2019 Novel Coronavirus (CoVID-19): Part XXV
2019 Novel Coronavirus (2019-nCoV (first named); COVID-2019 (later named disease); SARS-CoV-2 (final name of the virus causing COVID-2019), COVID-2019 Pandemic:

 

September 10-20, 2021 update Part 25
Paul Herscu ND, MPH
Herscu Laboratory 

 

Entering the third phase of this pandemic (Part 4 of 5)
A piece on drug therapies

 

Hello and welcome. It has been a while since I have written. We have just now arrived at the third phase, of my understanding of the 5 phase stages of this pandemic. I imagine many of you are feeling frightened, angry and frustrated, as well as simply confused. Things have not gone as well as they should have, as we are experiencing the next increase of incidence in the USA. The question is how to proceed from where we are. I am bombarded by questions from family, friends, patients and students. I would like to discuss several major aspects to help the general discourse. This is a difficult task as at this time as there are two paths, one for those who have been vaccinated and one for those who have not been vaccinated. As a result, I would like to break down the writing into 5 separate posts. They are:

 

1. A piece for those who have been vaccinated
2. A piece for those who have not been vaccinated
3. A piece on effective natural therapies
4. A piece on other pharmaceuticals
5. A short recap

 

Herein, I begin with the fourth piece, a piece on pharmaceutical therapies:

As I start discussing this topic, I reflect that I am about to attend a funeral in a few hours, which will have many people in attendance. And tomorrow, a wedding with 8 people present. How completely opposite these two events are in my mind. As I think about it, if one is lucky they get to have a very long, productive, useful, joyous life. And by the time they pass, most of the people they know may have already passed. And so, the funerals are lightly attended. We know this, and expect this. But when a younger person passes, the funeral tends to be more heavily attended, as family, friends and colleagues are still around. 

 

And then there are the weddings. Where in the best of all worlds, it is the community that comes to celebrate that union. It does not really matter to me what the actual celebration is, but that there is  community, and it comes together to celebrate the future. Here, we expect many. So, you can see my reflection, of how completely opposite these events are, where people die all too young. And others celebrate great joys, but with only a few in attendance. It should not be this way. More on this period of time in the next post. For now, let’s begin.

 

 An overview of drug therapies in this pandemic

Let me start with a similar disclaimer to the last post, that while there are many trials, and many studies, THERE ARE CURRENTLY only a couple NATURAL PRODUCTS THAT THE FDA CONSIDERS MARKETABLE FOR THE TREATMENT OR PREVENTION OF COVID-19. ALSO, WE DO NOT SELL ANY PRODUCTS, WE DO NOT SELL PRODUCTS THAT WILL BE DESCRIBED HERE. THIS IS JUST INFORMATION TO SHARE. OK, I trust that is enough of a clear disclaimer!

 

As an aside, and sad to me, while the proofs are similar in studies with some natural substances, it turns out that pharmaceuticals are more easily accessed, more easily advanced, used by physicians, in a sort of unfair unequal manner vis-a-vis natural products. This really should be remedied.

 

As we are all aware, since this is a novel disease, there were no prior therapies that were clearly proven to be effective for the treatment of COVID-19. No trials had taken place. And as time passed, there were many trials on various potential therapies. I discuss this below. However, I do want to once more highlight one important aspect of the past 18 months. Since we, as a society, decided to have one solution, vaccinations, as the main and perhaps only tool, we decided to deemphasize other potential solutions, though there should have been a broad exploration of solutions as well as the plan B concept. My primary tools are natural products. I believe that they always will be, for a variety of reasons. I mentioned this ‘deemphasizing’ in society when discussing natural product solutions in our last posts, but it really was the same for pharmaceutical agents as well. Drug interventions were deemphasized. And, for me, the most important rapid detection mechanisms- i.e., frequent, improved testing was and continues to be deemphasized. This really should be corrected.

 

A way to consider conventional interventions

As a consequence of this deemphasized state, there is a sort of confusion and a lot to grasp. I write this mostly for two categories of readers. First the ones that have minimal or no medical background, just to orient you around the different words and drugs you hear. And second for those in the medical profession that are like many, confused by the current situation, since treatments were not emphasized and many providers were left to their own devices.

