Experts monitoring coronavirus for signs of tipping point in coming weeks

It’s been one month since Chinese officials confirmed the appearance of a new form of coronavirus, dubbed 2019-nCoV by the World Health Organization, and experts say the unfolding outbreak is fast approaching a crucial inflection point.

Over the coming week or two, as authorities monitor rising case numbers in China and watch for person-to-person transmission among individuals who did not travel directly to China, it should become apparent if the outbreak can plausibly be held at bay or if it is destined to transition into a full-blown global pandemic.

One hopeful sign may have emerged on Friday, as WHO representatives noted a slight decrease in new cases reported in China. But they were quick to point out this might not mean much because of the tendency of numbers to zigzag in the early stages of an outbreak.

As of Friday, there were more than 34,000 cases of the new coronavirus reported worldwide, the vast majority in mainland China centred on Hubei, a single province with close to double the population of Canada.

At a news briefing in Geneva, Maria Van Kerkhove, technical lead of WHO’s health emergencies program, offered the following breakdown based on 17,000 case reports: Over all, the virus appears to produce only mild symptoms in 82 per cent of cases, with 15 per cent of cases classified as severe and the remaining 3 per cent going critical. The virus is currently fatal in 2 per cent of reported cases, although many experts suggest that percentage is likely to decline as more milder or asymptomatic cases come to light.

However, the total number of cases emerging at this point has experts puzzled, because it doesn’t fit with accounts that the virus emerged in mid-December, starting with a cluster of cases linked to a live animal market in the city of Wuhan.

To illustrate this, David Fisman, an epidemiologist at the University of Toronto’s Dalla Lana School of Public Health, created a model with minimal assumptions to try to fit the reported number of cases to what is known about the dynamics of an epidemic.

His results, published Wednesday in the Annals of Internal Medicine, strongly suggest the virus was more likely circulating in the human population of Wuhan as early as mid-November. This squares with other studies that argue there had to be more cases of the virus at an earlier time to match the current profile of the emerging outbreak.

Cumulative 2019-nCoV cases

A mathematical model shows how the reported cases of coronavirus fell short of what was more likely to be the actual number of cases by late January

Control

start

30 (in thousands)

Cumulative cases

Model estimates

Reported cases

20

Projected cases

No measures taken,

basic reproduction

number = 2.3

If reproduction number

reduced to 1.5

10

If reproduction number

reduced to 1

0

Nov. 18,

2019

Dec. 16

Jan. 13,

2020

Feb. 10

THE GLOBE AND MAIL, SOURCE: ASHLEIGH R. TUITE,

PHD, MPH; DAVID N. FISMAN, MD, MPH

Cumulative 2019-nCoV cases

A mathematical model shows how the reported cases of coronavirus fell short of what was more likely to be the actual number of cases by late January

Control start

30,000

Cumulative cases

Model estimates

Reported cases

Projected cases

20,000

No measures taken,

basic reproduction

number = 2.3

If reproduction number

reduced to 1.5

10,000

If reproduction number

reduced to 1

0

Nov. 18,

2019

Dec.

16

Jan. 13,

2020

Feb.

10

THE GLOBE AND MAIL, SOURCE: ASHLEIGH R. TUITE,

PHD, MPH; DAVID N. FISMAN, MD, MPH

Cumulative 2019-nCoV cases

A mathematical model shows how the reported cases of coronavirus fell short of what was more likely to be the actual number of cases by late January

Control start

30,000

Cumulative cases

Model estimates

Reported cases

20,000

Projected cases

No measures taken, basic reproduction number = 2.3

If reproduction number reduced to 1.5

If reproduction number reduced to 1

10,000

0

Nov. 18,

2019

Dec. 2

Dec. 16

Dec. 30

Jan. 13,

2020

Jan. 27

Feb. 10

Feb. 24

THE GLOBE AND MAIL, SOURCE: ASHLEIGH R. TUITE, PHD, MPH; DAVID N. FISMAN, MD, MPH

“I think [the outbreak’s] real age is greater than its official age,” Dr. Fisman said.

He added the dilemma for scientists trying to track the progress of the outbreak – both looking back and projecting forward – is akin to what astronomers must face when they peer into the universe and can only see distant galaxies as they once were, rather than as they exist now.

In this case, it is the serial interval of the virus – the time elapsed between successive cases as it is transmitted from person to person – that is partly to blame. If the serial interval is seven days, that means that the latest case numbers quoted by health officials are effectively telling us how active the virus was about one week ago and not what it’s doing right now.

