Health & BeautyJan 21. 2021Photo Credit: Bureau of Information office of Public Health ministry’s Permanent Secretary
By The Nation
Dr Yong Poovorawan, chief of the Centre of Excellence in Clinical Virology at Chulalongkorn University, appeared at a Public Health Ministry briefing on Wednesday in a bid to reassure the public after widespread concern over Thailand’s Covid-19 vaccine procurement.
“It is impossible for [every country] to get vaccines immediately even when they have enough money,” Dr Yong explained. “The global population is more than 7 billion. Just 50 per cent of population would need 8 billion vaccines since each person has to take two doses. So it will be impossible to vaccinate everybody within this year.”
How long before vaccine is approved – and will it be safe?
Vaccines usually take a long time to develop in animal and clinical (human) trials, which first need approval from the Food and Drug Administration (FDA), said Yong. Clinical trials have three steps: safety study, immunity test and effectiveness study. The final step usually takes more than a year or two for researchers to collect data from parallel trials where one group of volunteers is given the vaccine and a parallel “control” group is given a placebo.
However, that process has been accelerated as scientists around the world hurried to find a cure for the global pandemic. As a result, Covid-19 vaccines have been developed in just one year. They are now being screened for safety and efficacy by health authorities globally, including Thailand’s FDA.
Sinovac or AstraZeneca: Which is better?
We need to see which vaccines Western countries are using, said Dr Yong. The first available were mRNA vaccines – a new type of vaccine to protect against infectious diseases. These vaccines use strands of genetic material called mRNA inside a special coating called a nanoparticle. When injected, they instruct the human body to create a “spike protein” similar to the SARS-CoV-2 virus responsible for Covid-19. This immune response produces antibodies to protect our cells from getting infected if the virus enters our body. We could say it uses our body to create a vaccine, said Yong. The mRNA method is new for humans but draws on previous research on other diseases.
Another type is the viral vector vaccines produced by AstraZeneca and Russia’s Sputnik programme. These are similar to mRNA vaccines but use adenovirus as a vector instead of nanoparticles. This vaccine technology has a proven track record fighting the spread of Ebola in Africa. Moreover, viral vector vaccines will be cheaper in the future.
China’s Sinovac uses a third approach – the inactivated or killed vaccine method that has been in use for 70 years to combat viruses such as polio and rabies. The disadvantage of this vaccine is difficulty in manufacturing, increased cost per dose, and multiple immunisations required. Thailand has agreed to buy two million doses of SinoVac’s inactivated vaccine. As we know almost everything about traditional inactivated vaccines, it would be easier to handle, said Yong. But its relatively high cost of manufacturing makes it difficult to produce and purchase in high quantities.
Side effects of vaccine in Norway
Dr Yong also responded to news that 23 frail elderly patients had died soon after taking Pfizer BioNTec’s mRNA vaccine. The deaths might have been caused by side effects such as dizziness that triggered accidents, he said. Norwegian health authorities say common adverse reactions to mRNA vaccines that are not usually dangerous – such as fever, nausea and diarrhoea – may have played a role in the deaths. Dr Yong pointed out that death rates in general among the elderly had not risen after vaccination.
Will pregnant women and children get the jab?
Dr Yong said more research was needed on safety and dosage before pregnant women and children under 18 were given the vaccine in Thailand.
Addressing public calls to vaccinate people of working age first, he said there was no guarantee this move would prevent transmission. He explained that the vaccine may just prevent symptoms, meaning that even if they were inoculated, the working-age group could spread the virus to at-risk members of society.
People should understand that every disease can be prevented, Dr Yong said in conclusion. Vaccines were just one tool to help stop the virus from spreading. Meanwhile people should calmly continue using the tools in hand – keep their hands clean, wearing masks, and social distancing – to protect themselves. The results of vaccination would be seen soon, he predicted, since many wealthy countries had already rolled out inoculation programmes.
Long Island physician Benjamin Luft began receiving urgent calls from his elderly clinical trial subjects almost as soon as New York followed numerous other states last week and announced it would begin vaccinating anyone 65 or older with one of two authorized coronavirus vaccines, those made by Pfizer and Moderna.
