Coronavirus news & views

COVID-Diabetes Link Confirmed

As I penned in these virtual pages almost a year ago, COVID survivors have a high risk for developing diabetes. Early on, diabetes was identified as a risk factor for severe COVID illness, but two years later, scientists were surprised by the unforseen reverse correlation between COVID and the metabolic condition. The increased risk for diabetes in COVID survivors was recently confirmed by US and German scientists.

A study of more than 180,000 American veterans done at the St. Louis VA Health Care System found that COVID survivors were 40% more likely to get a new diagnosis of diabetes within a year of their COVID diagnosis than a control group of veterans who avoided the virus. That works out to about 13.5 extra cases of diabetes per 1,000 COVID patients.

The increased risk for diabetes was evident even in people who had a low risk of diabetes before COVID, and the likelihood of newly diagnosed diabetes increased with the level of care patients received for COVID. In other words, the sicker the patients were with COVID, the more likely they were to develop diabetes.

The other study from Germany found that people who had mild COVID cases were 28% more likely to be diagnosed with type 2 diabetes compared to a control group consisting of patients who had an upper respiratory tract infection caused by a different bug. That study was based on an analysis of electronic records from a nationwide primary care database that followed patients, including almost 36,000 COVID cases, for 3-5 months. This means that these newly diagnosed cases of diabetes arose quickly after COVID infection, and were not a result of general respiratory infection, but were a specific consequence of CoV-2 infection.

Questions remain about whether diabetes that follows COVID is just temporary and reversible after patients fully recover, or whether it leads to chronic disease. In other words, if you had even mild COVID, you should ask your doctor to screen you for diabetes, which simply entails a fasting blood draw to test for glucose and hemoglobin A1c levels, which are elevated in diabetic patients.

A lingering question is how COVID leads to diabetes. Does the virus directly affect the insulin-secreting beta cells in the islets of the pancreas, or is new-onset diabetes caused by metabolic changes in fat cells which we know are readily infected by the virus. It is also possible that insulin production is perturbed by viral damage to the cells that line vessels supplying blood to the pancreas, indirectly causing death of insulin producing cells. A more trivial cause for post-COVID diabetes could simply be an unveiling of incipient diabetes that might have gone undiagnosed because people have been away from the health-care system during the pandemic. It is also possible that steroid medications prescribed to tame the COVID inflammatory response could elevate glucose levels in the blood, leading to a diabetes diagnosis.

Research into the cause of the COVID-diabetes link continues apace—stay tuned.

Note: In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want.

The Long Haul, Part 4: The Cost of Long COVID In Terms Of Individual Health And Quality Of Life

Surviving COVID-19 is one thing, recovering is another.

My frustration with those who would minimize the impact of COVID-19 is reaching an apex. I constantly have to deal with their baseless rationalizations that “it is just a cold,” or “it only kills 0.01% of people” (actually the number is 2% around the world), etc. And I constantly reply to these iconoclasts that COVID has become, by far, the leading killer in the US. I also explain over and over that treating simple mortality percentage as the only relevant statistic to consider is falderal. For example, the Spanish flu also killed “only” 2% of those infected, but in just 24 weeks, that virus killed more people around the world than were killed in WWI AND WWII together! The percent figure is meaningless without considering the percent of what. Why do they continue to ignore the devisor and, hence, the total number of deaths?

A small percentage of a very large number is, in fact, another large number.

Those who wish to downplay the significance of the pandemic only focus on this mortality percent, but mortality is NEVER the whole story for any pandemic. A serious person will also consider the morbidity caused by the disease. In fact, the major CDC publication on health in the US is called the Morbidity and Mortality Weekly Report. Notice that it considers both morbidity and mortality, and further notice that morbidity is listed first in the title. I have made three prior posts in this series on Long COVID, about the significant lasting morbidity of COVID-19. You can see these posts here, here, and here. In those posts, I shared data showing that some ~10-30% of COVID survivors suffer serious health problems that last months.

