Coronavirus news & views

Studies Show That The COVID-19 Death Rate Is Underestimated

Because many COVID-19 deaths have been in high risk people who had comorbid problems such as obesity, diabetes, and cardiac problems, many new “experts” claim that the COVID-19 death rate is being conflated with deaths from other causes, and being over-inflated. That conclusion is overly simplistic and probably not true. In fact, actuarial studies in the UK and the US, and a recent CDC report show that the deaths attributed to the disease are under-counted.

The Johns Hopkins University pandemic tracker reports that, as of this week, 175,000 people have currently died from the disease. The same tracker reported that between January and July the mortality number was 150,000. But, the CDC just reported that also between January and July, the US had 215,000, or 35%, more deaths than expected based on actuarial data from the same period last year, before COVID-19. These data are broken down by state in an Associated Press news report. Many of these excess deaths are due to undiagnosed COVID-19, but some of them also may have occurred because people with other serious ailments were reluctant to seek medical care, fearing exposure to the novel coronavirus, or even being unable to obtain treatment as a result of medical resources being spread thin by the pandemic in some places such as NYC and Birmingham.

A study with similar results also was recently published using hospital and actuarial data from across the UK. It found a significant increase in total deaths compared to the same period last year. Weekly fatalities from all causes are up by more than 25%, and in some places almost 80%. Analysis of actuarial data for COVID-19 patients with other serious ailments who were admitted to intensive care units showed that their mortality rate was 10 times greater than would have been expected without the virus. In other words, without the virus, these already at-risk patients were expected to live significantly longer if they had not encountered CoV-2.

The bottom line: While there has been some confusion about what causes death in people with COVID-19 who also have other high risk conditions like heart disease, the actuarial data indicate that people are dying at a significantly higher-than-expected rate, making the coronavirus the culprit.

Update (9/7/2020): Data from Mexico's National Center for Preventive Programs and Disease Control show that between March and August, total deaths were 59% higher than expected from actuarial data. In fact, the country had to order a special printing of death certificates, because it had run out of them.

 

How To Get Updates To This Blog In Your Email

If you would like to get email updates of new blogs in your email, please follow these simple instructions.

1) On any blog page, click the "subscribe" link that is just below the banner. It should take you to a page that looks like the screen shot below.

++++++++++

+++++++

2) On the new page, ignore the box on the upper right that says "subscribe." It is useless for this purpose. Instead, go a few lines down the page until on the left you see a colorful line of icons. Click the orange, next to last, icon that looks like an envelope.

3) fill in your email address and subscribe.

I am sorry that it is not very obvious how to simply get blog updates sent to your email. I went back and forth with Typepad on this issue to little avail. Keep in mind that you can easily unsubscribe from email updates. Each update gives you an option to unsubscribe. It is interesting that unsubscribing is easier than subscribing.....

A Constellation Of COVID-19 Conditions

The specific set of symptoms COVID-19 patients experience at the onset of the disease may predict how severe their case will become, according to a study by researchers at King’s College London. The study identified six “symptom clusters” of COVID-19 disease, which are listed below in ascending order of severity:

• Type 1, “flu-like with no fever”: headache, loss of smell, muscle pain, cough, sore throat and chest pain.
• Type 2, “flu-like with fever”: fever and loss of appetite in addition to headache, loss of smell, cough, sore throat, and hoarseness.
• Type 3, “gastrointestinal”: diarrhea and loss of appetite, no cough, headache, loss of smell, sore throat, and chest pain.
• Type 4, “severe level one, fatigue”: fatigue in addition to headache, loss of smell, cough, fever, hoarseness, and chest pain
• Type 5, “severe level two, confusion”: confusion in addition to headache, loss of smell, loss of appetite, cough, fever, hoarseness, sore throat, chest pain, fatigue, and muscle pain.
• Type 6, “severe level three, abdominal and respiratory”: shortness of breath, diarrhea and abdominal pain in addition to headache, loss of smell, loss of appetite, cough, fever, hoarseness, sore throat, chest pain, fatigue, confusion, and muscle pain.

