Who shouldn't get vaccinated? The informed part of informed consent.

 Ten months after the vaccines became available, we now have meaningful data that can guide people deciding if they should or shouldn't get themselves or their children vaccinated against covid.

The best available data about the actual risks of the mRNA vaccines--specifically the Pfizer/BioNTech shots--come from a joint Israeli-Harvard Medical School study evaluating the medical records of more than 1.6 million people, half of whom received two Pfizer jabs while half remained unvaccinated. I reported on this study here, and you can find the peer-reviewed paper itself, published in the New England Journal of Medicine, here.

Of course. But what are the actual risks and benefits?

Credit: Nick Youngson

The study found that just five side-effects occurred more frequently in the vaccinated groups in the six weeks following vaccination relative to a comparable time period for the unvaccinated group. These included swollen lymph nodes (78.4 additional cases per 100,000 people), shingles (15.8 extra cases per 100,000), appendicitis (5 additional cases per 100,000), Bell's palsy (3.5 additional cases per 100,000) and myocarditis (2.7 additional cases per 100,000, almost all in young men).

If we add all those side-effects together we find an incidence of 105.4 per 100,000 fully vaccinated people.

It's worth noting that those symptoms vary in seriousness. The most frequent--swollen lymph nodes--is a predictable, rarely serious, reaction to vaccination, while the remaining four potentially more serious conditions represent a total of just 27 additional cases per 100,000 vaccinated people.

To keep things simple and clear, you can safely estimate that if you get two rounds of the Pfizer vaccine, your risk of suffering any reaction worse than a sore arm is around 1 in 1000, and your risk of a serious side-effect such as shingles or appendicitis is around 1 out of 3700.

We can compare these risks to the risks from covid itself in a variety of ways. Here are several that readers may find helpful:

Risks from covid in the Israeli-Harvard study: Among the 800,000 participants who remained unvaccinated, a significant number contracted covid. As is typical of covid, not all of those developed serious symptoms. However, far more did experience significant symptoms and sequelae from covid than were seen in their vaccinated peers. These included cardiac arrythmia (166 extra cases per 100,000), acute kidney injury (125.4 extra cases per 100,000), pulmonary embolism--a blood clot in the lung--(61.7 extra cases per 100,000), deep-vein thrombosis (43 extra cases per 100,000), myocardial infarction--a heart attack--(25 extra cases per 100,000), myocarditis (11 extra cases per 100,000), pericarditis (10.9 extra cases per 100,000) and intracranial bleeding (7.6 extra cases per 100,000).

So, in the same 6 week period, the unvaccinated group suffered serious, very serious or potentially fatal symptoms such as acute kidney injury, pulmonary blood clots or heart attacks at a combined rate of 443 per 100,000. That's more than four times the rate of all the vaccine side-effects combined, and 16 times the rate of the potentially serious vaccine side-effects.

Risk of contracting covid in the US as a whole. As of 10/18/21, there have been 45,798,599 recorded covid cases in the US. That's a case rate of 13,733 per 100,000 people, accumulated over 22 months. It's not possible to predict the exact course of the pandemic going forward, but for the average American the risk of contracting covid, say in the next 12 months, is probably 50 or 60 times higher than the risk of any side-effect from the vaccine, and several hundred times higher than the risk of any of the more serious side-effects.

As critics of covid vaccination point out, many covid cases are relatively mild. However, in the US over the course of the pandemic so far, about one out of every 20 people who contracted covid got sick enough to require hospitalization.

Risk of covid hospitalization in the US as a whole. As of 10/18/21, the cumulative covid hospitalization rate in the US reached 694 per 100,000. That implies that the average US resident is 6.6 times more likely to have been hospitalized because of covid than they would have been at risk for any negative reaction to the vaccine, and 26 times more likely to have been hospitalized from covid than to have risked a serious reaction to the vaccine.

Again, the first 22 months of the pandemic don't tell us what the next 22 months will bring, but the risk continues, especially among the unvaccinated.

Again, vaccination critics point out that "covid has a 99 percent survival rate." That's not quite true. In the US so far, 1.6 percent of recorded covid cases have resulted in recorded covid deaths. We can now compare that to the risks from vaccination.

Risk of death from covid in the US as a whole. As of 10/18/21 the cumulative rate of deaths from covid hit 224.5 per 100,000 people. That means that on average, a US resident is 2.1 times more likely to have died from covid since the start of the pandemic to date than to have risked any negative reaction to a vaccine, and 8.3 times more likely to have died as a result of covid than to have risked one of the serious reaction to the vaccine.

