(ASIDE FROM SOCIAL DISTANCING WHICH WE ALL KNOW ABOUT BY NOW):
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This blog is lengthy for the interested reader, but can be skimmed and is organized by topic to facilitate doing so. Information becomes outdated rapidly, and this post may well be out of date soon – hence liking us at facebook as above
- FATALITY RATE: The fatality rate of COVID 19 continues to diminish and may even turn out to be not much higher than a severe flu. The flu fatality rate is about 1/10th of 1 per cent. Early on the covid death rate seemed to be over 3%. However now the fatality rate has fallen to only about 1.5% in the USA and is continuing to diminish.
Let me tell you why the fatality rate will continue to diminish and roughly where it is likely to ultimately end up. The fatality rate is a fraction: fatalities/total infected. The numerator is fatalities, the denominator is total infected. The numerator is well known, hospitalized patients who do not survive. But there is no good way to know the denominator since most people who get the virus have mild or no symptoms and are never tested. However as testing increases the denominator gradually grows as more asymptomatic or minimally symptomatic infected cases are picked up causing the fatality rate, which is a ratio, to gradually decrease. Now that more testing kits are available and more people are being tested the fatality rate in the US has been gradually decreasing and is only a little above 1% in NY for example. Interestingly in Germany where the testing rate is much higher the fatality rate is only 0.6%, inching closer to the 0.1% rate for the flu. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease wrote in the February New England Journal of Medicine that the fatality rate may be “considerably less than 1%.” I expect the real fatality rate to ultimately be higher than a seasonal flu, but possibly not by much. At this point there is no way to know
It is important to realize that there has also been good and increasing success in treatment such that the numerator – deaths - will also be decreasing as logistical barriers to accessing the treatment are eliminated, and as newer data clarifies the relative efficacies of the various treatments. The result will be a smaller number of fatalities, the “numerator,” which will produce a correspondingly lower fatality rate. Thus we now know that the doomsday dire predictions of high fatality rates are clearly wrong and overstated. However there will still be substantial death and suffering and it is still critically impotant that the fight to avoid spread and defeat the virus not be relaxed so that this death and sickness can be mitigated as much as possible.
- TREATMENT WITH HYDROXYCHLOROQUINE: This drug has been FDA approved since 1955 for Malaria. It has been used off label for other diseases. This means that any licensed physician in the United States can prescribe it immediately for their patients for any reason they feel is appropriate. And indeed this is currently happening. And while there can be some side effects it is generally quite safe under a doctor’s care.
Here is a link to a French study that showed hydroxychloroquine to be quite effective on its own, and even more effective when used with azithramycin – the so called “z-pak.” The author is a famous universally respected French infectious specialist, Dr. Didier Guillemot. He clearly stated in an interview that he would definitely use it on himself. In a larger study he found that 79 of 80 severely ill hospitalized patients survived and made substantial improvement, and cleared the virus much more quickly from their system than is usually the case. The one fatality was an 87 year old man with other health conditions who was gravely ill when first treated. This survival rate in this patient population in his study is much higher than would otherwise be expected and is further evidence of the efficacy of the drug. Another study from China has also shown efficacy.
On the Laura Ingraham show on Fox news on Monday March 23rd, there is an interview with a patient who was near death and had a dramatic turnaround in one day on hydroxychloroquine. Here is the link. Notably this patient had to request that his doctor prescribe the drug and would not have gotten it, and possibly would not be alive, if he had not done so. Dr Oz has also endorsed its immediate use. Health officials are guarded in their endorsement because that is their culture, but there is no question that it works and on a risk benefit basis is well worth the risk of side effects for symptomatic patients. To be clear it is not an immediate cure all, it has some risks particularly in some types of heart disease, but is definitely worth using and is being used. It is one of the reasons that the fatality rate is falling in the US – and is much less than has been seen elsewhere - despite the large number of US cases. It is also quite inexpensive. Bayer corp in Germany recently donated 3 million doses to the USA and Novartis just last week committed to donating 130 million doses of hydroxychloroquine. Even though it costs under a dollar a pill in the US, and much less in Europe, this is a welcome action
Another study showed greater efficacy when hydroxychloroquine was also combined with zinc. The related drug chloroquine, an anti-inflammatory drug used for rheumatoid arthritis is also being used.
MECHANISM OF ACTION: The mechanism of action of hydroxychloroquine is immunomodulation. The COVID 19 virus does not destroy cells as some viruses do. Rather it elicits an overly aggressive inflammatory immune response in some patients resulting in fluid buildup in the lungs, pneumonia, and, in some cases, death. Thus immunomodulatory drugs that can blunt this immune response can mitigate the pneumonia and decrease fatalities
- TREATMENT WITH REMDESIVIR: Remdesivir appears to be effective against COVID 19. Equally importantly the drug appears to be quite safe. A recent Wall Street Journal article chronicled how it appeared to be effective for stricken patients on a Japanese cruise ship. It was designed to treat ebola but was not effective. However it was effective in the laboratory against another type of coronavirus than COVID 19. While the FDA had not approved the drug for any use, President Trump urged the FDA to allow its use in the current emergency and they have done so and it is being used in treatment in Washington State. This is extremely important because it would otherwise be unavailable for months or longer while trials are being conducted. And there is no reason to withhold use while these trials are being planned. As long as it is safe with some evidence of efficacy in the current emergency situation it should be allowed. A world health organization official recently stated that he thought it had the most likely efficacy of any of the drugs currently being tested.
