Information

Does a virus that spreads more rapidly have less chance to evolve?

Does a virus that spreads more rapidly have less chance to evolve?


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

Now that the COVID-19 pandemic has been going on for a while, there are reports of many new variants, which have presumably arisen in the past year through mutation and spread through natural selection.

I'll assume that the outcomes of COVID-19 infection are either death or a successful immuse , others would have developed antibodies. Suppose for the purposes of discussion that those are the two end consequences (or correct my answer in your thinking.)

If eighteen months ago, everyone in the planet had been infected with COVID-19 in one very bad day, then many people would die, and the others would end up with antibodies. That might stop the spread of the disease, which would stop its evolution. (Feel free to address Typhoid Mary-like scenarios in the answer; or of course any misconceptions in this paragraph.)

Is there a perspective from which-or set of circumstances under which-drawing out a pandemic can actually worsen the effect of a disease by giving it more chance to evolve?

(I've put the question in terms of COVID-19, but I think it's really a generally question, no less applicable to COVID-20 and above. :-) Please feel free to answer in general terms. I am not looking for a discussion about what public health measures may or not be appropriate to the current pandemic.)


Any evolutionary process has two components to it:

  • generation of genetic diversity in a population, and
  • shifts in the distribution of genetic variants under selective pressure.

For a virus like SARS-CoV-2, every infection results in a vast amount of replication, some of which will be variants generated through imperfect replication. Thus, the more rapidly a virus is spreading, the more opportunity it has to generate genetic diversity. Conversely, if there's not many infections going on, then there won't be much evolution because there won't be much diversity generation.

With regards to selection, the more actions that we take against the virus (e.g., mask wearing, social distancing, vaccination), the more selective pressure that it is under, since these actions differentiate between strains that are more or less effective in evading them. If the pressure goes too high, however, this breaks down. With highly effective countermeasures (e.g., rapid vaccine distribution while not letting our guard down), then there won't be much evolution because most variants won't have an opportunity to infect any new host: each new generation of infections will be driven more by countermeasure failures unrelated to viral efficacy, and thus there will actually be little effective selection.

The highest opportunity for evolutionary change, then, is with poorly coordinated countermeasures. This produces an intermediate rate of spreading, with both much viral replication and many opportunities for selective pressure on infections. It's really much the same as the problem with stopping a course of antibiotics prematurely, only on a societal rather than individual scale.

Bottom line: countermeasures are still a good idea, even when potential evolution of variants is included. People and governments that don't take the problem seriously, however, are threats to all the rest of us.


RNA viruses, like SARS-CoV-2, influenza, HIV, etc all have high mutation rates caused by an error-prone RNA replicating protein (known as an RNA dependent RNA polymerase or RdRP) that they use to reproduce their RNA genetic component. The error rates are high enough in these viruses that you can say that the virus exists not as a single species, but as something known as a quasi-species, which you can visualize as a cloud of individual virions, each with genetic variants from the "original" genome, some of which will be more "fit" than others in terms of evolution. These more fit ones are the variants that you see being talked about in the news. Note that the error rate of the RdRP is in terms of base changes per 1000 bases per 1 replication cycle, and the number is usually around 3-4.

The fitness of a virus is not necessarily related to any one variant, often a number of seemingly unrelated mutations in several proteins are required to make it fitter in any of the following characteristics:

  • Evading immune response
  • transmission
  • Invasion of the host/infectivity
  • viral titre (how many viral particles are produced)
  • replication rate
  • host-range (what species it can infect)
  • Tissues it can infect

Often, being better at one of these features means that it does poorly in others. A fine example of this is the H5N1 influenza that raged across the world a few years ago - it was great at killing people and even better at killing birds (it is an avian virus), but the real thing is it was terrible at actually infecting people, it just couldn't sustain transmission in humans.

SARS-CoV-2 has hit a pretty sweet-spot, it can transmit really well, it is highly infectious, has a fairly broad host-range, and has a long lag-time (~2 weeks) before people know they are infected, and some never do show symptoms. On the other hand, in some people it isn't at all great at evading the immune system, it actually seems to potentiate it, causing something known as a cytokine storm, where the immune system goes into hyperdrive and causes serious inflammation and the like. This is what actually kills people - the swelling of their airways in response to the infection limits oxygen transport and slowly suffocates them.

Now, you talked about antibodies: Antibodies are not the be-all and end-all like they are often considered. An antibody response to an infection does not necessarily mean that you can not get an infection from it again, it simply means that the infection is minimized to some extent. The extent of the protection is highly dependent on the individual (i.e. your response will be different to mine), and on the infection. If you had say Smallpox and survived, you (and I too if infected) would likely have a life-long immunity to smallpox. However, have an infection with Orf virus (a different pox virus), and you might only be protected for 6 months.

