Coronavirus news & views

HIV And Coronaviruses: A Bad Combo

Africa is the continent least vaccinated for COVID-19 and it also has been where several CoV-2 variants have arisen: Beta in South Africa, most recently C.1.2 (not yet given a Greek letter designation) also from South Africa, and Eta in Nigeria. A possible reason for the appearance of these variants is because Africa is also home to the most immunocompromised people. HIV is common in Africa and tuberculosis is rampant on the continent.

One HIV-positive woman in South Africa was reported to carry active CoV-2 infection for 216 days, during which time it mutated 30 times according to Tulio de Oliveira, who runs gene-sequencing centers at two South African universities. This is concerning since South Africa has the world’s largest HIV epidemic. It is estimated to have 8.2 million people infected with HIV. While most of these take antiretroviral drugs, which keep the virus at bay, many do not. And neighboring countries, Botswana, Zimbabwe, and Eswatini also have very high HIV infection rates. The burden of HIV, TB and other chronic diseases is higher in these countries than in other countries around the world due to extreme poverty and poor health care for millions of Africans. When these people also become infected with CoV-2, they grow and shed the virus longer than someone with a good immune system and good health care. That means that the virus has longer to mutate in an infected, immunocompromised person.

In wealthier countries in the West, a rich debate is ongoing about whether to add another shot (booster) to already vaccinated people. One of the biggest arguments against this is that those booster vaccines are needed much more in poorer, and woefully under-vaccinated countries, such as those in Africa. The concern is that our boosters come at the expense of basic immunization of these impoverished countries, which facilitates the generation of troublesome viral variants. On the other hand, if CoV-2 is running rampant because the health care infrastructure in these countries is not up to delivering those vaccines, maybe it would be better making sure that richer countries are as protected as possible.

These are the proverbial two horns of a dilemma. Which horn would you choose?

Great News On The CoV-2 Vaccine Front

The news: Pharma giant, Pfizer, and its German biotech partner, BioNTech, just announced that preliminary indications show that its two-shot anti-CoV-2 vaccine is 90% effective in preventing infection. The study is not yet complete, meaning that this is based on what is called interim data analysis. All large scale clinical trials schedule such interim analysis in order to detect potential problems with the study such as potential side effects, enrollment problems, and to make a preliminary assessment on the trial's outcomes. The review is done by a Data and Safety Monitoring Board (DSMB), an independent panel of scientists and statisticians who are not part of the study. Using an independent DSMB allows study personnel to remain blinded as the trial proceeds.

In this case, the interim review of data by the DSMB compared the number of subjects in the placebo control group who became infected to the number of infected subjects who received both vaccine doses. This showed that vaccinated subjects were 90% less likely to be infected. The interim analysis also showed negligible adverse effects in the group who received the vaccine. While still preliminary, these results are encouraging. The study will continue over the next couple of months and even beyond in order to learn how long the immunity lasts and how effective it is in different populations including the elderly and other high risk groups. There seems to be a good chance that final approval will come around the end of year and vaccinations begin shortly after that.

Pfizer began manufacturing the vaccine a few months ago so that they would have a stockpile ready to distribute as soon as FDA approval comes. While this eliminates the usual post-approval delay to ramp up production capability, this strategy is a major gamble for the company since it is not guaranteed that the vaccine would be approved. If the vaccine does not pan out, the company will have to eat the cost for manufacturing a useless vaccine. On the other hand, if the vax is approved, Pfizer is poised to immediately deliver hundreds of millions of doses while their production efforts continue.

This is the first RNA vaccine tested in humans. The potential advantage of this approach is that it completely avoids using the virus itself. “Old fashioned,” vaccines required growing the virus in mass quantities and then crippling or killing it for injection, which is labor intensive, entails certain risks, and is expensive. Instead, the Pfizer vaccine involves cloning part of the genome that is thought to be a target for the immune system, packaging it in an inert lipid nanoparticle, and injecting it in order to aggravate the immune system. The idea is that this fragment of the viral genome will be taken up by human cells and the cellular machinery will use it to produce the viral protein that can stimulate an immune response in the absence of the virus itself. The cells will soon degrade the cloned RNA fragment leaving only immunological memory with which to fight reinfection.

What is next? While this is encouraging news, this brings us to perhaps a larger problem to solve, which is how the early vaccine will be most effectively and fairly distributed. By the end of the year, Pfizer will have a few hundred million doses and predicts it can produce 1.3 billion doses in 2021. Since this is a two-dose vaccine, that means that that will be enough to vaccinate about 650 million people, or less than 10% of the 7.8 billion who live in the world. Who will have priority for the first doses of the vaccine? Will front line health care workers and high risk people be given the first doses? What about world-wide distribution? Since the vaccine is being tested and made by an American company (Pfizer) using technology developed by a German biotech (BioNTech), should those two countries reap the immediate benefit of the early limited doses of vaccine, while the rest of the world waits months for sufficient doses of the vax to meet their needs?

