Raul Andino knows his pathogens. For more than 30 years the University of California, San Francisco researcher has studied RNA viruses, a group that includes the virus that causes COVID-19. And yet he never imagined hed witness a pandemic of this scale in his lifetime.
The magnitude of it and the implications of it are still hard to comprehend, Andino says.
Although experts in his field suspected a pandemic would occur, its hard to know when, he says. Its similar to an earthquakeyou know the earthquake will happen, but normally you dont think about it.
On March 11, 2020exactly two years agothe World Health Organization declared COVID-19 to be a pandemic. The disease has since infected nearly 500 million people in almost 200 countries and killed more than six million people worldwide, and its not over yet.
Along the way, this coronavirus has presented scientists with a bevy of surprises: Many experts are still amazed by how quickly the virus evolves, what it does to the human body, and how it moves in and out of other species.
The original SARS-CoV-2 virus rapidly evolved into a string of variants that have hindered a return to pre-pandemic normalcy. Even with the viruss genetic blueprint in hand and the ability to decode the genomes of new variants within hours, virologists and healthcare professionals struggle to predict how its mutations will alter the viruss transmissibility and severity.
Millions of people are grappling with symptoms that linger for weeks to several months after theyd been diagnosed with an infection. Scientists are racing to understand the biology of this new and perplexing syndrome called long COVID.
Two years in, theres still a lot we dont know about SARS-CoV-2, says David Wohl, an infectious disease specialist at the University of North Carolina. Heres what scientists have uncovered so farand the mysteries that continue to tantalize and frustrate coronavirus experts.
Experts had been warning of some kind of looming pandemic for decades. As humans expand settlements into wild areas, they raise the odds of a new pathogen jumping from an animal to a person, giving rise to a deadly zoonotic disease. A study published in Natureshowed that emerging infectious diseases originating in wildlife had increased significantly between 1940 and 2004.
But most experts were worried about influenza viruses and would not necessarily have expected a coronavirus to cause such havoc.
That changed with the 2002-04 Severe Acute Respiratory Syndrome (SARS) outbreak, which infected more than 8,000 people in 29 countries and left 774 dead. Then the 2012 Middle East Respiratory Syndrome (MERS) outbreak infected more than 2,000 people in 37 countries; that virus has so far killed nearly 900.
Still, people werent paying as much attention to coronaviruses compared to the really bad guys like influenza, HIV, dengue viruses, Andino says.
Then SARS-CoV-2 arrived with a bang. It was spreading faster than previous coronaviruses, and one reason, scientists suspect, is its ability to move efficiently from one cell to the next. SARS-CoV-2 is also harder to contain because it causes so many asymptomatic cases, people who can then unknowingly spread the virus. In a way, SARS-CoV-2 has found a way in which it can [rapidly] spread and also cause disease, Andino says. Its the worst-case scenario playing out.
Adding to the oddities, the SARS-CoV-2 virus acquired genetic mutations much more rapidly than expected.
Coronaviruses usually mutate at lower rates than other RNA viruses, like influenza and HIV. Both SARS-CoV and SARS-CoV-2 accumulate approximately two mutations each month; half to one sixth the rate seen in influenza viruses. Thats because coronaviruses have proofreading proteins that correct errors introduced into the virus genetic material as it replicates.
Thats why we thought [SARS-CoV-2] would not evolve very fast, says Ravindra Gupta, a clinical microbiologist at the University of Cambridge.
But the virus quickly proved Gupta and his colleagues wrong. The emergence of Alphathe first variant of concern identified in the United Kingdom in November 2020stunned scientists. It had 23 mutations that set it apart from the original SARS-CoV-2 strain, eight of which were in the spike protein, which is essential for anchoring to human cells and infecting them.
It became clear that the virus could make these [surprising] evolutionary leaps, says Stephen Goldstein, an evolutionary virologist at the University of Utah. With this set of mutations, Alpha was 50 percent more transmissible than the original virus.
The next version, Beta, was first identified in South Africa and was reported as a variant of concern just a month later. It carried eight mutations on the viral spike, some of which helped the virus escape the bodys immune defenses. And when the Gamma variant emerged in January 2021, it had 21 mutations, 10 of which were in the spike protein. Some of these mutations made Gamma highly transmissible and enabled it to reinfect patients who previously had COVID-19.
