A friend of ours on the Maine island where we spent our vacation told us that her husband’s surgery had been cancelled at the last minute because the hospital in Portland was swamped with COVID cases, and all elective surgery was cancelled. This notification came at the last possible minute, as they were getting ready to get on the ferry to the mainland and make the trip down to Portland.

Our friend’s husband’s surgery was not an emergency. It was spinal surgery to correct a problem that had been plaguing him for some time. The physician who diagnosed the problem and prescribed the surgical procedure had said that the window of opportunity to correct the problem by means of surgery was perhaps six months, and three of those months had elapsed, so our friend and her husband were wondering whether the surgery could be rescheduled and completed sometime in the remaining three months. Considering the current state of the pandemic, they cannot be entirely sure when he will be able to have this necessary surgery.

What is particularly troubling about their situation is that the situation at the Portland hospital is almost entirely due to COVID-19 cases in the unvaccinated.

The effect of COVID-19 cases in the unvaccinated

I have no specific data on the proportion of the COVID cases in the Portland hospital in vaccinated versus unvaccinated patients, but data from some other locations sheds light on the overall picture.

For example, state health officials in Pennsylvania have stated that 94% of the new cases due to SARS-CoV-2 (the coronavirus that causes COVID-19) so far this year have been in unvaccinated people. And the unvaccinated account for 95% of the hospitalizations and 97% of the deaths.

In King County, in the state of Washington, the data for the month leading up to the 26th of August demonstrated that unvaccinated people were 7 times more likely to test positive for the COVID infection. But they were 49 times more likely to be hospitalized than vaccinated people, and 32 more times likely to die from COVID-19 than vaccinated people.

These data will certainly vary from state to state, but the overall picture can be summed up with a high degree of confidence. We can state unequivocally that the current surge in COVID-19 cases is primarily occurring in the unvaccinated fraction of the population. However, that surge in COVID infections has the potential to affect the vaccinated as well as the unvaccinated. Although the likelihood of infection in vaccinated individuals is much, much smaller than in unvaccinated persons, it is not zero, and a vaccinated person can get an infection transmitted from an unvaccinated person. And, of course, it is in the unvaccinated population that the variant strains are likely to emerge, because that is where the virus is mostly taking residence, multiplying, and mutating.

Beyond the data, there are economic consequences. It has been estimated that the cost of treating the COVID-19 infections in the unvaccinated now tops $5.7 billion, and that figure is soaring. Here is a chart showing the costs of treating COVID-19 cases in the hospital.

These cost estimates come from Fair Health, a non-profit enterprise that advocates for price transparency in health care. As you can see, the arithmetic average charges are significantly higher than the median charges. Even after insurance, the unpaid balances are quite substantial.
There has been discussion of ways to deal with those costs, a large part of which are simply absorbed by the hospitals and health-care providers. Suggestions have ranged from having health insurers refuse coverage to the unvaccinated, to permitting hospitals to refuse admission and treatment to the unvaccinated. Obviously, these suggestions are impractical and there is no chance of their being adopted. Moreover, leaving the unvaccinated who are infected with COVID-19 untreated and unsequestered from the general population only increases the spread of the disease.

However, suggestions of that kind are a sign that the frustration that the vaccinated feel about the vaccination refusers has been transformed into outrage. But for the obstinate refusal of a significant swath of the population of the US to accept vaccination, this pandemic would not have returned with such force.

As of today there have been 43,356,406 certified cases of COVID-19 in the US, and 695,196 deaths. COVID-19 deaths are on track to exceed the number of deaths in the US due to the 1918 Spanish flu epidemic, which took place when there was no vaccine and basically no effective treatment.

We have reached the point where 1 in 500 persons in the US has perished due to COVID-19. That ratio is 3 times higher in Hispanics and African-Americans, and 9 times higher in Native Americans.

In the meantime, a great deal of attention has been focused on the question of booster shots for people who are fully vaccinated.

Booster shots – yea or nay?

As you certainly know, on September 17th the FDA’s advisory committee approved the Pfizer booster shot for persons who had been fully vaccinated with the Pfizer vaccine, who are either over the age of 65 or have medical conditions which put them at higher risk, and also for health-care workers who are more likely to be exposed to infected individuals. This was a far cry from the previous statement issued by President Biden that boosters would be available for all by the end of September.

