Q: What are the risks of the newly identified coronavirus variants?

A: It’s not yet known whether mutant versions cause more severe disease, but some are likely more contagious. Scientists expect vaccines will work but are monitoring the situation.

FULL QUESTION

Subject: COVID-19 Mutation in Colorado

I know that viruses continuously mutate, but is this new mutation that was just found stateside actually more dangerous than any other mutations of the COVID-19 virus?

FULL ANSWER

On Dec. 29, Colorado officials reported the first confirmed case of COVID-19 in the U.S. due to a variant of the coronavirus that emerged in the U.K. in September.

Known as the B.1.1.7 lineage variant, but colloquially called the “U.K. variant,” the strain has spread rapidly in Britain, and scientists believe one or more of its nearly two dozen mutations have made the virus more transmissible.

A mutation is just one change to the genetic sequence. A variant usually has multiple mutations, making it a distinct virus. (To avoid stigma, we are not referring to the variants by their places of original identification.)

Meanwhile, another variant — dubbed the B.1.351 lineage variant and also referred to as 501Y.V2 — independently cropped up in October in South Africa. It shares a key mutation with B.1.1.7 and is also likely more infectious. Among numerous other genetic changes, B.1.351 has another mutation of interest that might allow it to partially evade immune responses in some people already exposed to the virus.

Researchers have also flagged another potentially concerning variant in Brazil, known as the P.1 lineage variant, that shares some of the mutations present in B.1.1.7 and B.1.351 and was observed in travelers to Japan.

There is no firm evidence yet that any of the variants cause more severe disease, although this is an active area of study.

As of Feb. 4, B.1.1.7 has been detected in 73 countries and at least 33 U.S. states, while B.1.351 has been observed in 32 nations and was first reported in the U.S. in two individuals in South Carolina. P.1 has been spotted in 11 countries. The first U.S. case was announced on Jan. 25 in a traveler returning to Minnesota from Brazil.

Before unpacking the implications of these variants for the pandemic, it’s important to emphasize that mutation itself is not surprising, as viruses mutate relatively quickly. These changes come about randomly as the pathogen replicates, making inevitable errors as the genome is copied again and again.

Variants appear all the time. “It’s very normal,” said Emma Hodcroft, a postdoctoral researcher at the University of Bern in Switzerland and a co-developer of the virus-tracking site Nextstrain, in an email to SciCheck.

Most mutations or collections of mutations don’t alter the virus’s biology or how human immune systems respond, although genomic scientists can track the alterations to understand how the virus is spreading. But on occasion, those types of mutations can arise and persist in populations, particularly if there is a competitive advantage for the virus.

“What causes us to take notice is when we see changes in how the virus behaves,” Hodcroft said, “like that one variant is expanding faster than others or than we expect.”

Even then, that’s no guarantee that a variant poses any extra threat. Over the summer, for example, Hodcroft said one variant expanded its reach across Europe, but that was mostly due to loosened restrictions and increased travel. When variants do exhibit such behavior, however, it’s worth investigating.

As the Centers for Disease Control and Prevention explains, the kinds of changes that might matter for the pandemic include those that allow the virus to:

• spread more quickly;
• increase or decrease the severity of COVID-19;
• lead existing diagnostic tests or therapeutics to fail;
• enable the virus to evade immunity resulting from natural infection or a vaccine.

With at least two variants that appear to be more contagious, scientists say concern is justified, but that the game plan remains the same: Get vaccinated and double down on public health precautions.

“The most important thing about new variants is that they still need humans in order to spread,” Hodcroft said, “so we can prevent them through the techniques we know work: masks, hand washing, staying home as much as possible, avoiding crowded spaces, & being aware of aerosol transmission risks.”

Nicholas Davies, an epidemiologist and assistant professor of mathematical modeling at the London School of Hygiene and Tropical Medicine who is studying coronavirus variants, echoed that call.

“It doesn’t spread in a different way, it just spreads more efficiently,” he told us, which means sticking to the standard public health measures will still work to limit transmission.

The other piece is immunization. “That’s really the end game for this pandemic, is getting people vaccinated,” he said. “And the emergence of these new variants I think makes that more important than it’s ever been.”

In a Jan. 15 report, the CDC likewise warned that with the arrival of B.1.1.7 to American shores and its increased transmissibility, the variant “warrants universal and increased compliance with mitigation strategies, including distancing and masking,” and said “[h]igher vaccination coverage might need to be achieved to protect the public.”

Variant Emerged in U.K.

Of all the known SARS-CoV-2 variants, B.1.1.7 has garnered the most attention and study. It has an unusually high number of genetic changes and was first identified in southeastern England when public health officials were investigating a spike in COVID-19 cases in early December, with the earliest instances stemming from patient samples taken in September. 

The variant began to quickly dominate in the region and also spread to other parts of the U.K., where it replaced other viral lineages. While it is not always easy to determine whether that type of pattern necessarily means a virus has evolved to become more contagious, Harvard epidemiologist Marc Lipsitch told us he believed there was now a consensus that B.1.1.7 is more transmissible, noting that “data from multiple places in the UK are compelling.”

The most direct evidence of an increase in transmissibility comes from contact tracing data, Davies said. Public Health England found that as of Dec. 20, 14.7% of those in contact with people infected with B.1.1.7 contracted COVID-19, compared with 11% for those not infected with the variant.

Researchers also have used modeling or other statistical techniques to estimate how much more infectious B.1.1.7 is. Davies’ group, for instance, pegged B.1.1.7 as 56% more infectious than preexisting versions of the virus in a preliminary, unpublished preprint released at the end of December.

Scientists at Imperial College London also released an unpublished report that estimated the variant increased the reproduction number, or how many people on average each person with COVID-19 infects, by 0.4 to 0.7.