Its surprising to see these variants make pretty significant leaps in transmissibility, Goldstein says. I just dont think weve observed a virus do that before, but of course, we have not actually observed any pandemics previously with the amount of genetic sequencing capacity we have now.
Then came Delta, one of the most dangerous and contagious variants. It was first identified in India and designated a variant of concern in May 2021. By late 2021 this variant dominated in almost every country. Its unique constellation of mutations13 overall and seven in the spikemade Delta twice as infectious as the original SARS-CoV-2 strain, led to longer lasting infections, and produced 1,000 times more virus in the bodies of infected people.
"It [SARS-CoV-2]s ability to come up with new solutions and ways to adapt and spread with such easeits incredibly surprising, Andino says.
However, Omicron, which is two to four times more contagious than Delta, rapidly replaced that variant in many parts of the world. First identified in November 2021, it carries an unusually high number of mutationsmore than 50 overall and at least 30 in the spikesome of which help it evade antibodies better than all the earlier virus versions.
These huge jumps [in mutations] make the pandemic far less predictable, says Francois Balloux, a computational biologist at the University College London Genetics Institute in the United Kingdom.
One of the most compelling explanations for the huge leaps in the number of mutations is that that the SARS-CoV-2 virus was able to evolve for long periods of time in the bodies of immunocompromised people.
During the past year, scientists have identified cancer patients and people with advanced HIV disease who were unable to get rid of their COVID-19 infection for months to nearly a year. Their suppressed immune systems enabled the virus to persist, replicate, and mutate for months.
Gupta identified one such mutation (also seen in the Alpha variant) in a sample from a cancer patient who remained infected for 101 days. In an advanced HIV patient in South Africa who was infected for six months, scientists recorded a multitude of mutations that helped the virus escape the bodys immune defenses.
That the virus is changing its biology this quickly in its evolutionary history is a huge find, Gupta says. Other viruses like influenza and norovirus also undergo mutation in immunocompromised individuals, but it is very rare, Gupta says, and they infect a narrow range of cells.
By contrast, SARS-CoV-2 has proven capable of infecting many different areas of the bodycreating yet more baffling effects for scientists to untangle.
Early in the pandemic medical professionals noticed that the virus wasnt just causing pneumonia-like illness. Some hospitalized patients also presented heart damage, blood clots, neurologic complications, and kidney and liver defects. Mounting studies within the first few months suggested one reason why.
SARS-CoV-2 uses proteins called ACE2 receptors on the surface of human cells to infect them. But because ACE2 is present in many organs and tissues, the virus was infecting more parts of the body than just the respiratory tract. There were also a few reports of the virus, or parts of it, in blood vessel cells, kidney cells, and small quantities in brain cells.
Ive studied a lot of pandemics, and in almost all of them, you look at the brain, youll find the virus there, says Avindra Nath, a neuroimmunologist at the National Institutes of Health. For instance, brain autopsy tissues from 41 hospitalized and dead COVID-19 patients revealed low levels of the virus. But there were also clear signs of damage, including dead neurons and mangled blood vessels.
Thats the biggest surprise, Nath says.
Its likely that the virus triggers the bodys immune system to go into a hyperactive mode called a cytokine storm, which causes inflammation and injury to different organs and tissues. An abnormal immune response can persist even after infection, resulting in lingering symptoms including chronic fatigue, heart palpitations, and brain fog.
But there are virus reservoirs that can cause chronic inflammation, says Sonia Villapol, a neuroscientist at theHouston Methodist Research Institute. A recent study thats not yet been peer-reviewed showed that SARS-CoV-2 genetic material could persist for up to 230 days in the body and brains of COVID-19 patients, even in those who harbored only mild or asymptomatic infections.
Susan Levine is an infectious-disease doctor in New York who specializes in the treatment and diagnosis of chronic fatigue syndrome, which has parallels with long COVID. She now sees 200 patients every week, compared to 60 in pre-pandemic times. Unlike CFS, long COVID hits you like a ton of bricks, Levine says. Its like a tornado inside your body where youre going from working 60 hours a week down to being in the bed all day within a week of getting the infection. The action is so compressed.
Scientists are now concerned about the persistence of SARS-CoV-2 outside human populations and its potential to spread to other animals and jump back into humans, possibly extending the pandemic.
