Category: Uncategorized

Not only has fall come to symbolize back to school, pumpkin spice lattes, and sweater weather, but fall has become synonymous with the flu. According to the CDC, flu season starts to increase in October and peaks between December and February, although it can last until May. 

The ripple effects of flu season on individuals and their families are well documented. Contracting the flu can lead to greater health complications and can result in lost work and missed school days impacting the dynamics of the entire family.

Flu season also negatively impacts employers. It is estimated that flu results in over 100 million lost work days and costs businesses about $15 billion every year in lost revenue.

Now is the time to start thinking about how you can protect yourself and your employees during flu season. Here is a list of five things you can do to keep you and your employees healthy this season:

1. Handwashing. Make sure to wash for at least 20 seconds. This is equal to two rounds of Twinkle Twinkle Little Star or the Happy Birthday song. As a reminder, post a sign with the lyrics on the bathroom mirror.
2. Sleep. This means trying to get 7 to 9 hours per night! Good sleep hygiene is key to a healthy immune system.
3. Diet and exercise. Regular exercise and a healthy diet boost the immune system so it’s easier to fight off infections. Experts suggest 30 minutes of moderate cardio exercise each day and a diet high in immune-boosting foods like oranges, berries, and broccoli.
4. Stress reduction. Stress can negatively impact your immune system making it easier to catch the flu. Consider adding extra stress-reducing activities during this time of year such as exercise or meditation.
5. Stay home! Encourage everyone to stay home if they are feeling sick or have flu symptoms to avoid infecting others.

In addition to these five tips, one of the best ways to make sure your employees stay healthy and productive this season is with a flu shot.  Lookout Health’s mobile vaccine clinics reduce the barriers to receiving vaccines and make it easy for your employees to get their annual flu shot without the hassle of scheduling, transportation, or missed work.

Dr. Mundi Attinasi suggests following these five key steps before coming in for your blood draw.

Multi-cancer early detection (MCED) tests screen for early warning cancer signals that are circulating in the bloodstream…

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

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.

Cellular immunity

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?

Dose:

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.

Janssen COVID-19 Vaccine | FDA

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.

Pfizer-BioNTech COVID-19 Vaccine | FDA

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.

Moderna COVID-19 Vaccine | FDA

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:

Vaccines and Related Biological Products Advisory Committee February 26, 2021 Meeting Announcement – 02/26/2021 – 02/26/2021 | FDA

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.