First Known Covid Case Was Vendor at Wuhan Market, Scientist Says

A scientist who has pored over public accounts of early Covid-19 cases in China reported on Thursday that an influential World Health Organization inquiry had most likely gotten the early chronology of the pandemic wrong. The new analysis suggests that the first known patient sickened with the coronavirus was a vendor in a large Wuhan animal market, not an accountant who lived many miles from it.

The report, published on Thursday in the prestigious journal Science, will revive, though certainly not settle, the debate over whether the pandemic started with a spillover from wildlife sold at the market, a leak from a Wuhan virology lab or some other way. The search for the origins of the greatest public health catastrophe in a century has fueled geopolitical battles, with few new facts emerging in recent months to resolve the question.

The scientist, Michael Worobey, a leading expert in tracing the evolution of viruses at the University of Arizona, came upon timeline discrepancies by combing through what had already been made public in medical journals, as well as video interviews in a Chinese news outlet with people believed to have the first two documented infections.

Dr. Worobey argues that the vendor’s ties to the Huanan Seafood Wholesale Market, as well as a new analysis of the earliest hospitalized patients’ connections to the market, strongly suggest that the pandemic began there.

“In this city of 11 million people, half of the early cases are linked to a place that’s the size of a soccer field,” Dr. Worobey said. “It becomes very difficult to explain that pattern if the outbreak didn’t start at the market.”

Several experts, including one of the pandemic investigators chosen by the W.H.O., said that Dr. Worobey’s detective work was sound and that the first known case of Covid was most likely a seafood vendor.

But some of them also said the evidence was still insufficient to decisively settle the larger question of how the pandemic began. They suggested that the virus probably infected a “patient zero” sometime before the vendor’s case and then reached critical mass to spread widely at the market. Studies of changes in the virus’s genome — including one done by Dr. Worobey himself — have suggested that the first infection happened in roughly mid-November 2019, weeks before the vendor got sick.

“I don’t disagree with the analysis,” said Jesse Bloom, a virologist at the Fred Hutchinson Cancer Research Center. “But I don’t agree that any of the data are strong enough or complete enough to say anything very confidently, other than that the Huanan Seafood Market was clearly a super-spreading event.”

Dr. Bloom also noted that this was not the first time the W.H.O. report, done in collaboration with Chinese researchers, was found to contain mistakes, including errors involving early patients’ potential links to the market.

“It’s just kind of mind-boggling that in all of these cases, there keep being inconsistencies about when this happened,” he said.

Toward the end of December 2019, doctors at several Wuhan hospitals noticed mysterious cases of pneumonia arising in people who worked at the Huanan Seafood Wholesale Market, a dank and poorly ventilated space where seafood, poultry, meat and wild animals were sold. On Dec. 30, public health officials told hospitals to report any new cases linked to the market.

Fearing a replay of SARS, which emerged from Chinese animal markets in 2002, Chinese officials ordered the Huanan market closed, and Wuhan police officers shut it down on Jan. 1, 2020. Despite those measures, new cases multiplied through Wuhan.

Wuhan authorities said on Jan. 11, 2020, that cases had begun on Dec. 8. In February, they identified the earliest patient as a Wuhan resident with the surname Chen, who fell sick on Dec. 8 and had no link to the market.

Chinese officials and some outside experts suspected that the initially high percentage of cases linked to the market might have been a statistical fluke known as ascertainment bias. They reasoned that the Dec. 30 call from officials to report market-linked illnesses may have led doctors to overlook other cases with no such ties.

“At the beginning, we presumed that the seafood market may have the novel coronavirus,” Gao Fu, director of China’s Center for Disease Control and Prevention, said in May 2020, according to China Global Television Network. “But it now turns out that the market is one of the victims.”

By the spring of 2020, senior members of the Trump administration were promoting another scenario for the origin of the pandemic: that the virus had escaped from the Wuhan Institute of Virology, which has a campus roughly eight miles away from the Huanan market, across the Yangtze River.