Davies said that while it’s hard to pin down an exact estimate — the numbers vary based on the models — B.1.1.7 is likely somewhere between 30% and 70% more contagious.

Preliminary data from the National Health Service initially suggested that B.1.1.7 does not cause more severe COVID-19 compared with past versions of the virus, as there was no statistically significant difference in the proportion of people infected with the variant who were hospitalized or died within 28 days compared with those infected with other strains.

Subsequently, however, British authorities revealed on Jan. 22 that four analyses indicated there was a “realistic possibility” that B.1.1.7 could be more lethal, although they cautioned that this was based on limited data and was still uncertain.

Even if B.1.1.7 doesn’t cause more severe COVID-19 symptoms, experts caution that an increase in transmissibility can still lead to a large number of deaths. In fact, because of the exponential nature of viral spread, an increase in contagiousness can have a bigger effect than the same uptick in a virus’s virulence, or ability to harm a host.

Running the math on a hypothetical virus with similar characteristics to SARS-CoV-2 in a city with 10,000 infections, London School of Hygiene and Tropical Medicine mathematician and infectious disease researcher Adam Kucharski explained on Twitter that a variant that’s 50% more deadly would eventually kill 64 additional people after a month, but a variant that’s 50% more transmissible would claim an extra 849 lives.

Of B.1.1.7’s 23 mutations, 17 change the protein sequence and eight of these occur in the virus’s spike — the protein that sticks out from the surface and is used to enter human cells.

Specifically, B.1.1.7 has a mutation known as N501Y (the name refers to a change in the protein sequence at position 501 from the amino acid asparagine to tyrosine). This is of particular note because it occurs in the receptor binding domain — the spot on the spike that binds to the ACE2 receptor on human cells — and previous experiments suggest it enables the virus to bind to the human receptor more tightly. A study in mice also found that making this change allowed the animals to be more easily infected and to get sick.

Other mutations of interest include a short deletion that is predicted to alter the shape of the spike protein and another change near an enzyme-binding site that could affect how the virus enters cells.

While the mechanism for why B.1.1.7 is more contagious still needs to be studied, tighter binding to human cells — due to the N501Y mutation or perhaps in combination with other mutations — could account for the phenomenon.

“As you breathe in some virus, if the virus is more efficient at latching on to its target surface, you’re more likely to get an infection,” explained Shane Crotty, an infectious disease researcher who studies COVID-19 at the La Jolla Institute for Immunology, in an interview with the YouTube channel MedCram.

Crotty also pointed to preliminary work from a governmental lab in the U.K. indicating that people infected with B.1.1.7 had higher viral loads, or levels of the virus, in their noses than people harboring other strains. 

“If that’s true, it would say that this U.K. variant has amassed a set of mutations that let it grow a lot better in nasal passages than the previous virus and that there’s literally just a lot more virus in people’s nose,” he said. “If there’s just more virus coming out of you when you’re breathing or sneezing or coughing, then obviously it’s going to be more likely to able to infect people near you.”

So far, B.1.1.7 remains rare in the U.S., and it does not explain the surge of COVID-19 cases and hospitalizations that began in the fall.

Duncan MacCannell, the chief science officer with the CDC’s Office of Advanced Molecular Detection, told the Washington Post on Jan. 11 that he estimated that only 0.5% of COVID-19 transmission in the country involves the variant.

But many scientists expect the proportion of COVID-19 cases due to the variant will rise.

Trevor Bedford, a computational biologist studying viral evolution at the Fred Hutchinson Cancer Research Center and co-developer of Nextstrain, said in a Jan. 7 interview with NPR that based on the timeframe observed in the U.K., he thought B.1.1.7 could become the dominant strain in the U.S. by March.

CDC modeling, shared in a Jan. 15 report from the agency, similarly concluded that B.1.1.7 could become the predominant variant in the month of March.

Variant Identified in South Africa

Compared with its U.K. counterpart, less is known about B.1.351, which was first observed in South Africa. In a preprint posted on Dec. 22, scientists noted that the variant quickly came to be the dominant virus in the country’s two most southern provinces and might be more transmissible.

Few research groups have attempted to quantify the variant’s possible increase in contagiousness, although one tentatively estimated it to be 50% more infectious, with a range between 20% and 113%.

According to the same unpublished report, the case fatality ratio did rise in the region as the variant took over, suggesting a possible effect on disease severity, but there is no firm evidence that B.1.351 is more deadly than ancestral viruses.

Davies, the London School of Hygiene and Tropical Medicine epidemiologist who also co-authored the preprint, explained that the proportion of people dying could have gone up for a variety of reasons unrelated to a change in viral virulence.

“When hospitals are under more pressure the standard of care that they’re able to provide tends to go down,” he said. “So it could be, for example, that because [the variant is] more transmissible, they’re seeing more cases, and they’re less able to treat the people coming in.”

B.1.351 harbors multiple mutations in its spike protein, three of which occur in the receptor binding domain. This includes N501Y — the key mutation in B.1.1.7 — and another one nearby, E484K. 

E484K is especially noteworthy, as researchers have found that the mutation reduces the ability of antibodies collected from people who recovered from COVID-19 to neutralize the virus. This raises concerns that the variant could pose more of a risk to populations because it could be better at reinfecting people and vaccines might not work as well against the variant.

Most scientists, however, caution against assuming the worst. As Jesse Bloom, a researcher who studies viral evolution at the Fred Hutchinson Cancer Research Center whose lab performed the antibody experiments, explained on Twitter, there is no reason to think that all immunity would be lost or that existing vaccines would suddenly fail.

“I’m confident current vaccines will be useful for quite a while,” he said, noting that the E484K mutation only reduced the neutralization activity of the antibodies present in some people’s blood, and didn’t eliminate it for anyone.

