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When a handful of doctors in northern Italy recently claimed that the virus that causes COVID-19 appears to be losing steam, that it no longer seems to be the same “biological bomb” it was when the pandemic first hit, expert reaction ranged from bewilderment to horror. Some thought something must have been lost in translation.
Then, only days later, Dr. Donald Yealy, chief of emergency medicine at the University of Pittsburgh Medical Centre, a US$21 billion health enterprise that spans 40 hospitals across western and central Pennsylvania, New York State and Maryland, gathered his notes for his latest press briefing. Yealy remarked that, anecdotally, COVID-19 cases seem less severe than a few weeks ago. People aren’t requiring as much intensive care. The proportion needing to be placed on a ventilator to help them breathe has fallen. The total amount of the virus in those who test positive seems “much less” than in the earlier stages of the crisis.
Yealy said he wasn’t attributing the observations “solely or even predominantly” to mutations. “We simply don’t know.” Viral pandemics are dynamic and complicated, he said. They wax and wane. Numerous factors could be at play.
He knows how hungry people are for a glimmer of hopeful news about a virus occupying so many minds. In an interview this week with the National Post, he chose his words carefully. “I am not saying it’s gone away — the message isn’t to declare victory, or say that we have this beaten,” Yealy said.
“But it’s fair to say that the experience with the virus is changing.”
It’s been more than 100 days since the World Health Organization declared COVID-19 a pandemic on March 11; 100 days since Tedros Adhanom Ghebreyesus, WHO’s director-general, called on countries to “prepare and ready hospitals.” By then, 4,291 people had lost their lives. One hundred days later, the global death toll is nearing 450,000. Even as cases fall in Canada, no one is ruling out a second wave. Instead, health officials are bracing for the unknown.
While Yealy said people in his regions “don’t seem to have the same level of sickness as a few weeks ago,” several doctors in Canada said they have seen nothing of the kind, that there’s no evidence the virus is losing potency. “In short, no,” said Dr. Alan Drummond, of the Canadian Association of Emergency Physicians.
While the number of total confirmed cases in Ontario is falling, Toronto General Hospital’s Dr. Niall Ferguson sees no sign of “weakening,” though the hospital, because of its heroic life support program known as ECMO, receives some of the most severe cases.
“In the last 10 days, we still put five patients on extracorporeal life support, the most extreme support that we have for people who are failing mechanical ventilation,” said Ferguson, head of critical care for Toronto’s University Health Network. The youngest patient was 22.
In London, Ont., similar proportions of people are still being admitted to hospital and the ICU. The proportion requiring mechanical ventilation hasn’t changed; it’s still around two-thirds of patients, said Dr. Wael Haddara, chief of critical care medicine at London Health Sciences Centre. “So, there is no indication that the severity has diminished at all.”
In fact, the opposite might be true. Doctors in China reported last month that people in a new cluster of cases in two northeast regions were taking longer to show symptoms, and longer to recover.
There is no indication that the severity has diminished at all
This week, scientists at Scripps Research in Florida reported, in a pre-print paper, that a genetic mutation in the virus circulating throughout Europe and the U.S. significantly increases its “infectivity.” The mutation, known as D614G, quadrupled the number of spikes the virus uses to latch onto, break into and infect human cells.
Genome Canada, with $41 million in federal backing, has launched its own massive viral genome-sequencing project. “We ourselves have seen the D614G gene in sequences of our own. So it’s here,” said Dr. Samira Mubareka, a medical microbiologist at Toronto’s Sunnybrook Hospital.
What’s not clear is what any of this means.
“Notions that SARS-CoV-2 will evolve into the Andromeda Strain or become as benign as the common cold prey on our ignorance and fear,” evolutionary biologists wrote in Undark Magazine.
The WHO said last week nothing has changed in terms of severity or transmissibility and that the last thing needed is to suggest the virus has suddenly mutated into something less dangerous. The virus, said the WHO’s emergencies chief Mike Ryan, remains a “killer.”
SARS-CoV-2 only showed itself to humans roughly seven months ago, and while it is changing, it seems to be mutating at a relatively low rate. “What’s hard to tease out is, when you do see changes — you might see anywhere between half a dozen and a dozen changes in any given virus — is to really understand what the significance is,” said Mubareka, a virologist and infectious diseases doctor.
