A health care worker places a bandaid on the arm of a man who has just been vaccinated.
Since the Delta variant became predominant in the United States on July 7, both scientists and the media alike have been full of mixed messages ("breakthrough infections rare"; "breakthrough infections common"; "vaccines still work"; "vaccines losing their effectiveness") but – if we remember our infectious diseases history- one thing remains clear: immunity is the only way to get through a pandemic.
What Happened in the Past
The 1918 influenza pandemic was far the deadliest respiratory virus pandemic recorded in recent human history with over 50 million deaths (maybe even 100 million deaths, or 3% of the world's population) worldwide. Although they used some of the same measures we are using now (masks, distancing, event closures, as neither testing nor a vaccine existed back then), the deaths slowed only after enough of the population had either acquired immunity through natural infection or died. Indeed, the first influenza vaccine was not developed until 1942, more than 20 years later. As judged by the amount of suffering and death from 1918 influenza (and the deadly Delta surge in India in spring 2021), natural immunity is obviously a terrible way to get through a pandemic.
Similarly, measles was a highly transmissible respiratory virus that led to high levels of immunity among adults who were invariably exposed as children. However, measles led to deaths each year among the nonimmune until a vaccine was developed in 1963, largely restricting current measles outbreaks in the U.S. now to populations who decline to vaccinate. Smallpox also led to high levels of immunity through natural infection, which was often fatal. That's why unleashing smallpox on a largely nonimmune population in the New World was so deadly. Only an effective vaccine – and its administration worldwide, including among populations who declined smallpox vaccine at first via mandates – could control and then eventually eradicate smallpox from Earth.
Fully vaccinated people are already now able to generate some antibodies against all the variants we know of to date, thanks to their bank of memory B cells.
The Delta variant is extremely transmissible, making it unlikely we will ever eliminate or eradicate SARS-CoV-2. Even Australia, which had tried to maintain a COVID-zero nation with masks, distancing, lockdowns, testing and contact tracing before and during the vaccines, ended a strategy aimed at eliminating COVID-19 this week. But, luckily, since highly effective and safe vaccines were developed for COVID-19 less than a year after its advent on a nonimmune population and since vaccines are retaining their effectiveness against severe disease, we have a safe way out of the misery of this pandemic: more and more immunity. "Defanging" SARS-CoV-2 and stripping it of its ability to cause severe disease through immunity will relegate it to the fate of the other four circulating cold-causing coronaviruses, an inconvenience but not a world-stopper.
Immunity Is More Than Antibodies
When we say immunity, we have to be clear that we are talking about cellular immunity and immune memory, not only antibodies. This is a key point. Neutralizing antibodies, which prevent the virus from entering our cells, are generated by the vaccines. But those antibodies will necessarily wane over time since we cannot keep antibodies from every infection and vaccine we have ever seen in the bloodstream (or our blood would be thick as paste!). Vaccines with shorter intervals between doses (like Pfizer vaccines given 3 weeks apart) are likely to have their antibodies wane sooner than vaccines with longer intervals between doses (like Moderna), making mild symptomatic breakthroughs less likely with the Moderna vaccine than the Pfizer during our Delta surge, as a recent Mayo Clinic study showed.
Luckily, the vaccines generate B cells that get relegated to our memory banks and these memory B cells are able to produce high levels of antibodies to fight the virus if they see it again. Amazingly, these memory B cells will actually produce antibodies adapted against the COVID variants if they see a variant in the future, rather than the original antibodies directed against the ancestral strain. This is because memory B cells serve as a blueprint to make antibodies, like the blueprint of a house. If a house needs an extra column (or antibodies need to evolve to work against variants), the blueprint will oblige just as memory B cells will!
One problem with giving a 3rd dose of our current vaccines is that those antibodies won't be adapted towards the variants. Fully vaccinated people are already now able to generate some antibodies against all the variants we know of to date, thanks to their bank of memory B cells. In other words, no variant has evolved to date that completely evades our vaccines. Memory B cells, once generated by either natural infection or vaccination, should be long-lasting.