“So we need to monitor these mutations, and be prepared to update vaccines eventually if needed,” he added. But, he said, less effective neutralizing antibodies, “while worrying,” are “not the same as complete elimination of all immunity.”

Indeed, Moderna announced on Jan. 25 that the antibodies collected from people immunized with its vaccine were still able to neutralize a virus with the full set of spike mutations present in the B.1.351 variant, but it took around six times more antibody to do so than for previous versions of the virus. The results have not yet been peer reviewed, but were posted in a preprint to bioRxiv in collaboration with researchers at the National Institutes of Health.

Although in theory the N501Y mutation, by virtue of being located where it is on the spike protein, might also be a concern for immune evasion, experiments thus far have not revealed any problems. 

Bloom’s lab, for example, did not find that mutations in N501 strongly diminished the ability of any person’s antibodies to bind to the virus. A similar test on antibodies from 20 people vaccinated with the Pfizer/BioNTech vaccine also found no reduction in the ability of those antibodies to neutralize a virus with the N501Y mutation, according to an unpublished report conducted by scientists at the University of Texas in collaboration with Pfizer.

Public Health England also reported on Jan. 14 that antibodies from people infected with non-B.1.1.7 viruses still neutralized the variant, and vice-versa.

Other experiments from the vaccine makers likewise suggest B.1.1.7 is unlikely to pose a problem for the current shots. As detailed in a report published in the journal Science, Pfizer found that antibodies from people immunized with its vaccine could neutralize a virus with B.1.1.7’s full set of spike mutations almost as well as an unmutated virus. Moderna reported similar findings for its vaccine on Jan. 25.

The good news is that should any variant prove to be evading a vaccinated person’s immune response, the two COVID-19 vaccines with emergency authorization in the U.S. can be quickly modified. Both use messenger RNA to train the immune system to recognize SARS-CoV-2, which can be revised by swapping in a molecule with a slightly different sequence.

Recent Variant in Brazil

Relatively little is known about the P.1 lineage variant, which a group of scientists first named in a Jan. 12 post on a virology discussion forum. Similar to the situation in the U.K. and South Africa, the variant was identified following a surge of COVID-19 cases, this time in Manaus, Brazil.

Although P.1 arose independently, it shares several genetic changes with the other variants of concern, including N501Y and E484K.

Editor’s note: SciCheck’s COVID-19/Vaccination Project is made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over our editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation. The goal of the project is to increase exposure to accurate information about COVID-19 and vaccines, while decreasing the impact of misinformation.

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Callaway, Ewen. “‘A bloody mess’: Confusion reigns over naming of new COVID variants.” Nature. 15 Jan 2021.

“New COVID-19 Variants.” CDC. Updated 15 Jan 2021.

Tegally, Houriiyah et al. “Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa.” medRxiv. 22 Dec 2020.

“B.1.1.7 report.” Global Report Investigating Novel Coronavirus Haplotypes. Updated 4 Feb 2021.

“US COVID-19 Cases Caused by Variants.” CDC. Updated 2 Feb 2021.

“B.1.351 report.” Global Report Investigating Novel Coronavirus Haplotypes. Updated 4 Feb 2021.

“South Carolina detects first US cases associated with variant first detected in South Africa.” Press release. CDC. 28 Jan 2021.

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“MDH lab testing confirms nation’s first known COVID-19 case associated with Brazil P.1 variant.” Press release. Minnesota Department of Health. 25 Jan 2021.

Faria, Nuno R. et al. “Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings.” Virological.org. 12 Jan 2021.

Meredith, Sam. “Japan has found a new Covid variant. Here’s how it compares to virus strains in the UK, South Africa.” CNBC. 11 Jan 2021.

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Hodcroft, Emma. Postdoctoral researcher, University of Bern. Email sent to FactCheck.org. 14 Jan 2021.

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Lauring, Adam S. and Emma B. Hodcroft. “Genetic Variants of SARS-CoV-2—What Do They Mean?” JAMA. 6 Jan 2021.

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“Quotes: Britain says new COVID-19 variant may carry higher risk of death.” Reuters. 22 Jan 2021.

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Lipsitch, Marc. Professor of Epidemiology, Harvard T.H. Chan School of Public Health. Email sent to FactCheck.org. 13 Jan 2021.

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Editor’s note: FactCheck.org does not accept advertising. We rely on grants and individual donations from people like you. Please consider a donation. Credit card donations may be made through our “Donate” page. If you prefer to give by check, send to: FactCheck.org, Annenberg Public Policy Center, 202 S. 36th St., Philadelphia, PA 19104. 

The post What Do the New Coronavirus Variants Mean for the Pandemic? appeared first on FactCheck.org.

Q: Did a recent study in Denmark show that face masks are useless for COVID-19?

A: No. The study found that face masks did not have a large protective effect for wearers — not that masks provide no protection at all or don’t offer benefits to others. 

FULL QUESTION

Are masks proven to be useless for COVID-19?

FULL ANSWER

News of the results of a recent randomized controlled trial in Denmark testing a face mask intervention has led some to conclude that masks are ineffective against the coronavirus, or SARS-CoV-2. 

But scientists say that’s the wrong takeaway — and even the authors of the study say the results shouldn’t be interpreted to mean masks shouldn’t be worn.

The trial evaluated whether giving free surgical masks to volunteers and recommending their use safeguarded wearers from infection with the coronavirus, in addition to other public health recommendations. The study didn’t identify a statistically significant protective effect for wearers, but the trial was only designed to detect a large effect of 50% or more. And the study didn’t weigh in on the ability of masks to prevent spread of the virus from wearers to others, or what’s known as source control, which is thought to be the primary way that masks work.

As a result, the most that can be said is that this particular study, under the conditions at the time in Denmark, didn’t find that the face mask intervention had a large protective effect for wearers — not that masks provide no protection at all or don’t offer benefits to others. 

