New Covid-19 Variants Reshape Our Understanding of Reinfection

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

In previous articles in this series, I have explored how SARS-CoV-2 changes, how these changes contribute to immune evasion, and what it all means for global vaccination efforts.

One aspect of SARS-CoV-2 of particular relevance to this discussion – which remains under-examined more broadly – is its ability to re-infect the same host twice. While re-infections of Covid-19 have been previously reported and confirmed, the case of a 45-year-old woman in Brazil is the first to involve the E484K mutation, a defining feature of the South African variant 501.V2. It’s also a mutation that experts fear will escape even a robust immune response.

The re-infected woman is a health worker who lives in the coastal city of Salvador, Bahia and has kept a detailed record of her symptoms. According to the pre-impression study documenting her case, her first infection, which began in mid-May 2020 and lasted for about seven days, caused diarrhea, muscle pain and fatigue. She took a corticosteroid called prednisone to treat it, and within three weeks, she was back to business as usual. The second time, however, was much worse. It started almost 150 days later in late October and involved severe symptoms in addition to those she had experienced before – including a sore throat, difficult breathing, and exhaustion.

Although the woman may have recovered very well from her first Covid-19 infection, that did not stop her from developing a severe case within months. This raises the worrying possibility that the natural immunity we develop against one variant of SARS-CoV-2 does not protect another. This follows the results of a preprinted study that mapped the effects of different advanced protein mutations on the potency of antibodies used in experimental Covid-19 treatments, including drugs based on monoclonal antibodies. Mutations at the E484 site, where E484K is found, prevented 9 of 11 different monoclonal antibodies from binding. (Another site on the spike protein, F456, inhibited 11 of 11.)

The Brazilian case of reinfection confirms what we should have recognized long ago: The recent outbreak of viral variations is just one piece of a much larger puzzle, which will challenge our understanding of the crisis for many. month. Our understanding of the immunology of SARS-CoV-2 remains tenuous at best. To truly make progress in our collective mission to reduce its impact on human life, we must accept the fact that this virus is not just here to stay, but in some ways, it is just beginning. Which brings me to the subject of my next piece in this series – the first reports of viral variation in the United States.