The subjects wanted to get out of the clinical trial Luft is helping oversee of an experimental vaccine made by another company, Novavax.
They wanted to be “unblinded” and find out if they had received a placebo in the Novavax study, and, if so, try to get the Pfizer and Moderna vaccines, which have already been proved to be about 95% effective at preventing coronavirus infections.
“The number who have been calling me has been significant, and the numbers are increasing,” Luft, an infectious-disease expert at Stony Brook University Hospital, said in an interview. Fresh recruits also have begun to dry up, he said: “As we are doing our recruitment, all of a sudden the people over 65 became less interested.”
States have responded to the confusing, uneven and slow rollout of coronavirus vaccine by expanding eligibility for the shots ahead of schedule, quickly moving from the goal of immunizing front-line medical workers and long-term care residents into much broader populations of millions of elderly people.
But the moves have instantly made it more difficult to recruit and retain test subjects for clinical trials of vaccines that have yet to win emergency authorization.
The most immediately impacted vaccine trial in the United States involves Novavax, which on Dec. 28 set out to recruit 30,000 people for a major domestic trial, including 25% in the crucial over-65 category who are at the greatest risk for serious covid-19 disease.
Two-thirds of the test subjects in the Novavax study are getting the experimental vaccine, and one-third get the placebo, in the type of double-blind clinical trial that is considered the gold standard for testing whether drugs and vaccines work. But without recruiting and keeping a robust cohort of elderly subjects in the trial, the value of the data generated by the trial will be diminished.
“We hope Novavax vaccine will not be derailed by the fact that subjects in the trial would leave the trial to get access to a known vaccine,” Moncef Slaoui, the chief scientific adviser to Operation Warp Speed, said last week at a JP Morgan conference. Novavax and the Food and Drug Administration, which oversees trials, say they remain hopeful the Novavax study can achieve full recruitment.
It is the latest in a series of challenges for Novavax, a Maryland biotechnology company that in July received $1.6 billion in federal taxpayer money via Operation Warp Speed development and manufacturing contracts. Earlier in the year it received nearly $400 million from the Coalition for Epidemic Preparedness Innovations (CEPI), a Norway-based nonprofit that supports global vaccine development.
The infusions of public and nonprofit money have dramatically boosted the prospects of a company that has never had a marketed product in its three-decade history. Its stock price began 2020 trading below $4 per share; it was worth $127.43 on Friday. But the company’s predictions last summer that it would produce 100 million doses by the end of 2020 and early 2021 proved overly optimistic.
The Novavax effort was crippled by manufacturing-related time lags that pushed its Phase 3 trial launch date from the fall into late December – a delay that has now put the company in its current bind over the trial.
Novavax did not have its own manufacturing facility, so it was forced to use contract manufacturers to make its vaccine for trials and eventually commercial operations.
The company said Operation Warp Speed last year kicked it out of its first contract manufacturer in Baltimore, Emergent, which made its early batches of vaccine for small-scale trials, and shifted it to a second manufacturer, Fujifilm, which is making the vaccine at plants in North Carolina and Texas.
The Novavax project was taken out of the Emergent facility to make way for manufacturing for Johnson & Johnson’s experimental vaccine, said Gregory Glenn, Novavax’s president of research and development. Slaoui also wanted Novavax to prove it could produce commercial-scale batches of 2,000 liters at a time in FujiFilm’s facilities, before it launched its Phase 3 trial, Glenn said.
The reason behind the switch and details about the delays have not been previously reported.
The changes pushed the pivotal trial so long into the competition among drug companies that the ability to recruit subjects is disappearing, Glenn said.
“The window is closing on the ability to conduct a randomized trial,” he said.
Asked to respond, Operation Warp Speed did not directly address the Novavax issues.
Novavax said it had 9,000 subjects as of last week toward its goal of 30,000 and intended to persevere. If it does not recruit enough people over 65 in the United States, it will ask the Food and Drug Administration to consider data from that age group from a smaller trial in the United Kingdom that is fully enrolled, Glenn said. Data from those trials is expected soon.
“If there is some reason we can’t complete the trial, we do have a large, 15,000-person placebo controlled trial from the U.K., and there is every reason to think the FDA would accept that,” Glenn said. He said 27% of the people in that trial were over 65 years old.