Social media posts nevertheless latched onto the study to claim that the trial “proves masks offer NO protection from COVID” or that masks “don’t work,” as several posts claimed. Another post inaccurately described the results as “conclusive,” despite the fact that the authors specifically wrote that their findings were “inconclusive.”

Other articles shared on Facebook failed to provide sufficient context for the study, with one headline from the Ron Paul Institute for Peace and Prosperity reading, “Your Face Mask Is Not Protecting You.” Yet another from Sharyl Attkisson, who has previously spread misinformation about vaccines, misleadingly states that there was “no statistically significant difference when it comes to wearing a mask or not outside the home to prevent Covid-19 spread.”

Again, the study only assessed the personal protective effect of a mask intervention, not the potential for masks to hamper spread of the virus to others.

The Danish trial, known as the Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection, or DANMASK-19, was published in Annals of Internal Medicine on Nov. 18 along with two editorials to provide more context to the findings.

It’s the first randomized controlled trial involving face masks and COVID-19 to report results. Around 6,000 people who left their homes for at least three hours a day participated, with approximately half being given a box of 50 surgical masks and being told to wear a mask whenever outside of their homes, while the other half was not given masks or such a mask recommendation.

The study was conducted at a time when Danish authorities were not recommending masks to the general public, so most people both groups would encounter were not likely to be masked. Both groups were told to follow national public health guidance, which included physical distancing, avoiding crowds and washing hands.

After a month, 42 people in the mask group, or 1.8%, had been infected with SARS-CoV-2, as measured by at-home finger-prick antibody tests, a positive PCR test result or a COVID-19 diagnosis, compared with 53 people, or 2.1%, in the control group.

While fewer people in the masked group became infected — equivalent to an 18% reduction in risk — the difference was not statistically significant, meaning the result may have come about by chance. Given the observed number of infections in each group, the plausible effect of the mask intervention ranged all the way from a 46% decrease in infection to a 23% increase.

It’s this negative result that some have interpreted to mean that masks are ineffective. But that’s not how the authors frame their findings.

Bundgaard, et al.: Our results suggest that the recommendation to wear a surgical mask when outside the home among others did not reduce, at conventional levels of statistical significance, the incidence of SARS-CoV-2 infection in mask wearers in a setting where social distancing and other public health measures were in effect, mask recommendations were not among those measures, and community use of masks was uncommon. Yet, the findings were inconclusive and cannot definitively exclude a 46% reduction to a 23% increase in infection of mask wearers in such a setting. It is important to emphasize that this trial did not address the effects of masks as source control or as protection in settings where social distancing and other public health measures are not in effect.

Elsewhere, the authors noted that the data were “compatible” with a less than 50% degree of self-protection and emphasized that their results “should not be used to conclude that a recommendation for everyone to wear masks in the community would not be effective in reducing SARS-CoV-2 infections, because the trial did not test the role of masks in source control of SARS-CoV-2 infection.”

University of Hong Kong infectious disease epidemiologist and mask researcher Benjamin Cowling told us he was not surprised by the findings and said it was important to distinguish between an absence of evidence and evidence of absence on the utility of masks.

“In the Danish mask study, their results are consistent with maybe 20% protection conferred by face masks, which is in line with my estimates for influenza,” he said in an email. 

“While some readers seem to conclude from the Danish study that masks are not effective, I would only conclude from the Danish study that masks are not /highly effective/, which we already suspected,” he continued, adding that it does not mean that masks are ineffective. “Even 20% protection would be very valuable when we are trying very hard to slow down COVID transmission as much as we can with a range of public health measures.”

The paper’s lead author, Dr. Henning Bundgaard of the specialty hospital Rigshospitalet and Copenhagen University Hospital, told Forbes much the same.

“Even a small degree of protection is worth using the face masks,” he said, “because you are protecting yourself against a potentially life-threatening disease.”

An accompanying editorial penned by the editor-in-chief of the journal and colleagues explained that while the study suggests that the personal protective effect of masks is “likely to be small,” the study “does not disprove the effectiveness of widespread mask wearing.”

On the contrary, the editorial argues that together with the other existing data in support of masks, the “results of this trial should motivate widespread mask wearing to protect our communities and thereby ourselves while we await more definitive evidence during this pandemic.”

The Centers for Disease Control and Prevention issued an updated scientific brief earlier this month that for the first time emphasized the ability of masks to protect wearers, based on lab studies that find masks can block virus particles and some observational and epidemiology studies.

The other editorial — by experts with the public health initiative Resolve to Save Lives, including former CDC director Dr. Thomas Frieden — highlighted several limitations of the study.

For one, the trial was done in April and May when there was relatively little virus circulating in Denmark, which might have made it more difficult to pick up a protective effect of mask wearing.

Not everyone in the mask group followed through on the advice to wear a mask, either, with 46% of people self-reporting that they wore the masks “as recommended”; 47% “predominantly as recommended”; and 7% “not as recommended.”

Most critically, Frieden and colleagues suggested that the antibody tests used to diagnose SARS-CoV-2 infection could have led to a fair number of false positives, especially given the low prevalence of the coronavirus at the time. Even with those false positives evenly distributed between the two groups, that would have biased the result to be negative.

Other scientists at Stanford University and George Washington University previously expressed concern with the study design, including the fact that the study was not large enough to identify protective effects less than a 50% reduction in risk, and the likelihood that any results would be misinterpreted.

The takeaway about masks, then, is still quite similar to the earlier public health advice, which is that people should wear them, but not assume that they will be protected. That means continuing to follow all public health guidelines, including washing hands and staying physically apart from other people whenever possible.

