When the Science is Hard

And the whimpering is easy.

This week the Pet Peeves department has been agitating for some upfront coverage and threatening to have me fired for, “Setting too high a bar”, in the journalistic field, particularly spelling. I’m sure everyone is familiar with this week’s story of the NYU professor who was fired because some students in his class complained his organic chemistry course was too hard. Just for a little perspective; Maitland Jones Jr. is a highly respected senior experimental chemist, who ran a very productive lab at Princeton for many years. He is an author on over 225 scientific papers and several texts on Organic Chemistry. Does that make him a good teacher? Absolutely not, but apparently a generation of Princeton students, and NYU students since 2014, have done just fine with his course—which I’d bet is no harder now than it was in past years. For his part, the Professor says the quality NYU students, their pre-college preparation and ability to study has noticeably deteriorated over the last few years. He further asserts that the students were not attending class and were not viewing the online lecture videos. This is emblematic for me of the decline in quality of education and intellectual environment at many universities in the US. The dumbing down of educational expectations to pander to political constituencies is a national disgrace, that will have disastrous repercussions for American competitiveness. Let’s consider for a moment who the complaining students are likely to be. The people who take Organic Chemistry, admittedly a challenging course, will be chemistry majors, other people in the physical sciences, who perceive a need to be familiar with the basic concepts of the field, and pre-medical students. My bet is on the premed students to be the ones complaining the subject is too hard, and the grade hurts their GPA. It’s one thing to be cancelled and vilified on campus for failing to drink this or that Kool-aid, or expressing conservative views—that’s unfortunately old hat by now. It’s the same ethos that is bringing you Jew Free zones at Berkley, so people can feel safe. But to be cancelled by numbskulls for allegedly making a scientific subject too hard, that’s a whole new ballgame. Where is the NYU faculty? Perhaps hiding in the basement, dumbing down their course syllabus and exams, and praying they’re not next on the student chopping block?

Epidemiologists and healthcare personnel in Europe are pointing to an uptick in COVID cases over the last 2 weeks. Hospitalizations in the UK have continued upward again this week, and new cases have surged by 25% to 1.3 million in one week. The canary in the mine is screaming fairly loudly right now, and his song is not “The Pandemic is Over”. No matter how many times we go through this, we hear some pundit quoted in the media as saying, “Yes, but deaths have not increased and perhaps this time it will be different”. We have enough experience with COVID to refer to the Winter Wave Season as more than a theoretical possibility, and this is the start. Although there is an explosion of new Omicron lineage variants, none of them are currently leading the pack and driving up infections. The most logical interpretation of the current situation is that infections are increasing due to a combination of waning immunity, and human cold weather behavior changes. It’s quite likely that within a few months we will see the ascendancy of one or more of the current crop of Omicron variants with greater immune escape, or a curveball from left field that will be called Pi. Since we are all comfortable now with 350-400 COVID deaths per day, for many months, and not giving it much thought; it’s worth reflecting that this number of fatalities per year would be considered a catastrophic Influenza epidemic. Influenza has been largely absent from the scene for the last two winters, due to social distancing efforts and masking, but there is good reason to think it will return this year in much greater force. If that happens the healthcare system could easily be faced with a doubling of respiratory virus patients and even deaths.

I have recently discussed the monoclonal antibody Bebtilovimab as the only monoclonal retaining activity against the current Omicron descendants. This week the FDA highlighted what has been predicted for sometime—that Evushield (the only monoclonal which had an EUA for prophylactic use in people at high risk for vaccine failure) was no longer active against the circulating variants. There is now a published paper showing real world clinical effectiveness of Bebtilovimab compared to Paxlovid, and in the Omicron era. This was not a randomized controlled trial, but observational. Many of the Bebtilovimab patients received it because they had contraindications to Paxlovid, or were more than 5 days from symptom onset. The paper is indirectly referenced below for you. It’s important to note that the group receiving the monoclonal treatment were “sicker” by almost all measures of co-morbid conditions, and despite this the monoclonal therapy was equally effective to Paxlovid in preventing progression to severe disease and death. Bebtilovimab is given as an IV injection over 1 minute, so not really different than having venipuncture for a blood test. The study did not look at this issue, but I would be willing to bet there would not be the same occurrence of viral and symptomatic rebound as is seen with Paxlovid.