In January of this year, researchers chosen by the W.H.O. visited China and interviewed an accountant who had reportedly developed symptoms on Dec. 8. Their influential March 2021 report described him as the first known case.

But Peter Daszak, a disease ecologist at EcoHealth Alliance who was part of the W.H.O. team, said that he was convinced by Dr. Worobey’s analysis that they had been wrong.

“That December the eighth date was a mistake,” Dr. Daszak said.

The W.H.O. team never asked the accountant the date his symptoms began, he said. Instead, they were given the Dec. 8 date by doctors from Hubei Xinhua Hospital, who handled other early cases but did not care for Mr. Chen. “So the mistake lies there,” Dr. Daszak said.

For the W.H.O. experts, Dr. Daszak said, the interview was a dead end: The accountant had no apparent links to an animal market, lab or a mass gathering. He told them he liked spending time on the internet and jogging, and he did not travel much. “He was as vanilla as you could get,” Dr. Daszak said.

Had the team identified the seafood vendor as the first known case, Dr. Daszak said, it would have more aggressively pursued questions like what stall she worked in and where her products came from.

This year, Dr. Daszak has been one of the strongest critics of the lab-leak theory. He and his organization, EcoHealth Alliance, have taken heat for research collaborations with the Wuhan Institute of Virology. Last month, the National Institutes of Health said EcoHealth was in breach of the terms and conditions of its grant for research on coronaviruses in bats.

While the doctors at Hubei Xinhua Hospital said that the onset of the accountant’s illness had been Dec. 8, a senior doctor at Wuhan Central Hospital, where Mr. Chen was treated, had told a Chinese news outlet that he developed symptoms around Dec. 16.

Asked about Mr. Chen’s case, China’s National Health Commission said it stood by comments made by Liang Wannian, the leader of the Chinese side of the W.H.O.-China investigation who led the interview with the Hubei Xinhua Hospital doctors. Mr. Liang told a news conference in February of this year that the earliest Covid case showed symptoms on Dec. 8 and was “not connected” to the Huanan market.

In their report, the W.H.O. experts concluded that the virus most likely spread to people from an animal spillover, but they could not confirm that the Huanan market was the source. By contrast, they said that a lab leak was “extremely unlikely.”

The report has come under fire for several errors and shortcomings. The Washington Post revealed in July that the report listed the wrong viral samples for several early patients — including the first official case — and mistakenly linked the first family cluster of cases to the Huanan market. The W.H.O. promised to fix the errors, but they remain in the report on the organization’s website. (The organization said that it would ask the report’s authors if and how they would correct the mistakes.)

In May, two months after the report by the W.H.O. and China was published, 18 prominent scientists, including Dr. Worobey, responded with a letter in Science complaining that the W.H.O. team had given the lab-leak theory short shrift. Far more research was required, they argued, to determine whether one explanation was more likely than the other.

An expert on the origins of influenza and H.I.V., Dr. Worobey has tried to piece together the early days of the Covid pandemic. Reading a May 2020 study of early cases written by local doctors and health officials in Wuhan, he was puzzled to see a description that seemed like Mr. Chen: a 41-year-old man with no contact with the Huanan market. But the study’s authors dated his symptoms to Dec. 16, not Dec. 8.

Then Dr. Worobey found what appeared to be a second, independent source for the later date: Mr. Chen himself.

“I got a fever on the 16th, during the day,” a man identified as Mr. Chen said in a March 2020 video interview with The Paper, a publication based in Shanghai. The video indicates that Mr. Chen is a 41-year-old who worked in a company’s finance office and never went to the Huanan market. Official reports said that he lived in the Wuchang district in Wuhan, miles from the market.

The New York Times was not able to independently confirm the identity of the man in the video.