In those posts, I mentioned the cases of a young, healthy MD, and of a young, healthy journalist, both of whom struggled with long COVID, and how it affected their careers and cost them thousands of dollars in out-of-pocket expenses for the dozens of tests and doctors they needed. In an article in Maclean’s magazine, a reporter interviewed many Canadian long COVID patients and heard how their lives have been turned upside down. They reported that they are unable to live like they used to and care for their families, do anything mildly strenuous, or even cook their meals. They spend long stretches of time in bed. Many of those interviewed had not returned to work several weeks after recovering from the acute disease.

Anecdotes like these have been repeated millions of times around a world that, according to the Johns Hopkins University COVID tracker, has seen more than 330 million cases of COVID (and this is a significant undercount since many countries do not record these data well). Research has corroborated these anecdotes.

+++

Common long-term symptoms include debilitating fatigue; respiratory problems; and “brain fog.”  Other common symptoms include compromised function of the heart, and kidneys, which sometimes require transplantation. Wide-spread clotting problems can cause significant illness and even limb amputation. There also are frequent neurological and neuropsychiatric symptoms as highlighted in Part 3 of this series. Surprising manifestations continue to emerge, such as new-onset diabetes.

Lung scarring often occurs in patients who experienced COVID-caused acute respiratory distress syndrome (ARDS), a common problem seen in acute COVID patients who required ICU care. ARDS is a serious respiratory problem that can be caused by different respiratory viruses and other things. About a third of patients with ARDS arising from any cause were unemployed 5-years later because of their lung damage. It is fully expected that patients with COVID-related ARDS will be found to fare similarly.

There also is the dysfunctional immune response common in many moderate to severe COVID cases that can cause long-term multi-organ damage, particularly in the liver and kidneys. It can also disrupt coagulation control of the blood, sometimes leading to amputations, mostly in patients in their 30s and 40s. It was reported that amputations due to vascular problems have doubled since the CoV-2 virus arrived. Compromised coagulation control in COVID patients can also precipitate adverse cardiovascular events such as heart failure, or hemiplegia due to strokes. Data from the COVID Infection Survey on long-COVID suggest that the risk of major adverse cardiovascular events and long-term illness is about ten times higher in COVID patients (even after mild COVID) compared to non-COVID matched controls. A Dutch study found that 31% of COVID ICU patients suffered thrombotic complications. These problems can unexpectedly pop up in people who had completely recovered from COVID.

A global survey tallied 205 different symptoms across 10 different organ systems that can persist after COVID infection has cleared. Typically, these manifold long COVID symptoms do not appear in isolation, but in multi-symptom clusters. A long hauler typically has several of these problems at a time.

While it is estimated that overall, 10-30% of COVID patients become long haulers, reports on the number of people suffering long COVID vary widely. Depending on the report, anywhere from 30-90% of COVID survivors suffer long term health problems. And even at the lower end of that range, 30% of over 330 million people world-wide who have been infected is a very large number. It represents an enormous personal toll in terms of lost health and diminished quality of life. Some of these reports are summarized below.

• Half of 70,000 hospitalized UK COVID-19 patients experienced long-term complications, according to a study published in July. Complications occurred regardless of age group: For instance, 25% of adults aged 19-29 developed complications, as did 33% of those aged 30-39. Complications affecting the kidneys and respiratory system, liver injury, anemia, and arrhythmia were the most common.
• Many COVID-19 survivors require extensive and prolonged rehabilitation. An European study found about one-third of 1,837 non-hospitalized COVID patients (i.e., those with mild disease) needed a caregiver three months after their symptoms started.
• In April the CDC reported in its Morbidity and Mortality Weekly Report that 69 percent of nonhospitalized adult COVID patients in Georgia required
• one or more outpatient visits 28 to 180 days after their diagnosis.
• A study published last February in the Journal of the American Medical Association found that roughly one-third of 177 people who had mild COVID disease not requiring hospitalization reported persistent symptoms and a decline in quality of life up to nine months after illness.
• 70% of people hospitalized for COVID-19 in the UK had not fully recovered five months after hospital discharge. They averaged nine long COVID symptoms requiring continued medical care.
• A study in South Korea found that 90% of patients who recovered from acute COVID experienced long-term side effects.
• According to a report in the journal, Lancet, 75% of people hospitalized with COVID-19 in Wuhan early in the pandemic, reported continued problems with fatigue, weakness, sleep problems, anxiety and depression six months after being diagnosed with the disease. More than half also had persistent lung abnormalities.