 

As before, I think it is best to think of the infection as a whole process rather than strictly the patient has an infection or does not have an infection. As an analogy, think of a car accident. We can work on the prevention of the accident, on mitigating the severity of the accident, on treating the accident at the moment, or then dealing with the aftereffects. It’s a process. The same here. And again, keeping it as simple and straightforward as possible, and as short as possible, you might think, leaving out the smaller details, in these categories:

 

1.     Limit exposure. Here I mean public health/behaviors. Discussed elsewhere.

2.     Limit infection load. Discussed next time.

3.     Killing viruses upon contact. Antivirals.

4.     Helping your immune system combat the virus. Anti-HIV, Anti-malarial.

5.     Managing a healthy inflammatory response that does not go overboard, anti-inflammatory, monoclonal antibodies.

6.     Managing clotting issues.

7.     Assisting in recovery, post infection

 

In many respects, and what I learned in naturopathic medical school, was that it is better to prevent an illness than to treat one, and if you have to treat one, it is better to mitigate it ahead of time than to deal with it in a fully formed fashion. That should make sense. It is less intrusive to the person’s life and less expensive to society in general. We pick up on this thought next time, but here, we start with antivirals.

 

Antivirals

The concept is a simple one. Can we somehow kill or alter the spread of the virus? And before you write in, I know there is a long and healthy debate in biology (here is one article) on whether viruses are living things or not, since they share only some aspects of life. But for now, here, let’s just use the language that they are alive. Simply put antivirals in some fashion are aimed at killing them or stopping their spread, by modifying different pathways such as ion channels or protease inhibition, as just 2 examples. 

 

One example of this most commonly used is Remdesivir, inhibiting the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. There has been a second new mechanism found to also help, which targets the SARS-CoV-2 protein nsP3, which the virus uses to suppress the person’s response,  thereby limiting the inflammatory response the patient can mount. The bottom line in this group, for the most part, is to cut down on the virus itself. It is less about us, the host, and more about the virus. The results are clearly positive. The noted improvements are clearly there, but at times it seems moderate at best. By the time people start to try this drug, it might be too late in the infectious process for it to be as effective as possible. (Using the analogy above, it might be too late to think about the speed limit once you are in the midst of an accident.) Or to put it more positively, if you have nothing else, then taking this is useful, but taking it earlier in the process might be the most useful of all. Though, if you are doing nothing else, then doing this is better than nothing. Expect an increased number of antivirals to be tested and approved.  The best way for me to think of these medications is for them to be utilized either early on in a severe, sudden-onset case, or as part of a mixed drug strategy later on. Here I mean you are treating the inflammatory response, and some bodily damage but at the same time hoping to knock down the overall viral load.

 

Anti-malarials and anti-parasitics

Hydroxychloroquine. Hydroxychloroquine is the one anti-malarial often discussed, though with mixed results. For example, one recent study showed no difference in outcomes, and perhaps a worsening side effect with its use. However, within the same month another study showed potential use of the drug as a prophylaxis. There have been multiple trials and as a group, overall, this drug disappoints. Overall, my takeaway is that it has a small overall effect if you look at everyone who is ill. This is why the studies seem to conflict. However, I believe there are subgroups where it might be very useful. Again, we have to stop thinking of everyone as the same, and in the same stage of the illness. It might be that this drug is useful at certain times in the process, in certain people, and if you give it early, or later it does very little, and if that is the case, you have a failed trial, and that is why we have mixed results. Which tells me that its sphere is finite, within the infectious process. For example, this was one idea I had on this. In an article on ChemRxiv, we read SARS-CoV-2 virus “attacks heme, on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide. The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images.” Where if this is the case chloroquine may help prevent this from happening.

 

Ivermectin. Similar to Hydroxychloroquine, Ivermectin has been used to prevent and treat Covid-19. And while there are some very positive trials here and here, as just two of many examples, there have also been tremendous failures, and the first large trial was withdrawn for problems, which modified the positive meta-analysis conclusions. Nevertheless, there is so much public demand for this drug, which seems to lead the science so that you can read about many trials are under way here and here. One way or another we will know more soon. One very large trial in Brazil to be reported soon showed poor results. I think one very sad case is that it is likely that the two molecules above work well for the right subgroup, at the right time, and that when looking at all infected, as if they were all the same, the effect gets washed out. In other words, the studies need someone on staff to look for latent subclasses. But that is for another time for us to discuss.