Along with his fever on Dec. 16, Mr. Chen said he felt a tightness in his chest and went to the hospital that day. “Even without any strenuous exercise, with just a tiny bit of effort, like the way I’m speaking with you now, I’d feel short of breath,” he said.

Dr. Worobey said that the medical records shown in the video might hold clues to how the W.H.O.-China report wound up with the wrong date. One page described surgery Mr. Chen needed to have teeth removed. Another was a Dec. 9 prescription for antibiotics referring to a fever from the day before — possibly the day of the dental surgery.

On the video, Mr. Chen speculated that he might have gotten Covid “when I went to the hospital” — possibly a reference to his earlier dental surgery.

The Washington Post noted in July that the details provided by the W.H.O. for the Dec. 8 case seemed to fit better with an entry from an online database of viral samples linked to someone who got sick on Dec. 16. In response, the W.H.O. had said it was looking into the discrepancy.

An agency spokesman told The New York Times it would be “difficult to comment” on the first known case because the W.H.O. team had limited access to health data. He said it was important for investigators to keep looking for patients infected even earlier.

In Dr. Worobey’s revised chronology, the earliest case is not Mr. Chen but the seafood vendor, a woman named Wei Guixian, who developed symptoms around Dec. 11. (Ms. Wei said in the same video published by The Paper that her serious symptoms began on Dec. 11, and she told The Wall Street Journal that she began feeling sick on Dec. 10. The W.H.O.-China report listed a Dec. 11 case linked to the market.)

Dr. Worobey found that hospitals reported more than a dozen likely cases before Dec. 30, the day the Wuhan authorities alerted doctors to be on the lookout for ties to the market.

He determined that Wuhan Central Hospital and Hubei Xinhua Hospital each recognized seven cases of unexplained pneumonia before Dec. 30 that would be confirmed as Covid-19. At each hospital, four out of seven cases were linked to the market.

By focusing on just these cases, Dr. Worobey argued, he could rule out the possibility that ascertainment bias skewed the results in favor of the market.

Still, other scientists said it’s far from certain that the pandemic began at the market.

“He has done an excellent job of reconstructing what he can from the available data, and it’s as reasonable a hypothesis as any,” said Dr. W. Ian Lipkin, a virologist at the Mailman School of Public Health at Columbia University. “But I don’t think we’re ever going to know what’s going on, because it’s two years ago and it’s still murky.”

Alina Chan, a postdoctoral fellow at the Broad Institute in Cambridge, Mass., and one of the most vocal proponents of investigating a lab leak, said that only new details about earlier cases — going back to November — would help scientists trace the origin.

“The main issue this points out,” she said, “is that there’s a lack of access to data, and there are errors in the W.H.O.-China report.”

Eleanor Goodman contributed translation and Liu Yi contributed research.

Austria Covid: Nationwide vaccine mandate announced, lockdown reimposed

Schallenberg reported his federal government would look to impose the nationwide vaccine prerequisite from February 1. Just less than 66{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of Austria’s overall inhabitants is totally vaccinated versus Covid-19, one of the lessen fees in the European Union, where conditions are surging.

The nationwide lockdown — the to start with in Europe this tumble — begins Monday and will previous for 10 times minimum amount, and could be extended for a further 10 days, Schallenberg instructed reporters at a information convention in Vienna.

“We do not want a fifth wave. We will not want a sixth and seventh wave. We don’t want to have this discussion upcoming summertime,” Schallenberg mentioned.

Less than those people measures, which came into force on November 15, the unvaccinated had been requested to remain at property other than for a number of limited explanations, with the principles policed by officers carrying out place checks on all those who ended up out and about.

Vaccinations are at present recommended for everybody aged 12 and over in Austria. On Monday, a pilot scheme to vaccinate youngsters aged five to 11 obtained under way in Vienna, the nationwide money.

