Gentlemen, place your bets

It’s time for us all to think like a doc who’s ordered a bunch of tests on a fairly sick patient.  The good ones don’t wait for them to come in and then figure out what to do.  They usually concentrate on the worst cases and make plans.

Before going any further, please read the following paragraph. I’m sorry to keep putting this in, but I don’t want to leave anyone behind. Finding the actual genome (RNA in this case) of a virus in an individual  is like seeing a real bear up close and personal.  This can do you some damage.  In contrast, antibodies to the virus are made by an individual who has been infected by the virus in the past.  Antibodies (proteins) and genomes (RNA) are completely different chemically.      Antibodies are like seeing the tracks of the bear without the bear itself. You can’t see tracks without the bear having been present at some point in the past.

Well we’re in that situation in the USA.  Based on many studies now (California, New York State, Prison systems) the number of people who’ve been exposed to the virus enough to develop their own antibodies to it, is anywhere from 10 – 100 times greater than the number of people in whom the viral genome has been found.  This means that the vast majority of infections with the new coronavirus are asymptomatic.

We’ll have a more accurate picture shortly, but what do you think will happen when New York State (and probably everyone else) repeats the test for antibodies in a few weeks?

Place your bets.

Once you have an antibody to a bug, you have it (at least for a few weeks to months).  This is not true for the elderly and my wife had to be re-vaccinated for measles so she doesn’t give it to our grandkids should she be exposed again.

So repeating the prevalence of antibody studies should show an increasing percentage of people with the antibodies.  The bets have to do with how much increase we will see.  Will NY go from 13% to 26% or higher?  The experience in nursing homes and the disaster in the Soldier’s Home in Holyoke MA, shows that in a vulnerable group the infection rate can explode — Out of 210 veterans living there 66 have died of COVID19 and 82 more have been infected (showing the genome), since the first case was discovered 21 March.

Showing the conflicting evidence docs have to deal with all the time — consider the prisoner studies —

It isn’t clear which test was being used (viral genome or antibodies to the virus).  But this is a younger and healthier population.  Very surprisingly in four state prison systems — Arkansas, North Carolina, Ohio and Virginia — 96% of 3,277 inmates who tested positive for the coronavirus were asymptomatic.

So if healthy people won’t be made sick, what will happen when restrictions on activity (both personal and business) are lifted as they will be shortly?   You have two conflicting pieces of evidence to help you place your bets.  Fortunately the country has not adopted a one-size-fits-all approach, and lots of different experiments of nature will occur.

New York is the epicenter, with the most cases and very high population density.  Symptomatic cases appear to have stabilized even with a 10fold higher transmission rate (as measured by antibody prevalence) than that measured by finding the viral genome itself.

What would be your guidance here?

It’s time to pay our respects to Dr. Janeway who first focused on the innate immune system 30 years ago —  Obviously if we had to wait the week or so for antibodies to develop to fight off infections, we’d all be dead.  The innate immune system is much older evolutionarily than antibodies and starts working immediately.  We are still finding out how complex it is.

Like everything else, the innate immune system weakens with age, possibly explaining the difference in clinical outcome between the vets at the Soldier’s home and the prison inmates.

It’s hard to place a bet when you’re wishing for the best possible outcome as are most of us. Some people are highly invested in the worst possible scenarios, particularly those who’ve predicted them.  My guess is that we won’t see a surge in fatal or symptomatic cases as things open up.  What’s yours?

Addendum 27 April ’20.  People who have predicted terrible things happening by opening up some of the restrictions have their egos and reputations involved if they are proved wrong.  So beware breathless reports of spikes in incidence, hospitalization, deaths occurring in the first few days after the restrictions are lifted.  Remember the mean incubation period is 5 days with a range of up to 11 days. 

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  • John Wayne  On April 28, 2020 at 5:08 pm

    On the positive side, you have reports of very high levels of apparent exposure to people in New York City. Makes sense, this is probably the highest population density in the USA with a lot of business travelers (original spreaders.) You also have very high levels of exposure in places like the homeless shelter in Boston. High population area, generally younger people probably with robust immune systems. On the negative side, there are reports of very high death rates in some nursing homes.

    To make policy, I’d like to know what the exposure numbers are in several high population areas. Are the they all the same? Are the death rates proportionate to number of cases? What is with India? Are all nursing homes getting decimated, or is it certain ones? Different homes have different patient populations. They are all run fairly poorly, but they are also a lot like cruise ships full of the most unhealthy people who aren’t in hospitals. These are a good worst case, if they tell the truth this would be great data.

    All of this highlights an issue I have seen more and more in my career – people including scientists ignore investing and understanding analytical assays. We just don’t know enough to make informed calls.

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