However now a new roadblock has occurred. While the FDA has allowed compassionate use, the company, Gilead, has suspended the program due to “overwhelming demand.” Instead they are ramping up studies. Hopefully access will be increased soon.
- TREATMENT WITH PLASMA OF RECOVERED PATIENTS. Blood plasma from recovered COVID 19 patients has been approved by the FDA for use on a case by case basis within only 4-8 hours of the request. There have been numerous reports from China of such plasma successfully treating patients seriously ill with coronavirus. Happily the US FDA has moved quickly and this treatment is currently being employed in New York and elsewhere: although actually physicians should be able to use this treatment without any approval as long as the patient is properly informed and consents.
Here is a fascinating story recently printed in the Wall Street Journal of just this use by a brilliant physician in the 1930s who used plasma to prevent other diseases before suitable vaccines existed. https://www.wsj.com/articles/how-a-boys-blood-stopped-an-outbreak-11582847330.
HOW PLASMA TREATMENT WORKS: After being infected patients develop antibodies to the virus which prevent the patient from becoming sick again. This plasma can be infused in others and can effectively treat the virus in that patient. This has to be done with proper testing under strict medical supervision at a hospital, but when properly done it is very safe and appears to be quite effective, even in very ill patients.
- TREATMENT WITH TOCILIZUMAB (ACTEMRA): Manufactured by Genentech of the Roche pharmaceutical group, Tocilizumab works by blocking the cytokine Interleukin 6 (IL 6) and is used for rheumatoid arthritis. IL 6 can promote inflammation. Inflammation brings fluid to the lungs, pneumonia can ensue, and fatalities can result. Blocking IL 6 can mitigate this process. On March 23rd they announced a controlled study in which Tocilizumab will be added to ongoing COVID 19 treatment in the study group and compared to another control group where placebo is added. We will watch this closely to see if it can provide another tool to help fight the ravages of COVID 19. It is currently not available for compassionate use outside of these studies.
- STEM CELL TREATMENT: A small study from China has used umbilical cord blood (ie not embryonic) stem cells and fluid to treat severely ill COVID 19 hospitalized patients. Seven patients received umbilical cord stem cells, three received placebos. All seven of the stem cell treated patients, recovered, were removed from respirators and were discharged. One of the placebo patients died and none improved as a direct result of the treatment. Another stem cell treatment avenue is to use adult mesenchymal stem cells derived from fat. Celltex corp is in discussions with the FDA to begin a trial. In addition substances called exosomes, vesicles that contain various cytokines and growth factors, have great potential in this area, although I am not aware of a trial at present of their use. While I usually favor autologous tissue, ie tissue from “you” not from “someone else”, in this case logistical and time constraints for hospitalized patients would preclude this avenue.
One minus to stem cell treatment is cost. While drugs like hydroxychloroquine and azaithramycin (z-pak) cost less than a dollar a pill, and much less in Europe, and have millions of doses being donated, stem cell treatment is inherently more expensive with costs in the thousands of dollars, (perhaps less in these times of distress) for even a brief treatment course. In the short term these treatments could be solicited at no cost to treat the crisis. In the long term it would likelier be a second line of treatment for difficult cases. Although ultimately we should be able to identify subgroups of patients who respond better to one treatment or another and allocate treatment to patients based on likely efficacy. What it does do though is give us one more very likely effective tool – along with hydroxychloroquine, remdesivir and plasma infusions – to treat the already afflicted.
- OUTDOOR EXERCISE: Mayor Lightfoot in Chicago correctly prohibited crowding outside. But she incorrectly said she was prohibiting “a 5k run” or a “long bike ride” outside. I’m sure she means well. But in fact studies from the Spanish flu pandemic showed infected patients did better, were healthier, if they got fresh air outside. Also exercise has been shown to improve how you deal with infection. Finally if you stop exercising you may experience “exercise withdrawal depression.” Therefore if you are fit and used to 5k runs or long bike rides you will be better off to continue them outside, weather permitting. Just make them solitary workouts and respect social distancing when you are outside.
- YOUR RIGHTS: The FDA is cautious and generally acts quite slowly. However, President Trump has strongly urged them to act quickly to make promising, safe treatment available to ill patients. Happily they have responded well and made these treatments readily available.
Doctors ARE able to freely prescribe hydroxychloroquine, and azithromycin for those infected with COVID 19. But they may not if you don’t ask. Doctors can also get permission for plasma infusion within a day from the FDA if it is available in your area if you are ill with COVID 19. You may also be able to get into a study on Remdesivir or Tocilizumab. But this likely won’t happen if you don’t take the initiative for yourself or a loved one if you decide this is what you want.