The Hidden Pandemic

Is a pandemic still a health emergency if nobody pays attention?

This past week the Director General of the WHO tried hard to draw attention to the fact that COVID-19 cases are exploding around the world again. The number of documented cases has increased 30% in the last 2 weeks, and of course that is the tip of the iceberg. Around the world much of this current surge in disease is due to BA.4/.5 replacing the prior Omicron lineages. They are out competing the earlier variants through increased transmissibility and significantly greater evasion of both vaccine and prior natural immunity. Here in the US, 18 states reported more cases last week than in prior 2 week period, and more importantly, hospitals in 40 states reported an increase in inpatients over the prior period. The inevitable result of the persistently sustained disease burden is evidenced by 38 states reporting a rise in COVID patients in ICU, and 17 states reporting an increase in daily deaths. Given that many states have changed to reporting data to the CDC only weekly now, instead of daily, or not at all in the cases of Nebraska and Mississippi, those numbers bear close watching for 7 day averages to increase. California is experiencing what the state Health Department is calling the third largest wave of COVID since the beginning of the Pandemic, but given what we know about the massive under-reporting of cases, the truth is the current surge is second only to the Omicron winter wave. Another useful metric of disease activity is the percentage of positive PCR tests (obviously we can’t track the results of self administered rapid antigen tests), and that has also increased to 17.5%, up 2% from last week. Take a quick time travel with me back to January 2020. If I told you then that over 110,000 Americans would be dying from a new infectious disease over the year, (the current annualized death rate) most people would be incredulous and horror stricken. Now the same situation is largely ignored by what seems to be the majority of the population. Call it what you will, pandemic fatigue, warning fatigue, normal adjustment to a new reality. When everything has a warning label, nobody reads any of them, and it’s exactly the same with the ubiquitous drug interaction warnings that pop up constantly in electronic medical prescription programs.

The following is a Tweet from Dr. Eric Topol, which pretty neatly sums up his and my view of the current CDC approach to the Pandemic. (Professor Topol needs no introduction unless you managed to take a much needed vacation from planet earth for the last 2 1/2 years). Pay no attention to the man behind the green curtain and let’s get your groove on here in the Emerald City.

We are now 3 weeks into the vaccination program for 6 mo - 5 yo’s, and 2% of eligible children have been vaccinated. The vaccination rate for the 5 yo - 11 yo group has fairly stalled at 29.5%. Ashish Jha says this is right in line with the administration’s expectations, given that parents usually want to have their young children vaccinated by their pediatrician, and not by a pharmacist or the Door Dash delivery person. While we are in the vaccine news department, I need to correct an error in my last post where I reported that the FDA VRBPAC committee had voted to recommend a fall booster dose targeting BA.1. That was the presumption of many people, including myself, going into the meeting, and the presumption of Pfizer and Moderna no doubt, since they were presenting data on that type of vaccine, and had already begun production. In fact the FDA committee recommended a vaccine to target the spike region of BA.4/.5. Moderna pointed out that it may not be possible to conduct efficacy and safety studies in time to meet a requested October rollout of new vaccine in time for the Winter Corona Season. I am left with a disconcerting sense that there is little to no strategic planning going on between the drug companies and FDA. Perhaps that is an unfair assessment given the rapidity with which this virus mutates, but it’s just one more bit of evidence that the current Whack A Mole vaccine approach is misguided. Beyond that, the prospect of potentially releasing an RNA vaccine with insufficient safety testing leaves me feeling about as secure as a Syrian Golden Hamster in somebody’s lab. It has been pointed out that we release Flu vaccine every year without human testing. Well that is true, however, we have an experience with that technology going back to the first bivalent inactivated Flu vaccine in 1942. Anyone as old as I am will remember the disastrous Swine Flu vaccine episode of 1976. Based on extremely scanty evidence, the US government launched an all out campaign to rapidly produce vaccine and massively inoculate the country. The predicted epidemic never showed up, and the vaccine had unacceptably frequent side effects, with about 500 people developing Guillain-Barre syndrome. Several historians of medicine and sociology have concluded that was a seminal event in the later twentieth century rise of vaccine skepticism, and a major source of deterioration in the population’s trust of governmental public health authority.

