Friday, July 3, 2020

Has COVID-19 Become A Lot Less Deadly?

Short answer

No. This graph shows the main reason why cases have increased recently, but deaths have not yet:
Figure 1:
Typical COVID-19 time periods for New York (April) and Florida (now)

Long answer

It's easy to come to the wrong conclusions when looking at graphs like this one:
Figure 2:
COVID-19 cases and deaths in Florida

Since the beginning of June, the number of confirmed COVID-19 cases in Florida has risen about tenfold, but the number of COVID-19 deaths has remained roughly the same. So it seems obvious that something else has happened - perhaps the higher case numbers are only due to testing? Or the virus has mutated and is less deadly now? Both answers seem logical, but they are wrong. Let me explain.

To start with, let's have a look at the cases and deaths curves from earlier in the pandemic. We'll start with New York:
Figure 3:
Cases and deaths in New York in March - April

We can see that the death curve followed the case curve with a delay of about 1 week. That's true for when cases and deaths were rising at the end of March, and it's also true for the peaks in early to mid April.

But things looked quite different in Germany:
Figure 4:
Cases and deaths in Germany in March-April

For Germany, the offset between cases and deaths was much longer - about two weeks instead of just one week. Let's also look at Spain:
Figure 5:
Cases and deaths in Spain

For Spain, the delay between cases and deaths was even shorter than for New York - only about 2-3 days.

We know with absolute certainty that the observed differences were not due to changes in the corona virus that causes COVID-19. Multiple virus isolates from New York, Germany, and Spain have been sequenced and compared to each other, and while there are small differences between almost all isolates, those are mostly "silent" mutations that have no biological consequence.

However, we do know what did cause the observed differences in time lags between confirmed cases and deaths: the availability of COVID-19 tests. Germany had sufficient tests available so that most people with COVID-19 symptoms or exposure to COVID-1 patients could get tested, and test results were generally reported within a couple of days. Therefore, the time difference of two weeks between test and deaths is close to the about 16-20 days that are the typical time from first symptoms to death for COVID-19.

The situation was very different in New York in March and early April. Test capacity was extremely limited, so that testing was mostly limited to patients with very severe symptoms, often patients that needed hospital care. At the same time, hospital capacity in New York City was fully used, which led to very strict criteria for hospital admissions. As a result, patients were testing much later after the initial infection: not when the first symptoms developed after about 5 days, but only after symptoms got a lot worse, which often took another week or longer.

In addition, test providers were severely backlogged, so that getting test results back often took up to two weeks. Together with the delayed ordering of tests, this reduced the typical time between test results and deaths to a week. In Spain, test availability early in the epidemic was even more restricted than in New York, which reduced the test-to-death time even further.

What about Florida?

Since April, COVID-19 testing capacity in the US has increased significantly. As a result, COVID-19 tests have often been available to anyone with symptoms, and even to people without symptoms who (for example) had been in contact with confirmed COVID-19 cases. This means that on average, anyone infected with COVID-19 can get tested about a week early than in New York in April. Furthermore, test results are usually available within a day or two. Together, these two factors extend the time between test results and deaths by almost 2 weeks, as shown in Figure 1 above. There are also indications that the reporting of confirmed COVID-19 deaths in Florida is slower than in New York, probably by several days.

Therefore, the expected delay between the rise in confirmed COVID-19 cases in Florida and the corresponding rise in COVID-19 deaths is more than three weeks. The rapid rise in cases started about three weeks ago, so the corresponding rise in deaths would be expected to start within the next week or so.

If we look at the cases and deaths for Arizona, where the rise in infections started about a week or two earlier than in Florida, we can indeed see that deaths are starting to increase:

Figure 6:
COVID-19 cases and deaths in Arizona

The number of confirmed cases in Arizona started to rise at the beginning of June; about 3 weeks later, the number of COVID-19 deaths started to rise from about 20 to almost 40.

The effect of younger people being infected

Many news reports have detailed that the current COVID-19 infection wave in the south differs from the initial infection wave: a much larger percentage of young people is infected now. To some extend, this is likely to be distortion linked to testing. A young person with COVID-19 is much less likely to have severe symptoms, require hospital care, or die from COVID-19 than an older person; this is a well-known fact that has been seen desribed in for initial epicenter in Wuhan. When testing was limited in the US, and therefore mostly restricted to patients with severe symptoms, the likelihood that a young infected person would get tested was significantly lower than it is now, with much more testing capacity available.

However, while this may distort the picture somewhat, it is nevertheless true that younger people are now driving the wave of infections. To some extend, this is due to younger people being less concerned about COVID-19, and therefore less likely to adhere to social distancing and face mask guidelines. But independently of that, younger people tend to have a much higher number of social interactions than older people, and are therefore more likely to be infected when restrictions are lifted.