You, yourself (assuming you are >10 years old) and everyone around you is likely to have antibodies against at least 1 of the influenza viruses, but this won't stop you from getting sick from them again, it might however limit your infection so that you don't feel so bad for as long (and can then spread it more effectively… ). So you have antibodies, but they don't eliminate the flu, so we have a vaccine against influenza. Now the vaccine also doesn't cause complete protection, but that's beside the point. The reason you need to get an influenza vaccine each year is because the viruses have mutated over that year so that they are no longer the same as the previous year's flu viruses, so your body doesn't fully protect against the new viruses.

In the case of the SARS-CoV-2 vaccines being distributed currently world-wide. If you have been following the data, even in a fairly superficial manner, you will have seen something like"the Pfizer vaccine has a 95% protection rate"this means that it protects against 95% of illness from SARS-CoV-2 (i.e. symptomatic infection and actual infection in 95% of people). However, you might have also heard about people being concerned that there is less protection against the "South African" variant. This is an example of evolution causing an escape mutant. Evolutionary pressure has been applied to the virus, and it has produced a means to get around that pressure, to some extent. This will be an on-going process in terms of SARS-CoV-2; we will need new vaccines regularly to cope with the new variants as they arise.

TLDR: the virus will evolve anyway, the evolution happens in as little as a single cycle of virus replication.


Global Warming Could Cause Viruses to Evolve, Making Them Harder to Kill

Enteroviruses and other pathogenic viruses that make their way into surface waters can be inactivated by heat, sunshine and other microbes, thereby reducing their ability to spread disease. But researchers report in ACS’ Environmental Science & Technology that global warming could cause viruses to evolve, rendering them less susceptible to these and other disinfectants, such as chlorine.

Enteroviruses can cause infections as benign as a cold or as dangerous as polio. Found in feces, they are released into the environment from sewage and other sources. Their subsequent survival depends on their ability to withstand the environmental conditions they encounter. Because globalization and climate change are expected to alter those conditions, Anna Carratalà, Tamar Kohn and colleagues wanted to find out how viruses might adapt to such shifts and how this would affect their disinfection resistance.

The team created four different populations of a human enterovirus by incubating samples in lake water in flasks at 50 F or 86 F, with or without simulated sunlight. The researchers then exposed the viruses to heat, simulated sunlight or microbial “grazing” and found that warm-water-adapted viruses were more resistant to heat inactivation than cold-water-adapted ones. Little or no difference was observed among the four strains in terms of their inactivation when exposed to either more simulated sunlight or other microbes. When transplanted to cool water, warm-water-adapted viruses also remained active longer than the cool-water strains. In addition, they withstood chlorine exposure better. In sum, adaptation to warm conditions decreased viral susceptibility to inactivation, so viruses in the tropics or in regions affected by global warming could become tougher to eliminate by chlorination or heating, the researchers say. They also say that this greater hardiness could increase the length of time heat-adapted viruses would be infectious enough to sicken someone who comes in contact with contaminated water.

Reference: “Adaptation of Human Enterovirus to Warm Environments Leads to Resistance against Chlorine Disinfection” by Anna Carratalà, Virginie Bachmann, Timothy R. Julian and Tamar Kohn, 2 September 2020, Environmental Science & Technology.
DOI: 10.1021/acs.est.0c03199

The authors acknowledge funding from the Swiss National Science Foundation.


Law of declining virulence

It was the bacteriologist and comparative pathologist Theobald Smith (1859-1934) who began the narrative of the “law of declining virulence” in the late 19th century.

Studying tick-borne disease of cattle during the 1880s, Smith realised that the severity of the disease was determined by the degree of prior infection. Cattle that had been repeatedly exposed to the pathogen suffered from much more moderate disease than cattle encountering it for the first time. Smith reasoned that this was because host and pathogen conspired over time towards a mutually benign relationship.

The story then takes a distinctly antipodean turn. In 1859, the year Charles Darwin published his Big Idea, European rabbits were introduced to Australia for sport, with devastating consequences for the indigenous flora and fauna. Having turned down Louis Pasteur’s offer of mass délapinsation using fowl cholera as a biological control agent, the Department of Agriculture turned to the myxoma virus that causes the lethal, but highly species-specific disease, myxomatosis in rabbits.

By the 1950s, the myxoma virus was spreading rapidly among the rabbit population. Recognising the opportunities provided by this unique experiment, the virologist Frank Fenner documented how the virulence of the disease decreased over a few years from 99.5% mortality to about 90%. This was taken as strong empirical evidence in support of Smith’s law of declining virulence – and occasionally still is.

Myxomatosis control trial, Australia,1952. Queensland State Archives/Wikimedia Commons


Answer

This week, we examine the old adage - is size important?

Paul - Hello. My name is Paul Thorpe, from Wigan in the northwest of England, and my question is: do smaller organisms evolve faster than larger organisms?

Hannah - So, does a fly evolve faster than a toad, a whale slower than a barnacle, or the plague faster than people? Over to Robert Foley, professor of human evolution at Cambridge University.

