The US is currently experiencing a surge and co-circulation of respiratory viruses, particularly in children. As we head into the holiday season and the gatherings…
The RNA virus SARS-CoV-2 (responsible for the illness COVID-19) continues to mutate and infect its hosts, despite vaccination. To understand why, we need to take a look at some basic mechanisms of virology.
RNA viruses are highly mutable
RNA viruses are highly mutable, acquiring approximately 1 mutation each replication, depending on the specific species and strain. In contrast, many DNA viruses have comparably robust proofreading mechanisms, mutating significantly less frequently than RNA viruses. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2937809/
Coronaviruses do have a proofreading mechanism, but it is less efficient than the proofreading mechanism of many DNA viruses. With the ability to correct some mutations, coronaviruses may mutate slower than other RNA viruses. However, coronaviruses possess the largest genomes among RNA viruses, so their size might allow for accumulation of mutations. Studies have yet to confirm the mutation rate of SARS-CoV-2, but it is likely similar to that of SARS-CoV and other coronaviruses.
The high mutability of RNA viruses is one reason that the current coronavirus vaccines do not inhibit SARS-CoV-2 transmission as effectively as the smallpox vaccine has inhibited smallpox, a DNA virus. But even among different RNA viruses such as SARS-CoV-2 and poliovirus, the mutational cost of viral success also varies.
RNA viruses SARS-CoV-2 and poliovirus have different levels of mutational success
As compared to SARS-CoV-2, why is poliovirus so highly inhibited by its vaccines, without the production of multiple different successful escape mutants?
In 2020, many doctors had postulated that a vaccine could effectively halt community transmission of SARS-CoV-2, similar to what we have seen with the highly effective poliovirus vaccine. However, SARS-CoV-2 and its current vaccines can not be compared to poliovirus and its vaccines, with respect to creating herd immunity to protect the vulnerable immunocompromised population. This is because the “mutational fitness” of poliovirus is significantly lower than the mutational fitness of many respiratory viruses such as coronaviruses and rhinoviruses.
Why are there differences in mutational fitness between poliovirus and respiratory viruses such as SARS-CoV-2?
The infectivity of poliovirus is more highly constrained by mutations than the infectivity of SARS-CoV-2
The poliovirus vaccine is highly effective at inhibiting productive infections of poliovirus, largely because even though it is a highly mutable RNA virus, its infectivity is highly constrained by mutations. This is in stark contrast to coronaviruses and rhinoviruses. These highly mutable viruses are not as highly constrained by mutations. This lower mutational constraint results in the rapid and successful generation of multiple coronavirus and rhinovirus variants that are infectious, and can reinfect people, including those who have been vaccinated against the original strain but not infected.
The mutational fitness of many respiratory RNA viruses (such as coronaviruses and rhinoviruses) is a contributor to why there has never been a human vaccine to the “common cold”. In fact, there are approved animal coronavirus vaccines that were developed many years ago, but many veterinarians today no longer give these to our pets, because their efficacy is low. With low efficacy, a vaccine risk can be considered higher than its benefit.
In other words, the fitness “cost of mutation” is higher in poliovirus than it is in many rhinoviruses and coronaviruses, where poliovirus is under more stringent evolutionary constraints. The outcome is that far more successful escape variants will be generated by rhinoviruses and coronaviruses, rendering a potential rhinovirus or coronavirus vaccine less effective than the vaccines to viruses (such as poliovirus) that have more stringent evolutionary constraints.
What is the mechanism underlying the significantly different costs of mutations between poliovirus and respiratory viruses such as SARS-CoV-2?
Differences in mutational fitness may depend upon the different receptors for SARS-CoV-2 and poliovirus
The significant difference in mutational fitness of SARS-CoV-2 versus poliovirus may be due in part to expression of different viral receptors in different tissues of the body. There is a greater expression of SARS-CoV-2 receptors in the respiratory system, whereas there is a greater expression of poliovirus receptors in the small intestine.
Possibly, most poliovirus mutations may disable the ability of the virus to survive the harsh environment of the gut. Additionally, the very short time between exposure to SARS-CoV-2 and binding of the virus to its respiratory receptors may allow less time for an immune response to kick in, as compared to poliovirus which travels through the gastrointestinal tract to reach its major receptors.
The endemic nature of respiratory viruses
Similar to influenzas, enteroviruses, rhinoviruses, and other coronaviruses, we can expect SARS-CoV-2 cases to be endemic in the population. As with any highly pathogenic microbe for which there is no hard stop, we must remain vigilant in our protection of populations such as the elderly and comorbid that are at high risk of severe disease and death.
With SARS-CoV-2, as with most other pathogens, the most important factor regarding how likely an individual is at harboring high viral loads and transmitting disease, is not solely whether or not the person is vaccinated, but what is the overall health picture of that individual. This can include many factors including age, activity level, immune status including comorbidities, and vaccination or infection status. For example, an unvaccinated 30-year-old healthy, active person is significantly less likely to transmit SARS-CoV-2 than a vaccinated 70-year-old individual.
