Learning From History

The televangelist, Pat Robertson, called the AIDS epidemic, “God’s harvest of sinners.” The sinners he was referring to were not rapists, murderers, pedophiles or human traffickers. They were homosexual men. This reflected the common feeling in the United States that AIDS would somehow disappear as the target population died off. But to the general public’s surprise, the epidemic spread beyond the gay community and started having a lethal effect on intravenous drug users. 

This still aroused no concern in the general population because little sympathy was felt for people seen as being self-destructive and making the choice to risk their lives to feed their addictions. This philosophy revealed itself as nonsense when a population of children became heavily infected. These were not sexually abused children or the offspring of drug addicts. They were children with hemophilia, a genetically determined bleeding disorder.

There was not only concern for this population but questions as to how they became infected. What they were exposed to was clotting factors transfused into their bloodstreams to keep them from bleeding to death. What most of the nonmedical and much of the medical population did not realize was that clotting factors for these treatments were collected from pooled blood. 

In other words, the amount of clotting factor in one unit of donated blood was not nearly sufficient to manage the bleeding tendencies of one hemophiliac child or adult. In fact, the clotting factors needed for one hemophiliac person had to be pooled from dozens, if not, in fact, hundreds, of donors. At that point in the AIDS epidemic, there was no reliable test to screen for the virus which proved to be the cause of the disease.

That brings us to the current dilemma of using plasma from individuals who have recovered from coronavirus disease-2019 or the so-called Covid-19. The general misconception is that blood can be taken from a person that has recovered from the disease, and the antibodies, bits of protein manufactured by the immune system to fight the virus, in that blood can be given to an individual struggling to survive the disease, and the antibodies in the survivor’s blood will help rescue the individual dying from the Covid-19 infection. 

In fact, the amount of antibody against anything in any unit of blood is quite small and to get a dose of antibody that even theoretically would make a difference in the management of an individual dying from Covid-19 would require the pooling of the blood fraction with the antibodies from numerous individuals.

The HIV virus may have been in only one of dozens of blood units pooled to extract clotting factors to treat hemophiliac patients, but the presence of even one tainted fraction of blood was enough to seal the fate of the person receiving this treatment. Without the treatment, many would die from the clotting disorder, and with the treatment, most would die from AIDS.

The use of antibody treatment has been in effect in the United States for several decades and is routinely referred to as intravenous immunoglobulin or IVIG treatment. It is used in a variety of presumably immune disorders and has been demonstrated to be helpful in managing signs and symptoms in the clinical course of some individuals. The problems with IVIG given to people with Covid-19 are much the same as they were with the use of clotting factors given to hemophiliacs. 

Specifically, the antibody dose must be pooled from dozens and sometimes hundreds of samples of donated blood. These samples are routinely screened for a variety of infectious diseases, including various forms of hepatitis, HIV, syphilis, and other potentially lethal infections. This means that if even one of the donors is carrying a potentially crippling or lethal disease and for whatever reason, it is not detected by screening techniques, that disease may be transmitted to the recipient of the antibodies.

Antibodies are materials made by the body to fight off various diseases, including viral infections, such as Covid-19. Unfortunately in many individuals who produce the antibodies, the desired effect is not sufficient to prevent their death. There remain numerous questions about the administration of this blood product. 

One obvious question is: Does it work? Another question is: Is it safe? The Food and Drug Administration (FDA) of the federal government has standard protocols for determining safety first and efficacy second. That intravenous antibody administration (IVIG) is safe for most people has been established. That the injection of antibodies from an individual who has recovered from Covid-19 is safe remains to be determined. 

This may seem like a contradiction, but commercially available IVIG is collected from healthy individuals with no recent history of a life-threatening viral illness. The Covid-19 infected (and recovered) population is not the same as the population routinely used for the collection of IVIG antibodies.

Additionally, it remains to be determined if, in fact, this somewhat risky treatment is effective. One obviously does not want to administer a treatment that makes the situation worse. There are numerous examples of treatments that were hailed as breakthroughs on the basis of anecdotes and observations that proved to not only be ineffective but detrimental to the individuals being treated. A case in point was the administration of high dose steroids to individuals with a progressive paralyzing disease of the nervous system called Guillain-Barre syndrome. 

This was accepted for decades as effective treatment until somebody reported that the outcome without giving steroids was not substantially different from that with giving steroids, except for the numerous side effects induced by the steroids. These side effects included cataracts, thinning of bones, high blood pressure and problems with sugar control. Further investigations comparing the administration of high dose steroids in this disease to the administration of an ineffective material called a placebo proved that giving the steroids resulted in a substantially worse outcome than not giving the steroids.

As of the first week of August 2020, the FDA indicated that it did not have enough information on the trials being run to determine the safety and efficacy of the antibodies collected from people surviving Covid-19 and administered to the people suffering from Covid-19. Under considerable pressure from various agencies and individuals, the FDA announced two weeks later that it was comfortable allowing the use of this material on an emergency basis.

Notwithstanding the fact that its usefulness had yet to be proven, the inevitable shortage of the material necessarily would result in individuals on long-term treatment with IVIG to find their supplies unavailable, as was the case with hydroxychloroquine for people who had used it to manage their lupus, a life-threatening disease affecting numerous different organs, including in the kidneys, when there was enthusiasm for this material as a possible treatment for Covid-19. 

Additionally, the cost for IVIG has routinely been prohibitive. The cost of the pooled antibody treatment from a highly select population will necessarily be even more prohibitive. IVIG treatments currently cost several thousands of dollars and that is using that treatment in situations where the appropriate dose and duration of the treatment have been established. No such guidelines have been provided for the pooled antibody material from individuals recovering from Covid-19.

Once this material is in general use, the cost to the nation as a whole will quickly reach into the billions of dollars, and although that cost is justifiable if it provides benefit, it is not justifiable if in fact it does not improve the survival or shorten the duration of illness in individuals suffering from Covid-19. The results of studies underway have not established the longterm safety or the short-term benefit of this antibody treatment. 

Without the benefit of the usual investigations provided by the FDA to approve a treatment, we face the risk as a nation of depriving individuals who need IVIG of this material. We run the risk of incurring an additional debt associated with this pandemic without getting any value for our investment, and most disturbing of all we run the risk of making a horrible situation worse by mismanaging individuals with a disease we don’t understand.

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.

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