Chasing mutations – the race to understand and curb the epidemic

3 Mar 2021

In his contribution to the Corona Lectures, LMU epidemiologist Michael Hoelscher discusses the implications of the emergence and rapid propagation of new mutants of the SARS-CoV-2 virus for vaccination strategies.

Syringe is filled with vaccine

© IMAGO / Eckel

The emergence of mutational variants of the coronavirus SARS-CoV-2 raises fundamental questions in relation to the future trajectory of the pandemic, the prospects of attaining herd immunity, and the efficacy of vaccines. In the UK, South Africa and Brazil, such mutants have already arisen, and spread rapidly. Such mutations are also being observed with increasing frequency in Germany, and researchers expect new variants to appear.

What are the implications of these developments for the effectiveness of vaccines? How can national and global vaccination strategies be modified to cope with novel variants? These are among the questions that Michael Hoelscher will address in his contribution to LMU’s Corona Lecture Series on March 9, 2021. As well as reviewing the course of the global epidemic, Hoelscher, Head of the Division of Infectious Diseases and Tropical Medicine at LMU, will focus in detail on the evolution of the disease in Munich and, in particular, on the data collected during the population-based KoCo19 study. Finally, he will consider what the insights gained so far can tell us about the probable future course of the epidemic.

Prof. Dr. med. Michael Hoelscher. Chasing mutations – the race to understand and curb the epidemic. Tue, March 9, 2021. 6.15-7.45 p.m.

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Three questions for Prof. Dr. med. Michael Hoelscher:

Mutant forms of SARS-CoV-2 are now in circulation in Germany. What are their implications for plans to relax lockdown restrictions?

Michael Hoelscher: That viruses mutate is a perfectly normal part of their life cycle. In every infected individual, mutations occur thousands of times every day. The vast majority of these mutations are so deleterious that the virus can no longer propagate. The only mutations that survive are those that confer a selective advantage, as for example in the case of the English and South African variants. While the English variant has a higher transmissibility and is somewhat more virulent, the South African mutation alters the virus in such a way that it is less likely to be recognized by the immune system. So, in principle, we are now dealing with three completely independent epidemics. – And while the measures taken have quite effectively reduced the numbers of new infections with the original, wild-type strain, the English variant is now spreading ever more rapidly. As soon as the current measures are relaxed, we will very probably see a steep rise in the numbers of new infections. The only factor that could have a suppressive impact is rising temperatures in April and May. So we must do everything we can to keep infection rates down for as long as possible.

Are the available vaccines likely to be less effective? If so, how long will it take to adapt them so that they provide protection against the new mutants?

Michael Hoelscher: As I just mentioned, SARS-CoV-2 viruses that carry the South African mutations are less efficiently recognized by the immune systems of already infected or vaccinated individuals. This does not automatically mean that vaccinations can no longer work at all. But it does look as if the body needs higher concentrations of antibodies to effectively fight this particular virus variant. That in turn means that we will probably require an earlier (third) injection – ideally with a vaccine that is specific for the variant. Adaptation of vaccines is feasible, but depending on the vaccine considered, it does raise various questions, some of which remain unanswered. Basically, RNA vaccines can be reconfigured within a few weeks. The question in that case concerns the tolerability of a third shot. Based on our practical experience, we already know that the second dose is significantly less well tolerated than the first. Whether or not this trend continues with a third shot is now under investigation. In the case of vector-based vaccines, it is conceivable that a third shot might have a markedly weaker effect because an immune response has developed against the vector itself, which leads to its rapid elimination. – Studies of these questions are now underway. A further possibility in this respect would be to use different vaccines in succession.

What can the trajectory of the epidemic so far and the data collected in your KoCo19 study tell us about the further course of the pandemic?

Michael Hoelscher: The changes observed in the estimated numbers of unrecorded cases are perhaps the most significant findings from the KoCo19 study. These results allow us to assess how effective our test strategy really is. Between early spring and early summer of last year, this parameter fell significantly, from a value of 4.5 to about 2. This shows that, by the end of this period, people were taking the disease more seriously and were more likely to be tested. We are about to begin a new third round of the KoCo-19 study to determine how many people were infected over the winter months. Overall, I expect that figure to be less than 10% of the inhabitants of Munich.

Our findings in relation to the temporal course of the antibody concentration in individuals who have recovered from SARS-CoV-2 infection are also of interest. We found that the antibody titer begins to decline slowly from around 240 days after infection. Seen in this light, the decision to postpone vaccination of already infected individuals for at least 6 months seems sensible.

Prof. Dr. med. Michael Hoelscher heads the Division of Infectious Diseases and Tropical Medicine at LMU, and has been involved in a variety of studies of coronaviruses. The first case of SARS-CoV-2 infection in Germany was diagnosed in his Institute.

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