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The man behind Brazil's search for miracle COVID-19 cures

By Gabriel Stargardter

RIO DE JANEIRO (Reuters) -Brazilian President Jair Bolsonaro, addressing the nation last month in a social media video, touted the latest in a string of unconventional drugs he says can ease the country's COVID-19 crisis.

Bolsonaro - a vaccine skeptic and promoter of discredited treatments such as hydroxychloroquine - said this new drug, Proxalutamide, would "soon be available to all Brazil." He invited a little-known Health Ministry official, Helio Angotti, to expand on its promise.

Angotti, an eye doctor with no epidemiological experience, cited a domestic Proxalutamide study showing a 92% decrease in mortality risk among hospitalized COVID-19 patients. It was a dramatic claim amid a global struggle to find effective treatments. He said he aimed to "get it to the Brazilian population as soon as possible."

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But the study - co-authored by a consultant Angotti hired - hasn't been peer-reviewed or published, beyond a cursory results presentation the authors released in a March news conference. The drug does not have regulatory approval and isn't available for sale.

Alexandre Cavalcanti, director of Sao Paulo's HCor Research Institute, said the claimed effectiveness in the study Angotti cited far exceeds any vetted COVID-19 treatment.

"I don't believe it," said Cavalcanti, who co-authored a major study, published last year in the New England Journal of Medicine, that found hydroxychloroquine essentially useless for COVID-19.

As a comparison, Cavalcanti cited the commonly used steroid, Dexamethasone, has been shown to reduce deaths by up to one-third in patients with severe COVID-19. The Chinese biotech firm that makes Proxalutamide, Kintor Pharmaceutical Limited [9939.HK], has seen its stock soar as it touted the Brazilian study and reported other progress, Reuters reported in a related story https://reut.rs/3uPlT8p today.

The appearance with Bolsonaro was the latest sign of Angotti's rising influence amid a pandemic that has killed about 430,000 Brazilians. Current and former Health Ministry employees say the mid-level official has quietly amassed power by elevating what they say is questionable science to support Bolsonaro's convictions: that masks are useless, lockdowns are dangerous, vaccines are no silver bullet, and other miracle cures are available or soon will be.

Angotti declined to comment for this story. Bolsonaro's office and the Health Ministry did not respond to requests for comment.

Carlos Wambier, one of the co-authors of the Brazilian Proxalutamide study, acknowledged it lacked peer-review but said its findings were "really very encouraging." He dismissed its critics as "more concerned with politics than with scientific results."

"If the article is published, I believe any government in the world will pay attention," said Wambier, a dermatology professor at Brown University who specializes in cosmetic procedures such as Botox injections and tattoo removal.

Reuters reviewed internal ministry documents and interviewed over two dozen current and former officials, scientists and politicians to chart Angotti's rise in Bolsonaro's administration. Angotti last year became chief of the Health Ministry's Science, Technology, Innovation and Strategic Inputs (SCTIE) department. Among other duties, the SCTIE decides which drugs - not including vaccines - Brazil's vast public health system purchases.

The sources said his department's focus on unproven coronavirus remedies such as hydroxychloroquine, along with its opposition to masks and lockdowns, contributed to the explosive spread of the infectious P1 variant, which originated last year in Manaus, the capital of Amazonas state, and made Brazil one of the world's worst hotspots.

Federal prosecutors in Amazonas have accused Angotti of administrative misconduct, in a civil proceeding that can result in fines or job loss, for pushing health workers there to prescribe hydroxychloroquine. Angotti declined to comment on that accusation.

Angotti is also under scrutiny in a high-profile congressional probe into Bolsonaro's pandemic response. The Senate has been grilling administration officials in public hearings for about two weeks, and three senators have formally called for Angotti to testify before the investigative committee, which has not yet considered their requests. The committee will produce written findings but has no power to punish administration officials.

Angotti's ascent reveals the central role that unproven treatments continue to play in Brazil. It also exemplifies the unconventional makeup of Bolsonaro's government, a coalition of soldiers, free marketeers and social conservatives.

"Helio is the face of that anti-science group that seized control of the ministry," said Adriano Massuda, who led the SCTIE department in 2015. "It's the ideological wing of the Bolsonaro government that now gives orders at the Health Ministry."

Angotti's efforts to support Bolsonaro's pandemic strategy came as the administration - now on its fourth health minister of the pandemic - was widely criticized for Brazil's delayed vaccine rollout. https://www.reuters.com/article/health-coronavirus-brazil-vaccines-idCNL1N2JW1R3 As other nations scrambled to cut deals with pharmaceutical firms, Bolsonaro's administration was slow to secure vaccines for Brazil's 210 million people. About 15% of Brazilians have now received at least one dose, compared with 36% in neighboring Uruguay, 46% in the United States and between 20% and 35% in many European nations, according to Our World in Data, a nonprofit public-service research organization.