One way to think of SARS-CoV-2 susceptibility is this: We all have been effectively “immunized” to respiratory viruses such as rhinoviruses that cause the common cold, because we’ve all been infected by them. But we are all still likely to be infected by new rhinovirus variants, and this happens all the time. How likely we are to transmit these variants to others depends not on whether or not we’ve already been “immunized’ to rhinovirus, but instead, depends upon how healthy we are, thus how well our immune status limits viral replication and thus controls transmission.
Can vaccination be considered part of an individual’s overall health status? With most vaccines, the answer is yes. But with the current SARS-CoV-2 vaccines, that answer really is not as straightforward. For example, take a look at Omicron.
Omicron has about 46 mutations, 23 of which are in the spike protein. 3D structural studies show that the omicron spike mutations disable efficient binding of the virus with the vaccine-induced antibodies, but the mutations do not significantly inhibit viral binding to the human receptor. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666303/
One research group has provided evidence that they believe the Omicron variant developed in a vaccinated individual. When the vaccinated person was infected with SARS-CoV-2, the vaccine-induced immunity recognized and inhibited the nominal virus as well as similar variants. However, the new variant that outcompeted the other variants was the one that was able to bind to cellular receptors while partially evading immunity. This variant successfully replicated and was transmitted among the population as omicron. Although we may never know the who/when/how of Omicron patient zero, the researchers present a plausible theory. https://doi.org/10.1002/jmv.27530
SARS-CoV-2 testing is more effective than proof of vaccination when screening people for infection
Because SARS-CoV-2 variants can infect and replicate to transmissible levels in both unvaccinated and vaccinated individuals, proof of vaccination can not detect whether someone is infected with and able to transmit a SARS-CoV-2 variant. However, a good quality SARS-CoV-2 test can provide a better indication that a person is harboring the virus.
Tests available to the public include the antigen test and the nucleic acid amplification test (NAAT). An antigen test is rapid, and can detect a symptomatic infection. A nucleic acid amplification test (NAAT) such as PCR or LAMP can detect asymptomatic and symptomatic infections. A test that can detect more than one different viral targets can be the most effective at detecting the widest variety of SARS-CoV-2 variants, thus the most effective at screening populations for infection.
Although the FDA states that “antibody testing is not currently recommended to assess immunity after COVID-19 vaccination”, a significant chunk of the population wants to discover their antibody status to SARS-CoV-2, the virus that causes the illness COVID-19. The widely held public belief is that the presence of antibodies confers some resistance to illness, while the absence of antibodies means a person is vulnerable to infection and illness. However, the answer is not that simple.
The FDA’s explanation
The FDA explains that “results from currently authorized SARS-CoV-2 antibody tests should not be used to evaluate a person’s level of immunity or protection from COVID-19 at any time, and especially after the person received a COVID-19 vaccination.” In other words, antibody test results may only be used to inform the presence or absence of antibodies, and not to assume the level of immunity that equates to protection from illness.
The full FDA statement can be found here: www.fda.gov/medical-devices/safety-communications/antibody-testing-not-currently-recommended-assess-immunity-after-covid-19-vaccination-fda-safety
Although the immune status of those with or without SARS-CoV-2 antibodies is officially uncertain at this time, there are a few things that we do know:
If you have SARS-CoV-2 antibodies:
Historically, medicine has assumed that the presence of antibodies to a pathogen equates to some level of protection from that pathogen. Repeated exposure to that pathogen (whether it be viral, bacterial, or other) would cause only mild or no illness. This long-held medical belief is the reason that adults can choose between receiving booster shots to certain pathogens such as measles, mumps, rubella, polio, etc, OR test their current antibody status to these pathogens. If there are significant levels of antibodies to the pathogens, then boosters aren’t required.
How is this different with SARS-CoV-2? Many experts believe that this traditionally held medical view also holds true for SARS-CoV-2: If you have antibodies, then you have protection from a significant illness from the virus. At the same time, many experts can’t state this as a fact for SARS-CoV-2, because the research to show that SARS-CoV-2 antibodies equate to immunity has not yet been completed. This virus just hasn’t been around long enough for long-term immunity studies to be finalized and published. As time marches on from the emergence of SARS-CoV-2, the research will continue, providing definitive answers to this question.
If you don’t have SARS-CoV-2 antibodies:
The scientific literature tells us that many people without detectable antibodies to the SARS-CoV-2 virus may still have immunity. In fact, multiple clinical studies have provided evidence that the majority of people exposed to SARS-CoV-2 but lacking antibodies have long-term immune cells known as cellular or memory cells. Long-term cellular immunity is not unique to SARS-CoV-2, as it is highly prevalent throughout the world of human pathogens.
In addition to antibodies, can we also measure cellular immunity? Currently, there is only one test with FDA EUA approval that can detect T cell memory, Adaptive Biotech’s “T-Detect”. There is also another cellular immunity testing company that is attempting to receive FDA EUA approval but that is currently only available RUO (research use only), Oxford Immunotec’s “T-Spot”. T-Spot has the added advantage of not just detecting cellular immunity to SARS-CoV-2, but also identifying whether someone has cellular immune cells that recognize the common human coronaviruses. This information is helpful because it can help researchers provide evidence to address a major question in our understanding of the SARS-CoV-2 pandemic: Can previous exposure to one or more of the common human coronaviruses lessen the severity of illness caused by SARS-CoV-2?
