E484K. The Delta variant has a more diverse repertoire of mutations than other variants. It lacks the N501 mutation, has a different mutation in position 484 (E484Q), and has several other unique mutations (including P681R and L452R). The Omicron variant has over 30 mutations in the spike protein alone.
The WHO also tracks variants of interest (VOIs), defined as variants with mutations that could affect transmissibility, disease severity, and the effectiveness of immune responses and therapeutics. Currently, there are five VOIs: Eta (B.1.525), Iota (B.1.526), Kappa (B.1.617.1), Lambda (C.37), and Mu (B.1.621).
SARS-CoV-2 Testing and Antibodies
Figure 2.1. The viral test involves a nose or throat swab and it detects the presence of the genetic material of the virus, telling you if you have an active infection. The antibody test involves a blood sample and it detects the antibodies created by your body to fight the virus. This tells you if you were infected in the past. Photo Credit: Mariana Bego
A viral test, also known as diagnostic test, can tell you if you have an active COVID-19 infection, which would require you to take steps to isolate yourself to prevent infecting others.
The test is often performed with samples obtained from a nose or throat swab, as these areas are most likely to have enough virus to be detected. If you test positive, that means you have an active infection. Once the infection is resolved, the test would yield a negative result.
More specifically, the test itself looks for the presence of the virus’ genetic material. In the case of SARS-CoV-2, the virus that causes COVID-19, this genetic material is RNA.
Obtaining a negative result from a throat or nose swab test (viral test) does not imply that a person has never had COVID-19. It means that the person is not infected with the virus currently, or that the virus is no longer present in the nose or throat mucus, or that there is so little of the virus present that it cannot be detected by the test.
A viral test can tell you if you are currently infected with SARS-CoV-2, while an antibody test can tell you if you have had an infection or vaccination in the past. Antibody testing can be used to differentiate between infection-acquired and vaccine-induced immunity. For example, someone previously infected with SARS-CoV-2 will have antibodies recognizing viral proteins (often tested as antibodies recognizing the viral proteins spike and nucleocapsid), whereas someone that received a COVID-19 vaccine will only have antibodies recognizing spike, but not nucleocapsid. The latter is because COVID-19 vaccines were designed using only the SARS-CoV-2 spike protein.
Serology tests are used to determine if a person has previously been infected with or vaccinated against SARS-CoV-2, the virus that causes COVID-19. Clinicians and researchers refer to them as serology tests, but often commercial laboratories will call them antibody tests. These tests look for the presence of antibodies, which are specific proteins made in response to infections and vaccinations. Antibody tests are particularly helpful in detecting previous infections in those who may have had few or no symptoms.
When our bodies detect the presence of a foreign or ‘never before seen’ protein, like a viral protein, we make antibodies. These antibodies are able to recognize and latch on to (or bind to) this foreign protein (called an antigen) in order to remove it from our bodies. This process is part of a healthy immune response targeting the foreign invader and is the basis for the protective effect of vaccines.
Antibodies can be detected in the blood of people who have been recently infected and vaccinated, in many cases, long after the initial exposure. Another name for antibodies is immunoglobulins, shortened to Ig, and they come in a variety of flavours: IgA, IgM, IgG, IgE, and IgD. Of these, IgM is the first to be made in response to a foreign protein and it can be found in blood for a short time after exposure to the foreign invaders (pathogens). IgG antibodies appear a little later in blood but can be detected for a longer period of time. Vaccines designed against COVID-19 approved and authorized for use in Canada primarily produce IgG antibodies recognizing the spike protein of SARS-CoV-2.
This binding is highly specific, meaning they cannot bind to just any protein – only their target. The strength and specificity of their binding is the basis for many of their important roles: they can alert several branches of the immune system of an ongoing infection, and they can mark foreign proteins (and consequently the virus attached to them) to be ingested by immune cells and destroyed.
A unique type of antibody called a neutralizing antibody, will recognize proteins of the virus and prevent them from binding to the cell receptor, thereby blocking the virus’ entry into human cells. For SARS-CoV-2, this protein is the spike (S).
Of the many proteins encoded by SARS-CoV-2, the spike (S), which coats the outer layer of the virus, and the nucleocapsid (N), which wraps and protects the virus’ genomic component, are the most abundant. These proteins are often targeted by the immune system and are often recognized by antibodies. COVID-19 vaccines were designed against the S protein. Antibodies recognizing the S protein are dubbed anti-spike IgG or (anti-S IgG, a-S IgG for short). Likewise, antibodies recognizing the N protein are named anti-nucleocapsid IgG (anti-N IgG or a-N IgG for short) and their detection is suggestive of a previous infection with SARS-CoV-2 as vaccination will only produce anti-S IgG.
Spike (S) proteins make up the outer layer of the virus. They are what give the virions (the viral infectious particles) the appearance of having a crown. Spike proteins are responsible for binding to the cellular receptor, an event required for the virus to enter into the human cell. COVID-19 vaccines were designed against the S protein.
Figure 2.2. SARS-CoV-2 has the spike (S) proteins that cover the outer membrane surface. These S proteins bind to a receptor called the angiotensin converting enzyme 2 (ACE2). The nucleocapsid (N) protein forms complexes with the viral RNA and is involved in viral replication. Photo Credit: Mariana Bego
People generally develop antibodies within the first 1-2 weeks after being infected with SARS-CoV-2. These antibodies, found in the bloodstream of recovering (convalescent) individuals, are able to bind to and render the virus incapable of infecting new cells.
Convalescent plasma therapy involves using the plasma (the liquid part of the blood that remains after removing all the cells) of these COVID-19 recovering patients to help treat patients who have been newly infected with SARS-CoV-2. Upon injection of this plasma into the bloodstream of newly infected patients, antibodies pre-existing in the injected plasma can immediately bind to and inactivate the SARS-CoV-2 virus. In doing so, the antibodies help control the virus while allowing the patient’s own immune response to catch-up and fully resolve the infection.
The CITF’s Immune Testing Working Party aims to enable accurate, quality assured, efficient, scalable, and safe immunity testing for SARS-CoV-2 across Canada. Given the novel status of SARS-CoV-2, all immune tests – whether based on blood draws from veins, pin pricks for blood spots, saliva samples, or others – require validation for accuracy. A test’s accuracy depends on its sensitivity and specificity, and the interpretation of a test is also dependent on the timing of testing in relation to an individual’s infection. Defining the duration of antibody responses will guide testing strategies and help understand the technology’s limitations.
At-home rapid antigen tests for COVID-19 have become more commonplace in the absence of widespread PCR testing. They are called antigen tests because they detect antigens, specific proteins that make-up the SARS-CoV-2 virus. Further, they provide test results in less than an hour, hence the designation ‘rapid’.
A rapid antigen test’s sensitivity, defined as its ability to detect the virus when present, is dependent on an individual’s viral load. Viral loads – the amount of virus in nasopharyngeal fluids and blood – are higher early on in infection when the virus is replicating exponentially4. Viral loads are generally detectable for some rapid antigen tests during the first five days of symptoms (Health Canada). After this initial period, rapid antigen test performance decreases quickly as viral loads decline, and the infection clears.
Rapid antigen tests detect current infections, including those caused by Omicron5. They cannot, however, tell whether an individual has had a previous infection with SARS-CoV-2. Vaccination against COVID-19 does not interfere with the test’s ability to detect a current infection.
Figure 1: Schematic depiction of the COVID-19 rapid antigen tests available in Canada.
Step 1 – Specimen collection.
A nasal sample is collected using the sterile swab provided. Blowing the nose prior to swabbing, tilting the head back 70 degrees, compressing the nostril with the aid of fingers, and using circular motions while in the nasal cavity have been known to aid with collection.
Step 2 – Test procedure.
The swab is submerged in a buffer solution to extract the SARS-CoV-2 virus (if present). After a rest period, the resulting liquid is dispensed with the aid of a nozzle into the sample well on the testing device. The sample then moves through the testing device during which antigens present in the sample bind to antibodies in the device, forming antigen-antibody complexes. The reaction lasts for 15-30 minutes (depending on the manufacturer’s instructions) after which results may be read.
Step 3 – Results interpretation.
Two lines detected at the T (test) and C (control) lines of the test window indicate a positive result. This means the sample is positive for SARS-CoV-2 and the person is most likely infected. Positive results can be reported at local/provincial/territorial Public Health units or at independent initiatives such as The Rapid Test Tracker. If only one line at C (control) appears, the result is negative, meaning that the individual is most likely not infected. *It is important to note however that a negative result may also indicate that a person is infected but below the level of detection. That said, if symptoms are present, individuals should continue to isolate and follow local public health guidelines. The test may be repeated a few days later to re-ascertain infection status. No lines or a faint T line indicates an invalid test. A test cannot be used more than once.
Some of the rapid antigen tests that have received Health Canada approval for diagnostic testing are shown below, and additional information can be found here.
Table 1: Specifications of some of the rapid antigen tests available in Canada.
|
|
Country of manufacture |
Sensitivity* |
Specificity** |
Overall agreement*** |
Limit of detection |
|
BTNX – Rapid Response COVID-19 Antigen Test |
Canada |
95.5% |
95.5% |
97.3% |
2×102.4 TCID50/mL |
|
Artron Antigen COVID-19 (SARS-CoV-2) Rapid Test |
Canada |
97.2% |
99.6% |
97.0% |
1×103 TCID50/mL |
|
Quidel Quickvue At-home OTC COVID-19 Test |
USA |
83.5% |
99.2% |
90.0% |
1.9×104 TCID50/mL |
|
BD Veritor System for Rapid Detection of SARS-CoV-2 |
USA |
84% |
100.0% |
96.0% |
800 genomic RNA copies/ml |
|
Roche Rapid Antigen Test |
Germany |
82.2% |
99.0% |
95.0% |
9.25×101.2 TCID50/mL |
|
Abbott – Panbio COVID-19 Antigen Rapid Test |
Germany |
75.5% |
94.9% |
90.0% |
Viral loads > 106 copies/ml |
|
Xiamen Boson Biotech – SARS-CoV-2 Antigen Test Card |
China |
96.5% |
99.0% |
98.7% |
130 TCID50/ml |
|
Empowered Diagnostics CovClear COVID-19 Rapid Antigen Test |
USA |
95.5% |
100.0% |
96.7% |
1.29×105 TCID50/ml |
* Sensitivity is a metric defining a test’s capacity to correctly identify people that are infected with SARS-CoV-2 when a test is positive. For example, a test with a sensitivity of 96% will, on average, correctly identify 96 people in every 100 who are truly infected with SARS-CoV-2.
