The government has said the real number of infected people is likely significantly higher than the confirmed cases.

(Writing by Drazen Jorgic; Editing by Sandra Maler)

(Reuters) - A U.S. federal appeals court on Monday blocked California from requiring that Bayer AG label its glyphosate-based weed killer Roundup with a cancer warning, handing the company a victory in its ongoing litigation over the product.

In his ruling, U.S. District Judge William Shubb called California's cancer warning misleading and said the state's label is not backed up by regulatory findings.

Regulators worldwide have determined glyphosate to be safe with the exception of the World Health Organization's cancer research arm, which determined the herbicide to be a "probable carcinogen" in 2015.

Shubb on Monday said that finding alone did not support California's requirement to label glyphosate products with the term "known to the state of California to cause cancer."

Bayer in a statement welcomed the decision, calling the ruling very important for California agriculture and for science.

The ruling, which permanently bars California from requiring a cancer warning on glyphosate-based products, is separate from the wider litigation over whether Roundup causes a type of blood cancer.

Bayer, which acquired Roundup with its $63 billion purchase of Monsanto in 2018, faces lawsuits by more than 52,500 U.S. Roundup users, and juries in three trials have ordered the company to pay billions after finding the product caused cancer. Plaintiffs allege that Bayer manipulated studies and deceived the scientific community.

Bayer, which is appealing the verdicts, denies the claims and insists glyphosate does not cause cancer and is safe for people to use.

The company is pursuing an out-of-court settlement of the litigation, which analysts estimate could result in a $10 billion agreement.

The office for California Attorney General Xavier Becerra did not immediately respond to a request for comment.

More than a dozen agricultural groups together with Bayer sued California in 2017, saying the warning label threatens significant disruptions to the U.S. food production supply chain if farmers are no longer able to use glyphosate.

(Reporting by Tina Bellon in Warwick, Rhode Island; Additional reporting by Jonathan Stempel in New York; Editing by Bill Berkrot)

DEATHS AND INFECTIONS

* More than 8.99 million people have been reported to be infected by the novel coronavirus globally and 468,134​ have died, a Reuters tally showed as of 1600 GMT on Monday.

* For an interactive graphic tracking the global spread, open https://tmsnrt.rs/3aIRuz7 in an external browser.

* For a U.S.-focused tracker with state-by-state and county map, open https://tmsnrt.rs/2w7hX9T in an external browser.

* Eikon users, see MacroVitals (cpurl://apps.cp./cms/?navid=1592404098) for a case tracker and a summary of developments.

EUROPE

* The UK reported its lowest daily COVID-19 death toll since mid-March, health officials said on Monday.

* A weekly testing regime using a "no-swab" saliva test is being trialled in southern England and could result in a simpler and quicker way to detect outbreaks of the virus, the British government said.

AMERICAS

* Many countries that have been successful in tackling the coronavirus are seeing an increase in cases due to religious or leisure gatherings or in closed quarters like nightclubs and dormitories since relaxing curbs, WHO officials said.

* White House economic adviser Larry Kudlow said there is no second wave of the pandemic, even though there are some flare-ups in states such as Florida, and it is unlikely there will be widespread shutdowns across the country.

* After more than 100 days of a coronavirus lockdown, New York City residents celebrated the lifting of more restrictions by getting their first haircuts in months, shopping at reopened stores, and dining at outdoor cafes.

* Toronto will allow businesses to reopen starting on Wednesday, Ontario Premier Doug Ford said.

ASIA-PACIFIC

* Health authorities in South Korea said for the first time it is in the midst of a "second wave" of novel coronavirus infections around Seoul.

* India reported a record number of new cases and a death toll of more than 400 people in the past 24 hours as foreign embassies warned their citizens in the country that hospitals might not have beds for them.

MIDDLE EAST AND AFRICA

* Drivers of minibus taxis in South Africa's financial hub Gauteng went on strike to demand more financial support from the government, leaving thousands of commuters stranded.

* People in Saudi Arabia ventured out on Sunday night for the first time in three months to celebrate the end of a nationwide curfew.

MEDICAL DEVELOPMENTS

* Gilead Sciences Inc said it expects to be able to supply enough of its antiviral drug remdesivir by year end to treat more than 2 million COVID-19 patients.

* Levels of an antibody found in recovered COVID-19 patients fell sharply in 2-3 months after infection for both symptomatic and asymptomatic patients, according to a Chinese study, raising questions about the length of any immunity against the novel coronavirus.