Editor’s note: FactCheck.org does not accept advertising. We rely on grants and individual donations from people like you. Please consider a donation. Credit card donations may be made through our “Donate” page. If you prefer to give by check, send to: FactCheck.org, Annenberg Public Policy Center, 202 S. 36th St., Philadelphia, PA 19104. 

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The post Danish Study Doesn’t Prove Masks Don’t Work Against the Coronavirus appeared first on FactCheck.org.

Q: Does vitamin D help protect against COVID-19?

A: Some scientists have hypothesized vitamin D might be helpful, but there is no direct evidence that vitamin D can prevent COVID-19 or lessen disease severity. Nevertheless, it should be part of a healthy lifestyle.

FULL QUESTION

Could vitamin D help decrease the chance of covid 19?

FULL ANSWER

As the coronavirus has spread around the globe, some scientists have proposed that vitamin D could help with COVID-19, the disease caused by the virus. 

Former Centers for Disease Control and Prevention Director Dr. Tom Frieden, for example, published a March 23 column on Fox News’ website suggesting that vitamin D could reduce a person’s COVID-19 risk.

“There are many crackpot claims about miracle cures floating around,” he wrote, “but the science supports the possibility – although not the proof – that Vitamin D may strengthen the immune system, particularly of people whose Vitamin D levels are low.”

The idea stems in part from experiments that have found that the vitamin, which is synthesized in the skin after sun exposure and is found in select foods, is used by the immune system. Some research also suggests vitamin D supplements might protect against respiratory infections, especially if someone is deficient in the vitamin. And many of the people most affected by the coronavirus, such as the elderly and minority populations, tend to have lower vitamin D levels.

But experts caution against overinterpreting preliminary correlations or hypothetical mechanisms. As Pennsylvania State University nutrition researcher A. Catharine Ross told us, associations are not the same as cause and effect, and the evidence either for or against vitamin D and COVID-19 is “extremely weak.”

A rapid review from Oxford University’s Centre for Evidence-Based Medicine found “no clinical evidence” that vitamin D could prevent or treat COVID-19, and another review on the topic published by nearly two dozen nutrition experts in BMJ Nutrition, Prevention & Health recommended avoiding vitamin D deficiency, but warned against taking high doses of the vitamin.

“As a key micronutrient,” the authors wrote, “vitamin D should be given particular focus—not as a ‘magic bullet’ to beat COVID-19, as the scientific evidence base is severely lacking at this time—but rather as part of a healthy lifestyle strategy to ensure that populations are nutritionally in the best possible place.”

Thus, while it’s a good idea to get enough vitamin D — pandemic or not — it’s too early to say that a lack of vitamin D makes COVID-19 worse, or that supplementing with vitamin D provides any protection against the disease. 

Vitamin D Basics

Although called a vitamin, vitamin D acts as a hormone in the body, and is best known for building strong bones, which is done in large part by promoting absorption of calcium and phosphorus in the intestine.

“It’s actually a prohormone, and of all the nutrients that we have, it’s the only nutrient where the main source is not diet,” said Susan Lanham-New, a vitamin D researcher at the University of Surrey in the U.K.

Instead, she told us, most of a person’s vitamin D is made in the skin upon exposure to sunlight, which is why darker-skinned people are more likely to have lower levels of the vitamin, and why people who go outside less frequently, including those who are older or less healthy, are susceptible to deficiencies.

For vitamin D to be used by the body, it must be converted into an active form, typically by the liver and kidney, according to a National Institutes of Health fact sheet. The nutrient is found naturally in only a few foods, such as eggs and oily fish, but is more widely available in the U.S. in food that has been fortified, including milk and cereals.

While there is a debate about exactly how much vitamin D a person needs, and what constitutes a deficiency, Lanham-New said a commonly used metric for deficiency is a blood level below 25-30 nanomoles per liter. Too little vitamin D can lead to rickets in children or osteomalacia in adults — conditions in which bones become soft and deformed. 

More is not always better, however, since vitamin D is fat-soluble, and is stored in the body. “You can get what we call hypercalcemia if you take too much vitamin D,” Lanham-New said, referring to elevated levels of calcium in the blood that can be especially dangerous for those with kidney diseases.

Vitamin D and Immunity

Beyond its role in bone health, vitamin D is also known to function in the immune system, which is a key reason why some think it’s plausible the nutrient might impact COVID-19.

Lanham-New, for example, said that vitamin D receptors are present on immune cells, and some immune cells make enzymes that help convert the nutrient into an active form.

“That very much provides the scientific rationale for the potential role of vitamin D in maintaining” the immune system, she said.

Some experiments in cultured cells have shown that vitamin D can trigger the production of antimicrobial peptides, including in lung cells, that might act to fight off invading pathogens.

Other lab experiments have found vitamin D might act to tamp down overactive immune responses by tilting those responses toward less inflammatory ones, including by reducing the production of certain pro-inflammatory cytokines, or signaling proteins. 

Some researchers have hypothesized that this mechanism might be relevant to the coronavirus, since some COVID-19 patients experience life-threatening surges of cytokines known as cytokine storms that can damage organs as immune cells rush into the lungs to clear the virus from the body.

But while a lot of basic research points to vitamin D having a role in the immune system, it is less clear if these mechanisms are applicable in clinical practice. Studies assessing whether vitamin D can treat or prevent infectious diseases have generally been inconsistent.

There is some evidence that vitamin D can protect against respiratory tract infections. In 2017, researchers at Queen Mary University of London published a meta-analysis in the journal BMJ that pooled individual patient data from 25 randomized controlled trials testing vitamin D supplementation in a variety of illnesses, including influenza, pneumonia, colds and ear infections. 

The authors identified a protective effect for those taking vitamin D supplements daily or weekly, with the greatest benefit going to those who had the lowest levels of the vitamin to start. Periodic large doses, or boluses, of vitamin D were not effective.

