Category Archives: Antibody

Case Update, September 23rd, 2020, Existing Immunity, Reinfection, Strains and Vaccines

This is a weekly update, but I’ll also talk about apparent existing immunity in some people, reinfection, and the 2nd wave of cases and what this all may mean about Coronavirus strains.

The 2nd wave of cases is apparently over in many places in the US, although not all.  The US new confirmed case numbers have risen slightly in the past week.  While the southern part of the country, California all the way for Florida, was the epicenter of cases for several weeks, new cases are primarily arising in the North Central part of the country.  I might speculate that this might be related to the coming Fall weather, but of course it’s too early to say for now.  The US also crossed a threshold of 200,000 total COVID deaths, outpacing a prediction I made several weeks ago that we would have 100 – 200 thousand deaths.  California is back down to pre-2nd wave new case numbers, but is not sinking below that.  In San Diego County, we had a small wave of cases related to a series of outbreaks at SDSU, but we’re back to a lower persistent new case rate.

Graph is by me, from data collected from Johns Hopkins University COVID site.
Endcoronavirus County Level Map, September 23rd, 2020
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. “Active Confirmed Cases” numbers are calculated based on the assumption that patients confirmed to have SARS-2 virus at least 17 days ago have recovered.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County.

Internationally, India now has the second most cases in the world, with 5.6 million cases as of this posting.  Of course India’s very high population and densely packed cities are likely a contributing factor. Brazil and Mexico have managed to slow the rate of new confirmed cases, having peaked in late July.  While things are improving in the US, many countries are experiencing first or second waves right now, including France, the UK, Israel, and Austria. 

Existing Immunity: I’ve resisted talking a lot about existing immunity because the information is complicated and may have phenomena with overlapping and opposing impacts.  Also, I’m not an immunologist! Be aware that what I say next may change.  There is data suggesting that the reason many, especially children, are asymptomatic is that there may be some existing immunity to Coronavirus in those individuals.  Coronaviruses is a large family of viruses which includes the SARS and MERS viruses, but also several viruses that cause the common cold.  As such, many may already have some kind of immunity to Coronaviruses as a group.  This is good news of course.

Reinfection:  On the other hand, I listened to a story on the September 2nd episode of the Nature Podcast about several cases of SARS-2 reinfection.  These cases appear to be rare, and most are not well studied.  In one case in Hong Kong, however, both the 1st and 2nd strains which infected a patient were sequenced and were found to be different strains.  This has several implications.  It suggests that immunity to a single strain may persist at least for a few months, but also that several strains are circulating, and immunity may not apply to other stains. 

If you’ve followed my page for long, you know that I’m concerned about Antibody Dependent Enhancement (ADE). In some cases of reinfection, symptoms were worse the second time, but in others, they were less severe. So unfortunately, these don’t necessarily provide clarity on whether ADE will be an issue, although if this is ambiguous now, it may be the issue will at least not be as serious as I feared.  We’ll have to see more of these cases to know for sure.

Strains and Vaccines: I’ve written about the D614G strain that arose in April and May. When I first heard about it, scientists were saying it may be several times more infectious than the already very infectious SARS-2.  I suspect that the 2nd wave we saw in the US may have been so large partially because of this strain.  All of this, as well as the reinfection story above, highlights that we have several strains moving around at once, and will likely have more.  Like HIV and Flu, Coronaviruses are RNA viruses.  RNA viruses use a RNA dependent polymerases to copy their genomes, and these enzyme tend to be VERY error prone as compared to DNA dependent polymerases.  Because of this, RNA viruses mutate quickly, and are resistant to the use of vaccines.  This is why we need a few Flu vaccine every year, and part of why we still don’t have a vaccine against HIV.  This of course also complicates the prospect of a vaccine against SARS, along with concerns about ADE. I’ll keep you posted as I learn more.

Don’t fear, but be smart,
Erik

Case Update: September 9th, 2020

Friends,
This is a case update from the last week. For the US and California, confirmed case numbers continue to improve. In San Diego, we seem to be having a small bump in cases right now, after a consistent fall since late July. My friend Brit Colanter who works at San Diego County Public Health tells me that there was an outbreak at SDSU in the last few weeks. 444 cases so far and 1 hospitalization.

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 Johns Hopkins University COVID site. “Active Confirmed Cases” numbers are calculated based on the assumption that patients confirmed to have SARS-2 virus at least 17 days ago have recovered.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County. Some data points of “Active Confirmed Cases” are from SD County, others are calculated.
From Rt Live.

