neurological problems

‘Tis The Season To…..Mask Up Again??

"It's a bug hunt!"

-Private Hudson, in “Aliens”

"Influenza-like illnesses" are increasing at an alarming rate across the country. Yup, ‘tis the season for respiratory diseases and we have more than one to worry about. In years past we mostly worried only about the flu and, sometimes as an afterthought, colds, which aren’t of much concern. But in late 2019, a brand new and very weird bug appeared on the scene, SARS-CoV-2 that caused COVID. It seems that the bug and disease will be an annual guest from now on. This year, we also see a surge of a third bad bug, respiratory syncytial virus, or RSV. All these viruses cause what have been collectively labeled “flu-like illnesses” and together they seem to be worse this year than recent years. The CDC reports that hospitalizations for flu-like illnesses have been steadily rising and that the peak is still to come.

As a result, we are beginning to see increasing reports of a return to local mask mandates. In my own community of Madison, Wisconsin, two major health networks just announced their return, like a bad TV rerun. This includes the University of Wisconsin Health network, where I receive health care. Glad I kept a few masks on hand. What’s in your glove compartment?

I also have read where some grocery stores are now requiring masks. Some stores only require masks on certain days of the week so that customers can select to shop on mask-required vs mask-optional days. Some colleges and large companies reportedly also are beginning to require masks again. So far these mandates are very local and are not a national phenomenon. It is feasible that mask mandates in public spaces and especially for travel could increase if infections and hospitalizations get more serious.

As I often say in these blog posts, “we will see.”

Why is the flu and RSV, which have been around almost forever now causing more than their usual problems? A hint was presented in a blog post I published about a year-and-a-half ago, “What Happened To The Flu And Other Respiratory Diseases?”  In that apparently prescient post, I reported that the world had seen a huge reduction of all infectious respiratory diseases due to the protective non-pharmaceutical interventions (masking, sanitation, isolation, quarantines, closings, etc.) designed to physically protect people from the new coronavirus. They were so effective that some strains of other common infectious viruses are thought to have gone extinct!

That is great news! But, it also means that the world also missed its regular natural booster of common bugs and our herd immunity to them waned. Our youngest were never exposed to those bugs and the rest of us became less resistant to future exposure and that future is now. We are now paying the piper for that lapse in a “bug boost.” Hence, flu and RSV temporarily are having their way with us and enjoying it. At least they are not nearly as nasty as the coronavirus initially was and still could be with a couple of insouciant genetic tweaks.

“Influenza-like illness,” is a catch-all term coined by the CDC to corral COVID and the other two viral diseases. Together, the three have reached an epidemic point in the US and other places across much of the world. The Figure below shows that the US epidemic is currently hitting Southern States the hardest, but expect it to migrate Northward in the next few weeks.

What do the different colors in the Figure mean on a practical level? I can offer one anecdotal example. According to the map, New Jersey, while not a Southern State, still is being hit hard. A family doc wrote about a week ago that all the hospitals in his health system are at capacity. He was unable to send a patient to the preferred ER because its hospital was full due COVID, flu and RSV cases. And the patients with these flu-like respiratory infections who were filling the beds were not necessarily elderly. Most are in their 40’s-50’s. Unsurprisingly, the hospitals and clinics in his health system again require masks. Their staffing is becoming a critical issue as providers also become ill and turn into patients. This is becoming too reminiscent of the early stages of the COVID onslaught when hospitals where overwhelmed and medical personnel were dropping like flies. So far, this experience is sporadic across the US. But, it is becoming concerning.

ORI
Outpatient Respiratory Illness Activity Map Determined by Data Reported to ILINet
This system monitors visits for respiratory illness that includes fever plus a cough or sore throat, also referred to as ILI, not laboratory confirmed influenza and may capture patient visits due to other respiratory pathogens that cause similar symptoms. From the CDC.

The incidence of RSV is high. RSV hospitalizations have increased 60% nationwide over the past four weeks. A couple of deaths in children have been reported in my state. The vaccine for RSV is brand new this year and recommended for people over 65 and for kids; i.e., those at highest risk for severe disease. It definitely is worth it.

Flu is moderate right now, but expect it to soon blossom. Hospitalizations among all age groups increased by 200% for influenza in the past four weeks but still remain below Covid-19 and RSV hospitalizations. For now. They are expected to increase as the peak flu season has yet to arrive.

And then there is our relatively new friend, COVID. On a national level, COVID virus transmission is “very high.” After the post-Thanksgiving surge, as determined by monitoring viral loads in wastewater samples (“take-your-kids-to-work” days in that profession must be fun!), virus levels plateaued. But expect another sharp rise after the Christmas/New Year’s holidays. We have consistently seen this pattern in previous years.

