Do SARS-CoV-2 mutations affect its transmissibility?

New research has found that no currently identified mutation of SARS-CoV-2 appears to make the virus better at transmitting.

After studying a significant number of SARS-CoV-2 mutations, the scientists behind a new study have not identified any that are likely to improve the virus’s transmissibility.

The research, published in the journal Nature Communications, may be valuable in helping scientists keep track of the virus’s possible mutations as it encounters people who have been vaccinated against it.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

Viral mutation

SARS-CoV-2, the virus responsible for COVID-19, has been present in humans for approximately 1 year. During that time, though, it has not stayed the same.

Viruses spread by replicating themselves within a host organism. If all goes to plan, this replication results in genetically identical copies of the virus taking over cells within the host. In the case of SARS-CoV-2, these are typically the cells of a person’s respiratory tract.

However, a virus can also mutate during its replication process.

Viral mutation happens for one of three reasons. Either there is an error during the replication process, or the mutation occurs because another virus is also present in the host. Or, the mutation may be a consequence of the effects of the person’s immune system on the virus.

Mutations are key for a virus’s evolution, as they are for other organisms. If a mutation improves the virus’s ability to replicate, the mutation is likely to be passed on and may spread exponentially.

If the mutation is detrimental to the virus’s ability to replicate, it is less likely to be passed on. Mutations that are neutral may be passed on, depending on other factors.

In the case of SARS-CoV-2, a key question is whether and how often the virus’s mutations are likely to improve its ability to replicate, for example, by making it more effective at resisting a person’s immune system.

The virus is already highly infectious, and the disease it can cause has resulted in more than 1.4 million deaths globally. If SARS-CoV-2 mutated to become more infectious, the death rate would likely increase even further.

Over 46,000 samples

To determine whether mutations of SARS-CoV-2 are increasing its transmission, the scientists behind the present study analyzed samples of its genome from 46,723 people across 99 countries.

According to the study paper’s co-lead author, Dr. Lucy van Dorp, of the UCL Genetics Institute, in the United Kingdom, “The number of SARS-CoV-2 genomes being generated for scientific research is staggering.”

“We realized early on in the pandemic that we needed new approaches to analyze enormous amounts of data — in close to real time — to flag new mutations in the virus that could affect its transmission or symptom severity,” she adds.

The dataset that the scientists analyzed included samples taken until the end of July 2020.

Of the initial 46,723 samples, the scientists identified 12,706 cases of viral mutation. However, the researchers were particularly interested in 398 mutations that likely occurred independently a number of times.

This would indicate that these mutations are more likely to increase the virus’s transmission, rather than having a neutral effect and being passed on incidentally.

The scientists finally identified 185 mutations that occurred independently at least three times.

To determine whether the mutations were improving the chances of transmission, the scientists created models of the virus’s evolutionary tree, tracing how common each mutation was along a particular evolutionary branch.

If the mutation occurred frequently in descendants, it likely increased the chances of the virus’s transmission.

Increased transmission?

After tracing the evolutionary progression of the 185 mutations that had each occurred independently three times, the scientists found no evidence that any were increasing the virus’s chances of transmission.

Instead, they found that the majority of the mutations were neutral, when it came to viral transmission.

The mutations seem to have mainly occurred as an effect of the human immune system. This was in contrast to how the virus behaved when it made the jump from humans to minks, which the scientists had analyzed separately.

As Dr. van Dorp says, “When we analyzed virus genomes sourced from mink, we were amazed to see the same mutation appearing over and again in different mink farms, despite those same mutations having rarely been observed in humans before.”

According to senior study author Prof. Francois Balloux, of University College London’s Division of Biosciences, this could mean that the key mutation event for SARS-CoV-2 in humans happened very soon after the virus made the jump from a still unidentified nonhuman animal host:

“We may well have missed this period of early adaptation of the virus in humans. We previously estimated SARS-CoV-2 jumped into humans in October or November 2019, but the first genomes we have date to the very end of December. By that time, viral mutations crucial for the transmissibility in humans may have emerged and become fixed, precluding us from studying them.”

With the first effective SARS-CoV-2 vaccines soon to be rolled out globally, the virus will likely go through a series of mutations in response, the scientists note. The approach that they have developed should be helpful in quickly identifying these mutations.

For Prof. Balloux, “The news on the vaccine front looks great. The virus may well acquire vaccine-escape mutations in the future, but we’re confident we’ll be able to flag them up promptly, which would allow [for] updating the vaccines in time if required.”

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Many parents want to celebrate Thanksgiving with others despite risk

A new poll has found that parents are weighing up the potential risks and benefits of celebrating Thanksgiving with extended family during the pandemic, and deciding that keeping up with tradition may be worth the risk.

A new poll has found that parents are weighing up the dangers of celebrating Thanksgiving during the pandemic against the potential benefits of allowing children to see extended family.

Many parents, the results suggest, may opt to attend family gatherings despite the risks.

The report, published by the C.S. Mott Children’s Hospital, Michigan Medicine, University of Michigan, also offers advice to parents on how to go about Thanksgiving as safely as possible.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

Close contact transmission

According to the Centers for Disease Control and Prevention (CDC), SARS-CoV-2 spreads mainly through close contact with a person who has contracted the virus.

In these situations, the virus can spread if people touch each other — for example, through a handshake or a hug.

It can also transmit when a person with a SARS-CoV-2 infection coughs, sneezes, speaks, or sings.

Here, what projects the virus from a person’s respiratory tract — the main part of the human body that the virus infects — is liquid droplets, which can then be breathed in by another person.

Large droplets that carry the virus quickly fall to the ground. However, scientists believe that the virus can also transmit via very small droplets known as aerosols.

Aerosols can float in the air, potentially significantly expanding the distance over which the virus can transmit to another person.

Considering these modes of transmission, the CDC recommend that people regularly wash their hands, maintain distance between themselves and other people, and wear a face mask, particularly when indoors and in places with poor ventilation.

