Category Archives: Fatality Rate

The Next Pandemic

All Articles, Communication, Contact Tracing, Fatality Rate, Masks, Quarantine, Testing, Treatments

In yesterday’s post, I outlined some of the factors that resulted in the very high COVID case rate in the US. Today I will discuss how we can prepare for the next pandemic.

I have a PhD in molecular biology, and I specialize in infectious disease testing. I am not a physician or epidemiologist. I have an informed but not expert opinion.

Identifying the threat:

First, most new infectious diseases do not pose a global threat.  SARS-2 was so dangerous because of its high infectivity, long incubation time, and asymptomatic spread. Most diseases do not have these parameters.  Whenever a new disease comes around, and they will, we should soberly and cautiously assess the real threat.  Coming to the wrong conclusions about the threat will lead to the wrong conclusions about combating it.

There have been several important new infectious disease outbreaks in the last few years, including Hantavirus (1993), SARS (2003), Avian Influenza (2004), H1N1 Swine Flu (2009), Ebola (2013), Zika (2015), and of course HIV in the 80s.  They all have different disease parameters which make them behave very differently.  Most of these diseases did not have global impact.  The first SARS for example was much less infectious than SARS-2, but much deadlier, so it was contained quickly and didn’t spread much beyond Asia.  HIV can be spread by asymptomatic victims for a full 8-10 years, avoids the immune system, and evades vaccination efforts, so it has become endemic in much of the world.

The following parameters determine how a new disease will behave:

  • Mechanism of spread
  • Infectivity
  • Asymptomatic/ambulatory spread – can the victim walk around and spread disease?
  • Incubation period
  • Fatality rate
  • Vector – what carries the virus to a new host
  • Non-human reservoir – diseases that come from non-humans are harder to control and cannot be eradicated.

Obviously, we cannot respond to different diseases in the same way. Part of the reason we failed to contain the virus was that we used measures that were designed for viruses that spread by droplet transmission against a virus that spreads through aerosol transmission.  Using the wrong measures was less effective.

Much of my concern with the SARS-2 virus was the Antibody Dependent Enhancement issue, which is very uncommon among viruses, so is not usually a concern.

Be cautious.
Whenever a new threat arises, it is wise to be extra cautious until information can be gathered.  Although many of our precautions turned out to be unnecessary, I still support taking extra precautions early on.  Remember that early estimates were that the fatality rate for COVID was 3.68%.  With the 82 million confirmed cases in the US, this would have been over 3 million deaths if the fatality rate had really been this high.  As it stands, we have had almost 1 million COVID related deaths, a death rate of approximately 1.2%.  Yes, I know we can debate how many of these are deaths really resulted from COVID and how many infections there really were.  But we cannot discount that COVID had an enormous impact.

What if COVID were deadlier? Or what if it had selectively killed children, or caused more long-term symptoms like polio did? Things would have been much different.

All this to say, I think caution was warranted in the beginning of COVID, and we should continue to be cautious in future pandemics. On the other hand, we should also learn to abandon precautions that are not effective.  Maintaining ineffective precautions wastes resources, causes extra economic and social suffering, and causes people to lose confidence in government agencies.  It started to become clear to me by May of 2020 that lockdowns were ineffective, and that transmission was happening mostly indoors, but I still see people wearing masks outside to this very day.

Persuasion, not coercion:
From the beginning of the pandemic, public communication was terrible.  Official guidelines were confusing and often contradictory.  Far worse, explanation or evidence was rarely given for policies.  Instead, disagreement was met with accusations of being anti-science, rather than persuasion.  This approach contributed to the loss in confidence in official channels. 

Going forward, officials need far better communication skills when dealing with emergencies.  Give evidence rather name-calling, and respect the population enough to tell the whole truth.

Then came the vaccine mandates.  Many people I know were coerced into getting vaccinated against their will, and many others were fired.  All at a time when information about the vaccines was being hidden from the public.  This is unacceptable, and no way to run an emergency.

Here is a link to my post on science communication:

Restoring Trust:
Both the CDC and FDA hid information from the public.  In order to restore confidence, senior leadership needs to be replaced and new leadership should explain how things will be better in the future.  Is likely to happen?  No, it is not.

Government agencies need to be far more transparent.  Lack of transparency forces people to wonder what is going on, and create their own theories.  Government agencies often decry conspiracy theories, but they had a big role in creating them.

Misinformation:
Freedom of speech, censorship, and misinformation had a major role in the public discussion over the pandemic.  Doctors and scientists were frequently censored, shunned, or fired for sharing ideas that went against WHO or CDC guidelines. This includes ideas like the lab leak hypothesis that later turned out to be likely.

Freedom of speech is a foundational principle of American life.  It’s in our DNA, as some would say.  We are not America without it.  Some will say that too much freedom of speech leads to misinformation and conspiracy theories.  While it’s true that this freedom allows the spread of falsehoods, it also allows all ideas to be debated, true ideas to be raised up, and false ideas to be discredited. Freedom of speech is the solution to misinformation, not the cause.  Most of the leaders in world history that wanted to control freedom of speech had something to hide. It is essential that we maintain this basic right.

State emergency powers:
As discussed in yesterday’s post, the US federal government has surprisingly little power to deal with a public health crisis.  The CDC can develop guidelines, but most of the real work is done at the state and local level.  State officials need to step up and realize it’s their responsibility to respond well.  Citizens need to hold state and local officials accountable.

Manufacturing:
The US needs to maintain manufacturing capacity for certain essential items like personal protective equipment, testing kits and equipment, and medications.  Tax incentives need to exist to encourage companies not to send these functions overseas.

In addition, we should have national and state stockpiles of certain equipment.  I know many hospitals and labs are now creating stockpiles of their own.

Testing:
Most countries that did well produced lots of COVID testing early.  In the US, the CDC tried to manage all the testing themselves, and quickly became overwhelmed.  By the time private labs were allowed to develop their own tests, it was way too late.  Testing capacity didn’t become nearly adequate until at least July of 2020. Next time, the CDC needs to allow testing by private labs right away.  Ideally, anyone who wants a test and anyone potentially exposed to an agent should be tested.

Quarantine, not Lockdown:
Countries that did well did not quarantine healthy individuals, although some of these countries had more restrictions during the big Winter waves.  Instead, only COVID positive people should be quarantined.  This is only effective when tests are readily available.

Later in the pandemic, some outlets acknowledged that most infections were happening in private settings.  Basically, people would get infected outside, then bring COVID home to infect everyone in the household.

Here is a very interesting video using computer models to show why our model of lockdown was not effective.  Computer models are only as good as they are programmed to be, so this is only for demonstration purposes, and is not data.

Contact tracing:
Contact tracing was very successful in some countries, but the long incubation time of COVID made this difficult.  Successful programs involved tracking of individuals by cell phone and credit card data, practices that would probably not be tolerated in the US. Such programs would need to be voluntary to not trigger the creepiness factor and violate constitutional rights.

Masking:
I was a big proponent of wearing a medical grade respirator (N95, KN95, or KN94) indoors during the pandemic.  Because COVID spread as an aerosol as well as droplet form, cloth and blue surgical masks were ineffective.  Simpler masks can be effective against colds and flu, however.  So the choice of mask depends on the agent in question.  CDC guidelines need to reflect the method of spread of the agent in question. 

So what should Dr. Fauci have said early on?  Something like this:

“N95 masks offer the best protection against infection by the SARS-2 virus. However, our current supply is very low, and we desperately need to save these masks for our medical professionals.  Please do not purchase N95 masks at this time.  In the mean time, there are some options that will help reduce the risk…”

In actuality, of course, I didn’t see an N95 in a store from March 2020 until at least February of 2021, so I couldn’t have bought one if I’d wanted to!

Treatment:
Most medical facilities in the US didn’t treat COVID until a patient was experiencing respiratory distress.  By then, treatment options were limited.  To their credit, intubation was largely abandoned by the medical community when it was learned that this treatment was largely ineffective.

However, controversy swirled over potential treatments that became disfavored by the medical community.  Doctors are usually granted the right to prescribe “off label” medications, meaning they can use medications for treatments outside the guidelines of the manufacturer.  But drugs like Hydroxychloroquine, Ivermectin, and others quickly become forbidden, and some doctors even got fired for prescribing them.  Research on these drugs were minimal.