Robert - The short answer is yes. It's not so much that smallness makes you evolve faster, but it's what' correlated with small size that matters. Small animals on the whole reproduce faster than larger animals. They grow up, reach maturity, have their babies and die over a much shorter period of time. So, the number of generations of a small animal is going to be much, much greater. This means that there will be more mutations and more exposure to selection in each generation, so that the potential for evolutionary change is just that much greater.

Hannah - So, size is important in evolution - the smaller, the better. In which case, not to sound all doom and gloom, but how have us, long-living and relatively gargantuan human beings managed to survive against the deadly invading bugs which are out there? Is the end of the world nigh? John Trowsdale, professor of immunology at Cambridge University, reassures us.

John - First, we must remember that it's not advantageous in fact for a microbe to kill its host. If it did that, it would then lose its livelihood. So, most bugs are adapted to live in harmony with us. In fact, it's been calculated that we each carry around in our gut and on our skin, maybe 10 times more bacteria than we have cells in our body. Second, we have many, many lines of defence and any pathogen has to overcome all of them to gain an advantage. It's been calculated that well over 15% of the genes in our genome are involved with the immune system. Third, if an infection does take hold, there's rapid selection within the individual by the adaptive immune system by a process of rearrangement and mutation. We each make many trillions of different antibodies and the best is selected at which time to respond to a specific infection. Finally, there is great variation in the immune systems of different individuals. This is to our advantage as if a virus mutates to overcome the defences of an individual, other people will be resistant. So, spread of the infection is limited.

Hannah - Thanks, Paul, Robert and John. Smaller organisms evolve faster, but our large bodies have clever immune systems evolved to help keep us humans one step ahead and bugs at bay. Next, we get ourselves in a bit of a tizz, trying to answer this.

John - Hello. My name is John and I live in Melbourne, Australia. My question is, are electrons orbiting atoms? I've always wondered how come electrons seem to perpetually spin around a nucleus? What forces are involved and how come friction doesn't play a part in stopping their movement? Thanks guys.

Hannah - So, you might remember from school that electrons whizz around the centre of your atoms. What keeps them whizzing? Don't they ever get tired? What do you think?


Plausible but not inevitable

Of course, these counter-examples do not in themselves present evidence that the virulence of SARS-CoV-2 will not decline. Declining virulence is certainly plausible as one of many potential outcomes under the trade-off model.

Conversely, mutations might simultaneously heighten both virulence and transmissibility by increasing viral replication rate. Although we will have to wait for more evidence to be certain – and the precise mechanisms may be difficult to pin down – the emerging evidence around the B117 variant currently points more towards increased mortality.

Ed Feil, Professor of Microbial Evolution at The Milner Centre for Evolution, University of Bath and Christian Yates, Senior Lecturer in Mathematical Biology, University of Bath

This article is republished from The Conversation under a Creative Commons license. Read the original article.


Will the Coronavirus Evolve to Be Less Deadly?

N o lethal pandemic lasts forever. The 1918 flu, for example, crisscrossed the globe and claimed tens of millions of lives, yet by 1920, the virus that caused it had become significantly less deadly, causing only ordinary seasonal flu. Some pandemics have lasted longer, like the Black Death, which swept out of Central Asia in 1346, spread across Europe, and ultimately may have killed as many as a third of the inhabitants of Europe, the Middle East, and parts of Asia. That pandemic, too, came to an end, roughly seven years after it started, probably because so many had perished or developed immunity.

As far as scientists and historians can tell, the bacterium that caused the Black Death never lost its virulence, or deadliness. But the pathogen responsible for the 1918 influenza pandemic, which still wanders the planet as a strain of seasonal flu, evolved to become less deadly, and it’s possible that the pathogen for the 2009 H1N1 pandemic did the same. Will SARS-CoV-2, the virus that causes Covid-19, follow a similar trajectory? Some scientists say the virus has already evolved in a way that makes it easier to transmit. But as for a possible decline in virulence, most everyone says it’s too soon to tell. Looking to the past, however, may offer some clues.

The idea that circulating pathogens gradually become less deadly over time is very old. It seems to have originated in the writings of a 19th-century physician, Theobald Smith, who first suggested that there is a “delicate equilibrium” between parasite and host, and argued that, over time, the deadliness of a pathogen should decline since it is really not in the interest of a germ to kill its host. This notion became conventional wisdom for many years, but by the 1980s, researchers had begun challenging the idea.

Related

In the early 1980s, the mathematical biologists Roy Anderson and Robert May, proposed that germs transmit best when hosts shed a lot of the pathogen, which may often mean when they are quite sick. If you’re really sick, you are — the argument goes — shedding lots of virus, which makes it easier for the next host to pick it up. So virulence and transmissibility go hand in hand, until the germ gets so deadly it winds up killing its host too soon, and therefore can’t spread at all. This is known as the transmission-virulence trade-off. The most familiar example is that of the myxoma virus, a pathogen introduced to Australia in 1950 to rid the country of rabbits. Initially, the virus killed more than 90 percent of Australian rabbits it infected. But over time, a tense truce developed: Rabbits evolved resistance, the myxoma germ declined in virulence, and both rabbits and germ remained in precarious balance for some time.