ECONOMIC FALLOUT

* Small and mid-sized businesses around the world are being hit hardest and about a fifth say they risk shutting down permanently within three months, a survey by the International Trade Centre showed.

* U.S. home sales dropped to their lowest level in more than 9-1/2 years in May.

* British industrial output recorded its biggest quarterly fall on record during the three months to June, and a further decline is likely in the months to come, a survey showed.

* Italy is preparing a new spending package worth 15-20 billion euros, which will push its budget deficit beyond 11% of national output, a government source told Reuters.

(Compiled by Linda Pasquini and Devika Syamnath; Editing by William Maclean and Maju Samuel)

A federal judge in Sacramento on Monday granted Bayer's request to block the state from requiring the company or any businesses from providing a "clear and reasonable warning before exposing any individual to glyphosate," the report said https://bloom.bg/2YUijv0.

Bayer did not immediately respond to a Reuters request for comment.

Bayer, which acquired Roundup manufacturer Monsanto in a $63 billion deal in 2018, to date has faced three juries over claims that Roundup causes cancer.

The company has denied the allegations made by more than 42,700 plaintiffs in the United States, saying decades of studies have shown Roundup and glyphosate are safe for human use.

(Reporting by Aishwarya Nair in Bengaluru; Editing by Maju Samuel)

(Reuters) - Black Americans enrolled in Medicare were around four times as likely as their white counterparts to be hospitalized for COVID-19, U.S. government data released on Monday showed, highlighting significant racial disparities in health outcomes during the pandemic.

"The disparities in the data reflect longstanding challenges facing minority communities and low income older adults," said Seema Verma, administrator of the Centers for Medicare & Medicaid Services (CMS), which released the data.

The data showed that more than 325,000 Medicare beneficiaries were diagnosed with COVID-19 between Jan. 1 and May 16. Of those, more than 110,000 were hospitalized.

Black Americans had a hospitalization rate 465 per 100,000 Black Medicare beneficiaries. For other groups measured by CMS, the rates of per capita hospitalizations were 258 for Hispanics, 187 for Asians and 123 for whites.

Hospitalization rates were high for people who qualified for both the senior-focused Medicare program and the low-income-focused Medicaid program, at 473 per 100,000.

"Low socioeconomic status all wrapped up with racial disparities represents a powerful predictor of complications with COVID-19," Verma said during a briefing about the data.

Medicare beneficiaries with end-stage kidney disease were hospitalized for COVID-19 at a rate of 1,341 per 100,000.

Medicare is a federal health insurance program designed primarily for seniors, as well as some people with disabilities and end-stage kidney disease.

Verma said that CMS' ongoing push to reimburse providers based on health outcomes rather than paying them fixed fees for their services could help address racial disparities.

"When implemented effectively, (value-based reimbursement) encourages clinicians to care for the whole person and address the social risk factors that are so critical for our beneficiaries’ quality of life," Verma said.

The data is based on claims filed for reimbursement from Medicare and therefore operates at a delay of several weeks.

(Reporting by Trisha Roy and Carl O'Donnell; Editing by Shinjini Ganguli and Cynthia Osterman)

RIO DE JANEIRO/GENEVA (Reuters) - Brazil reached more than a million confirmed coronavirus cases and 50,000 deaths over the weekend as throngs of people swarmed Rio de Janeiro beaches, but the World Health Organization said on Monday that even more cases were likely going uncounted.

Brazil's health ministry said on Monday that an additional 21,432 confirmed cases of the virus and 654 new deaths had been registered in the previous 24 hours.

A day earlier, swimmers and sunbathers packed Rio's famous beaches, with many neither wearing masks nor respecting the WHO's guidance to maintain 1 meter, or 3 feet, of distance between people.

As the toll climbs in Rio, the state with the second highest number of novel coronavirus cases, the local health secretary said on Monday he would resign after about month in office.

"I have only one thing to say: I tried," state health secretary Fernando Ferry said in a video on Brazilian broadcaster TV Globo, announcing his departure.

Ferry took the job after police began investigating the state health agency for suspicious state-level contracts and equipment purchases meant to address the pandemic. That triggered the state legislature to open impeachment proceedings against Rio's governor.

The turmoil among health officials in Rio mirrors that of the federal government, where two health ministers resigned in the span of a month. An active-duty military general with no medical background is now interim health minister.