** Specificity is a metric defining a test’s capacity to correctly identify people that are not infected with SARS-CoV-2 when a test is negative. For example, a test with a specificity of 96% will, on average, correctly identify 96 people in every 100 who are truly not infected with SARS-CoV-2.
*** Overall agreement: is the product of the equation: true positives + true negatives / total samples.
A viral test, also known as diagnostic test, can tell you if you have an active COVID-19 infection, which would require you to take steps to isolate yourself to prevent infecting others.
The test is often performed with samples obtained from a nose or throat swab, as these areas are most likely to have enough virus to be detected. If you test positive, that means you have an active infection. Once the infection is resolved, the test would yield a negative result.
More specifically, the test itself looks for the presence of the virus’ genetic material. In the case of SARS-CoV-2, the virus that causes COVID-19, this genetic material is RNA.
Figure 2.1. The viral test involves a nose or throat swab and it detects the presence of the genetic material of the virus, telling you if you have an active infection. The antibody test involves a blood sample and it detects the antibodies created by your body to fight the virus. This tells you if you were infected in the past. Photo Credit: Mariana Bego.
Obtaining a negative result from a throat or nose swab test (viral test) does not imply that a person has never had COVID-19. It means that the person is not infected with the virus currently, or that the virus is no longer present in the nose or throat mucus, or that there is so little of the virus present that it cannot be detected by the test.
A viral test can tell you if you are currently infected with SARS-CoV-2, while an antibody test can tell you if you have had an infection or vaccination in the past. Antibody testing can be used to differentiate between infection-acquired and vaccine-induced immunity. For example, someone previously infected with SARS-CoV-2 will have antibodies recognizing viral proteins (often tested as antibodies recognizing the viral proteins spike and nucleocapsid), whereas someone that received a COVID-19 vaccine will only have antibodies recognizing spike, but not nucleocapsid. The latter is because COVID-19 vaccines were designed using only the SARS-CoV-2 spike protein.
Serology tests are used to determine if a person has previously been infected with or vaccinated against SARS-CoV-2, the virus that causes COVID-19. Clinicians and researchers refer to them as serology tests, but often commercial laboratories will call them antibody tests. These tests look for the presence of antibodies, which are specific proteins made in response to infections and vaccinations. Antibody tests are particularly helpful in detecting previous infections in those who may have had few or no symptoms.
When our bodies detect the presence of a foreign or ‘never before seen’ protein, like a viral protein, we make antibodies. These antibodies are able to recognize and latch on to (or bind to) this foreign protein (called an antigen) in order to remove it from our bodies. This process is part of a healthy immune response targeting the foreign invader and is the basis for the protective effect of vaccines.
Antibodies can be detected in the blood of people who have been recently infected and vaccinated, in many cases, long after the initial exposure. Another name for antibodies is immunoglobulins, shortened to Ig, and they come in a variety of flavours: IgA, IgM, IgG, IgE, and IgD. Of these, IgM is the first to be made in response to a foreign protein and it can be found in blood for a short time after exposure to the foreign invaders (pathogens). IgG antibodies appear a little later in blood but can be detected for a longer period of time. Vaccines designed against COVID-19 approved and authorized for use in Canada primarily produce IgG antibodies recognizing the spike protein of SARS-CoV-2.
This binding is highly specific, meaning they cannot bind to just any protein – only their target. The strength and specificity of their binding is the basis for many of their important roles: they can alert several branches of the immune system of an ongoing infection, and they can mark foreign proteins (and consequently the virus attached to them) to be ingested by immune cells and destroyed.
A unique type of antibody called a neutralizing antibody, will recognize proteins of the virus and prevent them from binding to the cell receptor, thereby blocking the virus’ entry into human cells. For SARS-CoV-2, this protein is the spike (S).
Of the many proteins encoded by SARS-CoV-2, the spike (S), which coats the outer layer of the virus, and the nucleocapsid (N), which wraps and protects the virus’ genomic component, are the most abundant. These proteins are often targeted by the immune system and are often recognized by antibodies. COVID-19 vaccines were designed against the S protein. Antibodies recognizing the S protein are dubbed anti-spike IgG or (anti-S IgG, a-S IgG for short). Likewise, antibodies recognizing the N protein are named anti-nucleocapsid IgG (anti-N IgG or a-N IgG for short) and their detection is suggestive of a previous infection with SARS-CoV-2 as vaccination will only produce anti-S IgG.
Spike (S) proteins make up the outer layer of the virus. They are what give the virions (the viral infectious particles) the appearance of having a crown. Spike proteins are responsible for binding to the cellular receptor, an event required for the virus to enter into the human cell. COVID-19 vaccines were designed against the S protein.
Figure 2.2. SARS-CoV-2 has the spike (S) proteins that cover the outer membrane surface. These S proteins bind to a receptor called the angiotensin converting enzyme 2 (ACE2). The nucleocapsid (N) protein forms complexes with the viral RNA and is involved in viral replication. Photo Credit: Mariana Bego
People generally develop antibodies within the first 1-2 weeks after being infected with SARS-CoV-2. These antibodies, found in the bloodstream of recovering (convalescent) individuals, are able to bind to and render the virus incapable of infecting new cells.
Convalescent plasma therapy involves using the plasma (the liquid part of the blood that remains after removing all the cells) of these COVID-19 recovering patients to help treat patients who have been newly infected with SARS-CoV-2. Upon injection of this plasma into the bloodstream of newly infected patients, antibodies pre-existing in the injected plasma can immediately bind to and inactivate the SARS-CoV-2 virus. In doing so, the antibodies help control the virus while allowing the patient’s own immune response to catch-up and fully resolve the infection.
The CITF’s Immune Testing Working Party aims to enable accurate, quality assured, efficient, scalable, and safe immunity testing for SARS-CoV-2 across Canada. Given the novel status of SARS-CoV-2, all immune tests – whether based on blood draws from veins, pin pricks for blood spots, saliva samples, or others – require validation for accuracy. A test’s accuracy depends on its sensitivity and specificity, and the interpretation of a test is also dependent on the timing of testing in relation to an individual’s infection. Defining the duration of antibody responses will guide testing strategies and help understand the technology’s limitations.
Immunity
Figure 3.1. When an individual is infected with SARS-CoV-2, the innate immune response is initiated and characterized by dendritic cell (DC) activation. This is followed by an adaptive immune response where T and B cells are activated. T cells can perform many different functions, while B cells differentiate into plasma cells to produce antibodies. Both types of cells establish memory populations to prevent against re-infection. Photo Credit: Mariana Bego.
Immunity – a full defence against a virus or disease – is not offered by one element alone. There are several factors at play within immunity. Cell-mediated immunity (CMI) is the protective immune response generated by immune factors other than antibodies. This includes protection mediated by T lymphocytes (T cells), other white blood cells such as macrophages, and the soluble molecules (cytokines) which are produced by these immune cells. COVID-19 vaccines have been shown to activate cell-mediated immunity to help protect against infection with SARS-CoV-2, the virus that causes COVID-19.
T cells are an important part of the immune response mounted by our body in response to pathogens such as SARS-CoV-2. There are several subtypes of T cells that respond to different types of pathogens, and they play a critical role in shaping the overall immune response. T cells have proteins on their surface that can detect and kill SARS-CoV-2-infected cells. They can also release a wide range of small soluble molecules (cytokines) that can recruit other immune cells to help clear the infection. T cells also influence the antibody response against SARS-CoV-2 by shaping the type of antibodies generated against the virus. Finally, once the infection is cleared, T cells establish themselves as a small memory population that is pre-primed and ready to react to any future re-exposure to SARS-CoV-2, thus protecting against any subsequent infection that may occur.
In addition to cell-mediated immunity, antibody-mediated immunity is also a critical arm of the protective immune response. Antibody-mediated immunity is also referred to as humoral immunity and involves macromolecules found in fluids including antibodies produced by B cells and other blood proteins that are involved in fighting off pathogens. Antibodies have several functions, one of which is blocking a virus from entering and infecting a cell. This is known as “neutralization”. COVID-19 vaccines have been shown to activate antibody-mediated immunity to help protect against infection with SARS-CoV-2.
Once an individual has received a vaccine against COVID-19 or has recovered from SARS-CoV-2 infection, their immune system remains primed for exposure or re-exposure to the virus. This is enabled by immune cells that have recognized and resolved the initial SARS-CoV-2 infection, or in the case of a vaccine, recognized the parts of the SARS-CoV-2 virus included in the vaccine formula. These immune cells, specifically developed for SARS-CoV-2, establish long-living memory populations which are ready to respond to exposure or re-exposure to the same virus.
While early studies have indicated that antibody levels themselves may drop after the initial exposure to SARS-CoV-2 through infection or vaccination, both B cells (cells that produce antibodies) and T cells (cells that enable cell-mediated immunity) establish memory populations and form a protective response to prevent against infection or re-infection. Currently, it is unknown exactly how long the protective response following infection and/or vaccination can remain, but the CITF is funding several studies looking into this.
CITF-funded researchers are involved in characterizing SARS-CoV-2 humoral and cell-mediated responses resulting from infection and vaccination. These include antibody titers, neutralization, T cell exhaustion, immune senescence, longevity and durability of the immune response to SARS-CoV-2. Researchers are also involved in studying conditions and immune factors that are associated with re-infections, breakthrough infections and the correlates of protection.
Correlates of protection to a virus or an infectious pathogen are measurable signs that a person (or other potential host) is immune, in the sense of being protected against becoming infected and/or developing disease. For many viruses, antibodies serve as a correlate of immunity, but they are not the only element to consider when determining whether a person is completely immune. Unfortunately, the correlates of protection against SARS-CoV-2 are still not completely understood.
CITF-funded researchers are interested in defining the markers that are associated with protective immunity against SARS-CoV-2 infection. Factors under consideration include presence and minimum thresholds of binding antibodies and neutralizing antibodies against the SARS-CoV-2 spike and nucleocapsid proteins. T and B cells are also being studied to determine their role in protection as they are shown to last longer than antibodies. Researchers would like to determine if 1) If these are good markers and 2) how much of these markers are needed to confer protection.
Scientists have recently found strong evidence that the concentration of IgG antibodies against the SARS-CoV-2 spike protein and the level of neutralizing antibody against SARS-CoV-2 are “correlates of protection” for vaccines against symptomatic COVID-19 (3).
Humoral immunity (mediated by antibodies):
- Antibody-producing B-cells increase in the first month, and remain high for at least eight months, post-infection (8, 9, 11, 12).
- IgA antibodies against the SARS-CoV-2 receptor binding domain (RBD), developed in the nose and throat, decrease rapidly after infection. They peak 16-20 days, and start waning one month, after infection (4, 5), and are at undetectable levels within three months following infection (6).