Cov-2 is one of the most mutable viruses that the world has inflicted on us. That means we are constantly seen new variants arising. Surprise, the Omicron subvariant JN.1 is coming onto the scene. It’s the spawn of variant BA.2.86, which was discovered over the summer and was concerning because it came out of nowhere with a whopping 35 mutations in the spike protein (the more mutations, the greater the chance for another very nasty bug). While BA.2.86 caused a comparatively mild disease, it quickly mutated to JN.1 with just an additional single change in the spike protein that made it much more infectious, but it still remains fairly mild. With just one mutation, it became the fastest-spreading CoV-2 variant in the past two years. With all its changes, JN.1 is so different from its Omicron grandparent that there is considerable scientific debate about whether JN.1 should be given its own Greek letter designation, Pi. A weighty debate indeed.

But, a bigger question is whether COVID hospitalizations will follow wastewater sampling trends that show JN.1 (or Pi) viral levels surging through the world, especially in the US where vaccination rates are low. It is concerning that the UK and Singapore, which have high vaccination rates, are now seeing a steep increase in hospitalizations due to JN.1 (or Pi). So why not expect the same or even worse in the undervaxed US? Last week, the CDC warned about such a potentially huge impact due to the wretched combination of low US vax rates and the highly infectious JN.1 (or Pi) virus. As Private Hudson (aka Bill Paxton) in the movie Aliens might say, thanks to the antivaxers, “Game over, man! Game over!”

Also of new concern is that some scientists are now beginning to believe that COVID infection could be damaging our immune systems. If true, that could make infected people even more vulnerable to the other bugs out there such as flu, RSV, and others including bacteria and fungi. COVID could also cause immune dysregulation leading to new-onset autoimmune diseases. So get your COVID vaccines! They can protect you against illness beyond COVID!!

Finally, another concern is that the rapid home tests for COVID are proving to be only 30% reliable very early after infection before symptoms start. In other words, if you believe you have been exposed to COVID, but your home test comes up negative, don’t necessarily believe it. Retest yourself 24, or preferably 48 hours later or when you show symptoms like a fever, cough, etc. If that second test also is negative, you have pretty good confidence you are COVID free and have some other bug.

The pragmatic bottom line. There is a lot of coughing, sneezing and other respiratory distress going around, and it will increase in coming cold weeks as we bundle up and crowd around others indoors. To improve your odds of staying healthy, remember these things:

  • Limit your time around indoor crowds.
  • If you have indoor gatherings, crack your windows and bring out the fans to increase air circulation and air exchange with the outdoors. There is very good evidence that good ventilation really matters and that the amount of viruses we breathe in makes a big difference in terms of whether we get sick and how sick we get. It is worth a few extra dollars on the heating or electricity bill to avoid nasty illness.
  • Room air filters are also a good idea.
  • Get vaccinated!
  • Wash your hands often.
  • If you do get sick, STAY HOME! I have always hated the “brave” soul who came to work with a cough and sneeze. Don’t share your agony!!
  • And there are the good old fashioned masks for use in crowded places, especially in auditoriums, on planes, and other packed indoor situations. I don’t care what the naysayers say about masks, they are flat wrong. They don’t think twice when a store sign requires shoes and shirts to enter. So why do masks bother them so much? They WORK as I have written here before, over and over. Empirical evidence proves masks work. That is why the entire medical profession continues to use them.

Finally, as I have repeatedly admonished, please get vaccinated. Vaccine and booster uptake for all three viruses has been dismal this year. Failure to vax is a major driver in the surge of the flu-like respiratory diseases we are seeing. If you have not gotten vaccinated for all three circulating viruses, why the heck not?? It is way better to prevent disease than to treat disease. A sore arm is much less of an inconvenience than suffering the flu, RSV or lying in a specialized hospital bed turned on your stomach breathing with a ventilator because of COVID.

As I have written in these pages, having COVID can be worse than any flu you ever had. It also puts adults at risk for dealing with weeks of long COVID and getting new-onset diabetes and immune dysfunction. COVID also is much worse than the flu for many kids and puts them at risk for multi-system inflammatory syndrome (MIS).

Why risk what can be prevented by a simple vaccination?

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The Latest On Long COVID (So Far)

“After all, tomorrow is another day.” Gone With the Wind

In these pages, your humble bloggeur (me) has followed the evolution of what we know about the odd condition known as long COVID. You can find seven previous blog posts on the topic here. Because we were just learning what long COVID was all about, many of those posts ended with the disclaimer, “we will see.”

Well, we have seen and continue to see. Here is what we now know after over 2 years of experience with this complication. But, tomorrow is indeed another day.

