COVID-19 is our moment to rethink infection, and to rethink health. It’s a big moment.
By now, you know that we’ve seen corona viruses before: Middle Eastern Respiratory Syndrome (MERS) in 2012. Sudden Acute Respiratory Syndrome (SARS) in 2002. In fact, corona viruses were first discovered in the 1960s and have long been understood to cause a “substantial” portion of upper respiratory infections in children (that is, common colds). Despite decades of scientific effort, we haven’t emerged from any of this with sure fire preventives, drug treatments, or vaccines.
COVID-19 has been wreaking havoc and defying experts worldwide. COVID-19 behaves so differently in different persons that Atlantic Monthly has called it “a disease of the immune system”. Robert Murphy MD, a professor of medicine and the director of the Center for Global Communicable Diseases at Northwestern University, was quoted in that piece to say this: “’There’s a big difference in how people handle this virus…It’s very unusual. None of this variability really fits with any other diseases we’re used to dealing with’…When doctors see this sort of variation in disease severity, ‘that’s not the virus; that’s the host.’”
Essentially, COVID-19 kills people best when their immune systems over-respond with uncontrolled cascades of inflammation. It appears to exploit whatever your weak link is, and destroy from there, whether it’s lung, kidney, gut, heart, or brain tissue. Apparently, this virus isn’t picky, but it sure is wiley. Not everybody’s immune system is doing this. As more are screened for exposure status, we are seeing death rate drop, to perhaps as low as half a percent. #COVID19 is looking like an infection that serves up a catastrophic clinical course, but only for a subset of vulnerable people.
One option is to take the cue from Dr Murphy quoted above. It’s time to figure out why that half percent gets hit so hard.Maybe the solution is not about the virus. Maybe it is about our immune systems, which vary widely in their status, functionality, and readiness, and in our own risk factors, which are virtually exponential in complexity when we consider genetics, nutrition, health habits, toxic exposures, stress, drug use (recreational and prescription), and more. All of these impact each other, creating potential synergies in any direction, when you toss COVID-19 into the mix.
Right now, our health care system is a reductionist one that silos health problems into discreet specialties. It doesn’t pay much attention to nutrition or food, or toxic exposures, in routine care. COVID-19 has laid bare what a catastrophic fail this is, as it devastates a select few of us in so gruesome and terrifying a fashion. By “few”, I mean this: Tens upon tens of thousands of deaths is a lot. Relative to the total population, it’s a very little. A long list of other conditions, infections, and diseases affect many more of us. But we don’t shutter the globe in response. We figure it out.
We are likely to get it too, as COVID-19 becomes endemic. This appears to be well underway, as reports roll in of deaths from COVID-19 identified as having occurred in the US in early February. New York just announced a finding of positive antibodies in 14% of a sample of people tested in that state, suggesting that the death rate is closer to one half percent. Why are some of us getting so sick, some of us dying swiftly, some of us feel hit with a bad cold, or some just a minor sniffle, some GI symptoms – or even more peculiar, a fatal stroke? There are more viruses than there are stars in the universe; they are here to stay and part of life on earth. Can we figure out how to live with them, rather than die by them?
Developing a COVID-19 vaccine is fraught with challenges – not the least of which is that corona virus vaccine efforts have posed “unique safety challenges” in that it may trigger responses that vary as wildly as the infection itself. It may kill or injure people, it may cause infection in some, it may give some people immunity, and it may give others no immunity at all while weakening their response when re-exposed. In fact, a front runner vaccine candidate from summer 2020 triggered transverse myelitis – an incurable condition attacking the spinal cord – in three persons in its clinical trial. And the virus is similar enough to HIV – for which no vaccine has ever been successfully developed – to make it susceptible to the same fate: No vaccine with the durability, safety, or efficacy to really work.
Recently, the World Health Organization (WHO) suggested that immunity to this virus isn’t a protective certainty after infection. If that holds true, then a vaccine may be doomed. The entire premise of vaccination is that antibodies triggered by the injection will protect you. If naturally acquired antibodies don’t work, how could triggering you to make your own from an injected version of the virus work?
