Ebola:  No new cases and the last 46 contacts of the last known patient finished their follow up period this past week.  We’ll follow for another couple weeks just in case of an “Ebola Jane” flare up, but humanity appears to have triumphed again.

At least against Ebola.

As for coronavirus, again, more than I will be able to cover but I’ll hit the high points as I see it.

–CDC released the first preliminary look at the disease in the US.  1 in 8 patients known to be infected is hospitalized (note testing still heavily favors symptomatic patients).  A little over 1 in 5 of those (121 out of 508 hospitalized in the follow up period CDC bracketed) wind up in the ICU.  Of patients in the ICU, 48% were under age 64.  Mortality in those aged 64-85 is 3-11%, for those age 55-64 mortality is 1-3% and for those 20-54 mortality is <1%. 

–Quick call back to the “bubonic plague” comparison update.  Remember the “choose your own adventure” portion, where we said that during the plague, people largely broke into four main groups of behavior, and asked what you would do if the plague showed up?

Group 1:  YOLO.  These party hard, figuring if they get the disease, they get the disease and might as well enjoy the end of the world:

Pompano Beach, FL on St. Patrick’s Day, 2020 (AP Image).

Group 2:  Run far and fast, hoping you outrun the disease.

“Adam Twidell, chief executive of the private jet booking service PrivateFly, said his firm was continuing to see a jump in bookings as wealthy people arranged evacuation flights home from high-risk countries.”

–The Guardian, March 11, 2020

Group 3:  Hunker down in place and hope to ride it out

Group 4:  Live your life as normal as you can, just taking a few extra precautions to avoid getting sick

Social distancing in line at Dick’s, Seattle, WA this week

–All of this is expected behavior.  Just history laying some rhymes for its mix tape.

–Testing in the US is still hampered by reagent availability.  Most manufacturers remain on diversion, essentially triaging where reagent kits go worldwide.  Protective gear, like masks, remain in very short supply.  I hear swabs are having issues, but have not seen that here yet.  Viral transport media, on the other hand, to stick those swabs into is critically short.

–Calls like “we need to build more ventilators!” “We need to build more masks!” etc. have limited utility.  It takes time to build, test for proper quality, and ship all of those.  Yes, we need them, but we needed them a couple months ago if they were going to make the greatest impact.  And it wasn’t all that clear that we were going to need them then.  Again, we will be going to battle with the army we have, not necessarily the army we want.

–But the army is mobilizing.  More testing is coming up every week.  Tents are being put in front of hospitals.  Urgent Cares reorganized to respiratory clinics.  The Society of Critical Care medicine is offering a free, online course to update physicians from other specialties on how to run a vent.

–Fun fact I learned this week:  state labs can only run the CDC kit.  They are not permitted to develop their own tests, and thus get more tests available.  The reason, across the country, for so many test delays and the super strict criteria to get tested (unless you are a pro athlete or famous apparently) is that they must wait for CDC kits.  And CDC doesn’t exactly have a factory attached to it. 

–Chloroquine is looking worth pursuing, but the results reported in France are VERY early.

–This is our lab at <Paladin’s Employer Redacted> in the press release below: <Press release redacted to avoid naming employer as well. Our lab started providing, free of charge, RT-PCR testing for SARS-CoV-2 diagnosis for the state of Indiana. Others at my employer were scaling up to produce thousands of kits for swab testing for SARS-CoV-2>

–“Go live” email to the lab earlier this week:

As we are about to go live, I wanted to give my perspective on the stakes and significance of the diagnostic testing for SARS-CoV-2, the coronavirus responsible for COVID-19 respiratory infection.

As I am sure all are familiar with by now, SARS-CoV-2 is a novel coronavirus first reported in Wuhan, China late last year.  Coronaviridae are a family of ssRNA viruses known to cause mostly respiratory infection in humans.  Cousins of SARS-CoV-2 are a major cause of the common cold.  Other cousins are SARS and MERS, which have caused outbreaks of severe respiratory disease and patient deaths over the last couple decades.  Neither SARS nor MERS have been as widespread as SARS-CoV-2, which has reached pandemic spread. 

So what is different about SARS-CoV-2?

