After two days of more hopeful signs that new cases of the novel coronavirus in China might be stabilizing, a sharp increase of 14,840 new COVID-19 infections was reported Thursday by the Province of Hubei, more than 10 times the previous day.

Meanwhile, Vietnamese authorities had reportedly imposed a mass quarantine on a number of villages in the Son Loi commune, about 40 kilometers from Hanoi, where six among the 16 cases confirmed so far in Viet Nam, have been reported. It was the first mass quarantine to be placed on an entire community outside of China where over 50 million people remain under partial or total lockdown in the city of Wuhan and around Hubei Province, where the novel coronavirus first first emerged in a wild animal market in December 2019.

The upsurge in China cases was in part due to an expansion of diagnostic criteria, said Hubei officials in a statement. Those who show clinical signs of COVID-19 were previously not included in the count, which only tallied lab-confirmed cases. However, officials amended the definition so that patients who show clear symptoms of the disease based on clinical exams and chest x-rays “can receive standardized treatment…as early as possible to further improve the success rate of treatment”[translated from Chinese].

A total of 59,907 cases had been reported in China on Thursday, according to the latest Chinese government data, posted just before midnight Beijing time. There was also a steep 48-hour increase in deaths, with total fatalities inside China now at 1,368. The second death outside of China was registered in Japan, in a woman in her 80s. Some 500 people in 24 other countries were also infected with the virus as of Thursday evening, central European time.

“This increase that you have seen in the past 24 hours is largely due to a change in how cases are being diagnosed and reported,” said WHO’s Emergencies Director, Mike Ryan at a press briefing Thursday, explaining the huge leap in case reports in Hubei Province, the epidemic epicentre.  “We need to be very careful in interpreting any extremes.” He noted that some of the increase is also attributable to clinical cases reported days or even weeks ago, but only included now after the reporting criteria was changed.

There were further spikes in the two biggest COVID-19 hot spots outside of China.  On the Princess Diamond Cruise ship, where more than 3600 passengers and crew remained quarantined in Japan’s Yokohama harbor, a total of 218 passengers tested positive for the virus, a leap of 44 cases since Wednesday. Singapore, the next largest cluster, was reporting 58 cases Thursday evening, 11 more than Wednesday.

Experts are carefully watching trends in the Asian city-state, where original contacts for some of the Singaporeans falling ill cannot be traced. This has sparked fears that wider community-based spread of the virus may be occurring, making Singapore the next test ground for virus containment. Elsewhere, conferences and meetings were being delayed or cancelled, and school start dates suspended, as the fallout from the virus echoed across the Western Pacific region, Europe, and beyond.

The sharp uptick in reported cases on Thursday occured only hours after Dr Tedros Adhanom Ghebreyesus, World Health Organization director general warned that ¨the number of newly reported cases reported from China has stabilized over the past week, but that must be interpreted with extreme caution.”

“The outbreak could still go in any direction” he told reporters Wednesday after the conclusion of a two-day Global Research and Innovation Forum in Geneva, and just hours before Hubei province officials released the new daily numbers.

The forum sought to identify the best clinical care treatment for patients with the virus; explore why some people become seriously ill while others do not; as well as to forge ahead with a coordinated approach to research on potential treatments and vaccine candidates, said Dr Soumya Swaminathan, WHO chief scientist, describing outcomes of the meeting.

First Large-Scale China Study Finds Case Fatality Rate Higher Than Previous Estimates

Meanwhile, the first large-scale study of some 4,021 Chinese patients with COVID-19 reported that the case fatality rate of confirmed people who fell ill in January was averaging about 3%, significantly higher than the 2% fatality rate that had been cited previously.

According to a pre-print version of the study by researchers from China Centers for Disease Control (China CDC), published on MedRXiv, patients 60 years or older had even higher fatality rates of 5.4%, as compared to 1.43% for that of younger patients.

Male patients also had a case fatality rate more than triple that of female patients – 4.45% as compared to 1.25%, the study found.

The study, which examined cases in 30 Chinese provinces including the virus epicentre of Wuhan, also provides the first detailed age distribution of confirmed cases of the virus, which had been known to researchers as 2019-nCoV, until WHO gave it a formal name on Tuesday.

Despite the higher fatality rates than previously assumed, the new COVID-19 virus is still less deadly than Severe Acute Respiratory Syndrome (SARS), which had a case fatality rate of 9.2%, during the 2002-03 epidemic, the study’s authors conclude. The COVID-19 virus transmissibility is similar to that of SARS – with a single infected person passing the virus to nearly 4 other people [3.77], on average.

Among those studied, people aged 30-65 years comprised the majority of reported cases, while 47.7% of patients were age 50 and over. The lowest incidence of reported cases was among people under 20 years of age.

Overall, more men than women were reported to be infected, the study found – although gender differences in incidence were only significant outside of Wuhan.

“The high incidence subpopulation outside Wuhan tended to be younger than in Wuhan,” the study’s authors also noted.

The study is the first published report covering a large group of Chinese patients.  But WHO scientists have noted that the true case-fatality rate remains difficult to assess in the early stages. The fatality rate could also prove to be lower if many people with asymptomatic or mild infections are missed by hospital-based surveillance systems.

Experts Closely Watching new COVID-19 hubs like Singapore

Outside of China, global health experts were closely watching trends in Singapore, which has the largest concentration of COVID-19 cases outside of China – with the exception of the Diamond Princess cruise ship.

The most worrisome aspect of Singapore’s outbreak is the emergence of cases in people whose original contact with the virus couldn’t be traced, experts have observed. If the outbreak expands from known chains of contacts into more “community-based” transmission, then it’s “game over” in terms of containment and preventing a worldwide pandemic, in the words of one BBC commentator.