I just got back from a trip to a hospital lab in Rochester, New York, helping them expand their COVID testing. As much as we can grumble about conditions here in California, they are even more strict in New York. New York has a quarantine program going for residents of some states, including California! I was required to check in with Contact Tracing every day, and stay in my hotel room when I wasn’t at the lab. So I was kind of under house arrest!

I have a new appreciation for Door Dash and other delivery people working out there today. So thanks to all of you who are working hard to bring needed items to those who can’t leave their house! You have important work right now!

Don’t fear, but be smart!
Erik

PS. I’ve heard a rumor that many African nations are having official events to pray for the US. Many thanks to my African readers for your prayers. We certainly need them!

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

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 in SARS-1:



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



Is COVID-19 receiving ADE from other coronaviruses?



Possible mechanism for ADE:

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

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

COVID Vaccine, Herd Immunity, and California Re-Opening

Today I’m going to wade into the piranha filled waters of the vaccine discussion. I’m also going to talk about the issue of herd immunity, and my advice for re-opening.  I’m not prepared for a discussion of the MRM vaccine that has been raging for the last several years, I’m going to discuss vaccines in general, and the hopes for a COVID vaccine in particular. I will say to start out, that I’m a big fan of vaccination in general, but each vaccine is different, and I may not be in favor of a particular vaccine.

Vaccines: I’m not an immunologist and I haven’t made vaccines myself, I’m just sharing with you what I’ve learned from an informed perspective over the last few months.  When I first started sharing about COVID, I said something wrong, that it would take at least a few months to create a vaccine against COVID, which seemed like a long time to many.  This was based on the time it takes to develop a flu vaccine every year.  In the Spring and Summer, scientists find out that strains are likely to cause flu later that year, and they begin making a vaccine. This process takes several months. As it turns out, it’s only this fast for flu because there is a standard way to make a flu vaccine, they just need to know what strains will be likely to arise in the Winter. And sometimes they are wrong. 

Unfortunately, however, there isn’t just one way to make a vaccine.  There are many different ways, and it can be different for every virus or bacteria.  So for every new infectious disease, a vaccine must be developed from scratch, testing all these different methods.  The process can take from 2 to sometimes as long as 30 years!  Some scientists have said that Dr. Fauci’s prediction of a vaccine by next Summer is actually very optimistic! In my informed, but not expert opinion, we should not count on a vaccine for this current COVID-19 crisis.  However, the vaccine work being done will likely help with future outbreaks.  At least part of Dr. Fauci’s optimism is that a lot of red tape is being cut to speed the process, and that’s good, but less development time will also mean more risk for the final product.

Herd immunity: I have heard many people promoting the idea that herd immunity will help us get out of the crisis. Even some governments have been promoting this idea.  Herd immunity is a useful discussion for diseases for which there is a vaccine, but in my opinion, it is not something we should be striving for now with COVID.  We shouldn’t put a bunch of people in danger to keep fewer different people out of danger. Herd immunity requires a lot of people to be immune, and that number is different for every virus.  I’ve heard the numbers 50 – 70% for COVID thrown around.  That’s a majority of the population!  Why would we risk exposing the majority to the virus to save the minority? To be crass, it’s kind of like saying that once the pool is full of bodies, no one else will drown.

Reopening: More states continue to begin the reopening process. I actually strongly support this, as long as people continue to take care as they interact in public!  Even California has entered Phase 1 (CA calls it Stage 2) today, Friday May 8.  The stages CA will use, as well, as the announcement for the May 8th reopening were announced by Twitter by the Governor.  Not my favorite method of making an official announcement, but there it is.  Re-openings have a much higher chance of being successful if we continue to take care! Continue to wear masks in public, and continue to distance when appropriate (see my May 5th post).  I’m hopeful that we can advance quickly through the stages if people continue to take precautions.  Also, it will be important for us to continue to expand testing, and for businesses to take advantage of expanded testing by screening employees as appropriate.  Some municipalities are starting to have drive through testing, including parts of San Diego (you must still have an appointment to be tested).  Check with your health care provider or public health department to see if and how you can be tested.  Keep watching how other states are doing!  We can learn a lot by observing what methods are working, and what methods are not!  I predict that outbreaks will occur in places that become relaxed too soon.

2nd Wave:  Again, I’m not an epidemiologist, and the following is an informed guess, not an expert assessment.  In my informed opinion, we will have second wave in the Fall or Winter, and history suggests it may be more severe than the first wave.  But I’m still optimistic.  Why?  Because I think that with expanded testing, we will be able to test far more broadly this Fall than we could in March and April.  This will help us identify and quarantine infected people rapidly, and will help us control the spread much better than in the first wave. For the 2nd wave to go well, we will need to stay diligent!

Don’t fear, but be smart!

Erik

What is the Fatality Rate?, Antibody tests, 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: