Pharmacy giant Rite Aid is at risk of going out of business, according to a Deutsche Bank analyst who issued a downgrade for the retailer and said its stock could be worthless.
Analyst George Hill slashed his price target for Rite Aid from $16 to $1 and warned that the company may go under, Yahoo Finance reported. The stock plunged by 24% Thursday on the news, bringing its value down to $6.45/share.
“We believe COVID has hastened the decline of the retail pharmacy segment and we see the potential for a dramatic negative inflection point for [Rite Aid] shares,” Hill wrote in a research note issued on Thursday.
Rite Aid is the third-largest pharmacy chain in the country with more than 2,500 retail outlets across 17 U.S. states. But in recent years, the drugstore has felt the heat from its competitors, Walgreens and CVS, each with more than 9,000 stores nationwide. And with pharmacy profits sliding as the pandemic subsides, Rite Aid’s attempted expansions in recent years have resulted in the company taking on $3.2B of debt, Yahoo Finance reported. Hill said this now threatens to permanently dent its profitability rather than helping Rite Aid against its competitors.
Investors in the drugstore chain are now waiting for its 2023 fiscal guidance. Rite Aid needs to generate between $190M and $200M to cover its debt service costs as well as $200M to $250M for store maintenance capital expenditure requirements, according to Hill.
“Rite Aid needs to generate $400 to $450 million in annual adjusted EBITDA to continue as an operating company,” wrote Hill. “At a number below $400M, the equity arguably has no value as the company is not in a position to generate real returns to shareholders.”
Rite Aid has been in trouble for some time, surviving two failed merger attempts within the last five years at serious cost.
The first, a planned $10B acquisition of Rite Aid by the Walgreens Boots Alliance, was stamped out by the FTC in 2017. The result was a consolation prize: Walgreens bought approximately half of all Rite Aid’s stores for $5.2B, CNN Business reported at the time.
And in 2018, Rite Aid’s second merger plan — a deal with food and drug retailer Albertsons Cos. worth $24B — died at the hands of shareholders over equity concerns, Supermarket News reported at the time.
The coronavirus pandemic gave the big U.S. pharmacies a boost, as pharmacists joined the ranks of frontline workers and reached new customers by becoming vaccination and testing sites. But with foot traffic low and customer ability to order hair care, skin care and dental care goods online, big-box stores like Target were usurping a portion of traditional drugstore customer bases, CNBC reported in January 2021.
Lower foot traffic hurt Rite Aid’s mid-pandemic attempts to lure in customers via store revamps that prioritized its pharmacy offerings via virtual care rooms for customers to connect with pharmacists remotely. And by December 2021, Rite Aid’s struggles had been amplified: The pharmacy chain announced that it would be closing 63 stores over the next two years.
Analyst sentiment on Rite Aid has continued to decline in recent months, Barron's reported. Year-to-date gains for the drugstore fell by more than 50%, MarketWatch reported, compared to minimal 0.4% gains for rival CVS.
Coronavirus infections in England have climbed to a record level as the REACT programme reports the highest prevalence since it began in May 2020.
According to the study’s latest surveillance data, based on almost 110,000 swab tests taken between 8 and 31 March, around 1 in 16 tested positive during this period, or 6.37% of the population. This is more than double the study’s previous findings when 1 in 35 had the virus as of 1 March, or 2.88% of people, and 40% higher than the first Omicron peak in January.
The scientists from Imperial found that infections were doubling every 30 days with an estimated reproduction number (R) of 1.07.
The vast majority of the analysed positive samples were the Omicron BA.2 ‘stealth variant’ (named due to the absence of certain genetic changes that can distinguish this variant easily from others). As of 22 March, the team estimated that 94.7% of the samples were BA.2, which is double the study’s previous estimated figure from 19 February (47.2%). In January, 0.8% were BA.2.
A very small number of recombinant Omicron variants were also detected (five XE and three XL), which are hybrids of the original BA.1 Omicron strain and BA.2. Because the number of these recombinants was so small, it’s not possible to tell from the data whether these variants are more transmissible than others.
Compared to previous data infections have risen in all age groups and remain highest in primary school-aged children, with almost 1 in 10 (8.81%) 5-11-year-olds testing positive. However the most recent trends show that the rate of new infections is likely slowing or falling in the younger age groups aged 5-54. This was not seen in older people above the age of 55 where infections were found to still be rising, having almost tripled to 4.61% in the oldest age group, aged 75+.
Booster vaccines were rolled out by the NHS in September last year, starting with older age groups. Younger people therefore received their third dose more recently than older people, which may partly explain these findings as research has shown that vaccine effectiveness against infection falls over time.
Professor Paul Elliott, director of the REACT programme from Imperial’s School of Public Health, said: “These trends are concerning since when a very high number of people are infected, this may lead to more people becoming seriously ill and needing to go to hospital.
“Although restrictions have ended, I would urge people to still behave cautiously to help protect others who might be vulnerable, and avoid contact with other people if you have symptoms. This will help to slow the spread of the virus and lessen its impact on the NHS and our lives more broadly as we enter this next phase of the epidemic.”
These findings from the REal-time Assessment of Community Transmission (REACT-1) programme, led by Imperial College London with Ipsos MORI and commissioned by the Department of Health and Social Care, are available here in a pre-print report and are being submitted for peer-review.
Impact of vaccination in school children
For this latest round of the REACT study, 109,181 people swabbed themselves at home and their samples were analysed by PCR testing. 6,902 of these were positive, giving an overall weighted prevalence of 6.37%. Weighting is where the researchers make adjustments to their calculations to ensure the sample reflects England’s population. Infection prevalence rose to a high level in all regions of the country, with the highest in the South West (8.13%) and the lowest in the West Midlands (5.28%).
