COVID-19 had already spread in Brazil when measures to contain it were implemented

Study determined how the disease was transmitted using genomic data for SARS-CoV-2 obtained by sequencing almost 500 viral isolates from Brazilian patients and cross-referencing this with air travel data and deaths from the disease in the period.

By Karina Toledo  |  Agência FAPESP – More than 100 different strains of the novel coronavirus SARS-CoV-2 came to Brazil in February-March 2020, but only three (probably from Europe) continued to spread in Brazil, giving rise to the more than 805,000 cases of COVID-19 confirmed by June 12.

These three strains emerged in the states of São Paulo and Rio de Janeiro between February 22 and 27, and community transmission was already established by early March, well before the health authorities recommended the introduction of a ban on air travel and other “non-pharmaceutical interventions” (NPIs) to contain transmission of the virus. On March 13 the Brazilian Ministry of Health issued guidelines on mobility restrictions such as stay-at-home orders and lockdowns, which were implemented by state and city governments about a week later. Brazil closed its land borders on March 19 and banned the entry of foreigners by air on March 27.

These are some of the findings of a study supported by FAPESP and published in Science.

“Our results evidence the existence of two phases of the epidemic in Brazil. The first was transmission over short distances within the states of São Paulo and Rio. In the second phase, beginning in early March, the disease spread over longer distances, meaning that infected people were already taking the virus from these two states to other parts of Brazil when the NPIs were implemented,” said Ester Sabino, a researcher in the University of São Paulo’s Institute of Tropical Medicine (IMT-USP) and one of two co-principal investigators for the project.

The researchers used a mobility-based transmission model, cross-referencing air travel data, and confirmed deaths from COVID-19 between February and April with genomic data for SARS-CoV-2 obtained by sequencing 490 viral isolates from patients diagnosed in 21 of Brazil’s 27 states (including the Federal District). The study was conducted under the aegis of the Brazil-UK Center for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE).

Despite the sharp fall in domestic air travel after mid-March, the researchers found that the average distance traveled per passenger in the period increased by 25%. This rise coincided with the transmission of SARS-CoV-2 from the major cities to the rest of the country.

“Our results shed light on the role of large and highly connected population centers in the rapid ignition and establishment of SARS-CoV-2, and provide evidence that current interventions remain insufficient to keep virus transmission under control in Brazil,” they write in the article.

Impact of social isolation measures

The contagion rate in Brazil was around 3 before the introduction of social isolation measures, meaning that each infected person transmitted the virus to three people on average, favoring exponential growth in the number of cases.

Although mobility restrictions and lockdowns were implemented when community transmission was already established and the virus had spread beyond São Paulo and Rio, they initially resulted in a significantly slower contagion rate.

The mobility-oriented transmission model showed that the contagion rate fell to less than 1 in the cities of São Paulo and Rio de Janeiro shortly after the NPIs were introduced, preventing the number of cases from rising exponentially and keeping hospitals from being overwhelmed.

However, as more people began ignoring the social isolation measures, the contagion rate slowly but surely rose to between 1 and 1.3, after which it did not fall. According to epidemiologists, numbers of cases and deaths do not decelerate until the contagion rate stays below 1 for several weeks.

An analysis based on phylogeography, combining viral genome sequencing and transmission location data, enabled the researchers to conclude that 104 strains of SARS-CoV-2 entered Brazil from abroad in the period, mainly from the United States.

The researchers grouped 75% of the strains sequenced in Brazil into three clades, with clade 1 comprising 186 genomes or 38%, clade 2 comprising 161 genomes or 33%, and clade 3 comprising 19 genomes or 4%. A clade is a monophyletic group of organisms with a common ancestor and its lineal descendants.

“It’s possible that other strains failed to spread because the social isolation measures had already been implemented when they entered Brazil,” Sabino said. “However, it’s highly likely that different clades will be identified as more viral isolates are sequenced in this country. In the United Kingdom, where more than 20,000 samples from COVID-19 patients have been sequenced, over 1,000 introductions of the virus have been identified.”

SARS-CoV-2’s genome has some 30,000 base pairs forming the viral RNA chain, Sabino explained. If the virus that infects a person mutates at the 200th RNA chain position, for example, everyone contaminated by that person will carry the strain with this mutation. “By cross-referencing this information with the date and location of sample collection, we can track the trajectory of the epidemic, which is only just beginning,” Sabino said.

More samples from the North region of Brazil will have to be sequenced in order to determine the origin of the strain that spread strongly through states such as Amazonas and Pará, for example. “What we do know is that river journeys between towns in the Amazon region contributed a great deal to the transmission of the virus,” she said.

In Sabino’s opinion, this kind of research helps scientists understand how the epidemic develops and the main routes along which the virus is transmitted. “This knowledge may enable us to learn the lessons needed to ensure that next time the right measures are implemented sooner and more effectively,” she said.

The article “Evolution and epidemic spread of SARS-CoV-2 in Brazil” can be retrieved from science.sciencemag.org/content/early/2020/07/22/science.abd2161.