Data like these have been commonly reported around the world, pointing to a more chronic and expensive health problem than seen with the flu or common cold, which often is caused by different coronaviruses. A July 2021 article in Scientific American talked about how all of this indicates that long COVID will cause a “tsunami of disability” that will affect individual lives as well as create enormous strain on the health system. Consider the numbers: More than 60 million Americans (this is an underestimate since many COVID cases are not reported) have been infected with the CoV-2 virus. Therefore, if only 30% of these suffer long COVID, we are talking about 20 million long haulers and counting.

The related health care and disability costs of all of this are also still being calculated. How many “long haulers” will not be able to return to work for months, or at all? How many will need short-term disability payments, and how many will become permanently dependent on disability programs? As increasing numbers of younger people become infected, will we see a generation of chronically ill? This then moves us to consider the economic and financial cost of long COVID, which will be the topic of the next installation in this series.

Stay tuned.

Note: In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want.

The Long Haul, Part 2: What Is Long COVID?

In the 1890s one of the biggest pandemics in recorded history, known then as the “Russian flu”, swept the world and killed one million people (for perspective, that is out of a world population about ¼ of today’s population). That “flu” is now thought to have been a novel coronavirus. Like the current coronavirus, SARS-CoV-2, the Russian “flu” was a new human pathogen so few people had any natural immunity to it and it was quite lethal. Not only that, but as the pandemic waned, it left in its wake a global wave of long-lasting neurological problems in the survivors. A similar long-lasting post-acute disease wave followed the next big pandemic, the “Spanish” flu of 1918 (which really was due to the influenza virus). The common symptom following the Spanish flu was lethargy so bad that in Tanganyika (modern-day Tanzania), for example, it caused a famine because people were too debilitated to pick the harvest. Other viral outbreaks, including SARS, MERS, and Ebola, also have been associated with long-term sequelae in survivors. However, today’s long COVID complications are far more common and far more variable than the persistent symptoms following these other viral pandemics. The variety of unrelated long COVID symptoms has flummoxed doctors hard pressed to diagnose and, hence, treat the constellation of chronic problems that appear in each patient.

As I wrote in Part 1 of this series, a wave of what has become known as “long COVID” is emerging in many people who have recovered from the acute disease. A recent review chronicling the effects of long COVID reported that “long haulers” commonly experience fatigue, sleep problems, and joint and muscle pain long after their bodies cleared the virus. Other symptoms range from the mundane to the bizarre: brain fog, shortness of breath, fatigue, tremors, tooth loss, racing heart, glaucoma, and diabetes among others. Long haulers are also at a significantly increased risk of dying months after infection. A large study found that after surviving acute COVID-19, patients had a 59% increased risk of dying within six months after their initial diagnosis. This translates into an extra eight deaths per 1000 patients. Thus, the consequences of the acute disease itself are just the tip of the iceberg.

Because the official definition of the chronic problem is fluid, we are still learning what this new malady is. A UK study published last December simply defined the syndrome as a collection of symptoms lasting for more than 28 days after initial diagnosis. However, another British study as well as Britain’s National Institute for Health and Care Excellence vaguely and broadly define long COVID as “signs and symptoms that develop during or after an infection consistent with COVID-19, and that continue for more than 12 weeks and are not explained by an alternative diagnosis”. It does not specify a list of what the symptoms are.

But, there are many. A global survey tallied 205 different symptoms across 10 different organ systems that can persist after COVID infection has cleared, including those affecting the heart, lungs, gastrointestinal system, muscles, and joints. There also are frequent neurological and neuropsychiatric symptoms as highlighted in Part 1 of this series. A sufferer typically has several of these problems at a time (14 different symptoms on average), with the most debilitating usually being one of three: severe breathlessness, fatigue, or “brain fog”. Other common symptoms included compromised function of the lungs, heart, and kidneys sometimes requiring transplantation. There also have been skin rashes, and newly diagnosed diabetes.