By age, infections have also increased in all age groups, with the smallest rise seen in secondary school-aged children, which rose from 3.42% to 4.71%. The prevalence in this age group, a high proportion of whom have been vaccinated, is half that of primary school-aged children, where far fewer have been vaccinated. This suggests that vaccination is helping to reduce the spread of the virus in secondary school-aged children.
Dame Jenny Harries, Chief Executive of the UK Health Security Agency (UKHSA), said: “These latest study results are another reminder that the pandemic is not over, and there is still a real risk to many of us catching COVID with infection rates so high. That is why it is sensible to wear a mask in crowded, enclosed spaces, keep indoor spaces ventilated and stay away from others if you have any symptoms of a respiratory illness, including COVID.
“Vaccination continues to prevent a high number of cases resulting in severe disease, hospitalisation and death and remains the best way to protect us all. If you have not yet come forward for your primary or booster vaccine I would urge you to do so straight away – the NHS vaccine programme is there to help you and the sooner you are vaccinated the sooner you and your family and friends will be protected.”
“I’d like to thank each and every REACT participant for contributing to what has been a vital study throughout the course of the pandemic in giving us insight into how COVID-19 has impacted the country.”
Behaviours and risk factors
The study also looked at the rates of infections across different risk factors and behaviours. People who had been in contact with a confirmed COVID-19 case had a 1 in 5 chance of testing positive (17.84%). Of those who reported they had any of the ‘classic’ COVID-19 symptoms, almost 1 in 3 tested positive (27.57%).
There was very little difference in prevalence in people who said they always wear a face mask indoors (6.59%) compared to those who say they never wear one (5.48%). Those who were shielding also had a similar infection prevalence to those who were not (6.00%, 6.64%, respectively).
Health and Social Care Secretary Sajid Javid said: “Thanks to our plan to tackle Covid, we are leading the way in learning to live with the virus. We have made huge progress due to the success of our world-leading vaccination programme, access to antivirals for vulnerable people and increased scientific and public understanding about how to manage risk.
“Despite high infection rates, the population now has much stronger protection against Covid than at any other point in the pandemic.
“Vaccines remain our best defence and we are now offering spring boosters to the elderly, care home residents and the most vulnerable – so please come forward to protect yourself, your family, and your community, and continue to follow public health guidance if you test positive.”
As 2021 drew to a close, the highly contagious Omicron variant of the pandemic virus was racing around the globe, forcing governments to take drastic actions once again. The Netherlands ordered most businesses to close on 19 December, Ireland set curfews and many countries imposed travel bans in the hope of taming the tsunami of COVID-19 cases filling hospitals. Amid the wave of desperate news around the year-end holidays, one group of researchers hailed a development that had seemed as though it might never arrive. On 23 December, the World Health Organization (WHO) uttered the one word it had previously seemed incapable of applying to the virus SARS-CoV-2: ‘airborne’.
On its website, a page titled ‘Coronavirus disease (COVID-19): How is it transmitted?’ was quietly edited to state that a person can be infected “when infectious particles that pass through the air are inhaled at short range”, a process otherwise known as “short-range aerosol or short-range airborne transmission”. The website says that transmission can occur through “long-range airborne transmission” in poorly ventilated or crowded indoor settings “because aerosols can remain suspended in the air or travel farther than conversational distance”.
“It was a relief to see them finally use the word ‘airborne’, and to say clearly that airborne transmission and aerosol transmission are synonyms,” says aerosol chemist Jose-Luis Jimenez at the University of Colorado Boulder.
The seemingly uncontroversial statement marked a clear shift for the Switzerland-based WHO, which had tweeted categorically early in the pandemic, “FACT: #COVID19 is NOT airborne,” casting the negative in capital letters as if to remove any doubt. At that time, the agency maintained that the virus spreads mainly through droplets produced when a person coughs, sneezes or speaks, an assumption based on decades-old infection-control teachings about how respiratory viruses generally pass from one person to another. The guidance recommended distancing of more than one metre — within which these droplets were thought to fall to the ground — along with hand washing and surface disinfection to stop transfer of droplets to the eyes, nose and mouth.
It took until 20 October 2020 for the agency to acknowledge that aerosols — tiny specks of fluid — can transmit the virus, but the WHO said this was a concern only in specific settings, such as indoor, crowded and inadequately ventilated spaces. Over the next six months, the agency gradually altered its advice to say that aerosols could carry the virus for more than a metre and remain in the air (see ‘Changing views of how COVID spreads’).
But this latest tweak is the WHO’s clearest statement yet about airborne transmission of SARS-CoV-2. And it places the virus among a select group of ‘airborne’ infections, a label long reserved for just a handful of the world’s most virulent pathogens, including measles, chickenpox and tuberculosis.
The change brings the WHO’s messaging in line with what a chorus of aerosol and public-health experts have been trying to get it to say since the earliest days of the outbreak. Many decry the agency’s slowness in stating — unambiguously — that SARS-CoV-2 is airborne. Interviews conducted by Nature with dozens of specialists on disease transmission suggest that the WHO’s reluctance to accept and communicate evidence for airborne transmission was based on a series of problematic assumptions about how respiratory viruses spread.
For example, even in the middle of the fast-moving epidemic, the WHO dismissed field epidemiology reports as proof of airborne transmission because the evidence was not definitive, something that is difficult to achieve quickly during an outbreak. Other criticisms are that the WHO relies on a narrow band of experts, many of whom haven’t studied airborne transmission, and that it eschews a precautionary approach that could have protected countless people in the early stages of the pandemic.
