Debates, Uncertainty, Frustration, and the COVID 19 Pandemic

I struggle a little bit with the idea of debates.  

I understand the idea. Each side can argue the opposing points with conviction and strength. It is like making a “pros” and “cons” table to consider a hard decision. It is a way to get a really good understanding of the details on each side of a controversy.

I have participated in debates at medical meetings. It is a straightforward thing to do. I just need to come up with the strongest arguments possible for my assigned viewpoint. I don’t even really need to decide what I consider the best or correct viewpoint. That is not my job as a debater. My job is to argue my perspective. It is not my job to tease through or guide everyone through the conflicting arguments to come up with a final answer. Hopefully I will have been asked to argue the perspective that I really believe in, but my job as a debater is to argue whatever viewpoint I have been assigned.

I am told that a “good” debate has balance or equipoise between the two debaters.  When the debate is finished you should be able to really understand the points on each side. 

The problem is that often when leaving a debate, as a listener you don’t know what the best or “correct” viewpoint really is. At medical meetings I have commonly found myself going to watch a debate and leaving the session as confused as I was (sometimes more) than before the debate.  Often, I leave feeling just sort of frustrated.

Lots of information. Strong arguments. Not really sure what to think. Frustration. Sound familiar?

The past year has brought up a lot of debate.  With it I have heard from many people that they feel frustrated. They are feeling like me after the debates at the medical meetings. And it seems like the more they read or talk to people, the worse it seems to get. They don’t really know what is true, real or correct. What are they supposed to do? 

With the vaccination debate, the easiest thing to do when you don’t know what to do is to do nothing. Generally in life, if there is a question about doing something, the safest thing is to not do it. Is that the best approach with COVID? Or is there risk if you don’t act?

More recently as the pandemic has heated up again, the pressure has intensified. One podium yells at the other for inflicting harm by the large surge in numbers of cases predominantly among unvaccinated persons. The other podium yells that they are not evil people and how dare you judge them when they are acting out of their best conscience.

To be honest, it all grieves me.  I joke with people at work, “I just want to be clear about my stance on COVID. I am against it. I think we should not have it be a thing anymore. Can we just have it go away?” People will graciously laugh at my stupid joke, but I think we all get it. We are tired of the conflict, and we just wish we could all come together to fight this awful enemy that we share.

I have hesitated to write anything on this for some time. There is a LOT of information being posted in social media. I wasn’t convinced I would have much to add to the huge amount of information (and noise) that is “out there.” But this past week our health system set a new record with 406 patients in the hospital with COVID 19.  On my hospital rounds I saw so much death and grief from COVID this past week. It feels like it is time to say something. 

A few ground rules:

1. I am a cardiologist. I am not a virologist or a public health expert. I am sharing my opinions based on my scientific training and on my 30+ year experience as a physician rather than as an expert on COVID.
2. I am not sharing to enter into a debate. I know that you may disagree with some or all of what I say. You are welcome to your opinion. I am not stepping up to the podium to enter the debate. This blog post is instead an attempt to step away from the two debate podiums and sit down on the edge of the stage in the middle to share from the heart. It is funny but this is usually what has happened after I have been a part of debates at the scientific meetings. Once the crowd clears and the microphones are off, the two of us can sit and chat about what we really think. I am going for the “after the debate” thoughts with this blog.
3. I am not going to comment on mandates. We can have a very valid and vigorous debate about what governments or employers can and should do, the ability to choose vs. public health concerns, etc. That debate is beyond the scope of my comments.
4. I am hoping to share concepts that make sense to me. I do not have a specific agenda. My goal is not to convince you of anything. It is to share what and how I think.

COVID 19 is Real. I don’t know that anyone debates this at all anymore. While some people get only mild symptoms, it is not the same as a simple cold or flu. We have never dealt with anything like this. Over 1/4 of our hospital beds are filled with patients who are very ill (scary ill) with COVID. This is NOT business as usual. We really don’t have anything to compare it to within our professional careers. If it seems like we are making up rules and then changing them as we go, it is because all of this is new. The medical profession is doing the best it can to adapt and change as new information becomes available.