Risk of covid deaths state by state. As of 10/18/21, five states had cumulative covid death rates less than 105 deaths per 100,000 population. Those are Oregon (99), Utah (96), Hawaii (87), Alaska (59) and Vermont (55). For residents in those states, which comprise just three percent of the US population, the odds of having died from covid so far in the pandemic are somewhat less than the risk of having any negative reaction to the vaccine, but still two to three times higher than the risk of one of the serious vaccine side-effects. Even in those states, however, the risk of hospitalization from covid is significantly higher than any of the risks from the vaccine.

The remaining 97 percent of Americans live in states where the risks of contracting covid, becoming seriously ill, being hospitalized or dying from covid are greater than the risks of any negative sequelae from the vaccines.

Risk of covid deaths county by county. You can check your county's cumulative covid death rate on this map. If you're in one of the darker blue counties--most of which have very small populations--the cumulative death rate per 100,000 people is less than the risk of side-effects from the vaccine. Still, unless your county's cumulative death rate is less than 12 per 100,000, as it is in Orange County, Vermont (population 29,000) or Skamania County, Washington (population 11,066), your risk of hospitalization from covid is higher than any risk from the vaccine.

Risk of covid deaths from breakthrough infections: We now know that vaccine-induced immunity fades over time, and that the delta variant in particular is causing a significant number of fully vaccinated people to fall ill. However, the vaccines are still highly protective against severe illness and death. Perhaps the most striking statistic is that out of 187,000,000 fully vaccinated Americans, 7,178 have died from covid, or just 3.8 per 100,000. That's less than 6 percent of the 124,000 Americans who have died from covid since mid-July, when the delta variant became predominant.

In summary, for the large majority of Americans, the risks of getting covid, suffering one or more of the serious impacts of covid, having to be hospitalized because of covid, or dying from covid are all far higher than the risks of any side-effect of the mRNA vaccines, and, even against the delta variant, the vaccines remain highly protective against severe illness or death.

What about children?

There is one group, however, for whom this may not be true. As many critics of covid vaccination have pointed out, the risks from covid are significantly lower for young people. For example, the cumulative covid death rate for children under 15 is less than 5 per 100,000, comparable to the death rate for fully vaccinated adults. For 16 and 17 year-olds it's 9 per 100,000, and from 18 through 29, 16 per 100,000. If we were just comparing the risk of dying from covid to the much less serious but documented risks from the mRNA vaccines, one could potentially come down on the side of not vaccinating young children and teenagers.

The picture changes if we include the risk of children needing to be hospitalized because of covid. The cumulative covid hospitalization rate for children 0 through 4 is 87 per 100,000, and from 5 through 18, 51.8 per 100,000. These are less than the risk of any side effects of the vaccines, but higher than the risks of serious side effects. Luckily, young children are less likely to be severely sickened or to die from covid than adults, but a significant number do need to be hospitalized.

Safety and efficacy trials of covid vaccines for children from 5 through 11 are currently taking place, and the White House has announced plans to promote vaccination of children ages 5 through 11 once a children's vaccine is approved. We should have more data specific to that age group within the next few months.

Individual risks vs. social responsibility

The risk ratios discussed above refer to individual risks. That is, one could decide to be vaccinated or not based only on comparing one's own risk of contracting covid, or of requiring hospitalization, or of dying vs. the known risks from the vaccine. However, public health authorities point out that, much like choosing to wear a mask, getting vaccinated doesn't just protect the person getting the jab, it also protects others by reducing the likelihood that that person will infect others. This multiplicative factor becomes significant when large numbers of people in a population remain unvaccinated, and so provide a continuing medium for the virus.

Currently, 43 percent of the US population remain unvaccinated, or more than 143 million people. Around half of those are adults who would incur low risks from vaccination yet could protect themselves and others by doing so. As long as they choose not to get vaccinated, they remain a big, wide playing field across which the coronavirus can continue its advance.

Best data yet on the actual risks of the Pfizer mRNA vaccine

Many people don't trust even repeated assurances from official sources that mRNA vaccines like the Pfizer/BioNTech Covid shots are safe. In fact it's not unusual for opinion leaders opposed to these vaccines, and their followers, to warn that the Covid vaccines are extremely dangerous and have already caused high levels of serious illness and thousands of deaths. Millions of Americans appear to be far more afraid of the vaccines than of the Covid virus itself, and continue to refuse vaccination.