I am not arguing here that these drugs are effective against COVID.  I’m simply saying that forbidding doctors from working with or publishing papers about these drugs was a big mistake.  While it is of course wise for a doctor to consider guidelines, treating a novel virus may require some “outside the box” thinking.

Let me know in the comments if I missed something important!

Don’t fear, but be smart!
Erik

What Went Wrong?

All Articles, Contact Tracing, Fatality Rate, Masks, Treatments

Today I’ll discuss the approach to the pandemic in the United States, and all the factors which contributed to our very high case load during the pandemic.  This article ended up being longer than I thought, so I’ll have a separate post later in the week about how we can prepare for the next pandemic. I have a PhD in molecular biology, and I specialize in infectious disease testing. I am not a physician or epidemiologist. I have an informed but not expert opinion.

The COVID-19 pandemic finally seems to be drawing to a close.  For most of the pandemic, the US had the highest number of daily cases, and has had the most cases over all.  As I write this on May 17th, 2022, the US has 82,629,736 total confirmed cases, approximately 25% of the population, and an unknown but likely very large number of unconfirmed infections.

Meanwhile, the US has the most technologically advanced and well funded medical system in the world.  So what happened? This is a very important question because answering it correctly will help us respond to the next pandemic.

First, we can ask what policies the US had in place, and contrast them with policies that were successful.

Countries that initially did well were Taiwan, Japan, Singapore, and South Korea.  These countries are right next to China, which is the natural source for the seasonal flu.  This is because flu viruses exist natively in aquatic birds from southern China, and there is no practical way to eradicate the flu. We can expect dangerous respiratory viruses to arise from China from time to time.  Neighboring countries know this and are naturally vigilant.  The citizens of Asian countries are used to wearing a mask whenever they have the sniffles, and they are prepared for local epidemics. 

South Korea had the following strategy:

  • Early free testing for anyone who wanted a test.
  • Contact tracing of people exposed to infected individuals. Cell phone and credit card data was used to track residents and produce contact information for infected people.
  • Quarantine COVID positive patients at home, fines imposed for breaking quarantine.
  • Nearly all citizens wore masks in public.
  • Treatment of patients with moderate symptoms.
  • No “Lockdowns”, that is quarantining COVID negative individuals, but schools, cinemas, and gyms were closed. Most stores were open.  Vaccine passports allowed access to high risk areas during the Fall and Winter of 2021/22.

By contrast, the US, and most of the Western world, had the following policies:

  • Testing only for symptomatic people.
  • Treatment only for severe cases.
  • Early “Lockdowns” of all but essential workers.
  • Contact tracing applied too late to be effective.
  • Early communication on masks was incorrect and even deceptive to avoid a run on N95s which happened anyway.  Mask wearing remained controversial and unevenly applied, medical grade respirators unavailable or rarely used for most of the pandemic.

I will point out that most countries, even Japan, South Korea, and Taiwan, had major outbreaks during the Omicron wave.  These countries did have some COVID related restrictions during the Winter of 2020/21 and during the Omicron wave.  I leave China out of the analysis because I don’t trust their data.

Most respiratory viruses like cold and flu are spread by droplet or contact transmission.  However, SARS-2 is spread by aerosol transmission.  Droplets and aerosols are similar, but an aerosolized droplet is much smaller and can linger in the air for much longer than a droplet, more like a cloud than a spray.

Several precautions than became common and even required are designed to prevent droplet transmission rather than aerosol transmission.  These precautions include 6 foot distancing, cloth and blue surgical masks, and those plastic shields at the store.  These measures are mostly ineffective at preventing the spread of aerosols because they do not prevent the movement of small particles.  As you know, I was a strong advocate of masks indoors during the pandemic, but only the medical grade respirators like N95s, KN95s and KF94s.

Peculiarities of the US:
In addition to prevention policies, the US has several cultural and demographic factors which contribute to our high infection numbers. 

Population: Americans know that the 2 most populace countries in the world are China and India, with about 1 billion people each.  These populations appear to dwarf our own estimated population of 330 million.  But we forget that the US is the 3rd most populace country in the world, with number 4 being Indonesia at 272 million. Japan has 125 million, and the most populace European country, aside from Russia is Germany at only 82 million.

Mobility: The US is an enormous country, and Americans are used to traveling much more than other peoples.  We may not fly to other continents as much as the Germans do, but we don’t hesitate to drive several hours for the weekend, or fly across the continent. I was having lunch with an Englishman once who said they might plan for weeks to take a trip that would involve a 3 hour drive.  Many Americans may only plan for a few hours for such a trip. Our high mobility certainly contributed to our high COVID numbers.

Independence:  Our independent nature has been an enormously useful quality, contributing to our high innovation, personal freedom, and economic prosperity.  So I’m certainly not arguing against American individualism.  But I have to acknowledge that our fierce sense of independence did contribute to non-compliance with government recommendations.  And yes, I totally understand that many official recommendations were ineffective or unlawful. But this factor is part of the equation that we will need to consider in order to deal with future pandemics.

Federalism: The US Government has a lot less power than most people think.  The 10th amendment states:

The powers not delegated to the United States by the Constitution, nor prohibited by it to the States, are reserved to the States respectively, or to the people.

This means that the only powers the federal government has are those expressly given to it in the Constitution. Much of what the US government does now goes beyond the powers given by the Constitution, and is only done because no one has stopped them.  New federal powers are often popular, so they go forward unchecked. 

The pandemic has caused many to lose trust in several previously trusted federal agencies, and States have started to pull back power from the US.  Many were surprised to discover how limited the President’s power was during the pandemic, limited to suggesting guidelines and creating regulation for federal property and interstate travel.  The vaccine mandate attempted to use private companies to enforce vaccination, but even this was struck down by the Supreme Court. 

Emergency powers outlined in the Constitution only apply in the case of an insurrection or invasion. Unless a Constitutional amendment is passed, the Federal Government can only impose martial law if an emergency forces the courts to close (Duncan v. Kahanamoku, 1946).

States have much broader powers.  In California, the Emergency Services Act allows the Governor to declare a state of emergency at any time, a state which grants him broad powers, including the power to suspend certain laws.  Some have said that this state can only last 90 days without approval from the Assembly, but the ESA allows the Governor to end the state of emergency whenever he deems it necessary, “at the earliest possible date that conditions warrant.” (§8629).

All this to say, the states have much more power to address a pandemic than does the federal government.  Whether you find this good or bad news depends on your own political leanings, and the state you live in!

Manufacturing:
The national shortage of N95 masks early on in the pandemic painfully revealed that our domestic capacity for manufacturing certain necessary items fell woefully short. Other items in short supply were hospital gowns, gloves, disinfectant, certain medications, and yes, even toilet paper. 

This shortage meant that almost no-one had effective masks early on.  In addition, confused messaging from Dr. Fauci and the CDC later produced a condition in which ineffective masks were common in public areas.  This certainly had a big negative impact on our case load.

Misinformation and freedom of speech:
I have written on this before, so I won’t repeat this now.  Suffice it to say that many Americans lost confidence in government agencies, including the CDC and FDA during the pandemic.  Lost trust is hard to regain and it can take a long time to get back.  I’ll discuss this more in my next post.

Political polarization:
Similar to the erosion of trust in government agencies, the response to the pandemic quickly became a “team sport” with some responses being typical of the “blue team” and others typical of the “red team”.  Unfortunately, both sides often opposed reasonable ideas simply because they came from the other side.  Also, some terrible ideas had a longer life span than they should have because they were favored by certain political groups.  As I’ve said many times before, science and politics are a terrible combination.  When politics gets involved in science, the results are usually terrible. 

Frankly, things have become so polarized that I am pessimistic about the future.  Republicans and Democrats seem to disagree strongly about nearly everything these days, having fundamental worldview differences, not just differences in approach. I know lots of people who lost contact with friends and even family during the pandemic, as have I myself.

Let me know in the comments what factors you think contributed to our response. Later this week, I’ll post on the next pandemic, and how we can prepare.

Don’t fear, but be smart,
Erik

Case Update, December 21st, 2021; Omicron overtakes Delta in the US!

All Articles, Case Update, Fatality Rate, Most Popular, Omicron, Treatments

This is a case update. I’ll also discuss the new Omicron numbers in the United States, and reevaluate if Omicron will represent our way out of the pandemic.