What exactly is long COVID? About the only thing we can say with any certitude at this time is that long COVID exists but is not easy to describe, possibly because it really is more than one malady. The only constant between different long COVID patients with different symptoms is that the conditions are a collection of varied symptoms that persist long after the acute disease subsides, which sounds as vague as the British definitions described above. Long COVID clearly represents a new health malady or maladies since it is not generally found in uninfected people, but is common in COVID survivors; yet not all COVID patients experience it. Long COVID can affect any post-COVID patient at any age, but it mostly presents in middle-aged people and seems to slightly prefer women. Even people with asymptomatic CoV-2 infection can have late arising effects that fit the profile of long COVID.  Multiple studies have shown that infected people who do not get acutely ill can still show irregular lung scans, for example. One such study found that nearly 60% of people with asymptomatic infection showed some lung inflammation in CT scans. Other studies have shown that young people with asymptomatic or mild infections can have long lasting cardiac issues, while others show signs of small blood vessel damage.

Some of these symptoms can be similar to other recognized, if not fully understood chronic problems, such as chronic fatigue syndrome (CFS), which is one of the most common complaints that long haulers have. CFS remains a mystery malady with an unknown cause, but it often follows a viral or bacterial infection. It is, therefore, possible that long-COVID CFS-like problems might be no different from classic CFS. It also is possible that CFS-like long COVID symptoms are not at all related to what is recognized as classic CFS, and they are simply different illnesses with similar symptoms. Time and research will tell.

Broadly speaking, there are three types of long COVID patients, according to one NIH scientist. The first are generally characterized by “exercise intolerance”, meaning they feel out of breath and exhausted from even mild physical activity. The second are characterized by cognitive complaints like brain fog and/or memory problems. The third type experiences problems with the autonomic nervous system, which controls things like heartbeat, breathing and digestion. Patients in this group suffer from symptoms such as heart palpitations and dizziness. Impairments of the autonomic nervous system are known as dysautonomia, which is an umbrella term for a variety of syndromes. Physicians treating long-COVID patients say there has been a marked increase in dysautonomia since the pandemic began. A rehabilitation doctor at Mount Sinai Hospital, in New York, says that roughly 80% of people who show up at his long COVID clinic have dysautonomia of one type or another.

Not only do long COVID patients suffer chronic debilitation, they also are at increased risk of dying. One of the largest studies of Covid-19 “long haulers” found that COVID survivors had a 59% increased risk of dying within six months after contracting the SARS-CoV-2 virus. The excess mortality translates into about 8 extra deaths per 1,000 patients. Thus, the pandemic’s hidden toll is that many patients require readmission, and some die, weeks after the viral infection abates.

What causes long COVID? What causes the myriad of symptoms lumped under the long COVID umbrella are being studied, but it seems that not all are actually caused by the CoV-2 virus. Based on what we have gleaned from observations of a few million long COVID patients around the world, the focus is on three possible biological explanations. One is that long COVID is due to a persistent viral infection. A second possible cause could be an autoimmune disorder. The third possibility is that it is a lingering consequence of tissue damage caused by inflammation during the initial, acute infection.

Supporting the first hypothesis that the infection persists even after COVID disease has passed is that some patients very slowly clear the virus completely. The virus or its remnants persist along with the long lasting symptoms. These patients are not infectious so it could be that they harbor some altered form or fragment of the bug which does not replicate, but is nevertheless making some viral product that their bodies are responding to. This is known to occur with other viruses, including measles, dengue and Ebola. RNA viruses are particularly prone to this phenomenon, and CoV-2 is an RNA virus. Direct proof of this hypothesis is lacking, but pertinent clues abound. A study published recently in Nature showed that some people had traces of CoV-2 proteins in their intestines four months after they had recovered from acute COVID-19. Viral products from CoV-2 have also been found in people’s urine several months after their recovery. All this is circumstantial evidence, to be sure, but viral persistence is consistent with long COVID in certain patients.