The risk of death from COVID is now about the same as the risk of death from flu, which can vary from year to year, thanks to vaccines, natural exposure, and developing therapies. One study in Lancet found that people with COVID had a 3-fold greater chance than uninfected people of dying each year. But, as I explained before, mortality is only part of the story. There also is morbidity. Long COVID is "the rest of the story" as Paul Harvey used to drone. Some 54 studies on long COVID, involving 1.2 million people, have been reviewed and it was reported that about 6% of people with symptomatic COVID infection wind up with long COVID. This agreed with a massive Swedish study of COVID patients done between 2020-21. According to the new Census Bureau Household Pulse Survey, some 16 million working age Americans now suffer from long COVID, which creates a huge burden on our health system. Up to 4 million of these are unable to work, which is a major drain on a labor market already short of workers. The annual cost in lost wages is up to $230 billion! The total economic cost of long COVID in the US so far has been an astounding $3.7 trillion!!

And as the virus evolves, reinfections with new CoV-2 variants are becoming more and more common. Unfortunately, a large VA study on reinfections suggests that you want to avoid them. A second or third infection is associated with worse disease and increased chance for long COVID. And a large German study including nearly 12,000 children with COVID concluded that long COVID “cannot be dismissed among children and adolescents.”

A sobering study of medical records from millions of US military veterans in the VA medical system published in Nature Medicine found that 7% more COVID patients (compared to uninfected veterans) had lasting brain or neurological disorders. This extrapolates into about 6.6 million Americans with long-term brain impairments linked to COVID. Memory impairment was the most common brain malady. But those with a history of COVID also were at greater risk of ischemic stroke, seizures, anxiety and depression, and movement disorders.

The good news is that vaccines reduce the risk of long COVID—how much is still debatable at this point. The anti-COVID medicine, Paxlovid, reduces long COVID risk by 25% according to one study. And the Omicron CoV-2 variant shows a reduced risk of long COVID compared to the more pathogenic Delta variant.

Assessing the risk: How much should the risk of catching long COVID affect one’s daily decisions? Should I go to the concert? Graduation? Grocery store? Wear a mask everywhere? That is hard to say definitively. Perhaps it would help to compare COVID risk to other risks we face every day.

  • The annual risk of getting in a car accident is about 1 in 30 per year. Of those, ~43% involved injuries and ~10% of those cause permanent impairment. This makes the annual risk of permanent injury from an auto accident about 1 in 700.
  • The annual risk of serious injury in a house fire is ~1 in 20,000.
  • The risk of needing reconstructive surgery after a dog bite is 1 in 400 annually.
  • The risk of catching the Omicron variant (symptomatic or asymptomatic disease) is ~1 in 2 annually (it was 1 in 4 before Omicron). Say 3% of those get long COVID, and ~18% of them are so sick they are unable to work for an extended period. This makes the annual risk of severe long COVID about 1 in 370.

So, the risk of debilitating long COVID is about twice the risk of serious injury from driving and about the same as getting a serious dog bite. The risk of severe long COVID is much higher than being injured in a house fire. Of course, all of these risks are affected by our personal behaviors. We don’t drive drunk and wear seat belts (hopefully). We replace the batteries in home smoke detectors every year and avoid growling curs. And if we are smart, we vaccinate and stay home when we are not feeling well.

At least those are things that responsible people do to reduce the risks of life.


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.

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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.

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The Long Haul, Part 3: Long Neurological COVID

As I have noted before in this series, acute COVID-19 often appears with neurological symptoms ranging from loss of smell to severe depression to stuttering to brain fog, mania and psychosis. It sometimes has been linked to suicidal ideation. In addition, long haulers often have cognitive symptoms and structural brain changes similar to those seen in aging brains and in those with Alzheimer’s disease. An early survey of 153 COVID-19 patients in the UK and a more recent study of people hospitalized with the acute disease in Italy both found that about a third had neurological symptoms of some kind ranging from sensory problems, motor impairment, and cognitive issues that persist after clearing the acute infection. Other estimates of neuro involvement in long COVID have trended even higher. Many people who survived earlier coronavirus infections such as SARS and MERS also experienced neurological impairments up to 3.5 years after acute infection. Obviously many of these symptoms of long COVID are very serious while others are more annoyances. So, what is going on? Researchers have pretty well cataloged the unusual range of long COVID’s neurological symptoms and now are at the very early stages of understanding their causes and how to treat the problems. Here, I label long COVID that primarily manifests itself with neurological symptoms as “long neuro COVID” in order to distinguish it from other long COVID problems that primarily involve the lungs, heart, or other organs.