Austria to impose Covid lockdown for the unvaccinated age 12 and older

Asked by CNN from what age the necessary vaccination buy would implement, the Austrian Chancellory claimed: “Information are still to arrive, from what age and when you are considered absolutely vaccinated.”

Austrian Wellbeing Minister Wolfgang Mückstein explained Friday that universities and kindergartens would keep on being open during the future countrywide lockdown.

But Schallenberg explained it was doable for mom and dad to acquire their kids out of college if they so wished. “This is often a challenge, for just about every household,” he explained. Through the to start with Austrian lockdown, faculties and kindergartens were closed.

Mückstein also urged the wearing of FFP2 masks in all enclosed areas and explained employees could request the selection of doing the job from household in which attainable.

Once the nationwide lockdown is lifted, lockdown steps will keep on being in area for unvaccinated Austrians, Mückstein said, adding that every thing wanted to be done to steer clear of a “fifth wave.”

Schallenberg had harsh words for anti-vaccination activists as he tackled the news meeting Friday, indicating they experienced acted irresponsibly.

“We have too lots of political forces in this country that are battling from this [vaccination] vehemently, massively and publicly. That is irresponsible. This is truly an attack on our well being treatment procedure,” he mentioned.

“And incited by these radical opponents of vaccination, by specious faux news, sad to say as well lots of of us have not been vaccinated. The consequence is overcrowded intense treatment units and huge human suffering.”

At the time it goes into result in February, Austria’s Covid-19 vaccination mandate will be the most stringent evaluate to manage the coronavirus via vaccination still seen in Europe.

In Italy, all staff are expected to have a “eco-friendly move” — a wellness certification that shows proof of either complete vaccination, latest recovery from an infection or a damaging examination within just the earlier 48 several hours — or risk a fantastic and suspension devoid of pay back. Folks need to also exhibit their “inexperienced move” to enter community locations like theaters and cinemas.

Having said that, only wellness care employees are needed to be vaccinated.

Italy’s governing administration has credited the “eco-friendly move” technique with boosting vaccination costs.

Germany's Covid cases hit record high with Merkel warning of 'dramatic' situation

Neighboring Germany also introduced ideas Thursday to introduce focused Covid-19 restrictions on the unvaccinated in buy to tackle report concentrations of bacterial infections amid its fourth wave of the pandemic.

Outgoing Chancellor Angela Merkel explained the country’s Covid-19 situation as ”dramatic” and ”very worrying” at a news convention Thursday, pursuing a conference with Germany’s 16 federal point out leaders on stricter Covid-19 actions.

Merkel warned that intense care device beds were filling up a lot far too swiftly, introducing it was ”high time to acquire motion.”

Speaking Friday at a information convention in Berlin, acting Wellbeing Minister Jens Spahn explained Germany as being “in a nationwide crisis,” adding “we will not break this wave with vaccinations by yourself.”

Asked about the possibility of a lockdown for all people, Spahn explained to reporters ”we are in a situation exactly where we can’t rule nearly anything out.”

Lothar Wieler, head of Germany’s disease and command middle, the Robert Koch Institute (RKI), told reporters the place experienced under no circumstances observed these kinds of significant charges of an infection as now in the complete of the pandemic.

For a twelfth working day in a row, Germany has noted document new Covid-19 cases. The RKI on Friday claimed 52,970 new circumstances within just the earlier 24 hours. Additional than 98,000 persons have died as a result of coronavirus in Germany, in accordance to RKI knowledge.

The country’s recent day-to-day demise rate stands amongst 200 and 300, Wieler claimed. Nevertheless, because of to Germany’s document amount of bacterial infections around the past 12 days, “the demise level is likely to improve above the coming times,” he stated.

France is also dealing with a increase in Covid-19 infection premiums, but French President Emmanuel Macron has reported a lockdown of the unvaccinated is “not necessary” presented the country’s Covid-19 approach.

“The countries who are locking down the unvaccinated are those people who you should not have the ‘health pass’ in position,” Macron stated, in an job interview with French newspaper La Voix du Nord printed late Thursday.

