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Coronavirus

Coronavirus Update, 1500 GMT 24 Mar

The Timeline of the COVID-19 Infection

A publication 24-hr ago provides a good picture of the clinical stages of the disease and when they occur. The study is small, only 16 patients and, given that they all became hospitalized, remarkably young, with an average age of 36 years. But it let me draw a clear picture with one critical secret of the virus revealed.

The chart starts with Day 0, the day all patients were infected. That event is marked with a purple box.

In this trial the first evidence of disease is not a nasal viral swab but old fashion symptoms of any respiratory virus: fever, cough, and shortness of breath. You can see fever is present in almost all patients: 88%.

The chart shows the timing of symptoms, including fever, positive nasal swab tests, and the length of hospitalization, from Day 0, the day of infection, to Day 19, when the patients had recovered.

Symptoms: The red box at Day 5 after infection is the average day symptoms began and the green box is the average day symptoms ended. The range of dates is in yellow; these are days when some, but not all, of the patients had symptoms. So literally from the first 24 hours of infection out to 19 days post infection, you could have symptoms.

Take note: symptoms, on average, end 13 days after Day 0. Keep this fact in the back of your mind for later.

Fever, the most common symptom, starts on day 5 and runs, on average, through day 11 after infection.

So as a reminder, if a pre-symptom patient on Day 0 infects someone they can pass the disease on for, on average, five days before they have any symptoms. Just like closing the door after the horse leaves has never caught a horse in the history of equestrian pursuits, waiting to have symptoms before you perform social distancing will never stop the spread of this disease.

Virus Tests: The next event to occur is on Day 8 and that is a positive viral nasal swab test. The test is always positive after the symptoms have started and it takes over a week to become positive.

But here is where this virus is really diabolical. Notice the virus continues to shed for, on average, 15 days after infection on Day 0. And shedding can continue to occur out to at least Day 17.

Why is this critical?

Because SARS-CoV-2 continues to shed from a patient for two to four days after symptoms have ended. What do most patients and frankly many doctors think when the symptoms of a viral infection have ended? The conventional wisdom is you can no longer infect others.

This is wrong!

Note: this is the time line of the <15% who are sick enough to go in the hospital. So these times may not pertain to the 80% with mild symptoms.

Reference: Am J Respir Crit Care Med. 2020 Mar 23. doi: 10.1164/rccm.202003-0524LE. [Epub ahead of print]
Time Kinetics of Viral Clearance and Resolution of Symptoms in Novel Coronavirus Infection. Chang, Mo G, Yuan X, Tao Y, Peng X, Wang F, Xie L, Sharma L, Dela Cruz CS, Qin E.

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Coronavirus

COVID-19 Update, 0850 GMT, 24 Mar

Can you get the flu and Coronavirus at the same Time?

The general rule is that a patient can only get one virus at a time. So the rule for 80+% of people is no, you either get the influenza virus or the SARS-CoV-2 virus, but not both. But in medicine, like in life, there are always exceptions to the general rule.

On March 11th doctors in China published a case in Emerging Infectious Disease of a patient who had an infection with both SARS-CoV-2 and influenza A at the same time. 

Emerging Infectious Disease is a non-peer reviewed publication site run by the US CDC that infectious disease doctors can post cases to quickly, 24/7, to help their colleagues around the world. It is the modern equivalent of the conversations we used to have upon arriving at the hospital in the morning, over coffee, with the doctors and nurses that had just worked the night shift. Except now, with the internet, the medical coffee klatch includes every doctor in the world!

The timeline of this case is a good way to look at it:

Day 1: A 69 year old man is seen in a Beijing clinic for fever and a dry cough that began that day. He had returned the day before from a one month stay in Wuhan, where SARS-CoV-2 began. His x-ray was abnormal. Because of travel history he was isolated with the presumed diagnosis of COVID-19. Over eight hours he had three negative SARS nasal swab tests and one positive influenza A test. His diagnosis was changed to influenza A and he was sent home to rest, as is standard for the flu.

Day 7: He returned to the hospital with fever and shortness of breath. He required oxygen to help him breath. He had two more negative SARS swab tests. He worsened and was admitted with a diagnosis of severe influenza A pneumonia and put on a breathing machine.