Critics say that inaction at the agency led to national and local health agencies around the world being similarly sluggish in addressing the airborne threat. Having shifted its position incrementally over the past two years, the WHO also failed to adequately communicate its changing position, they say. As a result, it didn’t emphasize early enough and clearly enough the importance of ventilation and indoor masking, key measures that can prevent airborne spread of the virus. Lidia Morawska, an aerosol scientist at the Queensland University of Technology in Brisbane, Australia, spearheaded several efforts to convince the WHO and other health agencies of the airborne threat. She says that airborne transmission was “so obvious” as far back as February 2020, and that omitting it from official guidelines was disastrous.
But Dale Fisher, an infectious-diseases physician at the National University Hospital in Singapore and chair of the WHO’s Global Outbreak Alert and Response Network steering committee, doesn’t think that confusion over whether the virus is airborne has had a defining impact on how the pandemic has played out. “It’s not the cause of the catastrophe we’ve seen,” he says.
Some other researchers defend the agency’s response, given the rapidly evolving situation. “I really don’t think anybody dropped the ball, including WHO,” says Mitchell Schwaber, an infectious-diseases physician at Israel’s ministry of health and an external adviser to the WHO. “So many assumptions that we had about this virus were proven false. We always, we always were learning new things.”
Resolving this debate about how to assess the transmission of respiratory viruses matters, say researchers, because a more deadly variant of SARS-CoV-2 could emerge at any time, and new respiratory viruses will almost certainly plague humanity at some point. It’s not clear whether the WHO and the world will be ready.
Tension in the air
In the final days of March 2020, Morawska contacted dozens of colleagues — an international mix of aerosol scientists, infectious-disease specialists, and building and ventilation engineers — to get the word out about the airborne threat of SARS-CoV-2. On 1 April 2020, the group sent an e-mail laying out their case to Michael Ryan, head of the WHO’s Health Emergencies Programme, and Maria Van Kerkhove, technical lead of the WHO’s COVID-19 response.
Within an hour, the agency was on the phone. Two days later, the group attended a video conference with members of the Health Emergencies Programme and the Infection Prevention and Control Guidance Development Group (IPC GDG) — an external group of about 40 clinicians and researchers that advises the WHO on infection containment, especially in hospitals. At the time of the meeting, more than one million people had been infected with SARS-CoV-2, and 54,000 had died. Community spread was rampant in several countries.
Morawska presented what she says was a compelling case for airborne transmission. Two facts stood out. First, there was solid evidence that people were becoming infected even when they were more than one metre — the safe distance recommended by the WHO — from a contagious individual. Second, years of mechanistic studies had demonstrated how mucus in a person’s airway can spray into aerosols during speech and accumulate in stagnant rooms. Morawska felt rebuffed by the WHO and its advisers. “I didn’t have a feeling that they were trying to see this from our perspective,” she says.
She and other people who study aerosols and airborne disease transmission say that the IPC GDG is ill-equipped to assess this type of transmission because most of its members have focused on controlling infections in hospitals and they lack expertise in the physics of how airborne contagions spread. At the time of the 1 April meeting, no one in the IPC GDG had studied this type of disease transmission, say critics.
“If it is a new disease, you better include everyone,” says Yuguo Li, a building environment engineer at the University of Hong Kong, whose study of the SARS outbreak in 2002–03 had concluded that the virus responsible, SARS-CoV, probably spread through the airborne route1. He suspected that SARS-CoV-2 was also airborne, although he initially thought that only short-range airborne transmission was likely.
Marcel Loomans, an indoor-air-quality physicist at Eindhoven University of Technology in the Netherlands, says that it is often hard to find common ground between the two disciplines. “On the medical side, they were not aware of how aerosols behave in the air and what ventilation can do,” he says. People end up “talking past each other”.
Early WHO advice on masks recommended them only for infected people and their carers.Credit: S.C. Leung/SOPA Images/LightRocket/Getty
The disconnect was there even in the use of scientific terms. Infection-control experts have long drawn a hard line between droplet viruses and airborne ones, seeing only the latter as capable of travelling far and lingering in the air. “Dogmatic bias is certainly a big part of it,” says Don Milton, an occupational-health physician who studies aerosol transmission of infectious diseases at the University of Maryland in College Park. He says that he was disappointed but not surprised by the WHO’s lack of action in addressing the airborne threat after the 1 April meeting. “I’m just familiar with how the medical profession thinks,” he says.
But Schwaber, who chairs the IPC GDG, recalls the meeting differently. “We took very seriously the issues that they raised at the meeting, and responded to them,” he says. “Nothing was being blown off, nothing was being ignored.”
At the time, he says, the available evidence suggested that airborne precautions throughout hospitals — including N95 masks for staff, visitors and patients — were unnecessary. Still, faced with soaring deaths among frontline doctors and nurses, most hospitals and health agencies adopted these precautions on their COVID-19 wards, as well as less-stringent protections such as wearing surgical masks in other areas of the hospital.
Mark Sobsey, an environmental microbiologist at the University of North Carolina in Chapel Hill who is a member of the IPC GDG, says that especially in the early days, the concerns brought to the WHO about airborne transmission were “largely unfounded” and lacked credible evidence, such as the isolation of infectious virus particles from air samples. Epidemiological data from outbreak investigations were “especially weak”, he says.