A second theory, developed by evolutionary epidemiologist Paul Ewald, which he calls the “theory of virulence,” suggests that, as a rule, the deadlier the germ, the less likely it is to spread. The reason: If victims are quickly immobilized (think of Ebola, for example), then they can’t readily spread the infection. By this thinking, if a germ requires a mobile host to spread, its virulence will, of necessity, decline. Like the older conventional wisdom, the theory of virulence recognizes that many germs will evolve less virulence as they circulate and adapt to the human population. But Ewald’s theory also proposes that germs all have their own strategies to spread, and some of those strategies allow the germ to maintain high virulence and transmissibility.

Durability, Ewald says, is one such strategy. Variola virus, which causes smallpox, is very durable in the external environment, and it can have a high death rate of 10 to 40 percent. Ewald calls it and other durable germs “sit-and-wait” pathogens. Some deadly infections are spread from very sick hosts by vectors: fleas, lice, mosquitos, or ticks. Others, such as cholera, are spread in water. Still others, such as hospital-acquired staph infections, are spread by people taking care of the sick or dying. This is what happened in the women’s hospitals of the 19th century, when doctors spread puerperal or “childbed” fever from one postpartum woman to another.

All of these strategies, according to Ewald, may prevent a germ’s otherwise inevitable slide to lower virulence.

S o what do these evolutionary theories suggest about SARS-CoV-2 and its likely trajectory? Is the novel coronavirus likely to decline in virulence as it cycles from person to person across the world?

SARS, an earlier outbreak of a serious coronavirus that disrupted the world from 2002 to 2003, offers an interesting contrast. That virus seemed to spread late in the course of infection from people who were very sick, and it eventually infected around 8,000 people, killing 774 before being driven out of existence by a hard-fought global effort to isolate sick patients. But SARS-CoV-2, researchers know, is transmissible early in the infection. There is no necessary relationship between transmissibility and severity. Even asymptomatic cases may shed significant amounts of virus, and there doesn’t necessarily seem to be an increased risk with exposure to sicker people.

It seems unlikely, therefore, that the course of SARS-CoV-2 evolution will strictly reflect Anderson and May’s transmission-virulence trade-off model. To predict SARS-CoV-2’s evolutionary trajectory, Ewald looks to the durability of the virus instead. He points out that SARS-CoV-2 infectious particles last on various surfaces between hours and days, making it approximately as durable as influenza virus. He argues, therefore, that SARS-CoV-2 is likely to evolve virulence to levels much like that of seasonal influenza, with a typical death rate of 0.1 percent.

The idea that circulating pathogens gradually become less deadly over time is very old.

But there’s still no way to be certain that’s the course SARS-CoV-2 will take. And even the current death rate is uncertain because differences in testing for the coronavirus from country to country make a complete accounting of global infections impossible.

Still, scientists might have already observed evolutionary change in the virus, though apparently in the direction of increased transmissibility, not of lower virulence. A team led by Bette Korber, a computational biologist at Los Alamos National Laboratory, published a paper in the journal Cell in July showing that a strain carrying a mutation identified as D614G appeared to be replacing the initial strain that first emerged out of Wuhan, China. Korber and her team suggested that, on the basis of their research — conducted in cells in culture — the new strain seemed to be more infectious than the original. While the paper notes in its limitations that “infectiousness and transmissibility are not always synonymous,” Korber says the findings are consistent with higher transmissibility.

As with an earlier version of the study shared prior to peer review in April, this conclusion was soon subjected to a barrage of criticism: The replacement that Korber had taken for evidence that the change had been selected for, others ascribed to accident or to other evolutionary processes. Echoing a limitation noted in the Cell paper, critics further emphasized that cell culture studies aren’t able to replicate the complexities of real life, so results should be interpreted with caution. Shortly after the Cell paper was published, Yale epidemiologist and virologist Nathan Grubaugh told National Geographic, “There is a huge gap between infectiousness in a lab and human transmission.”

Neither Grubaugh nor his colleague Angela Rasmussen, a virologist at Columbia University who has also expressed skepticism regarding the mutation’s impact on transmissibility, responded to requests for comment.

But time has shown — and scientists including Grubaugh agree — that this new strain is now the primary one. As Korber puts it: “The D614G strain is now the pandemic. You can hardly even sample the [original] Wuhan virus anymore. In early March, the virus was a different virus than it is today.” This near-complete replacement of the original strain indicates that selection — likely selection toward greater transmissibility — was responsible for the shift, says Korber.