These measures are especially important given that scientists have found that people can become infected with the virus and show few, if any, symptoms, which significantly increases the risk of them unwittingly passing the virus on to another person.


While these measures may sometimes seem difficult to follow, more often than not, people appear to be complying with them. For example, an observational study found that over 90% of shoppers in the United States wore masks as mandated in late July and August.

However, according to the Mott Poll Report, significant holidays, such as Thanksgiving, are making extended families more willing to meet in person. This is despite an awareness that meeting in person may pose risks, particularly for older family members or those with underlying health conditions, who are especially vulnerable to the virus.

According to Sarah Clark, Mott Poll co-director, “As COVID-19 cases spike, many families are struggling with whether and how to continue their holiday traditions while balancing risks and benefits.”

“For many parents, holidays mean sharing special rituals across different generations and opportunities for children to connect with grandparents, cousins, and other relatives,” she adds.

“Our report suggests that while many children have spent less time with relatives during the pandemic, some parents may have a hard time foregoing holiday gatherings in order to reduce COVID-19 risks.”

– Sarah Clark

Majority intend to meet in person

The poll was nationally representative of the U.S. and involved 1,443 randomly selected adults who were carers for at least one child below the age of 12. The poll was completed in August 2020.

The poll found that 61% of parents who usually meet with extended family at Thanksgiving intended to meet them in person this year.

However, the poll also revealed that parents were taking measures to account for the pandemic.

For example, only 18% of respondents who have children who normally see family at Thanksgiving said they would involve family who lived in other states. In comparison, 40% of respondents said this would normally be the case.

The majority of participants — 88% — said that if a family member had COVID-19 symptoms or had been exposed to someone with the disease, then the family member would not be invited.

Around two-thirds of respondents said they would not invite a family member who had not been following mandated safety measures, such as wearing a face mask.

Celebrating and staying safe

The authors of the report make various suggestions on how to practice a safer Thanksgiving for those who do want to go ahead with the celebration.

The report’s authors suggest finding out to what extent children from other families have been able to socially distance and considering not inviting families where this has not been possible.

They also recommend maintaining social distance during any gatherings, spending as much time as possible outside, and discussing safety practices with children before the event.

However, they also highlight that in practice, it may be difficult to do this, and so families should seriously consider whether the benefits of holding a gathering outweigh the risks, particularly for vulnerable family members.

As Clark notes: “It may be difficult to maintain distance between children and high risk adults throughout a multiday visit or even during a lengthy dinner. Parents should be realistic about how feasible it will be to limit contact, and think carefully about whether to gather in person with high risk family members.”

As a way of maintaining traditions while keeping everyone safe, the report’s authors encourage people to think creatively about how they can reproduce significant parts of Thanksgiving at a distance.

“The key for parents is to focus on elements of the celebration that represent family traditions or that seem most important to children,” says Clark.

Parents could talk to children about what parts of Thanksgiving the children enjoy the most, and focus on reproducing aspects of these while staying at home. For example, they could use another family member’s recipe that is a favorite dish of the children.

The authors also recommend using video calls to help maintain connection.

Clark points out: “We all know that large public gatherings carry great risks of spreading COVID-19. But small and casual social gatherings where people feel most ‘safe’ are also part of what has been fueling transmission.”

“With COVID-19 cases increasing in every state, it is essential that all family members do their part to prevent further spread. That may mean celebrating the holidays a little differently this year,” she emphasizes.

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Thanksgiving 2020: 5 tips to protect mental health

For most people, Thanksgiving will be very different this year. In this article, we provide 5 basic tips to help bolster our mental health before, during, and after the 2020 holiday season.

Thanksgiving is traditionally a time to share food and frolics with our nearest and dearest. For most of us, this is unlikely to be the case this year. With travel restrictions and quarantines in place, we will need to adjust.

Although the pandemic has affected everyone in different ways, there seems to be little doubt that the average mental health of the population in the United States has declined.

At a time when family and friends are normally the closest, this year, they will be farther away. Looking after our mental health in a proactive way is more important than ever as we enter the holiday season.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

In this Special Feature, we will look at ways to fend off the seemingly inevitable blues of a physically distant Thanksgiving. Even without a pandemic to deal with, the holiday season brings stresses and strains, so with the added pressures this year has presented to us, we need to focus.

Right from the get-go, it is important to make it clear that nothing we provide below can fill the void or heal the anxiety that COVID-19 has produced. Perhaps, though, it might nudge the needle in the right direction. Sometimes, small steps, taken together, can produce significant benefits.

Before we dive in, here is something to bring to the forefront of your mind as often as possible over the coming days and weeks:

Each day, scientists are learning more about how SARS-CoV-2 works. Vaccines are coming. Yes, 2020 has been challenging, but, with medical research in our armory, we will defeat COVID-19.

1. Sleep

No article on maintaining mental health would be complete without mentioning sleep. We do not give it the space that it needs in our modern, neon-lit world. We all need to do better.

Losing sleep interferes with our mood. This is intuitive, but it is also backed by research. For instance, one study concludes, “Sleep loss amplifies the negative emotive effects of disruptive events while reducing the positive effect of goal-enhancing events.”

In other words, if we do not sleep enough, we are more likely to feel negative when things go wrong, and we are less likely to feel good when they go well.

Similarly, another study found that “individuals become more impulsive and experience less positive affect after a period of short sleep.” Once again, reduced sleep duration appears to dampen mood.

At a time when the mood of the nation is at a low ebb, sleeping a little extra might be a relatively simple way to tip the scales in our favor. For advice on getting better sleep, click here.

It is worth noting, though, that the relationship between sleep and mental health is complex and two-way — mental health issues can impact sleep quality, and a lack of sleep can damage mental health.

2. Keep active

As with sleep, any article that aims to boost mental health has to include exercise. As the temperature drops, forcing ourselves outside can become increasingly challenging. Scientists have shown that physical activity can boost mood both in the short and long term.

