Post #716: More epidemiology: Why is there no clear pattern?

I’ve been trying to make some sense of the current spread of infection of COVID-19 in the US.  I have to admit that’s been more-or-less a complete and total failure.  I’ve managed to turn up a lot of interesting facts, but nothing resembling a pattern.

So, for this post, I’m just going to explain briefly why that is, and then start arranging a list of states in some sensible format.  I’m doing that because, as far as I can tell, most of what gets written up in the popular press is un-usable, from the standpoint of actually understanding what’s going on.

You’ve seen a lot of popular press articles recently on rapid growth of COVID-19 in many states.  By my estimate, those articles are only partially true.  For one thing, they ignore places where there’s been “bad behavior”, but no problem (Post #709).  From a scientific standpoint, those area are every bit as interesting as the ones where case counts are growing.  For another, they commingle areas where there is a real threat to public health emerging (Arizona) with areas that are, really, no worse off than Virginia is (Texas).

The upshot of this analysis is my list of states and the level of COVID-19 problem that they currently face.   I think everybody has it right in that Arizona, pretty much all-of-a-sudden, is facing some serious problems.  But other states that are featured in the popular press do not — certainly not if my standard is how things stand currently in Virginia.  Which, already noted (Post #715), seem to be heading in the right direction now.  For no particular reason that I can put my finger on, other than a generally reasonable population, and good weather.


 

What makes this so difficult?  Why is there no clear pattern across the states?

In the main, what makes any analysis of COVID-19 so difficult is that there are no natural constraints on the disease.  Nobody has immunity and the number of persons infected so far is a tiny fraction of the population.

As a result, the US population is just one big wide-open field.  And as far as i can tell, what you  observe in one state versus another is largely a matter of happenstance.  E.g., it just so happened that nobody in Montana had traveled to China recently when the pandemic was starting.  But lots of people in New York had done so.  And so, even now, infection rates in New York are vastly higher than in Montana.  That doesn’t reflect any truly fundamental difference between the New York State and Montana populations.  More-or-less, that’s just an accident.  There is no more fundamental explanation.


What does a good epidemiological study look like?

In short, a good study is one that actually gives you some explanation of why things are happening.  That’s possible because most studies focus on diseases that are well-established and stable in the population.  And, typically, diseases where there is some clearly defined cause-and-effect link that you can hope to clarify.  Even if that link isn’t obvious.

A classic epidemiological analysis is the analysis of state-to-state variations in skin cancer.  There, the cause of disease is relatively well-established as lifetime sun exposure, tempered by skin color.  Briefly, the paler you are, and the more time you spent in the sun, the higher the odds that you’ll develop some sort of skin cancer late in life.  And once you have all those factors on the table — average sunlight, altitude, and racial mix, most of the variation in skin cancer rates makes sense.

Here’s an example I did years ago regarding oxygen use.  It took a while to uncover the cause-and-effect, but in the end, despite huge state-to-state variation in home oxygen use, the variation made some sense.

In the Medicare program, virtually the only reason for prescribing home oxygen is for chronic obstructive pulmonary disease (COPD).  And yet, Medicare’s spending for oxygen, across the states, seemed to have little to do with COPD.  There’s five-fold state-to-state variation in spending, with only a vague hint of some link to the disease that the spending is supposed to be for.

At some point, I was asked to look at this issue.  My client — a major manufacturer of oxygen equipment — was not particularly happy with the answer that the US DHHS Office of the Inspector General (OIG) seemed to be leaning toward, which boiled down to “fraud and abuse” answer.  Not that that’s a bad answer, in general, in the US health care system.  My client simply did not think it was true.

The first step in any such analysis is to sort the data a few ways, and see if anything catches your eye.  After a while, it dawned on me that many of the high-spending states were in the US Mountain region.  Like so:

Rocky mountain high?  Mile High Stadium?

It finally dawned on me that the primary driver of Medicare oxygen spending was altitude above sea level.  For a given COPD population, Medicare was spending a lot on oxygen in some states mostly because there wasn’t muich oxygen in the air.  Like so, a nice straight line:

Together, elevation and COPD prevalence explained nearly all (85%) of the state-to-state variation in oxygen spending.  That was enough to convince the relevant authorities that the state-level variation on oxygen spending wasn’t the result of massive amounts of fraud and abuse, but instead was (mostly) the result of natural forces.