Without usual process for safety and efficacy, such as has been proposed in the scramble to have a vaccine, these are ominous frustrations. Peter Hotez MD, PhD is a researcher who has tried to make a corona virus vaccine in the past. So far, no good. In Congressional testimony, he describes unexpected reactions from an experimental vaccine and mentions that two children died (at minute 25:40 in this transcript) in a human trial of his most recent attempt. As a vaccine scientist who invents vaccines, he’d like more than anyone to see this work. In a recent podcast, he eloquently thumbnails what we’re up against. He points out the footdragging the US had on testing and quarantine, which let COVID-19 circulate for a long time. He describes what we’ve all heard many times over too, about who is most at risk, with an odd twist not often mentioned. We know that kids and adolescents are less affected. The elderly are at high risk. Anyone who is immunosuppressed or with underlying conditions is in trouble too. And, this obvious, but rarely stated, twist: Health care workers contract a severe version of the virus, despite their age – young or old. Why? Why don’t they get sick like other exposed young people, and recover?
An opportunity lies there to dig for clues. Health care workers are the most highly vaccinated among us; they receive boosters at least annually for influenza (some workplaces require these biannually), and boosters of other vaccinations more often than most of us likely do. Shouldn’t this somehow be protective? Or is this part of the problem? Detecting a phenomenon called “vaccine interference”, a study of military personnel showed that those with prior flu vaccination had higher risk of contracting corona virus than the unvaccinated: “Vaccine derived virus interference was significantly associated with corona virus and human metapneumovirus”. In other words, in this study, having had a flu shot meant you were more likely to get sick with corona virus.
You might think Dr Hotez would be the loudest on the podium touting a shot as the single silver bullet that can fell this demon. He tried to make one just for this moment, but failed. He knows this can’t happen fast, and that we need action right now. One of the immediate solutions that he and colleagues are thinking of is “convalescent plasma coronavirus therapy.” That is, give immunoglobulin (antibodies to COVID-19) from a recovered person’s purified blood (plasma) and infuse or inject it into a sick person who is not recovering. This worked for SARS, Ebola, and MERS. Development of this biological product for COVID-19 is already underway, despite the WHO nay-saying on this strategy.
Immunoglobulin (Ig) therapy has been around since the 1950s, but not specifically for COVID-19 (no has had antibodies to it, until now). Ig is tried and true, effective, but costly; a pool of many hundreds of recovered persons is needed to extract enough immunoglobulin to treat just one person. It currently costs thousands of dollars per dose, even tens of thousands of dollars per dose, to receive Ig therapy for other conditions, so insurers are loathe to cover it. But Dr Hotez would like to see a low cost version of this made available.
Even if “low cost” means, say, $800 per dose, it sounds great – if you can manage to jump through the health insurance hoops and hurdles that will surely be raised to stop you. COVID-19 has laid bare many ills in the US in 2020, with one of the most glaring being that our for-profit health insurance and health “care” industries are a fail for consumers. There is no covered, federally coordinated access to screening to show who is infected. Millions have spotty access to health care, if they have any at all. It’s more profitable for insurers and care providers to patent and sell a vaccine, than it is to sell immunoglobulin therapy, screen everyone for antibodies, or screen everyone – before exposure – for a laundry list of risk factors like inflammatory markers or nutrients that our immune system draws on to fight infection (ferritin, ESR, homocysteine, serum iron, serum vitamin A, vitamin D, and zinc to name a few). Whether Ig works well or better than other tools isn’t relevant in our care model; whether it’s profitable is.
