Thursday, February 9, 2023

The potential human bird flu pandemic, Molnupiravir drives covid viral mutations, Global pandemic treaty

 Research, editing : Gan Yung Chyan, KUCINTA SETIA

News on disease control


News (1)

WHO warns the world about potential human bird flu pandemic as H5N1 avian strain jumps to mammals
Seven of the UK's animal avian flu cases detected were in 2022, including one fox in Cheshire and two in Cornwall, as well as one otter in each of Shetland and the Isle of Skye and two in Fife. Image : European otter


The World Health Organization has warned the world must prepare for a potential human bird flu pandemic — after the strain jumped from birds to mammals.

Cases of the strain H5N1 have already been reported in otters, mink and foxes, sparking fears the virus is one step closer to sweeping into humans.

During a virtual briefing today, the WHO's director-general Tedros Adhanom Ghebreyesus urged nations to monitor infections in mammals closely.

He said the risk of the virus jumping to humans was still low, but we 'cannot assume that will remain the case and we must prepare for any change in the status quo'.

It comes after the UK reported that its biggest-ever avian influenza outbreak had spilled over to mammals. There was also an outbreak among mink in North West Spain reported last month.

H5N1 has previously been detected in people, but cases have been sporadic and closely linked to close contact with infected dead or live birds.

The virus does not infect humans easily or other mammals.

News (2)

Bird flu could gain mutations enabling it to jump to humans

However reports of infections in mammals have raised concerns that the pathogen could gain mutations that make it easier for the virus to jump to humans, helping it to clear the biggest hurdle that has stopped it from sweeping the world.

Leading experts previously warned that the spread of bird flu poses a global risk until it is brought under control.

The US has faced a major outbreak of bird flu this year, with more than 58million poultry affected across nearly every state in the country and 6,100 in wild birds — approaching record levels for the country.

News (3)

Bird flu outbreaks among mink could lead to a hybrid virus

Experts have warned that outbreaks among mink could lead to a recombination event — when two viruses switch genetic material to make a new hybrid.

A similar process is thought to have caused the global 2009 swine flu crisis that infected millions across the planet.

The same biological phenomenon was also seen during the covid pandemic, such as the so-called Deltacron — a recombination of Delta and Omicron, first detected in France last February.

News (4)

Bird flu could merge with influenza, triggering the next pandemic

For decades, scientists have warned that bird flu is the most likely contender for triggering the next pandemic.

This could see a deadly strain of bird flu merge with a transmissible seasonal flu.

News (5)

The first bird flu outbreak among mink happens in Spain

The mink outbreak occurred on a farm in Galicia, north-west Spain, in October which housed 52,000 of the animals.

It was only spotted after a sudden surge in the animals dying. Up to four percent died in one week during the course of the outbreak, which was declared over by mid-November.

Farm vets swabbed the minks and the samples were analyzed at a Government lab, where they tested positive for H5N1.

News (6)

Measures taken to control the bird flu outbreak among mink

It led to all of the animals being culled, farm workers isolating for 10 days and heightened security measures in farms across the country.

These included wearing face masks and disposable overalls and showering before leaving the premises.

News (7)

H5N1 virus has gained a dozen mutations

Analysis of samples taken, which were published last month in the infectious disease journal Eurosurveillance, show the virus had gained nearly a dozen mutations — most of which had never or rarely been seen before in bird flu strains.

One was previously seen in the virus behind the 2009 global swine flu pandemic.

News (8)

Otters and foxes were infected with bird flu in the UK, humans could not be spared

In the UK, a December report showed four samples from the infected otters and foxes 'show the presence of a mutation which is associated with potential advantages for mammalian infection'.

The UKHSA warned that the 'rapid and consistent acquisition of the mutation in mammals may imply this virus has a propensity to cause zoonotic infections' — meaning it could potentially spread to humans. 