According to Trish Greenhalgh, a primary-care health researcher at the University of Oxford, UK, the IPC GDG members were guided by their medical training and the dominant thinking in the medical field about how infectious respiratory diseases spread; this turned out to be flawed in the case of SARS-CoV-2 and could be inaccurate for other viruses as well. These biases led the group to discount relevant information — from laboratory-based aerosol studies and outbreak reports, for instance. So the IPC GDG concluded that airborne transmission was rare or unlikely outside a small set of aerosol-generating medical procedures, such as inserting a breathing tube into a patient.
That viewpoint is clear in a commentary by members of the IPC GDG, including Schwaber, Sobsey and Fisher, published in August 20202. The authors dismissed research using air-flow modelling, case reports describing possible airborne transmission and summaries of evidence for airborne transmission, labelling such reports “opinion pieces”. Instead, they concluded that “SARS-CoV-2 is not spread by the airborne route to any significant extent”.
In effect, the group failed to look at the whole picture that was emerging, says Greenhalgh. “You’ve got to explain all the data, not just the data that you’ve picked to support your view,” and the airborne hypothesis is the best fit for all the data available, she says. One example she cites is the propensity for the virus to transmit in ‘superspreader events’, in which numerous individuals are infected at a single gathering, often by a single person. “Nothing explains some of these superspreader events except aerosol spread,” says Greenhalgh.
Throughout 2020, there was also mounting evidence that indoor spaces posed a much greater risk of infection than outdoor environments did. An analysis of reported outbreaks recorded up to the middle of August 2020 revealed that people were more than 18 times as likely to be infected indoors as outdoors3. If heavy droplets or dirty hands had been the main vehicles for transmitting the virus, such a strong discrepancy would not have been observed.
Although the WHO played down the risk of airborne transmission, it did invite Li to become a member of the IPC GDG after he spoke to the group in mid-2020. Had the organization not at least been open to his view that infections were caused by aerosols, especially at short range, “they would not have invited me there as they knew my standing”, he says.
Still, Li is disappointed that it took the WHO until October 2020 to acknowledge that aerosols play a part in disease transmission in community settings. And in its updated guidelines on mask use, in December 2020, the agency still emphasized shortfalls and gaps in the evidence for aerosol transmission, and the need for more “high quality research” to understand the specifics of how the virus spreads. It wasn’t until the end of April 2021 that long-range aerosol transmission was added to a question-and-answer section on the agency’s website about how the virus spreads. And the term airborne wasn’t officially added until December 2021.
Conservative approach
Some scientists note that the WHO’s decision to classify SARS-CoV-2 as airborne, belated as it was, is momentous. That’s because it flies in the face of the established view of respiratory virus transmission that held sway when the pandemic began — that nearly all infectious diseases are spread by droplets, not through the air. And researchers say that this change is particularly important because the organization generally takes a conservative approach. “What the WHO says is normally based on a consensus of expert advice and opinion,” says Christopher Dye, an epidemiologist who served as the scientific adviser to the agency’s director-general until 2018.
And although the WHO has drawn strong criticism for the way in which it assessed SARS-CoV-2 transmission, some researchers don’t find the agency’s response surprising. The international community looks to the WHO for early warnings of disease outbreaks. But when it comes to science, the agency “sees its role as certifying the current expert consensus, not (usually) advancing new, tentative knowledge”, says Peter Sandman, an independent risk-communications specialist based in New Jersey who has worked as a consultant to the WHO.
Schwaber says: “Individuals and governments and public-health bodies are looking to a WHO GDG, not to conjecture. They’re looking to a WHO GDG to put out guidance. That everything that we say can be backed by evidence.”
The WHO frequently gets attacked, “so you can understand how they’d be risk averse”, says Tom Frieden, president of the global-health initiative Resolve to Save Lives and former head of the US Centers for Disease Control and Prevention (CDC). Frieden is critical of some aspects of the WHO’s pandemic response, including how slow it was to recommend the use of masks. But he says that the agency is in a difficult position during health crises.
In 2009, for instance, it was accused of being alarmist over the H1N1 swine influenza outbreak that petered out with few lives lost. “WHO got hit hard for that,” says Dye, even though he thinks the agency was right to be cautious and declare a public-health emergency of international concern.
Hard line to tread
Virologist May Chu, a member of the IPC GDG at the Colorado School of Public Health in Aurora, says that the WHO treads a difficult line, and tends to be quite conservative in its recommendations to avoid putting out information that later proves to be incorrect. “You can’t be backtracking” on advice, adds Fisher, because “then you lose complete credibility”.
The gravity of the situation might have made the WHO even more cautious in its pronouncements and less likely to stray from consensus views, according to Sandman’s partner Jody Lanard, an independent risk-communications specialist who has also worked with the WHO in the past.
In previous situations — such as during the Ebola outbreak in West Africa, and in polio vaccine campaigns — the WHO was more nimble than it has been during the COVID-19 pandemic, Lanard says. “I’ve seen them be able to change what their approach was, or try different things,” she says. But during the pandemic “it’s so tempting to be very, very cautious”, because millions of lives will be affected by the agency’s recommendations. Loomans and others question why, when concerns were growing that SARS-CoV-2 could be airborne, the WHO didn’t adopt a precautionary approach by acknowledging the possibility of different risks, even without definitive proof.
Schoolchildren in Taipei eat lunch behind partitions to stop the spread of COVID-19 in April 2020, after the WHO stressed the dangers of respiratory droplets that travel short distances.Credit: Sam Yeh/AFP/Getty
And in May 2021, the Independent Panel for Pandemic Preparedness and Response (IPPPR), a body established by the WHO a year earlier to review the agency’s actions at the start of the pandemic, called out the WHO for not applying the precautionary principle to another crucial aspect of COVID-19 transmission — whether it could spread from human to human (see go.nature.com/3iqhfjm). “There is a case for applying the precautionary principle in any outbreak caused by a new pathogen resulting in respiratory infections, and thereby for assuming that human-to-human transmission will occur unless the evidence specifically indicates otherwise,” the IPPPR said in its 2021 report.