A review published in 2019, for instance, found a relationship between cardiorespiratory fitness and the risk of common mental health disorders. Similarly, a 2018 meta-analysis concluded that “[a]vailable evidence supports the notion that physical activity can confer protection against the emergence of depression.”

Importantly, we do not need to run a 4-minute mile to gain mental benefits from exercise. A study from 2000 found that short, 10–15-minute walks boosted mood and increased calmness.

So even if it is something simple, such as dancing in your kitchen or walking your dog for a little bit longer, it all counts.

It is true that neither exercise nor sleep can replace a hug from a friend or relative, but if our mood is momentarily boosted or our overall average mood is upped, it might help us manage disappointment better and reframe this difficult year.

3. Addressing loneliness

For many people, loneliness has already been a significant feature of 2020. Reflecting on friends and family during Thanksgiving is likely to intensify those feelings of isolation.

To combat this, make an effort to make contact. Whether it is a simple phone call or a video chat, schedule some conversations in. Remember, you are not the only one feeling lonely. If it is safe and permissible in your area, meet up with a friend somewhere outside and take a walk.

Check in with others — emails, texts, and social media can be useful in times like this. Rather than doomscrolling, send a “How are you?” to someone you miss. They likely miss you, too.

Stay occupied. Empty time can move slowly. Find a new podcast, listen to new or old songs, pick up that guitar, start drawing again, learn a new skill, or anything else. An occupied and engaged mind is less likely to dwell on the loneliness.

A recent study found that people who get involved in an enjoyable task and enter a state of flow fared better during lockdowns and quarantines. The authors write:

“Participants who reported greater flow also reported more positive emotion, less severe depressive symptoms, less loneliness, more healthy behaviors, and fewer unhealthy behaviors.”

4. Eat and drink well

Thanksgiving is associated in no small part with overindulgence. I don’t think it would be fair or reasonable to expect people, in 2020 of all years, to reduce their turkey intake.

With that said, there is growing evidence that what we eat impacts our mood. For instance, a recent review that appears in BMJ concludes:

“Healthy eating patterns, such as the Mediterranean diet, are associated with better mental health than ‘unhealthy’ eating patterns, such as the Western diet.”

With this in mind, ensuring that we eat well in the lead-up to and the days following Thanksgiving could help us keep a steady mind.

While we are discussing consumption, it is worth mentioning alcohol. In the long term, alcohol increases the risk of developing mental health issues, such as depression and anxiety. Although, at the time, alcohol might lift mood and reduce anxiety, it will not help in the long run.

5. Align expectations

Not everyone is on the same page when it comes to the pandemic. Some people might still be shielding, while others might have succumbed to “pandemic fatigue” and be returning to normal prematurely. Others still might use terms such as “scamdemic” and refuse to wear a mask.

Some family members might be pushing for a family meal, like the long distant days of 2019. Others, sensibly, might be visualizing a Zoom-based meal plan.

These differences in position have the potential to cause disappointment and additional stress. It is important to have clear and frank discussions with family members about what they can expect this year.

Remember, with any luck, next Thanksgiving will see a return to some form of normality. Hopefully, we will only have to endure this unusual and uncomfortable Thanksgiving once. If you are not comfortable with someone’s proposed plan, say “no.” And stick to your guns.

With spikes in case numbers across much of the U.S., the most sensible option is to limit human contact as much as possible.

Although laws, rules, and regulations vary between regions, the Centers for Disease Control and Prevention (CDC) have published a document outlining factors people should consider when planning get-togethers and events.

In general, gatherings with more people are risky, as are events in enclosed spaces. People can lower the risk in a number of ways, including:

  • inviting fewer people
  • meeting outdoors
  • wearing masks (unless eating)
  • remaining 6 feet (2 meters) apart
  • washing the hands frequently
  • keeping music low so that people do not need to shout
  • limiting alcohol intake

When it comes down to it, each individual has to make their own decision about how they act within the law. To protect your own mental health, make your own decision and do not allow yourself to be railroaded into doing something that you consider to be too risky.

The safest way to enjoy Thanksgiving this year, unfortunately, is to do it virtually.

The take-home

Individually, the tips outlined above cannot replace the good times we expect from Thanksgiving. However, if we make more of an effort to eat right, sleep right, and move around, the cumulative effect might be enough to enjoy some benefit.

Remember, we are on the home straight. Reach out and talk to friends and family if you are feeling low. The odds are they are feeling low, too. Never be afraid to talk about your emotions. No one is having the holiday season they expected.

As many people struggle during this time, it might be hard to see an end in sight. If you are contemplating self-harm or if you know someone who is, we have a list of excellent resources here. We are in this together, and it will end.

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

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Plasma therapy for COVID-19: Updates from Prof. Arturo Casadevall

Back in May, Medical News Today spoke to Prof. Arturo Casadevall, from Johns Hopkins, about the potential of using convalescent plasma therapy in the treatment of COVID-19. Now, we follow up with Prof. Casadevall on the latest findings.

In May, we spoke to Prof. Arturo Casadevall — chair of the Molecular Microbiology & Immunology Department at the Johns Hopkins Bloomberg School of Public Health in Baltimore, MD — about the possibility of using convalescent plasma to treat cases of COVID-19.

This procedure requires the use of donated plasma, a component of blood, from people who have had and recovered from COVID-19 to treat or prevent the disease in those most at risk of developing it.

That is because convalescent plasma from people who have recovered from COVID-19 usually contains antibodies against SARS-CoV-2. This is the virus that causes the disease.

On August 23, 2020, the Food and Drug Administration (FDA) granted emergency use authorization (EUA) for convalescent plasma in the treatment of COVID-19.

However, some scientists have called this move controversial due to a lack of conclusive evidence regarding this therapy’s effectiveness.