The WHO recommends that the vax be distributed to each country based on its population. Another recommendation from the National Academies of Sciences, Engineering, and Medicine is to distribute it based on each country's number of health care workers and high risk populations. Others argue that the US should base distribution on racial and socioeconomic disparities. U Penn doctor and medical ethicist, Ezekiel Emanuel (a primary author of Obamacare), proposed a Fair Priority Model that would favor countries with younger populations, weaker economies, and with poor health access--in other words, third world countries.

These suggestions seem moot since advanced purchase agreements already give 80% of that early vax supply to the US, UK, Canada, and Japan.

Another issue regarding distribution is that the vaccine needs to be stored and transported in ultra-cold conditions (-80 degree C. or -112 degrees F.). Such ultra-cold storage facilities are in short supply around the world, meaning that countries with poor health infrastructure will be at a significant disadvantage because they cannot store the vaccine. This ultra-cold storage requirement will also make it challenging for the vax to be administered in a normal doctor’s office or pharmacy, which typically do not have ultra-cold freezers. 

Logistics: Once the vaccine is approved, the enormous task of getting billions of doses distributed across the US and around the world begins. This is where Trump’s Operation Warp Speed comes into to play. Even though the Pfizer vaccine was not developed under that program, the logistics of its distribution will be part of Warp Speed, which also includes massive pre-planning for storing, distributing, and delivering two doses of the vaccine ultimately to 300 million Americans. The US Army Materiel Command, headed by four star general Gus Perna, has been tapped for this undertaking. He is the one who sees that American military forces around the globe have sufficient housing, clothing, food, and beer. So, he seems like a good choice to oversee the distribution of billions of doses of a vaccine. You can see more about this on the Nov 8 episode of 60 Minutes. The logistics and planning for this almost makes the development of the new vaccine a trivial issue.

There is joke that goes something like this: Hell is where the English are the cooks, Italians the managers, and Americans the soccer lovers. Heaven is where the English are the soccer lovers, Italians the cooks and Americans the managers. This is a good example of American large-scale management, so we must be in heaven.

Refusing To Treat COVID Patients Based On “Quality Of Life” Determinations

FYI: While your humble blogger earned a PhD in viral immunology from the University of Texas, and spent most of his career investigating the causes and cures of leukemia at UCLA and the University of Wisconsin, he also was trained in ethics at Indiana University, the University of Montana, and Calvin College. He taught bioethics and research ethics at the U of W. His closet hooks are full of different hats.

Biomedicine is rife with ethical conundrums, a few of which already have been mentioned in these pages about the coronavirus pandemic, to wit: Should we wave inspection of vaccine manufacturing facilities and risk production mistakes in order to speed release of a CoV-2 vaccine, which will save lives? Or, whose rights do we ignore during a pandemic—the freedom to live as we choose vs the freedom to remain free of infection? Or, do we abandon all social restrictions in attempt to achieve herd immunity via natural infection, realizing that we would be sacrificing many to the disease? All, conundrums, indeed.

Ethical dilemmas entail at least two conflicting choices, neither of which is perfectly good nor perfectly bad. That is why these problems are often referred to as “horns of a dilemma.” Which horn should we embrace, and which should we avoid, knowing that both can stick us?

An ethical dilemma has arisen in healthcare circles, but for which the popular press has largely been silent. This issue is about how “quality of life” factors into health care decisions for COVID-19 patients. The following example of how this ethical conundrum can play out is excerpted and modified from the journal, First Things.

A man, Michael, was refused treatment for COVID-19 because the hospital he was admitted to and State bureaucrats believed that he did not enjoy sufficient quality of life to warrant curative treatment for the disease. In 2017, Michael had a heart attack that caused brain damage leaving him a quadriplegic and suffering frequent seizures. But he was conscious, able to do simple math calculations, answer trivia questions, and interact with his family. Then, in late Spring of 2020, he caught COVID-19 and was hospitalized. The hospital decided to withhold his tube feeding despite the objections of his wife, and the fact that he had a fair chance of surviving if provided with appropriate COVID treatment and sustenance care. He died on June 11.

He was denied care because his doctors determined that he did not have a sufficient “quality of life” to justify treatment. Because of his disabilities, saving his life was deemed “futile.” The medical team and the “State,” through a court appointed guardian, reasoned that treatment for COVID-19 would not improve the quality of his life (meaning, he would remain quadriplegic and cognitively disabled if he survived the disease); therefore, they decided to end all treatment care except hospice comfort care.