And that is what a successful epidemiological study looks like.  You actually get an answer, and it appears to make sense.

And nothing about COVID-19 yields anything that looks like that.  Nothing.  Not the states that have high current prevalence.  Not the states where it’s growing rapidly and not.  To me, so far, the lineup of the states looks like one big accident.


Putting the state data into a sensible format.

The first step in trying to make sense of things is to put the state data in some uniform format.  Something more than just a simple count of cases.  At the minimum, put the new case counts on a per-capita basis.

You’ve seen a lot of popular press articles about how many states are having increases in new COVID-19 cases.  And yet, much of that seems to come from picking those states after-the-fact.  The popular press looks at the states with rising incidence, and talks about them.  It ignores the ones where behavior was superficially similar, but there is no increase in cases.

And as a result, you don’t hear about the Eat Cheese or Die states (Post #709).  Those who somehow skated past an expansion of the pandemic.  You only hear about the ones where trouble is brewing.

That’s good reporting, but bad science.  That’s why I have insisted on running an analysis of a fixed, predetermined list of states.  This list was, at one point, the New York Times list of states that re-opened early and states that did not.  Up until my last analysis, there was no difference between these two sets of states.  I did that last a month ago, and posted the results in Post #694.  Here’s how that contrast looked three weeks ago (updating Post #694.)

But nobody was seeing any impact three weeks ago.  Let me start by redoing that, updating to yesterday’s counts, and extending the time periods over which I compare those two groups of states.  I’m going to drop the pre-opening period (during which the two groups of states appeared similar).

And now, when I look over three time periods — May 1 to present, May 15 to present, and June 1 to present — sure enough, there’s a modest average difference between the two sets of states.  In the late-reopening states, on average, they’ve fallen to about a 1.3% per day increase in cases, over the past two weeks.  In the early-reopening states, by contrast, there’s been no improvement in new case growth.  In fact, the closer we get to the current day (here, June 14) the more their case growth rebounds.

But that doesn’t come close to telling the full story because there is so much variation among the states.  The problem is, much of what you see tabulated by state is useless from the standpoint of understanding where there are and aren’t problems.

First, it makes no sense to show the raw count of new cases, for the simple reason that some states have a lot more people than others.  So, in the table below, I should you the new cases per capita, from the last week of data, annualized.  In other words, the first column of numbers shows what fraction of each state’s population would be newly infected over the course of a year, if the currently-observed rate of new infections remained constant.

Second, you want to know whether or not that situation is getting worse.  So the second column shows the change in that annualized per-capita infection rate, comparing those week to the week prior.  Positive numbers flag states where the new infection rate (on a per-capita basis) is rising.  Negative numbers then (obviously) show where it’s falling.

Finally, as a kind of overall “misery index”, the last column of numbers is the sum of the first two.  In effect, that’s a crude projection of where that state will stand, next week, if it sees the same change in new infection rate as it saw this week.

I have sorted the data by the “misery index”, descending.   States at the top would appear to have a serious problem, in that they have both high and rising new infection rates.  States at the bottom either have a low rate of new infections per capita, or their rate of new infections appears to be falling rapidly.

To me, this table gives me the kind of ordering of the states that I was looking for.  For perspective, I’ve highlighted Virginia in green.  While we have a fairly high rate of new infections per capita, that’s now falling so fast that you would not project big problems here in a week or two.

And when I rank the states this way — that makes some sense to me — I get a somewhat different picture from what you may see in the popular press.  Yes, Arizona has a real problem, with a high and rising infection rate.  This has made the news.  But Alabama is not far behind.  And yet, it’s hard for me to think of two states that are more different than those, in terms of climate and population.

Note that North Carolina is near the top of the list.  But in terms of climate, I’d say North Carolina has a climate nearly identical to that of Virginia.  So if there is any seasonality to COVID-19, something about human behavior or biology in North Carolina is completely offsetting it, compared to Virginia.

And in general, when I look at that list, I see — nothing.  No rhyme or reason whatsoever.  Both New York and California were hit hard by this, early on.  New York is now seeing a relatively low and falling rate of new infections, California is seeing a relative high and rising rate.  So far, I see no way to make any sense of this.  Nothing comparable to the analysis of oxygen use.


