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December 2022

Three Years Ago Today

Yup. This is the three year anniversary of the COVID pandemic. On December 31 2019, the health commission of the city of Wuhan announced that they were investigating an outbreak of an unusual respiratory illness. The statement said that most of the afflicted had visited a food market in the city and that 27 people had contracted an unusual viral pneumonia. Seven were in serious condition. Things went down hill from there. China shut down and the rest of the world vaccinated.

I posted in these pages on those early days of the pandemic here if you want to revisit the beginning of this strange time.

At least I can say, all this has kept me occupied. My blog, going on 160 posts now, has earned me some new friends (I got a very nice message last week from someone in the Phillipines thanking me for "helping humanity." It made my day.) And it has earned me enemies from people who want to believe that Trump botched his response. He didn't. He launched Operation Warp Speed that gave us the vaccine and respirators in record time. On the other side of the political spectrum, I get vitriol from those who think that Tony Fauci is Satan incarnate for shutting down schools. He didn't, since NIH has no authority to do so.But that fact doesn't change anyone's mind.

So, among that cognitive dissonance, I thank my friend in the Phllipines and other readers who fined use in my blog.  I write it for you.


Take Your Vaccine Skepticism To A Cemetery

“Still a man hears what he wants to hear and disregards the rest”

            --Paul Simon, in The Boxer

They say you won’t find an atheist in a foxhole. Well, perhaps you shouldn’t find a vaccine skeptic in a cemetery, either. Bear with me and I will explain.

I have been reading about how vaccine skepticism is growing beyond the COVID vaccine to include other common vaccines against flu, measles, chicken pox, polio, etc. Perhaps this all began with parental resistance to Gardasil, a vaccine against human papillomavirus, or HPV, introduced in 2006. HPV is a sexually transmitted virus that causes genital, anal, and oral cancers. It is the most common cause of cervical cancer. In order to confer maximal and lasting protection, it is recommended that children around 11 and 12 years old be vaccinated. Some parents have railed that this promotes promiscuity. They fret that the vax licenses licentiousness in children, akin to giving them condoms with illustrated instructions in their use. Balderdash!  

While that medical insurrection continues to smolder, along came COVID and the anti-COVID mRNA vaccines accompanied by the surprising resistance of many people against the shots. It is a resistance that seems to be growing and spreading to vaccines in general including those listed above that have long been commonly accepted.

This is concerning because it portends that in the near future, kids will begin coming down with diseases that we have pretty well controlled. In fact, in the last year or so, de novo cases of polio have appeared in the US in unvaccinated people. Before this incipient vaccine resistance, polio had been eradicated in North America, thanks to the vaccine.

It is safe to expect that vaccine resistance will persist, and probably increase as new vaccines are developed to treat cancer and better protect against flu. The mRNA vaccine technology is being used to develop new vaccines against the deadly skin cancer melanoma, and research is underway to also develop vaccines to prevent breast, liver, prostate, and other cancers. This use of modern vaccine technology to prevent cancer is a very novel and promising approach to dealing with malignancy. Anti-cancer vaccines are a potentially exciting new weapon in the armamentarium for the war on cancer. Too bad for those who would reject an effective cancer-preventing vaccine. At least they can fall back on the standard harsh radiation and chemo therapies.

mRNA vaccine technology also is being used to try to develop a universal vaccine against the flu. Flu is a highly malleable virus because there are many strains out that that can mix and shuffle their genetic material. This means that every year, it is a guessing game as to which combination of flu we will contend with—hence the changing flu numbers each year-- H1N3, H2N4, H3N1, etc. Since the Southern Hemisphere’s flu season precedes ours in the North, flu sleuths follow what goes on down there and track which strains make their way Northward, often via migrating birds, and try to predict what flu strains will be prevalent here each year. Then flu vaccines are made based on the best predictions. Usually, the annual flu vaccine is a mix of 2-3 of the flu strains that we are most likely thought to encounter. Some years we better predict which flu strains to vaccinate against than in other years, hence the efficacy of the vaccine can vary from year to year. Therefore, the advantage of a universal vaccine effective against all strains would be to remove this uncertainty and variability. That is the goal of using mRNA technology to take genetic material that is common to all flu strains and package it into lipid particles as pseudo-viral particles to trick the immune system to make an immune response to these parts of the viruses. If successful, this would protect against all flu strains and eliminate the need to guess which strains to vaccinate against. Theoretically.

The point is, vaccine science is moving forward and continues to offer great promise to prevent diseases that have proven very difficult to treat. The vaccine naysayers will miss the boat if they continue their misguided dissent. I suggest that they test their skepticism in a cemetery.