In April 2020 tigers and lions at New Yorks Bronx Zoo tested positive for COVID-19, sparking interest in finding other animals that might be susceptible. Soon after a study identified mammals including certain primates, deer, whales, and dolphins to be among the most vulnerable to COVID-19 given the similarity between their ACE2 receptors and the counterpart in human cells.
Another study used a machine learning approach to assess the abilities of 5,400 mammal species to transmit SARS-CoV-2; it found that several animals most at risk of spreading COVID-19 were those living alongside people, such as livestock and even pets.
So far SARS-CoV-2 has infected pet cats, dogs, and ferrets, ravaged mink farms, and spread to tigers, hyenas, and other animals in zoos. Whats more, SARS-COV-2 has successfully jumped from humans to captive minks and back into mink farmers. And a person in Canada was potentially infected with COVID-19 when the virus jumped from a white-tailed deer.
The concern is if it continues to evolve in deer to a point where deer become more and more immune to it, their preexisting antibodies from their reinfection could also further drive viral evolution, says Samira Mubareka at Canadas Sunnybrook Health Sciences Centre. Also, the virus may be circulating in other animals out there.
Still, the spread of SARS-CoV-2 among humans continues to be a bigger concern for scientists, as they learn more about the virus and its presence and impact in both humans and animals.
We still dont know what the future holds, Wohl says. Well be two years plus of history and track record, and even then with that knowledge, its still hard to predict what will happen.
Some European countries, such as Spain, are making plans for the time they might be able to treat SARS-CoV-2 as an endemic disease one that's always around but fairly predictable. But the World Health Organization cautions that the pandemic is not over. Above: Masked pedestrians in Barcelona, Spain, in July 2021. Joan Mateu/AP hide caption
Some European countries, such as Spain, are making plans for the time they might be able to treat SARS-CoV-2 as an endemic disease one that's always around but fairly predictable. But the World Health Organization cautions that the pandemic is not over. Above: Masked pedestrians in Barcelona, Spain, in July 2021.
Each week, we answer frequently asked questions about life during the coronavirus crisis. If you have a question you'd like us to consider for a future post, email us at goatsandsoda@npr.org with the subject line: "Weekly Coronavirus Questions." See an archive of our FAQs here.
We all know what the word pandemic means now, but remind me what endemic means again and are we there yet?
It's been two years since the World Health Organization, on March 11, 2020, officially declared a global pandemic.
Since then, we're all become too familiar with the word pandemic and sister terms such as epidemic and outbreak.
(If you're fuzzy on the definitions, check out this glossary.)
"But now we're starting to hear the word 'endemic,' " says epidemiology professor Charlotte Baker at Virginia Tech in reference to a new stage for SARS-CoV-2.
So should we be looking forward to that?
First, let's explain the term.
The word "endemic" comes from the Greek word endmos, which means "in the population."
In epidemiology, it means that the disease is always present at a baseline level. So it's not down to zero. There are observable cases. But unlike a pandemic or epidemic, in which a disease's behavior is often surprising or unexpected, an illness that has become endemic has become more predictable.
A candy analogy might help.
If you think of a disease as a regular-size KitKat bar, Baker says, and you open the package one day and there are six pieces instead of four, that candy bar is acting more like an epidemic (that is, a sudden spike of a disease that could lead to a pandemic if it spreads globally).
"An epidemic means more cases than we expect," she explains. And if you unwrapped a KitKat bar to reveal six pieces, you'd know something was wrong "it throws you off, you know something's happening," she says, just as you know that you can't count on things staying the same when there's an epidemic.
As much as none of us want to be joined at the hip with COVID-19 forever that's the nature of an endemic situation this stage does have some advantages.
First of all, you know what you're getting: "Endemic means that the disease or infection reached a steady state where it doesn't cause large outbreaks but it still circulates, causing individual cases," explains epidemiologist Dr. Isaac Weisfuse, an adjunct professor in Cornell University's master's of public health program. "There's always a "background rate of infection causing cases or maybe more cases in enclaves of people who haven't been vaccinated," he adds.
Most strains of influenza are endemic, for example, and you can roughly predict when flu season will begin and end. (Every once in awhile, there are new variants that throw things off, like H1N1 in 2009, which caused a pandemic.) Other endemic diseases in the U.S. include pneumonia and chickenpox. With minimal precautions, such as vaccination, boosters and optional masking, life for most people proceeds as normal.