A

From macro to micro:  No denominator means no way to know the odds.

Consistent with that scrambled picture at the macro level, there appears to be no way to determine what’s risky and not at the micro level.

As you plot your return to a more normal existence, you’d like to have some idea of what’s a high risk situation, and what’s a low risk situation, in terms of likelihood of contracting COVID-19.  Wouldn’t we all.  The need to know your risk is now so mainstream that an entire Washington Post article was devoted to this idea, this past week:  How can we tell what’s risky and what’s not?

Having thought long and hard about this over the past week, it’s clear to me that we are never going to get any precise estimate of just how risky most real-life situations are.

And the reason for that is simple:  No denominatorThe risk of any activity is the number of persons who get infected through some activity (numerator) divided by the number of persons who engaged in that activity (denominator).

In an ideal world, we might plausibly get some notion of the numerator — the number infected through some activity.  Under no stretch of the imagination are we likely to get any good estimate of the denominator — the total number of people who engaged in that activity.  At least, not for most common activities.

Let me just take a simple example:  Indoor dining in the Town of Vienna.  Plausibly, through contact tracing, we might be able to identify which new COVID-19 infections in Vienna were contracted in restaurants.  Plausibly, the Commonwealth might even make such information public.  (It does not do so now.)  So that’s information that is not now made public, but could (in theory) be known.  In theory, we could know the numerator in our risk calculation.

But to know the risk of eating in a Vienna restaurant, you also need to know the denominator:  How many people, in total, ate in a Vienna restaurant that day?  And that’s a piece of information that nobody gathers, and that nobody has access to.  That’s where you just have to go totally by the seat of your pants.

For example, suppose you want to know the risk of (e.g.) going to your dentist for a routine checkup.  It’s not enough to know that (e.g.) N people appear to have gotten infected, via routine dentistry, in the past month, in Virginia.  (The numerator).  To know your odds, you have to know how many people went to the dentist.  (The denominator).  And that’s something that literally nobody can tell you.  Even making a crude guess, in today’s crazy climate, is probably out of the question.

All you can do is identify where new cases are and are not coming from.  And kind of wing it from there.


Summary.

So far, US epidemiologists have been remarkably, almost astonishingly unhelpful, in providing any guidance whatsoever on where people are picking up their infections.  That is, we here in the USA can’t even get information on the numerator, let alone the denominator.  Nothing about the state-level data seems to make sense, and nobody seems to be stepping up to put it into any context that makes sense.

Certain health care settings are tracked, sure.  So you can, in theory, estimate the odds if you are (e.g.) living in a nursing home.

But for the rest of us, living our daily lives, the Commonwealth (and I would say US epidemiology in general) has provided little in the way of useful information on what we should and should not be doing.  Maybe that’s just the way things are.  Maybe  nobody has quite figured this out yet, but somebody eventually will.

Post #715: Key graphs updated to 6/14/2020. Drop-off in new cases accelerates.

This post updates some key graphs to 6/14/2020.  Fairfax has seen a sharp dropoff in new cases.  We’ve been building up to that for the past couple of weeks, so that is not surprise.

As you can see from my just-prior post, my best explanation is that we’re finally seeing the seasonality of COVID-19 showing up in the data.  For sure, other than the Governor’s mandatory mask ordinance, it’s not like we’ve been doing hugely more to limit the spread.  And with just 1 person per 100 known to have been infected in Fairfax County (and likely no more than 5% of Fairfax residents actually having been infected), it’s far too soon for the “natural” end of the epidemic (typically estimated as herd immunity occurring with 70% of the population infected).

Whatever we’re doing under Phase I of re-opening, it’s not creating a spike in new cases.  If there are new cases attributable to this modest relaxation of restrictions, they are being swamped by this ongoing downward trend.

Continue reading Post #715: Key graphs updated to 6/14/2020. Drop-off in new cases accelerates.

Post #714: The seasonality of coronaviruses and the current decline of cases in Virginia

Seasonality of human coronaviruses (other than COVID-19) in Stockholm, Sweden.  Source:

Potential impact of seasonal forcing on a SARS-CoV-2 pandemic DOI: https://doi.org/10.4414/smw.2020.20224 Publication Date: 16.03.2020 Swiss Med Wkly. 2020;150:w20224 Neher Richard A., Dyrdak Robert, Druelle Valentin, Hodcroft Emma B. Albert J.

