Part 11 COVID-19 Knowledge Update IV
In this week’s update on COVID-19, I will focus on the evolutionary origins of the virus, its mutations to date, and what that means for finding treatment options. I will then dive into some of the areas that treatments should be targeting based on what we know about the virus.
Virus Origins and Mutations
Contrary to conspiracy theories that insist that COVID-19 was made in a lab, we as a society actually know quite a bit about this virus’ origins.1 For starters, we know that the novel coronavirus has been circulating in bats for decades, and similar viruses circulating in bats pose a risk of being transmitted to humans. Research on this topic has been an international collaboration of public researchers. It is important to note that there is a difference between tracking circumstantial evidence, such as publications and reports that the genetic stability of the virus is unexpected and could have escaped from a lab,2,3 and the fact that China only has one laboratory equipped to handle biohazards such as the novel coronavirus, located in Wuhan. Further circumstantial evidence in regards to a Chinese cover up is an inconveniently released report with new guidelines on containing biothreats at the start of the pandemic, which acknowledges that there is a problem with researchers selling animals that had been experimented on to meat markets for human consumption.4 All of this adds up to a big question on the legitimacy of the official story. But none of it proves that this is indeed what happened. It is all circumstantial evidence.
The difference between acknowledging there could be more to look at, and “knowing” that it was a Chinese conspiracy, is an individual’s ability to evaluate evidence. Fringe lunatics piecing together information to form conspiratorial views will say that the circumstantial evidence is “proof,” and take it a step further: “China knowingly created the virus as a weapon.” Skeptical reviewers will look at the circumstantial evidence and say “possible, but more proof is needed. The virus has natural origins, but could have accidentally escaped the lab in Wuhan.”
Regarding the origin of the virus, and not how it crossed to humans, I turn to Occam’s Razor, which is the principle that when two explanations are able to explain all facts, the simpler explanation is more likely to be correct. Therefore, I pose the following question: Which of these two is the more simple and believable explanation?
The novel coronavirus jumped to humans from bats, as the vast majority of experts in the field believe and accept. Viral jumping from different species5 was a well-documented and researched process before the emergence of the novel coronavirus.
A small minority of discredited researchers commenting outside of their immediate specialty, as well as Internet bloggers and YouTubers, have got it right—that all the world’s experts and public scientists dedicated to finding truth are either wrong or paid off in proposing that researchers created the virus in a lab, as sort of a chimera.
To me, it is crystal clear that option “1” is the simpler and more plausible explanation. This is not to say that China is not up to some shady and deplorable actions and tactics. I am not an apologist for the Chinese government; I find their actions terrifying. I believe that in all likelihood, they covered up the extent of their own pandemic, delayed notifying the world until they could not hide it any longer, and then lied repeatedly about what they knew.
They likely did this to buy time so that they could utilize Chinese nationals all over the world to stockpile protective equipment for the “motherland,” while ramping up their own productions to fill the world’s requirements and shortages, while further entrenching their own power. I would not doubt for an instant that they did this deliberately to further entrench the world’s need of Chinese manufacturing, utilizing the pandemic and allowing it to grow to the point of no return. China likely contributed to the pandemic knowingly, but I do not believe they created the virus in the first place. They simply exploited it once it had made the jump.
To answer the conspiratorial cries of “Why now, at a time where the world is pressuring China?” Many epidemics have originated in China — some recently, such as the SARS epidemic and the first human case of the Avian Flu in Hong Kong in 1997. The novel coronavirus likely won’t be the last, as even more recently new strains of the flu have been found in China with pandemic potential. China is the most populous nation on the planet and engages in some cultural practices that may increase the likelihood of cross-species viral jumps, such as their “wet markets.” If cross-species viral jumps are going to happen somewhere, the odds favour China, and in terms of infinity, anything that can happen will happen.
To understand this notion, the infinite monkey theorem was created. Basically, in the sense of infinity, if a single monkey is hitting the keys at random on a typewriter, eventually all of Shakespeare’s work will be written word perfect and in chronological order — and anything else ever written as well. This pandemic will not be our last, and while it is not guaranteed that future pandemics will originate in China, there is a significant likelihood of such events. This does not mean China is intentionally creating viral pandemics; it means that the statistics point to them as being the most likely, as a single nation.
