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In mutant variants, has the coronavirus shown its best tricks?

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The rapid rise in different parts of the world of deadly, more infectious coronavirus variants that share new mutations is leading scientists to ask a critical question - has the SARS-CoV-2 virus shown its best cards, write Kate Kelland and Julie Steenhuysen here?

New variants first detected in such far-flung countries as Brazil, South Africa and Britain cropped up spontaneously within a few months late last year. All three share some of the same mutations in the important spike region of the virus used to enter and infect cells.

These include the E484k mutation, nicknamed “Eek” by some scientists for its apparent ability to evade natural immunity from previous COVID-19 infection and to reduce protection offered by current vaccines - all of which target the spike protein.

The appearance of similar mutations, independent of one another, springing up in different parts of the globe shows the coronavirus is undergoing “convergent evolution”, according to a dozen scientists interviewed by Reuters.

Although it will continue to mutate, immunologists and virologists said they suspect this coronavirus has a fixed number of moves in its arsenal.

The long-term impact for the virus’ survival, and whether a limit on the number of mutations makes it less dangerous, remains to be seen.

“It is plausible that this virus has a relatively limited number of antibody escape mutations it can make before it has played all of its cards, so to speak,” said Shane Crotty, a virologist at the La Jolla Institute for Immunology in San Diego.

That could enable drugmakers to stay on top of the virus as they develop booster vaccines directly targeting current variants, while governments struggle to tame a pandemic that has killed nearly 3 million people.

The idea that the virus could have a limited number of mutations has been circulating among experts since early February, and gathered momentum with the posting of a paper showing the spontaneous appearance of seven variants in the United States, all in the same region of the spike protein.

The process of different species independently evolving the same traits that improve survival odds is central to evolutionary biology. The vast scope of the coronavirus pandemic - with 127.3 million infections globally - allows scientists to observe it in real time.

“If you wanted to sort of write a little textbook about viral evolution, it’s happening right now,” Dr. Francis Collins, a geneticist and director of the U.S. National Institutes of Health, said in an interview.

Scientists saw the process on a smaller scale in 2018 as a dangerous H7N9 bird flu virus in China appeared to begin adapting to human hosts. But no pathogen has evolved under such global scrutiny as SARS-CoV-2.

Wendy Barclay, a virologist and professor at Imperial College London and a member of a scientific advisory panel to the UK government, said she is struck by the “amazing amount of convergent evolution we’re seeing” with SARS-CoV-2.

“There are these infamous mutations - E484K, N501Y and K417N - which all three variants of concern are accumulating. That, added together, is very strong biology that this is the best version of this virus in the given moment,” Barclay said.

It’s not that this coronavirus is especially clever, scientists said. Each time it infects people it makes copies of itself, and with each copy it can make mistakes. While some mistakes are insignificant one-offs, the ones that give the coronavirus a survival advantage tend to persist.

“If it keeps happening over and over again, it must be providing some real growth advantage to this virus,” Collins said.

Some specialists believe the virus may have a limited number of mutations it can sustain before compromising its fitness - or changing so much it is no longer the same virus.

“I don’t think it’s going to reinvent itself with extra teeth,” said Ian Jones, a professor of virology at Britain’s University of Reading.

“If it had an unlimited number of tricks...we would see an unlimited number of mutants, but we don’t,” said Michel Nussenzweig, an immunologist at Rockefeller University in New York.

Scientists remain cautious, however, and say predicting how a virus will mutate is challenging. If there are limits on how the coronavirus can evolve, that would simplify things for vaccine developers.

Novavax Inc is adapting its vaccine to target the South African variant that in lab tests appeared to render current vaccines less effective. Chief Executive Stan Erck said the virus can only change so much and still bind to human hosts, and hopes the vaccine will “cover the vast majority of strains that are circulating.”

If not, Novavax can continue matching its vaccine to new variants, he said.

Researchers are tracking the variants through data-sharing platforms such as the Global Initiative on Sharing Avian Flu Data, which houses a huge trove of coronavirus genomes.

Scientists recently identified seven U.S. coronavirus variants with mutations all occurring in the same location in a key portion of the virus, offering more evidence of convergent evolution.

