How Will the New Strains of COVID-19 Affect Our Vaccination Plans?
When the world's first Covid-19 vaccine received regulatory approval in November, it appeared that the end of the pandemic might be near. As one by one, the Pfizer/BioNTech, Moderna, AstraZeneca, and Sputnik V vaccines reported successful Phase III results, the prospect of life without lockdowns and restrictions seemed a tantalizing possibility.
But for scientists with many years' worth of experience in studying how viruses adapt over time, it remained clear that the fight against the SARS-CoV-2 virus was far from over. "The more virus circulates, the more it is likely that mutations occur," said Professor Beate Kampmann, director of the Vaccine Centre at the London School of Hygiene & Tropical Medicine. "It is inevitable that new variants will emerge."
Since the start of the pandemic, dozens of new variants of SARS-CoV-2 – containing different mutations in the viral genome sequence - have appeared as it copies itself while spreading through the human population. The majority of these mutations are inconsequential, but in recent months, some mutations have emerged in the receptor binding domain of the virus's spike protein, increasing how tightly it binds to human cells. These mutations appear to make some new strains up to 70 percent more transmissible, though estimates vary and more lab experiments are needed. Such new strains include the B.1.1.7 variant - currently the dominant strain in the UK – and the 501Y.V2 variant, which was first found in South Africa.
"I'm quite optimistic that even with these mutations, immunity is not going to suddenly fail on us."
Because so many more people are becoming infected with the SARS-CoV-2 virus as a result, vaccinologists point out that these new strains will prolong the pandemic.
"It may take longer to reach vaccine-induced herd immunity," says Deborah Fuller, professor of microbiology at the University of Washington School of Medicine. "With a more transmissible variant taking over, an even larger percentage of the population will need to get vaccinated before we can shut this pandemic down."
That is, of course, as long as the vaccinations are still highly protective. The South African variant, in particular, contains a mutation called E484K that is raising alarms among scientists. Emerging evidence indicates that this mutation allows the virus to escape from some people's immune responses, and thus could potentially weaken the effectiveness of current vaccines.
What We Know So Far
Over the past few weeks, manufacturers of the approved Covid-19 vaccines have been racing to conduct experiments, assessing whether their jabs still work well against the new variants. This process involves taking blood samples from people who have already been vaccinated and assessing whether the antibodies generated by those people can neutralize the new strains in a test tube.
Pfizer has just released results from the first of these studies, declaring that their vaccine was found to still be effective at neutralizing strains of the virus containing the N501Y mutation of the spike protein, one of the mutations present within both the UK and South African variants.
However, the study did not look at the full set of mutations contained within either of these variants. Earlier this week, academics at the Fred Hutchinson Cancer Research Center in Seattle suggested that the E484K spike protein mutation could be most problematic, publishing a study which showed that the efficacy of neutralizing antibodies against this region dropped by more than ten-fold because of the mutation.
Thankfully, this development is not expected to make vaccines useless. One of the Fred Hutch researchers, Jesse Bloom, told STAT News that he did not expect this mutation to seriously reduce vaccine efficacy, and that more harmful mutations would need to accrue over time to pose a very significant threat to vaccinations.
"I'm quite optimistic that even with these mutations, immunity is not going to suddenly fail on us," Bloom told STAT. "It might be gradually eroded, but it's not going to fail on us, at least in the short term."
While further vaccine efficacy data will emerge in the coming weeks, other vaccinologists are keen to stress this same point: At most, there will be a marginal drop in efficacy against the new variants.
"Each vaccine induces what we call polyclonal antibodies targeting multiple parts of the spike protein," said Fuller. "So if one antibody target mutates, there are other antibody targets on the spike protein that could still neutralize the virus. The vaccine platforms also induce T-cell responses that could provide a second line of defense. If some virus gets past antibodies, T-cell responses can find and eliminate infected cells before the virus does too much damage."
She estimates that if vaccine efficacy decreases, for example from 95% to 85%, against one of the new variants, the main implications will be that some individuals who might otherwise have become severely ill, may still experience mild or moderate symptoms from an infection -- but crucially, they will not end up in intensive care.