So, whether you have been vaccinated or whether you just want to know if you have antibodies to SARS-CoV-2, an antibody test can help provide one piece of the puzzle, but it’s not the full picture. If you choose to discover whether you have antibodies, it’s important to remember that not all antibody tests are created equal.
Not all antibody tests are created equal
After an in-depth review of all available antibody tests with FDA EUA approval, Lookout Health has chosen to offer Sugentech’s antibody test “SGTi-flex COVID-19 IgG” for several reasons:
1. Superior to most other serology tests that only detect antibodies to one single viral protein, SGTi-flex detects two different viral antibodies (spike and nucleocapsid).
2. Because SGTi-flex detects both spike and nucleocapsid antibodies, it should be able to reliably detect antibodies to all known variants, including the delta variant.
3. SGTi-flex is one of only two serology tests that can detect two different antibodies via blood from a single fingerstick.
Whether or not you are vaccinated, if you are interested to discover whether or not there are SARS-CoV-2 antibodies in your system, a two-target antibody test can give you that answer.
Terms such as PCR, molecular testing, nucleic acid amplification test, isothermal amplification, and LAMP used to be discussed only by scientists and doctors. With the rise of the disease COVID-19 caused by the virus SARS-CoV-2, the public has become more aware of PCR, as that is the original molecular test for amplifying and detecting nucleic acids such as SARS-CoV-2 RNA, and the molecular test that has received the most media attention. With COVID lingering, while society moves forward toward a more functional state, multiple companies have generated contracts to hire COVID testing companies to regularly test their employees. However, the language used in these contracts often includes PCR but forgets to include another molecular test, isothermal amplification, that is similarly effective at amplifying and detecting nucleic acids while being cheaper and faster.
NAAT (Nucleic acid amplification testing) is the amplification and detection of the nucleic acids DNA or RNA. When testing a patient for active COVID infection, the test needs to detect RNA, because RNA is the genetic material of all coronaviruses. RNA is very unstable outside of the organism, so it can not undergo amplification without first utilizing an enzyme called reverse transcriptase to transcribe the RNA into cDNA (complementary DNA). This cDNA can then be amplified.
The classic, decades-old method of PCR is the original workhorse for amplifying nucleic acids. However, another type of NAAT is isothermal amplification, including the popular LAMP test.
PCR (polymerase chain reaction) amplifies and detects DNA by denaturing, annealing, and elongating increasing amounts of DNA in a chain reaction. Unless a user wants to spend hours repeatedly heating and cooling their samples manually, PCR requires the use of a thermal cycler to perform multiple repeated cycles of heating and cooling. In other words, PCR starts with a DNA sample and amplifies the DNA. Variations of PCR include:
RT-PCR (reverse transcription-polymerase chain reaction) detects the presence of RNA such as that of SARS-CoV-2 by reverse transcribing it to cDNA (complementary DNA). After the initial step of reverse transcription of RNA to cDNA, the remainder of the process is the same as PCR. In other words, RT-PCR starts with an RNA sample, utilizes a reverse transcriptase enzyme to create complementary DNA (cDNA), and then amplifies the cDNA.
qPCR (quantitative PCR or real-time PCR) is a method of PCR that enables the quantification of the abundance of nucleic acids during the exponential amplification phase relative to the abundance of other nucleic acids including controls. This differs from traditional PCR that gives a yes or no answer, without quantifying the relative abundance of nucleic acids.
RT-qPCR (reverse transcription-quantitative PCR, also known as reverse transcription real-time PCR) is a method of PCR that starts with an RNA sample, reverses transcribes the RNA to cDNA, amplifies the cDNA, and enables the relative quantification of cDNA during the exponential growth phase.
Isothermal amplification amplifies and detects nucleic acids at a constant temperature, eliminating the need for a thermal cycler. LAMP is a popular method of isothermal amplification.
LAMP (loop-mediated isothermal amplification) is an isothermal reaction that continuously amplifies nucleic acids at a constant temperature, eliminating the need for a thermal cycler. LAMP is faster than PCR, producing higher levels of nucleic acids than PCR within minutes. LAMP can also amplify and detect nucleic acids from crude samples without purification, such as saliva, although crude sample analysis has a lower percentage of accuracy than refined samples.
RT-LAMP (reverse transcription loop-mediated isothermal amplification) detects the presence of RNA such as that of SARS-CoV-2 by first reverse transcribing RNA to cDNA.
SARS-CoV-2 is an RNA virus, so molecular testing for COVID infection via PCR or LAMP is performed with RT-PCR or RT-LAMP.
Notably, a recent literature review illustrates the high accuracy of both PCR and isothermal amplification including LAMP in diagnosing human coronavirus infections: https://www.nature.com/articles/s41598-020-79237-7
Because LAMP has been shown to be comparably effective and accurate to PCR at detecting nucleic acids, while also being faster, cheaper, and omitting the need for a thermal cycler, the scientific community accepts both RT-PCR and RT-LAMP as valid tests for the detection of COVID infection. However, accuracy may vary from one test manufacturer to another.