The FDA is hopeful there will still be a few months left to push through trials with full participation, but it is willing to look at foreign trial data, said a senior agency official who spoke on the condition of anonymity to discuss internal deliberations.
“We have no problem with accepting data from foreign trials, provided they are conducted under good clinical practices,” the official said. “We’re in a place here where we’re going to do our best with the data we have because we are in the middle of a pandemic.
“We’re not going to cut corners, but we’re not going to stand on ceremony. . . . It’s not like were going to sit there and make rules to make it difficult to use foreign data.”
Specialists in clinical trials said the case of Novavax highlights the dilemma in trying to develop a roster of multiple vaccines simultaneously to battle a global pandemic. In the United States and the world, multiple vaccines will need to be deployed to reach the immunization levels needed to reach herd immunity, which is estimated to be upward of 70% of the population.
The first two vaccines to win emergency authorization from the FDA, Pfizer and Moderna, were made with novel mRNA technology that allowed the shots to be engineered extremely rapidly. Their rapid development, testing and authorization in December make it difficult to recruit and complete trials by competitors later in the pipeline, according to experts in clinical trials.
“The future of large-scale trials [for coronavirus vaccines] is in doubt,” said Arthur Caplan, a medical ethicist and clinical trial specialist at the New York University Langone medical center. “The more vaccines appear with either emergency approval, expanded criteria or plain licensing, there’s no way that people are going to sign up for trials with placebo controls.”
Alternatives to placebo-controlled trials are “non-inferiority” trials, or comparative trials that pit an investigational vaccine or drug up against an existing product. With the high degree of efficacy of the Moderna and Pfizer vaccines, it could be difficult to prove other vaccines are equal or better at immunizing against the coronavirus. But because Moderna and Pfizer require ultracold handling, and there is such a shortage of vaccines generally, there is intense demand for a competing vaccine that can be more easily distributed.
“Given that we need more vaccines on the market, the number of doses and storage requirements all matter. It may not just be about efficacy, it may be about those things,” said Walid Gellad, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.
The FDA official said a number of factors would have to be considered in non-inferiority trials.
“Obviously to do a non-inferiority trial with a vaccine that has 95% efficacy is very challenging and it really will depend on the specific vaccine,” the official said. Mitigating factors for a vaccine that is less effective could be a one-shot regimen, fewer side effects or easier shipping and handling, the official said.
Caplan said the problems with recruitment are bound to increase attention on the potential of “challenge trials,” in which subjects are given a vaccine then intentionally exposed to virus to see if the vaccines work.
Challenge trials are the subject of ethical controversy and would also be unlikely to be tried in elderly patients who are most at risk of developing severe disease or dying from covid.
Sanofi, which partnered with GlaxoSmithKline to develop a vaccine, also experienced significant setbacks in early stage clinical trials. It has opted to compare its vaccine candidate with another previously authorized vaccine (which has not been disclosed) in a mid-stage trial in February as well as a subsequent large Phase 3 trial in the second quarter.
Investigators are required to permit subjects to exit clinical trials once proven vaccines hit the market.
Johnson & Johnson said it had fully enrolled its Phase 3 placebo-controlled trial in December. It would not comment for this story.
AstraZeneca said it is nearing complete enrollment of its U.S. trial.
“Regarding unblinding, as vaccines receive emergency use authorization or approval, and participants in the AZD1222 trial are eligible to receive them, we have provided guidance to site investigators and trial participants so they can discuss the options that are available to them,” AstraZeneca spokesman Brendan McEvoy said in an email.
While Johnson & Johnson and AstraZeneca wrapped up enrollment of their placebo-controlled trials, and Sanofi’s delays are so severe it opted for its non-inferiority trial, Novavax appears to have been caught in the middle – with a placebo-controlled trial that risks falling short.
What Novavax really needs is more test subjects like Maureen Reininger, 65, a retired New York transit system supervisor and analyst who lives in the Long Island suburb of South Hempstead. Reininger was in charge of recovering cash and MetroCards from the booths in subway stations beneath Lower Manhattan after the 9/11 terrorist attacks, and she breathed toxic dust that she said has contributed to chronic sinus problems.
