Fall is Coming. Are You Protected?

The FDA has issued the first full COVID-19 vaccine approval for Corminaty, the Pfizer/BioNTech vaccine. The FDA authorized the use of a third dose (‘booster’) for immunocompromised individuals over the age of 12 earlier this month.?Shortly after that announcement, President Biden and the White House indicated they expect that mRNA vaccine recipients will be eligible for a booster shot starting the week of Sept 20th. Both Pfizer and Moderna have been working on third doses for their COVID-19 vaccines to help with refreshing their neutralizing antibody response against SARS-CoV-2, as well as addressing particularly infectious variants of the virus such as the Delta Variant (lineage B.1.617.2).

While just over a month ago on July 8th, 2021, the US FDA and CDC released a joint statement indicating that fully vaccinated Americans do not currently need a booster shot ’at this time’, the Delta variant is moving so quickly that by mid-August the White House and the CDC reversed course, and the FDA is expected to quickly follow suit. The vaccines are still protecting well against hospitalization and death, but antibody responses against these new variants have begun to wane in the vaccinated world according to a recent publication in Nature, which stated that “variant Delta spread is associated with an escape to antibodies targeting non-RBD and RBD Spike epitopes.” There are many conflicting signals from the policymakers with regards to forthcoming vaccine decisions for individuals, and so I will lay out a path forward for people struggling to understand and make decisions with regards to post-COVID infection vaccination and booster shots. ?

In order to really understand what is driving all the confusion we need to look at the facts and how the concept of herd immunity was initially presented.?The goal was to have 70% of Americans vaccinated with one dose by July 4th. Based on the models of earlier variants, 70% vaccination was estimated to be a good threshold to achieve herd immunity. The US did not achieve that objective, and the hyper-localization of low vaccination rates really created a dichotomy that left those jurisdictions at particular risk for a surge in cases based on the old variants. The first policy objective in response to low vaccination rates was to instill confidence that the vaccine was safe and effective at stopping infections. This led to a joint statement from the FDA and CDC that boosters were not needed and that vaccinations should continue.??In hindsight, that messaging backfired because no one paid attention to the very important disclaimer “at this time” and that “FDA, CDC, and NIH are engaged in a science-based, rigorous process to consider whether or when a booster might be necessary. This process takes into account laboratory data, clinical trial data, and cohort data – which can include data from specific pharmaceutical companies, but does not rely on those data exclusively. We continue to review any new data as it becomes available and will keep the public informed. We are prepared for booster doses if and when the science demonstrates that they are.” If you follow the science, in less than two months it has become clear that boosters are in fact necessary due to the waning immunity of the mRNA vaccines, especially in combination with a much more virulent Delta variant with its P681R mutation that gives it a much ‘stickier’ ability to latch onto cells and infect them more rapidly/efficiently than prior variants.

In the fine print of this joint statement from 3 government agencies they clearly indicate they didn’t have the data yet.?How could they?... The Delta Variant has only been circulating in the United States for 2-3 months.?It’s hard to believe, but the delta variant has gone from 6% prevalence at the beginning of June to 96-99% prevalence in August.?There is no conceivable way that data on the Delta variant is currently available in the United States due a prior decision to discourage fully vaccinated people from getting tested, and a CDC directive to stop counting breakthrough infections unless they led to hospitalizations and death, so we don’t really know in general terms when we actually need the booster, or what neutralizing antibody titers were present for those who experienced a Delta breakthrough infection.?People need to understand Delta is a completely different virus than what all the vaccines and the proposed path to herd immunity were modeled for. In fact, the Delta is so virulent that many scientists are now openly wondering whether herd immunity is even achievable.

Now there is talk of boosters being approved for people at the 8-month mark.?Let’s be clear that this number of 8 months is not based on any medical research, because all the research we have available which primarily comes from Israel and the UK suggests immunity wanes at the 6-month mark.?The facts are that we have a completely different virus than what the vaccines were originally designed to target, and the only public health solution to this problem is to further vaccinate in the hope that another vaccine boost will increase neutralizing antibody levels above the thresholds needed to ward off Delta, although the data for this is not yet 100% clear.?The vaccines do help against the Delta variant if people have high enough levels of neutralizing antibodies.?We also know the immunocompromised and elderly over 80 are at high risk and see an increase in neutralizing antibody levels (NAbs) in response to booster shots, but how long that increase in NAbs will last is completely unclear.?However for the broad population what is also true is that that everyone’s immune system is categorically unique, and a one size fits all strategy for booster shots is likely destined for failure.