 

Continue reading Post #714: The seasonality of coronaviruses and the current decline of cases in Virginia

Post #713: Another promising treatment: monoclonal antibodies

Convalescent plasma is a well-established technique for treating diseases that have no other type of treatment, such as Ebola.  You take blood from individuals who have recovered from a disease, separate out the antibodies that they have developed that fight the pathogen in question, and inject those antibodies into someone else.  Those antibodies then provide “passive immunity” to the person who was injected — they allow that person to fight to pathogen.

This technique has been in use for more than a century, for a wide range of diseases.  Case reports from China and elsewhere suggested that it has some significant benefit in treating COVID-19.  (A fairly exhaustive literature review can be found on this University of Michigan web page. )

Providing antibodies to an infected individual is helpful, but it’s not a silver bullet.  Although there were good early case reports, at least one clinical trial found only modest (and not statistically significant) improvement among critically ill COVID-19 patients.  But that had limitations, including small sample size and a focus on the critically ill (for whom almost nothing appears to work well, including anti-viral drugs).  The modest clinical improvement for the critically ill COVID-19 population appears similar to convalescent plasma results for the earlier MERS coronavirus epidemic (per this reference).  And, administration of convalescent plasma at earlier stages of disease appears to have better results (per this commentary).

Regardless of effectiveness, a shortcoming of convalescent plasma is availability.  Recovered donors with adequately high antibody levels can donate enough blood to treat a handful of cases.  And the equipment that separates out the antibodies appears to be relatively uncommon.

Thus, whatever the level of benefit, this treatment is limited by supply.  (Which is, I think, why it has largely been reserved for critically ill patients, so far.)  There simply does not appear to be a way to extract these naturally-occurring antibodies in large quantities.

So, why not just manufacture the antibodies instead?  And that’s precisely what several drug companies are now attempting to do, using monoclonal antibody techniques.  Under this approach, scientists develop cells that produce an antibody for some specific substance, culture (grow) those cells, then extract the antibody.

Monoclonal antibodies are now a mainstay of treatment for both autoimmune disease and cancer.  Any drug (biological) whose generic name ends in “-mab” is a monoclonal antibody.   Hence, Remicade (infliximab), Humira (adilumimab), Avastin (bevacizumab), among others.  Currently, it looks like 6 of the top 10 drugs sold in the US, by dollar volume, are -mabs.   The list of commercially-available -mabs includes hundreds of substances (per Wikipedia).

This is almost a plug-and-play technology at this point.  Several different systems are commercially available for developing -mabs to produce specific antibodies of interest.  These are common, but they are still high-end science, involving techniques that would have been unthinkable 30 years ago.  For example, one of the oldest and most successful -mabs — Remicade — is actually a mouse-human hybrid.

And so, that machinery is now being focused on COVID-19.  This is now at the clinical trials phase for one of them.  My only point being that this is a completely routine and feasible (if expensive) technology.  There’s no question that they can produce these COVID-19-specific monoclonal antibodies, in large quantities.  At this point, their effectiveness is not clear, particularly for the most severely ill patients.  But these should, at the minimum, add another set of therapies to the list of treatments for COVID-19.

 

 

Post #712: Key graphs updated to 6/11/2020.

This post updates some key graphs to 6/11/2020.  At the last update (6/6/2020), it looked like we were finally seeing a slowdown in new case growth in Fairfax and in Virginia (Post #704).  That has panned out.  For Fairfax County, the seven-day moving average of daily new cases is down to about 150 new cases per day.  For Virginia, it’s down to 750 new cases per day.  For Vienna (ZIP 22180), it’s down to maybe one new case per day.

Whatever we’re doing under Phase I of re-opening, it’s not creating a spike in new cases.  If there are new cases attributable to this modest relaxation of restrictions, they are being swamped by ongoing trends that have nothing to do with re-opening.  Near as I can tell, the trends in case counts have nothing to do with re-opening or not, in Virginia.

This matches my earlier analysis of US national data, and appears to match the European re-opening experience, as reported here.  I need to revisit the national data in light of recent events (e.g., in Arizona).

Continue reading Post #712: Key graphs updated to 6/11/2020.