An accompanying editorial, however, noted that the absolute risk of coming down with at least one respiratory infection when taking vitamin D supplements dropped by only 2 percentage points — from 42% to 40% — and that given differences between the studies that were analyzed, large randomized controlled trials were still needed.

Lack of Evidence for Vitamin D and COVID-19

Because the coronavirus is so new, little rigorous research has been done specifically on vitamin D and COVID-19.

Oxford’s rapid review, which was posted last month and reflected literature searches performed in April, did not identify any clinical evidence that vitamin D is beneficial for COVID-19. The report concluded that “well-masked randomized trials” were needed before specifically recommending the nutrient for COVID-19, but that Britons should already be taking vitamin D supplements anyway, per national guidance. 

Since then, a variety of published and unpublished studies investigating potential links between vitamin D and COVID-19 have appeared, but Dr. Joseph Lee, a general practitioner and co-author of the report, told us that he was not aware of any subsequent studies that would alter his group’s recommendation that “people should take vitamin D, but not because of COVID-19.”

Lanham-New, who was the lead author of the BMJ Nutrition, Prevention & Health review, also said her conclusions had not changed.

One U.K. study, published on May 6 in Aging Clinical and Experimental Research, identified a crude association between the average vitamin D level reported in 20 European countries and the number of per-capita COVID-19 cases and deaths in those nations. 

Another similar paper, appearing in the Irish Medical Journal, found an inverse relationship between the vitamin D levels in older people in different European countries, as reported in past studies, and a country’s COVID-19 mortality rate, with fish-loving Nordic countries generally faring better than those in southern Europe.

But these so-called ecological epidemiology studies can only hint at any effect of vitamin D, since they’re simple correlations at the population level. “This is not a design suited to identifying causal effects,” Lee said, “and I would not consider them as evidence of a role for vitamin D in COVID-19.”

Other reports also claim to identify links between lower levels of vitamin D and COVID-19 infection or disease severity in different cohorts of people, but most of these have not yet been vetted by other scientists through peer review. 

One unpublished report of 780 confirmed COVID-19 cases in Indonesia found that the majority of deaths occurred in patients with abnormally low vitamin D blood levels, and claimed to have found an association between vitamin D deficiency and COVID-19 mortality after controlling for other factors, such as other preexisting health conditions.

But as Lanham-New noted in an interview, the paper “doesn’t in any way prove cause and effect.” Lee, too, said that while the authors attempted to control for other health conditions, the group did so in an odd way, lumping all of the conditions together. And even if the team had controlled for them individually, that doesn’t necessarily eliminate bias, so the relationship could reflect the fact that people who are in poorer health generally fare worse with COVID-19.

“It is relatively easy to calculate associations, and that is what most of these papers have done,” Penn State’s Ross said. “But associations do not show cause and effect, and in fact, ‘reverse causation’ is not carefully considered.” The disease itself could cause a reduction in a person’s vitamin D levels, she said, noting that there are negative associations of serum vitamin D with diabetes, obesity and other infections. “I place little confidence on any of these studies,” she said.

More credible, Ross said, were two analyses of U.K. biobank data, neither of which support the idea that less vitamin D leads to a higher risk of COVID-19 infection. Given concerns that the disproportionate number of coronavirus infections in blacks and South Asians in the U.K. could be due to lower vitamin D levels in darker-skinned people, the researchers checked to see if there was any connection between a person’s vitamin D levels, which had been measured in participants about a decade ago, and testing positive for COVID-19.

While the published report affirmed that black and South Asian participants were several times more likely to test positive for COVID-19 than whites, there was no association with vitamin D. The authors concluded that vitamin D “is unlikely to be the underlying mechanism for the higher risk observed in black and minority ethnic individuals and vitamin D supplements are unlikely to provide an effective intervention.”

The other analysis, which Lanham-New said has since been submitted to a journal with additional participant data, found no difference in vitamin D status among those who tested positive versus negative for COVID-19. She said additional work was planned once COVID-19 severity and mortality data became available.

Another consideration when interpreting many observational studies, Lee said, is something called collider bias, which can sometimes result in spurious correlations when the people included in a dataset aren’t representative of the wider population. Some researchers have already noted that COVID-19 studies may be especially prone to collider bias, making it hard to identify risk factors and medications that work.

Consider a study analyzing outcomes among people who are tested for COVID-19. Some people are likely getting tested because they are quite ill and have been admitted to the hospital, while others may be tested because they’re a health care worker or because they’re more privileged and have access to testing.

In this scenario, Lee said, people with good levels of vitamin D will be less likely to test positive, compared to the sick people. “This selection will in itself induce an association between low vitamin D and COVID-19 positive tests or severity of disease,” he said, “even if it isn’t true in the general population.”

Recommendations

In the end, Ross is skeptical that vitamin D will prove to be beneficial for COVID-19, although she hesitated to entirely discount the possibility, given how much is still unknown about the disease.

“[I]t is hard for me to conceive that vitamin D has much chance of being as effective as other kinds of treatments, if at all,” she said. “We don’t know however.”

Several randomized controlled trials are in the works, which may reveal a more concrete answer.

Her recommendation, irrespective of COVID-19, is to consume vitamin D-rich foods or take a supplement to provide the recommended dietary amount, or RDA, of 600-800 International Units per day. This matches the Institute of Medicine’s national guideline, which Ross helped write, and which assumes minimal sun exposure.

One cup of fortified milk, for example, contains 120 IUs of vitamin D, while a 3-ounce serving of cooked salmon provides 570 IUs.

Lanham-New emphasized that excessive doses of vitamin D should not be used. But especially for those who have been cooped up indoors while social distancing, it may be a good idea to take regular supplements. 

“If you’re in self-isolation, definitely be taking a vitamin D supplement according to your government guidelines,” she said. 