Leading pharmaceutical companies understand this is a completely different virus. They are actively working on different types of boosters than the original vaccine, anticipating the virus to further mutate and avoid the protection of current vaccinations. There is also talk about mixing vaccines that are able to better handle the Delta Variant, and according to the WHO, this is a data-free zone, but "Data from mix and match studies of different vaccines are awaited - immunogenicity and safety both need to be evaluated.” Regardless, no studies have definitively proven exactly WHEN the vaccines wear off, though it is known that the first round of vaccines are experiencing reduced neutralizing potency against the Delta Variant.?As for clinical outcomes and protection against even newer variants, it is just a guess at this point, especially since new variants complicate any analysis. There is just not enough data to know, so scientists, regulators, and companies are speculating on WHEN vaccinations will be needed but they don’t have to speculate if they have the facts.?Getting the facts requires people to take a simple blood test.

The question of when to get a booster is rooted in medical science that doesn’t exist yet, but is now being created.?We already know the answer to the question of when you should get a booster to protect against the Delta variant. ?It’s when they find you don’t have high levels of neutralizing antibodies.?A study from The New England Journal of Medicine of 11,300 fully vaccinated healthcare workers in Israel looked at breakthrough infections.?The study found that there was a correlation between neutralizing antibody levels and getting a breakthrough infections.?Healthcare workers with lower levels of neutralizing antibodies got infected.?Even future vaccines are expect to use what is known as the correlate of protection biomarker as an endpoint.?Levels of neutralizing antibodies can confirm protection or identify a need for a booster.

Think of the moral hazard caused by saying people are eligible for a booster in 8 months. Vaccinated people might think they have a level of protection between months 6 and 8, when in fact they do not.?People with weakened immune systems are eligible now, but why aren’t they tested first to see what their actual level of immunity is instead of guessing because data will drive people to action??All this data would also be great in formulating a generalized policy to prioritize booster shots as needed.

The challenge is having the will to openly admit that a one size fits all strategy is flawed and that we need to test, test, test.?Remember, before the vaccines, it was all about testing.?Maria Van Kerkhove Emerging Diseases and Zoonoses Unit WHO said it best “knowing your risk helps you to take measures to lower your risk every day.“?With the Delta variant the vaccines are still a good weapon in the armamentarium, but testing is equally, if not more important.??Neutralizing Antibody Tests can identify people that are still protected from the vaccine or if they need a booster shot.?It will also tell those that were infected if their protection is still in place.?Then there is the elderly population over 80 where it is suggested that 30% of the vaccinations don’t result in neutralizing antibodies.?

Through its our CLIA/CAP lab Provista Diagnostics we offer the cPass neutralizing antibody test as a service to the community, and on a reference lab basis to potential lab clients who want to get started offering cPass and who may eventually have sufficient testing volume to justify implementing the cPass assay in their own labs.?It is imperative that we use all weapons in the fight against COVID-19 and we think that given the global scarcity of COVID-19 vaccines, it’s irresponsible not to get a test before administering a booster to make sure that booster is needed given the worldwide shorting of vaccines available. ?Think about all the data that we are missing out on as well to formulate a more optimized approach to fighting COVID-19, and understanding how close we may actually be to reaching herd immunity… only testing can tell us this information in the face of waning immunity from the vaccines.???

There needs to be more education on the subject that a EUA approved SEMI-QUANTITATIVE neutralizing antibody test exists (depicted above).?Just a few days ago NPR did a pod cast talking about a neutralizing antibody tests that aided in the development of the Pfizer vaccine.?The cPass test was approved for precisely this situation.?I believe the only reason why people aren’t embracing it is because they simply don’t know about its existence because testing has taken such a back seat to vaccine deployment.?

As breakthrough infections start to increase, and as a percentage, result in more hospitalization, it will become clearer that a shift in strategy will be needed and Todos has anticipated this need and stands ready to meet the demand.?Right now the administration’s policy is trying to balance between protecting people that got the vaccine and encouraging new people to get the vaccine.?That delicate balance can be achieved with neutralizing antibody testing.?Based on science, I expect to see more deaths from breakthrough infections in the coming months unless we let the tests help in the decision making process to drive smart administration of the booster.?While 8 months is a great, yet arbitrary, starting point to administer the booster; it’s better than nothing.?This is America, and surely we can reach for a higher level than ‘better than nothing’.?Under the current plan, a person whose immunity wanes at month 4 could go 4 months without protection in an environment where the Delta variant crowded out the other variants in less than 3 months.?In this example there is no protection for this individual unless the physician or patient intervenes and order the cPass test that will show a need for the booster.

Testing is expected to climb in the fall when it’s time to go back to school as schools can be breeding grounds for the coronavirus. Todos is aiming to aid in the ongoing fight against SARS-CoV-2 by providing novel testing options so people can make more informed decisions and communities can be better protected.