In fact, some experts are already using the so-called “P” word. Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, told Health Policy Watch.  There is a “real possibility that it’s a pandemic – which means it could be a worldwide epidemic where most citizens are at risk of being infected,” he said in an interview.

But while WHO is closely watching the “behaviour of the virus outside of China,” Mike Ryan, WHO’s Emergencies head, has sought to mitigate fears about virus expansion abroad. He notes that the number of cases where contacts cannot be traced remains limited.

Ultimately, public health officials need to  pursue a two-track strategy of both containment and preparation for further expansion. “We must stop the virus while preparing countries for the arrival of the virus…. even if that sounds like a contradiction,” Ryan said, speaking in a press briefing on Wednesday.

Speaking on Thursday he said, “We can only find eight cases [abroad] that are not linked in some way to one of the identified transmission chains,” he observed. He said that researchers are rushing to develop a simple blood test for virus antibodies. But in the absence of such a test, it is difficult to determine how much broader “community” transmission might be occuring. “This may be only the tip of the iceberg, or the iceberg may not be as great,” he said.

Clinical Trials For Vaccine Candidates Could Begin In April

Following the conclusion of the WHO Research and Innovation Forum, WHO’s Chief Scientist Swaminathan told Health Policy Watch that clinical trials of the first COVID-19 vaccine candidate, could begin as early as April.

She said that tests of the first vaccine candidate, an mRNA vaccine, are being supported by the Oslo-based Coalition Epidemic Preparedness Initiative (CEPI) as part of a collaboration with the pharmaceutical company Moderna and the US National Institutes of Health. The vaccine candidate functions on principles similar to vaccines tested against other coronaviruses, such as SARS.

Swaminathan said that she was optimistic about China’s ability to quickly ramp up manufacturing capacity to produce any new vaccine shown to be effective. “There was a Chinese vaccine company present at the meeting, and they were very interested in collaborating on this, and they did raise the issue of exploring manufacturing capacity from an early stage,” she said.

In terms of therapies, trials have already started on the widely-used HIV drug combination, lopinavir-ritonavir as well as on an experimental drug called remdesivir, she noted, although it is “too early” to identify what might be the most promising treatments.

Tests of other antivirals, some Chinese traditional medicines, and the FDA approved treatment for seasonal flu, oseltamivir (Tamiflu) are also rapidly being scaled up, she said.

But there are a broad range of other potential treatments as well, she observed: “When we look at our clinical study registry there are about 87 – 89 trials [of antivirals] already under way, and about one-third of them are clinical trials.”

WHO Protests Cases of Stranded Maritime Passengers

Meanwhile, cases of COVID-19 continued to climb aboard the Princess Diamond, the cruise ship that has been under quarantine in while docked in Yokohama, Japan, since 7 February.

Of the 48 new cases of infection outside of China that were reported on Wednesday, 40 were on the ship, noted WHO’s Dr Tedros in his briefing to the press. That adds up to 174 passengers with confirmed cases of the coronavirus.

Dr Tedros protested the fact that in the wake of the Princess Diamond case, two other cruise ships have also been turned away from ports, despite having no suspect cases of the coronavirus.

He said that WHO would be issuing a communique with the International Maritime Organization, asking countries to respect the principle of “free pratique”, for ships’ movement, and proper care of passengers.

And he praised Cambodia’s government for finally agreeing to allow one of two other cruise ships, the Westerdam, to dock, after days of being stranded in international waters.

“Based on what we have been told, there are no suspected or confirmed cases of COVID-19 on board the Westerdam,” he said, noting that the ship is due to arrive in Cambodia Thursday morning.

“This is an example of the international solidarity we have consistently been calling for,” he said.

Inside China – Rising Concerns Over Health Worker Infections & Freedom Of Speech

Inside China, there were growing concerns about the rate of health worker infections, as the South China Morning Post reported that over 500 medical workers had been infected by COVID-19 in Wuhan by mid-January. Although the Chinese government has been releasing daily case counts, no separate tally of health worker cases has been made public.

That issue surfaced against the continuing current of protest over how the Chinese authorities’ repression of free speech might have delayed warnings about the virus and exacerbated its spread in the early days, highlighted by a new petition circulating on freedom of speech. The petition has been signed by hundreds of Chinese, including a number of notable Chinese academics, reported the South China Morning Press.

The petition followed the widely-mourned death on 6 February of Li Wenliang, one of eight doctors punished by Wuhan authorities in early January for “spreading rumors,” after he tried to warn fellow health workers about the new coronavirus on a social media chat.

WHO and its Director General Dr Tedros have also been criticized for white-washing the Chinese repression of initial reports of the novel coronavirus, which is believed to have first infected people working in, or visiting, a wild animal market in Wuhan in December 2019.

Asked about such criticism at Thursday’s press briefing, the WHO head was adamant that he was not pandering to Chinese political pressures in his repeated praise for the Chinese response.

“China doesn’t need, or want, to be praised. Let the truth speak for itself and the world can judge,” he told journalists, adding that thanks to China’s response measures,  “The rest of the world is still safer and in a better shape.

“If there is any failure, that should be challenged. We will assess and learn from it,” he said, adding, “We should not be stigmatizing or attacking a country, but stand in solidarity and fight against this common enemy, COVID-19, as humanity because we are one. This virus attacks every human being.”

Grace Ren contributed to this story.

This story was updated 13 February 2020, at 3:19AM & 19:00 CET .

Image Credits: CNA News, Dingxiangyuan, Yang et al.2020, Medrxiv, Cattan2011.