Day 10: He improved. A flexible scope was used to go into his lungs through his mouth and get a big sample for testing. For the first time, he was positive for SARS-CoV-2 in that specimen. A sample of sputum was also positive but, at the same time, another nasal swab remained negative. This was his sixth negative nasal swab test! 

Day 11: He was well enough to be transferred to a non-critical care hospital where he stayed until he recovered and went home.

Lessons learned: 

  1. COVID-19 patients can be negative by nasal swab when they are so sick they need a respirator.
  2. The symptoms of influenza and COVID-19, fever, cough, shortness of breath, chest x-ray changes are the same. 
  3. Rarely, a patient can get both diseases at the same time, complicating things immensely.

Reference: Wu X, Cai Y, Huang X, Yu X, Zhao L, Wang F, et al. Co-infection with SARS-CoV-2 and influenza A virus in patient with pneumonia, China. Emerg Infect Dis. 2020 Jun [3/24/2020]]. https://doi.org/10.3201/eid2606.200299

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Coronavirus

COVID-19 update 0100 GMT, 24 March

A Shelter-in-Place Game to Teach your Children About Viruses and the New World We Live In

As a world society we have created a connected planet that is amazing. But every advance has a down side. Try this game with your family while you hunker down and learn the dimensions of the down side of our connected world.

The rules of the game are simple. The goal: Save the humans, starting with your family. Its a one team game, all the humans against the virus. So its your entire family against the virus.

First you pick any place in the world for the virus to start from. Only limitation: it has to have a commercial airport that services the place. But it can be a really small airport. Some places in the world have only one flight in and out a day!

Second, you pick the best place in the world you can take your family, instantly for purposes of the game, to avoid the virus getting to your family. Same rule applies here; it can be anywhere but it must have an airport nearly.

Now you see if the virus can get to your family.

Use Expedia or some other travel site. Put the airport near the virus as the departure city and your family’s location as the destination city. We are imagining one passenger carrying the virus and they caught it within 24 hours of the flight. Once the two cities are entered, click enter and see if your family is safe…or not so safe (remember its only a game 🙂 ).

How do you decide who wins?

It takes 72 hours for the FDA/CDC/WHO super-science swab test to be positive under the absolutely best circumstances. Probably longer but as the designer of the game, and as a human, I am going to bias the game against the virus.

It takes 120 hours, on average, for a cough or fever to appear with SARS-CoV-2. So if an airport can quarantine the passenger carrying the virus from the origin city you picked because they have a cough or fever, your family is safe.

Now the scoring:

If the virus can get to your family in under 72 hours, the virus wins.

If it takes between 72 and 120 hours it is a draw and your family gets to play the game again.

If it takes the virus more than 120 hours to get to your family, your family gets to live. You can then come up with your own version of family world dominance, as imaging who in your family gets to be Kings, Queens, Princes, Princesses, Knights, etc., as you see fit. Have fun with it.

Below are two examples of my family losing to the virus.

If a coronavirus starts in Wuhan, China and my family is in Columbus, Ohio it takes 38 hours for the virus to get to me. As a Michigan ‘Go Blue’-kind of guy, I picked Columbus to keep my family safe thinking no one, not even a virus, would want to go to Columbus, Ohio! 🙂 ).

Second run was putting the virus in Saudia Arabia, where the 2012 MERS coronavirus began in camels and jumped to humans. I put my family in Milwaukee, WI because I visited there once in mid-December and nearly froze to death. So I thought we would be safe. I was wrong. This is even worse for my family: 21 hours to catching the virus

How about a little friendly competition?

If anyone finds a city combination more than 72 hours or 120 hours apart. post the combination here. The winners will get a free copy of the book I am writing on COVID-19…

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Coronavirus

COVID-19 Update, 1246 GMT, 23 March 2020

The country-by-country report from the battleground of COVID-19.

In a previous blog on my website (drquay.flywheelsites.com/covid-19-update-2320-gmt-21-mar/) I described a proprietary toll I developed to provide a snapshot, a single moment in time, in the status of this battle. Based on how China and South Korea were able to declare victory (although pockets of fighting continue) the Days to a Ten-Fold Growth in case number (DTFG) is a predictive tool as to whom is winning. I have color coded the chart below and given the definition of each scoring possibility. Countries have four conditions: human victory, humans winning, a virus-human stalemate, and virus winning. I saw no reason to have a category of virus victory, at this time.