France’s “wellbeing go” confirms the bearer’s vaccination standing or proof of a destructive Covid take a look at and has ruled obtain to a broad assortment of institutions in France since its introduction in July.

Ireland, which has just one of Europe’s greatest vaccination costs, with 89.1{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of persons more than the age of 12 obtaining been immunized, imposed a midnight curfew on bars, dining establishments and nightclubs from Thursday as the place faces a fresh new wave of Covid-19 infections.

CNN’s Joseph Ataman contributed to this report.

Pfizer requests authorization for COVID pill Paxlovid: Updates

Long COVID may affect how women recover from exercise

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New research explores the link between long COVID and women’s ability to exercise. Artur Widak/NurPhoto via Getty Images
  • Long COVID or post-acute COVID syndrome is characterized by a multitude of symptoms that persist beyond the acute phase of 3–4 weeks after getting the SARS-CoV-2 virus.
  • Women hospitalized with COVID-19 are more likely to experience persistent deficits in cardiovascular and lung function than men in the months following discharge.
  • A new study found that even women with mild-to-moderate COVID-19 may experience slower declines in their resting heart rate after physical activity in the post-acute phase of the SARS-CoV-2 infection.
  • Such deficits in cardiovascular function during exercise are associated with reduced capacity for physical exercise and, potentially, activities of daily life.
  • Women presenting with specific long COVID symptoms, namely shortness of breath or joint or muscle aches, were also more limited in their ability to do a walking test than people who had had a SARS-CoV-2 infection but experienced no lingering symptoms.

Although the majority of individuals recover within the first 3–4 weeks after contracting COVID-19, a considerable number continue to experience lingering symptoms for weeks or months after this initial or acute phase of the disease.

These symptoms, which people refer to collectively as long COVID or post-acute COVID-19, include shortness of breath, loss of smell and taste, brain fog, headaches, and fatigue.

Studies have shown that more than half of the individuals hospitalized with COVID-19 during the initial phase of the SARS-CoV-2 infection show persistent impairments in cardiovascular and lung function several months after discharge. Furthermore, women hospitalized with severe COVID-19 are more likely than men to present with such persistent deficits in cardiovascular and lung function after discharge.

Individuals may present with persistent symptoms during the post-acute phase of COVID-19, regardless of the severity of symptoms during the acute phase of the illness. The effects of mild-to-moderate COVID-19 on lung and cardiovascular function and, subsequently, on daily physical functioning during the post-acute phase is not well-understood.

Researchers at Indiana University, Bloomington, recently examined how mild-to-moderate COVID-19 affected exercise capacity or tolerance during the post-acute phase in women. Exercise tolerance or capacity refers to the ability of an individual’s cardiovascular system to sustain physical activity.

The researchers used an exercise test called the 6-minute walk test to assess the persistent effects of SARS-CoV-2 infection on cardiovascular function in women during the post-acute phase of the infection.

They found that women with COVID-19 who had mild-to-moderate illness during the acute phase showed a slower decline in their heart rate after the 6-minute walk test than the participants in the control group. This difference was more pronounced in women actively experiencing long COVID symptoms.

However, encouragingly, they found no statistically significant differences in a range of other measures, including pre- and post-test oxygen saturations, pre- and post-test heart rate, ratings of perceived exertion, and ratings of perceived breathlessness.

The study’s lead author, Dr. Stephen Carter, a professor at Indiana University, told Medical News Today: “A puzzling feature of post-acute COVID-19 syndrome is the variable presentation of symptoms that appear to be independent of initial illness severity. The present work shows even those with mild-to-moderate initial symptoms can be affected with underlying cardiac-related irregularities with the potential to affect exercise tolerance and/or activities of daily living.”

“It’s also plausible that lingering symptoms, particularly muscle/joint pain and/or shortness of breath, may trigger a maladaptive pattern that accelerates systemic deconditioning. However, further research is needed.”