When choosing a COVID-19 infection test from among the plethora of tests that have received FDA Emergency Use Approval, an important criterium is not whether the test is PCR or isothermal amplification such as LAMP, but the quality of the test data.
Does the published test data display high degrees of specificity and sensitivity? Multiple PCR and LAMP COVID-19 tests with FDA Emergency Use Authorization (EUA) boast specificity and sensitivity values in the mid to high 90s.
It is also important to look at cross-reactive controls. For example, does the test also detect any of the common human coronaviruses that are present in about 90% of the human population, or is the detection specific to SARS-CoV-2? The less stringent the cross-reaction testing, the higher the possibility of false positives.
Additionally, the specificity of the test’s viral target is important. For example, some tests’ SARS-CoV-2 targets for detection are nearly identical to other common coronaviruses, whereas other tests’ SARS-CoV-2 targets are uniquely different from other organisms. (Although many targets unique to SARS-CoV-2 also react with SARS-CoV, this isn’t an issue because SARS-CoV is not believed to be circulating in the population at this time.)
Also, technical test parameters, including the limit of detection (LoD), can make a difference regarding the quality of the test. For example, the sensitive assays claim an LoD of about 100 copies of viral RNA per milliliter. However, the LoD of assays may be 10,000 fold higher. The higher the LoD, the higher the possibility of false negatives.
Finally, the number and quality of samples that were used to verify the test are important. For example, an assay that was tested with 500 samples from COVID-19 positive patients and 500 COVID-19 negative patients will have more accurate results than an assay that was tested with 25 positive and 25 negative patients. In another example, 60 samples that are actually 3 replicates of 20 patients will give less accurate results than 60 samples from 60 patients. In a third example, spiked samples (samples that are not patient samples, but rather samples that are spiked with the virus) are not truly independent samples.
In summary, PCR and isothermal amplification such as LAMP are two of the most popular methods of nucleic acid amplification that are highly effective at detecting active COVID-19 infection.
Today (Feb 27, 2021), the FDA issued an Emergency Use Authorization (EUA) for the third SARS-CoV-2 vaccine now available in the US. It is manufactured by Janssen, a subsidiary of Johnson & Johnson. How does the Janssen vaccine stack up against Pfizer and Moderna?
Janssen is a single dose. Pfizer and Moderna call for two doses.
Side effects comparison of the 3 vaccines now available in the US:
The FDA reported side effects of the Janssen vaccine are significantly milder and shorter duration than those of Pfizer and Moderna.
1. J&J: The most commonly reported side effects were pain at the injection site, headache, fatigue, muscle aches and nausea. Most of these side effects occurred within 1-2 days following vaccination and were mild to moderate in severity and lasted 1-2 days.
2. Pfizer: The most commonly reported side effects, which typically lasted several days, were pain at the injection site, tiredness, headache, muscle pain, chills, joint pain, and fever. Of note, more people experienced these side effects after the second dose than after the first dose, so it is important for vaccination providers and recipients to expect that there may be some side effects after either dose, but even more so after the second dose.
3. Moderna: The most commonly reported side effects, which typically lasted several days, were pain at the injection site, tiredness, headache, muscle pain, chills, joint pain, swollen lymph nodes in the same arm as the injection, nausea, and vomiting, and fever. Of note, more people experienced these side effects after the second dose than after the first dose, so it is important for vaccination providers and recipients to expect that there may be some side effects after either dose, but even more so after the second dose.
Efficacy of the Janssen vaccine:
100% effective at preventing hospitalization and death (28 days or more after the vaccination).
85% effective at preventing severe/critical infection (28 days or more after vaccination).
66% (72% in the US) effective at preventing all infection at any time after vaccination (which is a lower number than the 28-day post-vaccine immunity effectivity of severe infection because you shouldn’t have significant immunity within the first few days after most any vaccination, and also because the 66% value includes effectivity overall including the South Africa and other variants).
These numbers provide evidence that the Janssen vaccine is highly effective, especially considering that the FDA currently believes that 60% immunity is required for herd immunity to SARS-CoV-2.
The raw data in this paragraph was obtained from the 8-hour video of the 2/26/21 FDA advisory committee meeting, available at this link:
Previously reported efficacies of the Pfizer and Moderna vaccines, and why they can’t be compared to the current Janssen vaccine efficacy:
Some who misunderstand vaccine data have pointed only to the Janssen vaccine’s lowest category of published efficacy (66%), comparing it to Pfizer (95%) and Moderna (94%). However, this is like comparing apples to oranges. 66% only refers to one category of test data. Also, the Pfizer and Moderna vaccines were tested months before the Janssen vaccine, resulting in data that doesn’t include global efficacy against resistant viral variants that are prevalent today.
The current CDC guidelines regarding SARS-CoV-2 vaccination state that almost every person age 16 and over (Pfizer mRNA vaccine) or 18 and over (Moderna mRNA vaccine and Janssen vaccine) can be immunized without knowledge of prior infection status, as long as the person is not known to be infected with SARS-CoV-2 at the time of vaccination. According to the CDC, “Viral testing to assess for acute SARS-CoV-2 infection or serologic testing to assess for prior infection for the purposes of vaccine decision-making is not recommended.” The CDC does not promote testing before vaccination, largely because it believes it is safe for the majority of the population, wants to simplify the vaccination rules, and instill confidence in vaccination in order to reach herd immunity and reduce loss of life. However, the CDC outlines some examples of vaccine precautions and contraindications. Some physicians and researchers believe that testing to determine the status of infection and immunity prior to vaccination can be beneficial.