The scoreboard as of the time above:

Two countries have declared victory and two countries are winning.

There is a group of nine countries in which the virus and the humans are at a stalemate. Now, while it is always better to be winning, a stalemate is a good thing because, in almost all cases, the virus starts out on offensive, gets the ball first, and spends a week or two winning, moving the case number up quickly, marching down the field. So in American football terms, a stalemate is when the forward progress of the virus has been stopped and the virus has to kick on fourth down.

I welcome my international friends and colleagues to provide soccer or rugby analogies.

🙂

Also, not all stalemates are created equal. Sweden with a stalemate at about 1900 cases and Spain with a stalemate at over 33,000 are VERY different public health resource problems and disruption of life issues. The way to think about it is, with a stalemate, you will have a two-fold to four-fold increase in cases from where you are before you can declare victory. But this example is a difference of tens of thousands of cases.

A ‘good news first’ observation.

A short two weeks ago (Mar 7) over 95% of all cases in the world were in four countries: China, South Korea, Iran, and Italy. For many complex reasons, the medical response and societal response of each country differed. And of course one cannot look to the future without pausing to contemplate the devastation these four countries have experienced. But the good news is that, at least at the present time, all four of these countries are either winning or have declared victory. And because they got there by ‘different histories’ there seems to be a ‘yet to be understood’ factor that ends up putting a brake on absolute, exponential growth.

Now the bad news.

In five countries the virus is winning. In four of those the case number is low. This is like a team scoring on the first possession of the ball. If these countries can get to a DTFG above 10 in the next few days, they may end up looking like Switzerland or the UK. I think their window to end up like Sweden has passed.

But the US stands out for several reasons:

  1. It is at a DTFG of 8.5, the virus is winning, and it is not on the edge of 10, where the stalemate begins.
  2. It is over thirty-three thousand cases.
  3. When Italy was where the US is now, at roughly thirty-five thousand cases, they had a 13% 24 hour increase in cases; the US just had a 24 hour increase of 39%.
  4. The US is the first country in the world to have both more than thirty thousand cases and to have cases growing this fast.

The US trend line makes it impossible to know where it will level off but it is highly likely it will be above China’s eighty thousand cases.

Why is this happening in the US?

In a future blog I will lay out the data so you can make your own assessment but my conclusion is that there are three critical factors to change the dynamic to humans winning in this pandemic: frontier control to isolate pockets of cases and keep them from spreading (<10% of cases in China were outside the frontier lockdown of Hubei province, where Wuhan is located); shelter-in-place or social distancing to slow local spread (in Wuhan, <1% of the local population became infected); and virus testing to quickly find cases. Of these, virus testing is the least important.

Symptoms appear at five days, the virus test cannot pick up an infection before three days, and so spreading will occur during the symptom-free period in most patients or at any time in the one in five who have no symptoms (and when tested are equivocally positive) but can spread the disease.

Social distancing and frontier control, lock down, are what determine success.

The Twitter version of testing is: in a society that has universal symptom-based virus testing but the population are free-range humans, the virus will always win.

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Coronavirus

COVID-2 update 2320 GMT 21 Mar

SARS-CoV-2 versus The Humans: A Country by Country Analysis of Who’s Winning

Summary: A tool has been developed to determine whether the virus, SARS-CoV-2, or the residents of a given country, are winning in this pandemic. It measures how many days it takes for a ten-fold increase or one logarithm, in cases. For example, going from 10 to 100 or 1,000 to 10,000.

The tool is called Days to Ten-Fold Growth or abbreviated DTFG.

The tool is based on what happened in China and South Korea, the only countries in which the humans can “probably” declare victory. Here is how it works.

A DTFG of <10, that is, the virus is increasing ten-fold in less than 10 days means the virus is winning. A DTFG of 10-15 is a stalemate, no one is winning but both sides are fighting, neither the virus nor the humans are advancing. A DTFG of 15 to 24 means the humans are winning. In China and South Korea, where the humans have declared victory, the DTFG is now >24; it takes longer than 24 days for a ten-fold increase. There are still pockets of fighting going on but things are relatively normal.