Dr. Ziyad Al-Aly, chief of research and education service at Veterans Affairs St. Louis Health Care System, also spoke with MNT. Dr. Al-Aly, who was not involved with the study, said, “Studies like this are important to help us understand why some people with long COVID experience profound exertional fatigue that may limit their ability to exercise and their ability to carry out activities of daily living.”

The study appears in the journal Experimental Physiology.

The study included 29 women who had experienced mild or moderate illness due to COVID-19. These women had received a positive SARS-CoV-2 diagnosis at least 4 weeks prior to the study, with the average time of diagnosis being 94 days before the study. The control group consisted of 16 women who had never tested positive for a SARS-CoV-2 infection.

Out of the 29 participants in the test group, 17 women reported experiencing at least one long COVID symptom at the time of the study. These long COVID symptoms included shortness of breath, fatigue, cough, muscle or joint pain, loss of smell or taste, and skin irritation.

The researchers administered pulmonary function tests to assess various aspects of lung function. They found that the women who had tested positive for SARS-CoV-2 exhibited reduced total lung capacity compared with those in the control group.

The researchers then evaluated changes in cardiovascular function during and after the 6-minute walk test. The test measures the distance that participants walk in 6 minutes at their normal pace, and researchers use it to assess exercise tolerance. The team adjusted the results for age, sex, and body mass index (BMI) to prevent these variables from influencing the test results.

There was no significant difference between the distances that the two groups covered during the test.

However, women with SARS-CoV-2 who experienced shortness of breath or joint or muscle pain had a lower adjusted distance value than those with SARS-CoV-2 who did not experience these long COVID symptoms.

The researchers assessed the blood pressure, heart rate, and blood oxygen or oxygen saturation levels before and immediately after the 6-minute walk test. They calculated the heart rate response during exercise by subtracting the heart rate at rest from the heart rate after the completion of the test.

The heart rate response during exercise is a measure of cardiovascular function, with a lower heart rate response being a predictor of reduced exercise capacity and cardiovascular disease-associated mortality.

The women in the SARS-CoV-2 group showed a lower heart rate response than those in the control group.

Moreover, the participants in the SARS-CoV-2 group who reported shortness of breath as a long COVID symptom at the time of the study had a lower heart rate response during the test than those in the SARS-CoV-2 group who did not have this symptom.

The researchers also measured heart rate recovery, which is another indicator of cardiovascular health and all-cause mortality.

Heart rate tends to drop immediately after strenuous exercise. Heart rate recovery measures the decrease in heart rate after the cessation of exercise. Specifically, heart rate recovery quantifies the decrease in heart rate at a predefined time interval — generally 1 minute — from the end of the physical activity.

In the current study, the researchers measured the participants’ heart rate at the end of each minute during the 5-minute recovery period after the 6-minute walk test.

The SARS-CoV-2 group participants showed a less significant decrease in heart rate at 1 minute after the completion of the test than those in the control group. This suggests that the decline in heart rate occurred more gradually in the women in the SARS-CoV-2 group. Such a delay in heart rate recovery is associated with reduced exercise capacity.

Furthermore, women in the SARS-CoV-2 group who exhibited specific long COVID symptoms at the time of the study had decreased heart rate recovery compared with the SARS-CoV-2 group participants without these symptoms.

Specifically, women in the SARS-CoV-2 group with symptoms such as fatigue, loss of taste or smell, joint and muscle aches, or shortness of breath had decreased heart rate recovery compared with women who had not had SARS-CoV-2.

“A lot of long COVID-19 patients are placed into rehabilitation programs that are designed for non-COVID-19 patients. These programs may not be suitable for long COVID patients. It is important to understand that people with long COVID need programs designed for them (pacing, etc.). Findings from this study and others should be taken into account when designing rehabilitation programs for people with long COVID,” said Dr. Al-Aly.