Complete information from the CDC regarding mRNA vaccinations can be found here.
Cases where testing for SARS-CoV-2 infection or immunity before vaccination may be beneficial:
1. Testing for SARS-CoV-2 infection before vaccination can help reduce the chance of post-vaccine inflammation exacerbation.
The CDC states: “Persons… who have had a known COVID-19 exposure should not seek vaccination until their quarantine period has ended to avoid potentially exposing healthcare personnel and other persons to SARS-CoV-2 during the vaccination visit. ”The purpose of this caution is to protect the spread of SARS-CoV-2 to health care personnel, and not to protect the infected individual, because the CDC deems it safe to receive a vaccination if infected.
However, some physicians believe it is best to defer vaccination until SARS-CoV-2 infection has resolved for another reason: a compounding effect of simultaneous inflammatory response to infection and the vaccine. In other words, infection produces inflammation, and vaccination also produces inflammation. The level and severity of inflammation resulting from infection and vaccination varies from person to person. When infection and post-vaccination inflammation occur at the same time, the effect may exacerbate the inflammation response in the body.
Individuals tested for SARS-CoV-2 infection before vaccination can benefit from removing the possibility of vaccination inflammation exacerbating concurrent SARS-CoV-2 infection inflammation.
2. Testing forSARS-CoV-2 infection before vaccination helps distinguish the cause of post-vaccination symptoms.
If a person is infected with SARS-CoV-2 at the time of vaccination, then it will not be clear whether symptoms that develop after vaccination arose as a result of infection (including symptoms that may require antiviral treatment), or whether symptoms that develop after vaccination arose as a result of vaccination side effects (which may be reportable and require different management than symptoms that arose from active illness).
Individuals tested for SARS-CoV-2 infection before vaccination can benefit from the ability to distinguish symptoms of vaccination from symptoms of illness.
3. Testing for SARS-CoV-2 infection and immunity before vaccination can help with vaccine risk-benefit assessment of patients considered at higher risk of serious side effects from the vaccine.
Although no anaphylactic reactions were reported from either the Pfizer or Moderna vaccines during clinical trials, anaphylactic reactions have been reported following administration of the mRNA vaccines outside of the clinical trials. Anaphylaxis after receiving an mRNA vaccine is approximately ten times more likely than anaphylaxis after flu vaccination, and up to 100 times more likely than anaphylaxis with other vaccines in general. There is also a chance of anaphylaxis with the Janssen vaccine, although very small.
Although anaphylaxis after SARS-CoV-2 vaccination is more likely to occur in those who have experienced anaphylaxis or allergies in the past, it has also been reported in those without a history of allergies. The CDC page “Managing Anaphylaxis” after mRNA vaccinations can be found here:https://www.cdc.gov/vaccines/covid-19/clinical-considerations/managing-anaphylaxis.html
The CDC contraindicates vaccination for those who have a history of allergic reaction of any severity (including anaphylaxis) to a previous dose of a SARS-CoV-2 vaccine or any component of the vaccines, including polyethylene glycol (PEG) and polysorbate. The CDC states: “Persons with a precaution to vaccination should be counseled about the unknown risks of experiencing a severe allergic reaction and balance these risks against the benefits of vaccination.”
For individuals with any history of anaphylaxis, the CDC lists considerations that can be used to conduct a risk assessment for SARS-CoV-2 vaccination, to be discussed with a physician. This assessment should include a person’s risk of exposure to SARS-CoV-2, the person’s risk of severe disease or death from SARS-CoV-2 (depending on age and underlying medical conditions), and whether the person has previously been infected with SARS-CoV-2.
Although almost all cases of anaphylaxis can be treated in the medical setting, testing forSARS-CoV-2 infection and immunity prior to vaccination in individuals at higher risk for anaphylaxis could help assess an individual’s risk versus benefit of vaccination.
b. Frail, elderly population
In mid-January 2021, as Norway began immunizing its population with the mRNA vaccine, almost 0.1% of the people who were in the initial wave of vaccines died. The deaths occurred entirely in those age 75 and older. After review, the World Health Organization determined that the deaths were expected in the population of frail, elderly individuals, and that the benefits of the vaccine outweighed the risks:https://www.bmj.com/content/372/bmj.n149
Despite these findings, the Norwegian government has since contraindicated the vaccine to people over the age of 75.
Around the same time, the UK reported 143 deaths shortly after vaccination of elderly people and those with underlying illness, but the UK Medicines and Healthcare Products Regulatory Agency reported vaccination was not the cause: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/960861/Coronavirus_vaccine_-_weekly_summary_of_Yellow_Card_reporting.pdf
Amid these occurrences, the CDC believes the mRNA vaccine is safe, but some physicians contraindicate the mRNA vaccine in the frail, elderly population.