Go to an old cemetery and find the graves of people who died in the 1950s and earlier. See how many headstones belong to children.

Then go to the part of the cemetery where the grave stones are for people who died in the 60s and later and see how many graves are occupied by children.

The sharp drop in the number of childhood deaths after the 60s can largely be attributed to vaccines. Vaccines prevent serious disease and death in children who used to die from meningitis, pneumonia, dysentery, small pox, flu, and other diseases, but now do not. And to those who think that the vaccines are killing people, where are their headstones?

It is always better to prevent disease than to treat it. Vaccines prevent disease. Avoid vaccines if you wish. Darwin might approve.

The Latest On Long COVID (So Far)

“After all, tomorrow is another day.” Gone With the Wind

In these pages, your humble bloggeur (me) has followed the evolution of what we know about the odd condition known as long COVID. You can find seven previous blog posts on the topic here. Because we were just learning what long COVID was all about, many of those posts ended with the disclaimer, “we will see.”

Well, we have seen and continue to see. Here is what we now know after over 2 years of experience with this complication. But, tomorrow is indeed another day.

The risk of death from COVID is now about the same as the risk of death from flu, which can vary from year to year, thanks to vaccines, natural exposure, and developing therapies. One study in Lancet found that people with COVID had a 3-fold greater chance than uninfected people of dying each year. But, as I explained before, mortality is only part of the story. There also is morbidity. Long COVID is "the rest of the story" as Paul Harvey used to drone. Some 54 studies on long COVID, involving 1.2 million people, have been reviewed and it was reported that about 6% of people with symptomatic COVID infection wind up with long COVID. This agreed with a massive Swedish study of COVID patients done between 2020-21. According to the new Census Bureau Household Pulse Survey, some 16 million working age Americans now suffer from long COVID, which creates a huge burden on our health system. Up to 4 million of these are unable to work, which is a major drain on a labor market already short of workers. The annual cost in lost wages is up to $230 billion! The total economic cost of long COVID in the US so far has been an astounding $3.7 trillion!!

And as the virus evolves, reinfections with new CoV-2 variants are becoming more and more common. Unfortunately, a large VA study on reinfections suggests that you want to avoid them. A second or third infection is associated with worse disease and increased chance for long COVID. And a large German study including nearly 12,000 children with COVID concluded that long COVID “cannot be dismissed among children and adolescents.”

A sobering study of medical records from millions of US military veterans in the VA medical system published in Nature Medicine found that 7% more COVID patients (compared to uninfected veterans) had lasting brain or neurological disorders. This extrapolates into about 6.6 million Americans with long-term brain impairments linked to COVID. Memory impairment was the most common brain malady. But those with a history of COVID also were at greater risk of ischemic stroke, seizures, anxiety and depression, and movement disorders.

The good news is that vaccines reduce the risk of long COVID—how much is still debatable at this point. The anti-COVID medicine, Paxlovid, reduces long COVID risk by 25% according to one study. And the Omicron CoV-2 variant shows a reduced risk of long COVID compared to the more pathogenic Delta variant.

Assessing the risk: How much should the risk of catching long COVID affect one’s daily decisions? Should I go to the concert? Graduation? Grocery store? Wear a mask everywhere? That is hard to say definitively. Perhaps it would help to compare COVID risk to other risks we face every day.

  • The annual risk of getting in a car accident is about 1 in 30 per year. Of those, ~43% involved injuries and ~10% of those cause permanent impairment. This makes the annual risk of permanent injury from an auto accident about 1 in 700.
  • The annual risk of serious injury in a house fire is ~1 in 20,000.
  • The risk of needing reconstructive surgery after a dog bite is 1 in 400 annually.
  • The risk of catching the Omicron variant (symptomatic or asymptomatic disease) is ~1 in 2 annually (it was 1 in 4 before Omicron). Say 3% of those get long COVID, and ~18% of them are so sick they are unable to work for an extended period. This makes the annual risk of severe long COVID about 1 in 370.

So, the risk of debilitating long COVID is about twice the risk of serious injury from driving and about the same as getting a serious dog bite. The risk of severe long COVID is much higher than being injured in a house fire. Of course, all of these risks are affected by our personal behaviors. We don’t drive drunk and wear seat belts (hopefully). We replace the batteries in home smoke detectors every year and avoid growling curs. And if we are smart, we vaccinate and stay home when we are not feeling well.

At least those are things that responsible people do to reduce the risks of life.

Are COVID And Cancer Connected?

Nothing surprises me, I’m a scientist.” 