- IgG antibodies against the SARS-CoV-2 spike are more durable, and remain detectable, up to 12 months post-infection (7).
- Neutralizing antibodies against SARS-CoV-2 (antibodies that stop the replication of SARS-CoV-2 by affecting how the molecules on the pathogen’s surface can enter cells in the body) appear to wane about two to three months following the onset of infection. By six months, one study suggests, they are below the limit of detection (8-11).
Cellular immunity (mediated by T-cells, among other white blood cells):
- SARS-CoV-2 also induces cell-mediated immunity by activating SARS-CoV-2 specific CD4 and cytotoxic T-cells, which may last at least seven months post-infection (9, 11, 12).
References
- Röltgen K, Powell AE, Wirz OF, Stevens BA, Hogan CA, Najeeb J, Hunter M, Wang H, Sahoo MK, Huang C, Yamamoto F, Manohar M, Manalac J, Otrelo-Cardoso AR, Pham TD, Rustagi A, Rogers AJ, Shah NH, Blish CA, Cochran JR, Jardetzky TS, Zehnder JL, Wang TT, Narasimhan B, Gombar S, Tibshirani R, Nadeau KC, Kim PS, Pinsky BA, Boyd SD. Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome. Sci Immunol. 2020 Dec 7;5(54):eabe0240. doi: 10.1126/sciimmunol.abe0240.
- He Z, Ren L, Yang J, Guo L, Feng L, Ma C, et al. Seroprevalence and humoral immune durability of anti-SARS-CoV-2 antibodies in Wuhan, China: a longitudinal, population-level, cross-sectional study. Lancet. 2021;397(10279):1075-84.
- Gilbert PB, Donis RO, Koup RA, Fong Y, Plotkin SA, Follmann D. A Covid-19 Milestone Attained – A Correlate of Protection for Vaccines. N Engl J Med. 2022 Dec 10. doi: 10.1056/NEJMp2211314.
- Ma H, Zeng W, He H, Zhao D, Jiang D, Zhou P, Cheng L, Li Y, Ma X, Jin T. Serum IgA, IgM, and IgG responses in COVID-19. Cell Mol Immunol. 2020 Jul;17(7):773-775. doi: 10.1038/s41423-020-0474-z.
- Beaudoin-Bussières G, Laumaea A, Anand SP, Prévost J, Gasser R, Goyette G, Medjahed H, Perreault J, Tremblay T, Lewin A, Gokool L, Morrisseau C, Bégin P, Tremblay C, Martel-Laferrière V, Kaufmann DE, Richard J, Bazin R, Finzi A. Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals. mBio. 2020 Oct 16;11(5):e02590-20. doi: 10.1128/mBio.02590-20.
- Alfego D, Sullivan A, Poirier B, Williams J, Adcock D, Letovsky S. A population-based analysis of the longevity of SARS-CoV-2 antibody seropositivity in the United States. EClinicalMedicine. 2021 Jun;36:100902. doi: 10.1016/j.eclinm.2021.100902.
- Anand SP, Prévost J, Nayrac M, Beaudoin-Bussières G, Benlarbi M, Gasser R, Brassard N, Laumaea A, Gong SY, Bourassa C, Brunet-Ratnasingham E, Medjahed H, Gendron-Lepage G, Goyette G, Gokool L, Morrisseau C, Bégin P, Martel-Laferrière V, Tremblay C, Richard J, Bazin R, Duerr R, Kaufmann DE, Finzi A. Longitudinal analysis of humoral immunity against SARS-CoV-2 Spike in convalescent individuals up to 8 months post-symptom onset. Cell Rep Med. 2021 Jun 15;2(6):100290. doi: 10.1016/j.xcrm.2021.100290.
- Dan JM, Mateus J, Kato Y, Hastie KM, Yu ED, Faliti CE, Grifoni A, Ramirez SI, Haupt S, Frazier A, Nakao C, Rayaprolu V, Rawlings SA, Peters B, Krammer F, Simon V, Saphire EO, Smith DM, Weiskopf D, Sette A, Crotty S. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021 Feb 5;371(6529):eabf4063. doi: 10.1126/science.abf4063.
- Lumley SF, Wei J, O’Donnell D, Stoesser NE, Matthews PC, Howarth A, Hatch SB, Marsden BD, Cox S, James T, Peck LJ, Ritter TG, de Toledo Z, Cornall RJ, Jones EY, Stuart DI, Screaton G, Ebner D, Hoosdally S, Crook DW, Conlon CP, Pouwels KB, Walker AS, Peto TEA, Walker TM, Jeffery K, Eyre DW; Oxford University Hospitals Staff Testing Group. The Duration, Dynamics, and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Responses in Individual Healthcare Workers. Clin Infect Dis. 2021 Aug 2;73(3):e699-e709. doi: 10.1093/cid/ciab004.
- Wheatley AK, Juno JA, Wang JJ, Selva KJ, Reynaldi A, Tan HX, Lee WS, Wragg KM, Kelly HG, Esterbauer R, Davis SK, Kent HE, Mordant FL, Schlub TE, Gordon DL, Khoury DS, Subbarao K, Cromer D, Gordon TP, Chung AW, Davenport MP, Kent SJ. Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19. Nat Commun. 2021 Feb 19;12(1):1162. doi: 10.1038/s41467-021-21444-5.
- Cohen KW, Linderman SL, Moodie Z, Czartoski J, Lai L, Mantus G, Norwood C, Nyhoff LE, Edara VV, Floyd K, De Rosa SC, Ahmed H, Whaley R, Patel SN, Prigmore B, Lemos MP, Davis CW, Furth S, O’Keefe JB, Gharpure MP, Gunisetty S, Stephens K, Antia R, Zarnitsyna VI, Stephens DS, Edupuganti S, Rouphael N, Anderson EJ, Mehta AK, Wrammert J, Suthar MS, Ahmed R, McElrath MJ. Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells. Cell Rep Med. 2021 Jul 20;2(7):100354. doi: 10.1016/j.xcrm.2021.100354.
- Law JC, Girard M, Chao GYC, Ward LA, Isho B, Rathod B, Colwill K, Li Z, Rini JM, Yue FY, Mubareka S, McGeer AJ, Ostrowski MA, Gommerman JL, Gingras AC, Watts TH. Persistence of T Cell and Antibody Responses to SARS-CoV-2 Up to 9 Months after Symptom Onset. J Immunol. 2022 Jan 15;208(2):429-443. doi: 10.4049/jimmunol.2100727.
No, being infected with SARS-CoV-2 does not protect you against subsequent re-infection.
- While most people exposed to SARS-CoV-2 mount immune responses, some do not – or their immune response may vary substantially. More specifically, people with symptomatic SARS-CoV-2 infection tend to have higher antibody levels than those who are asymptomatic (no symptoms) (1-4). For at least two to three months following infection, those with moderate-to-severe COVID-19 illness have higher levels of antibodies than people with mild illness (2). These differences may persist for five to eight months following infection (3, 5).
- Hospitalized people tend to have higher antibody levels than those not hospitalized (1-4). Both binding antibodies (which are responsible for binding to a pathogen and alerting the immune system to its presence so that white blood cells can be sent to destroy it) and neutralizing antibody levels rise faster and reach a higher peak in people with more severe COVID-19 (1, 2, 6).
- Age, as well as chronic and immunocompromised health conditions are factors that mediate the immune response mounted against SARS-CoV-2. Older people can have a harder time mounting an immune response (7), but high peaks of antibody levels are observed among those who do mount an immune response (1, 3, 5, 7).
- In addition, Omicron and its subvariants are capable of reinfecting people who had the BA.1 Omicron strain or earlier variants. This is mainly due to the virus’s ability to evade the host’s immune response (8).
Several CITF-funded studies of populations that are particularly vulnerable because they are immune-compromised due to illness (e.g., inflammatory bowel disease or other autoimmune disorders) or treatment for other illnesses (e.g., solid organ transplant recipients, cancer patients) had a variable immune response toward infection. In many cases they had more severe disease but not necessarily more immune protection.
References
- Gudbjartsson DF, Helgason A, Jonsson H, Magnusson OT, Melsted P, Norddahl GL, Saemundsdottir J, Sigurdsson A, Sulem P, Agustsdottir AB, Eiriksdottir B, Fridriksdottir R, Gardarsdottir EE, Georgsson G, Gretarsdottir OS, Gudmundsson KR, Gunnarsdottir TR, Gylfason A, Holm H, Jensson BO, Jonasdottir A, Jonsson F, Josefsdottir KS, Kristjansson T, Magnusdottir DN, le Roux L, Sigmundsdottir G, Sveinbjornsson G, Sveinsdottir KE, Sveinsdottir M, Thorarensen EA, Thorbjornsson B, Löve A, Masson G, Jonsdottir I, Möller AD, Gudnason T, Kristinsson KG, Thorsteinsdottir U, Stefansson K. Spread of SARS-CoV-2 in the Icelandic Population. N Engl J Med. 2020 Jun 11;382(24):2302-2315. doi: 10.1056/NEJMoa2006100.
- Röltgen K, Powell AE, Wirz OF, Stevens BA, Hogan CA, Najeeb J, Hunter M, Wang H, Sahoo MK, Huang C, Yamamoto F, Manohar M, Manalac J, Otrelo-Cardoso AR, Pham TD, Rustagi A, Rogers AJ, Shah NH, Blish CA, Cochran JR, Jardetzky TS, Zehnder JL, Wang TT, Narasimhan B, Gombar S, Tibshirani R, Nadeau KC, Kim PS, Pinsky BA, Boyd SD. Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome. Sci Immunol. 2020 Dec 7;5(54):eabe0240. doi: 10.1126/sciimmunol.abe0240.
- Lumley SF, Wei J, O’Donnell D, Stoesser NE, Matthews PC, Howarth A, Hatch SB, Marsden BD, Cox S, James T, Peck LJ, Ritter TG, de Toledo Z, Cornall RJ, Jones EY, Stuart DI, Screaton G, Ebner D, Hoosdally S, Crook DW, Conlon CP, Pouwels KB, Walker AS, Peto TEA, Walker TM, Jeffery K, Eyre DW; Oxford University Hospitals Staff Testing Group. The Duration, Dynamics, and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Responses in Individual Healthcare Workers. Clin Infect Dis. 2021 Aug 2;73(3):e699-e709. doi: 10.1093/cid/ciab004.