News (9)

In the third stage of the mask "compulsory cancellation of mandatory wearing", Wang Bisheng revealed the evaluation indicators
Reporter : Wu Liangyi / https://news.ltn.com.tw/news/life/breakingnews/4206322 / Image :   As for when is the third phase of "Comprehensive Mask Free" expected to hit the road? Wang Bisheng, the commander of the command center, said that in the final stage, it is possible to cancel the mandatory wearing of masks just like Singapore, and leave it to the people to make their own decisions. (Picture provided by Command Center)
至於第三階段「全面可免戴罩」何時有望上路?指揮中心指揮官王必勝說,最後一階段有可能比照新加坡取消強制戴口罩,交由民眾自主決定。(圖由指揮中心提供)

The Wuhan pneumonia (covid, COVID-19) epidemic is gradually slowing down. The Central Epidemic Epidemic Command Center announced on 9 February 2023 that the second phase of mask measures in Taiwan will be relaxed from 20 February 2023, and indoor masks can be exempted, but hospitals, public transportation and other places are excluded, and as for when the third stage of "fully exempt from wearing masks" is expected to be on the road, Wang Bisheng, the commander of the command center, said that in the final stage, it is possible to cancel the mandatory wearing of masks just like Singapore, and leave it to the people to make their own decisions.
On 20 February, the second phase of the mask loosening measures only lists the places where masks are required to be worn, including "medical institutions, welfare institutions for the elderly, long-term care institutions, honorary national homes, children and juvenile service institutions, and disability service institutions, public transport and specific means of transport".
Wang Bisheng said at the epidemic press conference today that the relaxation of mask measures will continue to be promoted in the future. The mandatory measures will be abolished in the final stage, and people will wear them independently. He will continue to observe the implementation of the second stage, and then promote it as appropriate.
As for other control measures, including the isolation of confirmed cases, changes in the definition of confirmed cases, downgrading, etc., Zhang Shangchun, the convener of the expert group of the command center, said that these are also under continuous discussion but there are still some epidemics that continue, and the international trend has not been completely loosened. While the virus is still mutating, the next loosening measures will be carried out step by step and in stages.
Zhang Shangchun said that taking the isolation of confirmed cases as an example, it may be changed to recommended rest at home, etc., without mandatory isolation.
News (10)
Zhang Shangchun revealed 4 reasons for the loosening of indoor masks
Reporter : Qiu Zhirou / https://news.ltn.com.tw/news/life/breakingnews/4206269 / Image :  Zhang Shangchun, the convener of the expert advisory group of the command center, explained the considerations and reasons for the relaxation of the indoor mask order. He pointed out that herd immunity has been greatly improved, the threat of mutated viruses is not great, and most people will wear masks on their own. The loosening of the mask order is also in line with international epidemic prevention adjustments. (Picture provided by Command Center)
指揮中心專家諮詢小組召集人張上淳說明放寬室內口罩令的考量及支持理由,他指出,群體免疫已大幅提升、變異病毒威脅不大,且民眾多會自主戴口罩,鬆綁口罩令也與國際防疫調整方向一致。(圖由指揮中心提供)
The Central Epidemic Command Center announces on 9 February that the indoor mask order will be relaxed as soon as 20 February 2023. Zhang Shangchun, the convener of the expert advisory group of the command center, attended the epidemic press conference in particular, and explained the considerations and reasons for the relaxation of the indoor mask order. He pointed out that herd immunity has been greatly improved, the threat of mutated viruses is not great, and most people will wear masks on their own and loosen them. The order is also in line with the direction of international epidemic prevention adjustments.