In practice, applying the precautionary approach to the question of how SARS-CoV-2 — or any newly emerged pathogen — is transmitted would mean initially assuming that all routes of transmission are possible. “That should be your starting point, and then you can strike out routes if you’re sure,” says Loomans.
But Schwaber says that this approach carries risks. “To say, well, the best interests of the patient and the best interests of the health-care worker involve invoking the precautionary principle would also imply that there’s no downside to invoking it,” he says. Taking full precautions against airborne transmission would require major changes at hospitals, such as using negative-air-pressure isolation rooms and uncomfortable N95 masks for all staff and visitors. Such changes need to be weighed against the evidence that they are required, he says.
Sobsey says that the WHO did adopt the precautionary principle, in part because of the advice from aerosol scientists. That’s why, he says, the agency stated in July 2020 that airborne transmission couldn’t be ruled out — and why it started placing more emphasis on ventilation as a protective measure, even though the evidence for airborne transmission was weak at the time.
“They are not totally wrong,” says Li of those who claimed there were gaps in the evidence for airborne transmission, especially over larger distances. “It’s nothing bad to seek solid scientific evidence,” he says, but “when you see the spread so significantly, do you still wait for a nice Nature or Science article?” he says.
Still, other health organizations moved faster than the WHO despite the uncertainty. In February 2020, Li was contacted by the Chinese Center for Disease Control and Prevention for advice on air conditioning in public buildings and on public transport. At Li’s suggestion, he says, the centre recommended maximizing airflow in buildings from the outside, to help flush out any airborne contagion. At the time, Li didn’t think that ventilation would substantially reduce infection from a virus that he suspected was airborne only over short distances — an assumption that he later disproved. But he recommended improved ventilation because “I always support a precautionary approach,” he says.
Communication problems
One thing that’s still missing, says Jimenez, is a clear communication campaign from the WHO. Its director-general, Tedros Adhanom Ghebreyesus, acknowledged the challenges in his opening remarks at the agency’s global conference on communicating science during health emergencies, on 7 June 2021. “Scientific processes, decision-making in an emergency context and mass communication do not fit together easily,” Tedros said, adding that “high-quality research takes time, but time is something we don’t have in an emergency”.
During the early months of the pandemic, the WHO was fighting battles on other fronts. While it grappled with shortages of protective equipment and ventilators, it was also contending with misinformation about unproven treatments for COVID-19 and US threats to pull its funding from the organization.
But critics say that even two years into the pandemic, the WHO hasn’t clearly communicated the risks from airborne transmission. And, perhaps as a result, governments around the world spent much of the pandemic focusing on hand washing and surface cleaning, instead of ventilation and indoor masking.
“The cacophony of changing messages has undoubtedly contributed greatly to resistance to masks and other measures,” says Jimenez.
On 15 December 2021, less than two weeks before the latest change in wording on the WHO’s website, Jimenez put out a call on Twitter for evidence of how governments and organizations either “don’t know how to protect their citizens, or use @WHO’s ambiguity to avoid doing so”. He enumerated more than 100 examples in which health advice at the time was at odds with airborne precautions, indicating that the message was not filtering out from the agency.
Jimenez has continued to receive such examples. Now that the agency has changed the wording on its main website, Jimenez can call out these ‘COVID Hall of Shame’ offenders, as he labels them, for providing advice that is no longer in line with the international health agency.
“That is the arrogance, a bit, of what WHO is,” says Chu. “Once you post [new guidance], it’s pretty passive. They expect you to come to their website. They don’t necessarily broadcast it.”
But that’s exactly what’s needed, says Jimenez, especially given early communications that still haunt the agency, such as its tweet about COVID-19 not being airborne. “No doubt we owe the persistence of misinformation to that WHO announcement and firm position, at the time in which we were all scared and eager to learn how to protect ourselves, very early in the pandemic,” says Jimenez.
The agency defends its actions throughout the pandemic. In a statement to Nature last month, a spokesperson said: “WHO has sought the expertise of engineers, architects and aerobiologists along with expertise in infectious diseases, infection prevention and control, virology, pneumology and other fields since the early days of the COVID-19 pandemic. In August 2020, we established the Environment and Engineering Control Expert Advisory Panel (ECAP) for COVID-19 to provide expert contributions for the development of guidance through evaluation and critical interpretation of available evidence (benefits and harm of interventions) related to relevant technical questions including indoor air quality management and ventilation as an engineering control measure in the context of COVID-19.”
The organization says that initial guidance covered airborne precautions in health-care settings, but notes that: “As the evidence on the transmission of COVID-19 has expanded, we have learnt that smaller-sized infectious particles known as aerosols also play a role in transmission in community settings, and WHO has adapted its guidance and messages to reflect this in the December 2020 update to our mask guidance.”
In response to critics who say that it hasn’t adequately highlighted the changes it has made regarding the risks of airborne transmission, the WHO says that it has held about 250 press briefings and hundreds of live social-media events during the pandemic. It adds that it also pushes out information through social-media channels, meetings with doctors and mailing lists to scientists.
That’s not enough, according to some researchers. Stephanie Dancer, a microbiologist at the Edinburgh Napier University, UK, says that the WHO needs to be clear about its position so that others follow its lead. “They have to show true strength of character and stand up and say, ‘We got it wrong. We’re going to get this right. Here are our next set of guidelines. This is where we’re going to go. This is what we advise,’” she says.