His wife, Melissa, had been appointed Michael’s temporary guardian, but she was in a legal struggle with Michael’s sister over his custody, a dispute that predated Michael’s hospitalization. Family Eldercare, a nonprofit agency, was then appointed interim guardian until a final decision could be made about permanent guardianship. Hospital doctors convinced Family Eldercare to approve Michael’s transfer to hospice care where he would only receive palliative care and not curative or sustenance care. Michael died of pneumonia after six days on hospice; the withdrawal of nutrition and hydration having no doubt weakened his body’s ability to fight disease. Even without pneumonia, Michael would have soon died of dehydration.

Melissa recorded her conversation with an unnamed physician and posted it on YouTube so we can all hear for ourselves.  Here’s the substance of the conversation from the YouTube transcript, with my commentary.

Doctor: At this point, the decision is, do we want to be extremely aggressive with his care or do we feel like this will be futile? And the big question of futility is one that we always question. The issue is: Will this help him improve the quality of life, will this help him improve anything, will it ultimately change the outcome? And the thought is the answer is no to all of those.

Melissa: What would make you say no to all of those?

Doctor: As of right now the quality of life, he doesn’t have much of one.

Melissa: What do you mean? Because he was paralyzed with a brain injury, he doesn’t have a quality of life?

Doctor: Correct

My Comment: The doctor did not base his decision about Michal’s medical care on the illness for which he was hospitalized, but on his unrelated disability. This is a classic example of applying the invidious “quality of life” ethic, which deems people with disabilities, the elderly, the chronically ill, and the dying to have a lower worth than the healthy, able-bodied, and young. Back to the conversation…

Melissa: Who gets to make that decision whether somebody’s quality of life, if they have a disability that their quality of life is not good?

Doctor: Well, it’s definitely not me. I don’t make that decision. However, will it affect his quality, will it improve his quality of life, and the answer is no.

My Comment: After denying that he had any part in determining Michael’s quality of life, the Doctor then admits that he believes that Michael’s quality of life is negligible. By doing so, he is being duplicitous regarding his role in the decision, and he is not acting as Michael’s doctor, beholden to the Hippocratic Oath he took. Rather, he is acting as an agent for the hospital and State bureaucracies rather than acting in Michael’s interest, a dramatic violation of the Oath he took. Back to the conversation…

Melissa: Why wouldn’t it? Being able to live isn’t improving the quality of life?

Doctor: There’s no improvement with being intubated, with a bunch of lines and tubes in your body and being on a ventilator for more than two weeks. Each of our people here have COVID and they are in respiratory failure. They’ve been here for more than two weeks.

Comment: The Doctor again makes a statement of his opinion of Michael’s quality of life. He admits that many of their OOVID patients are in respiratory failure and on ventilators, but implies that they are more valuable than Michael and deserve such therapy, while Michael does not.

 Melissa: So the fact that you are killing someone doesn’t make sense in your mind?

Doctor: We don’t think it’s killing. Because I don’t know when or not if he will die. But at this point I don’t think it would be humane or compassionate to put a breathing tube in this man and do the lines and the tubes and all that stuff because I don’t think it will benefit him.

Melissa: And I totally agree with you on the intubation part of it. I don’t want him intubated. But I also don’t think you should just sit him somewhere to be comfortable until he finally just drifts away. That to me is futile too. That’s saying you’re not trying to save someone’s life. You’re just watching them go. The ship is sailing. I mean that just doesn’t make any sense to me to not try. I don’t get that part. I don’t like that part.

Doctor: But what I’m going to tell you is that this is the decision between the medical community and the State.

Melissa: And the State. Forget about his wife and his family and his five kids.

Doctor: I have nothing to do with that.

The recording ends there. 

At first blush, it might seem like a reasonable decision to withhold essential care from someone as damaged as Michael was, but what if we change the selection criteria from “quality of life” to “preciousness of life?” Wasn’t his life as precious as everybody else’s, especially to his family? It was not, according to Michael's doctors and faceless bureaucrats in his State who had never met him, all of whom believed that they could better judge Michael’s worth better than his family could. And, what about Michael’s wishes? The article did not indicate whether, after his hospitalization, he was able to express his desires in the matter, but I will assume he was incapable of doing so. In which case, the medical ethicist must look at Michael’s family as well as his life near the time he was hospitalized. Before catching COVID-19, were his actions consistent with someone who wanted to live, even with his disabilities? Even if a hospitalized patient cannot communicate, it is still possible to divine his wishes from the period before he became, possibly temporarily, non-communicative due to the disease. That divination is more relevant than faceless bureaucrats when making life and death decisions for him.

This is the great ethical problem of quality of life decisions being made by impersonal, anonymous administrators who can overrule the wishes of a patient’s immediate family and even the demonstrated wishes of the patient. The bottom line is to make sure you have your final wishes legally documented and use power of attorney to put your fate in the hands of highly trusted family or friends.

Even then, you still might encounter faceless bureaucrats making life and death decisions for you based on how they judge the quality of your life.

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