Dr. Carter noted: “SARS-CoV-2 participants and [people without the infection] were matched for age, BMI, smoking status, and history of cardiopulmonary disease. As such, we have better assurance that reported differences were attributed to SARS-CoV-2, as opposed to another comorbidity.”

“A strength of the work is that comparisons were performed among women — who appear to be susceptible to persistent SARS-CoV-2-related symptoms — during and following a 6-minute walk test.”

Dr. Carter acknowledged that the study had a few limitations. He said: “Indeed, the 6-minute walk test is a widely used clinical tool that offers insight into exercise capacity and walking autonomy. However, it should be noted we cannot disregard the possibility of undiagnosed pulmonary abnormalities and/or autonomic dysfunction that existed prior to a SARS-CoV-2 infection. Additionally, it is conceivable some controls may have had an asymptomatic SARS-CoV-2 infection and/or a previous false-negative diagnostic test for SARS-CoV-2.”

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‘Cupping’ technique could improve vaccine delivery

‘Cupping’ technique could improve vaccine delivery
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Inspired by ancient medicine, experts have tested a new technique to improve vaccine delivery. Pansfun Images/Stocksy
  • A team of researchers recently developed a novel way of delivering nucleic acid-based medicines using a method similar to an ancient cupping technique, Home Garden USA.
  • Their experiments indicate that the technique makes vaccine delivery more effective by several orders of magnitude.
  • The cupping technique is currently undergoing clinical trials to deliver a COVID-19 vaccine.

Over the past 20 years, scientists have developed a range of nucleic acid-based medicines as both treatments and vaccines.

Nucleic acids are present in all living cells, most notably as DNA and RNA.

Treatments and vaccines that use nucleic acids work by inhibiting, adding, replacing, or editing DNA and RNA in host cells.

How well these treatments and vaccines work depends on how well they can be delivered to the host’s cells. If directly injected into tissue, for example, most nucleic acids will rapidly degrade unless protected.

The Pfizer-BioNTech and Moderna COVID-19 vaccines are both nucleic acid-based medicines. Nucleic acids in these vaccines are enclosed and protected by lipid nanoparticles that deliver them across the host cell membrane.

Although they are effective, drugs delivered in this way are vulnerable to degradation during storage.

One delivery method for nucleic acid-based medicines is electroporation. This involves delivering nucleic acids to cells made more permeable using a pulse of electricity.

While somewhat effective, these electrical impulses can cause muscle contractions, tissue damage, and pain, and they may not be suitable for people who use implantable electrical devices such as defibrillators or pacemakers.

Using this method also requires substantial training, and equipment costs may make it inaccessible to regions and populations with fewer resources.

Creating a method for delivering nucleic acid-based medicines that overcomes unwanted side effects and cost barriers while still being effective could increase the accessibility of vaccines to areas with limited resources.

Recently, researchers from Rutgers, the State University of New Jersey in Piscataway, and GeneOne Life Science in Seoul, South Korea, developed a method based on an ancient cupping technique to deliver nucleic acid-based medicines.

“Development of enhanced delivery technologies plays an instrumental role in bringing nucleic acid-based biologics to broad use and clinical relevance, and worldwide vaccine distribution is just one example,” said senior study author Prof. Hao Lin.

“We have demonstrated an alternative, safe, and effective transfection platform that yields high levels of transgene expression.”

“The advantages also include device cost effectiveness, […] manufacturing scalability, and minimal requirements for user training,” he added.

“Because of the inherent advantages of DNA, not least of which is avoiding cold-chain requirements of other vaccines, this technology facilitates vaccination programs into remote regions of the world where resources are limited,” he added.

The study now appears in the journal Science Advances.

Cupping therapy is an ancient treatment method from the Middle East and China. It involves applying heated cups to the skin to create negative pressure and increase blood circulation to promote healing.