Reported in the Lancet this week is the following study from Italy on the real world effectiveness of Pfizer vaccine in the 5-11 yo age group. Studying 1 million, 2 dose vaccinated and 1.7 million unvaccinated children, they found overall vaccine effectiveness in preventing disease was 29%, and effectiveness in preventing severe disease was 41%. Those numbers are substantially inferior to the data from Pfizer’s small trial in this age group, which formed the basis for the FDA EUA in October. It’s important to look at actual numbers, rather than percent effectiveness, when dealing with rare events to get a true sense of the magnitude of risk and reduction—that is something I have mention several times in the past. Out of the 2.9 million children they followed (there were 134,000 with only 1 dose, that were analyzed as a separate group), there were 644 cases of hospitalization, 15 admissions to the ICU and 2 deaths. That would imply a reduction in ICU admissions from 9 in the unvaccinated group to 6 in the vaccinated and you can do the other multiplications if you are inclined.

https://doi.org/10.1016/S0140-6736(22)01185-0

Let’s explore the latest variant scare which hit the media outlets this week. That would be Grandson of Omicron BA.2.75, dubbed “Centaurus” by the Ministry of Catchy Names. I sent in my suggestion for “Putincron,” which was soundly rejected as ethnically insensitive and stigmatizing for all Russians. This so called second generation Omicron is descended from BA.2, and includes 9 unique mutations in the S gene component. It was spotted first in India and then rapidly reported from about ten other countries, including 2 cases confirmed in the US this week. It has several mutations in locations which experts feel are likely be good candidates for increased immune evasion, and in several media pieces this is already being heavily featured as the next thing to be afraid of. Looking at a GSAID message board, where virologists are reporting their findings in real time, it seems to me that several closely related variants BA.2.75, BA.2.74, BA.2.76 are being lumped together. These were initially reported in India as a new wave of BA.2, which would definitely not be expected, since that virus was rapidly fading from the scene. (This confusion was due to S gene drop out being used as a surrogate marker for BA.2., which these new variants also share.) Take note of the fact that once a variant has shown a rapid decline in frequency they go on to virtually disappear, and so far have never returned. Of course various experts, all vying for interviews and the honor of being first, are already offering their opinions as to its level of transmissibility, and even the severity of clinical disease; but we have been through this before, and we know it is far too early to form any cogent opinion on these issues. It looks like there have been a total of 80 sequences identified so far in India as of July 7th for the combined three variants. Prior experience also tells us that India has a very different Pandemic trajectory from the US. I’m marking this as unimpressive scare porn for the moment, but as usual reserve the right to contradict myself based on new data.

Anyone who has been reading here for some time will recognize that monitoring disease activity through analysis of waste water is a technology I feel has been very important in gaining insights into the Pandemic’s course and tracking of variants. This week an important paper was published in Nature detailing new laboratory techniques and computational algorithms, which allow for a significant advance in this field. Previously it was possible to measure fragments of the virus’ RNA genome and quantitate an overall amount, but it was very difficult to sequence whole genomes, and separate out and measure the relative amounts of different variants from the mix of shall we say, “other stuff”. The paper referenced here describes the ability to rapidly recover and sequence entire COVID genomes and quantitate the relative amounts of different variants in the mix. This is the difference between relatively slowly looking for something you have set the system up in advance to find (because you were specifically looking for that thing), and being able to very quickly and accurately measure the viruses you were looking for, plus also immediately recognize novel variants. This approach should be very productive in tracking the appearance and spread of new SARS2-Cov19 variants and the appearance of novel viral threats around the world. Here at home in tiny Telluride, CO. we are clinically identifying about 18 -20 COVID cases a week. My calculations based on our waste water levels of RNA suggest there are closer to 100 cases a week.

https://www.nature.com/articles/s41586-022-05049-6_reference.pdf

Finally I would like to alert you to the fact that Consumer Reports notified us this week that 30% of randomly selected ground chicken products tested from a variety of US stores showed Salmonella contamination. My initial reaction was “I don’t eat ground chicken only ground turkey so I guess I’m in the clear”, but that was quickly followed by, “Why is Consumer Reports telling me this and not the USDA/CDC?”. According to the CDC, Salmonella causes 1.35 million infections, 26,500 hospitalizations and over 400 deaths per year in the US. Young infants are especially susceptible to severe disease with Salmonella and frequently require hospitalization. The other biggest risk factor for Salmonella infection in the US is contact with pet turtles, and reptiles. In any event, make sure your chicken burgers or turtle canapés are well done, at least 165 F, and skip the chicken tartare for now.

Thanks for your attention. Forwarding to anyone you think would find these updates useful is always appreciated.