If memory B cells are formed by a vaccine, they should be as long-lasting as those from natural infection per various human studies. A 2008 Nature study found that survivors of the 1918 influenza pandemic were able to produce antibodies from memory B cells when exposed to the same influenza strain nine decades later. Of note, mild infections (such as the common cold from the cold-causing coronaviruses called 229E, NL63, OC43, and HKU1) may not reliably produce memory B cell immunity like more severe infections caused by SARS-CoV-2.
Right about now, you may be worrying about a super-variant that might yet emerge to evade all our hard-won immune responses. But most immunologists do not think this is very realistic because of T cells. How are T cells different from B Cells? While B cells are like the memory banks to produce antibodies when needed (helped by T cells), T cells will specifically amplify in response to a piece of the virus and help recruit cells to attack the pathogen directly. We likely have T cells to thank for the vaccine's incredible durability in protecting us against severe disease. Data from La Jolla Immunology Institute and UCSF show that the T cell response from the Pfizer vaccine is strong across all the variants.
Think of your spike protein as being comprised of 100 houses with a T cell there to cover each house (to protect you against severe disease). The variants have around 13 mutations along the spike protein so 13 of those T cells won't work, but there are over 80 T cells remaining to protect your "houses" or your body against severe disease.
Although these are theoretical numbers and we don't know exactly the number of T cell antigens (or "epitopes") across the spike protein, one review showed 1400 across the whole virus, with many of those in the spike protein. Another study showed that there were 87 epitopes across the spike protein to which T cells respond, and mutations in one of the variants (beta) took those down to 75. The virus cannot mutate indefinitely in its spike protein and still retain function. This is why it is unlikely we will get a variant that will evade the in-breadth, robust response of our T cells.
Where We Go From Here
So, what does this mean for getting through this pandemic? Immunity and more immunity. For those of us who are vaccinated, if we get exposed to the Delta variant, it will boost our immune response although the memory B cells might take 3-5 days to make new antibodies, which can leave us susceptible to a mild breakthrough infection. That's part of the reason the CDC put back masks for the vaccinated in late July. For those who are unvaccinated, immunity will be gained from Delta but often through terrible ways like severe disease.
The way for the U.S. to determine the need for 3rd shots among those who are not obviously immunocompromised, given the amazing immune memory generated by the vaccines among immunocompetent individuals, is to analyze the cases of the ~6000 individuals who have had severe breakthrough infections among the 171 million Americans fully vaccinated. Define their co-morbidities and age ranges, and boost those susceptible to severe infections (examples could include older people, those with co-morbidities, health care workers, and residents of long-term care facilities). This is an approach likely to be taken by the CDC's Advisory Committee on Immunization Practices.
If immunity is the only way to get through the pandemic and if variants are caused mostly by large populations being unvaccinated, there is not only a moral and ethical imperative but a practical imperative to vaccinate the world in order to keep us all safe. Immunocompetent Americans can boost their antibodies, which may enhance their ability to avoid mild breakthrough infections, but the initial shots still work well against the most important outcomes: hospitalizations and deaths.
There has been no randomized, controlled trial to assess whether three shots vs. two shots meaningfully improve those outcomes. While we ought to trust immune memory to get the immunocompetent in the United States through, we can hasten the end of this pandemic by providing surplus vaccines to poor countries to combat severe disease. Doing so would not only revitalize the role of the U.S. as a global health leader – it would save countless lives.
The Nose Knows: Dogs Are Being Trained to Detect the Coronavirus
Security workers walk with detection dogs in an airport terminal.
Asher is eccentric and inquisitive. He loves an audience, likes keeping busy, and howls to be let through doors. He is a six-year-old working Cocker Spaniel, who, with five other furry colleagues, has now been trained to sniff body odor samples from humans to detect COVID-19 infections.
As the Delta variant and other new versions of the SARS-CoV-2 virus emerge, public health agencies are once again recommending masking while employers contemplate mandatory vaccination. While PCR tests remain the "gold standard" of COVID-19 tests, they can take hours to flag infections. To accelerate the process, scientists are turning to a new testing tool: sniffer dogs.