So what is the score at the time I am writing this blog:

When China had between 10,000 and 30,000 cases, in the ‘zone’ as I call it, they were at a stalemate. China went on to win but the virus infected about 80,000 in total before they could declare victory.

France, Iran, and Italy are in the zone now, are doing well, and should end up with fewer than 80,000 cases. Italy is at a stalemate, like China was, so they need to transition to winning.

Sweden is also at a stalemate but with only 1770 cases, compared to Italy’s over 53,000, Sweden has the potential to transition from a stalemate to winning with significantly lower case numbers.

Spain and the United States are both in the zone and losing to the virus, and will probably end up with more than 80,000 cases. United Kingdom is not yet in the zone and so, if handled properly, could end up with fewer than 80,000 cases.

I imagined a ‘Perfect Land,’ where the medical scientists are always vigilant, the government makes public health policy decisions its first priority and doesn’t care if its decisions are unpopular, they have military-level control over their residents, and the residents will be obedient to the government, and if asked to quarantine for 14 days will be 100% compliant.

Perfect Land identified the new virus when there were <10 cases and locked down the country one week later. Repeating, they locked down an entire country when there were 10 cases! Perfect Land declared victory at about 7,000 cases. Since none of us live in Perfect Land, we should not beat ourselves up over the way we are handling this virus.

Humans will prevail but this virus is one of the fastest spreading microbes every witnessed.     

My thinking and analysis to come up with the DTFG tool

To look at how a country’s response to a viral pandemic is working, is the virus winning or are we humans on top, requires that we drop into the ‘mind’ and behavior of SARS-CoV-2, that 30,000 letter, twenty page pamphlet that is being so tough on humans.

Why can’t we think exponentially? It is probably because, as we shuffle off this mortal coil, we don’t live long enough to see beyond two or three generations of ancestors and descendants. Hobby tip: doing family history helps a little as you begin to realize that you have over 8,000 great grandparents in about the year 1600.

Back to the virus. A trick we humans can do is to plot the growth in cases over time on a special scale, where the equal spacing on the Y-axis is 10, 100, 1000, 10,000, etc. As crazy as it might seem, pandemics are a straight line when plotted this way. At that point, you can measure the time for each log growth to occur. From the virus’s perspective it will take the same time to go from 10 cases to 100, as it takes from 1,000 to 10,000, and so on. Finally, at some point the line stops being straight and ‘flops over’ as I like to say. This is when it runs out of humans to infect, the humans disappear into their houses, and stop travelling, etc.

Now to my chart. I looked at 10 real countries and how they have responded to the virus and collected data.

Based on this analysis I also created what I call ‘Perfect Land,’ an imaginary place where the doctors never make a mistake, there are no delays, scientists can see the future, government has perfect timing and formulates the perfect policies, and the citizens are 100% obedient to their government.

Please no political comments on which real country most resembles Perfect Land! 🙂

The data I collected was how long the virus took to grow from each 10-fold of patients. So how long from patient 1 to patient 10, how long from patient 10 to patient 100, how long from patient 100 to 1,000, how long from 1,000 to 10,000. Because China is the only country to get over 30,000 cases but were able to stop at about 80,000, I thought it was important to see what China was doing when they had between 10,000 and 30,000 patients, where the US and the other high case number countries are at the time of this writing.

I saw a few patterns in the data and I decided to color code them to make it easy to see patterns.

The most out of control growth for this virus is a ‘log growth’ of <10 days; going from 100, say, to 1,000 in <10 days. Basically, the virus is spreading at its maximum rate and the humans are doing nothing; haven’t responded yet. I gave this growth rate a red color. The red color means ‘THE VIRUS IS WINNING.’

I saw another growth rate that clustered between 10 and 15 days to grow 10-fold. Here is virus is struggling for reasons, maybe unknown, and the humans are starting to respond. Since I saw countries go from this rate go both ways (some get better and some get worse) I labelled this yellow, which means the virus and humans are at a ‘STALEMATE.’

Finally, either as the virus is just getting into a country, at the beginning, or much later, when the humans are winning, the 10-fold growth rate is 15-30. I picked 24 for this cut off because the two countries that seem to have won completely, are running at a >24 days per 10-fold growth. As you can figure out, if the virus is gone this number will gradually grow all the way to infinity.