Zhang Shangchun explained that at present, at least 40% of natural infections in the Republic of China are estimated to have exceeded 60%, and the three-dose vaccination rate has reached 76% to protect vulnerable groups.
Due to the improvement of herd immunity protection, Zhang Shangchun said that the currently known mutant strains are most likely to cause only a small epidemic, and the impact on the number of moderate and severe cases is limited, and the amount of medical treatment can be sufficient. In addition, according to domestic surveys and the experience of neighboring countries in Asia, such as South Korea, after the relaxation of indoor mask regulations, most people will still wear masks on their own, and the masking matter is up to the people to make their own decisions.
Zhang Shangchun emphasized that the domestic relaxation of the domestic mask order is consistent with the adjustment of international epidemic prevention. Many countries and regions in Asia have gradually loosened their restrictions from wearing masks to designated places such as medical care and public transportation. For example, Singapore changed it on 29 August 2022 and is now discussing a complete lifting of the ban. New Zealand and South Korea respectively relaxed it on 12 September 2022 and 30 January 2023. Japan and Hong Kong, which still maintain the mask order, are also discussing relaxation.
Regarding the media's questioning, there are still many patients with respiratory diseases, gastroenteritis adenovirus, etc., whether it will be risky to announce the loosening of the indoor mask order at this stage. Zhang Shangchun responded that whether it is influenza, enterovirus or other respiratory viruses, the command center has been continuously monitoring since the end of last year. After the annual holiday, the monitoring data during this period shows that so far no large-scale epidemic has been seen. As for the schools on the other hand, he hopes to observe for a longer period of time. From a professional standpoint, there is not much risk in loosening the indoor mask order situation at this time. 
News (11)
Masks still required in medical facilities but not on public transport of Singapore from 13 February 2023
Image : Researcher's Picture

Starting next Monday (13 February 2023), the public will no longer need to wear masks when taking public transportation. As for medical care facilities, the Ministry of Health will continue to require staff, patients and visitors to wear masks in medical care facilities where there is contact and communication with patients.
Starting next Monday (13 February), the public will no longer need to wear masks when taking public transportation. As for medical care facilities, the Ministry of Health will require staff, patients and visitors to continue to wear masks in the facilities and places where patients have contact with patients.
The Ministry of Health's statement pointed out that this is to better protect the health of patients and medical staff. This will be a requirement of the authorities, not a requirement under the covid regulations. In addition to the medical field, other institutions may also require personnel to wear masks. For example, the Singapore Food Agency requires food handlers to wear masks due to food safety considerations. Private businesses may also choose to maintain the mask requirement to maintain workplace hygiene.
Authorities pointed out that wearing a mask is still an effective way to minimize the risk of infectious diseases, so the public, especially the elderly or those with weakened immunity, are encouraged to wear masks in crowded places or when visiting the infirm. Those who are unwell and have symptoms of coronavirus or respiratory infection should also wear a mask if they need to go out.
News (12) to (16) / Report by : Ewen Callaway / https://www.nature.com/articles/d41586-023-00347-z / Image : Web Screenshot (Getty Images)

News (12)
Covid drug molnupiravior drives viral mutations -- and now some want to halt its use

A drug widely used to treat COVID-19 might be spurring the evolution of new SARS-CoV-2 variants.

The drug, molnupiravir, works by introducing a flurry of mutations to the viral genome; this helps to clear infections. But a study1 of more than 13 million SARS-CoV-2 sequences has uncovered sequences that bear molnupiravir’s fingerprints. The study’s authors say the results suggest that molnupiravir treatment has sparked the evolution of viral lineages carrying numerous mutations that, in at least some cases, have the capacity to spread to other individuals.

The study was posted on the medRxiv preprint server in January. It has not yet been peer reviewed.

“Whether this should be of concern — that is an open question,” says Jesse Bloom, an evolutionary virologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington. Mutations to the SARS-CoV-2 genome can help the virus to evade immunity and become more transmissible, but most mutations are likely to harm it.

News (13)

Molnupiravir mimics some of the building blocks of RNA, the genetic material in SARS-CoV-2

Molnupiravir was developed by the pharmaceutical giant Merck, based in Rahway, New Jersey, and was authorized by regulators in the United States and United Kingdom in late 2021, and in Australia in early 2022. A company-sponsored clinical trial found that the drug — a pill taken for five days — reduced hospitalizations and deaths in people at risk of severe COVID-19.