What is long neuro COVID like? In the early days of the pandemic, a newly minted English MD worked on the front lines in a COVID ward and soon became a patient herself. Being 35 and healthy she expected to quickly recover but underwent the long haul, which she has written about. The acute phase of the disease lasted about two weeks, but by 4-5 weeks, she was experiencing new persistent problems including tachycardia with a resting heart rate of 140 bpm (normal is 60-100) that would increase to 170 after minimal exertion such as getting a glass of water. She also was breathless with a resting respiratory rate of 20-24 (12-16 is normal), saying it felt like her “body forgot to breath.” She described cyclic bouts of pins and needles in all four extremities, and whole-body shaking as violent as if she were having a seizure. There were feelings of impending doom, and, despite extreme mental and physical exhaustion, she was unable to sleep, which eventually led to hallucinations. Those symptoms slowly subsided over a few months only to be replaced by intense pain very deep in one ear. This ultimately led to tinnitus and some hearing loss and a diagnosis of encephalitis. Ten months later, she wrote that  she was recovering but was far from normal. She suspected that these symptoms were driven by a dysfunctional autonomic nervous system, a condition called dysautonomia. The autonomic nervous system is what regulates your organs and allows you to breath, your heart to beat, your gut to move food through it, and controls your blood pressure without you having to think about it all. Since her experience in early 2020, it has been confirmed that long neuro COVID can wreak havoc with both the peripheral and central nervous systems.

 

After two years of long COVID, we now know that long neuro COVID symptoms are wide ranging; some are devastating, like stroke, encephalitis, and even psychosis or mania, or even suicide. Other neuro symptoms are more subtle such as cognitive decline, loss of smell, hearing loss, balance problems, fatigue, memory problems, and difficulty concentrating or brain fog. Others are bizarre, such as stuttering. This seemingly unrelated range of symptoms suggests that there might be several different subtypes of long neuro COVID, possibly arising from distinct pathologies.

Back in July 2020, one of the first studies was published describing neurological symptoms that appeared long after the initial COVID disease. This since has been followed by several other reports of neurological or neuropsychiatric problems long after recovering from acute COVID disease. One study by Oxford scientists published last February, found that about 33% of post-COVID patients are left with long term mental health or neurological symptoms including brain fog, headaches, dizziness, and cognitive problems such as difficulty doing simple math. Some studies have shown an elevated incidence of PTSD, and seizures or movement disorders  long after COVID recovery. Other post-COVID patients have new-onset depression, psychosis, and suicidal behavior as reported in JAMA Psychiatry by a Columbia University research team this past spring. In this large study investigators examined electronic health records of more than 236,000 COVID-19 patients, mostly in the US. The researchers compared their records with records from those who experienced non-COVID respiratory tract infections during the same time frame and found an increased incidence in anxiety and mood disorders in post-COVID patients. More than three months after diagnosis, these common psychiatric diagnoses were found in about 34% of COVID survivors. Other studies confirmed that having the disease led to doubled risk for anxiety, depression and sleep disorders.

Importantly, researchers did not see an increased incidence of other neurological problems such as Parkinson’s disease or Guillain-Barré syndrome in long COVID patients, both of which sometimes follow viral infection. This suggests that long neuro COVID involves a select subset of neurological problems rather than an indiscriminate neurological malady.

Similarities between long COVID and Alzheimer’s disease. The cognitive issues seen in many long neuro COVID patients share intriguing similarities with Alzheimer’s disease (AD) and normal aging. Thus, an international group of researchers found that more than half of patients 60 or older who had been infected with the CoV-2 virus showed acceleration of Alzheimer’s-like symptoms such as cognitive decline. Other researchers at the University of Texas Health Science Center, San Antonio studied more than 200 older adults from Argentina who had COVID-19. Those who had a persistent loss of smell were more likely to experience AD-like cognitive issues. Importantly, the area of the brain affected in AD overlaps with the area that processes smell. It also might be relevant that the sense of smell, which is often lost in COVID patients, is also often reduced in AD patients.

Three to six months after they were infected, more than half of these patients still struggled with AD-like cognitive challenges including persistent forgetfulness, difficulty sequencing tasks, and forgetting words and phrases. How sick a patient was with acute COVID-19 was not an indicator of whether they would experience this cognitive decline. In other words, AD-like symptoms also occurred in people who only had mild COVID.

COVID-19, of course begins as a respiratory disease and investigators have long been tuned in to the potential links between respiratory diseases and the brain. For example, AD-like changes in cognition and behavior were also observed in people with Severe Acute Respiratory Syndrome (SARS) and with Middle East Respiratory Syndrome (MERS). Infection with other respiratory viruses can also increase the risk of Alzheimer’s.