In terms of whole numbers, cases are still increasing in the US, mostly in the Northeast. In some amazing news, most of the cases in the Northeast are now from Omicron and not Delta (more detail on this below).

Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a linear format.
Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a linear format.
Endcoronavirus County Level Map, December 20th, 2021
Endcoronavirus State Level Map, December 21st, 2021

In California, cases are still at a persistent number, at around 5,000 new cases a day.

Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a linear format.
Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a linear format.

San Diego is continuing to experience a burst in cases right now.

Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County. Graph is presented in a linear format.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County. Graph is presented in a linear format.
Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a linear format.

Omicron rapidly overtakes Delta!: In amazing news, cases from Omicron already outnumbers cases due to Delta in the US, and are 90% of new cases in some regions. Last week, the CDC was reporting that 3% of US cases were from Omicron. This week, they revised that number upward to 12%, but also reported that for 12/18, 73% of COVID cases in the US were caused by Omicron, 60% in the Southwest. I expect 95% of cases in the US to be Omicron by next week, and virtually 100% by New Years. This is potentially great news!

From the CDC page on Variant Proportions. Accessed December 20th, 2021.
From the CDC page on Variant Proportions. Accessed December 20th, 2021.

While still very early, a few other countries have started to produce data that can tell us what we might expect. In South Africa, the peak of new cases is already coming down. In previous waves there, peak deaths have trailed peak case by about 10 days. But for the Omicron wave, there is only a modest increase in deaths 10 days after peak new cases. This seems to confirm reports that Omicron produces very mild disease.

From Worldometer.
From Worldometer.

In the UK, Omicron cases are surging dramatically, with cases doubling every few days. In spite of this, there were 909 COVID deaths last week. In total, only 14 people have died from an Omicron infection this far. As Omicron spreads in the UK, we will likely see hospitalizations and deaths go down dramatically. I will caution that in the UK, deaths trail cases by about 12-20 days, and we are still early in the Omicron wave in the UK.

From Worldometer.
From Worldometer.

Back in the US, 90% of new cases in the Northeast are due to Omicron right now. In spite of this, total case numbers in New York are roughly double what they were a week ago. This means that of the 20,000 new cases daily in New York State, only 1600 are from Delta, the rest are from Omicron. So Delta cases in New York have gone down by 80%! Indeed, Omicron appears to be displacing Delta!

From Worldometer.
From Worldometer.

Keep in mind that we are only a few weeks into the Omicron wave, and things are still early. I will also caution that there are still a few people dying due to Omicron, so it’s not all over. Cases may be extremely high in the next few weeks. That being said, Omicron definitely has the potential to essentially end the pandemic, maybe in just a few weeks! If you’re one of my colleagues in the medical industry, start polishing up your post-COVID business models now!

I am NOT saying you should run out right now and get a nice case of Omicron. It’s still to early to say if that will be a good idea. For now, keep it together and stay cautious for just a few more weeks until we know more. I will also caution that I have a track record of being overly optimistic on my expectations of when the pandemic will end!

Given that the vaccines have some inherent risks of their own, and that Omicron appears to have very mild symptoms and completely ignores previous immunization, I do not recommend a booster to prevent Omicron infection at this time. Instead, those with risk factors should simply take precautions until the Omicron wave is over, or until more is known. As always, consult with your medical provider when making health care decisions. I am a molecular biologist, not a physician.

Omicron scorecard: Here’s my revised “scorecard” from last week. As a reminder, I am not an epidemiologist, I’m a molecular biologist. This is my informed but not expert opinion.

1) Omicron must not use the ADE pathway to produce more severe cases: Looking at the available data so far, while Omicron may preferentially infect those who have been previously infected, cases are still mild, and fatality rates very low. So for now, this criteria is met.

2) Low fatality in older populations: South Africa has a relatively young population, so reports of mild symptoms may not carry over to countries with older populations. The UK data from this week suggests that Omicron deaths will be low, even in older populations.

3) Displace Delta: Delta has a much higher case fatality rate in the US than Omicron appears to have. For Omicron to end the pandemic, it must displace Delta from the COVID population of strains. With the super high infectiousness of Omicron, it might just do that. Total Delta cases are currently down 80% since the start of the Omicron wave in New York State. This is very encouraging. This criteria is provisionally met.

4) Omicron must not circulate independently from Delta: Related to the above, if Omicron is very different from Delta, it may act as a completely different virus. There’s a chance that Omicron may displace Delta on the short term but still allow Delta to persist. Since Omicron is displacing Delta, it looks like this criteria may be met, but we won’t know for sure until we can see if Delta pops back up after the Omicron wave is over.

5) Omicron infection must immunize against future SARS-2: Since Omicron appears to infect those with immunity to Delta, it may be that it is different enough that it will not provide immunity to Delta or other SARS-2 strains. This criteria is not strictly necessary if Omicron completely displaces other SARS-2 strains (see 3 above), but it would be really nice to have some protection against future strains. We won’t know for sure about this one until a new version of COVID arises.

Don’t fear, but be smart!
Erik

Omicron gives Delta an Atomic Wedgie!

All Articles, Case Update, Fatality Rate, Most Popular, Omicron

“Omicron” may sound like a killer robot, but it turns out, it’s OUR killer robot!

You’ll have to forgive my imprecise language this evening, but we have some potentially VERY good news, and I’m a little giddy. Last week I reported that 3% of the COVID cases in the US were because of the super infectious but mild disease causing Omicron variant. On Monday afternoon, the CDC updated their numbers from last week stating that 12% of the COVID was from Omicron. Today, they are reporting that for this week ending Sunday, a full 73% percent of COVID cases were from the Omicron variant! With only a doubling of cases in the last few days, that means at least 50% of Delta variant cases have been displaced by Omicron cases. This means that Omicron is displacing Delta. At the current rate of expansion, by Christmas, at least 95% of COVID in the US will be from Omicron, and nearly 100% by New Years! If we can keep Delta suppressed for at least 2 weeks, it will be eradicated from the US. This is so great!

From the CDC page on Variant Proportions. Currently, 73% of COVID cases are from Omicron.
From the CDC page on Variant Proportions. Currently, 60% of COVID cases in the Southwest are from Omicron.
Daily new cases in New York State. Note the doubling of cases in the few days. But 90% of these cases are from Omicron, so Delta cases are roughly 25% of what they were a week ago, having been displaced by Omicron.

I have often been overly optimistic, but literally, if things go they way they’re going now, the Pandemic could virtually be over by New Years!

Case Update, December 15th, 2021; Omicron update, will Omicron end the Pandemic?

You know that cop at the beginning of all those movies who is about to retire and then gets killed in the first 10 minutes? Don’t be that guy. We’re almost out of the woods. Don’t go crazy and get COVID now. Keep it together for another few weeks, for crying out loud.

After I’ve settled down a but, I’ll be adding more information, links to my blog post, and a more sober assessment on this topic tomorrow, so check again then. For now, crack open a Diet Coke, in the seclusion of your own home or sensible outdoor gathering and celebrate!

Don’t fear, but party on… sensibly of course,
EPJ

Antibody Dependent Enhancement

All Articles, Antibody, Fatality Rate, Most Popular, Risk Factors, Treatments

Note, March 26th, 2022: The first part of this post was written on July 7th, 2020. Since that time, there has been evidence that appears contradictory in the ADE story. Reading the entire post will help you understand how ADE and COVID are related, but it is a complex and evolving issue, so things may still change.

Originally posted July 7th, 2020

I’m going to bring up an issue that I’ve been avoiding talking about for some time. I’ve been avoiding talking about it because it’s not a certainty, and also because the possibility will be scary for some. The reason I feel compelled to talk about it now is that many are having a hard time understanding why I am still so concerned about the virus when the fatality rate is low and dropping, and folks want to get back to normal life. I’m even hearing about young people having COVID parties in which people gather with a sick individual so they can all get infected and be immune from the virus thereafter.