- Nantel S, Bourdin B, Adams K, Carbonneau J, Rabezanahary H, Hamelin MÈ, McCormack D, Savard P, Longtin Y, Cheng MP, De Serres G, Corbeil J, Gilca V, Baz M, Boivin G, Quach C, Decaluwe H. Symptomatology during previous SARS-CoV-2 infection and serostatus before vaccination influence the immunogenicity of BNT162b2 COVID-19 mRNA vaccine. Front Immunol. 2022 Oct 14;13:930252. doi: 10.3389/fimmu.2022.930252.
- Dan JM, Mateus J, Kato Y, Hastie KM, Yu ED, Faliti CE, Grifoni A, Ramirez SI, Haupt S, Frazier A, Nakao C, Rayaprolu V, Rawlings SA, Peters B, Krammer F, Simon V, Saphire EO, Smith DM, Weiskopf D, Sette A, Crotty S. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021 Feb 5;371(6529):eabf4063. doi: 10.1126/science.abf4063.
- Wheatley AK, Juno JA, Wang JJ, Selva KJ, Reynaldi A, Tan HX, Lee WS, Wragg KM, Kelly HG, Esterbauer R, Davis SK, Kent HE, Mordant FL, Schlub TE, Gordon DL, Khoury DS, Subbarao K, Cromer D, Gordon TP, Chung AW, Davenport MP, Kent SJ. Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19. Nat Commun. 2021 Feb 19;12(1):1162. doi: 10.1038/s41467-021-21444-5.
- Wei J, Matthews PC, Stoesser N, Maddox T, Lorenzi L, Studley R, Bell JI, Newton JN, Farrar J, Diamond I, Rourke E, Howarth A, Marsden BD, Hoosdally S, Jones EY, Stuart DI, Crook DW, Peto TEA, Pouwels KB, Walker AS, Eyre DW; COVID-19 Infection Survey team. Anti-spike antibody response to natural SARS-CoV-2 infection in the general population. Nat Commun. 2021 Oct 29;12(1):6250. doi: 10.1038/s41467-021-26479-2.
- Altarawneh HN, Chemaitelly H, Ayoub HH, Hasan MR, Coyle P, Yassine HM, Al-Khatib HA, Smatti MK, Al-Kanaani Z, Al-Kuwari E, Jeremijenko A, Kaleeckal AH, Latif AN, Shaik RM, Abdul-Rahim HF, Nasrallah GK, Al-Kuwari MG, Butt AA, Al-Romaihi HE, Al-Thani MH, Al-Khal A, Bertollini R, Tang P, Abu-Raddad LJ. Protective Effect of Previous SARS-CoV-2 Infection against Omicron BA.4 and BA.5 Subvariants. N Engl J Med. 2022 Oct 27;387(17):1620-1622. doi: 10.1056/NEJMc2209306.
Some studies have shown that having a previous SARS-CoV-2 infection along with vaccination confers better protection against infection and severe outcomes than does vaccination or infection alone (1-3). This is not, however, to imply that one should try to get infected with SARS-CoV-2, as there are risks of severe disease and complications, including post-acute COVID-19 syndrome (also known as long COVID). Instead, individuals should exercise caution to avoid becoming infected and continue to get booster doses to offset waning immunity.
A summary of specific study results on hybrid immunity:
- During the pre-Omicron period, infection-acquired immunity with vaccination provided more than 90% protection (after two vaccine doses) against reinfection. Protection did not wane more than 1 year after infection or more than six months after vaccination (3).
- During the pre-Omicron period, people with two vaccine doses and a prior infection had a further 66% lower risk of reinfection than those with just infection-acquired immunity (4).
- Previously infected individuals had a slower decline in antibody levels after vaccination than people who had been vaccinated but never infected or infected and never vaccinated (5).
References
- Goldberg Y, Mandel M, Bar-On YM, Bodenheimer O, Freedman LS, Ash N, Alroy-Preis S, Huppert A, Milo R. Protection and Waning of Natural and Hybrid Immunity to SARS-CoV-2. N Engl J Med. 2022 Jun 9;386(23):2201-2212. doi: 10.1056/NEJMoa2118946.
- Abu-Raddad LJ, Chemaitelly H, Ayoub HH, et al. Association of Prior SARS-CoV-2 Infection With Risk of Breakthrough Infection Following mRNA Vaccination in Qatar. JAMA. 2021;326(19):1930–1939. doi:10.1001/jama.2021.19623.
- Hall V, Foulkes S, Insalata F, Kirwan P, Saei A, Atti A, Wellington E, Khawam J, Munro K, Cole M, Tranquillini C, Taylor-Kerr A, Hettiarachchi N, Calbraith D, Sajedi N, Milligan I, Themistocleous Y, Corrigan D, Cromey L, Price L, Stewart S, de Lacy E, Norman C, Linley E, Otter AD, Semper A, Hewson J, D’Arcangelo S, Chand M, Brown CS, Brooks T, Islam J, Charlett A, Hopkins S; SIREN Study Group. Protection against SARS-CoV-2 after Covid-19 Vaccination and Previous Infection. N Engl J Med. 2022 Mar 31;386(13):1207-1220. doi: 10.1056/NEJMoa2118691.
- Nordström P, Ballin M, Nordström A. Risk of SARS-CoV-2 reinfection and COVID-19 hospitalisation in individuals with natural and hybrid immunity: a retrospective, total population cohort study in Sweden. Lancet Infect Dis. 2022 Jun;22(6):781-790. doi: 10.1016/S1473-3099(22)00143-8.
- Nordström P, Ballin M, Nordström A. Risk of SARS-CoV-2 reinfection and COVID-19 hospitalisation in individuals with natural and hybrid immunity: a retrospective, total population cohort study in Sweden. Lancet Infect Dis. 2022 Jun;22(6):781-790. doi: 10.1016/S1473-3099(22)00143-8.
Hybrid immunity has become the new normal because most Canadians have been infected at this point and have had two or more doses of vaccine.
Although our Seroprevalence in Canada webpage does not specifically show the percentage of Canadians with hybrid immunity, it does show the percentage with infection-acquired antibodies and the percentage with either infection-acquired or vaccine-induced antibodies. As of October 2022, over 70% of Canadians have infection-acquired antibodies, with most of the infections occurring during the Omicron wave.
Immunity – a full defence against a virus or disease – is not offered by one element alone. There are several factors at play within immunity. Cell-mediated immunity (CMI) is the protective immune response generated by immune factors other than antibodies. This includes protection mediated by T lymphocytes (T cells), other white blood cells such as macrophages, and the soluble molecules (cytokines) which are produced by these immune cells. COVID-19 vaccines have been shown to activate cell-mediated immunity to help protect against infection with SARS-CoV-2, the virus that causes COVID-19.
Figure 3.1. When an individual is infected with SARS-CoV-2, the innate immune response is initiated and characterized by dendritic cell (DC) activation. This is followed by an adaptive immune response where T and B cells are activated. T cells can perform many different functions, while B cells differentiate into plasma cells to produce antibodies. Both types of cells establish memory populations to prevent against re-infection. Photo Credit: Mariana Bego.
T cells are an important part of the immune response mounted by our body in response to pathogens such as SARS-CoV-2. There are several subtypes of T cells that respond to different types of pathogens, and they play a critical role in shaping the overall immune response. T cells have proteins on their surface that can detect and kill SARS-CoV-2-infected cells. They can also release a wide range of small soluble molecules (cytokines) that can recruit other immune cells to help clear the infection. T cells also influence the antibody response against SARS-CoV-2 by shaping the type of antibodies generated against the virus. Finally, once the infection is cleared, T cells establish themselves as a small memory population that is pre-primed and ready to react to any future re-exposure to SARS-CoV-2, thus protecting against any subsequent infection that may occur.
In addition to cell-mediated immunity, antibody-mediated immunity is also a critical arm of the protective immune response. Antibody-mediated immunity is also referred to as humoral immunity and involves macromolecules found in fluids including antibodies produced by B cells and other blood proteins that are involved in fighting off pathogens. Antibodies have several functions, one of which is blocking a virus from entering and infecting a cell. This is known as “neutralization”. COVID-19 vaccines have been shown to activate antibody-mediated immunity to help protect against infection with SARS-CoV-2.
Once an individual has received a vaccine against COVID-19 or has recovered from SARS-CoV-2 infection, their immune system remains primed for exposure or re-exposure to the virus. This is enabled by immune cells that have recognized and resolved the initial SARS-CoV-2 infection, or in the case of a vaccine, recognized the parts of the SARS-CoV-2 virus included in the vaccine formula. These immune cells, specifically developed for SARS-CoV-2, establish long-living memory populations which are ready to respond to exposure or re-exposure to the same virus.
While early studies have indicated that antibody levels themselves may drop after the initial exposure to SARS-CoV-2 through infection or vaccination, both B cells (cells that produce antibodies) and T cells (cells that enable cell-mediated immunity) establish memory populations and form a protective response to prevent against infection or re-infection. Currently, it is unknown exactly how long the protective response following infection and/or vaccination can remain, but the CITF is funding several studies looking into this.
CITF-funded researchers are involved in characterizing SARS-CoV-2 humoral and cell-mediated responses resulting from infection and vaccination. These include antibody titers, neutralization, T cell exhaustion, immune senescence, longevity and durability of the immune response to SARS-CoV-2. Researchers are also involved in studying conditions and immune factors that are associated with re-infections, breakthrough infections and the correlates of protection.
Herd immunity, alternatively known as community immunity, is when a large proportion of the population is immune to a specific disease such as COVID-19, reducing the spread of the disease from person to person. Although not every individual is immune to the virus or bacteria, the majority of those immune protect the rest of the individuals (including newborns or immunocompromised individuals who may not be able to get vaccinated) from getting infected.
Herd immunity can be achieved by having enough individuals infected with the virus or it can be achieved with vaccinations. Vaccinations are the ideal approach for achieving herd immunity and it was reported by some studies that at least 70-85% of the population would need to be immune to achieve herd immunity. Herd immunity depends on the reproduction number or R0, which tells us the average number of people that a single person with the virus can infect. A higher R0 indicates more people need to be immune to reach herd immunity.
Figure 3.2. Herd immunity is achieved when there is a large proportion of individuals that are immune to SARS-CoV-2 that would reduce the risk of the remaining individuals from getting infected. Photo Credit: Mariana Bego.
Correlates of protection to a virus or an infectious pathogen are measurable signs that a person (or other potential host) is immune, in the sense of being protected against becoming infected and/or developing disease. For many viruses, antibodies serve as a correlate of immunity, but they are not the only element to consider when determining whether a person is completely immune. Unfortunately, the correlates of protection against SARS-CoV-2 are still not completely understood.