Like all coronaviruses, SARS-CoV-2 is spread primarily through a respiratory route.  Most patients develop symptoms of fever (99%), fatigue (70%) and dry cough (59%) in four to five days after exposure.  97.% of patients have symptoms within 11.5 days; rare patients will develop symptoms up to 14 days after exposure.

Most patients will have mild disease (81%) that will not require much more than the common cold.  In fact, up to half of 619 patients testing positive on board one of the cruise ships with a major outbreak were asymptomatic at the time of diagnosis.

So why has the world gone crazy?

In short, because of the other 19% of SARS-CoV-2 cases.  14% of all SARS-CoV-2 patients will have severe disease, with dyspnea, hypoxia, or involvement of more than half their lungs with “ground glass” opacities on CT scan within 24-48 hours.  These patients will require hospitalization.  So too will patients with critical disease—fully 5% of SARS-CoV-2 cases.  Patients with critical disease have respiratory failure requiring the ICU and ventilators, or shock (multiorgan dysfunction).  In a little over half of the autopsies I have done in my career, shock (sepsis) was the cause of death.  The SARS-CoV-2 estimated case fatality rate ranges from 0.6/0.7 to 5.8%.  Deaths come largely from the patients with critical disease.  The variation in the case fatality rate comes largely from demographics (age and other underlying medical conditions the patient may have) and velocity of cases.

We’ll get into velocity in a second.

As you have no doubt heard, there are very few cases of SARS-CoV-2 in kids.  In adults under 60, unless they have severe underlying heart disease, immunodeficiency or are taking drugs that suppress the immune system, the case fatality rate is very low.

That said, France and Netherlands have been reporting that half of their ICU cases are adults under age 60.

After age 60, the case fatality rate creeps up, and becomes highest in those over 80, especially if they have underlying conditions like heart disease, diabetes, chronic lung disease, high blood pressure and cancer (as those over 80 are a bit more likely to have). 

In South Korea, the case fatality rate is estimated at up 0.9%.  In Italy, the case fatality rate is running 5.8%.  The median age of infection in South Korea is in the 40s; in Italy, it is 64.

Beyond that, Italy demonstrates the “velocity of cases” variable that is the primary reason the world has gotten weird since SARS-CoV-2 went pandemic.

All coronaviruses are highly contagious; SARS-CoV-2 is no different.  Hence, all of the “social distancing” and hand washing precautions to reduce the chance of spread.  And PPE that includes masks, gloves, lab coats etc.

Maybe not quite as extreme as our 14^th century plague doctor illustrated in a 17^th century manuscript there, but you get the idea.

What SARS-CoV-2 can do is infect a lot of people very quickly.  After that, it’s a numbers game.

Even if SARS-CoV-2 is not much of a direct threat to you (you are relatively young, healthy, and the case fatality rate is well below 1% for your demographics), it is VERY MUCH an indirect threat to you and everyone else.

That’s because it puts 1 in 8 it infects into the hospital, with 1 in 5 of those into the ICU.  In the ICU especially, they will be there awhile.  There is no vaccine.  There is no known effective treatment, although several anti-viral drugs and chloroquine (and derivatives) have shown in vitro activity and are being tested under compassionate use protocols. 

To put the problem in perspective, the state of New York currently projects its SARS-CoV-2 cases to peak in the next 45 days.  At that point, they will need 18,600 to 37,200 ICU beds.

New York has only 3,000 ICU beds.  And the United States leads the world in ICU beds per capita.

In Italy, not only were the patients older, there were so many so fast that all the ICU beds got taken.  An ICU bed, once taken, is taken.  For everyone.

Had a heart attack and need an ICU?  Bed’s taken.  Bad car accident, and need the ICU?  Bed’s taken.  Stroke, and need an ICU?  Bed’s taken.  Any kind of emergency surgery or other illness besides SARS-CoV-2 and need an ICU?

Bed’s taken.

Even if the direct risk of SARS-CoV-2 to you is low, the indirect risk that you might need an ICU bed, and it won’t be there because of the virus, is quite high.

When we say “flatten the curve”, that is why:

Nationally, the US numbers are approximately where Italy was 2 weeks ago.  The next 9-21 days will be critical for most parts of the US, including Indiana.  If the curve does not flatten, the health care system WILL be running out of beds.

