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How will the Corona crisis continue?: There’s a problem with predicting the pandemic’s future

How will the Corona crisis continue? : There’s a problem with predicting the pandemic’s future

More and more initiatives are calling for short and hard lockdowns to slow down the coronavirus. They rely on modeling of the pandemic. But it's hard to recreate epidemics in a supercomputer. One uncertainty factor is to blame: humans.

Humans would be only too happy to look into the future in the current pandemic. Obvious questions are: How much do which measures from the lockdown repertoire slow down the spread of the virus? How do border closures work? Are open opera houses more dangerous than open restaurants? Models can only vaguely approach such fine questions because, for example, each opera hall is an individual in terms of ventilation.

Nevertheless, the core of a pandemic can certainly be calculated with mathematical equations and its mechanics can be recognised.

An epidemiological model is much simpler than a climate model; on the other hand, the variables involved, such as individual human behavior, are more difficult to assess. Physics professor Dirk Brockmann, an epidemiology modeler at the Robert Koch Institute (RKI) and Berlin's Humboldt University, described it this way to Berlin's taz newspaper: Climate models, unlike pandemic models, were "based on solid physics that is known to be correct." They are more solid for long-term forecasts over many decades than epidemiological models over months, he said, the latter being most comparable to a weather forecast model. "Humans are the sticking point," Brockmann says. Specifically, how a person behaves in the short term in the midst of a virus outbreak.

Professor Michael Meyer-Herrmann, for example, explained his "model finding" at a Corona Prime Ministers Conference in October. "Turning the ship" meant at that time: avoiding loss of control over exponential growth. Six months earlier, the modeling epidemiologist, head of the Systems Immunology Division at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany, had already mathematically determined the alternatives: According to this, weak lockdowns in alternation cause the same number of infected people and costs, while a tighter lockdown would bring medium-term benefits for the economy and individual freedoms. Professor Clemens Fürst, head of the Ifo Institute for Economic Research, supported the "end with a scare" scenario. But policymakers lacked the courage to do so.

Half-hearted lockdowns have a major drawback

Now, there are more and more initiatives calling for short and hard lockdowns - and they are based on the very same modeling. Professor Viola Priesemann of the Max Planck Institute for Dynamics and Self-Organization is leading the way. Her findings in one sentence: Low case numbers are the best solution for society and the economy.

The debate has only touched on one major disadvantage of half-hearted lockdowns: that many infected people also increase the risk of mutations. The more virus carriers, the more selection pressure for Sars-CoV-2, the greater the "playground" for microbial evolution to create mutants, which then - recombined by chance - lead to virus variants that reproduce better.

Vaccines also increase this selection pressure: they provoke powerful and different antibodies in the human immune system, which are supposed to block the virus at its spike protein, with which it docks to the human cell. Because the virus does not want to die a vaccine death, it accelerates its evolution and forms a large number of mutants, from which those that can defy the antibodies are then filtered out. Researchers then speak of "escape mutants" (escape mutation). A similar pressure on the virus arises from herd immunity, when a large proportion of the population has become immune as a result of surviving an infection and - from the viral perspective - the number of new hosts to infect becomes scarce.

Some researchers interpret the emergence of the South African variant B.1351 as a response to the onset of herd immunity in some townships. The emergence of the new Brazilian variant P.1, which is causing re-infections in the Amazonian metropolis of Manaus, which is infested with the wild type, could also be explained in this way.

However, it is often not a single mutant that gives rise to a new virus variant. Take N501Y, for example. This has already emerged more frequently worldwide and in different regions of the world without spreading fear and terror. Specifically, the spike protein, with which the virus docks onto the human host cell, comprises around 1300 amino acids, and at position 501 the amino acid asparagine has been replaced by tyrosine. Hence the name N501Y. But this alone did not lead to a more infectious virus variant. Another mutation (or several) had to be added for infectivity to increase.

Evolution always works according to the survival-of-the-fittest principle

Which genetic changes have to combine and how in order for the virus to be up to 35 percent more effective in human-to-human transmission (as determined for the English variant) is still unknown. On the other hand, the fact that N501Y occurs in the English variant (B.1.1.7), in the South African variant (B.1.351) as well as in the Brazilian variant (P.1) fuels the suspicion that virus evolution is not purely clocked by chance. After all, the sites of origin are thousands of kilometers apart. On the other hand, the rule of the game is that evolution always "works" according to the survival-of-the-fittest principle. An invisible compass, calibrated for maximum offspring, seems to sort the mutants. In Brazil and South Africa, the E484K mutation has also emerged, which is suspected of enabling re-infection.

Can the formation of certain mutations be simulated in the laboratory in a similar way to the spread of a pandemic in a model? In principle, yes. Scientists use cell cultures to play out evolution in fast motion, so to speak. At the University of Washington in Seattle, a team led by Allison Greaney experimented and discovered that E484K is "the most important site" on the so-called receptor-binding domain (RBD) of the sting protein. The E484K mutation reduces the effect of human antibodies "by at least more than tenfold." In their study, the team concludes, "The evolution of Sars-CoV-2 could affect the recognition of the virus by human antibodies." On the other hand: the gene-based mRNA sera can be quickly adapted in such a case.

Laboratory experiments, however, can simulate only a tiny slice of the vast volume of mutation that exists in the free play of forces in nature. The dimension of possibilities is moving toward infinity, especially in the viral kingdom. The struggle between microbe and human can be imagined like the classic game of rabbit and hedgehog. The immune systems of the host organisms can hardly defeat the viruses with their ability to mutate, but neither can it happen the other way around. There remains a dynamic balance between attack (viruses) and defense (hosts), which has always been described as a "race" since the 1930s. From this point on, the invention of the electron microscope made it possible for humans to see viruses in the first place.

(Original text: Wolfgang Wiedlich; Translation: Mareike Graepel)