Together, these findings suggest that some patients with long neuro COVID might have an acceleration of Alzheimer’s-related symptoms and pathology, but it is too soon to conclude that long neuro COVID causes AD, or even that AD and COVID-related cognitive dysfunction are even related. A major distinction between classical AD and AD-like long COVID is that the latter do not show the amyloid brain plaques which are pathognomonic of AD, which suggests that these could be distinct cognitive maladies with overlapping symptoms. Furthermore, other studies showed that worse cognitive scores in long COVID patients correlated with patients who had lower oxygen saturation during a 6-minute walk test. This makes it possible that persistent oxygen deprivation in the brain due to lung compromise during COVID could cause cognitive difficulties in these patients.

At this point, these observations simply raise many unanswered questions on whether there is a real overlap with COVID and Alzheimer's disease. But, it is too soon to say that COVID-19 increases a person's risk for Alzheimer's vs causes a different neurological problem symptomatically related to AD.

What causes long neuro COVID? Long COVID represents a broad category of over 200, often unrelated symptoms encompassing 10 organ systems. It likely consists of multiple different maladies with manifold causes, of which long neuro COVID is at least one broad category. Based on its biology and range of symptoms, long neuro COVID also likely entails more than one specific problem. It makes sense then that the many different manifestations of long neuro COVID would arise from different causes. Such seems to be the case. Researchers have cataloged several genetic, structural, inflammatory, and infectious correlates to the various symptoms, painting a complicated picture. Then things get really confusing since viral infection of neurological tissues and/or the attendant inflammatory responses could cause the observed structural changes and all this could be predisposed or mitigated by genetics. In other words, things are as clear as mud right now about what causes long neuro COVID. Investigators are just now making basic observational correlates between the neurological changes and long neuro COVID symptoms, and these correlations will be followed by the harder studies to learn just how these changes might cause the plethora of symptoms that have been documented.

On the genetic front, a Stanford U team found that long neuro patients manifest widespread changes in gene expression in the region of the brain involved in complex processing of human thought. These genetic changes affected genetic pathways that play a role in mental illnesses such as schizophrenia and depression. Although these results were made in the brains of patients who died of acute COVID disease, such fundamental changes in gene expression in the brains of patients with acute COVID would plausibly lead to long-lasting post-COVID effects. Similar changes in gene expression were not found in the brains of people who died from flu or from nonviral causes, which strengthens a possible cause and effect relationship of gene expression changes to some long neuro COVID symptoms.

But, what causes changes in brain gene expression? Is it directly due to viral infection in the brain or secondarily due to the immune inflammatory response to the virus? Maybe both? Or is something else involved? Evidence exists for all these possibilities.

One report on 111 unvaccinated patients from the Chicago area showed that 56 who had long neuro COVID cognitive problems showed a particular immunological signature that was not found in people who cleared the acute infection without long term problems. The severity of cognitive deficits correlated with reduced memory T cell responses to certain parts of the virus, and with enhanced antibody (or B cell) responses to one of the viral proteins. Furthermore, it has been observed that females are more prone to devleop long neuro COVID. Since women also are more likely to get autoimmune disease, some have put these observations together to suggest that there might be an autoimmune component to some long neuro COVID symptoms.

The above study assessed the anti-CoV-2 immune responses of T and B cells from the peripheral blood but not from the brains of the patients. In other words, it did not address whether the immune response in the body affects brain function or whether an antiviral immune response directly occurs in the brain affecting cognitive function. Other researchers have shown that the virus can indeed enter the brain via the nose and spread from the olfactory lobe to the frontal and temporal lobes of the brain. Other confirmatory studies have found viral protein expression in cortical neurons of autopsied brain tissues, and have directly shown that the virus can infect neurons in tissue culture. While these findings are consistent with direct infection of the brain and the possibility of immunological damage to the organ, they do not settle the question of whether viral infection itself might directly damage the central nervous system, or whether it is the immune reaction to the virus that causes the problems.

Perhaps confounding all of this are the results of a large study on gross brain structure conducted by researchers at the University of Oxford and at the NIH. In this study, researchers used the UK Biobank, an existing database, which contains brain imaging data from >45,000 people in the UK going back to 2014. This means that there was pre-COVID baseline imaging data the researchers could compare to post-COVID brain images. New images were collected from 394 of these patients who caught COVID and compared to their pre-COVID images and to 388 controls who did not catch COVID-19. The groups were otherwise matched based on age, sex, common disease risk factors, etc. The results showed that those who caught COVID suffered significant loss of gray matter in the frontal and temporal lobes on the left side of the brain. This brain loss was found regardless of COVID disease severity. Those who were COVID-free had no brain tissue loss. Interestingly, these regions of the brain are responsible for smell, taste, memory, and emotion, all of which can be affected in long neuro COVID patients. We also often talk about the left temporal lobe in the context of aging and Alzheimer’s disease because that is where the hippocampus is located, which plays a key role in memory and other cognitive processes associated with aging and AD. While it is normal to see reduction in gray matter with age, the COVID-linked changes were greater than that typically seen during normal aging. All of this raises questions about how COVID might affect the natural aging process in the brain.

