Solving the Riddle of Long Covid

             Long Covid is a complex, multifaceted syndrome that consists of multiple lingering, newly emerging, and delayed symptoms of Covid-19. Many symptoms are not apparent during the initial acute phase of illness and take time to develop. The scientific name of Long Covid is post-acute sequela of Covid or PASC.  

            The SARS-CoV-2 virus infects cells by attaching to the ACE2 receptor found on the surface of many cell types. Because ACE-2 is one of the most common cellular receptors, it allows viral entry into the cells of all organ systems, including nerve cells. That is why Covid-19 and subsequent Long Covid affect all physiological systems within the body, especially the nervous system.

            At least two hundred various Long Covid symptoms have been recorded. A person has Long Covid if at least three or more symptoms linger for more than twelve weeks after initial infection. However many with Long Covid report dozens of different symptoms. Some other viral infections such as Ebola cause similar delayed sequela syndromes, but not on such a wide-ranging scale. No disease has ever produced such a widespread impact as Covid-19 has with its long tail of Long Covid causing so many health problems for so long in so many people. How can we understand this continuing multiplicity of conditions and find a solution to this multifactorial health challenge that has confronted over sixteen million Americans and tens of millions worldwide? 

            As with most challenging riddles, the solution is easier if one understands the underlying cause of the problem. That starts with the acute infection. But what are the essential viral, immunological, and cellular mechanisms of how SARS-CoV-2 causes Covid-19 and Long Covid? Although this is very simple, it goes largely unrecognized, glossed over by public health authorities due to the distorted medical research paradigm the National Institutes of Health uses to prioritize new drug development and high-cost, high-tech medical care over analyzing  and addressing the causative mechanisms that could open the door to additional preventative and early treatment interventions. The NIH frequently ignores existing safe, effective, inexpensive, repurposed therapies while waiting years to develop expensive new treatments that are often no better but frequently have worse side effects than existing medications. That happened with both HIV and Covid-19. With Covid, that approach resulted in two extra years of unnecessary deaths. Using existing therapies could have saved the lives of half those who perished.   

             First we must consider who is most likely to develop Long Covid. Most sources estimate that between 15% and 30% of people who are symptomatic for Covid go on to develop Long Covid. Generally, those who have more severe cases of Covid are more likely to suffer PASC. Up to 50% of those who are hospitalized and suffer more severe damage to their cells, nerves and organs end up with this tangled idiosyncratic buffet of symptoms after they recover from the severity of initial infection. Although anyone who has been infected can potentially end up with Long Covid, even a small fraction who were apparently asymptomatic. On average the more serious the initial disease symptoms, the more likely a person will develop post Covid syndrome. However scientists believe children are less susceptible.        

            One factor that make a person more likely to end up with Long Covid is being female. Although some report being between age fifty and seventy increases the odds of Long Covid, others suggest those in their twenties and thirties are just as susceptible. People who had poorer health or comorbidities prior to infection are more likely to suffer Long Covid, especially those who had lung problems or autoimmune disease. Other factors that favor this negative health outcome include, obesity, people who were in the ICU, and those with post-traumatic stress syndrome (PTSD), depression, or anxiety, and those who had higher levels of antibodies during acute infection. Scientists say that those who were not vaccinated are two and a half times as likely to get Long Covid than those who were. Lacking vaccine protection also contributes to more serious initial disease. Which SARS-CoV-2 variant one had also makes a difference. Percentagewise, the delta variant caused more than twice as many Long Covid cases as omicron did. According to Dr. Michael Brode of the University of Texas Medical School, at six-months post infection, 7% of all Covid cases still have Long Covid, 37% of those who had been in the ICU, 22% of all who were hospitalized, 4% of non-hospitalized, 11% of those who had delta, and 4.5% of those who had omicron. Other surveys have provided slightly different figures.     

            Although the list of symptoms of Long Covid are extensive and cover all the physiological systems in the body, some of the most frequently reported conditions include, fatigue, shortness of breath, “brain fog” or cognitive impairment, heart palpitations, sleep disturbances, anxiety, depression, and gastrointestinal problems. Finally there is a continuing underlying low level of systemic inflammation that continues to aggravate  many of these symptoms and is a negative factor for overall health. That is because inflammation causes cellular distress and can cause, DNA damage, initiate cancer, and advances the aging process. Blood clots and micro-clots are also factors in PASC. Some scientists theorize that a continuing low level of viral replication may also contribute to Long Covid. That is because the immune system may not have completely cleared the virus from the body.