Other teams are conducting experiments that expose the virus to antibodies to force it to mutate. In many cases, the same mutations, including the infamous E484K, appeared.

Such evidence adds to cautious optimism that mutations appear to share many of the same traits.

But the world must continue tracking changes in the virus, experts said, and choke off its ability to mutate by reducing transmission through vaccinations and measures that limit its spread.

“It’s shown a very strong set of opening moves,” Vaughn Cooper, an evolutionary biology specialist at the University of Pittsburgh School of Medicine, said of this coronavirus. “We don’t know what the end game is going to look like.”

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What you need to know about the coronavirus right now

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Here’s what you need to know about the coronavirus right now, writes Linda Noakes.

Brazil deaths on track to pass worst of US wave

Brazil’s brutal surge in COVID-19 deaths will soon surpass the worst of a record January wave in the United States, scientists forecast, with fatalities climbing for the first time above 4,000 in a day on Tuesday as the outbreak overwhelms hospitals.

Brazil’s overall death toll trails only the US outbreak, with nearly 337,000 killed, according to Health Ministry data, compared with more than 555,000 dead in the United States.

But with Brazil’s health-care system at the breaking point, the country could exceed total US deaths, despite having a population two-thirds that of the United States, two experts told Reuters.

India posts record cases

India’s second wave of infections continued to swell as it reported a record 115,736 new cases on Wednesday (7 April), a 13-fold increase in just over two months.

The federal government has asked states to decide on local curbs to control the spread of the virus, but has so far refused to impose any national lockdown after the last one in 2020 devastated its economy.

The total number of cases since the first recorded infection in India just over a year ago now stands at 12.8 million, making it the third worst hit country after the United States and Brazil.

Japan’s Osaka cancels Olympic torch run

Japan’s western region of Osaka on Wednesday cancelled Olympic torch events scheduled across the prefecture, as record infections prompted its government to declare a medical emergency.

Health authorities fear a virus variant is unleashing a fourth wave of infections just 107 days before the Tokyo Olympics begin, with a vaccination drive still at an early stage.

The prefecture reported 878 new infections on Wednesday, a second-straight day of record numbers. Severe cases have filled about 70% of hospital beds in the region.

UK begins rollout of Moderna vaccine

Britain begins rolling out Moderna’s COVID-19 vaccine on Wednesday in Wales and expects to be using it in the rest of the United Kingdom in the coming days in a boost to the country’s health system after supplies of shots started to slow.

Moderna will become the third vaccine to be used in Britain after the Oxford-AstraZeneca and Pfizer jabs and comes as the supply of shots from Astra starts to slow due to manufacturing issues including at a site in India.

The United Kingdom has vaccinated 31.6 million people with a first dose of a COVID-19 vaccine - and administered 5.5 million second doses. It will soon have vaccinated half of its total population.

A third of survivors suffer neurological or mental disorders

One in three COVID-19 survivors in a study of more than 230,000 mostly American patients were diagnosed with a brain or psychiatric disorder within six months, suggesting the pandemic could lead to a wave of mental and neurological problems, scientists said on Tuesday (6 April).

Researchers who conducted the analysis said it was not clear how the virus was linked to psychiatric conditions such as anxiety and depression, but that these were the most common diagnoses among the 14 disorders they looked at.

Post-COVID cases of stroke, dementia and other neurological disorders were rarer, the researchers said, but were still significant.

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IMF says more vaccine spending is fastest way to shore up public finances

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The COVID-19 pandemic will continue to swell global public debt in 2021, but spending more money to accelerate vaccinations is the fastest way to start to normalize government finances, the International Monetary Fund said on Wednesday (7 April), writes David Lawder.

The IMF said in its 2021 Fiscal Monitor report that if faster global vaccinations bring the virus under control sooner, more than $1 trillion in additional global tax revenue could be collected through 2025 in advanced economies.

If that same upside scenario in the Fund’s economic forecasts materializes, global GDP output could increase by $9 trillion during the same period as businesses reopen and hire more quickly, the IMF said.

“Vaccination will, thus, more than pay for itself, providing excellent value for public money invested in ramping up global vaccine production and distribution,” the IMF said in the report.

