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Coronavirus advances in Brazil

Covid-19 arrives with force as the country grapples with a dengue epidemic

Belo Horizonte, March 20, 2020: firefighters wearing protective gear participate in coronavirus training

Douglas Magno / AFP

With the number of Covid-19 infections and deaths growing daily, Brazil has gradually come to a stop as the population attempts to contain the spread of the virus. Having witnessed other countries dealing with the impacts of the pandemic, which started in China in December 2019 and arrived in Brazil in February 2020, the potential gravity of the situation is all too clear. By April 1, the SARS-CoV-2 virus had spread to 180 countries, with 926,000 reported cases and 46,000 deaths. In Brazil, there have been 240 deaths so far, and the number of cases—currently at 6,800—is doubling every 1–2 days and multiplying tenfold every week. The number is expected to increase even more rapidly from the end of April onward, when the temperature drops and respiratory diseases like Covid-19 spread more easily. The Pesquisa FAPESP website has a selection of maps showing the latest number of confirmed cases and deaths in Brazil and worldwide.

The first deaths in Brazil, recorded in São Paulo and Rio de Janeiro in March, led to rising apprehension about how the epidemic would spread around the country. Specialists from public health agencies and universities predict that the virus will infect tens of thousands of people in Brazil, with thousands of deaths as a result. The current global mortality rate, on average, is 3.4% of infected people, but this figure varies widely between countries—at 0.2% in Germany and Norway, 2.2% in France, 3.9% in China, 6.1% in Iran and 7.9% in Italy—depending on the health and age of those infected and their access to healthcare.

In the city of São Paulo, which has more than 12 million inhabitants, the streets are unrecognizable in the wake of SARS-CoV-2, with gridlock giving way to smoothly flowing traffic. In response to state government guidelines, schools, universities, museums, cultural centers, and shopping malls have all closed. Stores and public agencies have reduced their operating hours, while many companies have told their employees to work from home. Many other Brazilian cities followed suit, implementing measures similar to those already taken in other countries to restrict the circulation of people in an attempt to stop transmission of the virus.

The spread of Covid-19 can be compared to that of the Spanish flu, caused by a lethal strain of the influenza A virus, of the H1N1 subtype. Between 1918 and 1920, the Spanish flu spread around the world with devastating consequences: it infected around 500 million people—roughly one-third of the global population at the time—and killed between 25 and 50 million people, most aged 20 to 40 years old. In São Paulo, the epidemic killed 5,300 people, equivalent to 1% of the city’s population, within just a few months. Bodies accumulated on the streets waiting to be collected. In Rio de Janeiro, the situation was much the same. In 2009, a new pandemic (an epidemic that occurs worldwide) involving the H1N1 virus spread across the planet. Known as swine flu due to its origin in pigs, it was the first pandemic of the twenty-first century. It affected somewhere between 700 million and 1.4 billion people, causing 150,000–580,000 deaths. In Brazil, 58,000 individuals were infected and 2,100 died.

In March, Italy, Spain, and the USA suffered the most dramatic impacts of the coronavirus, with rapidly rising death tolls. China announced a drop in the number of cases and an end to local transmission, which allowed them to reopen factories and resume the many services that had been suspended as the virus spread. Other countries, meanwhile, were facing the arrival and spread of SARS-CoV-2, or were already feeling its economic effects: most businesses have closed while customers take refuge at home, stock markets have fallen, including Brazil’s, and production at companies that depend on parts imported from China has stopped. US President Donald Trump cited an increasingly likely recession when announcing an unprecedented $2 trillion set of economic measures to be imposed in the country.

Antonio Masiello / Getty Images Rome, March 17, 2020: medical team transports a Covid-19 patient to hospital on a sealed stretcherAntonio Masiello / Getty Images

Here in Brazil, the government announced emergency measures to reduce the economic impact of the epidemic, with the release of R$40 billion in aid over the next two months to help the most vulnerable sectors, such as informal workers (38 million people, 41% of the nation’s workforce) and small businesses. The federal government and the São Paulo state government have both declared a state of emergency, which should allow for increases in health spending and help reduce the economic impact of the pandemic in Brazil. The Central Bank estimated that instead of growing by 1.9% as forecast, the economy will shrink by between 3.2% and 7.7% because of the crisis.

Closing schools and stores, social distancing, encouraging people to stay at home, and quarantining those infected can all help to delay transmission and reduce the number of people requiring hospitalization at the same time, but they do not completely stop the virus from circulating, according to a report published in March by British epidemiologist Neil Ferguson of Imperial College London.

