November | 2021 | COVID-19 CENTRAL @THEU

mRNA vaccines slash risk of COVID-19 infection by 91 percent

November 2, 2021

People who receive mRNA COVID-19 vaccines are up to 91 percent less likely to develop the disease than those who are unvaccinated, according to a new nationwide study of eight sites, including Salt Lake City. For those few vaccinated people who do still get an infection, or “breakthrough” cases, the study suggests that vaccines reduce the severity of COVID-19 symptoms and shorten its duration.

Researchers say these results are among the first to show that mRNA vaccination benefits even those individuals who experience breakthrough infections.

“One of the unique things about this study is that it measured the secondary benefits of the vaccine,” says Sarang Yoon, D.O., a study co-author, assistant professor at the University of Utah Rocky Mountain Center for Occupational and Environmental Health (RMCOEH), and principal investigator of the RECOVER (Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel) study in Utah.

The study, published online in the New England Journal of Medicine, builds on preliminary data released by the Centers for Disease Control and Prevention (CDC)in March.

The study was designed to measure the risks and rates of infection among those on the front lines of the pandemic.

“We gave these vaccines to some of the highest risk groups in this country—doctors, nurses, and first responders,” Yoon says. “These are the people who are getting exposure to the virus day in and day out, and the vaccine protected them against getting the disease. Those who unfortunately got COVID-19 despite being vaccinated were still better off than those who didn’t.”

Sarang Yoon, D.O., assistant professor at the University of Utah Rocky Mountain Center for Occupational and Environmental Health.

The study found that mRNA COVID-19 vaccines were:

91% effective in reducing risk for infection once participants were “fully” vaccinated, two weeks after the second dose.
81% effective in reducing risk for infection after “partial” vaccination, two weeks after the first dose but before the second dose was given.

The HEROES-RECOVER network recruited 3,975 participants at eight sites. In addition to Salt Lake City, sites included Miami, Florida; Temple, Texas; Portland, Oregon; Duluth, Minnesota; and Phoenix and Tucson, as well as other areas in Arizona. Participants submitted samples for COVID-19 testing on a weekly basis for 17 weeks between Dec. 13, 2020 and April 10, 2021. Participants also reported weekly whether they had COVID-19-like symptoms, including fever, shortness of breath, and loss of taste and smell.

Only 204 (5%) of the participants eventually tested positive for SARS-CoV-2, the virus that causes COVID-19. Of these, 156 were unvaccinated, 32 had an indeterminate vaccine status, and 16 were fully or partially vaccinated. The fully or partially vaccinated participants who developed breakthrough had milder symptoms than those who were unvaccinated:

Presence of fever was reduced 58% percent among those vaccinated with a breakthrough infection.
Days spent sick in bed were reduced by 60% among those who developed a breakthrough infection.
Detection of the virus was reduced by 70% percent among those with breakthrough infections, from 8.9 days to 2.7 days.
The three people who were hospitalized were not immunized, meaning that no one who developed a breakthrough infection was hospitalized.

These findings also suggest that fully or partially vaccinated individuals who get COVID-19 might be less likely to spread the virus to others. The researchers found that infected study participants who had been fully or partially vaccinated when infected had 40% less detectable virus in the nose and did so for six fewer days compared to those who were unvaccinated.

Overall, the researchers conclude the study’s findings support the CDC’s recommendation to get fully vaccinated as soon as possible.

“I hope these findings reassure the public that mRNA COVID-19 vaccines are safe and protect us from this severe disease,” Yoon says.

The RECOVER study is ongoing, and results from future phases will help determine how long COVID-19 vaccines protect against infection and the real-world effectiveness of newer vaccines. A new study will test the same questions in children 12 and older who are now eligible to receive the COVID-19 vaccination. The research will also investigate how well COVID-19 vaccines protect against new variants now circulating in the U.S., including the highly transmissible Delta variant of SARS-CoV-2.

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The study, “Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines,” appears in the New England Journal of Medicine.