According to Ewald’s analysis, high transmissibility is often associated with lower virulence. He expects to see evidence that SARS-CoV-2 is evolving in that direction. Still, right now, it’s hard to tease apart this kind of viral evolution from improvements in testing, treatment, and social distancing. SARS-CoV-2 testing, for instance, is more accessible than it was earlier in the pandemic. This means patients are hospitalized and treated sooner, offering a better chance at survival, wrote Cameron Wolfe, an infectious disease physician and researcher at Duke University who treats many Covid-19 patients, in an email. Further, he wrote, experimental treatments might be helping hospitalized patients, while some of the most vulnerable people — those in nursing homes — are now better protected from exposure.

“Everyone talks about viral evolution” potentially leading to decreased mortality, wrote Wolfe. “But I haven’t seen any conclusive data to support that hypothesis yet.”

L ike plague , Covid-19 is a stealth infection, and that might ultimately slow evolution toward lower virulence. Yersinia pestis, the germ that causes plague, tamps down the early immune response, so that infected people can travel and spread infection for days before they feel sick. Similarly, people infected with SARS-CoV-2 seem capable of infecting others before experiencing any symptoms. This sly mode of viral spread may make the evolution of lower virulence less likely, as infected but asymptomatic people are the perfect mobile viral delivery systems.

Yet even without an evolutionary process pushing SARS-CoV-2 towards lower virulence, over time, the virus might affect people differently, said Columbia University virologist Vincent Racaniello. “SARS-CoV-2 may become less deadly, not because the virus changes, but because very few people will have no immunity,” he said. In other words, if you’re exposed to the virus as a child (when it doesn’t seem to make people particularly sick) and then again and again in adulthood, you’ll only get a mild infection. Racaniello points out that the four circulating common cold coronaviruses “all came into humans from animal hosts, and they may have been initially quite virulent.” Now, he says, they infect 90 percent of children at young ages. At later ages, all you get is the common cold.

Compared to influenza viruses, coronaviruses are more stable and less likely to evolve in response to pre-existing immunity. As a result, many experts argue, safe and effective vaccines remain the best chance for escaping the maze of Covid-19 infection. Regular boosters may be necessary as the virus cycles, not because the virus is rapidly evolving, but because human immunity may wane.

Such an outcome would mark the end of this current pandemic. Yet even then, experts believe, some version of the virus will continue to circulate, perhaps as a common cold virus or an occasional deadly outbreak among the unvaccinated, for many years, if not forever.

Wendy Orent is an Atlanta-based anthropologist and science writer specializing in health and disease. She is the author of “Plague: The Mysterious Past and Terrifying Future of the World’s Most Dangerous Disease” and “Ticked: The Battle Over Lyme Disease in the South.”


Will the Coronavirus Evolve to Be Less Deadly?

No lethal pandemic lasts forever. The 1918 flu, for example, crisscrossed the globe and claimed tens of millions of lives, yet by 1920, the virus that caused it had become significantly less deadly, causing only ordinary seasonal flu. Some pandemics have lasted longer, like the Black Death, which swept out of Central Asia in 1346, spread across Europe, and ultimately may have killed as many as a third of the inhabitants of Europe, the Middle East, and parts of Asia. That pandemic, too, came to an end, roughly seven years after it started, probably because so many had perished or developed immunity.

As far as scientists and historians can tell, the bacterium that caused the Black Death never lost its virulence, or deadliness. But the pathogen responsible for the 1918 influenza pandemic, which still wanders the planet as a strain of seasonal flu, evolved to become less deadly, and it’s possible that the pathogen for the 2009 H1N1 pandemic did the same. Will SARS-CoV-2, the virus that causes Covid-19, follow a similar trajectory? Some scientists say the virus has already evolved in a way that makes it easier to transmit. But as for a possible decline in virulence, most everyone says it’s too soon to tell. Looking to the past, however, may offer some clues.

The idea that circulating pathogens gradually become less deadly over time is very old. It seems to have originated in the writings of a 19th-century physician, Theobald Smith, who first suggested that there is a “delicate equilibrium” between parasite and host, and argued that, over time, the deadliness of a pathogen should decline since it is really not in the interest of a germ to kill its host. This notion became conventional wisdom for many years, but by the 1980s, researchers had begun challenging the idea.

In the early 1980s, the mathematical biologists Roy Anderson and Robert May, proposed that germs transmit best when hosts shed a lot of the pathogen, which may often mean when they are quite sick. If you’re really sick, you are — the argument goes — shedding lots of virus, which makes it easier for the next host to pick it up. So virulence and transmissibility go hand in hand, until the germ gets so deadly it winds up killing its host too soon, and therefore can’t spread at all. This is known as the transmission-virulence trade-off. The most familiar example is that of the myxoma virus, a pathogen introduced to Australia in 1950 to rid the country of rabbits. Initially, the virus killed more than 90 percent of Australian rabbits it infected. But over time, a tense truce developed: Rabbits evolved resistance, the myxoma germ declined in virulence, and both rabbits and germ remained in precarious balance for some time.