So are we there yet, endemically speaking?
"We're all in a rush to get to the endemic stage I would love it," Baker says. "But when it will happen is a really good question."
There are a few potential roadblocks in the way namely, variants.
"The problem hanging over all of us is what happens if a new variant should occur," Weisfuse says.
In other words, we're far from being able to predict what will happen next with COVID-19. If the disease were a candy bar, we still don't know what to expect when we unwrap it.
Also, Baker notes, the pandemic won't officially be over until the World Health Organization says it's over.
Once that's decided at a special meeting, some countries could still be stuck in epidemic status while others may skip right into endemic.
And, our experts noted, an endemic disease doesn't change the fact that people still need to protect themselves by getting vaccinated.
"The virus might find you if you're unvaccinated or if you have underlying risk factors," Weisfuse says. A small number of those people will still need to be hospitalized, he notes.
I've also heard the terms eliminated and eradicated. Is it too optimistic to hope for that?
Unfortunately, yes.
If a disease is "eliminated" from a country, that means no more transmission among its population (although cases might still be introduced from outsiders). That's the categorization for measles, for example, in the U.S. and a number of European countries.
Other diseases such as smallpox have been eradicated, which means there is zero transmission. (The last naturally occurring case of smallpox was in 1977.)
In both cases, vaccines were to thank for the decline of the diseases.
COVID-19, however, is unlikely to ever be eradicated and doesn't appear to be on track to be eliminated, either, since the virus has been found in animals such as mink, hamsters and deer.
"Once you have a disease with an animal reservoir, it's very hard to eradicate," Weisfuse says. That's because once it's in animals, it can find its way back to humans like the three people in Hong Kong who reportedly caught COVID-19 from pet-store hamsters.
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases," echoed that sentiment in January, when he pointed out that COVID-19 is not on a path to eradication.
"If you look at the history of infectious diseases, we've only eradicated one infectious disease in man, and that's smallpox. That's not going to happen with this virus. But hopefully it will be at such a low level that it doesn't disrupt our normal social, economic and other interactions," he said at the World Economic Forum's Davos Agenda.
And some places are already planning for the endemic stage: Spanish Prime Minister Pedro Sanchez has asked European officials to discuss when COVID-19 should be considered endemic, and California has adopted the first endemic policy for COVID in the U.S. According to The Associated Press, the California plan "emphasizes prevention and quick reaction to outbreaks over mandated masking and business shutdowns."
But it's also important to remember that endemic is not synonymous with harmless. Malaria, for example, is considered endemic in a number of countries. In 2020, the World Health Organization tallied 627,000 deaths from this mosquito-borne disease.
Sheila Mulrooney Eldred is a freelance health journalist in Minneapolis. She has written about COVID-19 for many publications, including The New York Times, Kaiser Health News, Medscape and The Washington Post. More at sheilaeldred.pressfolios.com. On Twitter: @milepostmedia.
Friday, March 11 marks two years since the World Health Organization declared COVID-19 a global pandemic.
It was very, very intense and very stressful, but also a lot of team building through adversity, said Dr. Amy Beth Kressel, Medical Director of Infection Prevention and Antimicrobial Stewardship at Eskenazi Health.
We would do one thing and then literally the same day we would have to change something because everything was changing so quickly. The hospital and my colleagues and I really came together.
A lot has changed in Central Indiana since WHOs declaration just about every COVID-19 metric continues to fall.
At Eskenazi Health, Dr. Kressel said frontline workers were caring for two COVID-19 inpatients as of Friday morning. That is compared to somewhere between 130 or 140 COVID-19 inpatients at the height of the Omicron surge.
We were able to take care of our patients through a lot of teamwork and a lot of grace for each other, said Dr. Kressel. So thats the positive.
On the flip side, Dr. Kressel said there is one lesson she hopes is learned: the nations supply chain is broken and needs to be fixed.
Supply chains basically broke, said Dr. Kressel. Personal protective equipment, we have shortages of critical medicines, we were concerned about our ventilators Its not as critical now but the supply chain issues are not completely resolved.
Dr. Kressel said she hopes there will be genuine action to make hospitals and the health care system more resilient to a future pandemic or any sort of future crisis.