The WHO is looking into a surge of more than 54,000 new coronavirus cases in Brazil in 24 hours, that was reported by the health ministry on Friday and is by far the most reported in the country in a single day, according to top WHO emergencies expert Mike Ryan.

Ryan told an online briefing on Monday that testing levels were still low in Brazil with a high percentage of positive results.

"That generally means there are probably more cases out there than reported," Ryan said.

As the toll continues to rise, local governments across Brazil have been gradually lifting lockdown orders.

(Reporting by Emma Farge in Geneva and Rodrigo Viga Gaier in Rio de Janeiro; additional reporting by Stephanie Nebehay in Geneva, John Revill in Zurich and Ricardo Moraes and Pedro Fonseca in Rio de Janeiro; Writing by Jake Spring; Editing by Aurora Ellis)

(Reuters) - The following is a brief roundup of some of the latest scientific studies on the novel coronavirus and efforts to find treatments and vaccines for COVID-19, the illness caused by the virus.

Metformin tied to lower risk of COVID-19 death in women

Women taking the widely used oral diabetes medication metformin may be at lower risk for fatal COVID-19, according to a study posted on Saturday that has not yet been peer-reviewed. Among more than 6,200 adults with diabetes or obesity and commercial insurance who were hospitalized with COVID-19, there were fewer deaths among women who had filled their 90-day metformin prescriptions than among those not taking the medicine. After adjusting for other risk factors, they were roughly 21% to 24% less likely to die of the disease. The link was not seen in men. "We know that metformin has different effects between men and women. In the diabetes prevention trial, metformin reduced CRP (the inflammation marker C-reactive protein) twice as much in women as men," study coauthor Carolyn Bramante of the University of Minnesota told Reuters. Metformin also decreases levels of TNF-alpha, an inflammation protein that appears to make COVID-19 worse, she said. Studies have suggested metformin may bring down TNF-alpha levels to a greater extent in women than in men, she added. "The fact that we saw the benefit in women only, and the fact that metformin lowers TNF-alpha in female mice, might suggest that the TNF-alpha effects of metformin are why it helps in COVID-19," Bramante said. Formal clinical trials are needed to confirm the theories raised by this observational study. Metformin is a safe, cheap and widely available medicine, making it "a very realistic treatment" if proven in larger trials, she added. (https://bit.ly/317D2yi)

Crucial immune cells failing to respond to virus

An important set of immune cells is failing to respond properly to the novel coronavirus, providing a possible explanation for why some patients appear mildly ill at first and suddenly deteriorate, according to new research from Hong Kong. The dendritic cells are supposed to alert the immune system to the presence of virus or bacteria, so that other immune cells, called macrophages, can attack and "kill" the invaders. While infected macrophages respond properly to the virus, infected dendritic cells fail to send out their usual alarms in the form of proteins called interferons, researchers reported on Sunday in the Journal of Infectious Diseases. Furthermore, in dendritic cells the virus inhibits a crucial protein called STAT1, which activates interferons and other important substances, they report. Coauthors Kwok-Yung Yuen and Jasper Fuk-Woo Chan of the University of Hong Kong told Reuters in a joint email that these dendritic cell dysfunctions may contribute to symptoms in some patients. (https://bit.ly/2YnCd2x)

Ceramic used in spine implants inactivates coronavirus

Silicon nitride, a ceramic often used in spinal implants because it kills bacteria by releasing disinfectant chemicals from its surface, can also inactivate the new coronavirus, according to a new study. In laboratory experiments, researchers in Japan exposed coronavirus particles to silicon nitride, aluminum nitride, and copper particles. All three materials showed greater than 99% viral inactivation after one minute, but silicone nitride is the safest of the three. Virus treated by the other two substances could still damage cells in other ways, the researchers reported on Saturday in a not-yet-peer-reviewed paper. "Further studies are needed to validate these findings and investigate whether silicon nitride can be incorporated into personal protective equipment and commonly touched surfaces, as a strategy to discourage viral persistence and disease spread," the researchers said. Shares of ceramics company SiNtx Technologies Inc, which makes the silicon nitride powder, jumped 170% on the report. (https://bit.ly/2YlscCO)