In addition to these genetic, immunological, and structural changes in the central nervous system of COVID patients, autopsies also have revealed clotting in multiple organs including the brains of many patients. About one in 50 COVID brains showed evidence for an ischemic stroke, which is when a blood clot interrupts blood flow to a region of the brain downstream from the clot. Ischemic strokes in COVID patients tended to be more severe and more likely to result in severe disability or death than stroke in non-COVID individuals. Again, while these findings were made on autopsies of patients suffering from acute COVID, these ischemic strokes would have caused long term manifestations presenting as long neuro COVID.

There are other, very specific and very peculiar neurological symptoms that might arise from more specific neurological abnormalities. For example, some long COVID patients display hearing loss and or balance problems which suggest vestibular involvement that could be due to CoV-2 infection of the inner ear. Scientists at MIT and Stanford found that the ACE2 protein, which is the cell receptor for the CoV-2 virus, is expressed on certain inner ear cells obtained from surgery patients. Since inner ear tissue is difficult to obtain, the researchers directed stem cells to develop into inner ear cell precursors or that could assemble into primitive inner ear  organoids in tissue culture and showed that the CoV-2 virus could infect them. Together, these observations support, but do not prove, that infection of the inner ear is a cause of hearing and balance issues in some long neuro COVID patients. It is relevant to note that it is not unusual for hearing loss and balance disorders to be caused by other viral infections of the inner ear.

Then there also are the rare long COVID patients who develop an odd stuttering problem. Typically, stuttering originates in the complex circuity of the brain that controls speech and this speech disruption usually appears when children are learning to talk. However, “neurogenic stuttering” can arise in adults after brain trauma. Since only a few researchers are investigating long COVID-associated stutter, the cause is not well understood, but, the link between neurogenic stuttering and brain injury raises the possibility that inflammation and/or micro-clotting caused by the virus or by the immune response to the virus in the brain microvasculature could lead to the neurological damage that causes stuttering.

Bottom line. These many new findings, while provocative, do not yet fully tell us how long neuro COVID arises, or how to treat it. But, they raise many new questions: What do these COVID-related brain changes mean for the process and pace of brain aging in long COVID patients? Over time does the brain recover? How do we medically deal with these patients? Can we prevent long neuro COVID? Etc.

Stay tuned, we will see.

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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.


Refusing To Treat COVID Patients Based On “Quality Of Life” Determinations

FYI: While your humble blogger earned a PhD in viral immunology from the University of Texas, and spent most of his career investigating the causes and cures of leukemia at UCLA and the University of Wisconsin, he also was trained in ethics at Indiana University, the University of Montana, and Calvin College. He taught bioethics and research ethics at the U of W. His closet hooks are full of different hats.

Biomedicine is rife with ethical conundrums, a few of which already have been mentioned in these pages about the coronavirus pandemic, to wit: Should we wave inspection of vaccine manufacturing facilities and risk production mistakes in order to speed release of a CoV-2 vaccine, which will save lives? Or, whose rights do we ignore during a pandemic—the freedom to live as we choose vs the freedom to remain free of infection? Or, do we abandon all social restrictions in attempt to achieve herd immunity via natural infection, realizing that we would be sacrificing many to the disease? All, conundrums, indeed.

Ethical dilemmas entail at least two conflicting choices, neither of which is perfectly good nor perfectly bad. That is why these problems are often referred to as “horns of a dilemma.” Which horn should we embrace, and which should we avoid, knowing that both can stick us?

An ethical dilemma has arisen in healthcare circles, but for which the popular press has largely been silent. This issue is about how “quality of life” factors into health care decisions for COVID-19 patients. The following example of how this ethical conundrum can play out is excerpted and modified from the journal, First Things.

A man, Michael, was refused treatment for COVID-19 because the hospital he was admitted to and State bureaucrats believed that he did not enjoy sufficient quality of life to warrant curative treatment for the disease. In 2017, Michael had a heart attack that caused brain damage leaving him a quadriplegic and suffering frequent seizures. But he was conscious, able to do simple math calculations, answer trivia questions, and interact with his family. Then, in late Spring of 2020, he caught COVID-19 and was hospitalized. The hospital decided to withhold his tube feeding despite the objections of his wife, and the fact that he had a fair chance of surviving if provided with appropriate COVID treatment and sustenance care. He died on June 11.

He was denied care because his doctors determined that he did not have a sufficient “quality of life” to justify treatment. Because of his disabilities, saving his life was deemed “futile.” The medical team and the “State,” through a court appointed guardian, reasoned that treatment for COVID-19 would not improve the quality of his life (meaning, he would remain quadriplegic and cognitively disabled if he survived the disease); therefore, they decided to end all treatment care except hospice comfort care.

