Gamma (P1) is more aggressive but can be contained with vaccine and lockdown, study shows

Correlating whole-genome sequencing with epidemiological data for the city of São José do Rio Preto in Brazil, researchers show that severe COVID-19 and deaths from the disease rose sharply when the variant became prevalent in the region. A two-week lockdown and vaccination of the elderly averted a collapse of the health system.

By Maria Fernanda Ziegler | Agência FAPESP – By correlating whole-genome sequences with epidemiological data, researchers have demonstrated the role played by the SARS-CoV-2 Gamma variant (P.1) in the surge in COVID-19 cases and deaths in São José do Rio Preto, state of São Paulo, Brazil. They found that the variant’s higher transmissibility was associated with sharp rises in severe cases (127%) and deaths (162%) in the city in March and April 2021.

The study is published on the preprint platform medRxiv and has not yet been peer-reviewed. It stresses the importance of vaccination to protect the population and the effectiveness of a two-week lockdown imposed in March to contain the spread of the disease.

“These findings were expected, but they needed to be clearly demonstrated because of all the fake news and confusion. Our study confirmed that vaccines protect people against dying from COVID-19 and that lockdowns genuinely do reduce circulation of the virus. We also showed, at a time when this wasn’t clear to the scientific community, that P.1 [the Gamma variant] is indeed more aggressive,” said Maurício Lacerda Nogueira, a professor at the São José do Rio Preto Medical School (FAMERP) and last author of the article.

The study was conducted by FAMERP’s Virology Laboratory in partnership with São Paulo State University (UNESP), the University of São Paulo (USP), the Bill & Melinda Gates Foundation, the University of Washington, University of Texas Medical Branch, and the City of São José do Rio Preto Department of Health. Funding was provided mainly by FAPESP, Rede Corona-ômica (a research network maintained by the Ministry of Science, Technology and Innovation via the Brazilian Innovation Agency (FINEP), and the National Council for Scientific and Technological Development (CNPq)), Butantan Institute, and the US National Institutes of Health (NIH).

Genomic surveillance of SARS-CoV-2 in the region has been ongoing as part of the project since October 2020. In the study, the researchers analyzed 272 whole-genome sequences to detect the prevalence of variants. They identified 12 lineages, among which the most prevalent were P.1 (72.4%), P.2 (11%), B.1.1.28 (5.6%), and N.9 (4.6%).

Dance of the variants

Variants are mutant forms of the virus, and although the epidemiological behavior of the vast majority of variants is similar to that of the ancestral strain, some are deemed “variants of concern” because they appear more transmissible, and possibly more lethal. P.1 (Gamma) was first detected in Manaus, Amazonas, in early November 2020, spreading rapidly to other parts of Brazil, especially the Southeast region.

B.1.1.7 (Alpha), first detected in the United Kingdom in December 2020, is considered 30%-50% more transmissible, with a 30% higher severity rate. B.1.351 (Beta), first detected in South Africa, is associated with a heightened risk of transmission and reduced viral neutralization by monoclonal antibodies, convalescent sera and post-vaccination sera. B.1.617 (Delta), detected for the first time in India at end-2020, has spread around the world and is considered responsible for the recent surge in cases in Europe, the United States and China.

Gamma variant case study

According to Nogueira, cases and deaths in São José do Rio Preto spiked in December 2020, and in February of this year. The numbers began rising very sharply in March.

“Our analysis showed that several variants were circulating in the city in October. In December, however, it pointed to the predominance of P.2 [first detected in Rio de Janeiro], possibly resulting in the rise in cases but without a rise in the severity rate,” he said. “We detected the first case involving P.1 in the city on January 26, 2021, and shortly afterward this strain became dominant. As of March, there was a rise of more than 100% in the numbers of severe cases and deaths.”

P.2 cannot be blamed for the rise in cases at end-2020, he added, because mobility, and hence transmission of the disease, increased nationwide in the holiday season. In the case of P.1 (Gamma), however, the correlation can be proven, bringing closure to a heated debate in the scientific community as to whether this variant was actually more aggressive and responsible for more deaths.

“Studies conducted in Manaus pointed to a large number of deaths, and health services in Amazonas state collapsed in January, with oxygen supplies running out, patients dying because they couldn’t breathe, and even babies in incubators having to be transferred for treatment in other states [not necessarily for COVID-19]. Besides the variant, several other well-known factors led to this humanitarian crisis,” he said.

The situation in São José do Rio Preto in March differed from the situation in Manaus in January. With 400,000 inhabitants, São José do Rio Preto ranks twelfth among the cities of São Paulo state by population. It has an efficient public health system, and opted for lockdown when the transmission of P.1 surged. “The health system wasn’t overwhelmed and there was no shortage of oxygen,” Nogueira said. “It was a very bad time, with 300 patients in ICUs [intensive care units] at one point, but even so there was some spare capacity. We had one or two days when no hospital beds were available. Nevertheless, mortality was much higher than in previous waves because P.1 is a more aggressive variant.”

Vaccines save lives

Another important factor was vaccination of the elderly during the period in which P.1 was driving up the numbers of cases and deaths in the city. “While P.1 was spreading in the city, practically 100% of our inhabitants over 70 had been vaccinated, mostly with CoronaVac,” Nogueira said. “According to the study, 60%-70% of this vaccinated population are protected against severe disease and death, which is very good news.”

The group’s genomic surveillance research continues, he added. They will investigate what happened last year, before the new variants were detected, and what happens during the months ahead. “We continue to do these analyses and correlations on a weekly basis,” he said. “We haven’t yet detected the Delta variant in the city, but I believe it’s a matter of time until we do. The study will enable us to track the probable competition between Delta and Gamma.”

The Gamma variant has been detected in the UK and US, but not yet on the European continent, he noted. “Gamma hasn’t competed directly with Delta in Europe, but it may be happening in Brazil, as evidenced by studies in Rio de Janeiro, where the prevalence of Delta is advancing,” he said.

The article “Effects of SARS-CoV-2 P.1 introduction and the impact of COVID-19 vaccination on the epidemiological landscape of São José do Rio Preto, Brazil” by Cecília Artico Banho et al. is at: www.medrxiv.org/content/10.1101/2021.07.28.21261228v1.