Medical Math: Covid-19 x 2 = 0 Vaccine

The White House recently announced that it will be promoting an expedited evaluation of a Covid-19 vaccine. This would be good news if, in fact, it resulted in a safe and effective vaccine in the near future. We certainly can have a vaccine before November 2020, if safety and efficacy are not deemed important. 

We have had many vaccines for HIV, the virus that causes AIDS, over the past 30 years, but none of them has proved safe and effective. The government decides if a vaccine is ready for distribution, and a widespread concern in the medical community is that the legitimate need for a vaccine against Covid-19 will lead to the release of a vaccine with no value. 

That the development of a safe and effective vaccine can be accomplished is uncertain for a variety of reasons. The most worrisome that recently appeared is the development of a recurrent infection in individuals who recently recovered from Covid-19 infections. In both China and the United States there are rare but well-documented cases of Covid-19 in individuals who were symptomatic for the disease and who appeared to have fully recovered and then developed the disease again within a few months and were again symptomatic.

The explanation for this phenomenon currently being publicized is that a slightly different strain of this virus reinfected these individuals. This is bad news in two respects:  first, it suggests that having the virus does not provide protection against a slightly different strain of the virus, and second, the mere fact that there has appeared another strain of the virus itself suggests the development of a vaccine may be frustrated by variability in the Covid-19 virus. This variability is what has frustrated the development of an effective vaccine against HIV for several decades.

Viruses are in fact just pieces of misinformation. They have genetic material (the information) wrapped up in a covering (viral coat) that can attach to cells in the human body and allow the genetic material in the virus to invade the human cell. This bit of genetic material takes over the infected cells machinery to create innumerable copies of the virus with its covering. This is not a living organism as is the case with bacteria, fungi, parasites and other such diseases of humans. This is merely misinformation that can get into human cells and wreak havoc. In the case of Covid-19, the effect is lethal in some individuals, and it is often transmitted to other individuals before it produces any signs of disease in the initially infected individual.

Why it is more lethal in elderly individuals is still unclear, but the current thinking is that the immune system, the body’s defense against all types of invaders, in the elderly is less equipped to fight off the virus than the immune system in younger individuals. Fundamentally the view is that the immune system degenerates with age, which is somewhat counterintuitive since much of the immune system’s ability to deal with disease depends upon its memory of exposure to the disease or pieces of the disease. The origin of the term “vaccine” derives from using material similar to the lethal virus to elicit a complete blockade of the virus when the immune system faces it for a second time.

Vaccination was developed at the end of the 18th century in an effort to eradicate another virus, smallpox, and in that case the efforts were entirely successful. Currently the smallpox virus is not known to be active in any area of the world, and the only known copies of the virus are in storage in Russia and the United States. The reason these stores have not been destroyed and the virus effectively eliminated from the face of the earth is justified as a need to do further work with the virus in case it somehow recurs outside of these “secure” locations. 

The vaccine against smallpox was first developed by a physician named Edward Jenner. He and many other physicians and non-physicians noticed that milkmaids appeared to be immune to smallpox despite their exposure to infected individuals. In most of Europe in the 18th century and for several centuries previously, smallpox had caused extensive disease and death. Nobility was at as much risk as commoners with the exception of the milkmaids.

Edward Jenner thought that the development of cowpox by milkmaids was what protected them.  He was correct. Taking pus from a cowpox lesion on a milkmaid’s hand and introducing it by scratches or needle punctures into a healthy individual gave the recipient protection against smallpox. The word “vaccination” itself comes from the Latin term for cow (vacca). 

Vaccination was established as an effective way of dealing with smallpox even though there was no knowledge of how the protection occurred. We currently understand that exposure to a closely related virus in some diseases, such as smallpox, enables the immune system to develop defenses against the actual virus being targeted. Unfortunately this has not succeeded in some of the most severe diseases with which we must currently deal. 

The most frustrating case to do date has been with the immunodeficiency virus HIV. Attempts to develop a vaccine against this deadly disease started nearly 40 years ago and have been frustrated by the variability of the external coat of the virus. From the very beginning of efforts to develop a vaccine, the appearance of various strains of the virus interfered with development of a vaccine. With the appearance of another strain of Covid-19 one must necessarily worry that this virus will also have a variability that will frustrate the development of a vaccine. This means that more than one Covid-19 strain may result in 0 effective vaccines. 

Hopefully this will not be the case, but mandating that the development of a vaccine for Covid-19 be expedited simply ignores the experience with vaccine developments. Essential elements of the development process include looking at the long-term effects of the vaccine, both in terms of its effectiveness and possible side effects. The widespread notion that vaccines cause autism is nonsense, but that a vaccine can result in problems of its own is certainly true unless the vaccine has been observed in a well-controlled population for a substantial amount of time. 

One might ask what could be the risk of widespread inoculation of the general population with the first vaccine developed against the virus, and the answer is quite simple. It may make individuals susceptible to complications of the vaccine while providing only temporary or no protection against the virus. The math cannot be ignored. There must be a large number of people treated in a highly controlled situation in order to get any insight into whether or not the vaccine is safe and effective. 

Viruses themselves complicate the development of the vaccine by their changeability and their variable effects in different populations. It is worth remembering that measles virus has at various times in history been highly lethal in some populations and relatively benign in others. This means that the variability in the virus itself can mislead investigators into believing they have developed something highly effective that is not effective at all but rather reflects temporary changes in the mortality rate associated with transient changes in the virus. 

Although the current death count directly caused by Covid-19 in the United States exceeds 195,000, the number of established infections in people who were not killed or were largely or completely asymptomatic exceeds several million. This means that the mortality rate in the general population is relatively small considering the mortality associated with other viruses, such as Ebola.

However, the late effects of what appears to have been a transient illness must be a concern. That you recovered from Covid-19 does not mean that it no longer poses a threat to you. There is a condition called SSPE that may develop months or years after a measles infection that is in and of itself lethal and appears to be a second bite out of the apple by the virus. 

The bottom line is that expedited vaccine development will not necessarily result in a safe and effective vaccine. It may provide little more than cold comfort to a population terrified by an unpredictable and potentially lethal virus infection. The flu epidemic of 1918 lasted fully three years in the United States and eight years as it traveled around the globe in its pandemic.

There has never been a vaccine developed against that lethal virus. That virus at least had a seasonal quality to its lethality, giving the population a break during summer months and hitting it hardest in the winter. Covid-19 is not seasonal. It may frustrate efforts to allow the development of a safe and effective vaccine, and it may persist as long as or longer than the flu epidemic of 1918, 1919, 1920. Our efforts need to be directed at developing safeguards against this and other potentially lethal viruses. If we are to develop a safe and effective vaccine, we must respect the math and abide by the science.

Dr. Lechtenberg is an Easton resident who graduated from Tufts University and Tufts Medical School in Massachusetts and subsequently trained at The Mount Sinai Hospital and Columbia-Presbyterian Medical Center in Manhattan.  He worked as a neurologist at several New York Hospitals, including Kings County and The Long Island College Hospital, while maintaining a private practice, teaching at SUNY Downstate Medical School, and publishing 15 books on a variety of medical topics. He worked in drug development in the United States, as well as in England, Germany, and France.