At the London School of Hygiene and Tropical Medicine (LSHTM), researchers deployed Asher and five other trained dogs to test sock samples from 200 asymptomatic, infected individuals and 200 healthy individuals. In May, they published the findings of the yearlong study in a preprint, concluding that dogs could identify COVID-19 infections with a high degree of accuracy – they could correctly identify a COVID-positive sample up to 94% of the time and a negative sample up to 92% of the time. The paper has yet to be peer-reviewed.
"Dogs can screen lots of people very quickly – 300 people per dog per hour. This means they could be used in places like airports or public venues like stadiums and maybe even workplaces," says James Logan, who heads the Department of Disease Control at LSHTM, adding that canines can also detect variants of SARS-CoV-2. "We included samples from two variants and the dogs could still detect them."
Detection dogs have been one of the most reliable biosensors for identifying the odor of human disease. According to Gemma Butlin, a spokesperson of Medical Detection Dogs, the UK-based charity that trained canines for the LSHTM study, the olfactory capabilities of dogs have been deployed to detect malaria, Parkinson's disease, different types of cancers, as well as pseudomonas, a type of bacteria known to cause infections in blood, lungs, eyes, and other parts of the human body.
COVID-19 has a distinctive smell — a result of chemicals known as volatile organic compounds released by infected body cells, which give off an odor "fingerprint."
"It's estimated that the percentage of a dog's brain devoted to analyzing odors is 40 times larger than that of a human," says Butlin. "Humans have around 5 million scent receptors dedicated to smell. Dogs have 350 million and can detect odors at parts per trillion. To put this into context, a dog can detect a teaspoon of sugar in a million gallons of water: two Olympic-sized pools full."
According to LSHTM scientists, COVID-19 has a distinctive smell — a result of chemicals known as volatile organic compounds released by infected body cells, which give off an odor "fingerprint." Other studies, too, have revealed that the SARS-CoV-2 virus has a distinct olfactory signature, detectable in the urine, saliva, and sweat of infected individuals. Humans can't smell the disease in these fluids, but dogs can.
"Our research shows that the smell associated with COVID-19 is at least partly due to small and volatile chemicals that are produced by the virus growing in the body or the immune response to the virus or both," said Steve Lindsay, a public health entomologist at Durham University, whose team collaborated with LSHTM for the study. He added, "There is also a further possibility that dogs can actually smell the virus, which is incredible given how small viruses are."
In April this year, researchers from the University of Pennsylvania and collaborators published a similar study in the scientific journal PLOS One, revealing that detection dogs could successfully discriminate between urine samples of infected and uninfected individuals. The accuracy rate of canines in this study was 96%. Similarly, last December, French scientists found that dogs were 76-100% effective at identifying individuals with COVID-19 when presented with sweat samples.
Grandjean Dominique, a professor at France's National Veterinary School of Alfort, who led the French study, said that the researchers used two types of dogs — search and rescue dogs, as they can sniff sweat, and explosive detection dogs, because they're often used at airports to find bomb ingredients. Dogs may very well be as good as PCR tests, said Dominique, but the goal, he added, is not to replace these tests with canines.
In France, the government gave the green light to train hundreds of disease detection dogs and deploy them in airports. "They will act as mass pre-test, and only people who are positive will undergo a PCR test to check their level of infection and the kind of variant," says Dominique. He thinks the dogs will be able to decrease the amount of PCR testing and potentially save money.
Since the accuracy rate for bio-detection dogs is fairly high, scientists think they could prove to be a quick diagnosis and mass screening tool, especially at ports, airports, train stations, stadiums, and public gatherings. Countries like Finland, Thailand, UAE, Italy, Chile, India, Australia, Pakistan, Saudi Arabia, Switzerland, and Mexico are already training and deploying canines for COVID-19 detection. The dogs are trained to sniff the area around a person, and if they find the odor of COVID-19 they will sit or stand back from an individual as a signal that they've identified an infection.