His wife, Melissa, had been appointed Michael’s temporary guardian, but she was in a legal struggle with Michael’s sister over his custody, a dispute that predated Michael’s hospitalization. Family Eldercare, a nonprofit agency, was then appointed interim guardian until a final decision could be made about permanent guardianship. Hospital doctors convinced Family Eldercare to approve Michael’s transfer to hospice care where he would only receive palliative care and not curative or sustenance care. Michael died of pneumonia after six days on hospice; the withdrawal of nutrition and hydration having no doubt weakened his body’s ability to fight disease. Even without pneumonia, Michael would have soon died of dehydration.

Melissa recorded her conversation with an unnamed physician and posted it on YouTube so we can all hear for ourselves.  Here’s the substance of the conversation from the YouTube transcript, with my commentary.

Doctor: At this point, the decision is, do we want to be extremely aggressive with his care or do we feel like this will be futile? And the big question of futility is one that we always question. The issue is: Will this help him improve the quality of life, will this help him improve anything, will it ultimately change the outcome? And the thought is the answer is no to all of those.

Melissa: What would make you say no to all of those?

Doctor: As of right now the quality of life, he doesn’t have much of one.


Melissa: What do you mean? Because he was paralyzed with a brain injury, he doesn’t have a quality of life?

Doctor: Correct

My Comment: The doctor did not base his decision about Michal’s medical care on the illness for which he was hospitalized, but on his unrelated disability. This is a classic example of applying the invidious “quality of life” ethic, which deems people with disabilities, the elderly, the chronically ill, and the dying to have a lower worth than the healthy, able-bodied, and young. Back to the conversation…

Melissa: Who gets to make that decision whether somebody’s quality of life, if they have a disability that their quality of life is not good?

Doctor: Well, it’s definitely not me. I don’t make that decision. However, will it affect his quality, will it improve his quality of life, and the answer is no.

My Comment: After denying that he had any part in determining Michael’s quality of life, the Doctor then admits that he believes that Michael’s quality of life is negligible. By doing so, he is being duplicitous regarding his role in the decision, and he is not acting as Michael’s doctor, beholden to the Hippocratic Oath he took. Rather, he is acting as an agent for the hospital and State bureaucracies rather than acting in Michael’s interest, a dramatic violation of the Oath he took. Back to the conversation…

Melissa: Why wouldn’t it? Being able to live isn’t improving the quality of life?

Doctor: There’s no improvement with being intubated, with a bunch of lines and tubes in your body and being on a ventilator for more than two weeks. Each of our people here have COVID and they are in respiratory failure. They’ve been here for more than two weeks.

Comment: The Doctor again makes a statement of his opinion of Michael’s quality of life. He admits that many of their OOVID patients are in respiratory failure and on ventilators, but implies that they are more valuable than Michael and deserve such therapy, while Michael does not.

 Melissa: So the fact that you are killing someone doesn’t make sense in your mind?

Doctor: We don’t think it’s killing. Because I don’t know when or not if he will die. But at this point I don’t think it would be humane or compassionate to put a breathing tube in this man and do the lines and the tubes and all that stuff because I don’t think it will benefit him.


Melissa: And I totally agree with you on the intubation part of it. I don’t want him intubated. But I also don’t think you should just sit him somewhere to be comfortable until he finally just drifts away. That to me is futile too. That’s saying you’re not trying to save someone’s life. You’re just watching them go. The ship is sailing. I mean that just doesn’t make any sense to me to not try. I don’t get that part. I don’t like that part.

Doctor: But what I’m going to tell you is that this is the decision between the medical community and the State.

Melissa: And the State. Forget about his wife and his family and his five kids.

Doctor: I have nothing to do with that.

The recording ends there. 

At first blush, it might seem like a reasonable decision to withhold essential care from someone as damaged as Michael was, but what if we change the selection criteria from “quality of life” to “preciousness of life?” Wasn’t his life as precious as everybody else’s, especially to his family? It was not, according to Michael's doctors and faceless bureaucrats in his State who had never met him, all of whom believed that they could better judge Michael’s worth better than his family could. And, what about Michael’s wishes? The article did not indicate whether, after his hospitalization, he was able to express his desires in the matter, but I will assume he was incapable of doing so. In which case, the medical ethicist must look at Michael’s family as well as his life near the time he was hospitalized. Before catching COVID-19, were his actions consistent with someone who wanted to live, even with his disabilities? Even if a hospitalized patient cannot communicate, it is still possible to divine his wishes from the period before he became, possibly temporarily, non-communicative due to the disease. That divination is more relevant than faceless bureaucrats when making life and death decisions for him.