Before I share this, I’ll also say that the medical community is doing a better job treating patients with COVID, and the disease is becoming more survivable. In addition, we now know a lot about how the virus is spread, and if a person wants to remain uninfected, they can do that, while still getting together with friends and family, and still working and getting on with life. You can be reasonably certain you will not get infected if you do the following:

1) Wear a mask or face covering in public. Avoid places with unmasked people.
2) Keep 6 ft away from others.
3) Avoid indoor gatherings, especially ones in which singing or shouting is likely.
4) Small outdoor gatherings are fine, even without masks, if everyone maintains a distance. Have guests bring their own food.
5) While many restaurants are open for limited indoor seating, I personally am still not comfortable eating indoors at a restaurant. I enjoy eating outdoors at restaurants, however.

Antibody Dependent Enhancement: Several years ago, scientists were developing a vaccine against Dengue Fever, a mosquito borne disease which causes debilitating joint pain in patients. Some time after trial vaccination, several vaccinated patients died suddenly of Dengue Fever. This became the most studied example of Antibody Dependent Enhancement (ADE). Normally, for the annual flu let’s say, a person gets infected by the flu, is sick for a few days, and the immune system develops a response by creating antibodies against that specific strain of the flu. If they are exposed again in a month, nothing will happen. If the patient is exposed to a different strain the following year, they may still get sick, but the antibodies they developed the year before may help them have less severe disease and recover more quickly. Part of the immune response is that some immune cells display antibodies on their surface to capture new invaders.

With Dengue and some other viruses, the first stages are normal. A person gets infected and develops a response. If they get re-infected a month later, nothing happens. But if they get infected with a slightly different strain months or years later, instead of being protected, the virus attaches to antibodies displayed on immune cells and uses the antibodies as a site of entry into the immune system. The immune system is quickly infected, and the patient has a more severe disease with the second infection. Some estimates are that disease may be 3-4 x more severe in these patients.

As it turns out, SARS-1, which arose in 2002, and MERS, which has small outbreaks every year, are both Coronaviruses and both appear to be able to use the ADE pathway. This raises the possibility that SARS-2, the current virus, can also use the ADE pathway. This means that a person infected for a second time with a different strain of SARS-2, or any other Coronavirus for that matter, may be at much higher risk for severe disease.

This is why I’m not in favor of pursuing herd immunity as a pathway out of this crisis, because it will prime people for ADE related problems if a similar strain should strike next year.

This is not a new idea. If you search for “ADE” or “Antibody Dependent Enhancement”, you will see many articles, some peer reviewed from respected journals, on the phenomena. Dr. Fauci has even referenced it using the term “enhancement” when talking about vaccine development.

Why haven’t the government public health departments been more open about this? They tend to make statements only based on what they can be reasonably certain of, which is why they have been so slow to react to many aspects of the current crisis.

Again, it’s not certain that ADE will play a role next year. It’s too early to know. I’m informing you of the possibility so you can make wise decisions for you and your family.

_________________________________________
Update: November 20, 2020

Since writing the above post, things have changed a little. There have been a handful of known cases of people being re-infected with SARS-2. In some of these patients, symptoms were worse, while in others, symptoms were less severe. In all of the well characterized cases, the 1st and 2nd strains that infected them were different, suggesting that it’s not a re-infection by the same strain, but a new infection by a different strain.

We’ve had at least 2 main strains in the US, SARS-2 which arrived in January or February, and a strain called D614G which probably arrived in April or May and likely caused the 2nd wave in June and July. The D614G strain is likely more infectious than the original SARS-2 strain, but is perhaps less virulent, since the fatality rate during the second wave appears to have been lower. In fact, there may have been several strains circulating around the world and the US for much of the pandemic.

How does this all relate to ADE? The fear with ADE is that a 2nd infection will cause worse symptoms than with the first infection. This may still be true. But we’ve had several circulating strains and so far, no real evidence the re-infections have universally been worse. So it appears for now that the ADE experiment is already going on, and that perhaps the phenomena will not have as great an impact as I feared. I am currently cautiously optimistic that ADE will not cause significant additional mortality.

This also has some impact on the vaccine discussion that is currently ongoing. If ADE will not have a significant impact, than the vaccine may be safer that I previously thought, and I have become cautiously optimistic about the success of the vaccine.

_________________________________________
Update: December 12th, 2020

More on ADE and Vaccines: Some potential very good news for me on the vaccine front. For months I’ve been warning about ADE, the phenomena that some viruses can be even more dangerous in a second infection than the first. Karen Parrott, a former colleague at Quest Diagnostics, often provides me with interesting COVID related stuff. This week she sent me a podcast featuring Paul Offit, the developer of the first Rotavirus vaccine and an author of many books on immunology and vaccine production. I am not an immunologist but he is. More importantly, he’s the first authoritative person that I’ve heard in the media speak at length on the ADE issue and how it relates to COVID. He claims in the attached clip (time stamped at 14:40) that the current vaccines do not appear to trigger the ADE pathway in animal models, and human trial subjects never displayed the signs that ADE was involved in secondary exposures. This difference from SARS-1 and MERS may be related to the fact the SARS-2 is much less virulent than these other 2 viruses.

This makes me more optimistic that the vaccine will be safe from an ADE perspective. I won’t be able to get the vaccine for some time, but I am more willing to get it now than ever before. Several physicians I know are eager to get it as soon as it is available. This is great news!

In the interest of full disclosure, I will point out the some patients receiving the vaccine the UK have experienced some injection site irritation, especially in those with allergies. This is actually somewhat normal for vaccines, and appears to pass within a few days.

Now that mRNA vaccines have been produced for the first time, future development of this new kind of vaccine should be even faster than this time!

________________________________________________
Update: April 13th 2021

ADE and the next SARS virus: I wanted to explain a little more about my continued concerns about ADE. As the pandemic progresses and we have numerous variants circulating around the world and the US, ADE does not appear to have had an impact on the current situation. This is certainly good news. If it did have an impact, we would be seeing additional deaths from the new variants, which we do not.

My continued concern comes because ADE impacts our ability to fight the NEXT virus. SARS viruses (SARS, MERS, SARS-2) have the ability to easily infect the immune systems of those previously infected with closely related but different strain of the virus. If a future strain of SARS comes out, let’s call it SARS-3 for now, ADE may become a big deal. I stress that this is only theoretical at this point. SARS was moderately infectious, but also very pathogenic, giving all known patients severe symptoms and killing 10%. It was actually less dangerous globally, since outbreaks tended to be detected early and quickly snuffed out. SARS-2 is highly infectious, but much less pathogenic. It’s greater global impact came from it’s very high infectiousness and very long incubation time, being passed even from pre-symptomatic patients. The tendency of all viruses is to become more infectious and less pathogenic over time, a pattern followed by SARS and SARS-2. If we have a SARS-3 someday, it will likely be even more infectious than SARS-2, but less pathogenic. On the other hand, MERS is more pathogenic than SARS, so this pattern doesn’t always follow. The next time another SARS coronavirus breaks out, we will need to be very careful initially until we understand the parameters of the new virus.

So what do you do if you had COVID or had a COVID vaccine if a SARS-3 comes out? If that happens, vaccine production will likely be much faster than this time. Be very careful with the virus initially, and get the new vaccine as soon as it is available to you, because you may be at greater risk for severe symptoms. I know some of this is confusing and counter-intuitive! Feel free to ask questions below!

Update: August 30th, 2021

Delta already using the ADE pathway? A doctor friend of mine sent me a pre-print paper from a lab in Japan. Please note, this is a pre-print paper and has not yet finished peer review! The paper describes experiments using antibodies derived from patients infected with the Wuhan strain, as well as with the Delta Variant. They then studied binding of these antibodies to artificial viruses. The paper argues that Delta variant viruses are less neutralized by vaccines against “wild-type” or Wuhan strain vaccines. While the “wild-type” antibodies against Wuhan can neutralize a region of the Delta Spike protein called the Receptor Binding Domain (RBD) (Figure 1C), other antibodies binding to another region of Delta Spike protein actually enhance infectivity. Figure 1D from the paper shows negative levels of “neutralization” for antibodies that bind the N-terminal domain of the Spike protein. The paper calls this “enhanced”. Yes, this is the ADE I’ve been talking about.

Figure 1 from Liu et al 2021.

They suggest that with rapid changes in COVID variants, a new version of Delta is going to be able to use the ADE pathway in the near future, when Wuhan era antibodies will no longer be able to neutralize a mutated Delta strain.