The second hypothesis, that long COVID is an autoimmune disease, holds that the virus causes something to go awry with the immune system inciting it to attack some of the body’s own tissues. Some evidence backs this idea, too. The immune system is a complex, tightly regulated machine designed to discriminate between your own cells and foreign entities such as viruses. Sometimes this ability to distinguish self from non-self fails and an immune response is generated to one’s own tissues. Some patients suffering from long COVID have badly behaving macrophages, which are immune cells responsible for gobbling up foreign invaders and displaying them to immune cells inciting them to make antibodies or to kill infected cells. Other long COVID patients exhibit abnormal activation of their B-cells, which churn out antibodies against the pathogen that can sometimes cross-react with the body’s own cells causing complications. Since antibodies circulate for several months after an infection, it makes sense that this could cause problems months after recovery from the disease. Again, this evidence is circumstantial, but consistent with the observations in some long haulers.

The third hypothesis about the cause of long COVID holds that the body’s inflammatory response during the acute illness causes long-term damage to cells and tissues leading to chronic inflammation. This sometimes happens with other viral diseases, but it could be particularly likely with COVID-19 since out-of-control inflammation, caused by a cytokine “storm” is a common hallmark of severe cases of acute illness. One guess is that the inflammation damages parts of the autonomic nervous system, or that the virus might damage the cells that line blood vessels, either by infecting them directly and/or via inflammation from the immune response. This could change the way blood flows to the brain and other organs, and may thus explain the brain fog and other organ failure that is sometimes seen. This too remains circumstantial, but consistent with current observations in certain patients.

Bottom line: Long COVID probably embraces several different chronic conditions with different causes. Studies to investigate each of these possibilities are under way.

We will see.

The Long Haul, Part 1: What Long COVID Is Like

This is the first part of a multi-part blog series on long term morbidity associated with COVID-19 infection (how many parts there will be in the series remains to be determined). When public health scientists assess the impact of a disease on society, they consider both mortality as well as morbidity. In fact, the CDC’s primary assessment of US health is a publication called the Morbidity and Mortality Weekly Report. This blog series was prompted, in part, by repeated assertions by vaccine nay-sayers that since the mortality of COVID is only about 1.5% of those infected (they usually cite a false and much lower mortality rate), the vaccines and mandates are unnecessary. To that naive statement I make three points that the nay-sayers typically ignore:

1. The Spanish flu had a similarly low mortality rate as COVID-19, but in just 24 weeks during its second wave, it killed more people around the world than were killed in the 10 years of WWI and WWII combined. Hence, just looking at the percent of infected people who die does not tell the whole story if you do not also mention the total number of people infected. One percent of a billion people is a very large number, for example.
2. By focusing only on the low mortality rate, the vax nay-sayers are engaging in a logical fallacy called “confirmation bias.” That is, they totally ignore the statistics that do not support what they want to believe. What they ignore here is the cost incurred by disease survivors, or the morbidity. Morbidity rates usually swamp mortality rates and, as we shall see in this blog series, long COVID can cause a disproportionate cost to individuals and society in terms of damaged health, lost productivity, increased burden on health systems (which also affects care of critical non-COVID patients) and insurance payors, lost earnings, interrupted careers, and even delayed deaths that are not attributed to COVID, such as suicide, which I discuss below.
3. Last December, just before the vaccines first rolled out, I reported that COVID-19 deaths had become, by far, the number one killer in the US, which contradicts the “negligible death rate” narrative of the nay-sayers. At that time COVID deaths far outpaced deaths due to cancer and heart disease, the previous top two causes of death in the US. That high COVID death rate dropped because of the vaccines. These facts put the lie to anti-vaxer’s claims that we do not need vaccines or public health mandates because the death rate from COVID is low. The COVID death rate had become very high, but is now much lower precisely because of the vaccines and mandates.

In this post, Part 1 in the series, I relate what long COVID is like to some long haulers. In future posts, I will focus on the costs of long-term COVID, and on the specific devastating health effects long-haul COVID can have on the neurological system, on the kidneys, lungs, and on new-onset Type 1 diabetes. And I will discuss what we have learned about the causes of long COVID and how to treat or manage it.

