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Why Remdesivir and Hydroxychloroquine for COVID-19?

Louis Proyect writes: “I understand the reluctance to put a plus where Trump does, but this article [“How New Jersey’s First Coronavirus Patient Survived,” in the New York Times, ~3 April 2020] indicates that a doctor who was close to death had a miraculous recovery after receiving Remdesivir and Hydroxychloroquine.”

Remdesivir: “Remdesivir (development code GS-5734) is a novel antiviral drug in the class of nucleotide analogs. Remdesivir is an adenosine analogue, which incorporates into nascent viral RNA chains and causes their pre-mature termination. It was developed by Gilead Sciences as a treatment for Ebola virus disease and Marburg virus infections, though it subsequently was found to show antiviral activity against other single stranded RNA viruses such as respiratory syncytial virus, Junin virus, Lassa fever virus, Nipah virus, Hendra virus, and the coronaviruses (including MERS and SARS viruses). It is being studied for SARS-CoV-2 and Henipavirus infections. Based on success against other coronavirus infections, Gilead provided remdesivir to physicians who treated an American patient in Snohomish County, Washington in 2020, who was infected with SARS-CoV-2, and is providing the compound to China to conduct a pair of trials in infected individuals with and without severe symptoms.”

Hydroxychloroquine: “Hydroxychloroquine (HCQ), sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, and porphyria cutanea tarda. It is taken by mouth. It is also being studied as an experimental treatment for coronavirus disease 2019 (COVID-19). Common side effects include vomiting, headache, changes in vision, and muscle weakness. Severe side effects may include allergic reactions. Although all risk cannot be excluded, it remains a treatment for rheumatic disease during pregnancy. Hydroxychloroquine is in the antimalarial and 4-aminoquinoline families of medication. Hydroxychloroquine was approved for medical use in the United States in 1955. It is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system. In 2017, it was the 128th-most-prescribed medication in the United States, with more than five million prescriptions.”

My CONJECTURE (a non-medical person’s hypothesis) is that the SARS-CoV-2 virus (causing COVID-19) may act in a somewhat similar manner to the Epstein-Barr Virus (EBV). If so, this hypothetical (and likely only partial) similarity might lead some doctors treating critically ill COVID-19 patients to administer the drug combination of: the antiviral drug Remdesivir to reduce the viral load, and the anti-malarial drug Hydroxychloroquine to buttress the patient’s immune system, which is assumed to be in a pre-existing weakened condition.

My following description of the Epstein-Barr Virus (EBV) and its several disease-causing effects are drawn from the book The Invisible Invaders, Viruses And The Scientists Who Pursue Them, by Peter Radetsky, (published by Little, Brown and Company, 1991, 1994). Passages quoted from that book are woven into my interpretive discussion, below.

Bone marrow produces a number of kinds of blood cells, including “the B and T lymphocytes, which comprise an essential part of the immune system. Without these disease-fighting cells [we] couldn’t fend off the mildest infection; something as insignificant as the common cold could kill [us].”

The Epstein-Barr Virus is ubiquitous in people (~95%), it invades B lymphocyte cells, but is usually held in check by the human immune system, which produce antibodies to eliminate EBV-infected B lymphocyte cells.

In poor regions with primitive and/or inadequate hygiene (e.g., parts of Africa) children are exposed to EBV early in life (3-4 years) and may only get a mild ‘childhood’ disease of sore throat, cough and flu-like symptoms for a few days, and that’s all. “For some reason, whether because of the immaturity of their B lymphocytes (the cells the Epstein-Barr virus invades) or the immaturity of their immune system as a whole, [most of these] children infected with EBV rarely come down with any kind of obvious illness.” (The EXCEPTION to this will be described further below.) Thereafter, these minimally affected and now recovered children have antibodies to EBV.

In the developed and generally very hygienic countries, children may not be exposed to EBV until much later: adolescence and early adulthood. “But when the virus invades later, the result is usually more severe: a case of mononucleosis. In causing a more serious illness in older people, EBV acts much like other viruses, hepatitis and poliovirus among them. The reason may be that in older individuals the immune system responds inappropriately to infection. In any case, as far as EBV is concerned, at least half of the people belatedly infected with EBV experience significant illness.”

“Mononucleosis is a disease in which blood cells proliferate out of control. Here [is] a virus, EBV, that was first detected in cancer tumors [Burkitt’s lymphoma], and now [has been shown] to be intimately involved in mononucleosis, a common cancer-like disease… Mononucleosis is essentially a disease of developed countries.”

Now for the EXCEPTION.