A second theory, developed by evolutionary epidemiologist Paul Ewald, which he calls the "theory of virulence,” suggests that, as a rule, the deadlier the germ, the less likely it is to spread. The reason: If victims are quickly immobilized (think of Ebola, for example), then they can’t readily spread the infection. By this thinking, if a germ requires a mobile host to spread, its virulence will, of necessity, decline. Like the older conventional wisdom, the theory of virulence recognizes that many germs will evolve less virulence as they circulate and adapt to the human population. But Ewald’s theory also proposes that germs all have their own strategies to spread, and some of those strategies allow the germ to maintain high virulence and transmissibility.

Durability, Ewald says, is one such strategy. Variola virus, which causes smallpox, is very durable in the external environment, and it can have a high death rate of 10 to 40 percent. Ewald calls it and other durable germs “sit-and-wait” pathogens. Some deadly infections are spread from very sick hosts by vectors: fleas, lice, mosquitos, or ticks. Others, such as cholera, are spread in water. Still others, such as hospital-acquired staph infections, are spread by people taking care of the sick or dying. This is what happened in the women’s hospitals of the 19th century, when doctors spread puerperal or “childbed” fever from one postpartum woman to another.

All of these strategies, according to Ewald, may prevent a germ’s otherwise inevitable slide to lower virulence.

So what do these evolutionary theories suggest about SARS-CoV-2 and its likely trajectory? Is the novel coronavirus likely to decline in virulence as it cycles from person to person across the world?

SARS, an earlier outbreak of a serious coronavirus that disrupted the world from 2002 to 2003, offers an interesting contrast. That virus seemed to spread late in the course of infection from people who were very sick, and it eventually infected around 8,000 people, killing 774 before being driven out of existence by a hard-fought global effort to isolate sick patients. But SARS-CoV-2, researchers know, is transmissible early in the infection. There is no necessary relationship between transmissibility and severity. Even asymptomatic cases may shed significant amounts of virus, and there doesn’t necessarily seem to be an increased risk with exposure to sicker people.

It seems unlikely, therefore, that the course of SARS-CoV-2 evolution will strictly reflect Anderson and May’s transmission-virulence trade-off model. To predict SARS-CoV-2’s evolutionary trajectory, Ewald looks to the durability of the virus instead. He points out that SARS-CoV-2 infectious particles last on various surfaces between hours and days, making it approximately as durable as influenza virus. He argues, therefore, that SARS-CoV-2 is likely to evolve virulence to levels much like that of seasonal influenza, with a typical death rate of 0.1 percent.

But there’s still no way to be certain that’s the course SARS-CoV-2 will take. And even the current death rate is uncertain because differences in testing for the coronavirus from country to country make a complete accounting of global infections impossible.

Still, scientists might have already observed evolutionary change in the virus, though apparently in the direction of increased transmissibility, not of lower virulence. A team led by Bette Korber, a computational biologist at Los Alamos National Laboratory, published a paper in the journal Cell in July showing that a strain carrying a mutation identified as D614G appeared to be replacing the initial strain that first emerged out of Wuhan, China. Korber and her team suggested that, on the basis of their research — conducted in cells in culture — the new strain seemed to be more infectious than the original. While the paper notes in its limitations that “infectiousness and transmissibility are not always synonymous,” Korber says the findings are consistent with higher transmissibility.

As with an earlier version of the study shared prior to peer review in April, this conclusion was soon subjected to a barrage of criticism: The replacement that Korber had taken for evidence that the change had been selected for, others ascribed to accident or to other evolutionary processes. Echoing a limitation noted in the Cell paper, critics further emphasized that cell culture studies aren’t able to replicate the complexities of real life, so results should be interpreted with caution. Shortly after the Cell paper was published, Yale epidemiologist and virologist Nathan Grubaugh told National Geographic, “There is a huge gap between infectiousness in a lab and human transmission.”

Neither Grubaugh nor his colleague Angela Rasmussen, a virologist at Columbia University who has also expressed skepticism regarding the mutation’s impact on transmissibility, responded to requests for comment.

But time has shown — and scientists including Grubaugh agree — that this new strain is now the primary one. As Korber puts it: “The D614G strain is now the pandemic. You can hardly even sample the [original] Wuhan virus anymore. In early March, the virus was a different virus than it is today.” This near-complete replacement of the original strain indicates that selection — likely selection toward greater transmissibility — was responsible for the shift, says Korber.

According to Ewald’s analysis, high transmissibility is often associated with lower virulence. He expects to see evidence that SARS-CoV-2 is evolving in that direction. Still, right now, it’s hard to tease apart this kind of viral evolution from improvements in testing, treatment, and social distancing. SARS-CoV-2 testing, for instance, is more accessible than it was earlier in the pandemic. This means patients are hospitalized and treated sooner, offering a better chance at survival, wrote Cameron Wolfe, an infectious disease physician and researcher at Duke University who treats many Covid-19 patients, in an email. Further, he wrote, experimental treatments might be helping hospitalized patients, while some of the most vulnerable people — those in nursing homes — are now better protected from exposure.

