Closer look at vaccines, delta and viral loads
Information available, but can be complicated
We’re doing it again.
We’re taking a scientific development that is already complicated — rising cases of the COVID-19 delta variant virus — and dividing into camps, often with little grounding in truth.
So here’s the truth: What is known at this moment is that COVID has killed more than 620,000 Americans, the delta variant is more transmissible than previous COVID variants, and vaccines help.
For those who won’t accept that, there’s not much to discuss.
For those interested in understanding where we’re at with this new version of COVID, there’s a growing body of information, however imperfect, to draw from.
To start, it’s worth going back to the original COVID-19, and the hopes for a vaccine.
In June 2020, the U.S. Food and Drug Administration’s guidance for vaccine development stated the “FDA would expect that a COVID-19 vaccine would prevent disease or decrease its severity in at least 50% of people who are vaccinated.”
The vaccines we got, in addition to being developed faster than had been thought possible, blew those expectations away.
“If we knew then that we would have a vaccine that was 90-some percent effective against that, I think we would all take it,” said Josh Petrie, an epidemiologist at the University of Michigan School of Public Health.
What gets lost, at times, is that the outstanding outcome still means some vaccinated people will get COVID. To the general public, that can seem surprising and dispiriting, as if it points out some flaw in the vaccines. To scientists, it is neither.
COVID spread isn’t as black-andwhite as “having the virus” or “not having the virus.” People can carry varying amounts of the virus throughout their infection.
If someone gets infected with a little bit of virus, the immune system might be able to fight it off without the person noticing. But the virus replicates — or grows — over time, which is why a person might not have measurable virus levels on the third day after exposure but might finally cross the detectability threshold and test positive on the fourth. The vaccine increases a body’s natural ability to fight off, or at least temper, the impact.
The amount of virus a person carries — or the amount of “viral particles” — is called “viral load.” That’s why wearing masks, following social distancing and avoiding large gatherings has been so important. They all help limit the viral load.
The more exposure people get, the higher amounts of virus they encounter, and eventually it can be too much even for someone who is vaccinated. It’s like walking outside on a cold winter day. The best chance to stay healthy is to put on warm clothes. But if a person intentionally walks through deep snow for hours, eventually even the warm clothes — the vaccine — just isn’t enough.
Since the initial outbreak, researchers have developed — and continue to develop — an array of treatments for patients with the virus. But the “biggest bang for the buck” remains the vaccine, said Abhijit Duggal, a staff intensivist and the director for critical care research at Cleveland Clinic.
“Once you get vaccinated, your risk of getting the disease goes down dramatically,” he said. “More importantly, the risk of you developing the severe infection goes down pretty significantly. And that is the most important thing for us to remember—that this remains the best weapon in our (arsenal).” Clinical trials back this up. These are the gold standard for medical studies — so-called double-blinded placebo-controlled clinical trials in which neither the researchers nor the subjects know who has the placebo and who has the vaccine. The process eliminates bias on either side.
“We do know that the vaccines are effective,” said Susan Ellenberg, professor emerita of biostatistics, medical ethics and health policy at the University of Pennsylvania Perelman School of Medicine. “That was very clearly demonstrated in large randomized clinical trials where one-half or two-thirds of the people got the vaccine and the rest of them got the placebo, and they were followed and we counted up the number of infections.”
Sorting through confusing reports
That brings us to the delta variant, which is largely the same as previous iterations of COVID but has a combination of mutations that make it more transmissible than other strains.
If the SARS-CoV-2 virus is a knitted scarf, the rapid tests and PCR tests we currently have can only detect scarves, and not other viruses that might be hats, mittens or sweaters. Variants are much harder to detect; they are like scarves with a couple of mutated knots and stitches here and there that form in patterns we recognize as the “alpha” or “delta” variants.
To tell the delta variant apart from other iterations of COVID, scientists have to sequence — or read — the 30,000 “stitches” in the SARS-CoV-2 virus, looking for the places where a set of “stitches” is different from the original version and matches the “delta” stitch pattern.
This is why agencies are only testing a subset of positive samples for the delta variant and extrapolating the percentage of delta samples to the general population. It’s too time- and resourceintensive to sequence every single test sample.
Nevertheless, the delta variant has reset the national discussion because it replicates so rapidly, and people infected with it appear to carry viral loads around 1,000 times higher than the original strains. In other words, what used to be a modest exposure to an infected person at a restaurant can now be a modest exposure times 1,000. Further, a person who just caught the virus is potentially exposing contacts to a huge viral load before they ever test positive.
It’s important to remember that every activity has risks, said David Dowdy, associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health. Exposure increases in areas that are indoors, crowded, with people who are unmasked or unvaccinated, over longer periods of time. Different combinations create varying levels of risk.
Determining the precise effectiveness of the vaccines against the delta variant is a challenge.
For one, those gold-standard clinical trials are hard to conduct for vaccines we already use because it’s unethical to give someone a placebo when we know the real vaccine works to some measure. Instead, for the most part, we have observational studies of real life, which aren’t controlled and are potentially subject to bias, according to M. Elizabeth Halloran, professor of biostatistics at the Fred Hutchinson Cancer Research Center and the University of Washington.
Because there are likely differences in vaccinated and unvaccinated people’s underlying conditions, socioeconomic status, behavior and other factors, “comparing the infection rates in vaccinated people (in an observational study) to the infection rates in unvaccinated people could be comparing apples and oranges,” Halloran said.
Two studies, in particular, seem to have caused confusion.