Post #711: “Asymptomatic cases” and the spread of COVID-19

If you read this blog, you realize I’ve been tracking the pandemic pretty closely.  So when the WHO was quoted today as saying that “asymptomatic cases don’t routinely spread COVID-19”, I said, why is that news?  They’ve been saying that for months.

 Then I read the coverage, and I realize that it’s news only because people don’t know what “asymptomatic cases” means.  And can’t be bothered to stop for ten minutes and figure it out.

Thus confirming the #1 problem in America today.  Everybody feels entitled to a firmly held and vehemently expressed opinion.  Nobody feels compelled to do even the tiniest bit of homework first.

So, let me fill in the homework.  As briefly as possible, “asymptomatic cases” means individuals who never, ever show any symptoms.  That does NOT mean “pre-symptomatic” cases, that is, individuals who are in the period between infection and onset of symptoms.  Guaranteed, 99% of what you read in the popular press will have confused the two. Continue reading Post #711: “Asymptomatic cases” and the spread of COVID-19

Post #710: Kicking off epidemiology week at savemaple.org

Source:  US CDC, The ten essentials of public health.

It’s epidemiology week here at savemaple.org.  I hope you’re as excited about that as I am.

Let’s kick it off with a practical piece outlining the goal of this.  So, what’s the point of reviewing what is known about the epidemiology of COVID-19?  It’s to help you decide which precautions make sense for you, if you are determined to return to something approaching your pre-COVID-19 lifestyle. Continue reading Post #710: Kicking off epidemiology week at savemaple.org

Post #709: Perhaps cheese protects against coronavirus?

Source: Wikipedia.

Little or nothing about the continued spread of COVID-19 in the US makes sense to me.  I can’t quite imagine why or how Virginia manages to have 1000 new cases a day, week in and week out.  Ditto for 300-a-day in Fairfax County, or 4 to 5 a day in Vienna (ZIP 22180).

For viral epidemics, I understand explosive “exponential” case growth.  I understand the disease fading away.  But this is one where it’s just kind of hanging out.  Where, aside from mask use and literal isolation from the rest of the world, there seems to be little to explain which countries are hard-hit and which have fully recovered.

Take the chaotic re-opening of retail establishments in Wisconsin.  That’s sort of an “acid test” for what we think we know.  There, the Supreme Court struck down all restrictions, all at once.  The Governor of that state described the result as a “wild west” situation.  There was a lot of press coverage of the resulting “party down” atmosphere showing crowded bars and restaurants full of non-masked younger patrons.

Clearly, this was nobody’s idea of a safe way to re-open businesses.  And there were widespread predictions that this would lead to a spike in cases.

Because?  Because, logically, if social distancing is necessary to prevent the spread of disease, then breaking all those social distancing rules, in a big way, ought to lead to an uptick in infections.

As a matter of logic, you can’t believe in one and not the other.  Unless you belive in luck, magic, divine intervention, or maybe that other factors are driving the actual transmission of disease.

Four weeks after than 5/13/2020 Wisconsin Supreme Court decision, here’s what you don’t see reported Because, by conventional wisdom, there’s no story here.  No uptick, no vast surge in new cases, hospitalizations deaths.  Nothing.  Bupkis.   Zip. 

Source:  New York Times accessed 6/7/2020.

Just … business as usual.  At least, that’s what I get from that graph, by eye.  A mild upward trend in new cases continued, after the wild west scenes.  Until it didn’t.  And daily new cases began to fall, some time prior to June 1.

I think this is a huge story.  The headline should read “massive violation of social distancing guidelines has no impact in Wisconsin”.  To me, with my generally scientific bent, that’s big news.  But not to the average person, I guess.

It’s tough to say just how massive a violation of social distancing actually occurred.  But if you’re going to wag your collective fingers at the Cheeseheads over it, I think that, by rights, you have to admit that you were wrong.  Not that this was a smart thing to do, or a good gamble on their part.  But the fact is, wrong is wrong.  And the idea of massive negative fallout from the chaotic and all-at-once removal of restrictions — that was wrong.

Just for a contrast, ask what they did wrong in Utah?  And the answer is, nobody knows.  For the first month of  their slow, measured, planned re-opening, nothing happened.  That’s from May 1 to June 1.  Now, new cases are spiking upwards.  And, these are dispersed state-wide — this isn’t the result of a few events (e.g., a meatpacking plant or similar).

Source: New York Times.

