In March 2020, the Brazilian city of Manaus, the largest urban area in the Amazon, identified its first case of Covid-19. Prevalence of the disease went on to peak in early May, bringing untold devastation to local hospitals, economies, and community life. Researchers estimate that by October, as many as 76 percent of the city’s two million residents had been infected—a proportion that exceeds most theoretical thresholds for population immunity, the World Health Organization’s included.
Were population immunity the glimmering light at the end of the tunnel some purport it to be, Manaus would be in the clear—and for a few short months, the virus did appear to recede. But recent weeks have seen a surge of fresh cases that is once again overwhelming the city, its health infrastructure, and its people. Cemeteries, already swamped the first time around, have traded individual plots for mass graves; many hospitals have run out of available beds and supplies of oxygen; and average deaths per day are up 22 percent from before. If three quarters of Manaus residents did develop some level of immunity as a result of last year’s outbreaks, it doesn’t appear to be doing much to deter the virus today.
So what gives? Epidemiological factors, for one. In Brazil, not unlike the United States, the adoption of public health interventions like mask-wearing and social distancing has been uneven, unsteady, and far too slow, obstructed at least in part by a central government, led by President Jair Bolsonaro, that denied and spread misinformation about the disease instead of implementing measures to contain it. But viral variation could also have a part to play in promoting the survival and resurgence of Covid-19 in Manaus—though to what extent, we’re not yet sure.
Here’s what we do know. Genomic sequencing, conducted retroactively on samples of viral RNA from Manaus residents dating back to late December, revealed that 42 percent belonged to a previously unidentified lineage of SARS-CoV-2. This new variant, now known as P.1, is the very same that Japanese travelers contracted and brought back to Tokyo earlier this month. P.1. was also confirmed, quite notably, to have caused at least one case of reinfection in Manaus, a 29-year-old woman with no chronic health issues or history of immunosuppression or chronic illness yet had Covid-19 twice, once in March and again in December.
How similar is P.1 to variants arising in other parts of the world? Quite similar, it turns out. P.1 has about 20 mutations, among them 17 unique amino acid alterations, three deletions, and an insertion. Two of these, which I’ve discussed at length in earlier stories, are N501Y and E484K—spike mutations that occur in the receptor binding domain and are associated with increased transmissibility. Along with an ORF1b deletion, P.1 has these mutations in common with B.1.1.7, the so-called UK variant, and 501.V2, the so-called South African variant. In all three, these mutations developed independently—a likely sign that they give the virus some kind of advantage, whether alone or in combination with other mutations, that increases its chances of survival.
If P.1 is now the dominant SARS-CoV-2 variant circulating in Manaus, that suggests it has an evolutionary edge that runs counter to the city’s immune defenses, meaning reinfections like the young woman’s will become more commonplace if they haven’t already. Either P.1 has found a way to directly evade the immune system, or it is so ruthlessly transmissible that partial immunity is no longer sufficient protection. Marcus Venecia Lacerda, an infectious disease specialist and resident of the city, told NPR he believes reinfections might be driving continued transmission. “What is happening,” Lacerda said, “is that people who had some small exposure to the virus in the past are becoming infected now.”
On the whole, Brazil has a population more youthful than most, which explains in part why Covid-19 has killed more Brazilians below the age of 60 than any other country. It could be the case that the youth of Manaus who developed asymptomatic or very mild infections last year had too weak an immune response to counter a more infectious virus. Regardless, the city’s second run-in with Covid-19 is a warning for anyone who still believes population immunity will take the edge of this disease. It also shows why remaining vigilant about safety measures, even with the arrival and distribution of vaccines, is so important. Whether through biological or epidemiological means, SARS-CoV-2 will find a way to exploit our weaknesses—just as P.1 did with the unfortunate people of Manaus.
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 sixth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, and part eight.