Lee also pointed to following state or national vitamin D recommendations. “There is no reason to think it will help with COVID-19, but that might change when the trials report,” he said of vitamin D. “Our advice is to take vitamin D in accordance with local guidelines.”

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Sources

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Johnson, Larry E. “Vitamin D Deficiency.” Merck Manual Consumer Version. Accessed 5 June 2020.

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Lanham-New, Susan. Head of the Department of Nutritional Sciences, University of Surrey. Interview with FactCheck.org. 5 June 2020.

Bischoff-Ferrari, Heike and Walter Willett. “Comment on the IOM Vitamin D and Calcium Recommendations.” The Nutrition Source, Harvard T.H. Chan School of Public Health. 25 Dec 2010. 

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The post Does Vitamin D Protect Against COVID-19? appeared first on FactCheck.org.

Q: Does ibuprofen make COVID-19 worse?

A: There is no evidence that ibuprofen or other non-steroidal anti-inflammatory drugs can make COVID-19 cases more severe. You should consult your doctor before changing medications.

FULL QUESTION

Is it true that using ibuprofen has been shown to worsen symptoms of Coronavirus?

I’m getting warning that Advil makes coronavirus condition worse in affected patients. Patients should only take Tylenol. Is there any evidence this is true?

Is it unsafe to use ibuprofen in the current outbreak of Covid-19 virus? Some state that it magnifies the symptoms of the virus by 10-fold?!

FULL ANSWER

Many readers have written in to ask whether ibuprofen or other non-steroidal anti-inflammatory drugs, or NSAIDs, can worsen COVID-19, the disease caused by the novel coronavirus. Other NSAIDs include over-the-counter painkillers such as naproxen (Aleve) as well as prescription-only pills such as celecoxib (Celebrex), which is used to treat arthritis.

The idea has been circulating on social media and also has been promoted to some degree by a few national governments. While there are some good reasons for certain patients to avoid NSAIDs generally, there is no evidence that ibuprofen — which is sold under the brand name Advil — or other similar drugs exacerbate the disease. Instead, the notion is simply a hypothesis that has not been tested.

Much of the hubbub over ibuprofen appears to have started with comments from the French health minister, Olivier Véran, who said in a March 14 tweet that taking anti-inflammatory drugs such as ibuprofen “could be a factor in worsening the infection.” He advised people with fevers to take paracetamol, the European name for acetaminophen, or Tylenol, instead. He also suggested that people already taking anti-inflammatories should consult with their physicians.

A few days earlier, a letter published in the British medical journal The Lancet Respiratory Medicine hypothesized that ibuprofen could make it easier for the new coronavirus, SARS-CoV-2, to enter cells. As we’ll explain, that’s possible, but there is no evidence yet to suggest that’s the case. There could also be positive effects of NSAIDs on the virus.

Soon after, inaccurate messages sounding the alarm about ibuprofen flooded social media networks and messaging apps. One of the viral warnings many of our readers asked about claims a lab in Vienna found that the “vast majority” of people who died from COVID-19 had taken ibuprofen and that a nurse at Vancouver General Hospital said, “Advil makes the virus 10x worse” and “kickstarts the virus into pneumonia.”

The message appears to be a modified version of a fake WhatsApp phone message circulating in Germany that also cited an institution in Vienna. The Medical University of Vienna called the messages “fake news” and told Politico that it had neither discussed the issue internally nor done any research on ibuprofen and COVID-19.

The name-checked Vancouver hospital has also been similarly targeted, with someone circulating a fake memo about ibuprofen and COVID-19 bearing the hospital system’s logo. The hospital system explains on its website that the memo “was not an authentic memo,” and told us in an email that they “did not issue” the message our readers asked about.  

After an initial news report that a World Health Organization spokesman endorsed the recommendation to avoid ibuprofen, the WHO clarified that it did not advise “against the use of ibuprofen.” 

The group said in a tweet that in its consultations with physicians treating COVID-19 patients, it has not heard of any negative effects of ibuprofen beyond its known side effects, and that it “is not aware of published clinical or population-based data on this topic.”

Q: Could #ibuprofen worsen disease for people with #COVID19?

A: Based on currently available information, WHO does not recommend against the use of of ibuprofen. pic.twitter.com/n39DFt2amF

— World Health Organization (WHO) (@WHO) March 18, 2020

Other medical groups and health agencies also chimed in, iterating that there isn’t evidence linking worse COVID-19 symptoms to ibuprofen.

For example, the National Institute of Allergy and Infectious Diseases, or NIAID, said in a statement that more research is needed, but there currently is “no evidence that ibuprofen increases the risk of serious complications or of acquiring the virus that causes COVID-19.”

Still, some governments are advising against ibuprofen for COVID-19 patients or recommending other medicines. England’s National Health Service, for instance, acknowledges that there is “currently no strong evidence” that ibuprofen can worsen COVID-19 symptoms, but recommends acetaminophen for people treating COVID-19 “until we have more information.”

So how legitimate is the concern? Experts told us that it’s possible ibuprofen could have a negative effect on COVID-19 patients, but it’s purely hypothetical at this point.

Potential Mechanisms

To begin to think about whether NSAIDs are a good idea or not for COVID-19 patients, it’s useful to review their chemistry and what they do in the body.

The drugs relieve pain and reduce fevers by blocking an enzyme known as cyclooxygenase, which prevents the formation of molecules called prostaglandins. Prostaglandins have a variety of effects, but generally promote inflammation, which is part of the body’s immune response.

In news articles, some scientists and physicians have proposed that ibuprofen or other NSAIDs could dampen the immune response to COVID-19 or otherwise make the infection worse, as some have contended is true for other respiratory infections. But as the NIAID has said, there is “no conclusive evidence that taking ibuprofen is harmful for other respiratory infections.”