Antibody levels in recovered COVID-19 patients decline quickly

Antibody levels in recovered COVID-19 patients fell sharply within a few months after infection, according to a Chinese study of 37 symptomatic and 37 asymptomatic individuals, raising questions about the length of immunity an infection may confer against the novel coronavirus. Over 90% of those who initially had IgG antibodies - one of the main types of antibody induced after infection - showed sharp declines in 2 to 3 months. The research, published in Nature Medicine, highlights the risks of using COVID-19 "immunity passports" and supports the prolonged use of public health interventions such as social distancing and isolating high-risk groups, researchers said. (https://reut.rs/2BsFjZZ; https://go.nature.com/2NkCay6)

New storage solution may allow safer collection, transport of coronavirus test swabs

Researchers in Brazil have developed a way to make handling infected test swab samples from COVID-19 patients less risky for healthcare workers. In every sample-collection kit, they include a storage solution that inactivates the infectious parts of virus without affecting the integrity of the viral RNA that diagnostic tests look for. The solution is made of a salt buffer with guanidine, explained Flávio Guimarães da Fonseca of Federal University of Minas Gerais in Belo Horizonte. "Guanidine is a denaturing chemical that destroys proteins. Therefore the protein components of the virus are degraded (killing the virus) while the virus genetic material is preserved for up to 16 days, even at room temperature," he told Reuters. "This is a particularly important feature in developing countries with limitations in diagnostic laboratory availability, as well as difficult logistics to take samples to the labs." The treated virus fails to grow on cultured cells, he said, adding that many laboratories in Belo Horizonte are already using the solution. One limitation of the work, he notes, is that researchers did not compare their results to those of labs working with a regular, non-denaturing sampling solution. The report, posted on Saturday on medRxiv, has not yet been peer-reviewed. (https://bit.ly/3epMdh9)

(Reporting by Nancy Lapid, Roxanne Liu and Se Young Lee; Editing by Bill Berkrot)

The death toll is likely to register a spike on Tuesday, when health authorities add weekly data from nursing homes to figures from hospitals. Excluding nursing home cases, France has averaged 22 deaths per day over the last seven days and 33 since the start of the month.

The number of new confirmed cases on Monday was 89 more than Sunday, but still lower than the daily average of 483 seen over the last seven days and below the 409 daily average since the beginning of June.

The number of people in hospital with COVID-19 infections fell by 130 to 9,693, and those in intensive care fell by 14 to 701. Both numbers have been on a downtrend for at least 10 weeks.

(Reporting by Benoit Van Overstraeten; Editing by)

The CDC reported its tally of cases of the respiratory illness known as COVID-19, caused by a new coronavirus, as of 4 pm ET on June 21 versus its previous report on Sunday.(https://bit.ly/30XDNtF)

The CDC figures do not necessarily reflect cases reported by individual states.

(Reporting by Vishwadha Chander in Bengaluru; Editing by Shinjini Ganguli)

GENEVA/ZURICH (Reuters) - Coronavirus cases are soaring in several major countries at the same time, with "worrying increases" in Latin America, especially Brazil, the World Health Organization (WHO) said on Monday.

The world recorded more than 183,000 new coronavirus cases on Sunday, the most in a single day since the outbreak started in December, WHO chief Tedros Adhanom Ghebreyesus said.

"Certainly the numbers are increasing because the epidemic is developing in a number of populous countries at the same time and across the whole world," WHO's top emergencies expert, Mike Ryan, told an online briefing.

"Some of that increase may be attributed to increased testing ... And certainly countries like India are testing more. But we do not believe that this is a testing phenomenon."

Global cases surpassed 9 million on Monday, with the United States, China and other hard-hit countries also reporting new outbreaks, according to a Reuters tally.

Ryan said there had been a jump in cases in Chile, Argentina, Colombia, Panama, Bolivia and Guatemala, as well as Brazil, which had passed the 1 million mark - second only to the United States - and reported a record 54,000 cases in the previous 24 hours.

He said some of the jump in Brazil might reflect changes in the reporting system, but added:

"There still are relatively low tests per population, and the positivity rates for testing are still quite high overall. From that perspective, we would say that this trend is not reflective of exhaustive testing, but probably under-estimating the actual number of cases."

1,000 DEATHS A DAY

Latin America's largest country has frequently recorded more than 1,000 deaths a day over the last month.

President Jair Bolsonaro, sometimes called the "Tropical Trump", has been widely criticised for his handling of the crisis. The country still has no permanent health minister after losing two since April, following clashes with the president.

Bolsonaro has shunned social distancing, calling it a job-killing measure more dangerous than the virus itself. He has also promoted two anti-malarial drugs - chloroquine and hydroxychloroquine - as remedies, despite a lack of evidence that they work.