CITF-funded researchers are interested in defining the markers that are associated with protective immunity against SARS-CoV-2 infection. Factors under consideration include presence and minimum thresholds of binding antibodies and neutralizing antibodies against the SARS-CoV-2 spike and nucleocapsid proteins. T and B cells are also being studied to determine their role in protection as they are shown to last longer than antibodies. Researchers would like to determine if 1) If these are good markers and 2) how much of these markers are needed to confer protection.
Serosurveillance and other population-based studies
Figure 4.1. Using a spring-loaded lancet provided in the test kit, drops of blood from a fingerprick are placed onto the DBS filter paper card. The DBS is then sealed, packaged, labelled and shipped to an analytical lab, where it is processed and analyzed for the presence of SARS-CoV-2 antibodies. A positive result would be indicative of a past infection. Photo Credit: Kristin Davis.
Seroprevalence is the number (or percentage) of people in a population who test positive for specific antibodies against a virus or infectious agent, based on blood tests. If the seroprevalence is 1%, for example, this suggests that 1% of the population studied has antibodies to the virus or infectious agent and therefore could have some form of resistance to it. Seroprevalence could refer to people with antibodies due to infection and/or antibodies due to vaccination.
Health surveillance is common in public health. It is a way of observing and monitoring the health and wellness of large groups of people. Serosurveillance monitors and estimates antibody levels in blood samples from certain groups of people against infectious agents, such as SARS-CoV-2, the virus that causes COVID-19. The goal is to measure how many people have been exposed to SARS-CoV-2 and have subsequently developed antibodies, which are an essential part of developing immunity. This will help researchers estimate population immunity resulting from a past infection or vaccination. When it’s known how many people have antibodies to ward off potential infection, or at least serious forms of infection, public health officials can more confidently inform and protect people.
To understand population immunity to the SARS-CoV-2 virus, blood samples from thousands of Canadians are currently being tested to check levels of antibodies directed against SARS-CoV-2 proteins.
As vaccines become available, serosurveillance can help us determine priority groups for vaccination by identifying populations that remain vulnerable to infection. Seroprevalence studies can also help us monitor the effectiveness of the existing vaccination programs.
SARS-CoV-2 is a relatively new virus so there are many questions that still need to be answered. For example, at this stage in the pandemic, we still don’t know for certain how long antibodies (from a COVID-19 infection or a vaccine) remain in the body. By continuing to gather as much information as possible about the virus, we improve our ability to mount a comprehensive and well-informed response against it.
Immune testing is not testing for an active virus (when you go get a nasal or mouth swab to see if you have SARS-CoV-2). Rather, it means testing individuals for the presence of antibodies made in response to SARS-CoV-2 (the virus that causes COVID-19). It is usually done with a blood sample, but other methods have been developed as well, including using saliva. Immune testing on a large scale can approximate the total number of individuals who have been infected and their socio-demographic distribution. Special techniques can be used to detect variants of concern in the samples. This information can be used to better understand SARS-CoV-2’s patterns of infection and inform measures to prevent transmission.
Vaccine surveillance studies look at vaccine effectiveness (How good are vaccines at preventing severe disease, new infections, and transmission?) and vaccine safety (identifying and quantifying the vaccine’s adverse effects). An adverse effect is an undesired harmful effect resulting from a medication or other intervention.
Vaccine surveillance also looks more precisely at the immune response generated by the vaccine (how successful is the vaccine at developing a protective immune response? What are the details of the vaccine-induced immune response? How long can these “markers of protection” be detected? How long will the vaccine work?).
Vaccine surveillance covers vaccine confidence which explores the driving factors behind any concerns people may have about getting vaccinated (aka. vaccine hesitancy).
Natural immunity is better termed “infection-acquired immunity”. It means the person has some form of defence against the virus due to an infection or exposure – not thanks to a vaccine. Vaccine-induced immunity refers to the body’s defence mechanism against a virus created in response to a vaccine.
Currently, there is no consensus on how long either type of immunity lasts.
Sometimes referred to as field studies, population-based studies aim to answer research questions for defined populations, based on a sample of that population. These populations of interest can be large, like the entire population of a city, or they can be defined by a single characteristic shared by a number of people, like children between the ages of 3 and 5.
These studies are traditionally described as studies that involve a defined “general population,” as opposed to a hospital-based or occupation-based population.
To extrapolate statistics from population-based studies, several minimum requirements need to be met:
- The sample of individuals needs to be big enough, randomly selected, and representative of the general population;
- The measurements need to be standardized;
- The tests used need to have adequate sensitivity and specificity.
Population-based seroprevalence surveys of COVID-19 help us to do things like estimate how infectious the virus is and its fatality rate. They can tell us, for example, how much transmission is due to asymptomatic and mild infections. They can also help us identify exposed and susceptible populations.
These types of studies are well suited to inform evidence-based policy decisions.
CITF-funded researchers are involved in large-scale projects estimating seroprevalence by region and province or territory. They are also involved in estimating infection-acquired and vaccine-induced seroprevalence among populations of interest such as school-aged children, long-term care facilities, healthcare workers, geographical hotspots, and people at higher risk due to pre-existing health conditions, among others. You can see a complete list of our funded studies here.
Core data elements are a standardized list of questions developed by CITF experts that must be integrated into surveys done by CITF-funded groups studying immunity. These core data elements aim to encourage the many CITF-funded research groups to acquire and record survey data in a standardized manner. The goal is for the CITF to be able to directly compare results from different COVID-19 studies and initiatives across Canada.
Specifically, the core data elements include questions and responses related to COVID-19 status, COVID-19 symptoms, quality of housing, risk factors, risk acquisitions, vaccines and health behaviour changes related to the virus.
A DBS, or dried blood spot kit, is an easy-to-use way to take a blood sample that people can do at home. It’s a great alternative to having blood drawn in a clinic, as people don’t have to leave home to do it. The participant is asked to follow a step-by-step process which involves them pricking their finger and depositing several blood drops onto a card which is then mailed back to a laboratory for analysis. Please see a video made by one of our funded studies here.
Currently, these kits are being used by a number of seroprevalence studies supported by the CITF in order to collect blood for antibody testing. Scientists use the collected blood spots to determine the presence of SARS-CoV-2 antibodies in a surveyed population.
Seroprevalence is the number (or percentage) of people in a population who test positive for specific antibodies against a virus or infectious agent, based on blood tests. If the seroprevalence is 1%, for example, this suggests that 1% of the population studied has antibodies to the virus or infectious agent and therefore could have some form of resistance to it. Seroprevalence could refer to people with antibodies due to infection and/or antibodies due to vaccination.
Health surveillance is common in public health. It is a way of observing and monitoring the health and wellness of large groups of people. Serosurveillance monitors and estimates antibody levels in blood samples from certain groups of people against infectious agents, such as SARS-CoV-2, the virus that causes COVID-19. The goal is to measure how many people have been exposed to SARS-CoV-2 and have subsequently developed antibodies, which are an essential part of developing immunity. This will help researchers estimate population immunity resulting from a past infection or vaccination. When it’s known how many people have antibodies to ward off potential infection, or at least serious forms of infection, public health officials can more confidently inform and protect people.
To understand population immunity to the SARS-CoV-2 virus, blood samples from thousands of Canadians are currently being tested to check levels of antibodies directed against SARS-CoV-2 proteins.
As vaccines become available, serosurveillance can help us determine priority groups for vaccination by identifying populations that remain vulnerable to infection. Seroprevalence studies can also help us monitor the effectiveness of the existing vaccination programs.
SARS-CoV-2 is a relatively new virus so there are many questions that still need to be answered. For example, at this stage in the pandemic, we still don’t know for certain how long antibodies (from a COVID-19 infection or a vaccine) remain in the body. By continuing to gather as much information as possible about the virus, we improve our ability to mount a comprehensive and well-informed response against it.
Immune testing is not testing for an active virus (when you go get a nasal or mouth swab to see if you have SARS-CoV-2). Rather, it means testing individuals for the presence of antibodies made in response to SARS-CoV-2 (the virus that causes COVID-19). It is usually done with a blood sample, but other methods have been developed as well, including using saliva. Immune testing on a large scale can approximate the total number of individuals who have been infected and their socio-demographic distribution. Special techniques can be used to detect variants of concern in the samples. This information can be used to better understand SARS-CoV-2’s patterns of infection and inform measures to prevent transmission.
Vaccine surveillance studies look at vaccine effectiveness (How good are vaccines at preventing severe disease, new infections, and transmission?) and vaccine safety (identifying and quantifying the vaccine’s adverse effects). An adverse effect is an undesired harmful effect resulting from a medication or other intervention.
Vaccine surveillance also looks more precisely at the immune response generated by the vaccine (how successful is the vaccine at developing a protective immune response? What are the details of the vaccine-induced immune response? How long can these “markers of protection” be detected? How long will the vaccine work?).
Vaccine surveillance covers vaccine confidence which explores the driving factors behind any concerns people may have about getting vaccinated (aka. vaccine hesitancy).
Natural immunity is better termed “infection-acquired immunity”. It means the person has some form of defence against the virus due to an infection or exposure – not thanks to a vaccine. Vaccine-induced immunity refers to the body’s defence mechanism against a virus created in response to a vaccine.
Currently, there is no consensus on how long either type of immunity lasts.
Sometimes referred to as field studies, population-based studies aim to answer research questions for defined populations, based on a sample of that population. These populations of interest can be large, like the entire population of a city, or they can be defined by a single characteristic shared by a number of people, like children between the ages of 3 and 5.
These studies are traditionally described as studies that involve a defined “general population,” as opposed to a hospital-based or occupation-based population.
To extrapolate statistics from population-based studies, several minimum requirements need to be met:
- The sample of individuals needs to be big enough, randomly selected, and representative of the general population;
- The measurements need to be standardized;
- The tests used need to have adequate sensitivity and specificity.
Population-based seroprevalence surveys of COVID-19 help us to do things like estimate how infectious the virus is and its fatality rate. They can tell us, for example, how much transmission is due to asymptomatic and mild infections. They can also help us identify exposed and susceptible populations.
These types of studies are well suited to inform evidence-based policy decisions.
CITF-funded researchers are involved in large-scale projects estimating seroprevalence by region and province or territory. They are also involved in estimating infection-acquired and vaccine-induced seroprevalence among populations of interest such as school-aged children, long-term care facilities, healthcare workers, geographical hotspots, and people at higher risk due to pre-existing health conditions, among others. You can see a complete list of our funded studies here.
Core data elements are a standardized list of questions developed by CITF experts that must be integrated into surveys done by CITF-funded groups studying immunity. These core data elements aim to encourage the many CITF-funded research groups to acquire and record survey data in a standardized manner. The goal is for the CITF to be able to directly compare results from different COVID-19 studies and initiatives across Canada.