What is it like for long haulers? I began this blog in April 2020, and one of the first posts I made was about the experience of an emergency room doctor who was on the front lines of the early pandemic working in an ER in NYC, which was very hard hit by the pandemic. She caught the disease and spent a couple of weeks in the ICU recovering from it. But, something was not right with her after she was discharged from medical care, and she was re-admitted to an in-patient psychiatric unit to treat her mind. After a few weeks, she was released to convalesce at her sister’s home. But, she was still not right in her mind and eventually shot herself in the head. Her suicide was not counted as a COVID death. There have been other post-COVID suicides since then.

There are the recent post-COVID suicides of Texas Roadhouse CEO Kent Taylor and "Dawson's Creek" writer Heidi Ferrer and several others, which reveal a heightened risk of suicide as a sequelae of long COVID.

Sometime early in the pandemic, a healthy, young journalist who had recently graduated from journalism school also caught the disease. She eloquently wrote about the ordeal, which began in full four weeks after she had been diagnosed and two weeks after she no longer tested positive for the virus. She wrote how her body shook for five days before checking into a North Carolina hospital not knowing what was wrong. She wrote that two nights before going to the ER, and after being “cured” from COVID-19, she was jolted awake by what felt like a “brain zap.” She staggered into the hallway which she described feeling like it was on a funhouse tilt. She said she felt like she was in a Salvador Dali painting, “distorted and oozing.” When she tried to speak to her husband, the words came out drowsy and slow. I personally found the description of her feelings interesting since a friend of mine who had experimented with drugs in her earlier life once told me about tripping on LSD and feeling like her “face was melting like in a Dali painting.” For the young journalist, long COVID was somewhat similar to the experience of my friend on LSD.

Like 10-30% of the ~200 million, globally (a large number), who have survived COVID-19, the journalist did not get better after she was declared to be COVID-free,  and in fact she said that what came next was much worse than the disease. After a month of non-stop post-COVID malaise, she found herself in the emergency room complaining that she had a “shaky, electric feeling” in her stomach, and that she could not think or sleep. Eight months later the waves of illness had not let up. She was one of the early cases of long COVID, which we now know occurs in 10-30% of COVID survivors (although one study from Italy claimed that >50% of COVID survivors experienced symptoms at least four months after their infection).

The journalist wrote in July 2021, “Since December (2020), I've seen 15 specialists, received eight scans, visited three ERs and--even with insurance--spent $12,000 seeking a return to normal life. Since February, I moved across the country (from North Carolina) to receive treatment from a post-COVID recovery clinic at (the) Keck School of Medicine at the University of Southern California. The clinic refers its patients to specialists depending on their symptoms and provides a social worker. I receive weekly treatment from a physical therapist, occupational therapist and neurologist there.”

“I've had more than 50 symptoms ranging from cognitive impairment, insomnia, vertigo, extreme light and sound sensitivity, and fatigue, to convulsion-like shaking, slurred speech, hair loss, muscle weakness, anxiety.” She said that she was too “foggy” to read or even to watch TV news, which was her occupation. She was unable to write for six months, and had not had a symptom-free day since November 6, 2020, the day she tested positive for Covid-19. Most of these symptoms occurred simultaneously.

She writes on, “Before my illness, I never had any thoughts about suicide. This changed after I got sick. I'm no longer in this dark place, but the months it held me hostage I inched closer to the edge than I ever wished to be. As my brain fog intensified, I developed such a palpable anxiety, it brought with it new compulsive behaviors like "trichotillomania," or hair pulling. The days blended into one dream-state. I had only what I can describe as brain zaps. I'd wash my hair, forget, then wash it again. The further I slipped away from reality, the deeper my depression became.”

“I found myself researching death-with-dignity laws. I learned that Northern European countries have some of the most lenient.” She entertained suicide for the first time in her life. Other post-COVID patients have also described having thoughts of suicide and some have acted on that.

