Monday, April 27, 2020

Covid-19 Uncertainty: Be willing to say “We don’t know”


Like many people, I find myself distracted by the virus, as if infected by a different virus that makes me into a zombie that has to read the news. I find myself unable to stop reading about models and what the exit strategy will be for the “stay at home” orders in the US and elsewhere. Policies in Sweden, Taiwan, Korea, and elsewhere are all fascinating. I know many others are infected, too; friends tell me, and journalists write about it.

At the root of the problem is uncertainty, which is something I’m thinking a lot about in my research on pesticides, too. Though we now know a lot more about the Covid-19 virus (and doctors are better able to treat patients), there are many things we still don’t know. Most importantly, we don’t know what the world will look like after the pandemic passes, and when that will be.

Some people are able to just live with the knowledge that we don’t know. A friend wrote to a small group of us proposing a trip sometime next fall, and when I wrote back “I think it is going to be more than a year before we can travel freely, don't you?,” another friend wrote curtly, “Guessing game at this point.” Since he is a surgeon, I was about to write back, “Well, you must have some model in mind.” But then I realized he was right; it is pointless to speculate, and I just have to accept the uncertainty.

And there is a lot of uncertainty. While China, Taiwan and Korea have done a great job containing the virus, how long can they maintain their containment policies, including closed borders? Paradoxically, the chaos in the US and much of Europe, including the lack of preparation, slow reaction and lack of testing, may lead the US to develop a herd immunity that allows the US to come out of the epidemic earlier than areas that contained it better.

We don’t know whether a vaccine is possible; after all, we don’t have a vaccine for other coronaviruses. So it is possible that the only exit strategy for the virus is to keep the epidemic at a low level, so that it does not overwhelm the hospitals, until the population develops enough immunity that the virus does not spread very easily. This, essentially, is the Swedish path, where people are encouraged to keep social distance but there has been no stay at home order.

As doctors learn how to treat patients better, the death rate is declining, and may soon be lower than the death rate for the annual flu. But at this point, we don’t know, because we don’t really know how many asymptomatic cases there are, so we do not know the total number of cases, which is the denominator for the death rate (death rate = # dead/# infected). So while we currently think the US is a mess, and that Southern governors opening up their economy now seem irresponsible, the US and Sweden may turn out to be the better way to get out of this pandemic. We don't really know.

Some people are obsessed with knowing whether they have had the virus. A friend of mine told me of a group of co-workers who decided to get antibody tests (which are starting to be available here for $200-$260 (see one example here). The test checks your blood for antibodies to tell you whether you have had a Covid-19 infection and developed the antibodies. I asked why they wanted this test; they said they “just want to know.”

This is very odd, because though they think they will be liberated after a positive test (meaning they have antibodies for Covid-19), actually, their behavior should not change whether it is positive or negative. If they are negative, they still have to wear a mask and stay home. If they are positive, they assume that if they have Covid-19 antibodies, that they cannot be re-infected. They are probably right, but we don’t know this for sure. One study found low levels of antibodies in recovered patients, suggesting they may have only weak or no immunity. There have been a few anecdotal cases of apparent “re-infection,” and while it is more likely that their original infection just lingered (i.e. that when they were supposedly recovered and virus free, that they still had the infection), we can’t be sure. So to be cautious, they should still practice social distancing. Furthermore, it is not like they can suddenly go to the movies or to restaurants: they are all still closed, and few of their friends can go anyway.

In addition, there are serious doubts about the reliability of these serological tests. There are now only four tests approved by the US Food and Drug Administration (FDA), but 107 that are merely self-validated andpossibly fraudulent or unreliable. Those are the tests that are easily available, of course.

Even with a “reliable” test there is a problem, because most tests are only 95% reliable, meaning that they make a mistake 5% of the time. If I test positive, it is more likely that it is a false positive. In Missouri, it is very unlikely that any one person has had a case of Covid-19. When rates of infection for California came back at between 1.5 and 2.4 percent, experts thought these figures were much too high. Though a recent study suggests NewYork City may already have a 14 percent infection rate, experts are skeptical. Certainly, in the St Louis metropolitan area, where we have 2,720 cases as of yesterday, (0.1% of our area population, and 127 deaths), the chances of anyone being infected is very small.

The main problem with testing, however, is that it is interesting and important for epidemiological understanding of the epidemic, but is not very useful for the individual. Specifically, if a population’s infection rate is low, say 2%, then a test that is 95% accurate is not very helpful. If I test positive, I have roughly the same chance of being truly positive and of being a false-positive. Ninety-five percent accurate sounds good, but it is not if you are testing for something that is very rare. (To think with another example, since Yellow Fever is extremely rare in the US and few have antibodies for it, if I take a test that turns out positive for Yellow Fever antibodies, it is a lot more likely that the test is wrong than that I had or was exposed to Yellow Fever.)

Testing is key for public health purposes. We need tests to see who has the Covid-19 disease so we can be sure to isolate them and then contact all who have been in contact with them, so they can self-isolate. And for public health purposes, everyone should wear a mask to avoid infecting others in case they have the virus, and they have to wash their hands regularly and avoid crowds.

But if you are sick, it does not matter whether what you have is the flu or Covid-19; the treatment is the same. You are going to have to let your body’s immune system fight the infection, just like you do for any cold or flu. You need to protect others as though you are infected with Covid-19 (or any communicable disease): isolate yourself, avoid contact with others, wash your hands and keep your dishes and cups separate, etc. From my individual point of view, if I have a fever and shortness of breath, I have to just assume that I have the coronavirus. But people want to know, so they want to take the test.

Models are the most sophisticated ways we try to predict how the pandemic will unfold, and they help us think clearly. There are even peoplewho take a “wisdom of crowds” approach and use multiple models to estimate more accurately (sort of what 538.com does for political polls). One expert claims that as the pandemic has progressed, predictions have become more accurate, but that is a bit like saying that as you drive closer to your destination, your prediction of your arrival time is more accurate. By the time the pandemic is ending, we will not have much uncertainty. In the meantime, I'm willing to say, "I don't know."



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