Off to a bad start
Part of the problem was how emphatic the WHO was at the beginning of the pandemic, says Heidi Tworek, a historian and public-policy specialist at the University of British Columbia in Vancouver. “To say that COVID was definitively not airborne unfortunately meant there was a massive hill to climb to undo that,” she says. Right from the beginning, the WHO and other public-health authorities and governments should have emphasized that SARS-CoV-2 was a new coronavirus, and that guidelines would inevitably change, she says. “And when they do, it’s a good thing because it means we know more.”
“We’re really talking here about two failures, not one,” says Sandman. “Being reluctant to change your mind, and being reluctant to tell people you changed your mind.” Like other public-health and scientific organizations, the WHO “are afraid of losing credibility by acknowledging that they got something wrong”, he says.
But when Lanard worked with the WHO in 2005 to draft its risk-communications guidelines, one tenet that she advocated — to admit mistakes and errors when they occur — was removed from the final draft. She says that there were good reasons behind that decision, including that health officials in some countries could have faced imprisonment — or worse — if they had promoted information from the WHO that turned out to be incorrect. Officials and scientific advisers in several countries have received death threats during the pandemic. “Inevitably you’ll get it wrong sometimes,” says Frieden. And the WHO is in a position that means “whatever they do, they get attacked”, he says.
On the science front, questions remain about how much of COVID-19 transmission is airborne. Sobsey says that researchers still need to come up with evidence that the airborne route makes “an important contribution to the overall disease burden”. Many on the other side of the aisle, such as Jimenez, are convinced that airborne transmission predominates. The US Office of Science and Technology Policy voiced strong support for this view on 23 March, when its head, Alondra Nelson, issued a statement called ‘Let’s Clear the Air on COVID’, which said “the most common way COVID-19 is transmitted from one person to another is through tiny airborne particles of the virus hanging in indoor air for minutes or hours after an infected person has been there.”
Other viruses long suspected of being airborne — including influenza and common cold viruses — will also be scrutinized. In September 2021, the US National Institutes of Health awarded Milton a multimillion-dollar grant to conduct trials that will determine whether airborne or droplet routes lead to influenza infection.
Li says that there’s much greater recognition of airborne transmission because of the COVID-19 pandemic, and research over the next few years will probably show that most respiratory viruses can spread in this way. So the whole world will be more alert to the possibility of the airborne threat when old or new infectious diseases start spreading.
In the WHO, too, attitudes have shifted, according to Sobsey. “I think there’s been a sea change in thinking at WHO as a consequence of the experience with this virus,” he says, “which is — be more precautionary, even if you’re not sure.”
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The discovery could help individuals find tailored treatments that work for them and guide the development of new drugs.
The study by researchers in Sydney, Hobart, Melbourne, Brisbane and San Francisco helps us understand why some treatments work well in some patients, but not in others. It's the largest study to date to link disease-causing genes to specific types of immune cells.
A trial is now underway in Sydney with Crohn's disease patients to predict which treatments will work for specific patients.
'Some autoimmune diseases can be notoriously difficult to treat,' says Professor Powell.
'Because of our immune system's complexity, and how vastly it varies between individuals, we don't currently have a good understanding of why a treatment works well in some people but not in others,' he says.
The study links specific genes and immune cell types to an individual's disease, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes and Crohn's disease.
This means an individual's unique genetic profile could be used to deliver treatments tailored to precisely tame their immune system.
'Our data also provides a new avenue for narrowing down potential drug targets. The potential health and economic impacts of this research are enormous,' says Professor Alex Hewitt, joint lead author and clinician-researcher at the University Of Tasmania's Menzies Institute for Medical Research.
'Most rare genetic diseases are like a major car accident in the body -- they are generally easy to identify and locate where they occur in the genome. But immune diseases are often more like traffic congestion, where genetic changes that hold up traffic are harder to specifically pinpoint. This study has helped us identify the trouble spots,' says Professor Hewitt.
'The greatest insight from this work will be identification of therapeutic targets and defining sub-populations of immune disease, which can then refine clinical trials to assess drug effectiveness,' he says.
Our bodies' immune systems are designed to fight external threats, but autoimmune diseases occur when our immune systems take aim at our own healthy cells. They affect about one in 12 Australians, are incurable and require lifelong treatments to minimise the damage.
Often, patients will trial many different treatments before finding one that works for them.
'Some medications may be very effective in only 15% of patients, so are not recommended as a first-line treatment,' says Dr Seyhan Yazar, co-first author of the study.
'We now have a way to link treatment response back to an individual's immune genetics -- and to potentially screen for that 15% of patients before a clinician even administers a treatment.'
The researchers say their data could lower the risks associated with developing new treatments.
'Pharmaceutical companies may have hundreds of targets and have to make decisions about which they will take forward to Phase I clinical trials, knowing that 90% of potential drug candidates fail during clinical development,' says Dr José Alquicira-Hernández, co-first author and researcher at the Garvan Institute.
'Understanding which cell types are relevant for a particular disease is key for developing new drugs.'
A million cells reveal complexity and provide certainty
The study provides unique insights by looking at genes in individual immune cells on an unprecedented scale. It analysed the genomics of more than one million individual immune cells from around 1,000 healthy individuals, exploring 14 different types of immune cells in total.
This individual approach paints a far clearer picture than previous studies which analysed combined cells in a blood sample.