Hypothesis generating vs. proven treatments. We are all eager to have wonderful and highly effective treatments. This takes a lot of time and study to figure out. Science generally looks to see if there is a “signal” that something might be effective. This could be in-vitro (test tube) or in-animal model data. It can also be observational data (not structured or randomized but noticing that people who do x,y or z do better than those who don’t.) Science has taught us that this early data is only “hypothesis generating.” This means that it gives you an idea of what to study, but it does not prove that it works. It is disappointing but very common that what looked promising in the test tube or in observational studies turns out not to work. For new drugs, it is estimated that only 1 in 5000 end up making it to market.^[1] Looking for common treatments or available drugs that might help treat COVID is an important and valuable thing to do. The early reports however are only hypothesis generating and not proof that they work. It should not be a surprise that most of these agents didn’t end up showing benefit in properly conducted, randomized controlled trials. The problem often is that the beneficial effect is too small to be relevant, or the effect occurs only at doses that prove toxic. This has become complicated by a few key reports that have subsequently been found to be fraudulent (included made up patients.) ^[2]We were all eager to have hydroxychloroquine, ivermectin, diphenhydramine or whatever treatment work. There is just no convincing evidence that they do.

Vaccine Risks. Are the vaccines perfectly safe? I think it depends on how you ask the question. The short answer is that by and large the vaccines are quite safe.  The rates of serious adverse events have been exceedingly low despite very intensive tracking to monitor for such events.  To date over 425 million doses have been administered. Out of the population who have been vaccinated, the number of deaths that have been reported has been 0.002% or 0.02 persons/thousand.^[3]  To compare this to the general population, the rate of death in the US is 8.7 persons / thousand per year.^[4]

The longer answer is that nothing in life is perfectly safe. Everything is a balance of risk and benefit.

Many don’t like the idea of introducing a foreign substance (antigen) into their body intentionally. Just to be clear, the mRNA part is not really the concern. The mRNA just causes your body to manufacture the spike protein. The concern is always with what could happen as a result of your body’s immune response to the spike protein. The immune system is very complicated. It is involved in fighting off infections (bacterial, viral, fungal) and even in fighting off cancer. On the one hand, if the immune system is too weak, you can get infections or even be more prone to cancer. We deal with this risk all the time with our immune suppressing medicines we must use for transplant. On the other hand, if the immune system is overactivated, it can cause the body to attack itself.  

So far, the risk of the vaccines appears to be low (not zero, but low). Many are concerned that we just don’t know what can or will happen in the next 20-30 years. The honest answer is that they are right. We don’t know nor do we have a way to know. In a perfect world you wouldn’t have to have any foreign substances enter your body. We are nowhere close to living in a perfect world at the moment. The odds are very high based on community prevalence and the persistence of the pandemic that if you are not vaccinated you will eventually get COVID. And if you get COVID 19 your body is going to be exposed to an enormous and very high level of not just the spike protein but all sorts of antigens that are part of the SARS-CoV-2 virus. That exposure in my opinion is far more concerning than the exposure that comes from the vaccine. We are already seeing a lot of concerning conditions that seem to be a result of having had COVID 19 including the poorly understood “long-haul COVID” syndrome. We will have a lot to learn in the next 20 years.

Let me share an example related to the heart: Myocarditis. Myocarditis is a condition where the heart becomes inflamed or injured as a result of the immune response. The SARS-CoV-2 virus enters the cells by the ACE2 receptor which is highly expressed in the heart and blood vessels. It is therefore important to look to see if the immune response to the vaccine can cause heart inflammation. There were a couple of reports earlier this year that noted myocarditis after mRNA COVID vaccines.^[5] This has fortunately been reported to be very infrequent (occurs in only about 2 out of every 100,000 persons or 0.002%.) In adolescent males, for uncertain reasons, the figure is higher at about 6 per 100,000 persons. Fortunately, the vast majority of these cases have been brief, mild, and with rapid recovery. 