Ryan said he thought there had been "great upticks" in cases in a number of U.S. states.

"I'm not 100 percent sure about the age profile, but I've seen the reports that some of this is amongst younger people. That may reflect the fact that younger people are more mobile and they are getting out and taking advantage of the reductions in restrictions of movement ...

"What is clear is that the increase is not entirely explained through just increased testing."

The WHO also said it was worried about Germany, where the reproduction rate of the virus hit 2.88 on Sunday, well above the maximum level of one transmission per person needed to contain the disease over the longer term.

Tedros said a lack of global leadership and unity in fighting the virus was a bigger threat than the outbreak itself, and that politicisation had made the pandemic worse.

The WHO has been criticised by some member states, especially the United States, which says it was too weak, too slow and too "China-centric" in tackling the disease at the outset.

(Reporting by Stephanie Nebehay, Emma Farge in Geneva, John Revill in Zurich and Alexander Cornell in Dubai; Writing by Nick Macfie; Editing by Kevin Liffey)

WASHINGTON (Reuters) - President Donald Trump has not directed any slowdown in coronavirus testing and does not regret using the term "kung flu," which many consider to be offensive, to describe the virus, the White House said on Monday.

The Republican president said at a political rally in Oklahoma on Saturday that he had directed his people to slow down testing for the virus because the process had led to an increased number of known COVID-19 cases.

The White House said at the time that he was kidding and made clear on Monday that no such request was made.

"It was a comment that he made in jest," White House press secretary Kayleigh McEnany said at a news briefing. She said Trump had not told officials to slow the rate of testing. "He has not directed that," she said. "Any suggestion that testing has been curtailed is not rooted in fact."

Trump sees numerical measures as signs of victory or failure. He has repeatedly lamented the fact that better U.S. testing has led to a higher known number of identified coronavirus cases across the country.

Trump has also sought to reinforce that the virus originated in China.

But he has faced criticism for referring to the virus as Chinese. He refrained from that characterization for a time but at the rally on Saturday used "kung flu" to describe it, despite criticism that the use of such terms had led to acts of discrimination against Asian Americans.

Asked by a reporter why the president was using racist language, McEnany said he was not.

"He is linking it to its place of origin," she said. "I think the media is trying to play games with the terminology of this virus where the focus should be on the fact that China let this out of their country."

(Additional reporting by Doina Chiacu; Editing by Cynthia Osterman)

The decision runs counter to moves by other governments in West Africa that have sought to ease restrictions, despite rising case numbers, to allow the resumption of day-to-day economic activities that millions of citizens depend on to survive.

Liberia has so far confirmed 626 cases of COVID-19 and 34 deaths since registering its first case in mid-March. A state of emergency was declared on April 8 that included the quarantining of 15 counties and a requirement to stay indoors after 3pm.

But despite restrictions on movement, social distancing and wearing of masks, the number of people infected has "exponentially increased", Weah said in a proclamation, explaining the decision to extend the state of emergency.

Over the next 30 days, the government will re-examine its response to the pandemic and introduce measures to better protect Liberians, he said without giving further details.

Liberia is one of the world's poorest countries, and most people live without reliable access to electricity and clean water. The 2013-16 Ebola outbreak killed more than 4,800 people there, including more than 150 healthcare workers.

(Reporting by Alphonso Toweh; Writing by Alessandra Prentice; Editing by Pravin Char)

The study suggests that patients may be delaying or avoiding seeking care because of fear of COVID-19, researchers from the U.S. Centers for Disease Control and Prevention said.

A CDC study in May showed that the number of deaths in New York City from causes other than COVID-19 rose by more than 5,000 people above the seasonal norm during the first two months of the pandemic

After the COVID-19 pandemic was declared a national emergency in the United States, public health authorities recommended that hospitals delay non-urgent medical procedures such as surgeries.

Visits to the emergency department because of heart attacks fell 23%, ten weeks after the pandemic was declared a national emergency, compared with ten weeks before the emergency declaration.

Similarly, emergency departments recorded a 20% decline in visits because of stroke, and 10% less visits for hyperglycemic crisis, which arises because of uncontrolled diabetes.

"A short-term decline of this magnitude in the incidence of these conditions is biologically implausible," the researchers said in the CDC's Morbidity and Mortality Weekly report.

The study authors said that health officials should make sure the public is aware that emergency departments are implementing infection control guidelines so that people seek emergency care when needed.