As more cities in Brazil decided to close schools, 41 million children aged 4–17 years have stopped going to classes and now spend their days at home with their parents. Because children can carry and transmit the virus even if they have only mild symptoms, leaving them with grandparents was not recommended, due to how lethal SARS-CoV-2 has proven in people over 60, especially those with cardiovascular disease, kidney problems, diabetes, or cancer.

The virus has changed people’s habits and given rise to the concept of social distancing, with recommendations including not to hug or kiss when greeting people, and to always stay at least 2 meters from others. “Social isolation measures have halved the virus’s contagion rate,” says infectious disease physician Júlio Croda, a researcher at the Oswaldo Cruz Foundation (FIOCRUZ), professor at the Federal University of Mato Grosso do Sul (UFMS), and member of the São Paulo State Coronavirus Contingency Committee, based on a study in its final stages at the end of March. The research indicates that the transmission rate has dropped from 4 to 2. According to Croda, the social isolation rate, based on data from cellphone operators, rose from 15% before the first Covid-19 case was recorded in Brazil to 60% at the end of March.

Although necessary to prevent the spread of the disease, this measure can have unwanted psychological effects. Pharmacist Poliana Carvalho, a researcher at the ABC Medical School, noted that depression, panic attacks, psychotic episodes, and delirium increased during the early phases of the severe acute respiratory syndrome (SARS) epidemic in 2002, which saw social isolation implemented as a means of stopping the virus. Caused by another variety of coronavirus that also emerged in China, SARS infected around 8,000 people and killed approximately 800 in 26 countries. Brazil was not affected. Even with the potential drawbacks, it is essential to maintain social isolation, as recommended by infectologists, to avoid an exponential increase in the number of cases and consequent collapse of healthcare systems (see report).

In a study published in the journal Psychiatry Research in April, Carvalho commented that the symptoms of the virus, such as fever, difficulty breathing, and a cough, added to insomnia and other side effects of drugs used against the disease, such as corticosteroids, can cause anxiety and aggravate mental illnesses. At a press conference in early March, when asked how to stop the contagious fear of epidemics, infectious disease specialist David Uip, coordinator of the São Paulo State Coronavirus Contingency Center—now in isolation having tested positive for SARS-CoV-2—replied to the media: “We rely on you.” “It’s very difficult,” says epidemiologist Eduardo Massad, a professor at the Getulio Vargas Foundation (FGV) in Rio de Janeiro.

In addition to encouraging social distancing, the Ministry of Health brought forward the start of the annual flu vaccination campaign for the elderly and health professionals—reducing the number of common flu patients makes it easier to diagnose coronavirus—and announced the possibility of increasing the number of beds in hospital intensive care units to prevent shortages if the number of serious cases grows beyond normal capacity.

Flu, measles, and dengue
The coming weeks of April, when the temperature drops—at least in the Southeast and South of the country—should give us an idea of the scale of this epidemic. “We must not forget about respiratory diseases caused by other viruses that are also more common in winter,” says Massad. From January to July 2019, the influenza virus, which infects many more people in the coldest months of the year (especially the H1N1 subtype, which is responsible for most cases), caused the death of 339 people in the country, with 1,576 serious cases recorded. According to the Ministry of Health, 81% of people who died from the flu last year were elderly, diabetic, had cardiovascular disease, or were under 5 years old. “In Brazil, we see most cases of influenza between May and October,” says epidemiologist Paulo Menezes, coordinator of the Disease Control Team at the São Paulo State Department of Health (SES-SP).

“On top of this,” he adds, “we are experiencing a measles epidemic.” Although it was eliminated from Brazil in 2016, the measles virus reappeared in 2018. In 2019, the country recorded 17,529 cases and 14 deaths. From January to March this year, the state of São Paulo had 280 cases of measles and one death.

And there is another problem: “We are also in the midst of a major dengue epidemic,” says physician Ester Sabino, a researcher at the USP School of Medicine. In the first 10 weeks of this year, the country recorded 332,000 cases of dengue fever—an increase of 45% over the same period in 2019—with 77 deaths.

“We have to learn from what other countries are doing to stop the coronavirus,” she says. Sabino is concerned about the virus being transmitted from infected people to other patients or staff at hospitals where they are being treated, as well as potential patient overload: “There is no healthcare system in the world that can handle so many people at the same time. Many died in China because there were not enough doctors or respirators available to treat everyone at the same time” (see interview).