While some with Long Covid recover from most of these symptoms after several additional months, others take a year or eighteen months to approximate full recovery. Not surprisingly, a chemical element that plays a central role in Covid-19 should also play a fundamental part in speeding recovery from PASC. Scientists have noted that following initial Covid illness, it takes several months before depleted selenium levels in the body are restored to normal. The gradual replenishment of the selenium the immune system requires to function contributes to and appears to parallel early recovery rate from Long Covid. Thus, unless selenium is supplemented, it takes several months longer for this trace nutrient to return to normal levels through dietary sources alone. That suggests that, as with the initial disease, selenium may be an effective treatment for Long Covid. Nevertheless, it is far from a cure.     

            To fully understand Long Covid one must appreciate the damage the virus has inflicted on the cells, tissues and organ systems that contributes to PASC. After the SARS-CoV-2 virus infects a cell and seizes control of the DNA protein production program located in the nucleus, it redirects that DNA cellular computer program to instruct the cell’s machinery to churn out viral proteins instead of cellular proteins. Viruses speed up that process by releasing the cell’s jet-fuel replication stimulant, the NF-kB protein. NF-kB quantumly increases the rate of viral production. The virus then proverbially scavenges the cell to acquire the construction materials it needs to assemble new viral proteins. It utilizes the same materials the cell usually uses to produce cellular proteins. One rare element the virus requires to form its outer protective envelop is selenium.

            The element selenium exhibits special protective qualities in biological systems. Within the cell, selenium forms the function center or active site of most of the antioxidants that protect cellular health. Antioxidants clean and detoxify cells and protect them from the damaging action of reactive oxygen species, also known as free radicals, oxidizing agents, or just plain oxidants. Scientists have noted that the SARS-CoV-2 virus aggressively attacks most but not all a cell’s antioxidants and cuts them up with their scissor-like protease enzymes. They do that to extract the selenium content so they can repurpose those molecules to construct the envelop to protect themselves. When a virus destroys a cell’s antioxidant protection, that damages the health of the cell, and it eventually receives an internal signal to self-destruct. When programmed cell death, also known as apoptosis, is repeated cell after cell, toxins are released from inside the cell, tissues are damaged, and a cytokine storm ensues. Eventually organs and organ systems are damaged – for instance the brain and nervous system. It takes time to repair that damage and selenium needs to be replaced to correct the oxidant-antioxidant balance and facilitate that cellular repair work. In acute Covid disease, if cells sustain enough cellular damage and selenium resources are overwhelmed, a person will expire. However if a person retains enough selenium or enough is supplemented back quickly enough, that person will survive and recover. But the damage has been done. That often results in Long Covid. Recovery is prolonged if cellular and tissue destruction is not repaired by replenishing the selenium supply that is also needed to improve the immune response. This process could be compared to a brick and cement wall that is damaged but cannot be repaired until new brinks and cement are supplied. However damage takes time to repair. That delay is what results in Long Covid. Understanding more about how the virus causes cellular damage and the disease itself points the way to treating the lingering symptoms that are due to the cellular destruction caused by the original disease. Raising the selenium level takes time because selenium exists at such low levels in the diet. Vegetarian and vegan diets take extra time to replace this essential trace nutrient. Like others, vegetarians should take selenium supplements to hasten physiological reconstruction and recovery. This also applies to other infections and injuries since many diseases deplete selenium resources, especially viral disease, chronic diseases, and serious traumatic injuries and burns. Both acute and chronic diseases place extra strain on the body’s selenium reserves.      

             Physicians have performed so poorly treating SARS-CoV-2 and Covid because, remarkably, almost unbelievably, they are mostly unaware of the cellular processes outlined above. The National Institutes of Health is to blame for this. Many therapies the NIH and the WHO initially recommended such as remdesivir, convalescent plasma and monoclonal antibodies simply did not work. This theoretical void also exists because there is a blind spot in medical education. This has been compounded by the media’s censorship of free speech were anything that deviates from official NIH doctrine, including actual science, must be suppressed. This has had the unfortunate consequence that both scientifically based information and misinformation is sometimes equally suppressed. Meanwhile, doctors have catastrophically failed to treat Covid-19 and other deadly viral diseases using either selenium supplements or NSAID antivirals because they are not taught this in medical school. Selenium is not a patented medicine and is thus outside the boundary of the usual medical school curriculum. Many old-line physicians dismiss selenium as merely “nutrition”, failing to appreciate the critical central roll selenium plays in both cellular and immune related health conditions. Many NSAID antivirals do not require a prescription, so they are mostly ignored by the medical profession.