To sum that all up in simpler language, it basically says that Delta is more infectious because it is partially using the ADE method of infection. Future versions may be less prone to be neutralized by Wuhan antibodies, making them fully enhanced. If this happens, we may have more severe disease in those who get infected with this new enhanced Delta.

They conclude by saying a booster against the Wuhan strain will not be effective in improving protection from Delta, and that a new vaccine against Delta will be required.

The material in the paper may help to explain why we have been seeing lowering levels of vaccine effectiveness in some countries.

Just to be very clear, they are not saying that this new enhanced Delta exists now, just that it may exist in the future.

I will pay close attention to this issue. If you have already been vaccinated or had COVID, a new Delta vaccine will be your best defense against possible ADE arising from a possible enhanced Delta.

If an enhanced Delta arises, and you have had Wuhan COVID or a Wuhan vaccine, and you haven’t had Delta, then you may be at greater risk for severe disease.

If you have had COVID since July 2021, you are likely already immune to the Delta variant, and this will not be an issue for you.

I am fully aware this complicated. Also, the CDC has rarely if ever discussed this possibility, so unfortunately, most of the people you talk to about this will not believe it. I am sharing this with you so you can make wise decisions for you and your family.

Some companies are already working on Delta versions of the vaccine. If you have had the current vaccines, or had COVID, you should get the Delta vaccines as soon as they are available.

Of course, discuss your medical history with your doctor before making medical decisions.

_________________________________
Updated: January 29th, 2022

The “Final” Verdict on Antibody Dependent Enhancement: As most of you know, ADE has been a major concern of mine from almost the beginning. I’m finally willing to give an assessment of how ADE impacted the pandemic. There were a smattering of cases in previously infected people who may have had more severe cases because of possible ADE, but not more than a smattering. It’s also becoming well acknowledged that Omicron infected everyone regardless of vaccination status and may have even preferentially infected vaccinated people. I know MANY people who are double vaxxed and boosted who got Omicron.

All that being said, I never saw any evidence that conclusively suggested that ADE was causing more severe symptoms because of natural or vaccine mediated immunity. In fact, even during Omicron, during which ADE was most likely to be operating, those with previous immunity clearly fared better than those without. Because I think Omicron is the death rattle of the pandemic, I’m willing to say that ADE never became the threat I was concerned about. For this reason, IF I didn’t already have natural immunity because of Omicron, I might actually get vaccinated IF I could find someone who would aspirate before injecting (see the post from earlier this week)!

I never saw any paper that dealt with the issue of ADE, not even a little. Those that mentioned it did so only in passing.
__________________________________
Updated March 25, 2022

Certain vaccinated individuals are more likely to be infected by Omicron than the unvaccinated:  A UK surveillance report shows that vaccine effectiveness against symptomatic Omicron infection goes from around 65% effective soon after 2 doses of vaccine, to around 5% 6 months later.  Protection from hospitalization goes down to just 35% after 6 months. These findings suggest that to maintain full protection against Omicron, a vaccinated person will need to get a booster every 3 to 6 months.

From UK Surveillance Report, March 17, 2022, Table 1b. Effectiveness of Pfizer vaccine at preventing symptomatic COVID infection after 2 doses, and after a Pfizer or Moderna booster.
From UK Surveillance Report, March 17, 2022, Table 2b. Effectiveness of Pfizer vaccine at preventing hospitalization after 2 doses, and after a Pfizer or Moderna booster.

In another finding from the report, people with 3 doses of vaccine are 3x more likely to be infected with Omicron than unvaccinated individuals.  This is the clearest evidence yet that Omicron may be using Antibody Dependent Enhancement (ADE) to infect people. The Lewnard et al paper from a few months ago has a similar finding.  For both studies, a certain number of vaccine doses are more likely to increase the chance of infection.  If viruses are using the ADE pathway, this effect would be explained more by the timing than by the number of doses per se.  For ADE to work, a person needs to have a mediocre immune response to an agent, not a strong or weak one. Since we know vaccine mediated immunity goes down over time, then a person becomes more likely to be reinfected as their immune response goes from strong to mediocre.

From UK Surveillance Report, March 17, 2022, Table 13. New case rates among UK residents with at least 3 doses of vaccine, and with no vaccination. Numbers are normalized for the percentage of people in each group.

So should you get a booster? Again, if you have risk factors like age, obesity or respiratory problems, you might want to get a booster every 3 – 6 months. Otherwise, you may choose instead to just take extra precautions as Omicron cases continue to fall in the US. If you choose to get a booster, ask them to aspirate before injection. Talk to your doctor when making medical decisions.

________________________________________________

More than ever, don’t fear, but be smart,
Erik


A selection of relevant papers:

ADE and it’s potential impact for SARS-2:ade-and-sars-2 Download



ADE in SARS-1:ADE and SARS-1 Download



Overlapping symptoms for SARS, MERS, and SARS-2:ade-sars-mers-sars-2-liu_et_al-2020-journal_of_medical_virology Download



Is COVID-19 receiving ADE from other coronaviruses?ADE_and_COVID Download



Possible mechanism for ADE:ade-mechanism-jvi.02015-19 Download

Case Update: July 7th, 2020; Antibody Dependent Enhancement

All Articles, Antibody, Case Update, Fatality Rate, Masks, Re-opening, San Diego

Dear Friends,
This is a case update. I’ll also have an important message about antibody dependent enhancement.

Cases continued to rise unchecked in the US, California and San Diego County in the last week, although the long holiday weekend did have impacts on reporting. Some good news is that the number of deaths reported in the US has been slowly declining despite the case increase. Keep in mind however, that deaths will lag behind cases by as much as 2 weeks, so we may yet see an impact from the higher caseload. The number of deaths have been trending flat in California.

Graph is by me, from data collected from Johns Hopkins University COVID site.
Graph is by me, from data collected from Johns Hopkins University COVID site.
Graph is by me, from data collected from Johns Hopkins University COVID site.
Graph is by me, from data collected from Johns Hopkins University COVID site.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County.
From Rt Live

Rt Live is reporting that all but 8 US states or territories have Rt values above 1.0, meaning that the virus is expanding in those states.

I’m going to bring up an issue that I’ve been avoiding talking about for some time. I’ve been avoiding talking about it because it’s not a certainty, and also because the possibility will be scary for some. The reason I feel compelled to talk about it now is that many are having a hard time understanding why I am still so concerned about the virus when the fatality rate is low and dropping, and folks want to get back to normal life. I’m even hearing about young people having COVID parties in which people gather with a sick individual so they can all get infected and be immune from the virus thereafter.

Before I share this, I’ll also say that the medical community is doing a better job treating patients with COVID, and the disease is becoming more survivable. In addition, we now know a lot about how the virus is spread, and if a person wants to remain uninfected, they can do that, while still getting together with friends and family, and still working and getting on with life. You can be reasonably certain you will not get infected if you do the following:

1) Wear a mask or face covering in public. Avoid places with unmasked people.
2) Keep 6 ft away from others.
3) Avoid indoor gatherings, especially ones in which singing or shouting is likely.
4) Small outdoor gatherings are fine, even without masks, if everyone maintains a distance. Have guests bring their own food.
5) While many restaurants are open for limited indoor seating, I personally am still not comfortable eating indoors at a restaurant. I enjoy eating outdoors at restaurants, however.

Antibody Dependent Enhancement: Several years ago, scientists were developing a vaccine against Dengue Fever, a mosquito borne disease which causes debilitating joint pain in patients. Some time after trial vaccination, several vaccinated patients died suddenly of Dengue Fever. This became the most studied example of Antibody Dependent Enhancement (ADE). Normally, for the annual flu let’s say, a person gets infected by the flu, is sick for a few days, and the immune system develops a response by creating antibodies against that specific strain of the flu. If they are exposed again in a month, nothing will happen. If the patient is exposed to a different strain the following year, they may still get sick, but the antibodies they developed the year before may help them have less severe disease and recover more quickly. Part of the immune response is that some immune cells display antibodies on their surface to capture new invaders.

With Dengue and some other viruses, the first stages are normal. A person gets infected and develops a response. If they get re-infected a month later, nothing happens. But if they get infected with a slightly different strain months or years later, instead of being protected, the virus attaches to antibodies displayed on immune cells and uses the antibodies as a site of entry into the immune system. The immune system is quickly infected, and the patient has a more severe disease with the second infection. Some estimates are that disease may be 3-4 x more severe in these patients.