Also, one of the main databases of post-vaccination side effects is from self-reported symptoms using a smartphone app called VSAFE. However, the elderly population is unlikely to use this app, and so this database underestimates the number of side effects in the population, particularly among the elderly.
Testing for SARS-CoV-2 infection and immunity prior to vaccination of the frail, elderly population could help assess an individual’s risk versus benefit of vaccination.
C. Guillain-Barre syndrome (GBS)
The CDC states that those with Guillain-Barre syndrome are not contraindicated from the SARS-CoV-2 vaccines. However, some doctors believe that individuals with a history of post-influenza-vaccine GBS should not receive these vaccines, because they could stimulate a similar response. Physicians of patients with a history of GBS can perform a risk assessment of the risk versus benefit of the vaccine.
Testing for SARS-CoV-2 infectionand immunity prior to vaccination of those with a history of GBS could help assess an individual’s risk versus benefit of vaccination.
4. Testing for SARS-CoV-2 infection and immunity before vaccination can help with vaccine risk-benefit assessment of patients with conditions for which there is very little or no data.
There is very little data on the safety of the SARS-CoV-2 vaccines in pregnant or lactating women, although the CDC believes the risk may be low. Pregnant or lactating women are allowed to choose if they receive a vaccine. However, given that there are other vaccines that are contraindicated in pregnant and lactating women, and there is very limited data on SARS-CoV-2 vaccines in pregnant and lactating women, some physicians advise against it.
Those who have conditions where there is little to no vaccination data, such as pregnancy, could benefit from being tested for SARS-CoV-2 infection and immunity prior to vaccination, in order to help assess the risk versus benefit of vaccination.
b. Other conditions for which there is little to no data
Other conditions for which there is very little to no SARS-CoV-2 vaccine study data, but for which the CDC believes are safe to take the vaccine, include the following:people with HIV or other immunocompromising conditions, people who take immunosuppressive medications, people with autoimmune conditions, people with Bell’s palsy, and people with dermal fillers.
Those who have underlying medical conditions where there is little to no vaccination data could benefit from being tested for SARS-CoV-2 infection and immunity prior to vaccination, in order to help assess the risk versus benefit of vaccination.
5. Testing for SARS-CoV-2 infection and immunity before vaccination can help conserve doses of vaccine for those with a greater immediate need and higher risk of infection.
The CDC states: “…while vaccine supply remains limited, persons with recent documented acute SARS-CoV-2 infection may choose to temporarily delay vaccination…”
The CDC states that it is not necessary to get a vaccine if you have been infected with SARS-CoV-2 in the past three months. While various researchers have reported varying lengths of time of immunity, recent research indicates that infection can protect from re-infection for at least five months: https://www.medrxiv.org/content/10.1101/2021.01.13.21249642v1
There has not yet been a sufficient length of time for the CDC to define the longevity of post-infection immunity, so currently, the general rule is three months.
Individuals who are tested prior to vaccination and confirmed to have SARS-CoV-2 infection or immunity could choose to delay vaccination, conserving the vaccine supply for those who have no immunity to the virus.
6. Testing for SARS-CoV-2 infection and immunity before vaccination may provide an option of receiving only one dose of the two-dose mRNA vaccine.
Although the CDC recommends two doses of the mRNA vaccine for almost everybody, some physicians and researchers think that one dose is sufficient for those who have been infected:
One argument against giving only one vaccine dose to those who were infected with SARS-CoV-2 is that it could provide a confusing precedent to the public. However, some physicians and researchers believe that a full course of vaccination is not necessary for those who have been infected and have immunity.
Individuals who are tested prior to vaccination and confirmed to have SARS-CoV-2 infection or immunity could decide with their health care provider to delay or forego immediate vaccination, thus reserving the supply of vaccines for those people who are at higher immediate risk of infection.
7. Testing for SARS-CoV-2 infection and immunity before vaccination can help prepare for the risk of side effects.
Approximately 85% of all people who receive the mRNA vaccines from Pfizer or Moderna experience at least one post-vaccination symptom, including but not limited to pain, swelling, erythema at the injection site, and localized axillary lymphadenopathy on the same side as the vaccinated arm. Approximately 70% experience systemic symptoms such as fever, fatigue, headache, chills, myalgia, and arthralgia. These symptoms are more frequent and severe following the second dose of the mRNA vaccine.
According to the CDC and post-vaccination data, those who have recovered from SARS-CoV-2 infection prior to vaccination are more likely to have severe side effects to the first mRNA dose than those who have never been infected. Those who have never been infected with SARS-CoV-2 are more likely to have severe side effects to the second mRNA dose than the first dose.
Because mRNA vaccine side effects commonly include flu-like symptoms lasting a couple of days, it would be helpful for those getting vaccinated to prepare in advance for post-vaccine symptoms. For example, hospital staff are advised to stagger vaccination of employees, so that there are not a significant number of people simultaneously calling out sick from work.
Side effects from the single-dose Janssen vaccine are possible, but typically shorter duration and less severe than the side effects from the vaccines of Pfizer and Moderna.
Individuals who are tested for SARS-CoV-2 infection and immunity prior to vaccination could benefit from knowing the chances of enduring more severe side effects after the first or second vaccine dose.