While bio-detection dogs seem promising for cheap, large-volume screening, many of the studies that have been performed to date have been small and in controlled environments. The big question is whether this approach work on people in crowded airports, not just samples of shirts and socks in a lab.
"The next step is 'real world' testing where they [canines] are placed in airports to screen people and see how they perform," says Anna Durbin, professor of international health at the John Hopkins Bloomberg School of Public Health. "Testing in real airports with lots of passengers and competing scents will need to be done."
According to Butlin of Medical Detection Dogs, scalability could be a challenge. However, scientists don't intend to have a dog in every waiting room, detecting COVID-19 or other diseases, she said.
"Dogs are the most reliable bio sensors on the planet and they have proven time and time again that they can detect diseases as accurately, if not more so, than current technological diagnostics," said Butlin. "We are learning from them all the time and what their noses know will one day enable the creation an 'E-nose' that does the same job – imagine a day when your mobile phone can tell you that you are unwell."
What to Know about the Fast-Spreading Delta Variant
A highly contagious form of the coronavirus known as the Delta variant is spreading rapidly and becoming increasingly prevalent around the world. First identified in India in December, Delta has now been identified in 111 countries.
In the United States, the variant now accounts for 83% of sequenced COVID-19 cases, said Rochelle Walensky, director of the Centers for Disease Control and Prevention, at a July 20 Senate hearing. In May, Delta was responsible for just 3% of U.S. cases. The World Health Organization projects that Delta will become the dominant variant globally over the coming months.
So, how worried should you be about the Delta variant? We asked experts some common questions about Delta.
What is a variant?
To understand Delta, it's helpful to first understand what a variant is. When a virus infects a person, it gets into your cells and makes a copy of its genome so it can replicate and spread throughout your body.
In the process of making new copies of itself, the virus can make a mistake in its genetic code. Because viruses are replicating all the time, these mistakes — also called mutations — happen pretty often. A new variant emerges when a virus acquires one or more new mutations and starts spreading within a population.
There are thousands of SARS-CoV-2 variants, but most of them don't substantially change the way the virus behaves. The variants that scientists are most interested in are known as variants of concern. These are versions of the virus with mutations that allow the virus to spread more easily, evade vaccines, or cause more severe disease.
"The vast majority of the mutations that have accumulated in SARS-CoV-2 don't change the biology as far as we're concerned," said Jennifer Surtees, a biochemist at the University of Buffalo who's studying the coronavirus. "But there have been a handful of key mutations and combinations of mutations that have led to what we're now calling variants of concern."
One of those variants of concern is Delta, which is now driving many new COVID-19 infections.
Why is the Delta variant so concerning?
"The reason why the Delta variant is concerning is because it's causing an increase in transmission," said Alba Grifoni, an infectious disease researcher at the La Jolla Institute for Immunology. "The virus is spreading faster and people — particularly those who are not vaccinated yet — are more prone to exposure."
The Delta variant has a few key mutations that make it better at attaching to our cells and evading the neutralizing antibodies in our immune system. These mutations have changed the virus enough to make it more than twice as contagious as the original SARS-CoV-2 virus that emerged in Wuhan and about 50% more contagious than the Alpha variant, previously known as B.1.1.7, or the U.K. variant.
These mutations were previously seen in other variants on their own, but it's their combination that makes Delta so much more infectious.
Do vaccines work against the Delta variant?
The good news is, the COVID-19 vaccines made by AstraZeneca, Johnson & Johnson, Moderna, and Pfizer still work against the Delta variant. They remain more than 90% effective at preventing hospitalizations and death due to Delta. While they're slightly less protective against disease symptoms, they're still very effective at preventing severe illness caused by the Delta variant.
"They're not as good as they were against the prior strains, but they're holding up pretty well," said Eric Topol, a physician and director of the Scripps Translational Research Institute, during a July 19 briefing for journalists.