Specifically, the core data elements include questions and responses related to COVID-19 status, COVID-19 symptoms, quality of housing, risk factors, risk acquisitions, vaccines and health behaviour changes related to the virus.
A DBS, or dried blood spot kit, is an easy-to-use way to take a blood sample that people can do at home. It’s a great alternative to having blood drawn in a clinic, as people don’t have to leave home to do it. The participant is asked to follow a step-by-step process which involves them pricking their finger and depositing several blood drops onto a card which is then mailed back to a laboratory for analysis. Please see a video made by one of our funded studies here.
Currently, these kits are being used by a number of seroprevalence studies supported by the CITF in order to collect blood for antibody testing. Scientists use the collected blood spots to determine the presence of SARS-CoV-2 antibodies in a surveyed population.
Figure 4.1. Using a spring-loaded lancet provided in the test kit, drops of blood from a fingerprick are placed onto the DBS filter paper card. The DBS is then sealed, packaged, labelled and shipped to an analytical lab, where it is processed and analyzed for the presence of SARS-CoV-2 antibodies. A positive result would be indicative of a past infection. Photo Credit: Kristin Davis.
Vaccines
Figure 5.1. The COVID-19 mRNA vaccine contains instructions (mRNA) to make a lot of SARS-CoV-2 Spike proteins. The release of this Spike protein outside of the host cell triggers an immune response and the host makes antibodies, B cells, and T cells against the virus, similar to what happens in natural infection. Photo Credit: Mariana Bego.
COVID-19 vaccines trigger our bodies to develop immunity against SARS-CoV-2 without us having to get the disease first. There are currently four main types of COVID-19 vaccines: messenger RNA (mRNA) vaccines (such as Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax), protein subunit vaccines (such as Novavax’s COVID-19 vaccine), viral vector vaccines (such as Johnson & Johnson and Oxford-AstraZeneca’s Vaxzevria), and inactivated virus vaccines (such as the Sinovac COVID-19 vaccine).
The mRNA vaccine teaches our cells to make a copy of a protein unique to SARS-CoV-2 called the spike protein. Our body recognizes these proteins as foreign and generates antibodies and build B cells and T cells to remember the virus so we can defeat it if we are infected in the future.
The protein subunit vaccines consist of harmless proteins of the SARS-CoV-2 virus, while vector vaccines contain a different harmless virus that enters our cells to produce the SARS-CoV-2 spike protein. Lastly, the inactivated SARS-CoV-2 vaccine consists of the killed virus that no longer replicates.
All types of vaccines have the same end goal: generate a supply of memory B and T cells to remember how to the fight the virus in the future. The levels and duration of immunity offered by these different vaccines, however, may vary.
There are currently four COVID-19 vaccines that are approved and authorized for use in Canada (see table below). On September 16, 2021, three of these vaccines were authorized under the Food and Drug Regulations Act, prompting the transition to using brand names instead of company names, notably, Comirnaty, Spikevax, and Vaxzevria.
| Brand name | Manufacturer(s) | Research name | Vaccine type | Number of doses administered |
| Comirnaty | Pfizer, Inc. and BioNTech | BNT162b2 | mRNA | 2 |
| Spikevax | ModernaTX, Inc. | mRNA-1273 | mRNA | 2 |
| Vaxzevria | AstraZeneca Canada Inc. and Verity/SII (COVISHIELD) | ChAdOx1 | Viral-vector | 2 |
| (Johnson & Johnson) | Janssen Pharmaceutical Companies of Johnson & Johnson | JNJ-78436735 | Viral-vector | 1 |
For more information on these vaccines, please the Government of Canada’s website.
Vaccines against SARS-CoV-2 have been developed to prime your body’s immune response to ensure that it fights against the virus, reducing the risk of you getting COVID-19. These vaccines are especially good at reducing the risk of severe COVID-19 symptoms, hospitalization, and death.
That said, the risk of a vaccinated person catching SARS-CoV-2 and developing COVID cannot be completely eliminated. Early data suggest fully vaccinated people can get the Delta variant and perhaps other variants. However, when compared to unvaccinated individuals, fully vaccinated people are less likely to acquire SARS-CoV-2, and when they do, they get less severe COVID-19 symptoms.
Studies suggest that vaccinated individuals have reduced numbers of virus in the blood and this could mean there is less virus to transmit, meaning reduced transmission. That said, vaccinated individuals can still transmit the virus for a period of time after infection. Therefore, it is extremely important that vaccinated people continue to follow public health guidelines including frequent hand washing, maintaining a safe distance from others, wearing a mask, and staying home if feeling unwell.
If you had COVID-19 previously, you should still get vaccinated because the level of immunity from infection and its duration is not entirely clear. The vaccine will also provide longer-term protection as it has been optimally designed to generate an effective immune response. There is no harm in getting a vaccine to boost your immune response to SARS-CoV-2.
Vaccine effectiveness is measured by the impact of vaccination on COVID-19-related hospitalizations, mortality, effects of COVID-19 vaccination on asymptomatic infection and transmission, and how groups of different ages, and overall health status respond to the vaccine. Some of the studies the CITF supports include assessing effectiveness with different combinations of vaccines, vaccinations in pregnant women and children, vaccinations in people at higher risk due to other health conditions, and vaccine effectiveness for prevention of serious outcomes among hospitalized adults.
The CITF is involved in supporting research studies which evaluate vaccine safety. Vaccine safety is evaluated by tracking adverse events following immunization (AEFIs) including an association with anaphylaxis and other allergic events, Guillain-Barré syndrome, Bell’s palsy, and vaccine-associated enhanced disease, among others. Some of the studies we fund are documenting health events including temporary local injection site reactions, systemic symptoms (fever, fatigue, myalgia), respiratory symptoms suggestive of the cold or flu, and gastrointestinal symptoms (nausea, vomiting, diarrhea, or stomach pain), among others. The populations studied overlap with studies measuring vaccine effectiveness and include pregnant women, children, people at higher risk due to other health conditions, and hospitalized adults.
The current vaccines approved for use were tested in clinical trials before the new variants emerged. Evidence to determine how effectively the vaccines will work against them has been coming out in bits as studies follow this issue closely.
Preliminary studies show that individuals vaccinated with the Pfizer-BioNTech Comirnaty mRNA vaccine can neutralize the variants of concern Alpha and Beta, originating from the UK and South Africa, respectively. Another study has shown that there was a reduction in the capability of Moderna’s Spikevax mRNA-1273 to ward off the Beta variant. Lastly, Novavax announced that their vaccine had a vaccine efficacy of 89.3% in a UK population where there was high prevalence of the Alpha variant, suggesting that it is effective against this variant. Altogether, these studies suggest the importance of continuous monitoring of the variants as this could indicate a need for a vaccine strain change.
Real-world data show that vaccines remain highly effective at reducing COVID-19-related hospitalizations and emergency department (ED) visits, even in the presence of the circulating Delta variant. Unvaccinated individuals who contracted the Delta variant are 5 to 7 times more likely to need ED care or hospitalization when compared to vaccinated individuals. Moderna’s Spikevax and Pfizer-BioNTech’s Comirnaty were both highly effective at preventing hospitalizations among adults ages 18 and older (95% and 80%, respectively). But vaccine effectiveness was lower for those aged 75 years and above. Vaccination is therefore highly important to ease the burden on the healthcare system.
A breakthrough infection occurs when individuals who are fully vaccinated against a disease, such as COVID-19, are subsequently infected. The term ‘breakthrough’ signifies the virus broke through the protective barrier that vaccines provide. The effectiveness of COVID-19 vaccines is not 100% and as such, breakthrough infections can occur, although they are predominantly asymptomatic or mildly symptomatic. COVID-19 vaccines remain the best way to be protected against severe disease, hospitalization, and death resulting from SARS-CoV-2 infection.
If a child has had a SARS-CoV-2 infection, regardless of the variant, the National Advisory Committee on Immunization (NACI) recommends that they still receive two doses of vaccine at the recommended eight-week interval, if currently eligible, and once symptoms have resolved and the child is no longer considered infectious (NACI). For specific recommendations, contact your healthcare provider.
If a child has recovered from an infection with SARS-CoV-2, including with the Omicron variant, between their first and second dose, they should still receive their second dose, as recommended by NACI. Since the extent of protection from infection versus vaccination in children is unknown, all eligible children should be vaccinated with the two-dose COVID-19 vaccine regimen. Although infection builds immunity, vaccination provides more robust protection. Importantly, provinces and territories have their own set of recommendations for the timing of vaccines after an infection, so it is highly recommended to verify with local public health units.
Vaccination is one of the best tools to limit severe disease. Being optimally protected includes receiving a third dose – even for those previously infected – while continuing to follow local public health measures. For specific recommendations, contact your healthcare provider.
It isn’t unusual for vaccines to provide immunity for relatively short periods of time; for example, we need to be vaccinated against the flu annually. Immune responses to COVID-19 vaccination have been shown to last up to eight months, but antibody levels decrease as early as three months post-vaccination, and this decay (or waning) varies among individuals of different ages and those with underlying medical conditions.
COVID-19 vaccines have been shown to:
- Induce long-lasting memory T-cell responses. CD4+ and CD8+ T cells continue to be relatively stable up to six to eight months following vaccination (1, 2).
- Induce specific memory B-cells against SARS-CoV-2 receptor binding domain (RBD) that are stable for six months (1-5).
- Offer a more consistent and higher-titer initial antibody response than from infection, particularly after two or more doses (6, 7).
- Confer anti-spike (S), anti-RBD and neutralizing antibodies that remain detectable at least six to eight months following vaccination (1, 2).
The immune response may be reduced in individuals who are immunosuppressed, and those with underlying chronic illnesses (8). Age, comorbidities, and the presence of chronic diseases are responsible for faster decay of both binding and neutralizing antibodies (9, 10). People over the age of 65 have significantly lower peak anti-S and neutralizing antibody levels following vaccination than those who are younger (11).
References
- Barouch DH, Stephenson KE, Sadoff J, Yu J, Chang A, Gebre M, McMahan K, Liu J, Chandrashekar A, Patel S, Le Gars M, de Groot AM, Heerwegh D, Struyf F, Douoguih M, van Hoof J, Schuitemaker H. Durable Humoral and Cellular Immune Responses 8 Months after Ad26.COV2.S Vaccination. N Engl J Med. 2021 Sep 2;385(10):951-953. doi: 10.1056/NEJMc2108829.