These six COVID-19 types help clarify what has been a confusing disease. It is like six different types of flu that require different kinds of treatment. Up to now, they were either not fully recognized as being COVID-19 disease, or treated as a single disease. Clearly, different people have different responses to the coronavirus. It also is possible that virus variants might lead to the different clusters of symptoms, but, at this point, we are not certain of that. What is important is that as we learn how the disease manifests itself, we learn how to better diagnose and treat it, which should bring mortality, and, hopefully, morbidity rates down. 

The study referred to above was done using a symptom self-reporting app called ZOE COVID Symptom Study app, which asks users to log health information and potential COVID-19 symptoms daily. The study analyzed data from 1,600 app users in the U.S. and U.K. with confirmed COVID-19 cases and who logged their symptoms during March and April. This showed that 20% of people with type 6, and 10% of people with type 5 symptom clusters  eventually required breathing support, compared to just 1.5% of people with type 1.

The 5 and 6 symptom types signaled a “high risk” for needing hospitalization, and almost half of type 6 COVID-19 patients were hospitalized. In just five days, the app was able to identify which symptom cluster the patient belonged to— which is eight days earlier than when most people who need breathing support go to a hospital. The study also found that people in types 4, 5 and 6 clusters were older, more likely to be overweight and more likely to have preexisting conditions than those in symptom cluster types 1, 2 and 3. Therefore, the app seems to be a useful diagnostic tool for a complicated disease.

Finally, the app showed that a cluster of nonspecific symptoms not previously associated with COVID-19, such as headache, sore throat and muscle pain, without fever and loss of smell, can detect potential COVID-19 cases before the classic symptoms of fever, shortness of breath, loss of smell, etc. set in. Such early symptom awareness can limit virus spread to colleagues, friends, and family. So, using this app to detect symptom clusters promises to not only provide more focused and timely therapy, it can also help limit the spread of the disease from people who have not been diagnosed with COVID-19, which has made this disease especially vexing to control.

This is a wholly new disease, which we are learning about on the fly. As we learn more about it, we improve our ability to diagnose, treat, and ultimately prevent it. This study takes us one step closer to that goal.

.

 

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.

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.

Science vs Nonscience In Understanding Hydroxychloroquine

A recently much shared video of America’s Frontline Doctors Summit shows several clinicians claiming that hydroxychloroquine (HCQ) is a "cure" for COVID-19. Their evidence for this claim is their personal experiences treating these patients with HCQ along with a cocktail of other drugs. The video was shared 14 million times before Facebook and other hosting services took it down, ostensibly for spreading inaccurate information. While the debate whether such censorship is reasonable, it is also reasonable to point out that the doctors were, in fact, sharing information that is not known to be accurate and that has a high chance to be inaccurate; in other words, scientifically unproven. They grossly overstated their conclusions from their non-scientific observations. It is irresponsible for a doctor to claim that her anecdotal experience “proves” the efficacy of any unproven therapy. If the docs had been honest, they should have said that their observations warranted further controlled clinical trials in order to prove or disprove their claims. 

One of these doctors said that she had treated 350 patients with the drug cocktail and that none died; therefore, she irresponsibly declared that she had a “cure” for the disease. While that sounds impressive, she did not do a controlled clinical trial, which means that we have no way of knowing whether the 350 also would have survived without the drug. She also claimed that her success was because the patients she treated with the cocktail were at the early stage of disease. Unfortunately, we don’t know what that means since she didn't report their clinical details as she would have been required to do in a gold standard clinical trial. This doctor also had a web page where she talked about how gynecological problems are caused by engaging in sex with demons, and that alien DNA was being used in modern medicines; all the more reason to suspect her credibility.

In other venues, I have pointed out these problems with the America’s Frontline Doctors Summit and received a lot of push-back from non-scientists. For some reason, some people bring a strong need to believe in HCQ without considering the science. So, they readily jump on ANY report that confirms their bias as proving that the drug is a cure. Several of these “experts” quickly pointed me to a recent report from the Henry Ford Health System that claimed that hydroxychloroquine saved lives. It was published earlier this month in the International Journal of Infectious Diseases. 