In Dr Hortez’ podcast mentioned above, he goes deeper into why rushing a COVID-19 vaccine is a bad idea. Among the obstacles is “immune enhancement”, a known phenomenon already seen in animal trials with corona virus vaccines (and others like AIDS) in the past. Industry scientists have long found this phenomenon to be a stumbling block that “proved to be counterproductive” in that it “renders vaccinated subjects more susceptible to infection rather than protects them.” To quote the podcast, “Vaccine trials have begun in Washington which is a positive, but we will also see immune enhancement in [the] volunteer population”. Make no mistake: Researchers know from past experience that COVID-19 vaccine trial test subjects are going to either step on a cytokine cascade landmine (potentially deadly), or suffer “immune enhancement” (potentially deadly if re-exposed), or may be just fine. Here’s how one reader put it, in the comments following Dr Hortez’ podcast:
March 17, 2020 at 4:03 am I think you heard Dr. Hotez correctly: vaccines for highly pathogenic viruses are problematic because they cause “enhanced immunity”. This is a heavy euphemism for the patient’s uncontrolled inflammatory cascade, called a cytokine storm, which causes illness and death in the ebola, MERS and SARS patient. So in a disease whose mechanism of fatality is the host’s immune over-reaction (cytokine storm manifesting as ARDS etc.), vaccines–whose adjuvants aim to “jolt” the immune system into action–can make the reaction even worse. This is one reason why a SARS-1 vaccine development was halted; although the mice survived the vaccine fine, they were dying at high rates after they were re-introduced to the virus after innoculation. For this reason, therapeutics may be the better solution to this SARS-2 virus than a vaccine.
What to do? Hopeful puzzle pieces are emerging. Persons with healthy immune systems show promise for recovering, provided that their immune systems do what they’re built to do, without going haywire.
Immune systems are complex with lots of opportunity for “haywire” to happen. The good news is, we can minimize the haywire and build functional, meet-your-COVID-exposure-safely immune performance with nutrients, food, supports for inflammation and detoxification, and with better monitoring and management of our own risk factors. So far, policy and practice in the industrialized world around infectious disease mostly disregards all that. On a policy and practice level, we haven’t looked much into how to enhance our own immune response so that it is balanced and effective, or why some immune systems do it right while others get it wrong. We’ve focused on drugs to control symptoms during infection, on vaccines, and on drugs to kill infection. But COVID-19 is shaking these foundations to the core. These 20th century strategies are failing us with this one. This is grim, but it means there is opportunity to pivot and integrate some cool new stuff. Practitioners in the functional medicine realm have been doing this all along. Some pearls have already emerged, more are sure to follow.
One shockingly simple finding may be right under our noses: Severe COVID19 patients can have dramatically high levels of ferritin, even exceeding a value of 1000 ng/mL. This is a very high level that reflects intense inflammatory process underway. Ferritin is a means to make iron safe in the blood. It scoops up free iron when iron, a powerful oxidative stress element when free in the blood, gets too high. This high level of iron will set off inflammatory cascades in itself and slowly poison patients. It’s possible COVID19 is doing this by knocking iron off of the hemoglobin on red blood cells, so it to floats free in the bloodstream. No iron on hemoglobin means no oxygen can attach to your red blood cells, and you will essentially suffocate while the inflammatory cascade is encouraged from too much iron.
A simple way to oppose iron is to supplement zinc. COVID19 patients who report a sudden loss of taste and smell are reporting one of the classic textbook signs of zinc deficiency. They may be rapidly depleting zinc to meet demands set off by infection. This may be just one of the trip-wires that sends some patients into a rapid decline, while others muddle through. It’s not exotic, but it’s worth exploring. It would be a lost opportunity if it were true but instead we took a detour into how COVID19 might affect olfactory nerves.
COVID-19 is ruthless and devastating for the vulnerable among us, and incidental for most of us. If we follow our own hallowed tenets of epidemiology and herd immunity, according to Scott Atlas MD, a health policy expert at Stanford University, the most protective-for-all thing to do is to “stop the panic and end the total isolation”. That is, go back to work, come out of hiding, and build population immunity naturally, while identifying and supporting those who are at risk. We have tools at hand right now, and they may be deceptively simple. From tapping older less profitable drugs (less profitable because they are off patent and available generically) to engaging essential tenets of the nutrition / immune interface, we have a lot to work with already.