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COVID-19 Update: Estimating case fatality rates for COVID-19

March 10, 2020

Welcome to this Medmastery
coronavirus update. I’m Franz Wiesbauer. I’m an internist, trained in epidemiology
and public health at Johns Hopkins and the founder of Medmastery where we teach
important clinical skills to doctors and other healthcare providers
around the world. Today we’re going to talk about case
fatality rates and how to estimate and calculate them. Let’s go to the Johns
Hopkins coronavirus map. There we have the total number of
confirmed cases, total deaths, and total cases recovered. Please note that these are the
data as of March 3rd, 2020. So here you can find the total confirmed
cases and the total number of deaths. Now you could calculate a case
fatality rate with these numbers. You could divide the number of deaths
by the number of total confirmed cases. Multiply it by 100 to receive a case
fatality rate in this present situation of 3.4%, but this way of doing
it is slightly erroneous. I have constructed a fictitious epidemic
showing new daily cases and new daily deaths of a certain disease in
green and red, respectively. Now, as you can see from the graph and
probably from your own reasoning, is that someone needs to be sick or classified as
a case for some time before they can die. In this fictitious population, the time
from being identified as a case to the time of death is two days on average. You can see that the peak of cases was
reached on day seven to nine whereas the peak of deaths occurred
between days nine and 11. Here you can see the same two curves of
daily deaths and daily new cases in light red and light green on the very bottom. These are the daily new deaths. These are the daily new cases. In addition, you can now also see the
cumulative cases and deaths in dark red and dark green. As you can appreciate when we are in
the ascending limb of the epidemic, the current number of cumulative deaths is
also delayed by two days when compared to the number of cumulative cases. So deaths that occurred over here
correspond to cases that occurred over here. So one would have to compare the
cumulative deaths from day ten to the number of cumulative cases from day
eight in order to arrive at an accurate comparison or a case fatality rate. So what’s that time delay in COVID-19? So over here, you have the time of
infection, the time of symptom onset, then the time when the case is
reported, and the time of death. Now the time between infection and symptom
onset is called the incubation period. The incubation period of COVID-19 has
been estimated to be around 5.2 days on average. However, there are cases with
the lower incubation period. But there are also patients with a much
longer incubation period of up to 21 days, possibly even 24 days have been described. So this interval is five days. And what’s the time from symptom
onset to the reporting of a case? The authors of this study found
a mean duration of 7.1 days. Obviously, this will be quite a bit
different from country to country. So let’s say that this period is seven
days; and what’s the time from symptom onset to eventual death? In an analyses done at the Imperial
College London, authors found that the time from disease onset to eventual death
was 22.3 days, very similar to the time of recovery. So this interval is 22 days
long according to this paper. So 22 minus seven days equals a time delay
between reporting and death of 17 days, and that’s the interval one should use to
determine where to take the current case number from. So instead of comparing the current total
deaths to the current total number of confirmed cases, one should compare the
current total deaths to the total number of confirmed cases from 17 days prior. This number can be retrieved from
enlarging this inset down here. So we said, these numbers were taken from
March three, going back 17 days means we need to retrieve the number of
total cases from February 15th. So on that day, the number of total cases
in mainland China was 68,300, and the total number of confirmed cases
in other locations was 685. So 68,300 plus 685 equals 68,985
total cases on February 15th. So what’s the new case fatality
rate using this lag time of 17 days? Remember this was the calculation from
the beginning of the video, which did not account for the lag time. And now we have 3,117 divided by
68,985 times 100, which equals 4.5%. Now, you should not only use a lag time of
17 days – but also see what a shorter lag time of say eight days will bring up. This is called doing a sensitivity
analysis or testing your numbers. Now, the problem in all of this, as
described by the researchers from Imperial College London, is these calculations are
likely skewed because we don’t know how many asymptomatic cases or mild cases
are out there whom we don’t know off. They argue that mostly the very severe
cases have been detected in mainland China. Whereas it appears that internationally,
all symptomatic cases, meaning deaths, severe cases, and symptomatic
cases are picked up. If there truly is a substantial number of
cases in the dark blue bottom part of the pyramid, then the true case fatality rate
will be much lower than what we have just calculated. The authors of this paper found that we
might be underestimating the true number of cases by a factor of 19. Which would mean that we would have to
divide our calculated case fatality rate by 19 in order to arrive at the true rate. Which would obviously make the
mortality rates seem much less scary. One argument in favor of
that view can be seen here. This graph from nucleus wealth shows that
there might be significant under-reporting of cases in most Chinese provinces,
but also in places like Iran. The bars depict the reported COVID-19
cases per million inhabitants. South Korea, which has done the most
extensive testing up until now, reports around 80 cases per million. The Chinese provinces are way lower when
they should be really higher, especially those provinces next to Hubei,
where the outbreak started. So this should be an indicator that
the true case fatality rate is lower. In reality. We will only be able to tell once
we measure antibodies in the general population in order to tell what
the true number of cases was. That’s it for now. If you want to improve your understanding
of epidemiology, make sure to register for a free Medmastery trial account and
attend our epidemiology essentials course. We’ve just opened it up to trial
users due to the huge demand. So stay safe and talk soon.


  • Reply Shviko March 9, 2020 at 4:01 pm

    amazing video you deserve more subscribers

  • Reply Claudio Dinapoli March 10, 2020 at 6:23 am

    Many people are focusing on assessing how dangerous this virus is in terms of deaths toll. Many say it's like a "silly influenza" comparing the two viruses in terms of fatality rates. In my opinion this is all misleading. What should be worried now is the lack of a therapeutic drug that targets the virus and blocks its replication in the body. Without this weapon all pneumonias caused by the virus that develops ARDS need ICU interventions (high flow oxigenation, mechanical ventilation, positive pressure assisted respiration and ECMO). Since the number of cases that suddenly appear in the population, the demand for this kind of interventions can overwhelm the numbers of beds, anesthesiologists, ECMO specialists available. Imagine a glass of water already full that needs to hold additional water. Here in Italy the number of cases seeking ICU attention in some part of my country are already overwhelming the hospitals capacity. Planned surgical interventions have already been postponed to add more anesthesiologists to the ICU wards. It should be also considered that some of the infected are the same health care workers who assists the patients. So it's a virus that suddenly overwhelms a health care system and weakens its capacity to react to the virus. That's a new view that should be taken into account when assessing how dangerous this virus is. In my humble opinion.

  • Reply Logos P March 10, 2020 at 10:20 am

    How about we apply a similar analysis to south Korea specifically? Right now there 7500 cases, with a growth rate of 10 percent per day we get 1384 cases 17 days ago. This means a mortality rate of 3.9 percent using this method, but let me be clear that this will not be accurate because it doesn't really work when you go that far back and the number of cases is so low. Since the average number of cases back then was so low many of the deaths we have seen now probably didn't test positive 17 days ago (which would be the average) but rather from the larger group of people that have tested positive a bit later and with a bit out of the average time for the lag between positive test and death.

  • Reply Abdelhalim Yousef March 10, 2020 at 10:36 am

    22-7=15 not 17!
    Would you please explain?

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