Meanwhile, in Virginia, as I continue to report, a similarly measured re-opening strategy has had no discernible impact.

The bottom line is that for a person with some scientific training, looking for cause and effect, this is an unsolvable puzzle.  The awful part being, of course, that if you can’t tell what you’re doing wrong, then you can’t fix it.  You take whatever precautions seem reasonable to you.  With no firm evidence basis for doing that.  And, otherwise, you just live with this seemingly random disease, until such time as a vaccine is produced and distributed.

 

 

 

 

 

Post #704 updated: Key graphs updated to 6/6/2020

This post updates some key graphs to 6/6/2020.  New cases appear to be slowing.  For Fairfax County, the seven-day moving average of daily new cases finally broke below 200 cases this week.

There’s no noticeable increase in new COVID-19 cases from Phase I re-opening in Virginia.  This matches my earlier analysis of US national data, and appears to match the European re-opening experience, as reported here.

Impact of re-opening, Phase I, in Virginia, update to 6/6/2020

Source:  Analysis of county-level data as reported by the Virginia Department of Health.  NoVA plus is Northern Virginia, Richmond City, and Accomack County.  The latter is in the late-reopening group because because they had 500+ cases of COVID-19 in two poultry processing plants.

The red line is the areas that entered Phase I re-opening on 6/15/2020.  Any resulting uptick in cases should have appeared by now.  Those areas are now entering Phase II of re-opening.

Continue reading Post #704 updated: Key graphs updated to 6/6/2020

Post #708: Mainstream churches understand the dangers of singing, but CDC removes all reference to them

Even within the astonishing incompetence of the Trump administration’s response to COVID-19, I find this one hard to fathom.

Mainstream denominations, and even whole countries, have figured out that singing at church creates a significant, avoidable risk of spreading COVID-19.  The reason is that singing generates large amounts of aerosol (under 5 micron) particles.  And all it takes is one infected individual, who is also a high-volume emitter of aerosols, to infect a large number of individuals.

See Post #682 and earlier posts for background, and a little simple math.

If you work through the list of religions in the DC area with significant top-down control, you’ll find that the leadership has figured out this issue.

For example, in the Catholic Archdiocese of Washington DC, re-opening of churches included this piece of guidance:  “5. The use of choirs should be omitted. The preferred musical accompaniment at Mass consists of one cantor and one organist or pianist. … ”

How about the Episcopal Church in DC.? No live singing with exception of vocalist with mask and microphone.”

The Presbyterians?  “Since congregational singing and choral music are particularly risky activities when it comes to the spread of Covid-19, these elements of worship should be omitted when churches first return to public worship, until such a time as it is deemed safe.”

That’s enough to get the drift.

And, in the past, the US government got that.  On 5/22/2020, my wife sent me the text of the newly-published CDC re-opening guidance to churches.  It said:

Consider suspending or at least decreasing use of a choir/musical ensembles and congregant singing, chanting, or reciting during services or other programming, if appropriate within the faith tradition. The act of singing may contribute to transmission of COVID-19, possibly through emission of aerosols.

Good advice.  And pretty mild stuff, really, when Germany has simply banned church singing outright, for the duration of the pandemic.  And when church-based superspreader events have been identified in many countries, starting with the Mount Vernon, Washington choral event.

To be clear, as with meat packing plants, church-based superspreader events are a universal phenomenon.  They aren’t some one-off, unique, random event.  They occur repeatedly, suggesting some underlying fundamental risk.  For example, it’s not that US meat packing plants have an issue.  It’s that meat packing plants around the world have been subject to outbreaks.  And it’s not that a US church choir or two has had a problem.  It’s that churches around the world have been the sites of superspreader events.   See Post #679 for a brief list of some such events.

Today I got a note from a colleague pointing to this NPR article.  Apparently, somebody at the White House objected to that language, so it’s gone. The CDC now no longer even mentions singing in its advice to churches.

You truly have to wonder what they were thinking.  Of all the material in that “interim guidance”, that one passage, referencing singing, had to go.   The one thing for which we have spectacular evidence of the risks involved, documented in detail by the US CDC.  NPR says that change to the guidance happened a few days ago, I think it happened just after 5/22/2020, when the CDC removed the word “aerosol” from that passage.

God save the Republic.  The people in charge certainly aren’t going to.