“Everyone talks about viral evolution” potentially leading to decreased mortality, wrote Wolfe. “But I haven’t seen any conclusive data to support that hypothesis yet.”

Like plague, Covid-19 is a stealth infection, and that might ultimately slow evolution toward lower virulence. Yersinia pestis, the germ that causes plague, tamps down the early immune response, so that infected people can travel and spread infection for days before they feel sick. Similarly, people infected with SARS-CoV-2 seem capable of infecting others before experiencing any symptoms. This sly mode of viral spread may make the evolution of lower virulence less likely, as infected but asymptomatic people are the perfect mobile viral delivery systems.

Yet even without an evolutionary process pushing SARS-CoV-2 towards lower virulence, over time, the virus might affect people differently, said Columbia University virologist Vincent Racaniello. “SARS-CoV-2 may become less deadly, not because the virus changes, but because very few people will have no immunity,” he said. In other words, if you’re exposed to the virus as a child (when it doesn’t seem to make people particularly sick) and then again and again in adulthood, you’ll only get a mild infection. Racaniello points out that the four circulating common cold coronaviruses “all came into humans from animal hosts, and they may have been initially quite virulent.” Now, he says, they infect 90 percent of children at young ages. At later ages, all you get is the common cold.

Compared to influenza viruses, coronaviruses are more stable and less likely to evolve in response to pre-existing immunity. As a result, many experts argue, safe and effective vaccines remain the best chance for escaping the maze of Covid-19 infection. Regular boosters may be necessary as the virus cycles, not because the virus is rapidly evolving, but because human immunity may wane.

Such an outcome would mark the end of this current pandemic. Yet even then, experts believe, some version of the virus will continue to circulate, perhaps as a common cold virus or an occasional deadly outbreak among the unvaccinated, for many years, if not forever.

Wendy Orent is an Atlanta-based anthropologist and science writer specializing in health and disease. She is the author of “Plague: The Mysterious Past and Terrifying Future of the World’s Most Dangerous Disease” and “Ticked: The Battle Over Lyme Disease in the South.”

This article was originally published on Undark. Read the original article.


Four Types of Bacterial Viruses Are Widely Used in Biochemical and Genetic Research

Bacterial viruses have played a crucial role in the development of molecular cell biology. Thousands of different bacteriophages have been isolated many of these are particularly well suited for studies of specific biochemical or genetic events. Here, we briefly describe four types of bacteriophages, all of which infect E. coli, that have been especially useful in molecular biology research.

DNA Phages of the T Series

The T phages of E. coli are large lytic phages that contain a single molecule of double-stranded DNA. This molecule is about 2 ×� 5 base pairs long in T2, T4, and T6 viruses and about 4 ×� 4 base pairs long in T1, T3, T5, and T7 viruses. T-phage virions consist of a helical protein “tail” attached to an icosahedral “head” filled with the viral DNA. After the tip of a T-phage tail adsorbs to receptors on the surface of an E. coli cell, the DNA in the head enters the cell through the tail (see Figure 6-16). The phage DNA then directs a program of events that produces approximately 100 new phage particles in about 20 minutes, at which time the infected cell lyses and releases the new phages. The initial discovery of the role of messenger RNA in protein synthesis was based on studies of E. coli cells infected with bacteriophage T2. By 20 minutes after infection, infected cells synthesize T2 proteins only. The finding that the RNA synthesized at this time had the same base composition as T2 DNA (not E. coli DNA) implied that mRNA copies of T2 DNA were synthesized and used to direct cellular ribosomes to synthesize T2 proteins.

Temperate Phages

Bacteriophage λ, which infects E. coli, typifies the temperate phages. This phage has one of the most studied genomes and is used extensively in DNA cloning (Chapter 7). On entering an E. coli cell, the double-stranded λ DNA assumes a circular form, which can enter either the lytic cycle (as T phages do) or the lysogenic cycle (see Figure 6-19). In the latter case, proteins expressed from the viral DNA bind a specific sequence on the circular viral DNA to a similar specific sequence on the circular bacterial DNA. The viral proteins then break both circular molecules of DNA and rejoin the broken ends, so that the viral DNA becomes inserted into the host DNA. The carefully controlled action of viral genes maintains λ DNA as part of the host chromosome by repressing the lytic functions of the phage. Under appropriate stimulation, the λ prophage is activated and undergoes lytic replication.