That’s why everything is cancelled.  That’s why work from home.  That’s why social distancing.

And that’s why we must test.

Already, the ICUs in central Indiana are filling.  With both known and suspected cases of SARS-CoV-2.  Already, Hoosiers have died of disease.  The Indiana State Department of Health for myriad reasons, and the healthcare systems themselves, cannot keep up with testing.  Without testing, we cannot quarantine effectively.  Patients get exposed on the hospital wards.  Nurses and doctors get exposed, and spread it to other patients.  They in turn spread it throughout the community.  And we cannot tell people in the community they have the virus, and to tell everyone they have seen lately to isolate, so the virus does not spread further.  If cannot test, we cannot get ahead of the virus to slow the spread, and flatten the curve—and if we don’t…

“Bed’s taken.”

And as a physician, if you need an ICU bed, but there isn’t one, my options are about as effective as this guy’s:

In a week, the small but mighty <specific lab where I work at my employer> has gone from support of clinical trials to operationalizing the highest capacity testing for SARS-CoV-2, for patient care, in the entire state of Indiana.  Possibly the country.  Make no mistake about it.  We are the testing for the state of Indiana for SARS-CoV-2.

So if you want the world back to normal, that same focus, that same teamwork, that same will that got this test ready to roll, must remain. 

We need to test fast.

We need to test right.

Every. 

Time. 

As many as we can; as many as it takes.

They are counting on us.

We few, we happy few, are all that stands between Indiana and Italy.  0.9% CFR vs. 5.8% CFR is how we execute on our part.

The world gone crazy – and we are one of the few granted the opportunity to do something about this.

Now, I can’t promise rewards on the other side.  They’re not mine to give, and we have a long road before those.

What I can promise you is that when they ask you, years from now, what you were doing when coronavirus stalked the earth and the sky was falling, you won’t have to answer that you were working at home, watching Netflix.

You were on the front lines.

You were doing something.

Something that made a difference.

Maybe, just maybe, the difference.

Yeah, when coronavirus rang the bell,  you answered.

And it’s ringing right now.

Let’s go.

 “

–That e-mail above highlights a few other salient points we’ve brought up here before, namely, that the main threat of the virus is the number of people it puts in an ICU bed.  Too many, too quick, and “bed’s taken” for everything else. 

–The next 7-21 days are critical across the country to see if we reach that tipping point, or flatten the curve.  That will also allow more testing to better understand how many cases there -really- are (as we have discussed), including how many more mild cases are out there to better understand the risk of winding up in the ICU with it, and a better estimate of the true CFR.  In the absence of better data, but based on the experience of Wuhan and Italy, restrictions in place around the country are prudent while this sorts itself out.  Please adhere to them.

–Because of my new clinical responsibilities with diagnostic testing for the state of Indiana, coupled with the need to flatten the curve, I do not expect to make the planned trips over the next couple months.

–Schools here are now cancelled out to May 1^st.  Which brings back the “flatten the curve.”  If the 1 in 8 into the hospital and 1 in 40 into the ICU hold up, and the number of infected patients is large, these restrictions will need to be in place for awhile.  If you are thinking “just a few weeks and back to normal”—well, maybe.  Maybe not.  If maybe not, restrictions may need to be in place until a treatment is available that can keep people with this virus out of an ICU.  Otherwise, you can -quickly- bounce back into an “overwhelmed healthcare system” and “bed’s taken.”  All cause mortality jumps then. 

–To protect your downside, -plan- for pretty severe restrictions out to May.  Again, expect a very unusual year.

–Economic disruptions will be tough, and probably get worse before they get better.  Take care of your neighbors if they are affected.

–Risk assessment graph for your chances of a coronavirus carrier being present in a group of a given size:

There are about 10,000 known cases in the US right now to guide you on the Y-axis.

Your chances of catching Ebola this week:  Pretty much zero.

Your chances of catching coronavirus:  Good and getting better.  Follow prevention guidelines folks.

Love in the Time of Coronavirus:

High stakes table. (nice hand too)

“You got arrested, while in quarantine, in Italy?!?!?!  For what?”

–Friend of ‘That Guy’

“Being awesome, bro”

–Yep, ‘That Guy’

<Paladin>