THREE CONSULTANTS AND A RESEARCH MEMO

Angotti taught at a university in southeastern Brazil before he joined the Health Ministry in 2019, when Bolsonaro took office. He served as a health education manager before being promoted last June. Like Bolsonaro, Angotti is an avowed follower of the esoteric Brazilian philosopher Olavo de Carvalho, who promotes false conspiracy theories including a claim that Pepsi used the cells of aborted fetuses as sweetener.

Bolsonaro, who took hydroxychloroquine when he contracted the virus last July, has questioned the safety and effectiveness of vaccines and declined to take a shot himself. Angotti declined to comment to Reuters on whether he considers vaccines effective.

By November of last year, Angotti had hired and assigned three consultants to find evidence to support Bolsonaro's medical claims, according to a Nov. 19 memo Angotti wrote. The memo, reviewed by Reuters, hasn't been previously reported.

Among the consultants were Ricardo Zimerman, an infectologist with some 60,000 followers on Instagram, where he regularly posts news about experimental COVID-19 treatments and photos of himself pumping iron. The two others were Bruno De Souza, a management professor at the Federal University of Pernambuco who also has a doctorate in psychology; and Rute Costa, a medical researcher.

The consultants did not respond to requests for comment.

Angotti's Nov. 19 memo instructed the consultants to "list and criticize the protocols and articles related to the different immunization proposals." The consultants were also to update the ministry protocol for treating COVID-19 with a cocktail of anti-malarials, such as hydroxychloroquine, along with other drugs. Angotti told them to add "the newest proposed therapies," showing how they can "save many lives."

The memo also directed the consultants to produce a "comprehensive assessment" of lockdowns, focusing on the "social and economic impacts of social isolation." In March, the consultants co-authored a study that went beyond examining social-isolation impacts and concluded that lockdowns were "associated" with the emergence of the P1 variant in Manaus, asserting that the virus had mutated in cooped-up households.

In early December, the consultants shocked some staffers on the ministry's coronavirus operations desk with a presentation on why masks don't work to control virus spread, according to two people present. Others were less surprised: When Bolsonaro visited the desk in October, officials were told not to wear masks, according to a person in attendance.

HYDROXYCHLOROQUINE TO THE RESCUE

As Angotti's team chased evidence for unproven treatments, the P1 variant exploded in Manaus, accounting for three-quarters of the city's cases by the end of January, according to a study by Fiocruz, a federally funded biomedical institute. The city's hospitals quickly ran out of oxygen; the variant soon spread across Brazil.

The Health Ministry sent at least 120,000 hydroxychloroquine pills to Amazonas state and flew 12 medical professionals to the city of Manaus to push healthcare workers to use anti-malarials. Zimerman, De Souza and Costa were in the group, according to a Feb. 23 statement sent by one of Angotti's colleagues to federal prosecutors in Amazonas, responding to their inquiries about the ministry's handling of the Manaus crisis. Angotti's SCTIE financed their trips, the statement says.

The ministry also deployed a short-lived phone app that purported to help medical professionals diagnose COVID-19 with a symptoms questionnaire - then instructed them to prescribe anti-malarials like hydroxychloroquine. The app was based on a diagnostic tool that Angotti's consultants helped to develop.

Less than two weeks after its January launch, Brazil's Federal Council of Medicine (CFM), which licenses and regulates medical professionals, asked the Health Ministry to deactivate the app because it claimed "scientific validation for drugs without international recognition." The council said the app had been available to people who were not doctors and that it encouraged them to self-medicate. The ministry shut the app down.

The focus on hydroxychloroquine in the Manaus crisis was emblematic of the Bolsonaro administration's failed pandemic response, said Felipe Naveca, one of the first scientists to study the P1 variant and the deputy research director at the Fiocruz Amazônia biomedical institute, the organization's outpost in Manaus.

"The scale of the problem was never taken seriously," he said. "So they focused on a miraculous solution that doesn't exist."

Amid the chaos in Manaus, one of Angotti's consultants, Zimerman, joined with other researchers to launch the study of Proxalutamide, the drug Bolsonaro and Angotti would later tout on the social media video. On March 10, just weeks after starting the study, the authors called a news conference in Manaus to announce their results.

"As a researcher, I can confirm that I've never seen anything like this - and I conduct a lot of trials," said Cadegiani, one of the study's co-authors. "We're not kidding around."

Cadegiani declined to comment on the criticisms of the study.

Cavalcanti, the Sao Paulo scientist, said the presentation of findings for the still-unpublished study didn't meet the standards for such research.

"That study is amateur," he said. "The way it was announced, how the data were presented, those guys are amateurs."

(Reporting by Gabriel Stargardter; editing by Brian Thevenot)