More than 40,000 genome sequences have been uploaded to publicly available websites. Scientists are scouring the genetic codes, reading through the 30,000 chemical letters, looking for blips and deletions and comparing sequences coming out of other countries, and while there are some subtle changes, none have resulted in differences in the way the virus spreads or the type of disease it causes, the WHO has said.
Yealy has no hard scientific data; “it’s just a general, crude observation” that cases under his care look different, he said. “Perhaps we’re better at treating patients.”
Western and central Pennsylvania are experiencing nowhere near the peak of people with suspected or actual disease. It’s possible physical distancing, face masks and better hygiene are having an effect. It’s possible that the most susceptible were the ones disproportionately attacked in the first wave of the pandemic. The warmer weather and humidity may be playing into this, Yealy added. But viruses can change over time. “This particular virus doesn’t look like it’s changing a lot. But it’s a possibility to think about.”
“There are probably six different factors at play and we won’t understand all of this. This is a virus that no one knew anything about eight months ago.”
What’s hard to tease out is, when you do see changes ... is to really understand what the significance is
Scientists are frantically trying to analyze outbreaks in real time, looking at regions where waves have come and gone. The virus that finally reached us in Canada “would have been passed so many more times in humans than it did at the beginning of the outbreak,” in Wuhan, Mubareka said. “We have a lot of blindspots as far as the genome goes.” Even with the process of sequencing itself, it’s hard to figure out what’s a signal of something of consequence, and what’s just meaningless noise.
When a virus enters a host, it replicates thousands of times. RNA viruses like this one can accumulate small, random mutations, because the molecular machinery it uses to copy itself sometimes gets sloppy. “It makes errors, and sometimes if those errors benefit the virus they’ll be selected for — they’ll persist and get passed on and on because there is some kind of fitness advantage,” Mubareka said.
But sometimes less lethal versions emerge. After sampling nasal swab samples from 382 COVID-positive people, Arizona State University researchers found a single sample that was missing a chunk of it’s genome, 81 of the letters gone. The deletion uncannily mirrors a mutation that arose in the SARS outbreak in 2003 that scientists believe caused much less severe disease later in the outbreak.
Still, “we have to make sure that whatever statements we make are backed up by good, hard science, so it’s reproducible,” said Dalhousie University immunologist David Kelvin. That means testing isolates of the virus in the lab, in cells and animals, before anyone can really say, yes, this means something.
“Because the downside is really bad if you mislead the public to think that the virus is no longer as potent as it once was. People will of course relax their vigilance and succumb to a disease they probably could have avoided,” Kelvin said.
Governments have also expanded testing to include people with more mild disease or no symptoms at all. And if we’re testing people with less severe disease, “well, sure, it will look like (the virus) is becoming less severe,” Mubareka said.
The amount of virus on a swab also isn’t a measure of potency, added Arinjay Banerjee, of McMaster University’s Institute of Infectious Diseases. Sampling time is critical. How much virus is scooped up on a nose swab depends on when in the course of the infection it was taken.
Still, an ideal pathogen, a clever virus, learns to co-exist with its host, Banerjee said, “because if a host dies, if the individual dies, the virus dies with it.” A virus has to be able to leap from the infected to the uninfected, spreading its progeny to the next victim, to sustain the virus population.
“I’ll just be honest and upfront: We don’t know. We just don’t know if it’s weakening,” Banerjee said.
The virus and the host learned to co-adapt
Some coronavirus scientists have speculated that perhaps centuries ago there could have been an outbreak like this with coronaviruses that today are seasonal bugs.
“We don’t have data on this; we haven’t tested this,” Banerjee said. “But who knows, maybe the coronaviruses that cause mild cold-like symptoms could have been lethal in human populations many, many years ago. The virus and the host learned to co-adapt.”
Italy has suffered some of the world’s worst COVID-19 death tolls, but fewer people are being admitted to hospital compared to three months ago, and in some regions, “even the patients that are admitted, especially in emergency, are less severe,” said Dr. Matteo Bassetti, director of an infectious disease clinic at San Martino Hospital in Genoa.
“They have fever, some respiratory symptoms. They have cough. But even in similar ages, they don’t have the same aggressive picture they had three months ago.”
“I am not suggesting not to use the masks, or not to wash the hands or not stay one metre (in Canada, the official advice is two metres) away from the other,” Bassetti said.
“I am just giving the clinical impression, and the clinical impression is the disease is different. I am more optimistic than I was three months ago.”
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