Denis Burkitt, a Scottish surgeon and physician practicing in Africa during the 1950s and 1960s, first identified the cancer “Burkitt’s lymphoma” in African children, by engaging in a massive study and expedition between 1957 and 1961. In 1963, EBV was isolated by M. Anthony Epstein and Yvonne Barr from specimen tumors sent by Burkitt to London in 1961. If so many African children were exposed to EBV as toddlers with little consequence (and certainly no mononucleosis in early adulthood), why did some of those children develop the specific cancer of Burkitt’s lymphoma?

Obviously, the fundamental factor that can lead to Burkitt’s lymphoma is exposure to and infection by EBV.

The first necessary co-factor to developing Burkitt’s lymphoma is having “been exposed to an unusually heavy dose of the [EBV] virus.”

The second necessary co-factor to developing Burkitt’s lymphoma is “a weakened immune system.”

“It has been suggested…that Burkitt’s lymphoma arises as a result of immunological disorders in children exposed since early infancy to heavy malarial infection.” [Guy de Thé, 1978].

The fact that infection with EBV in an individual with a weak immune system can lead to cancer was proved by the case of David, “The Bubble Boy.” David was born with no immune system and lived in the sterile interior of a plastic bubble (a tent). In 1983, he was given a bone marrow transplant from his healthy sister, but he died in 1984 at the age of 12. The cause of death was cancer, “the B cells that David had obtained through the bone marrow transplant had run amok. He died of cancer of the B lymphocytes, with tumors similar to Burkitt’s lymphoma. All the cancer cells contained Epstein-Barr virus. [David’s] sister had at some point been exposed without harm to EBV; she passed on this otherwise harmless dose to David through her bone marrow.”

Epstein-Barr virus causes a very broad stimulation of B-cell growth. Out of that a tumor can develop if given “some kind of other agent that compromises the immune system… In the case of Burkitt’s lymphoma, that agent is almost certainly malaria.”

Guy de Thé [1984]: “We know that very early viral infection can lead to Burkitt’s lymphoma. It’s a situation exactly like [that of] cigarette smoking and lung cancer. You don’t fully understand the mechanism, but you can measure the risk. Very heavy and early exposure to EBV is as though you were smoking all your life, two packs a day. Then malaria enters at the second level, by promoting further proliferation of the B cells infected with EBV. We’re all infected by EBV, but nothing happens to most of us because our immune system controls the infected B cells. Malaria specifically depresses the part of the immune system whose job it is to control the B cells. And after that, something, possibly a chance event, induced by nobody knows what, causes a change in chromosomes that transforms the cell into a tumor cell.”

Now, recall the CONJECTURE. Hypothetically, a similarity of causes exists between:

— the cause of serious COVID-19 illness and death (by the SARS-CoV-2 virus, plus an assumed immunodeficiency co-factor), and

— the cause of Burkitt’s lymphoma, as well David “Bubble Boy’s” cancer of the B lymphocytes (by the Epstein-Barr virus, plus an immunodeficiency co-factor; which for Burkitt’s lymphoma is malaria, and for David was a complete lack of an immune system).

Some doctors working under the stress of trying to save dying people during the explosive growth of this current COVID-19 pandemic, and who may have made conjectures about causes similar to the one stated here, arrived at the drug cocktail of:

— Remdesivir, to try a direct reduction the SARS-CoV-2 viral load in the patient’s respiratory tissues; and

— Hydroxychloroquine, to buttress an assumed immunodeficiency — as with malaria — of inadequate control of B lymphocyte cells presumably infected with the virus.

So much for my amateur speculations on the Remdesivir plus Hydroxychloroquine cocktail administered to some COVID-19 patients.

What I can see clearly as fact is that doctors and virologists are in a frantic race against death (within days to a couple of weeks for the unlucky patients), to save as many COVID-19 stricken as they can, while yet having incomplete knowledge about the mechanism, and its unknown associated co-factors, by which the SARS-CoV-2 virus actually causes fatalities. Also, they are simultaneously trying to ascertain the details of both the progression of infection and the nature of all associated co-factors that aggravate the disease to the point of fatality, so as to then be able to design drugs that cure COVID-19, and vaccines that can prevent people from developing the disease if exposed to the virus.

Both as individuals and as a society we should be very grateful to the medical people working so furiously — and for many at great personal risk — on COVID-19 today, and on all the as yet little-known and untamed viruses that might infect us in the future; and we should support their work fully (politically and financially) as a matter of public health national policy. “Public” as in Medicare-For-All, and as in drug and vaccine development that is as much a publicly funded and owned service, rather than only a for-profit exploitation of human need by a mercenary pharmaceutical industry.

Acknowledgement: I want to thank Gretchen Hennig for giving me a copy of Radetsky’s book, and for explaining the concept of “viral load” to me.

 

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Manuel Garcia Jr, once a physicist, is now a lazy househusband who writes out his analyses of physical or societal problems or interactions. He can be reached at mangogarcia@att.net

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