Bebtelovimab associated with reduced risk of hospitalisation, death in high-risk patients with SARS-CoV-2 Omicron variant. https://dgalerts.docguide.com/ncov-home/article/bebtelovimab-associated-with-reduced-risk-of-hospitalisation-death-in-high-risk-patients-with-sars-cov-2-omicron-variant

There have been a large number of epidemiology studies over the last 2 years suggesting that getting an Influenza vaccine was in some way partially protective from COVID infection. Immunology mavens, and experts in the media who parrot what they hear, have offered a number of “plausible” explanations about how that could be true. Below is a link to a paper just published from Ontario, which I think provides pretty convincing evidence that what has been reported previously is largely due to the “healthy vaccine recipient” effect. Older people showing up for Flu vaccination and a general checkup, have all sorts of behavioral and other health differences which may make them less likely to catch COVID, and perhaps more likely to have a higher rate of asymptomatic disease. It’s not the Influenza vaccine’s effect that is being measured, but the myriad other differences between these two groups of people.

Association of Influenza Vaccination With SARS-CoV-2 Infection and Associated Hospitalization and Mortality Among Patients Aged 66 Years or Older. JAMA Netw Open. 2022;5(9):e2233730. doi:10.1001/jamanetworkopen.2022.33730

The last section today will be an examination of whether the Pox virus is destined to make a monkey out of us. A bit of background on the family of Pox viruses is necessary. This large family of DNA viruses infects a wide range of host species. There are central regions of the genome which are fairly highly conserved between the different Pox virus species, and regions at the terminal ends which vary widely. Cowpox, which infects many species including man, has a very large genome compared to Variola (smallpox), which only infects humans, and is much more severe. It has been suggested by evolutionary virologists that loosing some of the terminal genetic material allowed Variola to evolve into a virus which was a “human specialist”, and increased it’s lethality. You might wonder how loosing genes could make the virus more fit for replication in humans, but if that genetic material was designed solely to help the virus circumvent the immune systems of other animals, it seems plausible. Now scientists at the CDC and other labs are reporting Monkeypox genome sequences with large deletions and rearrangements compared to the original sequences observed during the current outbreak. A look back a few years shows that in 2014 it was noted that the more lethal Congo clade of MPX had significant genetic deletions compared to the less severe West African clade. These are not the single nucleotide errors that happen in transcription of the DNA, but large block deletions or translocations to new locations of genes. If the deletion does not impair the basic function of the virus it may transmit forward to the next infection. This is largely a numbers game, and the current epidemic of Monkeypox is giving the virus vastly more opportunities to experiment with genetic rearrangements. What else might tip the scales to favor an even more fit “human specialist” MPX to evolve? How about a non-sterilizing vaccine which attenuates the severity of disease, but fails to prevent infection, replication under immune pressure, and transmission—I think we have some familiarity with that scenario. More reports of vaccine failure and breakthrough MPX cases are now being reported. We have no good information yet on how frequent this will be, how quickly vaccine immunity will fade, or how frequently asymptomatic infection favoring viral evolution is occurring. Unlike COVID, natural infection with MPX is highly likely to produce long term (?life long) immunity similar to smallpox. Following the links below is a quote from the authors of the 2014 paper on evolution of the MPX virus.

https://doi.org/10.1101/2022.09.16.508251 (CDC preprint on MPX deletions)

Genomic Variability of Monkeypox Virus among Humans, Democratic Republic of the Congohttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901482/ (Emerging Infectious Diseases 2014)

“The global effects of the emergence of MPXV strains that are highly adapted to humans could be devastating. Importation of MPXV by infected vertebrates is of concern because of the potential for establishment of new reservoirs outside Africa. In fact, American ground squirrels have been found to be susceptible to infection (39), suggesting that other rodent species worldwide might also be susceptible. Small genetic changes could favor adaptation to a human host, and this potential is greatest for pathogens with moderate transmission rates (such as MPXV) (40). The ability to spread rapidly and efficiently from human to human could enhance spread by travelers to new regions.”

It never fails to amaze me how some people’s ability to predict the future compares favorably with other people’s inability to recognize the present. My prediction is MPX is here to stay on the world stage, aided and abetted by human behavior, a feeble governmental response— manifested in a lack of will to inform people that vaccination was only a small part of the necessary response— and a vaccine that may be less efficacious than anticipated, and have unintended consequences. This genie is out of the bottle and we don’t get three wishes.

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