- Goel RR, Apostolidis SA, Painter MM, Mathew D, Pattekar A, Kuthuru O, Gouma S, Hicks P, Meng W, Rosenfeld AM, Dysinger S, Lundgreen KA, Kuri-Cervantes L, Adamski S, Hicks A, Korte S, Oldridge DA, Baxter AE, Giles JR, Weirick ME, McAllister CM, Dougherty J, Long S, D’Andrea K, Hamilton JT, Betts MR, Luning Prak ET, Bates P, Hensley SE, Greenplate AR, Wherry EJ. Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. Sci Immunol. 2021 Apr 15;6(58):eabi6950. doi: 10.1126/sciimmunol.abi6950.
- Sokal A, Barba-Spaeth G, Fernández I, Broketa M, Azzaoui I, de La Selle A, Vandenberghe A, Fourati S, Roeser A, Meola A, Bouvier-Alias M, Crickx E, Languille L, Michel M, Godeau B, Gallien S, Melica G, Nguyen Y, Zarrouk V, Canoui-Poitrine F, Pirenne F, Mégret J, Pawlotsky JM, Fillatreau S, Bruhns P, Rey FA, Weill JC, Reynaud CA, Chappert P, Mahévas M. mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants. Immunity. 2021 Dec 14;54(12):2893-2907.e5. doi: 10.1016/j.immuni.2021.09.011.
- Wang Z, Schmidt F, Weisblum Y, Muecksch F, Barnes CO, Finkin S, Schaefer-Babajew D, Cipolla M, Gaebler C, Lieberman JA, Oliveira TY, Yang Z, Abernathy ME, Huey-Tubman KE, Hurley A, Turroja M, West KA, Gordon K, Millard KG, Ramos V, Da Silva J, Xu J, Colbert RA, Patel R, Dizon J, Unson-O’Brien C, Shimeliovich I, Gazumyan A, Caskey M, Bjorkman PJ, Casellas R, Hatziioannou T, Bieniasz PD, Nussenzweig MC. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature. 2021 Apr;592(7855):616-622. doi: 10.1038/s41586-021-03324-6.
- Ciabattini A, Pastore G, Fiorino F, Polvere J, Lucchesi S, Pettini E, Auddino S, Rancan I, Durante M, Miscia M, Rossetti B, Fabbiani M, Montagnani F, Medaglini D. Evidence of SARS-CoV-2-Specific Memory B Cells Six Months After Vaccination With the BNT162b2 mRNA Vaccine. Front Immunol. 2021 Sep 28;12:740708. doi: 10.3389/fimmu.2021.740708.
- Walsh EE, Frenck RW Jr, Falsey AR, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Mulligan MJ, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fontes-Garfias C, Shi PY, Türeci Ö, Tompkins KR, Lyke KE, Raabe V, Dormitzer PR, Jansen KU, Şahin U, Gruber WC. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med. 2020 Dec 17;383(25):2439-2450. doi: 10.1056/NEJMoa2027906.
- Israel A, Shenhar Y, Green I, Merzon E, Golan-Cohen A, Schäffer AA, Ruppin E, Vinker S, Magen E. Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection. medRxiv [Preprint]. 2021 Aug 21:2021.08.19.21262111. doi: 10.1101/2021.08.19.21262111.
- Breznik JA, Rahim A, Kajaks T, Hagerman M, Bilaver L, Colwill K, Dayam RM, Gingras A-C, Verschoor CP, McElhaney JE, Bramson JL, Bowdish DME, Costa AP. Protection from Omicron infection in residents of nursing and retirement homes in Ontario, Canada. medRxiv 2022.06.28.22277016; doi: https://doi.org/10.1101/2022.06.28.22277016
- Canaday DH, Oyebanji OA, Keresztesy D, Payne M, Wilk D, Carias L, et al. Significant reduction in humoral immunity among healthcare workers and nursing home residents 6 months after COVID-19 BNT162b2 mRNA vaccination. medRxiv. 2021:2021.08.15.21262067.
- Abu Jabal K, Ben-Amram H, Beiruti K, Batheesh Y, Sussan C, Zarka S, Edelstein M. Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from healthcare workers, Israel, December 2020 to January 2021. Euro Surveill. 2021 Feb;26(6):2100096. doi: 10.2807/1560-7917.ES.2021.26.6.2100096.
- Brodin P. Immune determinants of COVID-19 disease presentation and severity. Nat Med. 2021;27(1):28-33.
Recent evidence suggests that vaccine effectiveness diminishes over time. By six months post-second dose, there has been a significant waning of antibodies (1, 2). In light of this evidence, a campaign for additional vaccine doses was initiated in Canada and many other countries. The National Advisory Committee (NACI) on Immunization recommends booster doses at an interval of six months following the previous COVID-19 vaccination or 3-6 months post SARS-CoV-2 infection (3). As the bivalent COVID-19 vaccines are now available, NACI provides some recommendations for booster doses based on age and health status (4).
Evidence suggests that booster doses have been very effective:
- In healthy (general) population, a third dose is highly protective (95%) against severe outcomes from Omicron (5).
- A booster dose induced a robust immune response (cellular and humoral) in individuals over 80 years old who previously did not respond to the first two doses (6), and effectively protected older people from the ravages of the Omicron wave.
- CITF-funded studies and international research have shown that third doses were highly protective against recent SARS-CoV-2 variants in people living with HIV (7), cancer patients (CITF CanPath studies), solid organ transplant recipients (8), kidney transplant patients on dialysis (9), and other immunocompromised populations (10).
References
- Levin EG, Lustig Y, Cohen C, Fluss R, Indenbaum V, Amit S, Doolman R, Asraf K, Mendelson E, Ziv A, Rubin C, Freedman L, Kreiss Y, Regev-Yochay G. Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months. N Engl J Med. 2021 Dec 9;385(24):e84. doi: 10.1056/NEJMoa2114583.
- Buchan SA, Chung H, Brown KA, et al. Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes. JAMA Netw Open. 2022;5(9):e2232760. doi:10.1001/jamanetworkopen.2022.32760.
- https://www.canada.ca/content/dam/phac-aspc/documents/services/immunization/national-advisory-committee-on-immunization-naci/naci-guidance-planning-fall-2022-covid-19-vaccine-booster.pdf
- https://www.canada.ca/content/dam/phac-aspc/documents/services/immunization/national-advisory-committee-on-immunization-naci/recommendations-use-bivalent-Omicron-containing-mrna-covid-19-vaccines.pdf
- Buchan SA, Chung H, Brown KA, et al. Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes. JAMA Netw Open. 2022;5(9):e2232760. doi:10.1001/jamanetworkopen.2022.32760.
- Romero-Olmedo AJ, Schulz AR, Hochstätter S, Gupta DD, Hirseland H, Staudenraus D, Camara B, Volland K, Hefter V, Sapre S, Krähling V, Müller-Kräuter H, Chung HR, Mei HE, Keller C, Lohoff M. Dynamics of humoral and T-cell immunity after three BNT162b2 vaccinations in adults older than 80 years. Lancet Infect Dis. 2022 May;22(5):588-589. doi: 10.1016/S1473-3099(22)00219-5.
- Brumme ZL, Mwimanzi F, Lapointe HR, Cheung PK, Sang Y, Duncan MC, Yaseen F, Agafitei O, Ennis S, Ng K, Basra S, Lim LY, Kalikawe R, Speckmaier S, Moran-Garcia N, Young L, Ali H, Ganase B, Umviligihozo G, Omondi FH, Atkinson K, Sudderuddin H, Toy J, Sereda P, Burns L, Costiniuk CT, Cooper C, Anis AH, Leung V, Holmes D, DeMarco ML, Simons J, Hedgcock M, Romney MG, Barrios R, Guillemi S, Brumme CJ, Pantophlet R, Montaner JSG, Niikura M, Harris M, Hull M, Brockman MA. Humoral immune responses to COVID-19 vaccination in people living with HIV receiving suppressive antiretroviral therapy. NPJ Vaccines. 2022 Feb 28;7(1):28. doi: 10.1038/s41541-022-00452-6.
- Hall VG, Ferreira VH, Ierullo M, Ku T, Marinelli T, Majchrzak-Kita B, Yousuf A, Kulasingam V, Humar A, Kumar D. Humoral and cellular immune response and safety of two-dose SARS-CoV-2 mRNA-1273 vaccine in solid organ transplant recipients. Am J Transplant. 2021 Dec;21(12):3980-3989. doi: 10.1111/ajt.16766.
- Oliver MJ, Thomas D, Balamchi S, Ip J, Naylor K, Dixon SN, McArthur E, Kwong J, Perl J, Atiquzzaman M, Singer J, Yeung A, Hladunewich M, Yau K, Garg AX, Leis JA, Levin A, Krajden M, Blake PG. Vaccine Effectiveness Against SARS-CoV-2 Infection and Severe Outcomes in the Maintenance Dialysis Population in Ontario, Canada. J Am Soc Nephrol. 2022 Apr;33(4):839-849. doi: 10.1681/ASN.2021091262.
- Dayam RM, Law JC, Goetgebuer RL, Chao GY, Abe KT, Sutton M, Finkelstein N, Stempak JM, Pereira D, Croitoru D, Acheampong L, Rizwan S, Rymaszewski K, Milgrom R, Ganatra D, Batista NV, Girard M, Lau I, Law R, Cheung MW, Rathod B, Kitaygorodsky J, Samson R, Hu Q, Hardy WR, Haroon N, Inman RD, Piguet V, Chandran V, Silverberg MS, Gingras AC, Watts TH. Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune-mediated inflammatory diseases. JCI Insight. 2022 Jun 8;7(11):e159721. doi: 10.1172/jci.insight.159721.
| Company | Current monovalent and bivalent Omicron vaccines | Approvals in Canada |
| Pfizer-BioNtech3,4
|
Three new COVID-19 vaccines are now complementing the original Pfizer-BioNTech monovalent mRNA vaccine:
§ The Omicron BA.1-adapted monovalent vaccine elicited a superior immune response against Omicron BA.1 compared to the original Pfizer-BioNTech vaccine, when used as a booster dose (nearly 14-fold improvement in neutralizing titers when using a 30µg dose)3. § The Omicron BA.1-adapted bivalent vaccine elicited a superior immune response against Omicron BA.1 compared to the original Pfizer-BioNTech vaccine, when used as a booster dose (9-fold improvement in neutralizing titers when using a 30µg dose)3. § The Omicron BA.4/BA.5-adapted bivalent vaccine generated a strong neutralizing antibody response against the BA.4 and BA.5 subvariants when used as a booster, according to early clinical data4. |
Both Omicron bivalent vaccines are approved as a booster dose in individuals 12 years and older. |
| Moderna5, 6
|
A new bivalent COVID-19 vaccine is complementing the original Moderna monovalent mRNA vaccine:
· The Omicron BA.1-adapted bivalent vaccine exhibited an 8-fold improvement in neutralizing titers against Omicron BA.1 above baseline levels5. The antibody levels were maintained for at least three months6. This vaccine also demonstrated high neutralizing response against Omicron BA.4/56. · The Omicron BA.4/5-adapted bivalent COVID-19 vaccine was also generated6. |
Both Omicron bivalent vaccines are approved as a booster dose in individuals 18 years and older. |
References
- Public Health Agency of Canada. Recommendations on the use of bivalent Omicron containing mRNA COVID-19 vaccines. September 1, 2022.