The rationale for booster shots is that the antibody immunity conveyed by the original vaccination wanes over time. There are many, many questions that need to be at least addressed, if not answered conclusively, regarding this issue. And it should be no surprise that the knowledgeable experts are by no means united on the issues relating to booster shots.

There are also questions regarding the specific boosters and their relationship with the original vaccines. The Pfizer booster consists of an additional shot of its original vaccine, COMIRNATY, to be used in the subjects who received the original Pfizer-BioNTech vaccine. Moderna and J & J are a bit behind in the race, as they have been from the start, although there is very positive recent news about both, which I will get to a bit later. Moderna and J & J boosters are expected to receive similar FDA approval in the next couple of weeks.

There is a certain amount of politics in the back and forth discussion of booster shots. Back in early August, Biden announced – perhaps prematurely – that booster shots would be available starting around September 20th. A couple of weeks later, he was obligated to temper that announcement with the statement that booster shots would be available only to people who had been initially inoculated using the Pfizer vaccine, since it didn’t look as though any other booster shots would be available by then.

It did seem as though our government here in the US was a bit muddled. Following the initial announcement implying that booster shots would be available for just about anyone, the CDC said boosters would be limited to people over 65 who had initially been vaccinated with the Pfizer-BioNTech shot, plus essential workers in high-risk occupations, especially in health care. Then a CDC advisory committee voted 16 to 2 to omit the essential workers, since most of them were under 65 and therefore, supposedly, at lower risk. And finally Rachel Walensky, the CDC director overruled the advisory committee and put those high-risk workers back in the pool. I don’t want to say that any of those decisions were wrong, but it left a muddled picture, which does not do anything to make the undecided any more confident in the leadership.

Leaving the politics out of the picture for the moment, let’s try to un-muddy the picture.

To begin with, why would boosters be necessary? The obvious answer would be that the immunity conferred by the vaccines wanes over time.

But that answer is only partially true. As Doc Gumshoe has pointed out several times, the mechanism of immunity is complex and has a number of different components. The first wave of the immune response is carried out by antibodies. A person who has neither been exposed to the coronavirus nor vaccinated has no antibodies against the coronavirus. However, vaccination and infection with the virus immediately generate antibodies, and as long as those antibodies continue to be present in that person, he/she has the capacity to resist infection.

It is those antibodies that wane over time. How long the antibodies last is not specifically known and likely to vary, but the usual estimate is several months and perhaps up to a year.

However, antibodies are not the only, or even the principal agents of immunity. Cellular immunity is carried by B-cells that have the capacity to remember the original invading virus, and also by killer T-cells that are programmed to search and destroy the virus. Cellular immunity lasts much longer than the immunity carried by antibodies. For example, persons who had the earlier coronavirus, identified as SARS-CoV-1, still demonstrate immunity to that virus, nearly 20 years after the initial infection.

What the antibodies do is immediately repel the initial invasion by the attacking virus. The antibodies, already present in the bodily fluids, are uniquely fitted to bind with and inactivate the specific viral particles. Thus, the protective effect of the antibodies is to prevent the initial infection.

Cellular immunity is activated after the virus has already entered the body. B-cells, which have been “taught” to recognize key segments of the virus through the process of vaccination, act as sentinels. The messenger B-cells summon up the army of killer T-cells, which do the job of killing the virus.

To reduce this complex immune function to simple terms, it can be said that the antibody response prevents infection, while the cellular response prevents serious illness and death. It is the antibody response that wanes, while the cellular response persists, often for decades.

In terms of reducing the toll of the pandemic, both are clearly important. The antibody response, in preventing initial infection, is also extremely important in preventing the spread of the disease, since newly infected persons are major sources of disease transmission, especially in the interval between infection and the emergence of symptoms. But the cellular response is extremely important, because it is that response that preserves life.

A brief digression: remember that one of the measures of the severity of HIV was patients’ T-cell levels. The virus (human immunodeficiency virus) attacked the patient’s principal means of defense. Thankfully, the coronavirus doesn’t do that.

So, yes, some of the immune response generated by the COVID-19 virus does wane over time – the antibody levels do decline over a period of months. But the cellular response persists. The chief value of the booster shot, then, is to restore the antibody levels and prevent the initial infection.

What are the data supporting boosters?