As it turns out, SARS-1, which arose in 2002, and MERS, which has small outbreaks every year, are both Coronaviruses and both appear to be able to use the ADE pathway. This raises the possibility that SARS-2, the current virus, can also use the ADE pathway. This means that a person infected for a second time with a different strain of SARS-2, or any other Coronavirus for that matter, may be at much higher risk for severe disease.

This is why I’m not in favor of pursuing herd immunity as a pathway out of this crisis, because it will prime people for ADE related problems if a similar strain should strike next year.

This is not a new idea. If you search for “ADE” or “Antibody Dependent Enhancement”, you will see many articles, some peer reviewed from respected journals, on the phenomena. Dr. Fauci has even referenced it using the term “enhancement” when talking about vaccine development.

Why haven’t the government public health departments been more open about this? They tend to make statements only based on what they can be reasonably certain of, which is why they have been so slow to react to many aspects of the current crisis.

Again, it’s not certain that ADE will play a role next year. It’s too early to know. I’m informing you of the possibility so you can make wise decisions for you and your family.

More than ever, don’t fear, but be smart,
Erik


A selection of relevant papers:

ADE and it’s potential impact for SARS-2:

ade-and-sars-2Download



ADE in SARS-1:

ADE and SARS-1Download



Overlapping symptoms for SARS, MERS, and SARS-2:

ade-sars-mers-sars-2-liu_et_al-2020-journal_of_medical_virologyDownload



Is COVID-19 receiving ADE from other coronaviruses?

ADE_and_COVIDDownload



Possible mechanism for ADE:

ade-mechanism-jvi.02015-19Download

Summary: What we know so far, June 22, 2020

All Articles, Antibody, Fatality Rate, Masks, Quarantine, Re-opening, Risk Factors, San Diego, Testing, Treatments

This long post will be a summary of what we have learned so far about the Coronavirus, and I’ll make some predictions about what to expect next.  Since I’ll be sharing so much information, I won’t give references for everything here. I also have to make the disclaimer that new studies are constantly being done, and some of the below information may need to be revised later. To make my standard disclaimer, I am not an epidemiologist or a physician.  I have a Ph.D. in molecular biology, and my specialty is infectious disease testing. On much of the below, I have an informed but not expert opinion.

Coronaviruses: Coronaviruses are a large group of viruses unrelated to the flu.  What we think of as the common cold, are actually member of several classes of viruses like Adenovirus, RSV viruses, Rhinovirus, and several Coronaviruses.  Many Coronaviruses cause diseases no more virulent than the common cold.  However, just like novel flus can cause extra trouble, so can novel Coronaviruses.  The first SARS virus was much more lethal that the SARS-2 virus, but because SARS had a short incubation period and made almost every infected person sick, it was much easier to contain.  The Middle East Respiratory Syndrome (MERS) Coronavirus infects a few people every year, and is very lethal, with a fatality rate of 34%, but it also has not made a global impact.  The reason SARS-2 is so dangerous is that it’s VERY infectious (Ro of between 2.5 and 5.7) and has a VERY long incubation time (2-14 days), making it very hard to track.  Plus, it’s at least 2x as deadly at the annual flu.

Name: The official name of the virus is SARS-2-CoV (for Severe Acute Respiratory Syndrome-2 CoronaVirus).  The official name for the disease it causes is COVID-19 (for COronaVIrus Disease-2019).  You may notice that the term SARS actually sounds a lot like a disease.  You would be right.  So why did they need a different disease name than SARS-2, or SARS-19? I don’t know.

Spread:  Early reports were that SARS-2 mostly spread like a flu, with droplets spreading from coughing or sneezing.  It became apparent later that the virus was also spread through aerosols by laughing, singing, shouting, or even just talking in close proximity for long periods.  As further study was done, it appears that most infected people don’t infect anyone else.  Rather, most infections come from “super-spreader” events, in which a single person infects a large group of people.  This usually happens indoors (at least 19 times more likely) during activities like fitness classes, funerals, concerts, and choir practices.  While outdoor activities aren’t completely immune to these events, they are much more rare.

Viral load upon exposure appears to be an important determinant of how severe a case will be.  Basically, this means that if you’re infected by a “low dose” of virus, your disease is likely to be less severe.  I have several physician friends who have stated that it seems to them that cases in the hospital are less severe than they used to be.  One likely reason for this is that since more people are wearing masks in public than early on, those who are infected are being infected by a lower viral load.

Early studies demonstrated that viable virus can exist on objects for hours or days.  However, it does not appear that a substantial number of people are being infected because they have touched a contaminated object. 

The WHO made a confusing claim recently that asymptomatic people cannot spread the virus.  While this is technically correct, they were not clear that “asymptomatic” is a technical medical term meaning someone who does not have, and will never have, symptoms.  Another group is “pre-symptomatic”.  These are people who currently don’t have symptoms, but will develop symptoms in a few days.  As it turns out, pre-symptomatic people do spread virus, and are likely responsible for up to 80% of new cases. So yes, people without symptoms can and do pass the virus to others.

Risk Factors:  Many believe that only old people are at risk. While it’s true that age is a dominant factor, other risk factors are important, and younger people have also experienced severe symptoms.  Other risk factors include respiratory conditions like asthma or COPD, heart conditions, kidney conditions, liver disease, diabetes, obesity, auto-immune disease, use of NSAID anti-inflammatory medications, being immunocompromised (HIV infected, undergoing cancer treatment, under medication for a transplant), vitamin-D deficiency, type A blood (Type O appears to be protective), inadequate sleep.

Always check with your doctor before changing your medications. I have an auto-immune disease and take daily anti-inflammatories, but my doctor has advised me to continue taking these unless I experience COVID symptoms.

Make sure your doctor is aware if you have any of the above conditions.

Symptoms: Many people who have SARS-2 experience no symptoms, or experience mild flu symptoms.  If you have ANY cold or flu symptoms, contact your doctor and see if you can be tested.  If you live in San Diego County, and your doctor cannot offer you a test, call 2-1-1 to get a free test from SD County Public Health.  If you have additional symptoms like shortness of breath (you just can’t seem to get enough air), loss of smell or taste, nausea or diarrhea, contact your health care provider or an urgent care immediately.

In severe cases, the virus can do wide spread and permanent damage to multiple organ systems.  Early treatment is necessary to prevent the most severe symptoms.

Precautions:  While lockdowns may have been effective in the US during the early stages of the pandemic, especially at a time when masks were hard to come by, recent evidence suggests that lockdowns provide only a moderate benefit over other means of control.  Here’s what appears to be beneficial:

Masks: Masks are not all the same and some are better than others.  Their main benefit is that they stop, reduce, or slow the travel of virus from infected people.  This prevents surrounding people from infection, or lowers the viral load of exposure.  Some, but not all, also prevent the wearer from inhaling airborne virus. N95 style masks without a valve are best if you can obtain one.

Best option: An N95 mask with no valve.

Social Distancing: Aerosolized virus can travel through the air. Staying 6 ft away from others helps prevent infection.

Handwashing:

Adequate sleep: Sleep is very important for a wide variety of body functions, including the immune system.  Get 7 – 8 hours of sleep per night.  A 26 minute power nap during the day is also beneficial if needed.

Vitamin D: Several studies have suggested that patients with the most severe cases of COVID also have the lowest levels of Vitamin D.  Because of our often indoor lifestyle, most Americans are Vitamin D deficient to some degree.  The best way of getting some Vitamin D is to make it yourself by going outside in shorts and a T-shirt for 30 minutes a day.  This is because Vitamin D is manufactured in our skin in response to sunlight.  If it’s not practical for you to do this, consider a Vitamin D supplement.  Darker skinned people are more likely to be Vitamin D deficient in the US.

Home isolation: If you have cold or flu symptoms, contact your doctor immediately and see if you can get a test.  Tests are much more available that early in the pandemic, and you should be able to get a test by request.  Also, if at all possible, isolate yourself from the rest of your family until you can be tested as negative.  Many new infections are taking place among family members.

Testing: There are several kinds of tests, and they tell you different things.

