The SARS-CoV-2 virus, from the moment it made the leap to humans, picked up mutations and created new sex lines as it spread to different populations. In practice, the vast majority of these mutations make absolutely no difference; the resulting virus has the same characteristics as the unmutated form from which it is derived.
But there have been a number of cases where variants increase in frequency. Early in the pandemic, it was often the product of the variation that passed into a previously exposed population – a matter of chance rather than a feature of the virus. Separating these cases from cases where mutations make the virus more dangerous is a serious challenge. But this week, an international team of researchers published evidence showing that a variant first characterized in Brazil is likely to be a significant additional threat.
There is a lot of uncertainty about the details, but the virus seems to be more contagious and more likely to infect those who have immunity to other viral strains, and it can be even more deadly. And when the paper was written, the gender line was detected in more than 35 countries.
The second wave
Earlier this year, we described the situation in the Brazilian city of Manaus, which hit the first wave of coronavirus infections hard. But after that, the Brazilian government followed a long period of low infections, despite an indifferent response to the pandemic, which resulted in the city being able to reach an infection level sufficient to provide herd immunity.
The hopeful thought ended in December when a second wave of infections began in the city, which derailed the health care systems and caused another increase in deaths. The infection rates were so high that it raised the suspicion that there may be a new virus strain that could evade the immune response generated by infections during the first wave.
Brazilian health workers have responded to the increase in cases by sequencing the genomes of some viruses that cause second-wave infections. Before this second wave, only seven viral genomes were obtained from Amazonas, the state where Manaus is located. The new attempt increased the number by 184, although not all were complete genomes.
The genome revealed the presence of a lineage that researchers call P.1, which is an offshoot of a strain that occurred during the first wave. Since then, P.1 has picked up a large number of mutations, including 17 individual mutations that have altered the amino acid sequences of the proteins it encodes, one insertion of new bases, and three deletions of bases. This is a significant number of changes and indicates a high level of mutations since March. Timings indicate that P.1 originated in November, just before the start of the big second wave in Manaus.
During the second wave, the P.1 variant was not detected in the samples picked up, but only seven weeks later it was 87 percent of the viruses sampled. Viral genomes from elsewhere in Brazil have indicated that it also spreads rapidly in the country and appears in cities on popular flight routes from Manaus. This indicates that P.1 probably originated in the city.
What is this thing?
Tests for the virus using polymerase chain reaction (PCR) involve a cyclic amplification of the genome of the virus. As a result, if you start with more viral genomes, you will reach an observable level of signal within fewer cycles. This is thought to mean that the cycle count required to detect the virus provides a rough measure of the viral load carried by the person from whom the sample comes. In the case of the P.1 strain, tests showed a fairly consistent, if small, indication of increased viral load.
However, because the samples came after infection at different times, the researchers could not know if this indicated higher maximum levels of the virus or a longer infection duration. None is particularly good.
To try to understand how P.1 could affect the second wave of infections in Manaus, the researchers developed an epidemiological model that enabled them to detect two different strains of the virus. The first strain was set up with the typical characteristics of SARS-CoV-2. For the second time, they were able to adjust the characteristics of the virus, such as the immunity provided by previous infections and its transmissibility. This allowed them to determine which characteristics correspond to the dynamics of the second wave in Manaus.
Overall, the model suggests that P.1 is probably more transmissible than previous strains of SARS-CoV-2, and that it is probably about twice as contagious. There is also an indication that it may to some extent evade the immune response caused by past infections. The model suggests that there is at least a ten percent chance that the variant may evade immunity, but that is probably no more than a 50 percent chance.
There was evidence of increased mortality due to infection by the P.1 strain. But the timing of the increase in stress was of such a nature that the evidence came from a period in which the hospitals were on the verge of being overwhelmed. The authors therefore treat this possibility with caution.
What can cause these changes? At least ten of the mutations seen in the P1 strain affect the vein protein of the virus, which the virus uses to attach to cells that infect it. At least eight of the mutations were apparently selected in the course of the evolution of the strain, suggesting that they help make it more contagious. Three of the specific changes have also been seen in another genus of virus that has caused concern, and at least one of them has been shown to interfere with antibodies that attack the virus.
Although these data are not really a conclusive indication that P.1 is a clear threat to us, it certainly agrees with the case. And that would help explain why Manaus had two distinct waves of infection that hit a significant fraction of the city’s population. As the authors of the new article point out, we do not yet understand the effects of mutations that alter proteins targeted by antibodies. Before we get over it, we will not really know how to worry about P.1 and other variants.
Science, 2021. DOI: 10.1126 / science.abh2644 (On DOIs).