"Plug and Play" Vaccine Platforms
One of the advantages of the technologies which have been pioneered to create the Covid-19 vaccines is that they are relatively straightforward to update with a new viral sequence. The mRNA technology used in the Pfizer/BioNTech and Moderna vaccines, and the adenovirus vectors used in the Astra Zeneca and Sputnik V vaccines, are known as 'plug and play' platforms, meaning that a new form of the vaccine can be rapidly generated against any emerging variant.
"With a rapid pipeline for manufacture established, these new vaccine technologies could enable production and distribution within 1-3 months of a new variant emerging."
While the technology for the seasonal influenza vaccines is relatively inefficient, requiring scientists to grow and cultivate the new strain in the lab before vaccines can be produced - a process that takes nine months - mRNA and adenovirus-based vaccines can be updated within a matter of weeks. According to BioNTech CEO Uğur Şahin, a new version of their vaccine could be produced in six weeks.
"With a rapid pipeline for manufacture established, these new vaccine technologies could enable production and distribution within 1-3 months of a new variant emerging," says Fuller.
Fuller predicts that more new variants of the virus are almost certain to emerge within the coming months and years, potentially requiring the public to receive booster shots. This means there is one key advantage the mRNA-based vaccines have over the adenovirus technologies. mRNA vaccines only express the spike protein, while the AstraZeneca and Sputnik V vaccines use adenoviruses - common viruses most of us are exposed to - as a delivery mechanism for genes from the SARS-CoV-2 virus.
"For the adenovirus vaccines, our bodies make immune responses against both SARS-CoV-2 and the adenovirus backbone of the vaccine," says Fuller. "That means if you update the adenovirus-based vaccine with the new variant and then try to boost people, they may respond less well to the new vaccine, because they already have antibodies against the adenovirus that could block the vaccine from working. This makes mRNA vaccines more amenable to repeated use."
Regulatory Unknowns
One of the key questions remains whether regulators would require new versions of the vaccine to go through clinical trials, a hurdle which would slow down the response to emerging strains, or whether the seasonal influenza paradigm will be followed, whereby a new form of the vaccine can be released without further clinical testing.
Regulators are currently remaining tight-lipped on which process they will choose to follow, until there is more information on how vaccines respond against the new variants. "Only when such information becomes available can we start the scientific evaluation of what data would be needed to support such a change and assess what regulatory procedure would be required for that," said Rebecca Harding, communications officer for the European Medicines Agency.
The Food and Drug Administration (FDA) did not respond to requests for comment before press time.
While vaccinologists feel it is unlikely that a new complete Phase III trial would be required, some believe that because these are new technologies, regulators may well demand further safety data before approving an updated version of the vaccine.
"I would hope if we ever have to update the current vaccines, regulatory authorities will treat it like influenza," said Drew Weissman, professor of medicine at the University of Pennsylvania, who was involved in developing the mRNA technology behind the Pfizer/BioNTech and Moderna vaccines. "I would guess, at worst, they may want a new Phase 1 or 1 and 2 clinical trials."
Others suggest that rather than new trials, some bridging experiments may suffice to demonstrate that the levels of neutralizing antibodies induced by the new form of the vaccine are comparable to the previous one. "Vaccines have previously been licensed by this kind of immunogenicity data only, for example meningitis vaccines," said Kampmann.
While further mutations and strains of SARS-CoV-2 are inevitable, some scientists are concerned that the vaccine rollout strategy being employed in some countries -- of distributing a first shot to as many people as possible, and potentially delaying second shots as a result -- could encourage more new variants to emerge. Just today, the Biden administration announced its intention to release nearly all vaccine doses on hand right away, without keeping a reserve for second shots. This plan risks relying on vaccine manufacturing to ramp up quickly to keep pace if people are to receive their second shots at the right intervals.
"I am not very happy about this change as it could lead to a large number of people out there with partial immunity and this could select new mutations, and escalate the potential problem of vaccine escape."
The Biden administration's shift appears to conflict with the FDA's recent position that second doses should be given on a strict schedule, without any departure from the three- and four-week intervals established in clinical trials. Two top FDA officials said in a statement that changing the dosing schedule "is premature and not rooted solidly in the available evidence. Without appropriate data supporting such changes in vaccine administration, we run a significant risk of placing public health at risk, undermining the historic vaccination efforts to protect the population from COVID-19."
"I understand the argument of trying to get at least partial protection to as many people as possible, but I am concerned about the increased interval between the doses that is now being proposed," said Kampmann. "I am not very happy about this change as it could lead to a large number of people out there with partial immunity and this could select new mutations, and escalate the potential problem of vaccine escape."