I also thought it was important to get an ‘instantaneous rate’ of the last data point today from the WHO and use that to project into the future. So the values that are not true 10-fold growth numbers have a T by them to signal they are a terminal growth rate. Taking the number of cases on the latest day, dividing that number by ten, and counting back to get a 10-fold, backward looking, growth rate.

Okay, let’s see what SARS-CoV-2 does in Perfect Land. The virus appears out of nowhere and 10 citizens of Perfect Land can see the future growth and they announce a policy to Lock Down the country. The policy is rolled out and is fully in place in one week, seven days. The citizen’s cooperate. Using data from China and South Korea, if Perfect Land locks down the country when there are 10 cases they will end up with about 7,000 cases.

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Coronavirus

COVID-19 update, 21 Mar

You didn’t get your flu shot. What should you do?

I strongly urge you NOT to get the flu shot. Three reasons:

1. It is too late for this season for the flu shot. The flu season is almost over and so your chances of getting it are small. Look at this graph from the CDC website . Along the Y-axis are the number of patients who go into the hospital for influenza (the flu) per 100,000 people. The X-axis is the CDC’s version of the calendar. They start on January first with week 1 and it goes from there. So what we call Thanksgiving week, a time of food, fun, and football for the rest of us, those party animals at the CDC call ‘Week 48.’

Each different colored curve is the flu season for a given year. So you see a pattern over the years. Beginning December 1, the number of cases begins. From January 1st to about March 15th (week 10) you see the most rapid weekly increases. This is what the rest of us call ‘flu season.’ From March 15th to May 7th (week 17) the cases are tapering off as spring begins, things start to get warmer, and we spend more time outside (this virus is a vampire; show it to the sun and it explodes!).

Notice the worse flu season recently was the 2017-2018, about 50% worse than this year, when over 100,000 people were hospitalized with 61,099 flu related deaths! I bet you didn’t hear about that then, did you?

Back to the present. The flu season for 2019020 is that incomplete red line (news flash; the CDC cannot predict the future and so the line stops with this week) is literally over with less than 10% of the cases left in the season.

2. Exposure to COVID-19 in medical facilities. You have to go to the pharmacy, local clinic, doctor’s office, or hospital to get a flu shot. These are exactly the locations where all the cOVID-19 patients are going when symptoms begin. A US-educated physician colleague of mine living in Shanghai says the medical community rumor there is that it takes 15 seconds in a room with a COVID-19 patient to become infected.

3. Free up non-essential medical resources. As a community we need to allow the medical community to focus on this pandemic for the next few weeks or months while it is still growing so fast. So all elective procedures, routine check-ups, wellness evaluations, etc. should be postponed until this crisis resolves.

This data can be found here: https://www.cdc.gov/flu/weekly/#S2

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Coronavirus

COVID-19 update, 20 Mar

Drug combination works in hospitalized patients!

A small French study shows that an old malaria drug, hydroxychloroquine (HCQ) combined with (AZ) azithromycin.

The graph below shows the percent of patients with a nasal swab that contains the virus.

Black line (control), no change over six days.

Blue line, HCQ alone, nice reduction that is different from control on day 3 but is not cured by day six.

Green line, HCQ plus AZ together, better reduction than HCQ alone and NO VIRUS by day 5!

Caveat: a 20 patient study so results may differ on a big scale but this is a major breakthrough.

Note: my previous analysis of HCQ based on test tube data was that it would fail. I am glad it was tested!

Here is the paper if you want details.

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Coronavirus

COVID-19 update, 20 Mar

Why does it spread so easily?

When you are sick you stay away from people, right? Even without the CDC, our government officials, Prime Ministers, etc. telling us what to do we all have common sense. So why is it spreading so fast and extensively?

Simple: it combines fast spreading between humans with slow expansion inside humans!

The graph below shows the number of days from being infected to showing symptoms; fever, cough, aches and pains, etc. The data is from the CDC and a journal publication yesterday concerning the cruise ship infection.

The virus spreads fast, in human terms, because the virus infects quickly and easily but then expands slowly, in virus terms. This makes it slow to trigger the bodies defenses. And it is our RESPONSE to the virus, not the virus itself, that we recognize as feeling sick.