The experience of this journalist and a few million others like her quickly became noticed anecdotally by the medical establishment and the patients were referred to as “long haulers.” Their constellation of symptoms became known as “long COVID,” or more formally Post-Acute Sequelae of COVID-19 (PASC). As long COVID became increasingly recognized, the medical establishment realized that it was something entirely new and that they had little clue on how to deal with it other than try to manage the myriad symptoms, now numbering at more than 200. We now know that long haulers can suffer months of “brain fog,” persistent headaches, chronic fatigue-like symptoms, breathing problems, lung failure (sometimes requiring transplants), new-onset diabetes, depression and/or anxiety, dizziness, muscle and joint pain, and more. These occur in 10-30% of old and young infected people, and even in those who had mild COVID-19.

Medical science is slowly catching up, but progress is slow, not for lack of effort, but simply because medical research takes time. The very recent FAIR Health study of COVID-19 patients, the largest to date, analyzed health records of nearly two million people who have been infected with the virus in the US and found that hundreds of thousands have sought care for new health conditions after their acute illness subsided. New research points to neuropsychiatric changes in Covid-19 survivors potentially due to brain inflammation or to a disruption of blood flow to the brain. Then there are other theories, partly borne out by an Oxford study, that the virus affects serotonin and dopamine neurotransmitters, affecting brain function and physiology. A recent case published in the Journal of Psychiatry Neuroscience and Therapeutics reported that "autoimmune-mediated psychosis" caused a 30-year-old without previous health or psychological conditions to become delusional after recovering from COVID. In response to this increasing concern over long COVID, NIH launched a large nationwide study of long COVID and recently  awarded $470 million to New York University Langone Health. This NIH REsearching COVID to Enhance Recovery (RECOVER) Initiative aims to learn why some people have prolonged symptoms or develop new or returning symptoms after they recover from the acute phase of infection.

In future posts in this blog series, I will cover in more detail what we have learned to date about long COVID. Since the data keep coming in, I cannot predict when this series will end.

So, stay tuned and please ask questions.

Note: In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want.

Left-Over Neanderthal DNA Affects Our Vulnerability To COVID-19

Biden recently called Texas “Neanderthal” (pronounced “ne-ander-TALL,” not “THall”) for doing away with pandemic restrictions. Texas did so because it has seen a sharp decline in COVID-19, and it just reported its first day with no COVID-19 deaths. Maybe Biden is right, who knows? But maybe Texan’s residual Neanderthal genes could explain its drop in infections and deaths.

Neanderthals evolved in Western Eurasia about half a million years ago and died out around 40,000 years ago, but they did leave a bit behind. In the past decade, sequencing of DNA extracted from fossils and other samples from ancient hominids have shown that Neanderthals and Homo sapiens co-existed, and even consorted, producing hybrid offspring. Almost half of the Neanderthal genome still survives, scattered among almost all modern people’s DNA. The exception is those with mostly Sub-Saharan African ancestors, since Neanderthals seem never to have lived in Africa.

Such ancient genes in modern humans have been associated with things like hairiness and fat metabolism. Some of the left over Neanderthal genes also are linked with how our system affects things like risk of lupus, Crohn's disease, allergies, and diabetes. A pair of recent papers now suggests that COVID-19 belongs on that list as well. Two long stretches of DNA we inherited from Neanderthals, appear to confer either resistance or susceptibility to severe COVID-19.

Researchers at the Max Planck Institute for Evolutionary Anthropology in Leipzig, where research on Neanderthal DNA was pioneered, published in the Journal Nature last September that one Neanderthal DNA string on human chromosome 3 provides the major genetic risk factor for serious COVID-19 illness (other non-genetic risk factors include co-morbid conditions such as age, being male, obesity, diabetes, etc.). Those who carry one copy of that archaic DNA sequence have a 2-fold risk of a trip to the ICU upon infection. Those who have two copies of that sequence, one from each parent, have another doubling of risk for serious disease. The distribution of that ancient sequence around the world is uneven, possibly explaining regional differences in the incidence of severe COVID-19. In Bangladesh, 63% of Bengalis carry at least one copy, whereas it is found in only about 16% of Europeans. Not surprisingly, it is almost absent in Africa, and more surprisingly, rare in large areas of Eastern Asia. One can only speculate that it also might be rare in Texans.