Much of what scientists know about selenium and viral disease has been discovered since 1995. The critical importance of this nutritional element for the treatment of viral illness has been lost in the corrupted scramble to discover more expensive drugs to treat viral diseases instead of treating the cause and terminal results of these diseases that almost always involve selenium depletion as a critical aspect of disease progression. Rapid depletion occurs, especially in terminal, end-stage disease. The National Institutes of Health failed miserably to appreciate the mechanics of viral replication and how that depletes this vital nutrient. They ignored that indisputable fact because it runs contrary to their preferred pandemic paradigm that prioritizes new drug development above the need to protect the lives of taxpaying citizens. Their highly touted “public-private partnerships” are a euphemism for what is at its core, government welfare for the pharmaceutical industry. Those partnerships are a way for industry to temper the burden of arm-length regulation and rake in billions in government subsidies. With 1,800 highly paid lobbyists in Washington DC, the most profitable industry in the world has taken out a legislative insurance policy to keep drug and medical care costs high while allowing the health indices of the American people to gradually slip each year compared to other developed nations. The fact that the United States suffered the greatest comparative death toll from Covid-19 is just one example of how this misguided national health strategy has failed miserably. Ignoring the basic facts of cellular, viral, and immune system science is not a recipe for improving health. It is a recipe for an approaching national health catastrophe.      

             Late in 2020 the Harvard School of Public Health suggested it would be wise for people with Covid-19 to consider taking “painkillers”. This mild-mannered, seemingly off-the-cuff recommendation did not specify what kind of painkillers. Thus this over generalized, poor attempt at advice would have led many to take Tylenol, a brand of acetaminophen, for pain, instead of an anti-inflammatory drug.  Anti-inflammatories like non-steroid anti-inflammatory drugs – NSAIDS - inhibit both inflammation and viral replication. They kill two birds with one stone by inhibiting the NF-kB jet-fuel protein that stimulates both replication and inflammation. Acetaminophen does not inhibit NF-kB or viral replication. It works via a different mechanism to block pain. While the Harvard P. Chan School of Public Health mentioned neither selenium nor NSAIDs, Anthony Fauci of the NIH was claiming as late as December 2020 that there were no drugs that could help treat early Covid infection. To the contrary, there were more than half a dozen non-steroidal anti-inflammatory drugs that could have been used to slow the progression of Covid from its earliest stage. Selenium also inhibits NF-kB and should be used from day-one of infection. However selenium is even more critically essential once a person has been hospitalized. By the time people are hospitalized with Covid, 100% are seriously deficient in selenium. Lack of sufficient selenium has been shown to be the dividing line between those who live and those who die with Covid. Survival is demarcated between those who retain enough selenium resources to keep their immune systems functional, and those who lack or lose so much selenium that their immune systems collapse, and they succumb. Unfortunately, people over age sixty-five progressively experience lower levels of selenium as they age. Accordingly, the strength of their immune systems also decline in line with that fall in selenium. That is one of the primary reasons those over sixty-five are the most vulnerable to  severe Covid, death from Covid, and other potentially deadly viral diseases like influenza. So how can medical practitioners treat Covid and Long Covid more successfully? As with most diseases, it is best to treat both the cause of the disease and its symptoms.          

            The first thing to consider in treating Long Covid is the underlying cause of the condition and the various factors contributing to the continuation of the syndrome. The primary cause of progression to serious disease and then death from Covid is the dramatically progressive, devastating loss of selenium caused by uninhibited viral replication. The second underlying factor is a continuing low level of inflammation and probably low-level viral replication that promotes the perpetuation of symptoms and the immune response. Thus the obvious partial therapeutic solution to Long Covid is replenishing the level of selenium in the body by using selenium supplements, plus the use of anti-inflammatories to tamp down the two factors that contribute to the persistence of symptoms.  

            Thus, three continuing underlying conditions contribute to the unextinguished symptoms of long Covid. First, a continuing low level of viral replication. Second, an obvious lingering wide-spread  inflammatory condition. And third, blood clots that continue to form, in many cases micro-clots within organs, including the lungs that block blood flow and can damage those organs.  

            Taking selenium supplements directly addresses all three problems. But selenium alone is not a panacea. Selenium works both as an antiviral and an anti-inflammatory because it inhibits NF-kB. It possesses additional antiviral activity working through several other mechanisms, including in the case of SARS-CoV-2 as a protease inhibitor. It also assists against blood clots because selenium helps prevent platelet aggregation. Unsurprisingly, the underlying cause of distributed intervascular coagulation - DIC – that consists of massive blood clotting throughout the body is the viral depletion of selenium that normally assists in the free-flowing circulation of blood. This is most dramatically demonstrated in Ebola and other hemorrhagic fever diseases where selenium is rapidly and  drastically depleted causing DIC systemic clotting throughout the body. In part, this explains how selenium helps prevent heart attacks and stroke.