This is the great ethical problem of quality of life decisions being made by impersonal, anonymous administrators who can overrule the wishes of a patient’s immediate family and even the demonstrated wishes of the patient. The bottom line is to make sure you have your final wishes legally documented and use power of attorney to put your fate in the hands of highly trusted family or friends.

Even then, you still might encounter faceless bureaucrats making life and death decisions for you based on how they judge the quality of your life.

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COVID On The Brain

  • A previously healthy 50 year old emergency room physician on the pandemic front lines caught COVID-19, suffered a stroke and lived on a ventilator for 39 days.
  • As reported earlier, another ER doctor in NYC caught COVID-19, recovered, but had a mental breakdown that led to her suicide.
  • An executive secretary at a major medical center caught COVID-19 and began hallucinating, causing her to call 911. Her neurologist said that if she had not called, she would likely have been dead in the morning—her lungs were the consistency of chocolate pudding. The hallucination saved her life.
  • Another woman with COVID-19 hallucinated that lions and monkeys were in her house.

200708030217-coronavirus-brain-damage-study-intl-hnk-scli-scn-exlarge-169
Brain scans from the University College London study, published on July 8.

Many COVID-19 victims lose their sense of smell, suffer cognitive impairments, seizures, hallucinations, loss of motor skills, and paralysis, and these can take months to recover, or are permanent.  What is especially concerning is that young COVID-19 patients and even those with mild cases are also susceptible to these neurological problems. Some of these patients develop neurological symptoms weeks after recovering from other COVID-19 symptoms causing some researchers to be concerned that neurological symptoms could arise in recovered patients in the years to come, leading to an epidemic of "pandemic-linked brain damage."

These long-term neurological effects of COVID-19 were described in a recent study by researchers at the University College London and published in the journal Brain. Interestingly, none of the patients in the study who showed neurological symptoms had CoV-2 virus in their cerebrospinal fluid, indicating that the virus did not directly attack their central nervous system. This means that the neurological problems might be due to indirect effects of the virus, possibly triggered by the immune response to the infection. This is a bit surprising since the virus binds to cell receptors that are found on cells that line blood vessels, so it would not have been surprising to find the virus in cells along vessels in the brain and spinal cord, which could have explained the occurrence of micro-infarcts, and hemorrhages that lead to mini-strokes.

There might be different mechanisms that affect neurological activity in COVID-19 patients. Some patients suffer intense, system wide inflammation caused by an overactive immune system. The immune system inexplicably goes haywire and releases hormone-like proteins called cytokines that help activate other immune cells and cells that cause inflammatory responses. If too many cytokines leak into the bloodstream, immune and inflammatory cells start killing anything they encounter. This response, called a cytokine storm, creates massive inflammation that weakens blood vessels, causing fluid to seep into the lungs’ air sacs, triggering respiratory failure. A cytokine storm can also inflame the brain, causing encephalitis as well as damaging other organs resulting in multi-organ failure.

When “cytokine storms” inflame the lungs that can lead to reduced oxygen transfer to the blood, which affects brain function. The storms can also cause inflammation and swelling in the brain or spinal cords. Both of these effects can cause hallucinations, motor dysfunction, and psychological problems. This is sometimes seen in other viral infections such as chickenpox, measles and tick- or mosquito-borne viruses that cause encephalitis.  

Since the US now has 5 million cases of COVID-19 and growing, this portends for thousands of people with lasting cognitive and motor deficits in the future. This is similar to a phenomenon observed in the decades following the 1918 Spanish flu pandemic: Between 1917 and the 1930s, more than 1 million people who had the flu were diagnosed with encephalitis lethargica, or "the sleepy sickness." The disorder, caused by swelling in the brain, brought excessive sleepiness and severe neurodegeneration that left many Spanish flu patients disabled.

Many COVID-19 patients, including young, healthy ones, also suffer systemic clotting in microvessels throughout their bodies that can affect multiple organs including the brain where they cause strokes. Although it’s surprising to see strokes in young people, these strokes should perhaps be expected given that they were also observed during the 2002-2003 outbreak of SARS, a related coronavirus. Most of the strokes reported with COVID-19 have been “ischemic,” meaning a clot plugs vessels supplying blood to the brain. If an ischemic stroke blocks the supply of blood for too long, it can kill the downstream area of the brain. However, a smaller number of stroke-related COVID-19 cases involve hemorrhagic stroke, which occurs when a weakened blood vessel ruptures and bleeds into the brain, damaging the fragile surrounding brain tissue.

It is not yet known how common strokes might be among COVID-19 patients since the virus is so new, and because most of the observations have been in ICU patients. That means the record is missing patients who were discharged from the hospital and later developed a COVID-related neurological sequela, or people with neurological symptoms whose infections were mild or even asymptomatic and not diagnosed as COVID-19.

In other words, we will see.