Yet despite New York’s moves last week that made her eligible for the proven vaccines, she said she wants to continue in the Novavax trial, not knowing if she received the vaccine candidate or the placebo. The reason she joined the trial in the first place was altruism, and a sense of contributing to the quest for vaccines, rather than her own possible early access to a shot, she said.
“I just wanted to be of assistance, to be helpful to our fellow humans,” she said. Reininger added that she is still taking precautions that will protect her if she received the placebo.
“I’m basically not going anywhere outside of my home, and when I do go out, when I go to the supermarket, and I’m in and out, and the mask is on, and I wear gloves,” she said. “When I do go into areas where there are other people, I physically will remove myself, even when I have my mask.”
Reininger acknowledged one factor that makes her different from other many people over 65 who want faster access to a vaccine: She does not have grandchildren.
The highly contagious variant of the coronavirus first seen in the United Kingdom will become the dominant strain in the United States within about two months, its rapid spread heightening the urgency of getting people vaccinated, the Centers for Disease Control and Prevention predicted Friday in its most sobering warning yet about mutations in the virus.
In every scenario explored by the CDC, the U.K. strain, which British researchers estimate is roughly 50% more transmissible than the more common coronavirus strain, will account for a majority of cases in the United States by some point in March.
The CDC released modeling data to back up its forecast showing a rapid spike in infections linked to the U.K. strain. The agency said the emergence of these mutation-laden variants requires greater efforts to limit viral spread – immediately, even before the U.K. variant becomes commonplace.
So far, no variant is known to cause more severe illness, although more infections would inevitably mean a higher death toll overall, as the CDC made clear in an informational graphic released Friday: “MORE SPREAD – MORE CASES – MORE DEATHS,” it said.
The CDC report “speaks to the urgency of getting vaccines out. It’s now a race against the virus,” said William Hanage, an epidemiologist at the Harvard T.H. Chan School of Public Health.
Scientists both in and out of government have stressed the need for the public to stick to proven methods of limiting viral spread, such as wearing a mask, social distancing, avoiding crowds and having good hand hygiene.
“We know what works and what to do,” Jay Butler, the CDC deputy director for infectious diseases, said Friday.
The emergence of highly contagious variants has grabbed the full attention of scientists, who in recent weeks have warned that these mutations require closer surveillance. The CDC and its partners in private and academic laboratories are ramping up genomic sequencing efforts to gain better awareness of what is already circulating. Experts think there could be many variants containing mutations worth a closer look.
“This is a situation of concern. We are increasing our surveillance of emerging variants. This virus sometimes surprises us,” Butler said.
Mutations could limit the efficacy of vaccines or therapeutic drugs such as monoclonal antibodies. Scientists believe vaccines will probably remain effective because they produce a robust immune system response, but such reassurances have been paired with cautionary notes about how much remains unknown.
The coronavirus mutations are not unexpected, because all viruses mutate. There are now several “variants of concern” receiving scrutiny, including ones identified first in South Africa and Brazil, and U.S. officials have said genomic surveillance is still ramping up here and that there may be other variants in circulation, not yet identified, that are enhancing transmission.
“We’re going forward with the assumption that these three variants that we know about now are not going to be the only variants that emerge that are of concern to us,” Greg Armstrong, head of the CDC’s strain surveillance program, said Friday.
The CDC model suggests that the level of pain and suffering in late March, when the new variant is forecast to be dominant, depends on actions taken today to try to drive down infection rates.
The emergence in recent weeks of mutation-laden variants has alarmed the CDC and the scientific community. Because the threshold for herd immunity depends in part on how infectious a virus is, the emergence of a more transmissible strain can prolong efforts to crush a pandemic.
There has been particular scientific focus on the United Kingdom variant, known as B.1.1.7, which has been spreading with stunning speed in Britain, Denmark and Ireland and has been identified in dozens of countries. The United Kingdom conducts extensive genomic sequencing, and first detected the variant, which has 17 mutations, in September. But it was not flagged as a “variant of concern” until December, when it began circulating at explosive rates and quickly became dominant among the coronavirus infections in southern England.