But it's worth emphasizing that the virus is unlikely for now to accumulate enough harmful mutations to render the current vaccines completely ineffective.
"It will be very hard for the virus to evolve to completely evade the antibody responses the vaccines induce," said Fuller. "The parts of the virus that are targeted by vaccine-induced antibodies are essential for the virus to infect our cells. If the virus tries to mutate these parts to evade antibodies, then it could compromise its own fitness or even abort its ability to infect. To be sure, the virus is developing these mutations, but we just don't see these variants emerge because they die out."
New study: Hotter nights, climate change, cause sleep loss with some affected more than others
Data from the National Sleep Foundation finds that the optimal bedroom temperature for sleep is around 65 degrees Fahrenheit. But we may be getting fewer hours of "good sleepin’ weather" as the climate warms, according to a recent paper from researchers at the University of Copenhagen, Denmark.
Published in One Earth, the study finds that heat related to climate change could provide a “pathway” to sleep deprivation. The authors say the effect is “substantially larger” for those in lower-income countries. Hours of sleep decline when nighttime temperature exceeds 50 degrees, and temps higher than 77 reduce the chances of sleeping for seven hours by 3.5 percent. Even small losses associated with rising temperatures contribute significantly to people not getting enough sleep.
We’re affected by high temperatures at night because body temperature becomes more sensitive to the environment when slumbering. “Mechanisms that control for thermal regulation become more disordered during sleep,” explains Clete Kushida, a neurologist, professor of psychiatry at Stanford University and sleep medicine clinician.
The study finds that women and older adults are especially vulnerable. Worldwide, the elderly lost over twice as much sleep per degree of warming compared to younger people. This phenomenon was apparent between the ages of 60 and 70, and it increased beyond age 70. “The mechanism for balancing temperatures appears to be more affected with age,” Kushida adds.
Others disproportionately affected include those who live in regions with more greenhouse gas (GHG) emissions, which accelerate climate change, and people in hotter locales will lose more sleep per degree of warming, according to the study, with suboptimal temperatures potentially eroding 50 to 58 hours of sleep per person per year. One might think that those in warmer countries can adapt to the heat, but the researchers found no evidence for such adjustments. “We actually found those living in the warmest climate regions were impacted over twice as much as those in the coldest climate regions,” says the study's lead author, Kelton Minor, a Ph.D. candidate at the University of Copenhagen’s Center for Social Data Science.
Short sleep can reduce cognitive performance and productivity, increase absenteeism from work or school, and lead to a host of other physical and psychosocial problems. These issues include a compromised immune system, hypertension, depression, anger and suicide, say the study’s authors. According to a fact sheet by the U.S. Centers for Disease Control and Prevention, a third of U.S. adults already report sleeping fewer hours than the recommended amount, even though sufficient sleep “is not a luxury—it is something people need for good health.”
Equitable policy and planning are needed to ensure equal access to cooling technologies in a warming world.
Beyond global health, a sleep-deprived world will impact the economy as the climate warms. “Less productivity at work, associated with sleep loss or deprivation, would result in more sick days on a global scale, not just in individual countries,” Kushida says.
Unlike previous research that measured sleep patterns with self-reported surveys and controlled lab experiments, the study in One Earth offers a global analysis that relies on sleep-tracking wristbands that link more than seven million sleep records of 47,628 adults across 68 countries to local and daily meteorological data, offering new insight into the environmental impact on human sleep. Controlling for individual, seasonal and time-varying confounds, researchers found the main way that higher temperatures shorten slumber is by delaying sleep onset.
Heat effects on sleep were seen in industrialized countries including those with access to air conditioning, notes the study. Air conditioning may buffer high indoor temperatures, but they also increase GHG emissions and ambient heat displacement, thereby exacerbating the unequal burdens of global and local warming. Continued urbanization is expected to contribute to these problems.
Previous sleep studies have found an inverse U-shaped response to temperature in highly controlled settings, with subjects sleeping worse when room temperatures were either too cold or too warm. However, “people appear far better at adapting to colder outside temperatures than hotter conditions,” says Minor.
Although there are ways of countering the heat effect, some populations have more access to them. “Air conditioning can help with the effect of higher temperature, but not all individuals can afford air conditioners,” says Kushida. He points out that this could drive even greater inequity between higher- and lower-income countries.