Since 1950, doctors have used the method in hospitals in China and elsewhere for conditions such as acne, facial paralysis, and dyspnea.

Although evidence of its health benefits is lacking, the authors of the new study decided to investigate a similar technique as a potential delivery method for nucleic acid-based medicine.

To test the method, the researchers gathered two groups of rats and injected both with DNA in the upper layers of their skin. One group received the “suction cup treatment” on their injection site, whereas the other group did not.

The researchers monitored the activity of the DNA with fluorescence microscopy. They found that gene expression from the vaccine was detectable at 4 hours post-vaccination. In the rats who also underwent cupping, however, gene expression was detectable at 1 hour post-vaccination.

At 24 hours post-injection, the researchers saw that gene expression was detectable eight times deeper under the skin among the rats who underwent cupping than among those who received DNA injections alone.

To investigate whether or not this technology could work to deliver potential COVID-19 vaccines, the researchers next injected the rats with a synthetic SARS-CoV-2 DNA candidate vaccine.

They split the rats into three groups:

  • The first group received two injections of the vaccine candidate without suction on days 0 and 14.
  • The second group received one vaccine, followed by dermal suction on day 0.
  • The third group received two vaccinations and dermal suction on days 0 and 14.

The researchers collected blood samples from the rats on days 0 and 14, before vaccination, and again on day 29.

They found that the rats who received cupping after the vaccine had a significantly stronger immune response than those who received the vaccine alone.

The researchers also found that immune responses in the rats who received a single vaccine followed by suction were not statistically different from those who received two vaccines followed by suction.

They also note that the rats who underwent suction had no evidence of tissue damage or lymphocyte infiltration in their injected areas.

The researchers say that the underlying mechanisms for suction-enhanced delivery are not clear. They hypothesize, however, that it may work via the CG pathway. This plays a role in determining which molecules travel through membranes and enter cells.

The researchers explain that it will be challenging to confirm the underlying mechanisms of cupping due to the complexity of the processes involved and a lack of availability of drugs used for testing.

Nevertheless, the researchers say that even without mechanistic understanding, it is still possible to improve the method.

“Currently, the procedure is two-step: an injection followed by suction,” Dr. Lin told Medical News Today.

“We are working on a combination device/method to render one-step application — that is, injection and suction in a single step by a single device,” he continued. “Furthermore, we are trying to reduce suction time even further to increase patient and staff acceptance.”

When asked whether this method could work for COVID-19 vaccines, Dr. Lin said, “Theoretically, this may be possible, but we cannot answer without testing since, except for DNA vaccines, COVID-19 vaccines are delivered into the muscle, whereas this device delivers [the] vaccine to the upper layers of the skin.”

“The [suction] device is being tested currently in phase 1 and phase 2 clinical trials of a COVID-19 vaccine. The documentation to enable filing with regulatory agencies for general and widespread clinical use is being readied,” he said.

The researchers conclude that cupping is a promising method for nucleic acid-based medicine delivery. However, further research is necessary to see whether it could work to deliver COVID-19 vaccines to humans.

“The suction device has numerous advantages relative to other devices for DNA vaccine delivery. First, it is very inexpensive and easy to use, requiring minimal training,” Dr. Lin told MNT. “Secondly, the device is run from a battery that is easily rechargeable.”

“Third,” he continued, “is the high degree of patient acceptance, as the device will help deliver DNA vaccines without pain or discomfort.”

“And fourth, unlike the significant setup times with other devices, this only requires changing out a cap and then pressing the power button; the machine will turn off in a few seconds.”

“This, coupled with the many advantages of DNA as a vaccine type — the greatest advantages being the ability to completely avoid the need for freezers from the clinician’s perspective, and low side effects and discomfort from the patient’s perspective — makes this an ideal vaccine platform for resource-limited and remote regions,” he concluded.

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CVS, Walgreens open COVID vaccine appointment for kids: Updates