Scientists say B.1.1.7 has mutations in the “receptor binding domain” of the virus, and this may be enhancing the ability of the virus to bind with cells in the human body. There is evidence it leads to higher viral loads, which in turn could boost the amount of virus that a person is shedding, or prolong the period in which someone can transmit the virus.
None of these mutations appears to change the basic mechanics of infection, and people should stick with common-sense measures to limit viral spread, said James Cutrell, an infectious-diseases physician at the University of Texas Southwestern Medical Center in Dallas.
“The same things that worked to protect you from this virus are going to work for these new variants as well,” Cutrell said.
The CDC did not call for new government restrictions to crush the pandemic but emphasized the need to drive down infection rates.
“Increased SARS-CoV-2 transmission might threaten strained healthcare resources, require extended and more rigorous implementation of public health strategies, and increase the percentage of population immunity required for pandemic control,” the CDC wrote. “Taking measures to reduce transmission now can lessen the potential impact of B.1.1.7 and allow critical time to increase vaccination coverage.”
It is unclear if the winter surge in the United States is at a peak, but the numbers are staggering, with more than 200,000 new infections confirmed every day on average.
This is not the first warning from the CDC about variants of the virus, but it is the first to offer a plausible timeline for when and to what degree the mutations seen recently could complicate efforts to end the pandemic.
It shows that vaccination, performed rapidly, is critical to crushing the curve of viral infections. Without vaccines, under one CDC scenario, the country could be dealing with even greater levels of infections in May than in January.
But if public health agencies can ramp up to 1 million vaccinations a day, the CDC model forecasts that daily new infections will decline in the next few months – even with the extra boost from the highly contagious U.K. variant. It has been identified in 12 states, the CDC said Friday, and the agency has informed officials nationwide that they should assume the variant is present in their state.
The CDC and unaffiliated scientists have said they see no evidence that this particular variant is driving the winter surge in cases. So far, it has been involved in fewer than 0.5% of infections nationwide, testing data suggests.
Friday’s sobering CDC forecast is based on simple models and has limitations, the agency acknowledged.
The model looks at just the B.1.1.7 variant and does not consider the impact of other variants already discovered or not yet identified. The variants in South Africa and Brazil could prove to be even more problematic, though they have not been spotted so far in the United States. Researchers have noted the disastrous spike in cases in Manaus, Brazil, in recent weeks, despite the high percentage of the population believed to have been previously infected – a situation that raises suspicions, not confirmed by data, that some people who had recovered are becoming reinfected by the new strain.
The CDC model treats the United States as a single unit even though the virus is spreading at different rates locally and regionally. No one knows, even at the national level, the current “R,” the reproduction number, of the common coronavirus variant. That’s the number of people an infected person will infect, on average.
The CDC model used plausible reproduction rates of 1.1 (faster spread right now) and 0.9 (slower). The CDC then used British data to project that the U.K. variant is 50 percent more transmissible than the common variant. The model assumes that between 10 and 30% of the population has been infected already and recovered and now has immunity.
“It would be foolish to say that this is never going to end, and we might as well stop trying,” the CDC’s Butler said. “But there is reason to be concerned. We’re not out of the woods on this pandemic yet. We need to continue to press ahead.”
The coffee market in Thailand has been expanding significantly, with new cafes popping up in every city.
A report from Nestle (Thai) shows that the coffee market in the Kingdom has risen by 10.7 per cent or by Bt60 billion in 2020 alone, despite the Covid-19 outbreak.
Coffee is grown in several parts of the country, with Chumphon province being the largest producer. According to Spring News, Chumphon has devoted 104,326 rai to the bean and produces as much as 11,537 tonnes of Robusta per year.
After Chumphon, the other biggest producer of coffee is Ranong, where 44,080 rai has been devoted to the crop and 4,667 tonnes is produced on a yearly basis.
Other provinces where coffee is grown are Chiang Rai, Chiang Mai and Nan in the North, where 42,215 rai, 23,125 rai and 22,500 rai has been devoted to the crop, producing 3,402, 2,283 and 3,825 tonnes per year, respectively.
Coffee plantations in the North grow the Arabica variety of coffee.