Equitable policy and planning are needed to ensure equal access to cooling technologies in a warming world. “Clean and renewable energy systems and interventions will be needed to mitigate and adapt to ongoing climate warming,” Minor says. Future research should investigate “policy, planning and design innovation,” which could reduce the impact of sweltering temperatures on a good night’s sleep for the good of individuals, society and our planet, asserts the study.
Unabated and on its current trajectory, by 2099 suboptimal temperatures could shave 50 to 58 hours of sleep per person per year, predict the study authors. “Down the road, as technology develops, there might be ways of enabling people to adapt on a large scale to these higher temperatures,” says Kushida. “Right now, it’s not there.”
Why we need to get serious about ending aging
It is widely acknowledged that even a small advance in anti-aging science could yield benefits in terms of healthy years that the traditional paradigm of targeting specific diseases is not likely to produce. A more youthful population would also be less vulnerable to epidemics. Approximately 93 percent of all COVID-19 deaths reported in the U.S. occurred among those aged 50 or older. The potential economic benefits would be tremendous. A more youthful population would consume less medical resources and be able to work longer. A recent study published in Nature estimates that a slowdown in aging that increases life expectancy by one year would save $38 trillion per year for the U.S. alone.
A societal effort to understand, slow down, arrest or even reverse aging of at least the size of our response to COVID-19 would therefore be a rational commitment. In fact, given that America’s older population is projected to grow dramatically, and the cost of healthcare with it, it is not an overstatement to say that the future welfare of the country may depend on solving aging.
This year, the kingdom of Saudi Arabia has announced that it will spend up to 1 billion dollars per year on science with the potential to slow down the aging process. We have also seen important investments from billionaires like Google co-founder Larry Page, Amazon founder Jeff Bezos, business magnate Larry Ellison, and PayPal co-founder Peter Thiel.
The U.S. government, however, is lagging: The National Institutes of Health spent less than one percent of its $43 billion budget for the fiscal year of 2021 on the National Institute on Aging’s Division of Aging Biology. When you visit the division’s webpage you find that their mission statement carefully omits any mention of the possibility of slowing down the aging process.
There is a lack of political will and leadership on the issue, and the idea that we should seek to do something about aging is generally met with a great deal of suspicion and trepidation. In a large representative study conducted by the Pew Research Center in 2013, only 38% of the respondents said that they would want a treatment that could slow the aging process and allow them to live at least 120 years. Apparently, most people prefer, or at least do not mind, to age and die within a natural lifespan. This result has been confirmed by smaller studies and it is, I think, surprising. Are we not supposed to live in a youth-culture? Are people not supposed to want to stay young and alive forever? Is self-preservation not the strong drive we have always assumed it to be?
We are inundated and saturated with an ideology of death-acceptance.
In my book, The Case against Death, I suggest that we have been culturally conditioned to think that it is virtuous to accept aging and death. We are taught to believe that although aging and death seem gruesome, they are what is best for us, all things considered. This is what we are supposed to think, and the majority accept it. I call this the Wise View because death acceptance has been the dominant view of philosophers since the beginning. Socrates compared our earthly life to an illness and a prison and described death as a healer and a liberator. The Buddha taught that life is suffering and that the way to escape suffering is to end the cycle of birth, death and rebirth. Stoic philosophers from Zeno to Marcus Aurelius believed that everything that happens in accordance with nature is good, and that therefore we should not only accept death but welcome it as an aspect of a perfect totality.
Epicureans agreed with these rival schools and famously argued that death cannot harm us because where we are, death is not, and where death is we are not. We cannot be harmed if we are not, so death is harmless. The simple view that death actually can harm us greatly is one of the least philosophical views one can hold.
In The Case Against Death, philosopher Ingemar Patrick Linden argues that we frown on using science to prolong healthy life only because we're culturally conditioned to think that way.