Molnupiravir mimics some of the building blocks of RNA, the genetic material in SARS-CoV-2. The drug peppers the viral genome with mutations, which add up to make SARS-CoV-2 worse at replicating. This results in a marked reduction in SARS-CoV-2 levels in infected human cells and hamsters2.

But scientists have raised the possibility that, in rare cases, molnupiravir treatment might not entirely eliminate SARS-CoV-2, allowing some individuals who have taken the drug to continue to transmit the virus.

News (14)

Ryan Hisner first discovers a number of covi variant lineages carried more mutations than the others

Those concerns were largely theoretical until Ryan Hisner, a US schoolteacher who is part of a loose-knit community of SARS-CoV-2 variant spotters, started noticing peculiar patterns in sequencing data from around the world: a number of lineages carried many more mutations than their nearest relatives. Most of the genetic changes were of the type induced by molnupiravir.

The researchers’ analysis of global sequences showed that the prevalence of the suspect lineages rose substantially in 2022, the first year molnupiravir was widely used. The lineages were also much more likely to show up in sequencing data from countries where the drug was used — the United States, the United Kingdom and Australia — than in data from countries that hadn’t approved it, such as France and Canada.

News (15)

Viral lineage in Australia carrying 25 mutations is related to molnupiravir

Where SARS-CoV-2 sequence data include the age of the individual sampled, the telltale lineages tended to have come from older people, who are more likely to take molnupiravir. In Australia, where molnupiravir was pre-placed in care homes, the researchers identified a viral lineage carrying 25 mutations that had infected at least 20 people, mostly in their eighties and nineties.

Among the lineages that showed molnupiravir’s influence, a few — including the one from Australia — were represented by multiple sequences, indicating that they were capable of spreading. “I would say that our work closes down the possibility that these viruses can never be transmitted,” says team member Theo Sanderson, a computational biologist at the Francis Crick Institute in London.

News (16)

Molnupiravir treatment is yieding highly mutated viruses with the capacity to spread

Evidence linking molnupiravir to the mutation-heavy sequences is “circumstantial”, Merck said in a statement. “The authors assume these mutations were associated with molnupiravir treatment without evidence the viral sequences were isolated from treated patients.”

Bloom thinks the researchers make a good case that molnupiravir treatment is yielding some highly mutated viruses with the capacity to spread. But it’s not clear whether this could contribute to new coronavirus variants, or whether it is simply creating weakling viruses that are unlikely to spread very far. “SARS-CoV-2 is already generating plenty of mutations even in the absence of drug treatment,” he adds.

Rustem Ismagilov, a quantitative bioscientist at the California Institute of Technology in Pasadena, says the study underscores the need to quickly measure any risk that molnupiravir poses in terms of sparking new variants, and to weigh them against the drug’s benefits. “If we are playing Russian roulette, we’d better know our odds.”

Sarah Otto, an evolutionary biologist at the University of British Columbia in Vancouver, Canada, says the paper is another blow to the continued use of molnupiravir. She notes that a large-scale UK study found that the drug had no effect on hospitalizations or deaths3. “Given the large-scale risks of this mutagen producing new variants faster, including variants that are immune evasive, I encourage public-health leaders to call for a global halt to its use,” Otto says.

Ref.: doi: https://doi.org/10.1038/d41586-023-00347-z

News (17) to (20) / Source : Nature 614, 195-196 (2023) / https://www.nature.com/articles/d41586-023-00339-z

News (17)

Global pandemic treaty: Learning from climate-change errors

The global response to COVID-19 represented a “catastrophic failure of the international community in showing solidarity and equity”. This frank assessment comes in the opening line of the first, or ‘zero’, draft of a new international pandemic agreement, published by the World Health Organization (WHO) last week. The agreement is intended to help the world to better prepare for future pandemics. Negotiations over the details are due to start later this month and are likely to last at least a year.