The IMF and the World Bank during their virtual Spring Meetings this week are urging member countries to keep up fiscal support for their economies and vulnerable citizens and businesses until the pandemic is firmly under control.

The Fund estimated governments have deployed some $16 trillion in pandemic-related fiscal support since the pandemic started through March 17 this year. That includes $10 trillion from additional spending and foregone revenue, and $6 trillion worth of government loans, guarantees and capital injections for businesses.

In 2021, the Fund projects fiscal deficits will shrink slightly in most countries as pandemic-related support expires or winds down, unemployment claims drop and revenues start to recover as businesses reopen.

Average overall budget deficits reached 11.7% of GDP for advanced economies in 2020 -- quadruple their 2.9% share in 2019 -- but they should narrow to 10.4% in 2021, the IMF said.

Deficits in emerging economies will also shrink slightly in 2021 to 7.7% of GDP for emerging market economies and to 4.9% for low-income economies.

Average worldwide public debt is projected to hit a record 99% of GDP in 2021 and to stabilize at that level after rising slightly from 97% in 2020. For advanced economies, debt will peak at 122.5% in 2021, up from 120.1% in 2020.

The IMF called for more targeted support for vulnerable households, including minorities, women and workers in low-paying jobs in the informal sectors of many economies. More focused support for small businesses was also needed, it said.

But it said some advanced countries with high debt levels may need to start rebuilding fiscal buffers to prepare for future shocks. It said those countries should develop multi-year frameworks for increasing revenues and rationalizing spending, giving priority to investments to fight climate change and reduce economic inequality.

In a Fiscal Monitor chapter released last week, the IMF said advanced economies could use more progressive income taxes, inheritance and property taxes, and taxes on “excess” corporate profits to help reduce inequalities exposed by the COVID-19 pandemic.

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A third of COVID survivors suffer neurological or mental disorders: study

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One in three COVID-19 survivors in a study of more than 230,000 mostly American patients were diagnosed with a brain or psychiatric disorder within six months, suggesting the pandemic could lead to a wave of mental and neurological problems, scientists said this week, writes Kate Kelland.

Researchers who conducted the analysis said it was not clear how the virus was linked to psychiatric conditions such as anxiety and depression, but that these were the most common diagnoses among the 14 disorders they looked at.

Post-COVID cases of stroke, dementia and other neurological disorders were rarer, the researchers said, but were still significant, especially in those who had severe COVID-19.

“Although the individual risks for most disorders are small, the effect across the whole population may be substantial,” said Paul Harrison, a professor of psychiatry at Oxford University who co-led the work.

Max Taquet, also an Oxford psychiatrist who worked with Harrison, noted that the study was not able to examine the biological or psychological mechanisms involved, but said urgent research is needed to identify these “with a view to preventing or treating them”.

Health experts are increasingly concerned by evidence of higher risks of brain and mental health disorders among COVID-19 survivors. A previous study by the same researchers found last year that 20% of COVID-19 survivors were diagnosed with a psychiatric disorder within three months.

The new findings, published in the Lancet Psychiatry journal, analysed health records of 236,379 COVID-19 patients, mostly from the United States, and found 34% had been diagnosed with neurological or psychiatric illnesses within six months.

The disorders were significantly more common in COVID-19 patients than in comparison groups of people who recovered from flu or other respiratory infections over the same time period, the scientists said, suggesting COVID-19 had a specific impact.

Anxiety, at 17%, and mood disorders, at 14%, were the most common, and did not appear to be related to how mild or severe the patient’s COVID-19 infection had been.

Among those who had been admitted to intensive care with severe COVID-19 however, 7% had a stroke within six months, and almost 2% were diagnosed with dementia.

Independent experts said the findings were worrying.

“This is a very important paper. It confirms beyond any reasonable doubt that COVID-19 affects both brain and mind in equal measure,” said Simon Wessely, chair of psychiatry at King’s College London.

“The impact COVID-19 is having on individuals’ mental health can be severe,” said Lea Milligan, chief executive of the MQ Mental Health research charity. “This is contributing to the already rising levels of mental illness and requires further, urgent research.”

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