(Reporting by Manas Mishra in Bengaluru; Editing by Alistair Bell)

(Reuters) - The death toll from the novel coronavirus reached over 120,000 in the United States, according to a Reuters tally on Monday, as new cases spike in several states.

More Americans have now died from COVID-19 than were killed fighting in World War One.

About 800 Americans have died on average each day so far in June, down from a peak of 2,000 a day in April, according to the tally of state and county data on COVID-19 deaths. (Reuters interactive: https://tmsnrt.rs/2w7hX9T)

Total U.S. coronavirus cases are over 2.2 million, the highest in the world, followed by Brazil with more than 1 million cases, and infections are rapidly rising in India.

After weeks of declining, U.S. coronavirus cases nationally are rising again with 12 states reporting record increases in cases last week as all states moved forward with reopening their economies. On Saturday, over 30,000 new cases were reported, the highest daily total since May 1, according to a Reuters tally.

Among states with record increases was Oklahoma, where President Donald Trump on Saturday addressed a less-than-full indoor arena in Tulsa, where only a handful of attendees wore masks.

In remarks that his campaign said later were a joke, he told cheering supporters he had asked U.S. officials to slow down testing for COVID-19, calling it a "double-edged sword" that led to more cases being discovered.

A White House official said Trump was "obviously kidding. We are leading the world in testing and have conducted 25 million-plus in testing."

Health experts say expanded diagnostic testing accounts for some, but not all, of the growth in cases. They also call it a key tool in fighting the spread of the disease.

Of the 20 most severely affected countries, the United States ranks seventh based on deaths per capita, according to a Reuters tally. The United States has 3.6 fatalities per 10,000 people. Belgium is first with 8.5 deaths per 10,000, followed by the United Kingdom, Spain, Italy and Sweden, according to the Reuters analysis.

(Writing by Lisa Shumaker; Editing by Nick Zieminski)

"What is clear is that the increase is not entirely explained through increased testing. There is some evidence of increasing hospitalisation," he told an online briefing.

(Reporting by Stephanie Nebehay, Emma Farge and John Revill, Writing by Nick Macfie; Editing by Hugh Lawson)

South Korea said for the first time on Monday it was in the midst of a "second wave" of infections around Seoul, driven by small but persistent outbreaks stemming from a holiday in May.

"There are many countries right now that have had success in suppressing transmission and bringing human-to-human transmission to a low level that are starting to see increasing cases," WHO epidemiologist and technical lead on the pandemic Maria Van Kerkhove said, naming South Korea as one of them.

She stopped short of describing it as a "second wave".

"Any opportunity that the virus has to take hold, it will," she said, urging countries to "put everything they can" into isolating such cases to prevent renewed community transmission.

The WHO’s top emergencies expert, Mike Ryan, said that there seemed to be new clusters in South Korea linked to clubs, shelters and amusement parks but said that overall case numbers were "very, very stable or actually dropping" and praised Seoul's approach.

"My understanding is that the vast majority of cases being detected are linked to existing and recognised clusters and as such the South Korean authorities still have great visibility over where the virus is and the dynamics within which the chains are transmitting," he said.

(Reporting by Stephanie Nebehay, Emma Farge and John Revill; Editing by Nick Macfie)

He said the next big challenge was to increase production and distribution of dexamethasone, the first drug shown to lower the risk of death in severely ill COVID-19 patients.

Global infections surpassed 9 million on Monday, as Brazil and India grappled with a surge in cases and the United States, China and other hard-hit countries reported new outbreaks, according to a Reuters tally.

(Reporting by Stephanie Nebehay, Emma Farge and John Revill, Writing by Nick Macfie; Editing by Hugh Lawson)

(Reuters) - Global cases of the novel coronavirus surpassed 9 million on Monday, as Brazil and India grappled with a surge in infections, and the United States, China and other hard-hit countries reported new outbreaks, according to a Reuters tally.

The first case was reported in China in early January and it took until mid-May to reach 4.5 million cases. It has taken just five weeks to double to 9 million cases, the tally shows.

The United States leads the world with the highest number of infections, at about 2.2 million or 25% of all reported cases.

The tally shows the disease is spreading fastest in Latin America, which now accounts for 23% of all cases.

Brazil has the second most cases behind the United States, and India is on track to overtake Russia as the third most affected country by cases.

The number of global infections continues to rise at a rate of around 1%-2% a day since the beginning of June, even as many countries are taking steps to ease lockdown measures.