Regardless of whether the likely explanation is the correct one, the virus is now out and there is no containing it now. The following questions need to be answered, “How do we treat it?” and “Is it mutating too fast to effectively treat it?” The good news is that despite there being different strains of the virus, the levels of variability from the virus, despite mutations, is quite low. This suggests that once we develop effective treatment methods and vaccines, they are likely to remain effective with little changes made for a significant amount of time. This is great news at a time of often horrid news.
What Should COVID-19 Treatments Target?
One of the key takeaways from the research is that when infected with the virus, a key component of our immune defense, our inflammatory response, becomes dysregulated. In some severe cases, our inflammatory response is overactive or kicks in too soon and too aggressively, which can lead to cytokine storms and death.6 In other cases, there is no inflammatory response,7 which indicates an underactive immune response to the viral threat. Moreover, an underactive immune response will increase susceptibility to a viral threat. Pursuit of treatments that aim to regulate the inflammatory response, rather than just suppress it, based around the knowledge that our immune response is largely from “nurture” and not just nature, should be a target of future research.
It has recently been discovered that significant amounts of “DNA NETs” have been found within the lungs of patients who died from COVID-19.8 DNA NETs, which is an abbreviation for neutrophil extracellular traps, is the immune system’s first line of defense. However, NETs may play a deleterious role in certain autoimmune diseases such as lupus9 and in infant sepsis.10 In COVID-19, the significant accumulation of DNA NETs, which are “capturing” the virus, can lead to toxic outcomes.11 In fact, this increased accumulation of NETs could be a chain reaction from the dysregulated inflammatory response, as NETs and inflammatory levels are closely linked.12
Fortunately, there are numerous clinical trials underway looking to target NETs, as stated in Technology Networks by Prof. Thomas Marichal, WELBIO, and an ERC investigator, as well as the head of the Immunophysiology Laboratory at the GIGA Institute of the University of Liège.
"Clinical trials aimed at degrading these NETs in the hope of improving the condition of patients with advanced disease are being conducted by other teams around the world. Our study validates these therapeutic approaches by demonstrating that NETs are associated with the severe complications of Covid-19."
“A molecule known as ACE2 sits like a doorknob on the outer surfaces of the cells that line the lungs. Since January 2020, researchers have known that SARS-CoV-2, the novel coronavirus that causes COVID-19, primarily uses ACE2 to enter these cells and establish respiratory infections. Finding a way to lock out that interaction between virus and doorknob, as a means to treat the infection, has become the goal of many research studies.”
Just weeks ago, the first case report was published utilizing a recombinant soluble human ACE2 (APN01) to treat a female 45-year-old patient who was diagnosed with severe COVID-19.13 This treatment reported results ranging from decreased viral load, development of high levels of neutralizing antibodies, and a marked reduction in the pro-inflammatory cytokine IL-6 and chemokine IL-8. This is fantastic news, as therapeutic interventions targeting this approach have been at the center of the research, meaning it is likely that “more is coming.”
“Providing first data on the effect of blocking the viral spike glycoprotein in patients with COVID-19 is of paramount importance. These data confirm the mode of action of APN01 specifically targeting the SARS-CoV-2 virus,”
says Dr. Josef Penninger, MD, co-inventor of APN01, founder of the developer and manufacturer of the drug, APEIRON Biologics AG, and senior author of the publication.
“Our findings from the first SARS epidemic and recent research have identified ACE2 as the critical entry door for both corona viruses, SARS-CoV and SARS-CoV-2, to infect human cells. The new data further support the ability of APN01 to lock the door against the virus.”
It has been a big few weeks regarding knowledge evolution pertaining to the virus’ use of ACE2, as researchers from University of California San Diego School of Medicine have reported that SARS-CoV-2 can't grab onto ACE2 without a carbohydrate called heparan sulfate, which is also found on lung cell surfaces and acts as a co-receptor for viral entry.14 It’s important to know that there is a long way to go before therapeutics that incorporate these findings are developed. However, it is quite exciting that now that we are learning more on how it is happening, we have an entirely new avenue to pursue in therapeutics.
Next week, I will continue with a breakdown of the treatments, including both currently available drugs and experimental approaches, that have been demonstrated to be effective, have the potential to be effective, and/or that could reduce the damage from COVID-19.