'The problems with bulk RNA analysis is that we only observe an averaged signal. But there is vast variation in cell functions and cell types that allow the body to defend against attack,' explains says Dr Yazar.
'Average analysis doesn't reflect what happens in the full variety of immune cells.'
Integrating into clinical trials
The findings have led to clinical trials.
'We are working on a study of Crohn's disease in collaboration with St George Hospital that will determine how a patient's immune genotype affects their response to different treatments and are looking to establish new trials in a range of autoimmune diseases' says Professor Powell.
'It is a significant milestone of Garvan's pioneering OneK1K study aimed at showing how genetics contribute to the risk of immune disease at a cellular level.'
Seyhan Yazar, Jose Alquicira-Hernandez, Kristof Wing, Anne Senabouth, M. Grace Gordon, Stacey Andersen, Qinyi Lu, Antonia Rowson, Thomas R. P. Taylor, Linda Clarke, Katia Maccora, Christine Chen, Anthony L. Cook, Chun Jimmie Ye, Kirsten A. Fairfax, Alex W. Hewitt, Joseph E. Powell. Single-cell eQTL mapping identifies cell type–specific genetic control of autoimmune disease. Science, 2022; 376 (6589) DOI: 10.1126/science.abf3041
Researchers have developed a wearable device that plays specific sounds to enhance deep sleep. The first clinical study has now shown that the device is effective, but not at the same level of effectiveness for everyone.
Many people, especially the elderly, suffer from abnormal sleep. In particular, the deep sleep phases become shorter and shallower with age. Deep sleep is important for the regeneration of the brain and memory, and also has a positive influence on the cardiovascular system.
Researchers have shown that the brain waves characterizing deep sleep, so-called slow waves, can be improved by playing precisely timed sounds through earphones while sleeping. While this works well in the sleep laboratory under controlled conditions, there has thus far been no at home solution that can be used longer than just one night.
SleepLoop to the rescue
As part of the SleepLoop project, researchers at ETH Zurich have developed a mobile system that can be used at home and aims to promote deep sleep through auditory brain stimulation.
The SleepLoop system consists of a headband that is put on at bedtime and worn throughout the night. This headband contains electrodes and a microchip that constantly measure the brain activity of the person sleeping. Data from this is analysed autonomously in real-time on the microchip using custom software. As soon as the sleeping person shows slow waves in the brain activity characterising deep sleep, the system triggers a short auditory signal (clicking). This helps to synchronise the neuronal cells and enhance the slow waves. What makes the solution unique is that the person sleeping is not conciously aware of this sound during deep sleep.
The first clinical study
Researchers from ETH Zurich and University Hospital Zurich, led by Caroline Lustenberger, group leader at the Neural Control of Movement Lab, have conducted a clinical study with this device for the first time. The results have just been published in the journal Communications Medicine.
The study involved equipping participants, between 60 -- 80 years old, with the SleepLoop system, which they were required to operate themselves in their own home. The system is designed to function independently even by users with little technical experience. "This worked very well. We had surprisingly little data loss and the participants rated the device as user-friendly," says Lustenberger.
They wore the device every night for a total of four weeks, with the auditory stimulation given on a nightly basis for two weeks and no stimulation for the next two weeks. Neither the subjects nor the researchers knew in which two weeks the auditory signals were played and in which two they were not.
Auditory stimulation is indeed feasible
The results of 16 participants of the study show that it was indeed possible to enhance the slow waves through auditory signals during deep sleep in most participants. However, the individual differences were extensive with some of the subjects responding very well to the stimuli, while others responded minimally or not at all.
According to Lustenberger, the question of whether a person reacted to a stimulus did not depend on their well-being during the day. "Some people generally responded well to the stimuli and clearly showed enhanced slow waves, while others showed no response, regardless of their daily well-being."
The researchers have used these individual differences to better predict how a given individual will respond to the auditory stimulus. This in turn helps them to optimise and improve the performance of SleepLoop.
On track for market launch
A spin-off company Tosoo AG, is currently working on developing the device further and preparing it for the clinical market. It is already clear that it will not be freely available, but only via a doctor's prescription.
"This is a medical device, not just a wellness consumer product you can order online when you have trouble sleeping," emphasises Walter Karlen, who developed the technology at ETH Zurich. 1 Karlen has been appointed Director of the Institute of Biomedical Engineering at Ulm University in May 2021. "Use of the device must be medically indicated and supervised by a doctor," he says. Further development of the technology will now continue also in Ulm.
Story Source:
Materials provided by ETH Zurich. Original written by Peter Rueegg. Note: Content may be edited for style and length.
Caroline Lustenberger, M. Laura Ferster, Stephanie Huwiler, Luzius Brogli, Esther Werth, Reto Huber, Walter Karlen. Auditory deep sleep stimulation in older adults at home: a randomized crossover trial. Communications Medicine, 2022; 2 (1) DOI: 10.1038/s43856-022-00096-6
Research from the Babraham Institute has developed a method to 'time jump' human skin cells by 30 years, turning back the ageing clock for cells without losing their specialised function. Work by researchers in the Institute's Epigenetics research programme has been able to partly restore the function of older cells, as well as rejuvenating the molecular measures of biological age. The research is published today in the journaleLife and whilst at an early stage of exploration, it could revolutionise regenerative medicine.
What is regenerative medicine?
As we age, our cells' ability to function declines and the genome accumulates marks of ageing. Regenerative biology aims to repair or replace cells including old ones. One of the most important tools in regenerative biology is our ability to create 'induced' stem cells. The process is a result of several steps, each erasing some of the marks that make cells specialised. In theory, these stem cells have the potential to become any cell type, but scientists aren't yet able to reliably recreate the conditions to re-differentiate stem cells into all cell types.