On Friday, global cases rose by a record 176,000 in a day, according to the tally, when Brazil reported over 54,000 cases in a single day, the most of any country throughout the pandemic.

Global deaths stand at over 464,000 and have doubled in seven weeks.

The crisis is deepening in Brazil where the death toll is over 50,000, widespread testing is absent, and the country is still without a permanent health minister.

In the United States, which has about 120,000 deaths, cases are rising again after declining for more than a month and wearing a mask is not mandatory in most states.

China is also trying to contain a fresh outbreak in Beijing, where it asserts it has a capacity to test over 1 million people a day in the city alone.

On its best day, the United States tested over 594,000 people nationwide but often tests fewer than half a million a day.

Even in Germany, a country seen as successful in curbing the virus and limiting deaths, infection rates are rising above the level needed for long-term containment. Australia is also battling a spike in cases in Victoria where other states have seen few, if any, new cases in weeks.

Still there are bright spots such as Spain reopening its borders, death rates plunging in the former hot spot of Italy, and Greece welcoming a return of foreign tourists.

Just under half of all reported cases have recovered, though the number is likely higher as some countries do not report the statistic.

(GRAPHIC- World-focused tracker with country-by-country interactive: https://graphics.reuters.com/HEALTH-CORONAVIRUS/COUNTRIES/oakveqlyvrd/index.html?id=united-kingdom)

(Writing by Lisa Shumaker and Cate Cadell; Editing by Howard Goller)

NEW YORK (Reuters) - New York City residents, gradually emerging from more than 100 days of coronavirus lockdown, celebrated an easing of social-distancing restrictions on Monday by shopping at reopened stores, dining at outdoor cafes and getting their first haircuts in months.

But even as New Yorkers, confined for weeks at the epicenter of the global pandemic, returned to some semblance of normalcy, alarming spikes in coronavirus infection rates elsewhere around the country worried public health experts.

Chief among the latest hotspots was Florida, one of the last states to impose stay-at-home restrictions and one of the first to begin lifting them, with nearly 3,000 new infections reported over the previous 24 hours. Arizona, meanwhile, had almost 2,200 additional cases since Sunday.

The two are prime examples of a troubling trend, mostly in the South and West, where the percentage of positive test results among all people who are screened - a metric called the positivity rate - has climbed.

That is a consequence of people venturing back into public spaces without wearing masks and not practicing safe social-distancing, said Eric Toner, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore.

"Wherever people mix, wherever people have person-to-person contact, there will be spread of the virus," Toner told Reuters. "The question is not whether it will spread - that's a certainty. The question is how big that increase will be, and that's largely a function of what government and individuals do."

The World Health Organization considers positivity rates above 5% to be especially concerning, and widely watched data from Johns Hopkins University shows a dozen states with average rates over the past week exceeding that level and rising.

At least four were averaging double-digit rates, according to Johns Hopkins - Arizona at 20%, Florida and Utah both at 11%, and Texas at 10%. Texas also reported a record 5,000-plus new cases in a single day. The same states often have experienced surging hospitalizations.

BEGINNING TO RELAX

States hardest hit earlier in the pandemic, mainly in the Northeast, have generally been slower to resume commerce and public life.

New York City, the nation's most populous metropolitan area, was the last region to move into Phase 2 of New York state's economic reopening plan. Restaurants and bars began offering outdoor service and many retailers started to allow patrons back into their stores. Barber shops and hair salons welcomed customers for the first time since mid-March, with some fully booked for the next two weeks.

Playgrounds also reopened on Monday in New York City, which still accounts for more than a quarter of all U.S. lives lost to COVID-19, more than 120,000 to date, as the number of known infections nationwide rose above 2.3 million.

At the height of the outbreak, New York City's usually bustling streets were largely deserted, echoing around the clock with the wailing of ambulance sirens. New York state as a whole was losing 1,000 lives a day, hospitals were overwhelmed, and the dead filled makeshift morgues.

On Monday the state reported 10 additional deaths from the coronavirus. The usual traffic jams clogged city streets, and the sound of honking cars brought a welcome sense of a return to the ordinary.

Customers wearing face coverings lined up outside Clementine Bakery in the Brooklyn neighborhood of Bedford-Stuyvesant on Monday, and a few enjoyed the warm summer morning sipping iced coffee at scattered tables on the sidewalk.