Now, MNT have caught up with Prof. Casadevall, who was the co-senior author on one of the trials that informed the FDA’s decision. We asked Prof. Casadevall what he thinks of the EUA and what has changed in convalescent plasma research since the last time we spoke.

We have lightly edited the interview transcript for clarity.

The EUA and research since May

MNT: The FDA granted EUA for plasma therapy on August 23, but this decision sparked some controversy. What is your take on the matter?

Prof. Casadevall: The first thing I would say is that all the issues of controversy have been [based on] newspaper reports. The truth is that I don’t even know if there is any real controversy. I think that it’s been reported to be a controversy. But let’s just assume that what they reported is correct.

I [and Prof. Nigel Paneth] wrote an op-ed in The Wall Street Journal a couple of weeks ago, arguing that the issue seems to be [based on] differences on the degree of certainty. That is, the FDA made this decision based on its regulatory power for the laws of the land that say that once […] the information is there that [a treatment] may be effective and that it is reasonably safe, that they can issue an EUA. That’s what it says.

Everyone, including myself, feels that just because an EUA has been issued doesn’t necessarily mean that one has proven beyond reasonable doubt the efficacy of plasma.

[Given] the regulatory landscape [of] the FDA, this was, in our mind, the correct decision. It is also the correct decision to continue to do randomized clinical trials. So these two are not in conflict with one another.

Because in many places, there is no randomized clinical trial. So if you get sick in a place and you go to a hospital where there is no randomized clinical trial, you can’t even join to be able to be randomized to the plasma group.

So, what this decision says is [that] the available data suggest[s] that this [therapy] may be effective if given early with a sufficient amount of antibodies.

That’s the decision. In the meantime, it is very important to continue to do all we can to establish efficacy.

MNT: Some have expressed a worry that, like vaccines, plasma therapy may be pushed out too soon.

Prof. Casadevall: You know, I’m not worried about that. I will tell you that I worked with the government scientists, the FDA, [and] the people who made this decision for months before it was [taken], and I can assure you — and I can assure [your readers] — that these government scientists are very devoted and dedicated people, and I’m not worried about that myself, based on what I know.

I think that when the regulatory agencies give the go-ahead, it will be based on science. And I would say to you, look at hydroxychloroquine: Based on the initial results, [the FDA] issued an EUA, [but] when the data was not there [to support the initial findings], they pulled it.

And that’s very important to keep in mind — that these agencies are responding to the available knowledge. And we’re in the middle of a pandemic, and we’ve got to try to make the best decisions with the available information.

MNT: The last time we spoke, in May, there was less research and less evidence around the safety and efficacy of plasma therapy for COVID-19. How has the research around plasma therapy developed since?

Prof. Casadevall: There has been a lot of new evidence. The evidence comes in four categories. The first one is — we now have reports [from] five randomized control trials.

Three had to be stopped prematurely because they ran out of [participants]. That’s in China, in Spain, and in the Netherlands.

And then there are two [more]. One was completed in India, and it did not show an effect [on] mortality, but there were problems in the study because over a third of the units did not have antibodies.

So that is a problem in the study itself. And then there is another small study from Iraq, [a] randomized control trial, showing that [plasma therapy] reduced mortality.

So the data that you have out there in the randomized control trials is suggestive that this is doing some benefit, but it’s not conclusive for a variety of issues, ranging from the changing epidemic to the problems with trials.

Then, you have the observational studies, and those are suggesting that, if given early, [convalescent plasma] is associated with a great reduction in mortality. [By] great, I mean about half.

And the two studies that I would point people to look at [are] the Houston Methodist [Hospital] study, published in the American Journal of Pathology, and then there’s one from [Mount] Sinai [Icahn School of Medicine], published in Nature Medicine.

The third piece of data — it comes from the FDA themselves, where they looked at a large number of people in a cohort that didn’t have a control [group].

But it didn’t matter, [because] when you looked at it, you saw that if you gave [convalescent plasma] early and if you gave a significant amount, there was less mortality than if you gave it late or if you gave less.

In that study, there is a really important piece of data. There is a dose response. And whenever [we] see a dose response in science, we tend to consider that [to be] very important because it’s part of what we use for assigning causality — that is, causality that [the] antibody is the active agent.

And then the fourth piece of data is coming from experiments of nature. These are people who don’t have antibodies because of congenital disease. When they get COVID-19, it becomes intractable.

And then [for] the administration of plasma — even though these are case reports, they are powerful evidence that when you give the plasma, you shut down viral replication and you clear it.

So what I would say to you is, do we have the definitive data today? No, definitive data is coming. Numerous randomized control trials have been done in the United States, in England, and [in] other parts of the world, and we will know more in the next few months, but it’s October 9 [at the date of this interview]. As you look at the data that we have today, it is suggesting that the early administration of plasma with sufficient titer is beneficial.

‘What have we learned?’

MNT: Based on the information that has emerged from the studies conducted since May and until now, have your views about plasma therapy changed in any way?

Prof. Casadevall: Certainly there is a massive amount of data available in October that was not available in May, and most of it is positive.

So [some important things that] we learned is that this is a therapy that is going to take a while to figure out how to make work well, that this is not a simple therapy, that you need to have a set amount of antibodies in the plasma, that you need to give it early, [and] that it works best in non-intubated patients.

We did not know any of this in May. In fact, I would argue that if we had designed a randomized control trial then, it would have become obsolete by now, because the information used to design the trial would have been superseded by what we have learned since then.

So I think that we have learned a lot since then.

MNT: With the research that you were involved in, what were the main challenges, and how do you think you might overcome them in future trials?

Prof. Casadevall: So [one of the trials] I’ve been involved with [is] the Mayo study, [where] Michael Joyner was the [principal investigator]. So the challenge there is to try to understand efficacy in a situation where you don’t have a control group. And that is a big challenge. It hasn’t been done before, and yet, I think that we learned a lot from that.