And scientists who study these mechanisms say it’s not necessarily the case that NSAIDs would tamp down the immune system and hamper the body’s efforts to eliminate a pathogen. That’s because while prostaglandins are thought of as pro-inflammatory, some can have the opposite effect. And it’s not always clear whether a more or less active immune response is better. While a patient wants a robust enough response to clear the virus, too strong of a response can be deadly.

“The prostaglandins suppressed by NSAIDs can be harmful or beneficial in an inflammatory reaction like the one that proves fatal in COVID-19,” University of Pennsylvania prostaglandin researcher Garret FitzGerald told us.

In a letter published in the journal Science, FitzGerald called the French minister’s advice on ibuprofen “misguided,” and he outlined examples from the literature that demonstrate a number of different possibilities. 

In one instance, mice infected with a different coronavirus were more likely to die when a particular prostaglandin was reduced because the molecule played an important role in limiting an overactive immune response.

But on the flip side, one prostaglandin can inhibit replication of the SARS virus, which is highly similar to the coronavirus behind the current pandemic. And researchers have previously found that the anti-inflammatory drug indomethacin can actually prevent the SARS virus from assembling its RNA genome.

There’s also some evidence that the SARS virus boosts prostaglandin production.

“Based on these findings, if we see a clinical signal, we can rationalize it,” FitzGerald wrote, “but therein lies the challenge. Many clinical anecdotes remain stalled in biological plausibility.”

In an email, FitzGerald cautioned that all of these pieces of evidence are from in vitro experiments in cells or in animal models with related, but distinct viruses. “So the message is that we need to do the basic research with COVID-19 itself and carefully model different stages of the human disease to see if there might be a place for NSAIDs or that they make things worse,” he said. “We are a long way off a public health advisory either way.”

He also found the recommendation for acetaminophen to be curious, since it also acts on cyclooxygenase to inhibit prostaglandin formation, albeit to a lesser extent than standard NSAIDs. So if there is a problem with the drugs and COVID-19, that doesn’t necessarily mean acetaminophen is a good choice.

Other scientists agree that it’s plausible that ibuprofen could affect COVID-19 patients, but that it’s simply impossible to say without more research.

“You could imagine that by using NSAIDs that you do change the balance of these prostaglandins and other small lipid mediators, and that that changes your immune response,” said University of Iowa coronavirus researcher Stanley Perlman.

“That being said,” Perlman added, “there’s not lots of data showing that you make an interpretable difference in these levels, and then how that affects outcomes. So right now, it’s really more speculative than anything else.”

The other main hypothesis for why ibuprofen might be especially dangerous for COVID-19 patients comes from a March 11 correspondence letter in the The Lancet Respiratory Medicine. 

Much of the article, which was not peer-reviewed, discusses potential reasons why people with high blood pressure or diabetes appear to be more susceptible to COVID-19. The basic claim, which the authors later emphasized was only a hypothesis, is that these patients could be at higher risk because of the medications they take to manage these conditions. 

Drugs known as angiotensin-converting enzyme, or ACE, inhibitors and angiotensin II type-I receptor blockers, they said, raise the levels of a protein called ACE2, which happens to be the protein the novel coronavirus uses to enter human cells. As a result, the authors argued, the drugs might “facilitate infection” and increase “the risk of developing severe and fatal COVID-19.”

Ibuprofen is not one of these drugs, but got a nod in a single, unsourced sentence that claimed that it, too, can increase ACE2 levels.

That fundamental claim, however, appears to have little to back it. Rachel Graham, a coronavirus expert at the University of North Carolina Gillings School of Global Public Health, told NPR that there’s virtually no evidence that ibuprofen raises ACE2 levels.

Indeed, we could find very little in the literature to support the idea — just one study suggesting ibuprofen could increase ACE expression in diabetic rats, and nothing about an impact in humans.

Even if it is the case that ibuprofen raises ACE2 levels in humans, that doesn’t necessarily mean taking the drug would make people more likely to catch the virus.

“Virus entry into cells is a funny business because viruses need very, very little receptor on the surface of a cell to enter it,” said Perlman. “So if you went from having zero to some, that would make it susceptible, but some to more may not do very much.” 

Studies have shown that ACE2 is present in a variety of human cell types, including the epithelial cells that line the lung.

There is also some research to suggest that ACE2 may actually have a protective function — so it’s not a given that more ACE2 would be a bad thing for a COVID-19 patient. Although limited to a specific set of circumstances, one study found that ACE2 protects mice against lung failure.

“If there are effects on ACE2, ACE2 has both positives and negative effects in the infection by itself,” said Perlman. “So we just don’t know where it’s all going to come out.”

So, there are some possible ways ibuprofen or other NSAIDs might negatively impact COVID-19, but the biological plausibilities can also be spun in the other direction — and there’s certainly no evidence that ibuprofen makes the disease 10 times worse, as some of the viral messages claim. 

There are nevertheless valid reasons for COVID-19 patients to avoid NSAIDs, if only because of their previously known drawbacks. NSAIDs have gastrointestinal, kidney and cardiovascular side effects, which may be especially dangerous in very ill or elderly patients or in those with preexisting conditions.

Stanford University pulmonologist Angela Rogers told NPR that most patients in the hospital for an infection would receive acetaminophen rather than NSAIDs, since those patients are at a higher risk of organ damage.

Given the side effects, Perlman said that not using NSAIDs is “probably a good thing” generally. But, he added, “that has nothing to do with COVID-19. That’s just the way NSAIDs work.”

For his part, FitzGerald does not recommend NSAIDs for COVID-19 patients, but doesn’t think patients in chronic pain, for example, should stop taking their NSAIDs and switch to opioids.

Indeed, without more evidence, no one can come to a firm conclusion about the effects of these drugs on COVID-19. In the meantime, patients should not change their medications without speaking with a physician.

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