 

As an aside, I have had numerous exposures to people with Covid-19. During that time, and in fact at this very minute, I had a lot of soul searching to do, knowing these drugs, knowing the literature, and while I do take a fair number of natural medicine substances, and continue lifestyle factors that are protective, I have not taken either of the above medications.

 

Anti-HIV

When we discussed Ebolavirus seven years ago, we delved into the concept that sooner or later Anti-HIV drugs would get tested against these sorts of viruses. While currently the WHO is against the idea, it should come as no surprise that this is currently under way. There is a lot of science as to why this is being tested. (And at another time, when we are more comfortable with how to handle SARS-CoV-2, I would like to discuss the benefit that all this research would have led to in the treatment of HIV and cancer, but that is for another time.) Think of HIV as a virus that tends to escape the immune response, and that the antiretrovirals try to keep it in check. With that as a rough way to introduce the subject, and even though most studies have failed thus far, there are and will continue to be studies to see if these molecules work on SARS-CoV-2. As just one example, there is a new study looking at this concept by Pfizer and Merck. I am not sure what to say here, except that once drugs are approved they seek extensions on their patents, which can be attained if a new usage is discovered, so they will definitely continue this inquiry. Also, many times drugs are developed but never get approval, or are no longer marketed, for one reason or another. Expect to read about this, even if most trials are failing, another one will be launched.

 

Monoclonal Antibodies

This is the big one! The simplest way to describe these is if you take what they think is the best antibodies from people who had SARS-CoV-2, combine it with some mouse cells and immortalize these, then take those antibodies and put them into a person who currently has COVID-19, then hopefully, the antibodies do the same job your own antibodies would have done if you were producing enough of them yourself. This is pretty straightforward and is used in a variety of illnesses already, both acute and chronic. Since the science is known here this was eventually developed as a first line treatment option.

 

There are many companies working on this and a few that are already being used. A few main problems are that since they are antibodies, that as the virus mutates, it is possible that these will no longer work, but that is true for the vaccine and the natural antibodies your body makes. As a solution, some companies are combining two or more antibody types into the same infusion. One such cocktail from AstraZeneca, AZD7442,is designed to prevent infection as well, for perhaps nine months to a year. In all respects, the antibodies are modified in some way or optimized. For example, making one version called Sotrovimab, hang out longer in the lung, so that it can attack the virus more locally there. There will likely be an evolving number of versions of this concept. As in this one, REGEN-COV from Regeneron, recently approved, which is also a combination of two antibodies. I imagine there will be an ever-increasing number for a variety of purposes, some to prevent illness and some to treat at the onset of symptoms.

 

Downsides include the fact that you have to receive an infusion of these, that they have side effects, and that they are expensive. The main downside is the ever-mutating virus and the fact that if they mutate too far from where the antibody is aimed, they will lose efficacy.

 

I guess this is where I should really slow down and re-emphasize one concept. Think of this infection as a process, from the start, being exposed, to having the immune system start working, to the virus doing too much damage, to the damage hurting us. (More on this in the next update, but I just need to underscore this again.) With that in mind, it seems as though the antibody concept works best at the start of exposure, or at the start of symptoms, and then has less and less impact as the disease progresses. The reason for this will make sense in the next update, but think of monoclonal antibodies having their best effort in the early days of exposure and illness, up to the point that the body is hurting itself.

 

Also, it should make sense that the antibody you start to develop impacts success. The better the fit, the better the result. In other words, antibodies are not all created equal. For example this one is supposed to help greatly. But it just turns out not only do some people have an overall better immune response, but even this part of the immune system, the antibodies, seem to be better able to do their job. Here is another study discussing this. How all of this fits into a good plan, if you are going to use these, we discuss next time. Suffice it to say that the lowering of case fatality rates in the past months is in part due to these monoclonal antibodies.