                            -Indiana Jones   

In 2019, the world was introduced to a brand new pathogen, the SARS-CoV2 coronavirus, that caused a brand new, and very odd disease, COVID-19. Between then and now, your humble bloggeur has penned 153 blog posts, many of which focused on how strange the disease is and describing our learning process as we figured it out on the fly. Many of these posts were necessarily equivocal because we simply did not have enough information to make firm conclusions on how the virus affects different people. Over time, we learned how to better treat the disease, and that learning curve continues. It was necessary to end many blog posts with the weak statement, “We will see.” Well we are still seeing and learning about this odd malady that consists of a melody of symptoms across myriad organs.

Research is now beginning to reveal a possible link between CoV-2 infection and cancer. As before, these observations are preliminary and will be further scrutinized, but they are bolstered by the discovery of a possible mechanism that could explain how the CoV-2 virus might cause cancer.

We know of many different viruses that cause cancer in animals. We also have a good understanding of how the viruses do that. There also are a few viruses, but not many, that cause human cancer, and we also mostly understand how they exert their oncogenic effects. These human cancer viruses include human papilloma virus (HPV), which causes cervical, and head and neck cancers. Hepatitis B virus can lead to liver cancer. Human T cell leukemia virus causes leukemia, and Epstein Barr virus can lead to lymphoma and a few other types of cancers. And so on.

To date, there has been very little association between any coronaviruses and cancer in animals or humans. But, that might be changing.

Several recent papers have revealed a genetic link between COVID-19 and cancer. One paper showed that people with an increased genetic risk of COVID-19, were also at increased genetic risk of developing endometrial cancer. The limitation of this study is that it cannot distinguish between a correlated high risk of COVID and cancer, vs whether COVID causes the cancer. It is the old conundrum of discerning between correlation vs cause-and-effect.

A second study incrementally advanced the above findings. Using a low resolution genetic mapping technique called genome-wide association, it found a positive correlation (there is that “C” word again) between people genetically predisposed to both severe COVID and increased risk for endometrial cancer. While still a correlation, one would predict that if there was a cause-and-effect relationship between COVID and cancer, that the risks for both would be similar. This is what the study showed.

Finally, a third study uncovered a possible mechanism by which SARS-CoV-2 could cause cancer. Having a possible mechanism in hand bolsters the possibility that the theoretical link between COVID and cancer is true. But first, a little back story about cancer genetics.

Cancer genetics.  Basically, cancer is a genetic disease. That does not necessarily mean that it is always inherited. Most cancers probably are not. But, when the genetic fidelity of a cell messes up, it can become immortal, can grow in an unregulated fashion, and can become resistant to normal signals that should cause it to die. In a nutshell, that is cancer. Generally speaking, there are two kinds of genes that contribute to this process. 1) Dominant acting oncogenes are aberrant genes that when expressed, drive the above activities. 2) Suppressor genes provide brakes to the above activities, and when absent, the brake is released. In both cases, genetic abnormalities either activate oncogenes to drive cell immortality and growth, or eliminate expression or activity of tumor suppressor genes removing the brakes to cell growth. Usually, cancer is a stepwise process in which cells sequentially accumulate different abnormal oncogenes and suppressor genes. The combination of which leads to full blown cancer.

One of the first tumor suppressor genes to be identified is called P53. In several different tumors, it was noticed that expression of this gene was missing due to DNA mutation. Further research showed that when expressed, P53 provides a brake on cell growth. There are many ways that P53 can be inactivated. Genetic mutation can prevent its expression, or hinder its function. We also know that a few viruses that cause cancer in people, like hepatitis B virus and Epstein-Barr virus, produce proteins that can interact with and inactivate the P53 gene product. A paper published in November, now reports that two CoV-2 proteins interact with cellular proteins to stimulate complex pathways that lead to degradation of the P53 gene product, releasing the anti-cancer brake in infected cells. The research also shows that that P53 activity is lost in patients with severe COVID disease but not in those with less severe illness. P53 loss also correlates with length of COVID symptoms. In other words, the more severe the COVID disease, the greater the chance that the P53 brake is lost.

This observation does not yet prove that inhibition of P53 by the CoV-2 virus causes cancer, but it now presents an important hypothesis that will be given much research attention. Questions remain regarding the association between CoV-2 infection and cancer. Also, since COVID infections are generally relatively short-lived, how long does the loss of P53 function last? Are long-COVID patients at increased risk for chronic loss of P53 and cancer? Is this loss of function sufficient to launch the multistep pathway that leads to cancer?

Once again, we will see.