Pfizer argued that while protection against severe disease continues to be very strong in the US, immunity against milder infection wanes somewhere around six to eight months after the second dose. Pfizer gave an extra dose to 306 people at that point and recorded levels of virus-fighting antibodies threefold higher than after the earlier shots.

What booster supporters in general most strongly relied on were data coming from Israel, which leads the world in terms of the percentage of its total population having been fully vaccinated. Israel experienced a surge in infections due to the Delta variant, and began offering booster shots over the summer. A study in Israel tracked about one million people aged 60 years and older and found that those who got the booster shot were far less likely to become infected soon after the shot. Pfizer, which presented the Israel data to the FDA is support of its booster shot, stated that the Israel data translated to “roughly 95% effectiveness” in preventing the spread of the Delta variant.

Critics of the Israel study included two members of the FDA team charged with making the decision whether to approve the Pfizer boosters – Dr Marion Gruber and Dr Philip Krause. They pointed out that the some of the Israeli evidence was collected just a week or so after the booster dose, and that the very short-term protective effect would not necessarily imply long-term benefit.

Supporters of the booster, including Dr Anthony S. Fauci, argue that the Israeli data clearly indicated a clear waning of immunity against infection, although it showed only hints of declining immunity against hospitalization in persons under 65 years of age. Nonetheless, declining immunity against infection constitutes a significant threat in terms of preventing the spread of the pandemic, since infected asymptomatic individuals are perhaps the most dangerous spreaders.

Recent news about both the Moderna and J & J vaccines

Regarding Moderna, recent research done by Dr Wesley Self of the Vanderbilt University Medical Center reported that the Moderna vaccine offered the best protection against COVID-19 hospitalizations. This was based on data from 21 hospitals in the US, from March to August 2021. After 120 days from the time of vaccination, Moderna’s vaccine effectiveness against hospitalization had declined only slightly, from 93% to 92%, while Pfizer’s dropped to 77%.

The Johnson & Johnson news was that the efficacy against mild to severe COVID-19 increased markedly after a second dose. The J & J vaccine, you will remember, was initially used as a single-dose. The J & J vaccine’s initial effectiveness is somewhat lower than that of the Pfizer-BioNTech and Moderna vaccines, but it is less susceptible to the waning effectiveness of those vaccines. Data based on a study comparing 390,517 vaccinated persons with 1,524,153 unvaccinated individuals showed that in this cohort, up to five months after vaccination, the effectiveness of the J & J vaccine against hospitalization remained steady at about 81%.

A new trial, which recruited 32,000 volunteers around the world, compared persons who received one shot of the J & J vaccine with those who received two shots eight weeks apart. The second shot lifted the antibody levels in the blood of these subjects four times as high as the level produced by the first shot. As reported by Johnson & Johnson, the efficacy against mild to severe COVID-19 rose from 74% after the single shot to 94% after the second shot.

A major obstacle to the development of new vaccines against SARS-CoV-2

It’s questionable whether we really need new COVID-19 vaccines, but even if there were a miraculously effective and really long-lasting vaccine in the works, it would be extremely difficult to conduct the clinical trials that would be essential to get approval for this potentially transformative vaccine. The essential reason is that it would be unethical and unacceptable to test this new vaccine against placebo. It would therefore be necessary to conduct a clinical trial in which the candidate vaccine was compared with the current standard of care, namely, one of the currently-approved COVID-19 vaccines. And, according to the Coalition for Epidemic Preparedness Innovations (CEPI), getting access to a sufficient number of doses of the current vaccines is well-nigh impossible. The contracts with the vaccine manufacturers stipulate in what nations the vaccines are to be used, and also stipulate that the vaccines are to be used for treatment. And the vaccine manufacturers have very little incentive to furnish their vaccine for a clinical study in which it might very well turn out that their vaccine comes out second best. So it looks like, for the present at least, we’ll have to make the best of what we’ve got.

COVID-19 vaccines for kids?

On September 20th, Pfizer and BioNTech announced that their vaccine had been demonstrated to be safe and highly effective in children 5 to 11 years of age. FDA authorization is should come through sometime before the end of October.