If we compare that, however, to the risk of myocarditis from getting COVID, while the risk is also rare it is much higher at about 150 out of 100,000.^[6]  This means that the risk of myocarditis from the vaccine is about 75x lower than the risk of myocarditis from getting COVID. Ideally, we would be able to not have either. If we could be confident that every person would not get COVID, we would not want to take the risk of the vaccine. Unfortunately, however, there is a real, large and tangible risk that the unvaccinated are going to get COVID. This means that the decision is straightforward. The risk of the vaccine in regard to myocarditis is tiny compared to the risk of getting COVID, even in the higher risk group of adolescent males. 

This does not even take into consideration the other tangible risks from getting COVID. From the data that we have to present, the risk of a serious complication from a COVID vaccine is much less than the odds of getting COVID and having a complication or dying. When it comes to a risk vs. benefit calculation the odds are strongly in favor of vaccination.

Why are people who have been vaccinated still getting ill from COVID? Does this mean that the vaccine is not working?  The vaccines have shown significant benefit. The answer, however, is more complicated than a simple answer.  Last week our health system reported the vaccination statistics. Unvaccinated patients account for 86% of the patients with COVID requiring hospitalization, 90% of the COVID patients in the ICU, and 97% of the COVID patients requiring a ventilator. On average, patients who are vaccinated who get hospitalized with COVID are older with 2 more comorbid medical conditions than those who are not vaccinated. 

This means that the current surge is mostly a surge of the unvaccinated. It is a moral challenge and a source of frustration with our ICU teams. The vast (97%) majority of patients dying in the ICU are unvaccinated. Many of these persons were alive and well and healthy as soon as 1 week prior. There are a few breakthrough cases of vaccinated patients getting very ill. These patients however are generally persons with a lot of other health conditions. 

We are used to sick people getting sicker. We see patients get pneumonia or influenza and die when they have other conditions. It is really hard to see someone who was healthy get suddenly ill. Often I find myself thinking about how a week before they were out working in their yards or going to their jobs and now they are dead. It makes it even harder to think that this might have been prevented if they had been vaccinated.

Vaccines are not perfect. They provide an advantage to your immune system so that when you are exposed to the virus you are less likely to become infected. If the virus is able to get around your immune response and you do get infected, your immune system is able to fight it off sooner so that you should have a milder illness. We wish the vaccines were perfect and you could be impervious and never get infected. That is just not possible and is just not reality. It doesn’t mean that they don’t work. It just means that they may not work as well as you or I would wish they did.

If your favorite football team is going to be competing against a hard team, you would hope that they would prepare for the fight. Going into the Michigan / Ohio State game, I am assuming (and hoping) that the Michigan coaching staff and team members have been looking in depth at the Ohio State games. I want them to be know the usual plays and ways that they have been successful. I want them to be preparing a defense against what Ohio State has done to other teams with their offense. I want them also to have an offense that can get around the ways that Ohio State has shut down other teams.

They could just walk into the game blind. They could decide to not look at film clips or study or prepare. Even if they prepare there is no guarantee that they will win. But they have a much better chance if they do. They can look at a set up and it will trigger a memory, “I know that play. We have seen this before. We can defend against that.”

In the gamble of life that is COVID 19, the vaccine gives you a much better chance.

Do the vaccines really prevent infections, or do they just keep you from getting as sick when you get it?  This is hard to answer in the current state with a delta variant predominance for COVID. Early studies after the mRNA vaccines became available had health care workers who volunteered for weekly testing in order to be able to assess reduction in symptomatic and asymptomatic infections. The rates of both symptomatic and asymptomatic infections dropped significantly shortly after vaccination. Prior to the vaccination the rates of COVID 19 in the health care workers participating in the trial matched the community rates. After vaccination the rates of detected virus on weekly tests showed a sustained and progressive reduction in infection rates in those who were vaccinated. The peak effect occurred 3 weeks after the 2nd vaccination dose and showed a 94% reduction in both symptomatic and asymptomatic infection compared to the rates of symptomatic infections in the community.^[7]  

As time has gone by and the delta variant has become predominant, the degree of protection has become less from the vaccines. There has however been no signal to suggest the vaccines only protect against symptoms. The data that is available suggest that the vaccines reduce infections, symptoms, and serious illness.  