8. Testing for SARS-CoV-2 cellular immunity before vaccination can provide valuable information regarding previous exposure to SARS-CoV-2 in the significant portion of the population that does not have detectable antibodies to SARS-CoV-2.
A weak antibody response that wanes quickly might be the reason why many people who tested positive for SARS-CoV-2 had no antibodies a few weeks or months later. A lack of antibodies doesn’t mean a person is not immune, because that person may have long term cellular immunity in the form of memory T cells.
A study published in Emerging Infectious Diseases found T cell immunity in 80% of patients who had been infected with SARS-CoV-2 but did not have detectable antibodies: https://wwwnc.cdc.gov/eid/article/27/1/20-3772_article
Individuals who are tested for SARS-CoV-2 cellular immunity prior to vaccination could benefit from knowing whether or not they have been exposed to SARS-CoV-2 and may have immunity not detectable by antibody tests.
With increasing information from SARS-CoV-2 post-vaccination data, some physicians and researchers are seeing the benefit of testing for SARS-CoV-2 infection and immunity prior to vaccination. Testing need not delay vaccination more than a few minutes, as many tests for active infection (particularly antigen tests) and tests for immunity can be performed in 10-15 minutes, and can take place immediately prior to vaccination. Although testing before vaccination is not a CDC recommendation for most people, same-day testing can provide a possible significant benefit to the patient. Each person is an individual case with different risks and circumstances, and determining the status of infection and immunity prior to vaccination can help to provide information regarding vaccination timing, symptom response, risk assessment, vaccine dispersal, dosing, and preparation for vaccination side effects during this active pandemic.
On December 2nd, the CDC provided options to reduce the quarantine period for those who have been exposed to SARS-CoV-2, the virus that causes the illness COVID-19. The purpose of the options is to reduce the amount of time that people must stay home from work, and also, the options may lessen the stress on the public health system. This update results from increased knowledge of the SARS-CoV-2 incubation period, infectious period, and effective testing window.
The CDC continues to endorse a quarantine of 14 days after the last known contact with a person infected with the virus, but now offers alternative, shorter options:
A person who is exposed to SARS-CoV-2 but who remains asymptomatic may quarantine for 10 days instead of 14, without testing.
Alternatively, a person may quarantine for only 7 days after exposure to SARS-CoV-2 if that person remains asymptomatic and receives a negative test result. The negative test result must occur on or after the fifth day of quarantine.
Because regional public health departments make the final decisions regarding length of quarantine, the revised CDC quarantine options may or may not be adopted by every region and institution.
The CDC guidelines regarding isolation of patients who are known to be infected with SARS-CoV-2 remain the same:
Isolate at least 10 days from the onset of symptoms, and at least 24 hours with no fever without fever-reducing medication. Isolation can then be discontinued, but only if Covid-19 symptoms are improving. One exception is that loss or distortion of taste and smell may persist for weeks or months, but the patient does not need to remain in isolation or quarantine during recovery of those senses.
Those with severe Covid-19 illness that require hospitalization and those with weakened immune systems may need to isolate for 20 days after the onset of symptoms. This period of time is flexible, depending on the discretion of the patient’s doctor and the local health department.
If a person has tested positive for SARS-CoV-2 and has recovered from Covid-19 symptoms, that person should wait a minimum of three months before testing for the virus again, unless symptoms of Covid-19 develop again. (This does not preclude a person from serology testing during that time, to look for evidence of antibodies to the virus, as opposed to testing for an active viral infection.)
The CDC guidelines align with what scientists and doctors have learned about the incubation period and infectious period of the SARS-CoV-2 virus, the duration of illness that this virus causes, Covid-19, and the effective testing window of time.
Most SARS-CoV-2 infections can be detected by PCR or antigen testing by the fifth day after infection.
Most people infected with SARS-CoV-2 who become symptomatic will develop symptoms before the seventh day of exposure.
Most people infected with SARS-CoV-2 are not infectious beyond 10 days after the onset of Covid-19 symptoms. (Exceptions include immunocompromised individuals and those with severe disease.)
It is not uncommon to continue to test positive for SARS-CoV-2 for an extended time after infection, because non-infectious viral particles may remain at detectable levels in the body for weeks or months after infection. Unless a person has an immune system deficiency, a positive test result within three months after infection does not mean that person is still infectious to others. Most likely, a person with a positive test result within three months of infection is not infectious to others and doesn’t need to quarantine unless symptoms reappear.
Immunity to SARS-CoV-2 is hypothesized to last at least one year in healthy individuals who are not immunocompromised. This estimate is based upon the known length of immunity to SARS-CoV-1.
SARS-CoV-2 is the coronavirus that causes the disease Covid-19.
Covid-19 is the disease that is caused by the SARS-CoV-2 virus.
Quarantine: A person who has been exposed to the SARS-CoV-2 virus must quarantine to stay away from others. Quarantine after exposure to SARS-CoV-2 is most commonly done at home.
Isolation: A person who is infected with the SARS-CoV-2 virus must isolate to stay away from others, even those living with them at home.
The quarantine update can be found at the CDC website here.
The isolation information can be found at the CDC website here.