How the gene affects COVID-19 severity is not known, but one gene within the sequence encodes a protein that interacts with the cell receptors used by the CoV-2 virus to enter cells. The sequence is also thought to affect cytokine production. An over-exuberant cytokine “storm” response to infection is one way that COVID-19 leads to severe disease. It is interesting that such a cytokine response is protective against cholera and that cholera has long been a problem in Bangladesh and India. That could explain why this specific Neanderthal DNA sequence has been fixed at a high frequency in the genomes of those populations—it confers a survival advantage to an endemic infectious disease. This is reminiscent of why the sickle cell genetic trait is prevalent in Sub-Saharan Africa. That genetic trait protects carriers against malaria, so it confers a survival advantage to people living in areas endemic with malaria.

The second study, published by the same lab in February in the Proceedings of the National Academy of Sciences links another Neanderthal DNA sequence found on human chromosome 12 to protection from serious disease. Carriers of this sequence are 22% less likely to develop serious disease. About 25-35% of the population in Eurasia carries at least one copy of the sequence, while about 50% in Vietnam and Eastern China do. Even before this area of chromosome 12 was discovered to come from Neanderthals, a gene in the area was known to hinder spread of RNA viruses like CoV-1 (SARS), West Nile virus, hepatitis C, and perhaps CoV-2. It instructs cells to commit suicide when they are infected by one of these viruses, hence reducing the viral load the infected cell can pump out.

All of this provides genetic clues on why some countries and populations have been hit harder by COVID-19 than others, and why others do better.

So, just how Neanderthal are Texans? Do they have more of the good gene or just less of the bad gene? Alternatively, it might just be the chili—eat a bowl of Texas red and go maskless…..

Note: In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want.

Independent Analyses Suggest COVID-19 Can Cause Diabetes

We know that having co-morbid conditions such as asthma, heart disease, diabetes, and others are risk factors for significant COVID-19 disease and death. Now, independent reports out of the US and the UK strongly suggest that having COVID-19 can also lead to the swift onset of diabetes, even in people with mild infections. This includes children. These observations add to the list of long-term health problems for the millions of COVID-19 survivors living with chronic conditions following infection called "long-haulers."

Some 10-30% of COVID-19 survivors develop persistent and sometimes debilitating symptoms after apparent recovery from the disease. It has been known for a few months that in a subset of these long-haulers, lingering metabolic complications require high doses of insulin suggesting that they are developing diabetes. This possible link between COVID-19 and new-onset diabetes was noticed as early as last summer and was reported in Scientific American last February. Two more recent analyses of patient data strengthen the COVID-diabetes link.

• In the US, researchers at the Veterans Affairs St Louis Health Care System’s clinical epidemiology center recently published their findings in the journal, Nature. They used data from VA national health-care databases and found that COVID-19 survivors were about 39% more likely to have a new diabetes diagnosis six months after infection compared to non-infected users of the VA health system. This means that there about 6.5 extra diabetes cases per 1000 COVID-19 patients who are not hospitalized. For hospitalized patients, the risk jumped 5-fold to 37 per 1000, and it is even higher for patients who required intensive care.

• In the UK, a study of 50,000 hospitalized COVID patients was published about three weeks earlier than the US study. The UK study reported that the patients were 50% more likely to develop diabetes 20 weeks after discharge than matched control patients.

How does the virus do this? CoV-2 primarily is a respiratory disease, but we have known since the early days of the pandemic that it also can ravage other organs including the kidneys, brain, and others. The leading theory of how COVID-19 can cause diabetes is that the pancreas, where insulin is produced, also can be damaged by the virus, or by the immune inflammatory response that follows infection. Other possible mechanisms are also being considered.

 Bottom line: As of this month, 153 million people around the world have been infected with the virus. That means that the pandemic has caused a LOT of new cases of diabetes, a chronic disease, for the world to absorb. To monitor global COVID-related diabetes, a world-wide registry has been set up by King’s College London and Monash University in Melbourne. Almost 500 doctors around the world so far have agreed to share data via the registry.

Maybe this information will convince people who down play the disease by only focusing on the low mortality rate of COVID-19 that they also need to consider the accompanying long-term health consequences of the disease.