I really think resiliency is going to have to be baked in across all the systems, said Dr. Kressel.
Meanwhile in Monroe County, health officials agree the pandemic caught many sectors by surprise.
We didnt have resources in place and infrastructure in place for a lot of things that we have now, said Penny Caudill, Health Administrator for the Monroe County Health Department. It can be an eye opening experience Why didnt we have those things? Well, we didnt have the infrastructure. We didnt pay for the infrastructure. But we can do that going forward and certainly more money is being put into public health. I guess that thats a good thing to come from this.
Caudill said another positive to come out of the pandemic is more open lines of communication and better relationships.
Weve had good relationships with our community partners, with the hospital and the university, but certainly the pandemic has forged new ones, said Caudill.
Friday also marked the last weekly scheduled COVID-19 press conference for the city of Bloomington. Caudill said the county now has the tools and ability to quickly orchestrate another meeting if necessary.
My staff has been incredible the past couple years. Incredible, said Stephenie Mellinger, Administrator for the Madison County Health Department. They may not interact on a daily basis, but they did during this pandemic and so it was really great to see how the whole department came together.
Mellinger said she has done a lot of reflection in this past week leading up to the two-year milestone. While she does remember this day in history, she said she remembers another day more vividly.
I remember more clearly the first case we had in our county, which would have been two years next week, said Mellinger. It was March 17th and I remember not being surprised by it. It was just a matter of time. I mean, we were watching all of this unfold.
Now, eyes are set on the future of public health in Madison County. Mellinger said the pandemic led to the county getting its first-ever mobile unit.
That was a goal of mine and it happened sooner as a result, said Mellinger. I want it to be a health clinic on wheels.
For a little less than a year, the mobile unit has been making its way across Madison County providing a variety of services outside of COVID-19. It now operates four days a week.
We have plans bigger, better, greater plans for that mobile unit and I want to run the wheels off of it, said Mellinger. Definitely, there have been some good things that have come out of [the pandemic].
Three more Mainers have died and another 282coronavirus cases reported across the state, Maine health officials said Saturday.
Fridays report brings the total number of coronavirus cases in Maine to 232,293,according to the Maine Center for Disease Control and Prevention. Thats up from 232,011 on Friday.
Of those, 168,193have been confirmed positive, while 64,100were classified as probable cases, the Maine CDC reported.
One man and two women from York County have succumbed to the virus, bringing the statewide death toll now to 2,145.
The number of coronavirus cases diagnosed in the past 14 days statewide is 6,173. This is an estimation of the current number of active cases in the state, as the Maine CDC is no longer tracking recoveries for all patients. Thats down from 6,758 on Friday.
The new case rate statewide Saturday was 2.11 cases per 10,000 residents, and the total case rate statewide was 1,735.60.
The most cases have been detected in Mainers younger than 20, while Mainers over 80 years old account for the largest portion of deaths. More cases have been recorded in women and more deaths in men.
So far, 4,440Mainers have been hospitalized at some point with COVID-19, the illness caused by the new coronavirus.
Of those, 122 are currently hospitalized, with 23 in critical care and six on a ventilator. Overall, 83 out of 354 critical care beds and 266 out of 328 ventilators are available.
The total statewide hospitalization rate on Saturday was 33.17 patients per 10,000 residents.
Cases have been reported in Androscoggin (22,250), Aroostook (12,311), Cumberland (47,630), Franklin (5,602), Hancock (7,155), Kennebec (22,368), Knox (5,775), Lincoln (5,080), Oxford (11,006), Penobscot (26,879), Piscataquis (2,928), Sagadahoc (4,914), Somerset (9,430), Waldo (5,909), Washington (4,184) and York (38,862) counties. Information about where an additional 10 cases were reported wasnt immediately available.
An additional 525 vaccine doses were administered in the previous 24 hours. As of Saturday, 990,933 Mainers are fully vaccinated, or about 77.4 percent of eligible Mainers, according to the Maine CDC.
As of Saturday morning, the coronavirus had sickened 79,507,030people in all 50 states, the District of Columbia, Puerto Rico, Guam, the Northern Mariana Islands and the U.S. Virgin Islands, as well as caused 967,126deaths, according to the Johns Hopkins University of Medicine.
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