                                                                 Anti-vaccine protester

Credit: Fibonnaci Blue/Flickr

A new, peer-reviewed study appearing in the New England Journal of Medicine injects solid data into this fraught debate. The study provides an accounting and analysis of adverse events that occurred among more than 800,000 people within 42 days of receiving the Pfizer vaccine in Israel between December 20, 2020 and May 24, 2021, compared to an equal number of carefully matched peers who remained un-vaccinated, and to 173,000 peers who were diagnosed with Covid during the same time period. All the data came directly from anonymized medical records.

It's the largest controlled, peer-reviewed study of the side-effects of the Pfizer vaccine to date--nearly 40 times larger than Pfizer's phase III study--and provides the most accurate and detailed evidence to date of its risks when administered to large numbers of people on a national basis.

Anyone interested in reading the full research paper, carried out by researchers at the Clalit Institute in Israel and Harvard Medical School, can find it here.

The study evaluated 25 potentially serious adverse effects that earlier studies and clinical experience since the vaccines were released had identified as possibly linked to the Pfizer or other Covid vaccines, or to Covid itself. It did not look at mild, short-lived symptoms that typically accompany many vaccinations, such as fever, tiredness, or soreness near the injection site. It also did not attempt to evaluate any potential long-term effects.

Results:

Of the 25 adverse effects studied, 5 appeared more frequently following vaccination than they did in the same time period in the group of matched, but un-vaccinated peers:

Myocarditis--inflammation of the heart muscle--was 3.24 times more frequent in the vaccinated vs. un-vaccinated groups. However, since the incidence was low overall, that meant just 2.7 extra events per 100,000 people. In this study 91 percent of cases occurred in young men.

Lymphadenopathy--swollen lymph nodes--were 2.43 times more frequent among vaccinated compared to un-vaccinated people, appearing in 78.4 more cases than expected per 100,000. Swollen lymph nodes can be a sign of a serious condition such as cancer, but usually are simply an indication that the body is mounting an immune response.

Herpes zoster--shingles--was 1.43 times more frequent in the vaccinated group, and accounted for 15.8 additional cases per 100,000 vaccinated individuals.

Appendicitis occurred 1.4 times more often in vaccinated than unvaccinated individuals, adding 5 cases for every 100,000 people.

Bell's palsy--dysfunction of a facial nerve--occurred 1.3 times as often among the vaccinated group, but was also rare, accounting for 3.5 extra cases per 100,000 vaccinated individuals.

An unexpected finding was that vaccination lowered the risk of some of the adverse effects being studied, compared to the un-vaccinated group. Those included acute kidney injury, intracranial bleeding, anemia, and lymphopenia--low levels of white blood cells. The researchers suspect that those benefits appeared because of un-diagnosed Covid cases among the 800,000 un-vaccinated participants, which raised the incidence of those conditions--known complications of Covid-- in the un-vaccinated group.

As is true of almost any medical intervention, this study shows that the Pfizer/BioNTech mRNA vaccine is not risk-free. More importantly, the study gives us a clear measure of just what the vaccine's short- to medium-term risks are. Out of 25 potential side effects, 5 appeared at higher rates in the vaccinated vs. un-vaccinated groups. Of those, the most most serious was myocarditis, which added just 2.7 cases per 100,000, and the most frequent, which added 78 cases per 100,000, was not particularly serious--swollen lymph nodes.

In order to provide further context for those risks, the researchers looked at the same 25 potential adverse effects among 173,000 un-vaccinated study participants in the 42 days after they were diagnosed with Covid. The results reflect many of the all-too-well-known risks of Covid infection:

Cardiac arrythmia--3.8 times more frequent; 166 extra cases per 100,000

Acute kidney injury--14.8 times more frequent; 125.4 extra cases per 100,000

Pulmonary embolism--blood clot in the lungs--12.4 times more frequent; 61.7 extra cases per 100,000

Myocardial infarction--heart attack4.47 times more frequent; 25 extra cases per 100,000

Deep-vein thrombosis--3.78 times more frequent; 43 extra cases per 100,000

Myocarditis--18.3 times more frequent; 11 extra cases per 100,000

Pericarditis--5.39 times more frequent; 10.9 extra cases per 100,000

Intracranial bleeding--6.89 times more frequent; 7.6 extra cases per 100,000

Relative risks from Pfizer vaccination vs Covid infection

Credit: Noam Barda et al./NEJM

The vaccine is not risk free, but equally clearly, it does not cause anything like the degree or kinds of risk that anti-vaccination advocates and believers warn of. And the risks from the vaccine pale in comparison to the far higher risks from a Covid infection.