At Hopkins, we have two randomized control trials. They’re headed by David Sullivan and Shmuel Shoham, and these are in the outpatient space. And when we talked in May, they were theoretical.

Since then, they have been put in place, and they are rapidly accruing [participants]. The most important thing that we learned is how hard it is to set up randomized control trials in the middle of a pandemic and to keep them going when the [number of] cases switch from one part to another.

For example, one of the things that have become very apparent is that these trials are very difficult to do in any one location.

So the trials now in the U.S. [take place] in many states because the epidemic changes, you know. You had [a high number of cases in] New York City in March and April, and then you had [the same in] Arizona in the summer, and now it is moving to the Midwest.

So that is the big lesson, but the good thing is that they’re in place, they’re recruiting, [and] they’re very clean studies, because they’re happening in the outpatient space.

These [participants] are not [taking] corticosteroids. They’re not on remdesivir. They are at home, and if they’re sick, you give them a unit of plasma and you ask the question: “Do [they] progress?”

Or, the other trial looks at prophylaxis. [The participants] are at home. They’re exposed [to SARS-CoV-2] because a family member may have [COVID-19]. If you give them human plasma, do you prevent disease?

So these [studies] are happening, and I guess what you asked me [was], if we had to do everything over again, what have we learned? I think the most important thing to have learned is that […] we need to think about flexible trial design, because even if you had been able to get all the resources and get going in March and April, the information that we have learned on a weekly basis often makes the assumption that you start with obsolete.

And one of the great challenges in getting really good information in the middle of a pandemic, where science is generating information by the week, is the ability to do flexible clinical trial design that would allow some of these things to happen. And this falls into the science of clinical trials, and I think “trial” is an issue on how to go forward.

MNT: Earlier, you also mentioned a lack of resources. What resources did you feel you were missing?

Prof. Casadevall: Early on, there were very [few] resources. The only resources that we had was … the Bloomberg Philanthropies gave us some money, and the state gave us some money. We used that money to set up the clinical trials, which, months later, the government funded very well. We are funded now by the Department of Defense.

So I think the early lesson is that [receiving] money upfront can make a big difference. Because the early days are critical. The other thing that we have learned is … think about it, if you were designing a clinical trial in March or April, you didn’t have the assays.

They had not been validated. How would you have decided what plasma to use when the antibody assays and the neutralization assays and all that [were] being validated very rapidly? It’s another example of the need for flexibility, and we need to think [about] how to do this thing and how to do it better, because humanity is going to be confronting other pandemics.

And the question is, you know, how are we going to do it when bird flu comes, or when another pox virus or something [comes], or coronavirus number seven?

Out of this experience, one of the things that I hope people focus on is that the line of defense — humanity’s line of defense — is science.

You know, the military budget doesn’t help you against coronavirus.

And […] the line of defense, science‚ was actually pretty stressed before this began, you know, with funding cuts in most places, problems […] with employment and all that. Yet it is amazing when you think over 100 vaccines are in development.

We can always do things better, but we also have to celebrate the tremendous amount of work that has gone on and the options that are available in October as a result of having a vibrant worldwide scientific enterprise.

More conclusive data may be available ‘in the next 2 months’

MNT: It is sometimes easier to judge than it is to celebrate, especially when the world is in this atmosphere of anxiety, where people do not always understand what is going on, and they may start to lose trust in science. So, on a related note, what will it take to conclusively prove or disprove the efficacy of plasma therapy for COVID-19?

Prof. Casadevall: I think that certainly having a large, well-designed randomized control trial, where the plasma is given early, in high amounts … if you got [confirmation of] efficacy [in such a trial], then it would be very convincing.

If you do not get efficacy, then I am the first person to say to you: “We read all the trials, bias has crept in.”

Because we need to retain equipoise — as a scientist, one always has to basically say what will convince you that it didn’t work. And to me, it would have to be a confirmation from those [new] trials.

Trials in which this is done in patients who are intubated, or [where] there are problems with the plasma, are inconclusive. One of the most frustrating things is that a lot of the information that is coming out is simply inconclusive.

[This is] not because people aren’t working really hard to [find conclusive evidence], but because the trials [were] often designed without all the information that was needed.

The best example of that appears to be the Indian trial — a massive amount of effort … [I have] great admiration for my Indian colleagues, but when this decision was made to seek plasma, a lot of their donors had mild disease. Mild disease does not result in high antibody titers. They didn’t know that when [the trial] was set up.

But I will tell you, plasma has already given humanity a tremendous piece of information. It is safe. It cleared the way for monoclonals. It cleared the way for a lot of things.

Back in May, when we were talking, there was still a lot of discussion of an antibody-dependent enhancement. Are you going to give anti-antibodies to a patient? Are you going to trigger a cytokine storm [by doing that]?

None of that happened. So the great use of plasma […] [in] over 100,000 patients established the safety of giving antibodies to somebody who’s sick.

That is a huge contribution, because we heard, for example, that monoclonal antibodies … they are now trying to push them forward with a fraction of the experience, but that experience is resting on the plasma experience.

That is a big, big, big contribution.

And the other thing is that we — certainly [if we are based] in well-resourced areas — we have a tremendous responsibility to figure out what’s going on with plasma, because in regions that don’t have a lot of resources, this is going to have to be the therapy for the next few months, even years, because monoclonal antibodies are going to be unaffordable. We don’t have, in the immediate future, any new antiviral[s].

So plasma may be — in the U.S., in well-resourced areas — plasma may be a stopgap between a time in which you have nothing to a time when you have monoclonals and you have other reagents. [M]uch of the world may still need plasma, and we need to figure out when and how and if to use it, because that information can be life saving in those circumstances.

MNT: One last question: How long until we know when, how, and if to use plasma therapy for COVID-19?

Prof. Casadevall: Since we talked in May, we have learned that [plasma therapy] is safe, we have learned that [it has to have] high titer, and we have learned that you have to use it before people get ventilated.