Getting kids vaccinated could be a major boost in quelling the pandemic. About one in five of the new COVID-19 cases are in kids under the age of 12, and although these infections mostly don’t cause severe illness, infected kids are a major source of contagion. Perversely, a child with a serious case of the disease is more easily kept from contact with others, including susceptible older adults in whom the disease is much more likely to result in severe symptoms. If Timmy keeps to his bed, it’s a whole lot easier for Grandma to keep her distance. But if Timmy is running around the house and hopping into Grandma’s lap for hugs, Grandma is at considerably higher risk.

But it may take some serious convincing to get some parents of kids in that age group to agree to get their kids vaccinated. Many parents are wary of possible side effects, and they are apt to weigh these potential side effects against the benefits of the vaccine – which, they may reason, are not so great, because after all, kids mostly don’t get seriously sick. So, why take the risk of the vaccine, even if it’s a small risk?

Although by and large children do not develop the most serious symptoms, there is one life-threatening condition in children infected with the SARS-CoV-2. It is called multisystem inflammatory condition (MIS-C). The symptoms include fever, rash, stomach pains, vomiting, diarrhea, and some heart symptoms. Its prevalence is low – in persons younger than 20 years, there are about 11.4 cases per 100,000 persons.

Also in young children, mild COVID symptoms can persist for months, postponing any quick return to normal.

So there are certainly good reasons for parents to get their children vaccinated. However, the most important reason may be that vaccinating children will have an important effect on preventing more transmission of the coronavirus. And we should not have to be reminded that further transmission of SARS-CoV-2 is a threat to everyone.

More information about vaccinating children under the age of 5 years is expected in the next couple of months. Without doubt, that will be even more controversial.

Reminding ourselves that COVID-19 is not the only threat to our lives and the state of our health, let us shift our attention to other matters of interest.

A cancer vaccine that shows signs of doing what it is supposed to do

Just possibly a huge promise here. At first glance, we would suppose that cancer vaccines were impossible, or at least highly unlikely, because, as we know, every cancer is different. Cancer cells originate in human cells, and, as the cells divide and reproduce, tiny errors take place in the process of transcribing their genetic material. These errors are mostly meaningless; the cells with the errors die out. Once in a very great while, the transcription error results in a small advantage. Those cells persist and reproduce; that’s how evolution takes place. But more often that we would like, errors occur that permit the cell to go on multiplying and multiplying and multiplying more, taking up space and robbing other cells of their nourishment. Those are cancer cells, and they are essentially unique to the host in which they emerge. The only characteristic that they share with other cancer cells is this cursed tendency to reproduce endlessly. So how is a cancer vaccine even possible?

Vaccines, as you know, are essentially warnings to our immune system: if you spot something that looks like this, call the cops. But since there isn’t any “something that looks like this” that occurs in cancers in general, there’s no way to warn the immune system against cancer.

Except when the cancer is a recurrence. And, unfortunately, many of the cancers that wind up being fatal are recurrences. The patient had prostate cancer which was supposedly successfully treated, but the cancer had spread. So, in cases like that, “something that looks like this” persists in the body of the patient, and perhaps there is the possibility of a vaccine.

Research at the Harvard Medical School., the Dana Farber Cancer Institute, Brigham and Women’s Hospital, and the Broad Institute of MIT and Harvard focused on eight patients who had high-risk melanoma. These patients had their melanoma resected surgically and were free of the melanoma. They then were inoculated with a vaccine (NeoVax) to prevent recurrence. The vaccines had been developed to be effective against each patient’s specific tumor.

According to the researchers, these vaccines were safe and generated robust and durable immune responses. According to Dr Patrick Ott of the Harvard Medical School, “With high-resolution tools to dissect vaccine-specific immune responses, we found changes very much as one would expect after vaccination. Weeks after the treatment, genes that are important to kill tumor cells were upregulated. Eventually, after several months, they took on a memory T-cell type toward the end of the vaccination course.”

Work along this line is being done at several academic centers and by the pharmaceutical industry, including, as it happens, the companies that pioneered the RNA vaccines against SARS-CoV-2 – Pfizer and Moderna, as well as Genentech and others. The research so far has focused on melanomas, lung, and bladder cancers, but Dr Ott is convinced that the approach can be made to work for any cancer. Even though the vaccines will need to be tailored to the individual patient, the availability of some cancer vaccines may be years away – but not decades!
It may be something of an overstatement to call these prospective treatments 
“vaccines,” which would imply that they prevent the occurrence of cancer. The mechanism described above is the same as the mechanism of a vaccine, which is that the active agent teaches the patient’s immune system to recognize and attack the pathogen; the pathogen in this case being a cancer cell with some of the genetic properties of the cancer that had previously affected the patient. But is it a vaccine if it prevents the recurrence, rather than the initial occurrence? Is it a vaccine if it prevents the spread, say, of a melanoma to lung cancer? Whichever, if it actually does prevent those recurrences, we could hardly hope for better news!