However, the Henry Ford report was not a clinical trial, but a much weaker retrospective chart review of more than a thousand COVID-19 patients seen in the system’s nine hospitals. In other words, the patients were not randomized, the “study” was not blinded, and patients were not treated according to a controlled, standardized study protocol. Hence, it was only marginally better than the undocumented anecdotes of America’s Frontline Doctors. At least, because the Henry Ford docs published a report on their personal observations, interested clinicians and researchers could look at the aggregate patient data. That was not the case regarding the claims by the America’s Frontline Doctors.

On Wednesday, in response to the Henry Ford report, the same journal published several scathing critiques claiming the report had serious errors. The major problem was that the patients given the HCQ cocktail regimen were healthier than the patients that were not given it. The patients not given the cocktail had more advanced disease and more frequent comorbidities that put them in a higher risk group compared to those who received the treatment. Furthermore, the HCQ treatment group was more aggressively treated and more than twice as likely to receive steroid therapy, which has been shown to help certain COVID-19 patients.

In other words, in this chart review of patient experiences, the two groups that were compared were very different and it is highly possible that the death rate difference between them would have been the same even if the HCQ protocol was not used. An important goal of randomized, blinded, controlled clinical trials is to make sure that the treatment and non-treatment comparison groups are as similar as possible in order to eliminate such bias that can skew the study’s results. This is why scientific clinical trials and not chart review reports are the gold standard for determining the best health care.

Unfortunately, people who take these anecdotal testimonies, and poorly controlled chart review reports as proof that HCQ is the panacea for COVID-19, also selectively ignore other recently reported gold standard clinical trials that show that HCQ is ineffective. This week, a randomized clinical trial in Brazil showed that hydroxychloroquine doesn't work to treat patients with Covid-19. Another randomized trial last month at the University of Minnesota showed it also doesn't help prevent infection. Other clinical trials -- one in the US, and one in the UK were halted early because interim data analysis showed the drug wasn’t working.

Like America’s Frontline Doctors emphasized, the authors of the Henry Ford report pointed out that HCQ worked for their patients because it was prescribed very early in their hospitalization. But, University of Albany researchers earlier reported that the HCQ cocktail approach was ineffective in a randomized, blinded trial employing subjects at the same point of disease as the patients in the Henry Ford report.

As reported earlier in these pages, because of similar negative clinical trials, the FDA recently pulled its approval for HCQ to treat COVID-19.

There is a very good reason why we rely on carefully designed and controlled clinical trials rather than anecdotal information or retrospective chart reviews in determining the best way to treat disease. The best the latter should contribute is to generate interest in testing the observations in controlled clinical trials to see if they are accurate.

While your humble blogger initially was enthused about the potential of HCQ to treat COVID-19, I increasingly sour on it as science continues to show it doesn’t work. So far, the reports claiming that HCQ is effective against COVID-19 are mostly based on unsubstantiated doctor’s anecdotes, or on uncontrolled retrospective chart reviews. In contrast, the reports that indicate that HCQ is ineffective are based on stronger randomized and controlled clinical trials.

Who are you going to believe?

An Invitation To Those Who Refuse To Wear Masks

I have been seeing a LOT of resistance to using face masks during this pandemic, mostly from libertarian or anti-authority types who "don't like to be told what to do." For these people I have a question: do you also believe no one should tell people not to  steal your wallet, or drive drunk? After all, preventing people from hurting others is one of the common features of our laws. Masks protect people from others just like drunk driving laws do.

On other forums, and in this blog here and here, I have presented scientific evidence that masks are effective in retarding the spread of infectious diseases, but these nouveau "experts" keep arguing and ignoring the evidence.

So, I have an invitation for those who think masks are ineffective and say that they will never wear one.

Next time you have surgery, tell your surgeon that you don't believe in face masks and insist that he not wear one during the operation.

Tell him that, even though your insides might be open, you are not worried about the spray from his mouth when he utters spray-worthy things like, "scalPel, Please," "sucTion  Please," and "reTracTion Please."

At this point, I am reminded of the Seinfeld episode when Kramer et al., were in a surgical theater overlooking an operation. Kramer brought in a box of Junior Mints like he was just watching a movie, and while leaning over the rail to watch the operation, he popped the candy in his mouth. Just before the surgeons were getting ready to close, he was putting a mint in his mouth, but it dropped into the body cavity of the patient. That would have been prevented if he had been wearing a mask.