Because Delta is better at evading our immune systems, it's likely causing more breakthrough infections — COVID-19 cases in people who are vaccinated. However, breakthrough infections were expected before the Delta variant became widespread. No vaccine is 100% effective, so breakthrough infections can happen with other vaccines as well. Experts say the COVID-19 vaccines are still working as expected, even if breakthrough infections occur. The majority of these infections are asymptomatic or cause only mild symptoms.
Should vaccinated people worry about the Delta variant?
Vaccines train our immune systems to protect us against infection. They do this by spurring the production of antibodies, which stick around in our bodies to help fight off a particular pathogen in case we ever come into contact with it.
But even if the new Delta variant slips past our neutralizing antibodies, there's another component of our immune system that can help overtake the virus: T cells. Studies are showing that the COVID-19 vaccines also galvanize T cells, which help limit disease severity in people who have been vaccinated.
"While antibodies block the virus and prevent the virus from infecting cells, T cells are able to attack cells that have already been infected," Grifoni said. In other words, T cells can prevent the infection from spreading to more places in the body. A study published July 1 by Grifoni and her colleagues found that T cells were still able to recognize mutated forms of the virus — further evidence that our current vaccines are effective against Delta.
Can fully vaccinated people spread the Delta variant?
Previously, scientists believed it was unlikely for fully vaccinated individuals with asymptomatic infections to spread Covid-19. But the Delta variant causes the virus to make so many more copies of itself inside the body, and high viral loads have been found in the respiratory tracts of people who are fully vaccinated. This suggests that vaccinated people may be able to spread the Delta variant to some degree.
If you have COVID-19 symptoms, even if you're fully vaccinated, you should get tested and isolate from friends and family because you could spread the virus.
What risk does Delta pose to unvaccinated people?
The Delta variant is behind a surge in cases in communities with low vaccination rates, and unvaccinated Americans currently account for 97% of hospitalizations due to COVID-19, according to Walensky. The best thing you can do right now to prevent yourself from getting sick is to get vaccinated.
Gigi Gronvall, an immunologist and senior scholar at the Johns Hopkins Center for Health Security, said in this week's "Making Sense of Science" podcast that it's especially important to get all required doses of the vaccine in order to have the best protection against the Delta variant. "Even if it's been more than the allotted time that you were told to come back and get the second, there's no time like the present," she said.
With more than 3.6 billion COVID-19 doses administered globally, the vaccines have been shown to be incredibly safe. Serious adverse effects are rare, although scientists continue to monitor for them.
Being vaccinated also helps prevent the emergence of new and potentially more dangerous variants. Viruses need to infect people in order to replicate, and variants emerge because the virus continues to infect more people. More infections create more opportunities for the virus to acquire new mutations.
Surtees and others worry about a scenario in which a new variant emerges that's even more transmissible or resistant to vaccines. "This is our window of opportunity to try to get as many people vaccinated as possible and get people protected so that so that the virus doesn't evolve to be even better at infecting people," she said.
Does Delta cause more severe disease?
While hospitalizations and deaths from COVID-19 are increasing again, it's not yet clear whether Delta causes more severe illness than previous strains.
How can we protect unvaccinated children from the Delta variant?
With children 12 and under not yet eligible for the COVID-19 vaccine, kids are especially vulnerable to the Delta variant. One way to protect unvaccinated children is for parents and other close family members to get vaccinated.
It's also a good idea to keep masks handy when going out in public places. Due to risk Delta poses, the American Academy of Pediatrics issued new guidelines July 19 recommending that all staff and students over age 2 wear face masks in school this fall, even if they have been vaccinated.
Parents should also avoid taking their unvaccinated children to crowded, indoor locations and make sure their kids are practicing good hand-washing hygiene. For children younger than 2, limit visits with friends and family members who are unvaccinated or whose vaccination status is unknown and keep up social distancing practices while in public.
While there's no evidence yet that Delta increases disease severity in children, parents should be mindful that in some rare cases, kids can get a severe form of the disease.
"We're seeing more children getting sick and we're seeing some of them get very sick," Surtees said. "Those children can then pass on the virus to other individuals, including people who are immunocompromised or unvaccinated."