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Why do we (possibly) overestimate the lethality of COVID-19

! Attention, I am not a doctor, my personal opinion is stated here. This post is NOT intended to evaluate your risks and make any decisions regarding your health!

Now, when all countries of the world introduce one way or another prohibitive measures, the most important is the correct assessment of the mortality of the disease. Unfortunately, almost no attention is paid to this, however, it is this factor that should determine the scope of prohibitive measures. The uncontrolled spread of quarantine can completely paralyze the global economy (which we are already observing) and worsen the quality of life and investments in healthcare of people on the whole planet. There is a widespread belief that PCR diagnostics show us the exact picture, but this is not so. PCR diagnostics is only a tool with its limitations. If the wrong sample in the population is added to this, then we will see “weather on Mars” instead of at least some reasonable estimate.

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I do not do bioorganic chemistry now, all conclusions are based on a university course and discussions with familiar biologists and people involved, including in molecular diagnostics. If anyone has more accurate information on the sensitivity and specificity of testing, I can add it to the article.

Any binary test is subject to false positive and false negative results. If the test is false positive: we diagnosed a person with COVID, but he really isn’t. If the test is false negative: the person has a COVID, but we did not diagnose it. Strictly speaking, real-time PCR is not a binary test and can even determine the concentration of a virus, but its interpretation for COVID, as far as I know, is now binary (detected / not detected).

Now we will consider at what stages errors can occur.

PCR diagnostics include several stages.

  • sampling
  • conveying the sample to the amplifier
  • reverse transcription (we have an RNA virus, and we make DNA by PCR)
  • PCR in real time

Real-time PCR alone is a very accurate method for determining the presence of virus DNA. However, it is important that the virus DNA is present! If the sample is not selected correctly or the virus concentration is below the detection limit of the method, the test will produce a false negative result. Also, the sample can be destroyed even before it enters the amplifier, which will also lead to a false-negative result. A special problem is reverse transcription, if it is done incorrectly there will simply be nothing to amplify. It was to this part that there were serious questions for the Vector test. Also, mistakes can be made in the process of introducing PCR reagents (theoretically there is a positive and negative control, but you can even mess with it). That is, to obtain a truly positive result, it is necessary thatstars agreed all points of the program were executed correctly.

Let us now consider in what cases we can get a false-positive result. There are several such options:

  • sample contamination
  • non-specific amplification
  • technical error when setting up the device

With the contamination of the sample, everything is clear, it is necessary to work carefully. More difficult with non-specific amplification, it can be caused, for example, by improper primer design or poor cleaning of primers / reagents. From my point of view, the probability of this is not very high: the selection of primers is a purely bioinformatic task that can, in theory, be performed once at the WHO level (although theoretically it can be assumed that different coronaviruses "walk" in different regions of the world and some may give positive test). The synthesis and purification of primers is a long-established technological operation and there should be no problems with their quality either.

Nevertheless, a number of tests, including the Vector and CDC tests, were criticized for the high share of false-positive results. However, this concerned the tests themselves and not the entire procedure, including the selection of tests, sample delivery.

From my personal point of view, for the reasons stated above, now there is a higher probability of receiving false negative results. If so, this leads to very sad consequences.

What happens if an easily ill (of which the vast majority) person has a false negative result? He rejoices and goes home. System resources are limited and in this case no one will test a second time. At the same time, a person is removed from the statistics of patients, increasing the observed mortality (we see only severe cases). Even if he is still sick, the insurance company simply will not allow him to do a second test until the situation requires hospitalization. Moreover, if a person arrived in serious condition, and the first test is negative, he will most likely be given a second test, thereby increasing the overall accuracy of the diagnosis. In the case of a false positive test, a person is likely to undergo the whole complex of diagnostic measures, take another test, do CT, etc.And he has a chance to get out of the statistics with the comment "The diagnosis was not confirmed."

Thus, the above model of the process (and this is precisely the model, pay attention), leads to the exclusion from the statistics of easily sick even! in the case of advanced PCR diagnostics.

But the situation is even more interesting, most cases of COVID go away with symptoms that do not require the attention of a doctor. People may simply not seek help and this also contributes to a decrease in the observed mortality rate. This was especially true a month or two ago when the epidemic did not reach such proportions as now and the epidemic, presumably, was gaining momentum.

The most characteristic example of a very strange approach to testing and maintaining statistics was shown to us by Italy. The almost complete absence of testing for easily ill patients, plus testing of all the dead with recording in the statistics of mortality from coronavirus, everyone who was diagnosed with a positive diagnosis (I wonder if the person was hit by a car and he has a coronavirus?) - this is the same “explosive mixture” that leads to a huge overstatement mortality approximation rate. The opposite approach is shown to us by South Korea and Germany. In these countries feasible (!) Records of easily ill patients are kept, which immediately leads to a decrease in mortality rates by almost an order of magnitude. But in these countries there are unaccounted for easily sick people, which should make an additional contribution to reducing mortality.

Thus, we should get a more accurate assessment of mortality as early as possible, because the state of the economy is critically dependent on it (I think everyone already felt this himself).

This can be done by deploying accelerated IgG antibody testing, and I believe that developing an IgG test should be a high priority right now. Knowing this, we will be able to estimate the true mortality much more accurately (exactly, only at the end of the epidemic).

Of course, someday this will be done, and I'm sure we will get many surprises. In the author’s personal opinion, even the estimates for Germany and South Korea are very high. In the most optimal case, mortality can be even lower than the severe seasonal flu virus (unlikely, but possible). This estimate is for developed countries, but with an honest death count system.

! Attention, the estimates presented here are the personal opinion of the author, and are not based on any confirmed theoretical basis. For decision-making, use only the official recommendations of WHO, Rospotrebnadzor, CDC or the services of your country of residence! I recall that according to WHO, the mortality rate of COVID-19 is 3.4%

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