PCR: These tests use material collected from the nose and need to go to a specialized laboratory for processing.  They are very sensitive and specific, and indicate whether the patient is currently infected. This is the most common kind of test.

Antibody:  These tests detected antibody from a patient’s blood to see if the patient has been infected for at least a few days.  IgG tests may also tell if a patient was infected weeks or months previous, but are no longer infected.  Some patients do not mount an immune response that will provide long term antibody.

Isothermal amplification:  The Abbott ID Now COVID tests uses this relatively new technology.  These tests are similar to PCR and are both sensitive and very fast. 

If you have cold or flu symptoms, contact your doctor immediately and see if you can get a test.  Testing is much more available than it was early in the pandemic.  San Diego County is encouraging anyone who wants a test to be tested.

Treatments:  Treatment for COVID is complicated and not all patients can be treated in the same way.  Additionally, treatments are evolving rapidly, and your doctor many not treat you in the ways listed below.

Ventilators:  Some doctors now state that ventilators carry risks that may be unacceptable for COVID patients.  Many doctors now favor a nasal cannula, using ventilators only as a last resort if breathing is labored. 

Hydroxychloroquine, Azithromycin, Zinc: Several doctors from several countries have reported success with this combination.  Studies on the effects of these drugs have as yet still been non-conclusive.  Some positive studies suggest that Zinc is the main virus fighter of the treatment, with Hydroxychloroquine allowing better penetration of Zinc into cells.  Unfortunately, the debate on the efficacy of this regimen has taken on a strongly political tone, which almost always interferes with the scientific process.  Now pundits, as well as scientists, weigh in on this regimen.  I’m still holding a “wait and see” posture with this treatment.

MATH+: This regimen uses Methylprednisolone (an anti-inflammatory), Vitamin C, Thymine, and Heparin, as well as optional other treatments including Vitamin D and Zinc.  Early reports suggest success with this treatment.

Vaccines: Each spring, scientists learn which flu is likely to be prominent by the following Fall.  They make some guesses and create a vaccine for the flu season.  The manufacture process takes a few months. But it’s only this short because they already know how to make a flu vaccine.  Development of a brand new type of vaccine takes between 4 and 30 years!  There are many methods to make a vaccine, and scientists must try many of them before finding one that works.  Then they must try the vaccine on patients and make sure they are relatively safe.  Every vaccine carries some risk of side effects.

Early estimates for a Coronavirus vaccine were around 18 months.  My guess is that this is too optimistic.  Personally, I wouldn’t count on a vaccine for at least a few years.  In addition, some studies have suggested that Coronavirus vaccines in particular may cause side effects that may make vaccine development challenging.  My standard practice for my family is to wait on new drugs for a few years before using them myself. While I pro-vaccine in general, I would personally recommend waiting for a few years before getting a Coronavirus vaccine.

Herd Immunity: Some are promoting herd immunity as a way to move through the crisis faster.  The idea of herd immunity was popularized in pre-pandemic discussions on vaccines, promoting the idea that the more people are vaccinated, the more protection for those who can’t be.  This is a good idea when a vaccine is available, but not when there is no vaccine.  Putting many people in harm’s way to protect fewer others is not wise and is not standard medical practice.

The Future: Of course, it’s impossible to know what will happen next. My initial prediction was that the first wave would be over by July, and at this point, this doesn’t look likely.  New confirmed cases have started to rise or rise faster in the 3 areas I monitor most closely, the US, California, and San Diego County, and cases are rising fast in some countries previously unaffected, especially Brazil, Russia, and India. So I’m starting to think we may not be out of the first wave before the Fall season.

In addition, RNA viruses, such as Coronavirus, can mutate very quickly because the proteins used to copy their genomes are very error prone.  This means that a virus may change to a new form that can re-infect a person who has already had a previous version. Some reports suggest that this may already be happening with SARS-2. Some good news is that on the very long term (years), novel viruses tend to evolve to be less virulent, because it’s not in the “interest” of the virus to make the host very sick. The message is, we may need to adapt to a new reality for the next few months or years.  We can’t really afford to be “locked down” anymore, but mask wearing and elbow bumps may be a part of the landscape for some time.

Don’t fear, but be smart,
Erik

Dr. Erickson’s Video and the Fatality Rate

All Articles, Fatality Rate, Re-opening, Video

Originally posted on April 25th, 2020 on Facebook

Friends,
This one is going to be a little mathy. Several people have sent me the video titled “Dr. Erickson COVID-19 Briefing”. I’ve watched the first 12 minutes of the 52 minute video. Dr. Erickson argues that we have a large number of current cases, and that when comparing this number to deaths, he calculates the fatality rate at between 0.03 and 0.07%. This is less than the typical flu. He uses data from his home county of Kern County in California, NYC, the US, Spain, and others. Unfortunately, Dr. Erickson makes a critical error in his calculations.

For the US, he says we have 802,000 confirmed cases (around April 20th) and around 4 million tests. This would give him a positivity rate of 20% for the country. He then calculates that we then have 64 million cases in the country and only 45,000 deaths, giving us a fatality rate of 0.07%

The mistake he makes is that he assumes that tests given represents a random sampling of the population. Anyone who has tried to get a test and failed knows that not everyone who wants a test gets one. And not everyone requests a test either. Dr. Erickson has what’s called a sampling bias. You have to make sure you have a sample that represents the group you want test if you want to say anything about that group. Instead of testing the general population, Dr. Erickson is testing just people who meet the criteria for testing by the CDC or other health care body. This group is far smaller, and far more likely to have the virus than the general population. He over-estimates the number of COVID cases, by maybe 10 fold.

Several studies, some not yet published, have tested random selections of the population using PCR and antibody tests (see references 1, 2, 3, below). In those studies, fatality rates range from 0.12 – 0.7%, 2 – 23x higher than Dr. Erickson’s estimate. Also, the studies by Bendavid and Sood (2, 3) suggested that approx. 4% of the populations of Santa Clara County (San Jose) and Los Angeles were infected in early to mid April. So 96% of the population is still susceptible. At the 0.12 – 0.7 death rate, that’s 6,000 – 37,000 potential deaths for those 2 places alone. Even these studies, with fatality rates far higher than Dr. Erickson’s, have been criticized for an estimate that is too low because of sample bias (4).

We won’t really know how many people have had it until there is wide spread testing. South Korea has done extensive testing, and their fatality rate is 2.24%. This might be in the ballpark of the rate in the US.

So I have to reiterate, SARS-2 is not the average flu. In addition to being up to at least 5x more deadly, it’s also 4x more infectious. The very good news is, our efforts are paying off, and the daily rate of new cases for the US is now just 2.46%, down from a terrifying 46% on March 19th. It’s right for some living in rural areas to wonder if they can begin the process of going back to normal. Some can, but it needs to be done carefully and watchfully, with lots of testing for exposure, not just for symptoms (See my April 9th and April 22nd posts). The entire state of Minnesota plans to do just that. We can watch in real time to see how it goes for them. We don’t want another Albany, Georgia! Urban areas like coastal California and the Acela Corridor will have to wait awhile longer.

Don’t fear, but be smart!
Erik

1. Sutton et al., Universal Screening for SARS-CoV-2 in Women Admitted for Delivery. April 13, 2020. NEJM, nejm.org
2. Bendavid et al., COVID-19 Antibody Seroprevalence in Santa Clara County, California, April 11, 2020, preprint by medRxiv
3. CBS report on upcoming study
4. Experts demolish studies suggesting COVID-19 is no worse than flu

PS. If you want me to watch something later in Dr. Erickson’s video, please tell me what the time reference is. I really don’t want to watch the whole thing!

What is the Fatality Rate?, Antibody tests, Re-opening

All Articles, Antibody, Communication, Fatality Rate, Re-opening

Originally posted on April 22nd, 2020 on Facebook

Friends,
This is a little longer post, this time with lots of science. I’ll talk about new measures of the fatality rate, some of the new Antibody testing, and also about the new re-opening guidelines. As always, consult with your doctor when making health care decisions!

First, very briefly, I’ll just say that we have seen a big up-tick of cases in the last few days. I’m trying to be optimistic about this and assume for now that this is because of increased testing. The large labs have been purchasing new instruments of different types to broaden their offerings.