So I think that there is a very high probability that, in the next 2 months, some of these trials will provide additional information. My hope is that they are conclusive.

However, if you publish a trial with 1,000 people where the average day when the plasma was given was day 8, day 10, that’s not conclusive. But I would say that if you go to PubMed and if you go to the archives and if you look [for] “convalescent plasma,” you would see an enormous amount of information that has been generated since May.

And the information is already telling you that [it] is [safe], and if you’re going to use it, use it early and make sure that the plasma has sufficient antibody content.

So I think that those are tremendous advances in relatively few months, when you consider what the situation is.

MNT: Thank you so much for your time and for all of the updates. Do you have any final remarks for our readers?

Prof. Casadevall: I would say that papers are coming out by the week, and […] I urge the [readers] and I urge anyone who’s interested to approach the data carefully […] [and] ask the question: Did they give [convalescent plasma] early, did they give enough, and what were the conditions of the [trial]?

And you can often find that information [in the studies]. And certainly, even when [convalescent plasma] is given late, we’re not getting [conclusive] results or side effects. But [in terms of establishing] the efficacy — it’s early [days].

And for those of you who are planning clinical trials, please incorporate this information into [the study papers], because it’s very important to have conclusions.

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COVID-19: Pain-numbing effect of virus may boost its spread

A new study that researchers conducted in animal models suggests that SARS-CoV-2, the virus that causes COVID-19, may deactivate a pain signaling pathway. This could explain why so many cases of the infection do not cause any symptoms, promoting viral transmission.

Estimates vary widely, but according to the Centers for Disease Control and Prevention’s (CDC) current best estimates, 40% of people with COVID-19 may experience no symptoms.

These people may carry on with their daily activities as usual, without necessarily realizing that they have contracted the virus. This may cause them to spread it unintentionally. For this reason, some scientists refer to people without symptoms as “silent spreaders.”

The CDC also estimate that up to 50% of all SARS-CoV-2 transmission occurs before the onset of symptoms.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

One recent study provides a possible explanation for asymptomatic cases and the lack of symptoms early in the course of more serious infections.

SARS-CoV-2 gains entry to its host cells via a receptor in their outer membrane called ACE2. The spike proteins that give the coronavirus its characteristic crown-like appearance latch onto these receptors.

However, the virus can also invade cells when its spikes bind to another membrane receptor called neuropilin.

This receptor’s usual binding partner is called vascular endothelial growth factor A (VEGF-A), which, among other things, promotes the growth of blood vessels.

Crucially, when VEGF-A binds to neuropilin, it also stimulates a pain signaling pathway in the nervous system.

Researchers at the University of Arizona in Tucson have now discovered that the spike protein of SARS-CoV-2 blocks these pain pathways when it locks onto neuropilin.

This suggests that the virus numbs the pain of infection, possibly to the extent that people feel few, if any, symptoms early in the disease.

The findings of this study appear in the journal Pain.

Feeling fine

“It made a lot of sense to me that perhaps the reason for the unrelenting spread of COVID-19 is that in the early stages, you’re walking around all fine as if nothing is wrong because your pain has been suppressed,” says corresponding study author Rajesh Khanna, a professor in the Department of Pharmacology at the University of Arizona College of Medicine.

“You have the virus, but you don’t feel bad because your pain is gone,” he adds. “If we can prove that this pain relief is what is causing COVID-19 to spread further, that’s of enormous value.”

Using cell cultures grown in the laboratory, the scientists showed that when VEGF-A binds to neuropilin in the membranes of rat sensory nerve cells, their firing rate increases.

When the researchers added spike proteins from SARS-CoV-2 to the culture medium, it prevented VEGF-A from stimulating the nerve cells.

Next, they demonstrated that injecting rats with VEGF-A increased the animals pain sensitivity. However, when they added the viral spike protein to the injected solution, the rats’ pain sensitivity remained at normal levels.

“The spike protein completely reversed the VEGF-induced pain signaling,” says Prof. Khanna. “It didn’t matter if we used very high doses of spike or extremely low doses — it reversed the pain completely.”

Opioid substitutes

For the past 15 years, Prof. Khanna’s team has been studying the neuropilin pain pathway with a view to developing substitutes for opioid drugs. Many people blame these drugs for an epidemic of addiction.

“We are moving forward with designing small molecules against neuropilin, particularly natural compounds, that could be important for pain relief,” explains Prof. Khanna.

“We have a pandemic, and we have an opioid epidemic. They’re colliding. Our findings have massive implications for both. SARS-CoV-2 is teaching us about viral spread, but COVID-19 has us also looking at neuropilin as a new non-opioid method to fight the opioid epidemic.”

– Prof. Rajesh Khanna

It is important to note, however, that the new study was laboratory-based. Therefore, it was unable to prove whether or not inhibiting the neuropilin pain pathway plays a significant role in humans with COVID-19.

Interestingly, scientists already know a lot about VEGF-A because of its role in promoting blood vessel growth, or angiogenesis, in cancer. Scientists have developed drugs that prevent VEGF-A from binding to neuropilin, such as Avastin, as anticancer treatments.

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

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What was the impact of Sweden’s soft approach to lockdown?

A new study suggests that Sweden’s limited lockdown measures have resulted in fewer deaths than expected.

Sweden’s softer approach to lockdown involved closing universities and other schools for older pupils and recommending that anyone with COVID-19 symptoms and everyone over 70 self-isolate.

Now, a new study suggests that these limited measures contributed to fewer deaths than expected. Still, Sweden saw more deaths from the pandemic than neighboring countries Denmark and Norway.

The new research, published in the journal Clinical Infectious Diseases, makes clear the complexity of determining which strategies for reducing the spread of the virus and saving lives are most effective.

Lockdown choices

The sudden emergence and rapid spread of SARS-CoV-2 and the accompanying disease COVID-19 have forced governments across the world to quickly decide which measures to implement to protect their populations.