- Public Health Agency of Canada. Pfizer-BioNTech Comirnaty COVID-19 vaccine. October 7, 2022.
- Pfizer Press release. June 25, 2022.
- Pfizer. Press release. October 13, 2022.
- Moderna News release. June 8, 2022.
- Moderna News release. July 11 2022.
- Novavax Press release, 2022.
- Novavax Press release May 31, 2022.
- Reuters News article, Feb 24, 2022.
Long COVID is an umbrella term that refers to a group of disorders that can develop after SARS-CoV-2 infection. Common symptoms include fatigue, shortness of breath, and cognitive dysfunction, or “brain fog”. Symptoms may start following a recovery from COVID-19 or persist from the initial illness. Symptoms may also fluctuate or relapse over time (1).
A higher percentage of Canadian adults with severe symptoms at the time of their first COVID-19 infection experienced symptoms at least three months later (2). Risk factors for long COVID include: female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities (3). The CITF is funding a few studies on long COVID, including one by Statistic’s Canada called the Canadian COVID-19 Antibody and Health Survey cycle 2 (CCHAS-2).
Figure 1. Long-term effects of COVID-19. This was adapted from a meta-analysis by Lopez-Leon et al. (4) and it shows the percentage for each long-term symptom of COVID-19. Symptoms were categorized under general, brain, and heart and lungs. The most common symptoms were fatigue, headache, attention disorder, hair loss, and shortness of breath
References
- https://www.who.int/srilanka/news/detail/16-10-2021-post-covid-19-condition
- https://www150.statcan.gc.ca/n1/daily-quotidien/221017/dq221017b-eng.htm
- https://www.nature.com/
- Lopez-Leon, S., Wegman-Ostrosky, T., Perelman, C. et al. More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. Sci Rep 11, 16144 (2021). https://doi.org/10.1038/s41598-021-95565-8
COVID-19 vaccines trigger our bodies to develop immunity against SARS-CoV-2 without us having to get the disease first. There are currently four main types of COVID-19 vaccines: messenger RNA (mRNA) vaccines (such as Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax), protein subunit vaccines (such as Novavax’s COVID-19 vaccine), viral vector vaccines (such as Johnson & Johnson and Oxford-AstraZeneca’s Vaxzevria), and inactivated virus vaccines (such as the Sinovac COVID-19 vaccine).
The mRNA vaccine teaches our cells to make a copy of a protein unique to SARS-CoV-2 called the spike protein. Our body recognizes these proteins as foreign and generates antibodies and build B cells and T cells to remember the virus so we can defeat it if we are infected in the future.
The protein subunit vaccines consist of harmless proteins of the SARS-CoV-2 virus, while vector vaccines contain a different harmless virus that enters our cells to produce the SARS-CoV-2 spike protein. Lastly, the inactivated SARS-CoV-2 vaccine consists of the killed virus that no longer replicates.
All types of vaccines have the same end goal: generate a supply of memory B and T cells to remember how to the fight the virus in the future. The levels and duration of immunity offered by these different vaccines, however, may vary.
Figure 5.1. The COVID-19 mRNA vaccine contains instructions (mRNA) to make a lot of SARS-CoV-2 Spike proteins. The release of this Spike protein outside of the host cell triggers an immune response and the host makes antibodies, B cells, and T cells against the virus, similar to what happens in natural infection. Photo Credit: Mariana Bego.
There are currently four COVID-19 vaccines that are approved and authorized for use in Canada (see table below). On September 16, 2021, three of these vaccines were authorized under the Food and Drug Regulations Act, prompting the transition to using brand names instead of company names, notably, Comirnaty, Spikevax, and Vaxzevria.
| Brand name | Manufacturer(s) | Research name | Vaccine type | Number of doses administered |
| Comirnaty | Pfizer, Inc. and BioNTech | BNT162b2 | mRNA | 2 |
| Spikevax | ModernaTX, Inc. | mRNA-1273 | mRNA | 2 |
| Vaxzevria | AstraZeneca Canada Inc. and Verity/SII (COVISHIELD) | ChAdOx1 | Viral-vector | 2 |
| (Johnson & Johnson) | Janssen Pharmaceutical Companies of Johnson & Johnson | JNJ-78436735 | Viral-vector | 1 |
For more information on these vaccines, please the Government of Canada’s website.
Vaccines against SARS-CoV-2 have been developed to prime your body’s immune response to ensure that it fights against the virus, reducing the risk of you getting COVID-19. These vaccines are especially good at reducing the risk of severe COVID-19 symptoms, hospitalization, and death.
That said, the risk of a vaccinated person catching SARS-CoV-2 and developing COVID cannot be completely eliminated. Early data suggest fully vaccinated people can get the Delta variant and perhaps other variants. However, when compared to unvaccinated individuals, fully vaccinated people are less likely to acquire SARS-CoV-2, and when they do, they get less severe COVID-19 symptoms.
Studies suggest that vaccinated individuals have reduced numbers of virus in the blood and this could mean there is less virus to transmit, meaning reduced transmission. That said, vaccinated individuals can still transmit the virus for a period of time after infection. Therefore, it is extremely important that vaccinated people continue to follow public health guidelines including frequent hand washing, maintaining a safe distance from others, wearing a mask, and staying home if feeling unwell.
If you had COVID-19 previously, you should still get vaccinated because the level of immunity from infection and its duration is not entirely clear. The vaccine will also provide longer-term protection as it has been optimally designed to generate an effective immune response. There is no harm in getting a vaccine to boost your immune response to SARS-CoV-2.
Vaccine effectiveness is measured by the impact of vaccination on COVID-19-related hospitalizations, mortality, effects of COVID-19 vaccination on asymptomatic infection and transmission, and how groups of different ages, and overall health status respond to the vaccine. Some of the studies the CITF supports include assessing effectiveness with different combinations of vaccines, vaccinations in pregnant women and children, vaccinations in people at higher risk due to other health conditions, and vaccine effectiveness for prevention of serious outcomes among hospitalized adults.
The CITF is involved in supporting research studies which evaluate vaccine safety. Vaccine safety is evaluated by tracking adverse events following immunization (AEFIs) including an association with anaphylaxis and other allergic events, Guillain-Barré syndrome, Bell’s palsy, and vaccine-associated enhanced disease, among others. Some of the studies we fund are documenting health events including temporary local injection site reactions, systemic symptoms (fever, fatigue, myalgia), respiratory symptoms suggestive of the cold or flu, and gastrointestinal symptoms (nausea, vomiting, diarrhea, or stomach pain), among others. The populations studied overlap with studies measuring vaccine effectiveness and include pregnant women, children, people at higher risk due to other health conditions, and hospitalized adults.
The current vaccines approved for use were tested in clinical trials before the new variants emerged. Evidence to determine how effectively the vaccines will work against them has been coming out in bits as studies follow this issue closely.
Preliminary studies show that individuals vaccinated with the Pfizer-BioNTech Comirnaty mRNA vaccine can neutralize the variants of concern Alpha and Beta, originating from the UK and South Africa, respectively. Another study has shown that there was a reduction in the capability of Moderna’s Spikevax mRNA-1273 to ward off the Beta variant. Lastly, Novavax announced that their vaccine had a vaccine efficacy of 89.3% in a UK population where there was high prevalence of the Alpha variant, suggesting that it is effective against this variant. Altogether, these studies suggest the importance of continuous monitoring of the variants as this could indicate a need for a vaccine strain change.
Real-world data show that vaccines remain highly effective at reducing COVID-19-related hospitalizations and emergency department (ED) visits, even in the presence of the circulating Delta variant. Unvaccinated individuals who contracted the Delta variant are 5 to 7 times more likely to need ED care or hospitalization when compared to vaccinated individuals. Moderna’s Spikevax and Pfizer-BioNTech’s Comirnaty were both highly effective at preventing hospitalizations among adults ages 18 and older (95% and 80%, respectively). But vaccine effectiveness was lower for those aged 75 years and above. Vaccination is therefore highly important to ease the burden on the healthcare system.
Based on clinical trials, the manufacturers of the SARS-CoV-2 vaccines recommend two doses at specific intervals to achieve optimal efficacy. Due to vaccine supply shortages, countries were faced with the difficult decision to delay the second dose to maximize the number of people receiving their first dose. However, it has now been shown that a longer interval between the vaccine doses could actually improve immunity.
Canada’s National Advisory Committee on Immunization (NACI) has recommended that individuals can receive their second dose up to four months after receiving their first dose. Modelling by the Public Health Agency of Canada also suggested intervals could be extended up to six months between doses. However, ongoing long-term follow-up in clinical trials and in the real world will be imperative to understand the actual duration of protection.
Most vaccines are given as two doses to offer the maximum benefit of protection against SARS-CoV-2. Pfizer-BioNTech’s Comirnaty, Moderna’s Spikevax, and AstraZeneca’s Vaxzevria COVID-19 vaccines are all given as a two-dose series, while the Johnson & Johnson vaccine is a single-dose shot. All four vaccines have been shown to be effective at preventing symptomatic COVID-19 disease beginning two weeks after the first dose in clinical trials.
In two-dose series, the first dose acts to prime immunological memory, while the second dose acts as a ‘boost’ to extend protection over the longer term. This essentially means that more exposure time allows the body a chance to produce more antibodies and memory cells to fight off the virus. Protection offered by the first dose is lower than the efficacy achieved after the second dose. Peak levels of humoral and cellular responses are observed after this second dose.
A breakthrough infection occurs when individuals who are fully vaccinated against a disease, such as COVID-19, are subsequently infected. The term ‘breakthrough’ signifies the virus broke through the protective barrier that vaccines provide. The effectiveness of COVID-19 vaccines is not 100% and as such, breakthrough infections can occur, although they are predominantly asymptomatic or mildly symptomatic. COVID-19 vaccines remain the best way to be protected against severe disease, hospitalization, and death resulting from SARS-CoV-2 infection.