“When you look at the numbers, what you’re seeing is not what’s happening today," Dr. Fisman said.

This explains why no one is yet prepared to say whether the extraordinary measures Chinese officials have imposed to contain the virus are having the desired effect. For example, if the virus has been present for longer than officially stated, then it has had more opportunity to spread before controls were imposed. New cases could be emerging and escaping detection in places where there is limited capacity to diagnose the pathogen.

“We currently have big blind spots in our global surveillance system,” said Steven Hoffman, a professor of global health, law and political science at York University in Toronto.

Dr. Hoffman added that prime territory for unreported cases includes Africa – a continent that is well connected to China through air travel, but where the WHO is still racing to deliver the necessary tools that would allow regional health agencies to test for the virus. Given what is known about the transmissibility of the coronavirus, it is implausible that it has not landed in Africa already, he said. (No confirmed cases had been reported in Africa.)

Another confounding factor is that relative to the SARS outbreak of 2003, the new coronavirus appears to be more transmissible but less lethal. That suggests it has evolved a better compatibility with its human hosts, making it harder to pin down.

Anatomy of a coronavirus

Coronaviruses get their name from the surrounding crown of “spike” proteins that protrude from the envelope of the virus. The shape of the spike protein functions as a key that can unlock the membrane of a host cell and allow the virus to deposit its RNA.

Spike protein

RNA

Envelope

Transmission of the Wuhan coronavirus

A virus survives by finding a host and using its living cells in which to replicate, or to have itself reproduced. When a virus invades a host, it enters its cells and hijacks the cell’s natural production systems to make new copies of itself. The replication process can result in tiny mistakes or changes in the new viruses produced, leading to the virus mutating.

HOST CELL

CELL

RECEPTORS

VIRUS

RNA

Virus attaches itself to cell receptor prior to entry

RNA released

RNA replicated

and packaged

NUCLEUS

Assembly

Release

REPLICATED

VIRUS

Small

changes

MURAT YÜKSELIR / THE GLOBE AND MAIL,

SOURCE: REUTERS; SCIENTIFIC ANIMATIONS

Anatomy of a coronavirus

Coronaviruses get their name from the surrounding crown of “spike” proteins that protrude from the envelope of the virus. The shape of the spike protein functions as a key that can unlock the membrane of a host cell and allow the virus to deposit its RNA.

Spike protein

RNA

Envelope

Transmission of the Wuhan coronavirus

A virus survives by finding a host and using its living cells in which to replicate, or to have itself reproduced. When a virus invades a host, it enters its cells and hijacks the cell’s natural production systems to make new copies of itself. The replication process can result in tiny mistakes or changes in the new viruses produced, leading to the virus mutating.

HOST CELL

CELL

RECEPTORS

VIRUS

RNA

Virus attaches itself to cell receptor prior to entry

RNA released

RNA replicated

and packaged

NUCLEUS

Assembly

Release

REPLICATED

VIRUS

Small

changes

MURAT YÜKSELIR / THE GLOBE AND MAIL,

SOURCE: REUTERS; SCIENTIFIC ANIMATIONS

Anatomy of a coronavirus

Coronaviruses get their name from the surrounding crown of “spike” proteins that protrude from the envelope of the virus. The shape of the spike protein functions as a key that can unlock the membrane of a host cell and allow the virus to deposit its RNA.

Spike protein

RNA

Envelope

Transmission of the Wuhan coronavirus

A virus survives by finding a host and using its living cells in which to replicate, or to have itself reproduced. When a virus invades a host, it enters its cells and hijacks the cell’s natural production systems to make new copies of itself. The replication process can result in tiny mistakes or changes in the new viruses produced, leading to the virus mutating.

HOST CELL

CELL

RECEPTORS

VIRUS

RNA

Virus attaches itself to

cell receptor prior to entry

RNA released

RNA replicated

and packaged

NUCLEUS

Assembly

Release

REPLICATED

VIRUS

Small

changes

MURAT YÜKSELIR / THE GLOBE AND MAIL, SOURCE: REUTERS; SCIENTIFIC ANIMATIONS

For Samira Mubareka, a microbiolgist and infectious disease specialist at Toronto’s Sunnybrook Health Sciences Centre, which handled the first Canadian cases of the new coronavirus, all of this underscores why it’s important for people to reduce the occurrence of seasonal respiratory viruses by getting flu shots, washing hands and staying home when sick. The point, she said, is to deny cover to anything new working its way through the population.

“I realize people may not make the connection," she said. "But the higher the level of baseline activity for respiratory viruses in the community, the more noise there is going to be.”