Turning back time
The new method, based on the Nobel Prize winning technique scientists use to make stem cells, overcomes the problem of entirely erasing cell identity by halting reprogramming part of the way through the process. This allowed researchers to find the precise balance between reprogramming cells, making them biologically younger, while still being able to regain their specialised cell function.
In 2007, Shinya Yamanaka was the first scientist to turn normal cells, which have a specific function, into stem cells which have the special ability to develop into any cell type. The full process of stem cell reprogramming takes around 50 days using four key molecules called the Yamanaka factors. The new method, called 'maturation phase transient reprogramming', exposes cells to Yamanaka factors for just 13 days. At this point, age-related changes are removed and the cells have temporarily lost their identity. The partly reprogrammed cells were given time to grow under normal conditions, to observe whether their specific skin cell function returned. Genome analysis showed that cells had regained markers characteristic of skin cells (fibroblasts), and this was confirmed by observing collagen production in the reprogrammed cells.
Age isn't just a number
To show that the cells had been rejuvenated, the researchers looked for changes in the hallmarks of ageing. As explained by Dr Diljeet Gill, a postdoc in Wolf Reik's lab at the Institute who conducted the work as a PhD student: "Our understanding of ageing on a molecular level has progressed over the last decade, giving rise to techniques that allow researchers to measure age-related biological changes in human cells. We were able to apply this to our experiment to determine the extent of reprogramming our new method achieved."
Researchers looked at multiple measures of cellular age. The first is the epigenetic clock, where chemical tags present throughout the genome indicate age. The second is the transcriptome, all the gene readouts produced by the cell. By these two measures, the reprogrammed cells matched the profile of cells that were 30 years younger compared to reference data sets.
The potential applications of this technique are dependent on the cells not only appearing younger, but functioning like young cells too. Fibroblasts produce collagen, a molecule found in bones, skin tendons and ligaments, helping provide structure to tissues and heal wounds. The rejuvenated fibroblasts produced more collagen proteins compared to control cells that did not undergo the reprogramming process. Fibroblasts also move into areas that need repairing. Researchers tested the partially rejuvenated cells by creating an artificial cut in a layer of cells in a dish. They found that their treated fibroblasts moved into the gap faster than older cells. This is a promising sign that one day this research could eventually be used to create cells that are better at healing wounds.
In the future, this research may also open up other therapeutic possibilities; the researchers observed that their method also had an effect on other genes linked to age-related diseases and symptoms. The APBA2 gene, associated with Alzheimer's disease, and the MAF gene with a role in the development of cataracts, both showed changes towards youthful levels of transcription.
The mechanism behind the successful transient reprogramming is not yet fully understood, and is the next piece of the puzzle to explore. The researchers speculate that key areas of the genome involved in shaping cell identity might escape the reprogramming process.
Diljeet concluded: "Our results represent a big step forward in our understanding of cell reprogramming. We have proved that cells can be rejuvenated without losing their function and that rejuvenation looks to restore some function to old cells. The fact that we also saw a reverse of ageing indicators in genes associated with diseases is particularly promising for the future of this work."
Professor Wolf Reik, a group leader in the Epigenetics research programme who has recently moved to lead the Altos Labs Cambridge Institute, said: "This work has very exciting implications. Eventually, we may be able to identify genes that rejuvenate without reprogramming, and specifically target those to reduce the effects of ageing. This approach holds promise for valuable discoveries that could open up an amazing therapeutic horizon."
Diljeet Gill, Aled Parry, Fátima Santos, Hanneke Okkenhaug, Christopher D Todd, Irene Hernando-Herraez, Thomas M Stubbs, Inês Milagre, Wolf Reik. Multi-omic rejuvenation of human cells by maturation phase transient reprogramming. eLife, 2022; 11 DOI: 10.7554/eLife.71624
Though overall COVID-19 case counts continue to drop nationally, that’s not the story in every U.S. state.
About half the states have reported increases in COVID cases fueled by the Omicron subvariant, Axios reported. Alaska, Vermont, and Rhode Island had the highest increases, with more than 20 new cases per 100,000 people.
Nationally, the statistics are encouraging, with the 7-day average of daily cases around 26,000 on Wednesday, down from around 41,000 on March 6, according to the CDC. The number of deaths has dropped to an average of around 600 a day, down 34% from 2 weeks ago.
National health officials have said some spots would have a lot of COVID cases.
"Looking across the country, we see that 95% of counties are reporting low COVID-19 community levels, which represent over 97% of the U.S. population," CDC Director Rochelle Walensky, MD, said Tuesday at a White House news briefing.
"If we look more closely at the local level, we find a handful of counties where we are seeing increases in both cases and markers of more severe disease, like hospitalizations and in-patient bed capacity, which have resulted in an increased COVID-19 community level in some areas."
Meanwhile, the Commonwealth Fund issued a report Friday saying the U.S. vaccine program had prevented an estimated 2.2 million deaths and 17 million hospitalizations.
If the vaccine program didn’t exist, the U.S. would have had another 66 million COVID infections and spent about $900 billion more on health care, the foundation said.
The U.S. has reported about 982,000 COVID-related deaths so far with about 80 million COVID cases, according to the CDC.
"Our findings highlight the profound and ongoing impact of the vaccination program in reducing infections, hospitalizations, and deaths," the Commonwealth Fund said.
"Investing in vaccination programs also has produced substantial cost savings — approximately the size of one-fifth of annual national health expenditures — by dramatically reducing the amount spent on COVID-19 hospitalizations."