SARS-CoV-2 is transmitted through droplets of saliva. It is highly contagious and while some infected people get sick quickly, others remain asymptomatic, but continue to spread the disease. It has had a much greater impact than that of recent epidemics, such as Zika and dengue fever, both of which are spread by the Aedes aegypti mosquito, common in tropical and subtropical regions. The current measles outbreak affects people who have not been vaccinated. Covid-19 is potentially the most dangerous because it is directly transmitted between individuals, there is no vaccine, and it is not specific to any particular climate.

In the lab
“The coronavirus epidemic will hopefully reinforce the fact that influenza is a disease and needs to be taken more seriously,” says biomedical scientist Danielle Oliveira, a researcher at USP’s Institute of Biomedical Sciences. “Health professionals often say that the flu is ‘no big deal’ and send patients back to work, when they should recommend isolation to prevent transmission.”

On February 29, Oliveira received samples of SARS-CoV-2 from the first two patients identified in the city of São Paulo, tasked with isolating and multiplying them to facilitate the diagnosis. Having previously studied another coronavirus, NL66, which causes respiratory disease mainly in children, she had a culture medium made from monkey kidney cells ready and waiting for the new biological material. Three days later, she already had samples of genetic material—the virus’s RNA—to send to other laboratories.

The virus has been studied intensively. In a paper published in the journal Science on March 13, researchers from the University of Texas and the National Institutes of Health, both in the USA, described the molecular structure of a protein on the surface of the novel coronavirus that allows it to infect human cells. According to the study, the spikey surface of the Sars-CoV-2 molecule is similar to the structure of the virus that causes SARS. However, antibodies that recognized the agent responsible for SARS proved to be ineffective in stopping the novel coronavirus. The research showed that the ability of SARS-CoV-2 to bind with the angiotensin-converting enzyme (ACE2) and release its genetic material inside human cells is up to 20 times greater than that of the SARS virus (view infographic).

Due to underreporting, it is believed that the virus could be spreading faster than official records indicate. Only 14% of the people infected before Wuhan, China, adopted travel restrictions on January 23 were officially recorded, argued researchers from the University of London, UK, in an article published in Science on March 16. According to the study, unrecorded infections were the source of the virus in 79% of confirmed cases.

In a study completed in early March, Massad found that one in 1,333 travelers could be infected with SARS-CoV-2, with each having a 23% chance of generating secondary cases in disease-free areas. Every infected person, he estimated, could transmit the virus to an average of five others.

“New diseases are initially spread by the middle class, who travel more,” says epidemiologist Gizelda Katz, from the Epidemiological Surveillance Center at SES-SP. This was the case in 2009 with the H1N1 flu virus, which was brought to Brazil from the USA; in 2010 with measles, which arrived with people who were infected in Norway, Israel, and Malta; and now with SARS-CoV-2, coming from Italy. “The Spanish flu took three months to spread worldwide in the early twentieth century—this coronavirus took just 48 hours,” observes virologist Edson Durigon, from USP’s Institute of Biomedical Sciences.

In search of a solution
FAPESP issues emergency calls for coronavirus research proposals

In March, FAPESP issued two emergency calls for research proposals, worth a total of R$30 million, to support projects developed by teams at research institutions or micro and small companies interested in studying the infection caused by SARS-CoV-2 and developing new containment strategies, diagnostic tests, or medications to slow or stop the epidemic.

The first call for proposals, with a planned investment of R$10 million, is aimed at research groups wishing to partially redirect projects already underway to attempt to learn more about Covid-19 risk reduction, prevention, and management, or about the SARS-CoV-2 virus itself. The projects must be linked to Thematic Project or Young Investigator grants, a Research, Innovation, and Dissemination Center (RIDC), or the Engineering Research Center (CPE). Each proposal must have a maximum term of 24 months and a budget of up to R$200,000. The deadline for submitting research projects is June 22, 2020. Due to the urgency of the topic, proposals will be analyzed as they are received.

The second call, issued in partnership with the Brazilian Funding Authority for Studies and Projects (FINEP) and worth R$20 million, will support companies of up to 250 employees wishing to create or implement innovative processes or products, such as diagnostic tests, ventilators, protective equipment for healthcare professionals, digital technologies, and artificial intelligence for patient care and health services. The call for proposals is part of Phase 3 of the Research for Innovation in Small Businesses program (RISB, or PIPE in the Portuguese acronym). Each research project will be granted up to R$1.5 million and must be carried out within 24 months. The deadline for submitting proposals is April 6.

The calls can be read in full at fapesp.br/14082 and fapesp.br/14087.

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