Small DNA Phages

The genome of some bacteriophages encodes only 10 –� proteins, roughly 5 –� percent of the number encoded by T phages. These small DNA phages are typified by the Φ� and the filamentous M13 phages. These were the first organisms in which the entire DNA sequence of a genome was determined, permitting extensive understanding of the viral life cycle. The viruses in this group are so simple that they do not encode most of the proteins required for replication of their DNA but depend on cellular proteins for this purpose. For this reason, they have been particularly useful in identifying and analyzing the cellular proteins involved in DNA replication (Chapter 12).

RNA Phages

Some E. coli bacteriophages contain a genome composed of RNA instead of DNA. Because they are easy to grow in large amounts and because their RNA genomes also serve as their mRNA, these phages are a ready source of a pure species of mRNA. In one of the earliest demonstrations that cell-free protein synthesis can be mediated by mRNA, RNA from these phages was shown to direct the synthesis of viral coat protein when added to an extract of E. coli cells containing all the other components needed for protein synthesis. Also, the first long mRNA molecule to be sequenced was the genome of an RNA phage. These viruses, among the smallest known, encode only four proteins: an RNA polymerase for replication of the viral RNA, two capsid proteins, and an enzyme that dissolves the bacterial cell wall and allows release of the intracellular virus particles into the medium.


Replicating genetic codes

A successful virus is one that makes more of itself. But these tiny entities can’t do much on their own. Viruses are essentially coils of genetic material stuffed into a protein shell that’s sometimes blanketed in an outer envelope. In order to replicate, they must find a host. The virus binds to its target’s cells, injecting genetic material that hijacks the host’s cellular machinery to make a new generation of viral progeny.

But each time a new copy is made, there’s a chance that an error, or mutation, will occur. Mutations are like typos in the string of “letters” that make up a strand of DNA or RNA code.

The majority of mutations are harmful to a virus or cell, limiting the spread of an error through a population. For example, mutations can tweak the building blocks of proteins encoded in the DNA or RNA, which alters a protein’s final shape and prevents it from doing its intended job, Duffy explains.

“It doesn’t make the nice little curlicue alpha-helices it’s supposed to,” she says of a common structure found in proteins. “It doesn’t make the nice folded sheets it's supposed to.”

Many other mutations are neutral, having no effect on how efficiently a virus or cell reproduces. Such mutations sometimes spread at random, when a virus carrying the mutation spreads to a population that hasn’t been exposed to any variants of the virus yet. “It’s the only kid on the block,” Anthony says.

However, a select few mutations prove useful to a virus or cell. For example, some changes could make a virus better at jumping from one host to the next, helping it outcompete other variants in the area. This was what happened with the SARS-CoV-2 variant B.1.1.7 that was first identified in the United Kingdom but has now spread to dozens of countries around the world. Scientists estimate the variant is roughly 50 percent more transmissible than past forms of the virus, giving it an evolutionary edge.


On average, the coronavirus accumulates about two changes per month in its genome. Sequencing SARS-CoV-2 genomes helps researchers follow how the virus spreads. Most of the changes don’t affect how the virus behaves, but a few may change the disease’s transmissibility or severity.

One of the earliest candidates was the wholesale deletion of 382 base pairs in a gene called ORF8, whose function is unknown. First reported by Linfa Wang and others at the Duke-NUS Medical School in Singapore in a March preprint, the deletion has since been reported from Taiwan as well. A deletion in the same gene occurred early in the 2003 severe acute respiratory syndrome (SARS) outbreak, caused by a closely related coronavirus lab experiments later showed that variant replicates less efficiently than its parent, suggesting the mutation may have slowed the SARS epidemic. Cell culture experiments suggest the mutation does not have the same benign effect in SARS-CoV-2, Wang says, “but there are indications that it may cause milder disease in patients.”


Will social distancing measures cause coronavirus to evolve into a more deadly strain?

Viruses, like COVID-19, evolve rapidly. Each time the virus replicates, mutations can occur in its genome. Most of these mutations have no effect, or are even damaging to the virus. However, occasionally a mutation will arise that is advantageous for the virus. These mutations may allow the virus to grow faster, spread better or evade our immune system. The longer a virus continues to circulate, the greater the chance of these mutations occurring and the virus evolving into a new strain that behaves differently.

However, causing more severe disease isn’t necessarily advantageous to the virus. One of the reasons the COVID-19 virus is so difficult to contain is that it spreads very well before people become sick. If the virus spreads while causing more severe symptoms, people with COVID-19 would likely stay home instead of going out (reducing transmission) and would seek medical attention (enabling more effective testing and contact tracing). Sometimes mild viruses are the most difficult to eliminate.

Because the COVID-19 pandemic has been so difficult to contain, we have all had to take precautions, such as social distancing, washing hands and wearing masks. Each of these individual precautions limits the amount of virus that can spread from one person to another. These actions could put pressure on the virus to evolve, possibly resulting in mutated strains that are more transmissible and more difficult to control (though not necessarily deadlier). However, by combining all of these precautions, together with strong public health infrastructure (such as test and trace), we can still effectively stop the transmission of COVID-19, even if it evolves into a more virulent strain.