One of the COVID tests currently used by Lookout Health is the Becton Dickinson BD Veritor system for the rapid detection of SARS-COV-2 virus. This is an FDA-authorized antigen test that detects current infection with the virus. The sample for this test is obtained via a nasal swab,and results are available in 15 minutes.
The data provided to the FDA by Becton Dickinson demonstrated an overall percent agreement (OPA) of 98% when compared to a three-hour polymerase chain reaction (PCR) which is currently considered the benchmark for evaluating new tests. The definition of overall percent agreement (OPA) is True Positives + True Negatives / Total Samples. In this same data set, the positive percent agreement (PPA) of the BD Veritor was reported as 84% and its negative percent agreement (NPA) as 100%. For the most part, people want to know if this means the BD Veritor is a “good test.” To address this question, it is helpful to understand the methods used for detecting viruses and other pathogens and how these methods have evolved over time.
Over the years, the strategies for detecting infections have progressed immensely. Just two decades ago, the medical community primarily relied on cultures to determine whether or not infections were present. Cultures were considered the gold standard but could be finicky and often took days. With this method, samples were placed in petri dishes and needed time to grow before one could ascertain whether or not a particular bacteria or virus was present. Some pathogens grew quickly and others more slowly, so the amount of time it took to receive results actually depended on the organism itself. For some infections, there was a high rate of false negatives due to sampling and processing difficulties. It was accepted that many cultures did not have an accuracy (or sensitivity) of greater than 75%.
Then, Polymerase Chain Reaction (PCR) technology was created, and throughout the 1990’s and early 2000’s, this method was customized and adapted to detect a wide variety of pathogens, including viruses. This was a true technological breakthrough for diagnosing infections, as clinicians could detect the presence of a pathogen by identifying a specific fragment of its DNA as opposed to requiring it to grow in culture. PCR was soon found to have superior sensitivity to cultures and became universally utilized by clinicians. These tests are also known as molecular or nucleic acid tests.
Paralleling the growth of PCR technology was yet a third method used to diagnose activeinfections, and this was the antigen test. These tests detect the presence of proteins on the surface of a pathogen as opposed to its genetic material. Prior to the development of COVID antigen tests, such methodology was used for the diagnosis of influenza, tuberculosis, and strep, among other infections. Unlike PCR tests, antigen tests don’t require complex laboratories. With these tests, antigens are identified by antibodies located within a test cartridge. When the antigens from the pathogen are present, a strip on the cartridge signals that fact.
The two types of tests routinely used for detecting active COVID infections are PCR and antigen tests. The FDA has issued Emergency Use Authorizations for over 200 COVID diagnostic tests that fall into these categories, so it is impossible to address each specific test, but as the number of COVID cases rise and communities increasingly engage, it might make sense to ask the question which type of test is best? And the answer to that is… it depends.
PCR tests amplify genetic sequences, making it possible to identify small amounts of virus. This makes PCR tests for the SARS-CoV-2 virus very sensitive and very specific, meaning almost all active infections are detected, and only rarely will an uninfected person receive a positive result. Antigen tests don’t amplify their protein signal, and because of this they are less sensitive when compared to PCR. The trade-off is that antigen tests have results in minutes and can be read in an ambulatory setting, whereas PCR tests take several hours and require the complexity of a laboratory. Still, given that antigen tests have lower sensitivity, does this mean PCR tests are superior despite the time needed to obtain results Well, maybe not.
To control the spread of COVID, it is important to find people who are asymptomatic yet are shedding virus in great enough numbers to be infectious. It is also important to identify these individuals in a timely manner. A highly sensitive PCR test may find virus in a sample, but that doesn’t necessarily mean that the person has a high enough viral load to infect others. PCR tests can remain positive for weeks after someone is no longer infectious, as a small amount of viral genetic material can still be present. This lesson was learned years ago when PCR was first used to diagnose Chlamydia. At that time, clinicians would often repeat tests two weeks after treatment to ensure that the treatment was effective. When PCR was used for these repeat tests, treated patients could still be positive weeks later. At the time, it was thought that this indicated a treatment failure or recurrent infection, but as it turned out, that was not true. The majority of those patients were adequately treated and not at risk for spreading infection to others, but their Chlamydia PCR tests continued to be positive because those tests were detecting genetic material from dead bacteria. This is now an understood drawback of nucleic acid tests as opposed to cultures, which by definition require a pathogen that can multiply and grow.
This scenario shows that higher sensitivity isn’t always better. The best test would be one that can identify individuals who pose a risk to others and can do that quickly. It may be that the sensitivity of rapid antigen tests is ample for this purpose, and asymptomatic patients who may be detected by PCR but not captured by antigen tests do not have enough live virus to transmit the disease. Anecdotal evidence from the University of Arizona supports this notion, as they have been using rapid antigen tests for their screening and have avoided major outbreaks thus far. The viral load at which one is infectious and the ability of rapid antigen tests to identify truly infectious individuals is an important area for additional research. It is already clear that the speed and ease of antigen tests makes them a compelling tool in the armamentarium against COVID. If it is also shown that they are sensitive enough to unequivocally identify persons who are most at risk for transmitting the disease, one could make the case for considering these tests to be the best for many scenarios.