There have been a handful of studies trying to discern the number of asymptomatic cases. One recent study in New York tested all pregnant women coming in to deliver. It showed that at least in this sampling, there we about 7x more asymptomatic women testing positive for COVID than symptomatic women (Sutton et al, Universal Screening for SARS-CoV-2 in Women Admitted for Delivery. April 13, 2020. NEJM, nejm.org). If this is roughly correct, then most confirmed cases numbers you see can be multiplied by 8 to get the real number of cases, as least until testing becomes more comprehensive. This also means the real fatality rate may be approximately 0.7%, about 5x higher than the typical flu.

Some have suggested that the fatality rate for COVID is the same as the flu, but this is the low end of new estimates, and for now, my guess is that it is higher. I think 0.7% is a good estimate for now. The rate for the typical flu 0.14%. Keep in mind that the Ro value for SARS-2 is about 5.7, much higher than the flu at 1.28.

On to Antibody tests! There has been a lot of excitement recently about antibody tests, and I have promoted them in my posts as well. As many of you know, the PCR based tests look for viral RNA in nasal swabs and detect an active infection. They are very sensitive, but they are more expensive, and need to be performed at specialized sites. Because the virus mostly lives in the lungs, nasal swabs don’t always collect virus from an infected person, and the false negativity rate has been estimated to be around 29%, at least initially. This is very high.

Antibody (Ab) tests detect an immune response by the patient by isolating antibody from the blood. Most detect 2 kinds of antibodies. IgM antibodies are produced during infection, and start appearing after about 3 days. IgG antibodies are produced later, at about 7 days, but continue to be produced for weeks to months after infection. The antibody tests are often less sensitive than the PCR tests, and they do not work during the first few days, since antibodies are not produced that early.

As you might guess, combining PCR and Antibody tests may give a good indicator if and even when an asymptomatic person was infected. Below is a table of possible interpretations of test results, assuming testing is accurate. Always confirm results and discuss with your doctor when making health care decisions! The FDA regulates testing in the US, and several tests have received Emergency Use Authorization (EUA) status. This is not FDA approval, but allows tests to be performed under emergency conditions. Several labs have started to perform antibody testing along with PCR. At first, Ab tests will be given in combination with PCR tests to see if health care workers have already been infected. If you want an antibody test, you’ll need to check with your doctor to see if you meet availability criteria. Many other companies have tried to offer tests without EUA status, including at home tests. Many of these tests have very high false negativity rates, and are basically no good! As of this writing, I would not use any at home test kit. Before taking any test, check with your doctor, or confirm with the FDA or CDC websites to see if a test has EUA status.

Re-opening: The federal government has released guidelines on the re-opening process. These are recommended guidelines, and most states are likely to adopt them, but the final decision will be up to the Governor of each state. I’ll provide the link below. In short, to enter the first phase of re-opening, states or counties must show a downward trajectory of cases and symptoms for 14 days, and must have certain hospital capacities and infectious disease surveillance procedures in place. Each additional phase can be entered if these conditions continue to be met for an additional 14 days. Some states or counties may already meet the criteria for phase 1, and some states plan to enter phase 1 on May 1st. Looking at the criteria, the guidelines seem reasonable to me, and I hope Governors will learn from the experiences of other countries and states while making these decisions.

Until next time, don’t fear, but be smart!
Erik

FDA Emergency Use Authorizations:

Federal Reopening Guidelines:

When should we re-open? Opposite valid interests

All Articles, Communication, Fatality Rate, Re-opening, Testing

Originally posted April 13th, 2020 on Facebook

Friends,
This will be a longer post, so buckle up!

While I certainly have political opinions, I’ve been trying to minimize them for the purposes of these posts, in order that more of you will be willing to read! Today, some of you may be able to figure out where I stand on some things, although I’ll still try to keep the controversy to a minimum. This last weekend, there were protests in many cities of the US asking for the economy to be opened up. Of course, most of these requests took the form of slogans shouted or written on signs, rather than specific policy proposals. I’m very sympathetic to the need of many to get back to work so they can provide for their families, pay the rent, etc. I also share the frustration that much of the information provided by the media and government agencies is untrustworthy or incomplete. This is why I write these posts!

I want to reiterate the differences between the typical flu and the SARS-2 virus:

The R0 value (a measure of infectiousness, see my April 13th post) for the flu is 1.28. For SARS-2, it’s 5.7, 4.5 times higher!

The incubation time for the flu is 2-4 days, for SARS-2, it’s 2-14 days, and asymptomatic people are often contagious!

Yes, the fatality rate for both is impossible to know. And it’s probably over-estimated for both, since we don’t know the number of infected people with mild to moderate symptoms for either disease. But estimates are that the fatality rate for the typical flu is 0.14%. The current rate for COVID-19 in the US is 5.36% (deaths/confirmed cases), 38 times higher.

In short, SARS-2 is not the typical flu.

We have to concede that in an event like this one, there are many valid interests that are in some ways are opposed to each other. People at risk want to stay safe. Doctors and nurses want to treat their patients, but also face constant exposure of themselves and their families to the virus. Those in government do not want to expose their constituents to unnecessary risk. On the other hand, many have lost their jobs and need to get back to work. Mental health workers worry that their patients cannot withstand prolonged isolation and stress. Employers wonder if they have to lay off more people or close their businesses. All of these are real concerns, and they can’t be dismissed.

It will be difficult moving forward to strike a balance between these competing interests, and no solution will be perfect. We need to understand that most are doing their very best to manage a very difficult situation. There is lots of blame to go around, but remember that the nature of the virus has never been completely clear. For myself, I gave a talk at my church on March 13th (Posted here on March 18th). During the previous week, I was trying to determine if the virus was spread by droplet transmission (coughing and sneezing), or by aerosol transmission (shouting, laughing, singing, even talking). At the time, most outlets including the CDC said it was only spread by droplet transmission, but a few scientists were warning that it may be aerosol. Should I really be giving a talk on virus safety to room full of people? It appeared at the time that it would be OK, so I moved forward. Luckily for me, the decision was made to cancel gatherings, and my talk was recorded for the web. As it turned out, the SARS-2 virus is much more infectious that originally thought (see my post from April 13th), so add me to the list of people who were wrong! Thank God I didn’t have a crowd in the room during my talk!

Again, I am not an epidemiologist, I am a molecular biologist specializing in infectious disease. But in my informed opinion, reopening the economy without great care is a mistake. A similar experiment has already been done. On March 11th, California Governor Gavin Newsom banned large gatherings including sporting events, church services, and university classes. On the same day, New York Mayor Bill De Blasio was encouraging people to eat out and enjoy themselves. As of this writing (April 19th), California has 31,000 confirmed cases, and New York City alone has 138,000, more than all but 6 countries (yes, I’m including China, the Chinese Communist Party is almost certainly heavily under-reporting their case load)1. For a time, New York hospitals were overwhelmed, and bodies were being temporarily buried on Hart Island. This is the possible consequence of going back to normal too quickly! If you choose to gather in large groups during this time (for example at protests in downtown San Diego), I would strongly encourage you to take extra care to isolate yourself from those at risk or those who may come in contact with them.

I am less sympathetic to those who want to get back to normal just so they can go to Disneyland or to their favorite restaurant. As we reopen the economy, we have to do so carefully. Theaters, restaurants, and amusement parks are among the last things that should be reopened.

We will need have adequate testing and hospital capacity to handle the additional case load. Each area will be different in this regard, and New York City should not be treated the same as Ennis, Montana. We will also need to have grace for one another, as well-intentioned mistakes will be made along the way. Ideally, we should also have contact tracing, contacting those potentially exposed to an infected person. This practice, along with aggressive testing, was used very effectively in Taiwan, So. Korea, and Singapore, to minimize caseload. Unfortunately, we are not yet able to do contact tracing in the US.

While I am very sympathetic to individual rights, and am in general for small government, we may need to voluntarily lay down certain rights for a time in order to protect each other. Pray for our leaders, regardless of party, and take care of each other!

I’ll have another post soon on the topic of antibody testing.

Don’t fear, but be smart!
Erik

Workers temporarily bury bodies on Hart Island in New York City

1 Editor’s note: As of the date of posting, the statistics here were correct. As of July 7, 2020, however, the situation has reversed. New York State as 398k confirmed cases, California has 284k confirmed cases. New York state daily cases are trending downward, while California daily cases have been trending upward.