“Polypills,” with or without aspirin, to reduce cardiovascular disease?

The idea has been around for quite some time – thirty years or so, I would reckon – but it has just resurfaced in Lancet (Joseph, P. Lancet 2021;398:10306). The idea is to make a pill combining a blood-pressure lowering agent, a cholesterol-lowering agent, and perhaps also aspirin. The pill would be sold over the counter, no prescription necessary, recommended for all adults over 50 years of age. The rationale is that a very large percentage of such adults already have either elevated blood pressure or elevated cholesterol, or both, and are already experiencing the early physiologic changes that could later lead to significant heart disease.

The Lancet study specifically aimed to determine whether aspirin should be included in fixed-dose combinations and the size of the effect on specific cardiovascular disease events. More than 18,000 participants (about half were women) from 26 countries were included in the total, with a median follow-up of five years. Compared with the control group, the group receiving fixed-dose combination strategies including aspirin had a 47% reduction in the primary outcome (a composite of cardiovascular death, myocardial infarction, stroke, or arterial revascularization), compared with a 32% reduction for fixed-dose combination strategies without aspirin. These results were judged to be statistically highly significant (P < 0.0001)

In spite of the greater reduction in the risks of cardiovascular events in the cohort receiving the polypill that included aspirin, the authors conceded that the benefit of the polypill with aspirin was somewhat offset by the risk of a major bleeding event potentially caused by aspirin. And that, in turn, was somewhat offset by the reduction in hemorrhagic strokes and some cancers associated with aspirin. So they didn’t come out unequivocally favoring the polypill with aspirin. But they did unequivocally favor the polypill.

Doc Gumshoe views this proposition with skepticism. For one thing, it seems to me that the control group, which was not taking blood pressure or cholesterol-lowering medications, is not representative of the population at large, many of whom are taking such medications. For another, making a recommendation of an over-the-counter drug to the multitudes invites a range of erratic practices. If one daily pill is good for me, why not two, or three? And since I’m following this official recommendation, why do I need to bother going to the doctor for my annual physical?

What Doc Gumshoe favors is having a regular primary care physician – a “medical home,” so to speak. A physician who knows you better than the code numbers and boxes checked on your computerized medical records. A physician who listens to you and to whom you listen, and whose guidance and advice you are more likely to follow. This physician will look for those signs that point to early risk of cardiovascular disease, and advise – and prescribe! – accordingly. Prevention of cardiovascular disease is not a “one size fits all” solution.

A couple of years ago, a Doc Gumshoe piece was posted with the title “Looking Out for Your Own Wellbeing”. It relied heavily on several articles by Dr Barbara Starfield of Johns Hopkins, in which she strongly and convincingly made the case that individuals who had primary care physicians had considerably better health outcomes than individuals who relied on specialists, whom they saw only when their symptoms became concerning.

There has been news lately that primary care is getting short-handed. When youngsters get into medical school, they opt for higher-paying specialties, which of course is natural. Medical school is tough going; you want a good reward when you emerge from the slog.

Therefore, Doc Gumshoe’s advice to the denizens is, latch onto a good primary care physician, and try to make sure he/she is younger than you are.

* * * * * * * * *

Like all of you readers, Doc Gumshoe wishes the COVID thing was over, and he could think about something else, which he tries to do anyway, from time to time. But COVID-19 will be with us for the duration, however long that is. In the meantime, there continue to be subjects of concern regarding our health, and I will try hard to keep these in my field of attention. Do please let me know of any particular topics you’re interested in and I will check up of them. Thanks for all comments and be well. Best to all, Michael Jorrin, aka Doc Gumshoe.

[ed. note: Michael Jorrin, who I call Doc Gumshoe, is a longtime medical writer (not a doctor) who writes for us about medicine and health a couple times a month. He has agreed to our trading and disclosure restrictions, but does not generally write directly about investments. His ideas, thoughts and words are his own, and you can see all his past pieces here.]