Because the virus was new, governments relied heavily on computer models to determine the best courses of action. Even with these models, a significant number of unknowns made making any decision with certainty difficult.

Nonetheless, many governments followed a broadly similar approach, mandating significant lockdowns of large sections of society. Authorities typically ordered people to stay at home as much as possible and gave police powers of enforcement.

An outlier to this approach was Sweden. Rather than enforcing a hard lockdown, the Swedish government only closed universities and other schools with pupils aged 15 and older. It also recommended that everyone older than 70 and anyone with symptoms typical of COVID-19 self-isolate.

Given the major economic and social cost of a hard lockdown, there has been much interest in Sweden’s approach. Because the virus is highly infectious and, in serious cases, causes death, it was a controversial approach.

Now that the first wave of the pandemic is receding, researchers have been able to look back at the choices that governments have made to get a better sense of their effects.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

Mortality rates

In the present research, the authors analyzed data from Sweden to determine the effects of the softer approach to lockdown.

Drawing on household, employment, and population data, the researchers used computer models to examine the effects of various policy decisions made by the Swedish government.

As of May 15, Sweden had a per capita death rate of 35 in every 100,000 people, which is significantly higher than the corresponding figures in Denmark, Finland, and Norway, which were 9.3, 5.2, and 4.7, respectively.

Still, the death rate in Sweden was lower than those in other countries in Europe, including the United Kingdom, Spain, and Italy, which had respective rates of 51, 58, and 52.

Denmark, Finland, and Norway all had stricter lockdowns than Sweden, and they implemented the measures quickly. This speed, the researchers believe, accounts for the lower death rates than those in the U.K., Spain, and Italy.

By taking a softer approach, Sweden sidestepped the issue of quickly implementing large-scale changes, ending up with mortality rates between the two extremes.

Fewer deaths than expected

After analyzing Sweden’s data, the researchers found that the country’s actual death rate was lower than expected, given its lockdown policies. Rather than there being 40 times as many patients as available intensive care unit (ICU) beds, as predicted, there were five times as many patients.

Reducing the workload in ICUs is crucial, as overwhelmed ICUs are unable to cope with many who have life threatening illnesses, including COVID-19.

The researchers believe that the willingness of a significant portion of the Swedish population to voluntarily self-isolate was key to Sweden’s lower-than-expected mortality rate.

“Our study shows that individually driven infection control measures can have a substantial effect on national outcomes, and we see Sweden as a good example of this case. Higher levels of individual action would further suppress the infection, while a complete lack of individual action would likely have led to runaway infection, which fortunately hasn’t happened.”

– Dr. Peter Kasson, study author and researcher at Sweden’s Uppsala University

In addition, the researchers found that despite there being five times as many patients as ICU beds, Swedish ICUs were never overwhelmed. They speculate that people over the age of 70, who were not expected to survive, may have been turned away from ICUs.

“Analyzed by categorical age group, older Swedish patients with confirmed COVID-19 were more likely to die than to be admitted to the ICU, suggesting that predicted prognosis may have been a factor in ICU admission. This likely reduced ICU load at the cost of more high-risk patients dying outside the ICU,” the researchers observed.

“The key finding is that individual actions matter,” said Dr. Kasson. “If enough individuals stay home and take precautions when in the community, it can really change the infection curve. And we can’t let up now.”

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Convalescent plasma therapy for COVID-19: Why is it promising?

Some researchers and doctors have started using plasma from people recovering from COVID-19 to treat others who have developed the disease. Medical News Today spoke to Dr. Arturo Casadevall, from Johns Hopkins University, to learn more about this approach.

In the search for an effective treatment for COVID-19, an old method of fighting infectious diseases has recently resurfaced: transfusions with convalescent plasma. Plasma is a component of blood.

This method has a simple premise. The blood of people who have recovered from an infection contains antibodies. Antibodies are molecules that have learned to recognize and fight the pathogens, such as viruses, that have caused disease.

Doctors can separate plasma, one of the blood components that contain such antibodies, and administer it to people whose bodies are currently fighting an infectious disease. This can help their immune systems reject the pathogen more efficiently.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

Recently, researchers and healthcare professionals have been looking into the possibility of using this method to treat people with COVID-19, the respiratory disease caused by the SARS-CoV-2 virus.

In the United States, a group of researchers and doctors from 57 institutions, including Johns Hopkins University, the Albert Einstein College of Medicine, and the Icahn School of Medicine at Mount Sinai, are investigating and applying convalescent plasma therapy for COVID-19.

This is a concerted initiative — called the “National COVID-19 Convalescent Plasma Project” — born after the publication of a viewpoint paper in The Journal of Clinical Investigation in March, 2020.

The paper argued for the potential merits of passive antibody therapy in the treatment of COVID-19. It was authored by immunologists Dr. Arturo Casadevall, chair of the Molecular Microbiology & Immunology Department at Johns Hopkins Bloomberg School of Public Health, and Dr. Liise-anne Pirofski, professor of Infectious Diseases in the Department of Medicine at the Albert Einstein College of Medicine.

To understand more about convalescent plasma therapy, its merits, its risks, and its current use in COVID-19 treatments, Medical News Today recently spoke to Dr. Casadevall.

Here is what he told us, alongside more information on the current state of convalescent plasma therapy.

A therapy ‘used for over 100 years’

So, where did the idea of using convalescent plasma, or passive antibody therapy, come from?

This notion was first introduced in the late 19th century when physiologist Emil von Behring and bacteriologist Kitasato Shibasaburou discovered that they could use antibodies present in serum — another blood component — to fight the bacterial infection diptheria.

Since then, doctors have used passive antibody therapy, on and off, at least since the 1930s to treat or prevent both bacterial and viral infections, including forms of pneumonia, meningitis, and measles.