As a consequence, one of every two infected people spend almost ONE week with no symptoms. During that week they can spread the virus. From the conveyance outbreak on the cruise ship, almost one in five NEVER show symptoms.

So if you are sick, stay home and if you are not sick, stay home. Even if you aren’t sick that very moment, social distancing is still the right thing to do.

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Coronavirus

COVID-19 update, 19 Mar

A drug-virus interaction I am concerned about and watching carefully.

I reported earlier an association of COVID-19 (the official name for the disease caused by the SARS-CoV-2 virus, the official name for the virus) with pre-existing heart disease. While that still may be true there is also the nightmarish possibility the association is the result of the medication given for heart disease and not the disease itself.

There is a class of drugs for both high blood pressure and heart failure called ACE Inhibitors, for angiotensin converting enzyme inhibitor. For healthy life the ACE protein sits on the surface of your cells, in your lungs, heart, intestine, etc. and processes hormones, sort of like the immigration officer stamping the hormones passport, and letting things across the cell border in an orderly fashion. Well it turns out SARS-CoV-2 hijacks the officer and forces them to open the cell door. Here is where your medicine comes in. When you take an ACE inhibitor the cell says something is wrong and its response is to send more ACE proteins to the surface of your cells. The more ACE on your cells, the easier it is to for the virus to get into your cells.

ACE inhibitors are very common for hypertension and heart failure. Here is a list of the FDA approved ACE inhibitors you might be taking.

If you are taking one of the following drugs, do these four things:

1. Don’t panic; it is not the end of the world and its increased risk to you is real but still small.

2. Don’t stop taking the medicine; its important for your health and you want to stay healthy. You DO have a medical condition the drugs are needed for; don’t trade that to eliminate something that MIGHT happen at some future date.

3. Start with a call to your pharmacy. Laws are different state-to-state but in some states a pharmacist can change you to an alternative class of drugs for your condition(s).

4. Finally, as a last resort, call your doctor’s office. They are really swamped so you, the patient, have to be a little patient (not in a pediatric sense, of course. 🙂 ) Tell them a friend shared this and ask if it is relevant to your care. Unfortunately, medicine is an art so they will take your entire medical picture in mind, weigh things, and maybe change you or maybe not. Only they know what’s best for you.

So there you go for today.

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Coronavirus

Coronavirus update, 18 Mar

Testing for COVID-19: Why I like the combination breath hold/temperature test for screening

The internet can be a dangerous place to get medical advice; some of what you read is just plain false and some of what you read is true in a selected way but makes doctors respond, weighing in to ‘debunk’ something they think is misunderstood by lay people. But when the doctors do this, this miss the nugget of truth buried in the pile. This is an example of something that was absolutely right, had a false association with it, and then got debunked by the medical profession.

What I am talking about is, of course, the breath hold test for COVID-19. The two step test, (which takes eleven seconds!) works like this: Step 1, take a deep breath; Step 2, hold your breath for a slow count of 10 (about 10 seconds). A fail is having to break the hold for any reason; cough, sputum, dizziness, etc. As I will show below, it is a nice screening test. The internet said the reason a COVID-19 patient fails the breathhold test is because the disease caused “50% fibrosis of the lungs.” This is medically impossible. I don’t know the upper limit of fibrosis you can have and still be alive but it is way less than 50%; maybe 10% or so.

But the test is not worthless. For screening purposes I propose combining the two tests, breathhold and temperature, and that you do them every morning with your family: the 10 second breath hold test and forehead temperature test. You should be less than 38 C (100.4 F). For the combination test if you have EITHER a fever or can’t hold your breath, the test is positive. You don’t need to have both. The numbers below in the table come from the medical articles themselves in the best infectious disease journals.

As the table shows, a screening test should be quick, easy, cheap and not miss patients with the disease. It’s purpose is to separate the ‘not sick’ from the ‘sick for any reason.’ that is ALL a test needs to do to be useful. Another useful test is one which, if positive, means you have a particular disease with high probability. The CDC/FDA cheek swab test is such a test; my screening test picks up COVID-19 and many (100s ?) of other disease. But it is not useful!

So study this table. Every test has good points and bad points. Here the good points are in the yellow boxes. Keep this in mind as we handle…and overcome this pandemic!