Corticosteroids to put the immune response to sleep

Specifically, here I am talking about dexamethasone. In very severe cases, increase in survival rates were seen according to an early trials. The best way to think of this, as a steroid, is that it puts the immune system to sleep a bit. Here this is done when the inflammatory process of the body is so intense that it seriously harm or even kill the person. Putting the immune system to sleep at that time may save lives. However, putting the immune system to sleep as a general rule is a terrible risk at other times. For example, one of the reasons people get so sick in the first place is that their system is lagging behind the virus initially. It takes time to bring the whole immune system online to deal with the virus appropriately. If you delay the process by using steroids, I think you are more likely to harm yourself rather than help yourself. Just like I think the antivirals make more sense at the start of illness, it makes more sense to use dexamethasone in the midst of a bad version, to quiet the immune response a bit. So really a double-edged sword. But it clearly has saved many lives, used at the right time during the course of the infection.

 

Convalescent blood

We spoke about this 7 years ago, when discussing EBOLAVIRUS in 2014, but also at the start of this epidemic. Here, you basically give blood products, plasma exchanges, etc., from someone who survived the infection, or by creating a hyper-immune response in animals, like horses, and then giving the blood products, like filtered plasma to someone who is currently having the infection. In general, the trials have failed. But I think this may be a misread. I think by itself it is not enough, which should be obvious, given the fact that most people who end up critically ill are showing you that they really need more than passive immunity. But I think a nuanced approach might be convalescent blood product, in combination with an antibody drug, mentioned above. Again, more on this the next time. Convalescent blood seems to succeed in some elegant tests and fail in others, but I think for the right person, at the right time, it can be useful.

 

Adding/Removing blood products to calm down the immune response

Here we are discussing what we can do to further limit the inflammatory response that led to dire outcomes for many people. With regard to limiting the cytokine storm, I think looking a specific removal of these immune components, as we discussed elsewhere, by adapting the sort of technology that Cytosorbents uses, is not out of reach, as a way to filter out some molecules that might lessen an intense inflammatory response. It turns out FDA tried this, and while it has not worked well thus far, studies continue to work out best practices. From my point of view, the main concern is filtering out potentially important blood products, is that used at the wrong time it may make things worse rather than better.

 

In the same post, I mentioned and still believe that both checking the level of serum C1-INH in the most ill patients and then giving those with a relative deficiency of plasma C1INH more C1-INH is a workable, affordable, targeted solution. I hope they will soon start to measure C1-INH in severely ill patients, using it as a sort of biomarker for treatment and prognosis. Not much has happened here. But more and more papers refer to this as a great target. I am glad that this is not being left behind, as understanding where this fits in may help understand why some get so sick or die.

IL-6 inhibitors

One of the most interesting molecules that we track to measure severity of COVID-19 is the pleiotropic cytokine IL-6 (Interleukin-6) levels, as it seems as the higher the number, the worse the outcome. And since IL-6 has many different cross functions within inflammation, the higher this number goes, the more inflammation there is. Therefore, if we can inhibit IL-6, we might lessen the severity of inflammation that is damaging the body. This is being done as well. So for me, it makes most sense to use these just before or during a massive inflammatory response, just to keep the body from hurting itself.

 

In Summary

As I mentioned above, my main tools are homeopathy and natural substances. But I believe that you should be informed as best you can, in the midst of a lot of news, and information. Very confusing. And here we are in this next phase of the pandemic, where we realize that there was a mistake, where  now we are finally not putting all our eggs into the vaccine basket and starting to give more time to treatment options. (Though hopefully, soon, the majority of energy will go to where it belonged in the first place, in rapid, affordable, easy to access and easy to use, accurate testing.)

 

I would like to make one final comment on drugs, from a naturopathic point of view. One very good way to think about these is to consider how similar their mechanism of actions are to what the body is already trying to do when working optimally. In other words, if you have to take a drug, it is probably better to take one that works or mimics a natural bodily process. When that is the case, then the side effects are generally less, the dosage are lower, and a potential benefit is greater. With that in mind, the antibodies, steroids, convalescent blood and other specific immune ‘temporary replacements’ will probably be good choices from this list. In the next post, I am excited to put it all together.