When we asked him how the idea of using convalescent plasma therapy to treat COVID-19 came about, Dr. Casadevall told us: “I have worked on antibodies my entire life professional life […], and I knew that convalescent plasma — or sera […] — was being used for over 100 years.”

“In fact, the first Nobel Prize was given [to Behring] for the use of serum to treat diphtheria, so I knew the history.” This long history of successfully using this method against different infectious diseases suggested that it might also be effective against the disease caused by SARS-CoV-2.

“I knew that in epidemics when you don’t have a lot of things, […] the blood of those who recover can have antibodies that can be used [as treatment],” Dr. Casadevall explained.

“So it’s an old idea, it’s been around for a long time, and I think that my contribution was, in fact, to alert my friends, authorities, that this [therapy] could be used in this epidemic.”

Recent research has already shown that people who have contracted SARS-CoV-2 have developed antibodies that can react to the coronavirus.

“There [are] now multiple studies that have shown that when people recover from the virus, they have in their blood neutralizing antibodies that are able to kill the virus,” Dr. Casadevall also told MNT.

Although “[p]eople differ greatly in the amount of antibodies that they make — some make large amounts, some make small amounts — […] the good news is that most have [them],” he added.

Given the willingness of people who have recovered from COVID-19 to donate blood, the method seems feasible right now. In fact, some doctors are already using convalescent plasma therapy in some cases.

Settling the matter of safety

In the U.S., the National COVID-19 Convalescent Plasma Project have already been trailing this method as widely as possible.

Dr. Casadevall told MNT that “in the United States, we have close to 12,000” people who have received the convalescent plasma treatment for COVID-19.

Based on the data obtained from a little less than half of this cohort, Dr. Casadevall and his colleagues have concluded that this approach is safe for the patients receiving treatment — the first step necessary before ascertaining the method’s effectiveness.

The team has reported these findings in a preprint that they have made available online.

“[On May 14], we put out a paper on the first 5,000 [patients] showing that [this therapy] was relatively safe. That’s the first step,” Dr. Casadevall explained.

“You want to show safety. And then the question of efficacy will be coming in the next few weeks. Right now, the data [is] being analyzed. We are hopeful,” he also told MNT.

“And,” he added, “especially since [the] Italians are reporting already that the use of convalescent plasma was associated with a drop in mortality [due to COVID-19]. We are hopeful that similar insights [will] come from the analysis of the data in the United States.”

In Europe, the European Blood Alliance — a non-profit association — report that 20 countries have initiated the use of convalescent plasma in the treatment of COVID-19 or are considering it for the near future. These include Italy, Spain, and the United Kingdom, some of the European countries most aggressively hit by SARS-CoV-2.

Demonstrating this procedure’s safety is essential because of the risks inherent to the transfusion of blood or blood components.

“[One] of the issues that we were worried about 2 months ago [when the initiative started] was whether the administration of antibodies would make things worse. Even though there’s very little precedent about that, you have to always worry that your intervention can do harm. Fortunately, we did not see any of that, so we are now focusing on efficacy.”

– Dr. Arturo Casadevall

There is also the issue that adding more liquid volume into a person’s vascular system could lead to a risky overload, Dr. Casadevall explained.

“The concerns when you give plasma [include the fact that] rarely, you can get a transfusion reaction, [and] rarely, you could have a volume overload. What do I mean by that? I mean that […] you’re putting volume into blood, and if it goes in too rapidly, it could [lead to an] overload [of the] cardiac system,” he said.

“So when we looked at the experience of the first 5,000 [patients], we were very reassured that we did not see any major problems.”

Worries and hopes going forward

While different centers in the U.S. are already using convalescent plasma in the treatment of COVID-19, Dr. Casadevall expressed a worry that the therapy is not as effective as it might be because most patients receive it too late in the course of the disease.

Aside from its use in clinical trials, the Food And Drug Administration (FDA) have approved the administration of this form of therapy only in emergency situations to patients in a severe stage of the disease, which may not be soon enough.

“Often, physicians are using the plasma on patients that are very ill, and we don’t really know whether that’s going to be as effective as if you gave it early in the course of the disease,” Dr. Casadevall pointed out.

“Here in the United States, patients have been treated when they’re intubated, but we think that is relatively late. Many physicians are trying to move it earlier, that is, when people begin to decompensate,” he added.

But even where there is a will, getting this treatment to the patients who need it sooner rather than later is not always straightforward. “Some of the problem […] is that it takes time,” Dr. Casadevall explained.

“Because let’s say the doctor orders plasma and people are getting worse. It sometimes takes a while for the plasma to arrive. Some hospitals have it on site, others have to get it from blood banking centers.”

Despite these obstacles, the use of convalescent plasma therapy is so attractive to healthcare practitioners because they can access it and use it now.

Unlike with vaccines, whose development takes time, or experimental medication, which needs to go through several different stages of testing before it can obtain formal approval, this approach allows doctors to use what is already there — the blood of those who have recovered from the illness — to treat hospitalized patients.

“People often get confused [about the difference between convalescent plasma therapy and some vaccines] because they both involve antibodies,” Dr. Casadevall told MNT.

But while vaccines also operate on the premise of stimulating a person’s immune system to block or kill the virus, they do not use “ready made” antibodies, and testing them for safety and efficacy could take a year or more.

“When you get plasma, someone else is giving you the antibodies, and you get them immediately,” Dr. Casadevall explains.

Going forward, he thinks that doctors could use this therapy alongside other options as they gradually become available.

“This [therapy] will provide something that is immediately available. I think what you [will] see in the United States [will be its] continuous use. I hope that there will be better options down the line. For example, [I and my colleagues] are trying to make antibodies from convalescent plasma that may become available in a few months. There is also a hope for monoclonal antibodies in the future and various antivirals.”

– Dr. Arturo Casadevall

“[C]onvalescent plasma provides something that can be used today with standard knowledge and standard procedures […] But we do hope that better options will be available in the future,” he reiterated.

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

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