Although it doesn’t say so explicitly, the WHO’s statement can be read as a rebuke to the leaders of high-income nations, highlighting the fact that their response to the ongoing pandemic has not been a model of cooperation or compassion. A promise to properly support a vaccine-distribution scheme called COVAX went unfulfilled, undermining its potential. Rich countries over-ordered and hoarded vaccines, stopping them from reaching people in other countries who needed them. Some of the world’s best-known and well-respected pharmaceutical companies fought to stop intellectual property (IP) being shared. Had they not done so, more manufacturers could have produced vaccines and treatments, and more lives could have been saved. The treaty drafted by the WHO is intended to ensure that this behaviour is never repeated. But as Nature has argued before, a treaty on its own offers no guarantee that promises will be kept.

News (18)

Waiving of applicable IP rights for a defined period duirng a pandemic

The draft text encourages the waiving of applicable IP rights for a defined period during a pandemic. In addition, at least one-fifth of relevant vaccines must be deposited with the WHO, to ensure that sufficient numbers reach the world’s poorest and most vulnerable people at the same time as they reach people in richer countries. Prices and contracts should be made public — something that didn’t happen during the COVID-19 pandemic, allowing countries to outbid each other for vaccines by offering higher prices that only pharmaceutical companies were a party to.

News (19)

The importance of open science and sharing of data is critical

The current wording also recognizes the importance of open science and the sharing of data such as viral genome sequences. Last month, the WHO urged China’s authorities to share sequence data, as well as information on cases, hospitalizations and vaccination rates. Another point emphasized in the zero draft is that countries that share their scientific knowledge — as many low-income countries did during the pandemic — should also share in the benefits.

All of this is necessary and overdue, and has the backing of scientists and campaigning organizations. But researchers are rightly concerned about the lack of clarity on how the treaty will work in practice, and how signatories will be held to their promises. The WHO recommends that countries make decisions through a conference of the parties (COP), a democratic forum in which all countries have an equal voice in decision-making.

But COPs are expensive to run, and the creation of such a framework would mean that the WHO — which faces a constant struggle to get countries to fund it properly — would struggle even more. COPs also take their time to reach decisions, as we know all too well from those governing international action on concerns such as climate change and biodiversity loss.

Perhaps most important of all, a forum of 200-odd countries, plus tens of thousands of observers and lobbyists, is, arguably, not the best way to ensure that an agreement is adhered to, especially when the onus for action lies with a relatively small number of high-income nations. There’s good evidence from the climate-change COP process that even legally binding agreements cannot compel nations to meet their commitments.

News (20)

WHO wants countries to agree on a shared monitoring system to avoid repeating "some of the worst of" pandemic behaviours

Sensibly, the WHO wants countries to agree on some kind of monitoring system — a way to get them to report back on whether promises on funding, IP or vaccines are being kept but negotiators and their teams would also be well advised to explore alternative ways of achieving the agreement’s aims. Researchers who study the impact of international treaties could advise on other potential models.

It is clear from the WHO’s zero draft text that the agency is determined to avoid a repeat of some of the worst of the behaviours seen during the pandemic. It is reassuring to see, throughout the text, encouragement for governments and companies to be transparent and willing to share, particularly when it comes to know-how and products that are based on publicly funded research. Had this happened previously, the coronavirus pandemic might well have been behind us by now.

The world has little more than a year to convert the draft into finished text. The commitments in the current version will probably be watered down before an agreement is reached. However as researchers prepare to publish their studies, and campaigners rush to accelerate campaigning, it is easy to forget the need to determine the kinds of institution and structure that are essential to ensuring an agreement is delivered on. Institutional structures are as important as the content of treaties. The WHO and national negotiators need to ask themselves what value an agreement has if it includes everything in the WHO’s zero draft, but proves unworkable in practice.

Source : Nature 614, 195-196 (2023)

Ref.: doi: https://doi.org/10.1038/d41586-023-00339-z

Video

Zhiyuan High School video on Hu Xinyu's case recovered and exposed

https://twitter.com/juanli324/status/1621370825340506118?cxt=HBwWjMDS2ZuLooAtAAAA&cn=ZmxleGlibGVfcmVjcw%3D%3D&refsrc=email

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