Here's what Dr. Ran Balicer, the study's lead author, concludes:

"These results show convincingly that this mRNA vaccine is very safe and that the alternative of 'natural' morbidity caused by the coronavirus puts a person at significant, higher and much more common risk of serious adverse events. These data should facilitate informed individual risk-benefit decision-making, and, in our view, make a strong argument in favor of opting-in to get vaccinated, especially in countries where the virus is currently widespread."

I'd add that the United States, which leads the world in Covid cases and deaths, qualifies as one of those countries.

If you want to compare your own risks from the vaccine with your risks from Covid, here's an approach:

If you're in the US and you're not vaccinated, as a rough approximation you have about a one percent chance--1000 out of 100,000 people--of getting Covid in any given six-week period. 

If you're vaccinated, your odds are somewhere between 10 and 20 times better, depending on where and with whom you live, work and recreate.

Six weeks is the same length of time used in the above study, so you can get an idea of your chance of developing any or all of the Covid complications that the study quantified.

To those conditions you can add yet another risk. Over the course of the pandemic in the US, 1.6 percent--1600 out of every 100,000 people--who were diagnosed with Covid died from it.

So, as a first approximation, your chance of coming down with Covid during a given six-week period--and dying from it--is about the same as your chance of getting a case of shingles within six weeks of a Covid vaccination.

From what I hear, shingles isn't fun, but dying is worse.

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REA 9/8/21

AN INFECTIOUS IDEA -- A VIRUS-LIKE PROTEIN MAY BE CRUCIAL TO LEARNING AND MEMORY

We've all heard the phrase, "an infectious idea." It turns out that this may not just be a metaphor--new research has revealed that a virus-like protein in all of our brains may be vital for learning and memory.

"If it looks like a duck and quacks like a duck," the saying goes, "it probably is a duck." So, no matter how surprising it is, finding a crucial protein in the brain that looks like a virus and acts like a virus raises the intriguing possibility that our ability to learn and remember may stem from a chance infection of some ancestral four-legged creature by a retrovirus 350 to 400 million years ago.

The protein in question is called Arc. It's found in animals as different as flies, mice and humans. It's been known for some time that Arc is important for learning and memory. Mice lacking Arc forget what they've learned within 24 hours, and lack the kind of brain plasticity that lets young animals, most notably human children, soak up new information quickly and easily. Arc continues to be important for learning and memory throughout life, and impaired Arc functioning is associated with autism, amnesia and Alzheimer's disease.

Arc (long purple proteins inside the perimeter of the vesicle) can encapsulate and deliver its own genetic material to brain cells (light green branching blobs) in a manner similar to the way in which viruses infect host cells.  

Credit: Jacobo Lopez, Yi-Chu Su, Hugo Vaca

Jason Shepherd, a neuroscientist at the University of Utah, and his colleagues first suspected that something was different about Arc when they found that the protein self-assembles into structures called capsids that look like a lunar lander or the HIV retrovirus. Intrigued, they found that not only can the Arc capsid jump from cell to cell like a virus, it also transfers its own genetic material in the form of messenger RNA into the new cell.

Learning takes place when interconnected brain cells are activated at the same time. Intriguingly, the researchers found that when neurons "infected" by Arc are activated, they release newly minted Arc capsids. This suggests that the transfer of this virus-lilke protein from cell to cell may be a previously unknown and unsuspected mechanism for learning and memory.

Neuron expressing Arc and transferring it to other neurons

Credit: Elissa Pastuzyn 

“We went into this line of research knowing that Arc was special in many ways," says the study’s lead author, postdoctoral fellow Elissa Pastuzyn. "But when we discovered that Arc was able to mediate cell-to-cell transport of RNA, we were floored. No other non-viral protein that we know of acts in this way.”

Geneticists have been able to trace back the history of the Arc proteins found in all mammals. Sometime between 350 and 400 million years ago, a primitive four-limbed creature, or tetrapod, was infected by a retrovirus that left some of its genetic material in the animal's DNA. That chance addition to the mammalian genetic code has apparently proven extremely useful, perhaps laying the groundwork for the success of our mammalian ancestors, and even for our remarkable capacity for learning and remembering.

REA

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You can read more about this research at this URL.

The scientific article describing this research can be found in Cell, January 11, 2018.

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