"It feels like my life is starting to get back to normal a little bit. It feels really nice the fact that I can sit and have a coffee," said Arden Katine, 34, a teacher who lives nearby.

The outbreak in distant parts of the country worried New York Governor Andrew Cuomo, who said he was talking with neighboring states about placing restrictions on travelers from places such as Arizona and Florida. Earlier this year, Florida ordered arriving New Yorkers to self-quarantine for two weeks.

"It's more effective if we act as a regional collaboration, and I'm talking to them about putting in guidelines so we don't have people coming from these other states," Cuomo told MSNBC.

Even if the growth in confirmed cases partly reflects transmission among younger people less likely to require hospitalization, those individuals are still contagious and could infect the elderly and others at high risk of severe illness due to underlying health conditions, experts warn.

New York and New Jersey, another major hotspot months ago, are now at record lows of infection rates with 1% or 2% of diagnostic tests coming back positive.

On the West Coast, the number of new cases hit a record of nearly 5,400 in California, the first to impose statewide stay-at-home orders. Los Angeles County, the most populous in the state with 10 million residents, accounted for the bulk of the latest tally with 2,588 new infections.

(Reporting by Maria Caspani in New York and Nathan Layne in Wilton, Connecticut; Additional reporting by Julie Steenhuysen in Chicago, Peter Szekely in New York and Lisa Lambert in Washington; Writing by Lisa Shumaker and Steve Gorman; Editing by Howard Goller and Cynthia Osterman)

NEW YORK (Reuters Health) - Activation of delta opioid receptors inside cells is important for the relief of inflammatory pain, researchers report.

"Most medicines targeting receptors are designed to hit receptors at the cell surface and many can't cross the cell membrane," Dr. Michelle L. Halls of Monash University, in Parkville, Australia, told Reuters Health by email. "We are finding that in some cases, medicines would be much more effective if they were sent directly to the intracellular site where the receptor is active - in this case, endosomes."

G protein-coupled receptors (GCPRs), the targets of about a third of approved drugs, are considered to function principally at the cell surface, but endosomes are important sites of continued GPCR signaling. It remains unclear whether opioid receptors at the plasma membrane or in endosomes mediate the endogenous system of pain control.

Dr. Halls and colleagues investigated their hypothesis that opioids from the inflamed colon activate delta opioid receptors (DOPr) in endosomes of pain receptors (nociceptors) to evoke signals that bring long-lasting inhibition of excitability and analgesia and that DOPr in endosomes represent a superior therapeutic target for inflammatory pain.

Opioids from the inflamed colon cause a DOPr-mediated inhibition of nociceptors, and both opioids from the inflamed colon and agonists that evoke DOPr endocytosis cause a sustained decrease in excitability of nociceptors, the researchers report in PNAS.

DOPr endosomal signaling within the peripheral projections of colonic nociceptors appears to induce a sustained inhibition of mechanical sensitivity.

The researchers coupled the DOPr agonist DADLE to a liposome shell for targeting DOPr-positive nociceptors and incorporated it into a silica core for release in the endosomal environment. These nanoparticles activated DOPr at the plasma membrane, were preferentially endocytosed by DOPr-expressing cells and were delivered to DOPr-positive early endosomes.

These nanoparticles provided sustained inhibition of nociceptive excitability and relief from inflammatory pain in mice.

In contrast, similar nanoparticles containing a DOPr antagonist abolished the sustained inhibitory effect of DADLE.

"Prolonged activation of the delta-opioid receptor from endosomes inside the cell (and not at the plasma membrane) is really important for sustained pain relief," Dr. Halls said. "This occurs normally in response to inflammatory pain in the gut. We were able to cause sustained activation of delta-opioid receptors (and therefore prolonged pain relief) by delivering drugs directly to endosomes in preclinical models of pain."

Co-author Dr. Nigel W. Bunnett, also at Monash University, told Reuters Health by email, "Nanoparticles that deliver opioids to endosomes of pain-sensing neurons might provide superior relief from inflammatory pain. This finding has implications for treatment of inflammation-associated pain in many tissues - gut, joints, etc. The approach may allow use of lower doses of opioids, with fewer side effects."

"We can use nanoparticles to deliver simultaneously multiple drugs to relieve pain, thereby targeting the inherent redundancy of pain signaling," said Dr. Bunnett, a founding scientist of Endosome Therapeutics Inc.

The study did not have commercial funding.

SOURCE: https://bit.ly/2ANA0o3 PNAS, online June 16, 2020.