The first, reported by the U.S. Centers for Disease Control and Prevention, focused on an outbreak in Provincetown, Massachusetts, in early July. Nearly three out of every four people infected had been vaccinated, and 90% of the cases involved the delta variant.
However, people infected at the Provincetown outbreak reported attending “densely packed indoor and outdoor events at venues that included bars, restaurants, guest houses, and rental homes,” which, as Dowdy noted, is intense and atypical exposure.
In Provincetown, only four people were hospitalized out of the 346 fully vaccinated people who got the infection — that’s barely above 1% — and there were no deaths, which is the ultimate goal of the vaccine and showed it was still effective even in a super-spreading situation.
Dr. Ashish Jha, dean of the Brown University School of Public Health, called the framing of the study a “borderline disaster in terms of public health messaging” because in addition to the unusual conditions for the outbreak, the 74% number is misleading if taken out of context.
The news of “74% breakthrough cases” sounded dramatic. But it’s natural that the higher number of people who were vaccinated, the higher number of breakthroughs would occur. If no one was vaccinated, there would have been no breakthroughs — not because there were no cases, but because none of them broke through anything.
The number of cases, hospitalizations and deaths per 100,000 people, as well as the percentage of the population vaccinated, are all necessary to properly assess the situation in a given community, said Prathit Kulkarni, assistant professor of medicine in infectious diseases at Baylor College of Medicine. As more people become vaccinated, the percentage of breakthrough cases may rise, but deaths and hospitalizations will be lower because the vaccines prevent severe disease.
The second study was from Dane County, published as a non-peer-reviewed preprint on the medRxiv repository in late July. Researchers reported that both vaccinated and unvaccinated people with the delta variant had similar viral loads, which was unexpected.
Some have taken this to mean vaccinated and unvaccinated people are equally contagious. However, Kulkarni pointed out that vaccinated people are more likely to have milder symptoms, which means less coughing and sneezing that would produce aerosols and droplets that might spread the virus.
In addition, “It’s a snapshot in time,” Kulkarni said. “It tells at the moment you did the test, what was (your) viral load? But what it doesn’t tell you is what is it in 24 hours or 48 hours.”
Preliminary studies in a preprint from Singapore suggest that vaccinated people clear the virus faster, meaning their viral loads decrease quicker than in unvaccinated people. This also decreases the chance that vaccinated people are as likely to spread the virus to someone else, Kulkarni said.
Petrie, at the University of Michigan, also pointed out that the Dane County preprint lacked data on how comparable the vaccinated and unvaccinated people were — for example, if the breakthrough cases were more likely to come from people with underlying conditions who didn’t respond as well to the vaccine.
What are your chances?
The delta variant just started accounting for the majority of cases in the United States around the beginning of July, according to the CDC’s variant monitor. As a result, solid scientific information about the so-called breakthrough cases is still in the building process.
It’s a lot of work to piece together, even for experts. Data on COVID cases has to be cross-checked with vaccination registries.
“It’s a totally separate data system. It has different data rules, there are different people working on it,” said Katarina Grande, a public health supervisor and COVID-19 data team lead at Public Health Madison and Dane County. “In health departments, you’ve got your immunization team and you’ve got your communicable disease team. It’s literally separate systems. Getting them to talk to each other is not easy (and) takes a long time.”
Obtaining this data at the county level is not perfect, either. Grande said that she can only access the vaccination records for people with a Dane County address, meaning she doesn’t have any records for UW students whose vaccination records are in different counties. Statewide data would smooth out some of those data wrinkles, but the state DHS’ breakthrough cases dashboard is a work in progress
In the meantime, Dane County has compiled and released data on COVID-19 cases in both vaccinated and unvaccinated people since February in its weekly COVID-19 data snapshots. Both kinds of cases have been increasing in Dane County since the beginning of July and are currently at their highest point since at least February. The Aug. 12 report shows there were 29.1 cases per 100,000 unvaccinated residents and 10.5 breakthrough cases per 100,000 vaccinated residents.
What that data doesn’t include is the severity of the cases, Kulkarni emphasized.
Further complicating matters, it’s difficult to determine whether the rise in delta cases has been related to vaccines, or simply a function of people returning to pre-COVID routines, taking off masks and becoming more vulnerable.
But amid those unknowns, there is already some basic information that reinforces the message of scientists all along.
While almost 167 million Americans have been fully vaccinated against COVID-19, the number of hospitalized breakthrough cases represents less than 0.005% of the vaccinated population, according to the CDC.
In other words, 99.995% of vaccinated people do not end up in the hospital because of any form of COVID.
“I have seen too many previously healthy people come in with really bad disease processes where we’ve had to really provide them with very extensive care —mechanical ventilators, extracorporeal life support — and despite all of that, there were many individuals who did not make it through despite being young and previously healthy,” said Duggal, at the Cleveland Clinic. “We have something available for us that can prevent you from: one, developing the disease; and two, developing severe disease. And it is important that we utilize that. Vaccinations are important and people should get them.”
And for the vaccinated people who are looking at the rising delta variant numbers and asking: What are my chances?
“If you’ve gotten vaccinated, thank you for doing that; the community is grateful to folks who are doing that. Number two, you are overall very protected, especially from bad outcomes,” Kulkarni said.
Duggal also pointed out that vaccines have other functions besides personal protection. The more that COVID is in circulation, the more the risk of new, possibly more dangerous, mutations.
“This is a public health concept,” he said. “Whenever it comes to a pandemic, we have to stop thinking about ourselves as individuals and we have to think about ourselves in the context of society.”
Brittany Trang has been reporting on science this summer at the Journal Sentinel through a program with the American Association for the Advancement of Science.