Over time, however, younger people interact with older people - their parents, grand parents, coworkers, and others. As a result, the infection wave spreads to older population groups, albeit with a noticeable delay.  A study by Dr. Jeffrey Harris, an economics professor at the MIT, found this to be the case in infection time lines for Florida. Here is a graph from this study:
Figure 7:
COVID-19 infections by age group in Florida (from Harris, 2020)

The figure shows that the growth in the older (60+) age group trails the growths in the younger (20-39) age groups by about 1-2 weeks, but then increases at about the same pace. The effect of the age distribution and timing on COVID-19 deaths amounts to an additional delay of 1-2 weeks between confirmed infections and deaths.

As a result of all the factors discussed above, the overall delay between the rise in confirmed COVID-19 cases in Florida and a corresponding rise in deaths is likely to be approximate one month.

But the CFR is down!

Another argument made by "partially informed" people that "proves" that the corona virus is getting less harmful is that the case fatality ratio (CFR) is going down. The case fatality ratio is easy to calculate: just divide the number of COVID-19 deaths by the number of confirmed cases. Do this for New York on May 1, and you get 7.6%. Do this for Florida on July 2, and you get 2.1%. Quod erat demonstrandum? Not so fast!

The biggest problem with the CFR is that it uses "cases". Increase testing, and the number of confirmed cases goes up. But the number of deaths does not change (or changes only minimally, assuming most severe cases still get tested). So do more testing, and your CFR goes down! That's exactly what we are seeing - Florida has done a lot more testing than New York. But testing has changed nothing about how deadly the virus is. More testing only warns us that we have a problem earlier, giving us more time to do something to reduce transmissions.

The really relevant number is not the CFR, but the IFR: the infection fatality ratio. But to calculate that, we need to know the actual number of infections - something we usually do not know. There are multiple ways scientist can try to estimated the true number of infections, and all of them must take age distribution into account. For different countries and regions, the studies have returned numbers in the range of 0.4% to 1.4%; these numbers have not really changed much since the first thorough estimates based on Wuhan data in February and March. One of the higher infection fatality rates of 1.45% was estimated for New York City. For age group from 25-44 years, the estimated IFR was 0.12%; for the oldest age group (75+), the infection fatality rate was 17%.

One likely reason why the IFR in New York City was relatively high was the overloading of hospitals and ICU units. Failure to understand the delays between the rise in reported COVID-19 cases and the corresponding deaths has already lead to delayed actions in several affected states, and will likely cause similar hospital capacity problems in many areas in these states - and similar high fatality rates.

Herd immunity still means more than a million COVID-19 deaths in the US

Some individuals who looked at case curves and deaths curves and then wrongly concluded that COVID-19 had mutated to a less deadly form (which it has not) have also advocated to go for "herd immunity".  To reach this point where new COVID-19 transmissions would stop "naturally", at least 60-70% of the population would have to be infected: more than 200 million Americans.  With the fatality rate seen in New York, this would lead to almost 3 million COVID-19 deaths. Even with a fatality rate at the low end of the estimates, 0.5%, "herd immunity" would still mean more than a million deaths from COVID-19.

The vast majority of Americans still considers a million deaths absolutely unacceptable. But some people value their "freedom" to party and not wear face masks higher. Often, they hide their real opinions, instead downplaying how dangerous COVID-19 is. But the science is clear, and it is not "just another opinion". Don't be fooled.

Is the more infectious mutant G614D more deadly?

A couple of hours after writing this post, I found a couple of interesting publications that describe a mutant of the corona virus called "D614G". One study by a large group of researchers from Los Alamos, Duke, Harvard, WUSTL, and the UK looked at 28,576 sequences from corona virus isolates, and tracked the changes over time. The study found solid evidence that the original strain, D614, has been largely replaced by a mutant strain, D614G, in many different countries and continents. The likely reason for this observation is that this strain is more infectious, which is supported by the observation that the mutant virus appears to be present in higher concentration in the upper respiratory tract than the original D614 strain. Such a higher concentration of viral particles would explain a higher infectivity, and it could also cause more severe disease symptoms.

A second study had looked at how common the original and mutant virus strains were in different countries, and correlated this to the reported CFR rates. The study concluded that the mutant D614G strain (called G614 in the study) was linked to higher fatality rates, and therefore more pathogenic - in other words, more deadly. However, as discussed above, the CFR rate depends on both fatalities and testing, and the larger changes in observed rates are linked to testing differences. The testing rates vary dramatically between the countries included in the study, so any conclusion about the mutant being more pathogenic is, at best, tentative.  The study did note that the isolates from New York had a higher percentage of the D614G strain; if this strain is indeed more  pathogenic than other strains, then this could explain the observed higher infection fatality ratio, possibly in combination with, and addition to, other factors like hospital overloading.

Additional studies will be needed to clarify whether or not the D614G strain is indeed more pathogenic than the original D614 strain. At this point in time, we only know that this mutant strain that has become dominant on most countries is more infectious, and can only speculate that it may be more deadly. Still, the scientific evidence we have today points towards more, not less, deadly corona virus variants.

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