A second common medication that would help attenuate all three lingering underlying contributing factors in Long Covid is aspirin. First developed in 1897 by Dr Felix Hoffman of the Bayer company in Leverkusen, Germany, aspirin, acetylsalicylic acid, or ASA is the original miracle drug. In moderate doses it is much safer than most other drugs. Today the pharmaceutical industry has tried to discredit many off patent drugs in favor of much higher cost patented medicines that are often no better than the medications they replace. In this case aspirin helps reduce blood clotting, inflammation, and NF-kB stimulated viral replication. However it is less effective in reducing NF-kB than stronger NSAID drugs that might be recommended. Still, aspirin is safe, cheap, and reliable, and a first line of defense against viral illness. Although all NSAIDS will reduce inflammation and viral replication, some may not work as anticoagulants.

Aspirin’s peak concentration in blood is two hours after ingestion. It has a half-life of four hours so then there is only half as much in the bloodstream as at its peak. In the mid-1990s when I investigated whether aspirin is bad for the stomach, I reviewed twenty-one articles in the medical journal Gastroenterology. Four journal articles explained how bad aspirin is for the stomach. The other  seventeen articles explained that since the lining of the stomach completely replaces itself every three days, it quickly adjusts to even a moderately high dose of aspirin. Years later when I did a deep dive on the side effects of aspirin, I learned that the people who mostly had problems with aspirin were over seventy and took large quantities of the drug, essentially overdosing or abusing it. Due to a four-hour half-life, if a person takes one aspirin every four hours the body maintains the equivalent of one aspirin in the blood stream at any one time. Taking that dose of aspirin has also been shown to increase CD4 count for up to one year. It is not known if some other NSAIDs might also have that effect.

 Before protease inhibitors came on line in 1996, I suggested that those with HIV take four aspirin per day, four to five hours apart as complementary therapy for HIV disease. I still suggest taking one full-strength tablet per day since that can even help slow some cancers. However since aspirin triggers a molecular switch to prevent platelet aggregation and that switch stays switched off for approximately six days, to prevent blood clotting, one could take just one regular aspirin tablet twice a week and use a stronger NF-kB inhibitor like naproxen to inhibitor NF-kB, inflammation, and viral replication. In case of more serious pain, diclofenac or curcumin may be considered. A list of stronger NF-kB inhibitors found on page 48 should only be considered if one experiences a more serious case of Covid-19. Those should not be necessary for Long Covid unless serious pain exists. Thus a foundational therapy for Long Covid may consists of selenium 200 to 400mcg daily, plus 100mg ASA on average daily, plus a standard dose of Naproxen. This will reduce the impact of the underlying perpetuating causes of Long Covid. Selenium supplementation will boost the immune system and supply enough of this essential trace element to assist in rebalancing the antioxidant system and help with other cellular repairs. Physicians should add on to this basic foundational therapy program of selenium plus NSAID antivirals by prescribing a therapeutic regimen to directly address the unique combination of symptoms each patient is experiencing.  

A five-pronged explanation of the cause of Long Covid includes 1) continuing inflammation, 2) low-level viral replication, 3) selenium depletion-related blood clots, and 4) the damage that has been done to tissues and organs, and 5) damage sustained by the endocrine, nervous, and immune systems. The combined effect of all those deleterious factors fully explains the continuing problem of Long Covid. The damage that has been done to physiological systems must be addressed so they can slowly repair themselves. Making sure the body has an adequate selenium supply is essential to this recovery process.

One additional factor that deserves additional consideration is nerve damage. Unusually, SARS-CoV-2 can infect and damage nerve cells and cross the blood brain barrier. Thus many of the sequelae that are apparent in Long Covid are due to the specific damage to the nervous system There are three communication networks in the human body that Covid damages - the nervous system, the immune system, and the endocrine system. Covid-19 severely impacts all three. That contributes greatly to Long Covid. In the past it was believed that nerve cells did not regenerate so if nerve cells were damaged, they were gone for good. That is no longer  accepted knowledge. However nerve or brain damage may take longer to repair itself and may contribute to the length of neurological aspects of Long Covid.  

 

A myelin sheathing protects the outside of nerve cells the same way plastic sheathing protects an electrical cord. Because SARS-CoV-2 can infect nerve cells, they become vulnerable to attack by the immune cells that are sent to attack viruses.  

Oxidants and Macrophages

Damage to the myelin sheathing….. Higher levels of antibodies may contribute to this’ Aspirin has also been shown to help reduce damage to myelin sheathing and thus the nerves.   

To understand and establish a framework to explain Long Covid, many scientists have tried to compare the complexities of Long Covid to other syndromes that share some of but all the characteristics that Long Covid exhibits.     

3 triggers to autoimmune diseases – pregnancy, viral disease, and severe trauma