Many of the stories we tell promote the Wise View. One of the earliest known pieces of literature, the Epic of Gilgamesh, follows Gilgamesh on a quest for eternal life ending with the wisdom that death is the destiny of man. Today we learn about the tedium of immortality from the children’s book Tuck Everlasting by Natalie Babbitt, and we are warned about the vice of wanting to resist death in other books and films such as J.K Rowling’s Harry Potter, where Voldemort must kill Harry as a step towards his own immortality; C.S. Lewis’ The Chronicles of Narnia where the White Witch has gained immortal youth and madness in equal measures; J.R.R. Tolkien’s Lord of the Rings trilogy where the ring extends the wearer’s life but can also destroy them, as exemplified by the creep Gollum; and Doctor Strange where life extension is the one magical power that is taboo. In Star Wars, Yoda, a stereotype of the sage, teaches us the wisdom handed down by philosophers and prophets: “Death is a natural part of life. Rejoice for those around you who transform into the Force. Mourn them do not. Miss them do not.”
We are inundated and saturated with an ideology of death-acceptance. Can the dear reader name one single story where the hero is pursuing anti-aging, longevity or immortality and the villain tries to stop her?
The Wise View resonates with us partly because we think that there is nothing we can do about aging and death, so we do not want to wish for what we cannot have. Youth and immortality are sour grapes to us. Believing that death is, all things considered, not such a bad thing, protects us from experiencing our aging and approaching death as a gruesome tragedy. This need to escape the thought that we are heading towards a personal catastrophe explains why many are so quick to accept arguments against radical life extension, despite their often glaring weaknesses.
One of the most common objections to radical life extension is that aging and death are natural. The problem with this argument is that many things that are natural are very bad, such as cancer, and other things that are not natural are very good, such as a cure for cancer. Why are we so sure that cancer is bad? Because we assume that it is bad to die. Indeed, nothing is more natural than wanting to live. We seem to need philosophers and story tellers to talk us out of it and, in the words of a distinguished bioethicist, “instruct and somewhat moderate our lust for life.”
Another standard objection is that we need a deadline, and that without death we could postpone every action forever. “Death brings urgency and seriousness to life,” say proponents of this view, but there are several problems with this argument. Even if our lives were endless, there would still be many things we would have to do at a certain time, and that could not be redone, for example, saving our planet from being destroyed, or becoming the first person on Venus. And if we prefer pleasant endless lives over unpleasant endless ones, we will have to exercise, eat right, keep our word, develop our talents, show up for time at work, pay our taxes by the due date, remember birthdays, and so on.
The Wise View provides us with a feel-good bromide for the anxiety created by the foreknowledge of our decay and death by telling us that these are not evils, but blessings in disguise. Once perhaps an innocuous delusion, today the view stands in the way of a necessary societal commitment to research that can prolong our healthy life.
Besides, even if we succeeded in ending aging, we would still die from other causes. Given the rate of accidental deaths we would be fortunate to live to age 2000 all things equal. So even if, contrary to what I have argued, we do need a deadline, we can still argue that the natural lifespan that we now labor under is inhuman and that it forces each human to limit her ambitions and to become only a fragment of all that she that could have been. Our tight time constraint imposes tragic choices and inflated opportunity costs. Death does not make life matter; it makes time matter.
The perhaps most awful argument against radical life extension is grounded in a pessimism that holds life in such little regard that it says that best of all is never to have born. This view was expressed by Ecclesiastes in the Hebrew Bible, by Sophocles and several other ancient Greeks, by the German philosopher Arthur Schopenhauer, and recently by, among others, the South African philosopher David Benatar who argues that it is wrong to bring children into the world and that we should euthanize all sentient life. Pessimism, one suspects, largely appeals to some for reasons having to do with personal temperament, but insofar as it is built on factual beliefs, they can be addressed by providing a less negatively biased understanding of the world, by pointing out that curing aging would decrease the badness that they are so hypersensitive to, and by reminding them that if life really becomes unbearable, they are free to quit at any time. Other means of persuasion could include recommending sleep, exercise and taking long brisk walks in nature.
The Wise View provides us with a feel-good bromide for the anxiety created by the foreknowledge of our decay and death by telling us that these are not evils, but blessings in disguise. Once perhaps an innocuous delusion, today the view stands in the way of a necessary societal commitment to research that can prolong our healthy life. We need abandon it and openly admit that aging is a scourge that deserves to be fought with the combined energies equaling those expended on fighting COVID-19, Alzheimer’s disease, cancer, stroke and all the other illnesses for which aging is the greatest risk factor. The fight to end aging transcends ordinary political boundaries and is therefore the kind of grand unifying enterprise that could re-energize a society suffering from divisiveness and the sense of a lack of a common purpose. It is hard to imagine a more worthwhile cause.