Booster Data: Going back to my football analogy, it is not enough to have studied the Ohio State plays 6 months ago. You must continually be looking and studying and preparing. Your immune response weakens the further out you get from the vaccine (or from having had COVID). Fortunately, the Pfizer booster study data looks very good. The Pfizer trial studied > 10000 patients randomized to a booster dose or placebo who were 6 months or greater after their first series of shots.^[8] The booster shots were well tolerated with a small percent having minor symptoms (transient fatigue or achiness). Serious adverse events (SAEs) were very rare and were actually more common in the placebo group than the treatment group (0.48% vs 0.32%).^[9] COVID was detected in 6 patients who received the booster and 123 who received the placebo. This is a significant 95.3% reduction in odds of getting COVID in persons who got the booster shot compared to those who got the placebo. The benefit happened quickly with the incidence curves separating 7 days after the vaccination.

Why are we having such a big surge now?  The answers are not completely clear but likely reflect two factors: (1) Relaxed social distancing and (2) the predominance of the more highly infectious delta variant.  We easily forget but November 2020 was a different world than what we are living in now. Remember the Michigan restaurant restrictions were not lifted until June 2021. Many schools and jobs were virtual. Social events and concerts were unheard of. If you scroll through your Facebook or Instagram feed, look at the difference between November 2020 and November 2021 in regard to masks and social distancing. The contrast is real and significant. In my opinion this is the driver of the surge. We are all tired and fed up with COVID and because of it we have let down our guard. We are paying for it with a much higher number of cases.

Will this ever end? The honest answer is that no one knows. There is a snowball effect. If community prevalence goes up, more people get COVID and community prevalence goes even higher. The opposite can become true, however. If the cases begin to drop then your odds of being exposed go down and the community prevalence goes down further. Cases can go down through any of the following: (1) Enough people get COVID to have a degree of immunity, (2) Enough people get vaccinated to not get infected or if they do become infected, they tend to shed virus for a shorter period of time, or (3) Social distancing goes up.  Christmas vacation may help (school age children not being exposed at school). Warm weather also helps (people tend to be outside which reduces the risk of transmission.)  I am dreaming of a day where these forces have become enough that community prevalence drops so low that COVID is only a small or infrequent thing.

Conclusions:

• COVID is bad. I don’t like it.
• The vaccines work. The booster data looks really good.
• Vaccine risks are much smaller than the risks to you and your body from getting COVID 19.
• I wish we didn’t have to deal with any of it. We are all doing our best to navigate our way through it to the best of our ability and our conscience. I am not claiming to be an expert on all things COVID. This is my personal effort to navigate my own way through it.
• There is still a lot we don’t know. We have good things coming including promising new vaccines and new medications. I hope and pray that they prove to be effective. We have reports of new variants coming. We have no idea if they will amount to a problem or not. None of us know everything. I hope that we can extend a little bit of grace to each other as we try to find our way through this.

---

^[1] https://www.medicinenet.com/script/main/art.asp?articlekey=9877

^[2] https://www.medpagetoday.com/special-reports/exclusives/93658

^[3] https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html

^[4] https://data.worldbank.org/indicator/SP.DYN.CDRT.IN?locations=US

^[5] https://www.nature.com/articles/d41586-021-02740-y

^[6] https://www.cdc.gov/mmwr/volumes/70/wr/mm7035e5.htm

^[7] https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781727

^[8] https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-11-19/02-COVID-Perez-508.pdf

^[9] The SAEs with the vaccine each had explanations by other conditions the patients had and each resolved quickly without long term sequelae, similar to the placebo group. It is important to always have a placebo group because in any large group of persons, illnesses or events are going to happen that are completely unrelated to the study.