Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the fourth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part onepart two, and part three.

In the previous articles of this series, I explored how SARS-CoV-2 changes, how those changes contribute to immune escape, and what this all means for global vaccination efforts.

An aspect of SARS-CoV-2 particularly relevant to this discussion—one that remains under-examined more broadly—is its ability to reinfect the same host twice. While Covid-19 reinfections have been reported and confirmed previously, the case of one 45-year-old woman in Brazil is the first to involve the mutation E484K, a defining feature of the South African variant 501.V2. It is also a mutation experts fear might evade even a robust immune response.

The woman reinfected is a health executive who lives in the coastal city of Salvador, Bahia and kept an extensive record of her symptoms. According to the preprint study documenting her case, her first infection, which began mid-May 2020 and lasted about seven days, caused diarrhea, muscle pain, and fatigue. She took a corticosteroid called prednisone to treat it, and in three weeks was back to business as usual. The second time around, however, was much worse. It began nearly 150 days later in late October and involved severe symptoms on top of ones she had already experienced—among them a sore throat, belabored breathing, and exhaustion.

Although the woman was able to recover from her first Covid-19 infection just fine, that didn’t prevent her from developing a severe case within months. This raises the worrying possibility that the natural immunity we develop to one variant of SARS-CoV-2 may not protect from another. This tracks with the findings of a preprint study that mapped the effects of different spike protein mutations on the potency of antibodies used in experimental Covid-19 treatments, including monoclonal antibody drugs. Mutations at site E484, where E484K is located, prevented 9 of 11 different monoclonal antibodies from binding. (Another site on the spike protein, F456, prevented 11 of 11.)

The Brazilian reinfection case confirms what we should’ve recognized long ago—that the recent surge in viral variation is only one piece of a much larger puzzle, one that will challenge our understanding of the crisis for many months to come. Our grasp of the immunology of SARS-CoV-2 remains tenuous at best. To truly make progress in our collective mission to lessen its toll on human life, we must accept the fact that this virus is not only here to stay, but in some respects just getting started. Which leads me to the subject of my next piece in this series—the first reports of viral variation in the United States.