In addition to Dr. Yoon, Kurt Hegmann, M.D., director of RMCOEH, Matthew Thiese, Ph.D., associate professor, and Andrew Phillips, M.D., assistant professor of RMCOEH, were co-investigators on the Utah portion of the study.

Report provides evidence that lab leak theory unlikely

November 2, 2021

Today’s COVID-19 pandemic likely began when an infected animal passed the SARS-CoV-2 virus to a human at a live animal market in Wuhan, China. In a critical review published in the peer-reviewed journal Cell,21 scientific experts from across the world present evidence that this scenario is much more probable than the novel disease originating from a laboratory accident, a theory that has received attention in the media.

“The discussion over the origins of the pandemic have become politicized and heated, and we felt the time was right to take a critical look at all of the available evidence,” says Stephen Goldstein, PhD, an author on the paper and evolutionary virologist at University of Utah Health. Corresponding authors are Edward Holmes, PhD, The University of Sydney, Australia, and Andrew Rambaut, University of Edinburgh, UK. “Preventing future pandemics requires the political will to cut off the routes by which these viruses enter the human population. Focusing in the wrong direction will preclude those efforts from occurring.”

The experts laid out the evidence. Learn more in an interview with Goldstein.

Animal markets are an epicenter for early COVID-19 cases

Maps showing the first documented cases of COVID-19 in Wuhan, China. Originally published in Cell, adapted with permission.

Maps pinpointing geographic locations of the first wave of COVID-19 cases in December 2019, show they initially emerged close to the site of the Huanan Seafood Wholesale Market in Wuhan, China, as well as other markets reported to have live animal trading. In the weeks following, cases radiated outward geographically. Those cases were followed by excessive deaths in January 2020, a second marker of how the virus spread through the population. Similarly, those deaths were initially localized to near the animal markets.

“It tells us where the epidemic began and where intense transmission began,” Goldstein explains. “This suggests that the epidemic began in markets in this district: the Huanan market and possibly other markets as well.”

Lack of evidence for laboratory leak

The Wuhan Institute of Virology, often cited as the source of a lab leak, is also marked on the map, but is a distance away from the live animal markets. None of the very first documented cases—or excessive deaths within the first week of emerging—were located near the institute. None of the first documented cases were reported as being related to staff at the laboratory. There is no evidence that researchers at the institute worked with SARS-CoV-2 nor a closely related virus.

Human infectious disease frequently originates in animals

COVID-19 isn’t the first coronavirus-based infectious disease associated with animal markets. The 2002 and 2003 outbreaks of SARS, the disease caused by the SARS-CoV virus, were associated with markets in China that sold live animals. In addition to SARS-CoV and SARS-CoV-2, five other coronaviruses have crossed into humans from animals in the past 20 years. Combined with the observation that the majority of viruses in humans, both coronaviruses and other virus types, came from infected animals, it would not be unexpected for SARS-CoV-2 to have entered the human population in the same way, the authors say.

“Preventing future pandemics requires the political will to cut off the routes by which these viruses enter the human population. Focusing in the wrong direction will preclude those efforts from occurring.”

No signs of man-made changes to the virus

A recurring argument for the lab leak theory is that the virus, SARS-CoV-2, carries a specific short genetic code that is sometimes engineered into laboratory products, called a furin cleavage site. To investigate, researchers have previously analyzed genetic sequences from multiple coronaviruses and found the code in question to be commonplace among them. The authors of this review further determined that the specific code in SARS-CoV-2 is imperfect and therefore would not perform its function well.

“There is no logical reason why an engineered virus would utilize such a suboptimal furin cleavage site, which would entail such an unusual and needlessly complex feat of genetic engineering,” the authors write. Examination of the virus’ sequence has not turned up other potential signs of deliberate manipulation.

While a substantial body of scientific evidence supports SARS-CoV-2 originating from wildlife, those animals have not been found. “We can’t rule out the possibility of a lab accident,” Goldstein says. “It can’t be dismissed entirely, but it is highly unlikely. There’s no evidence for it right now.”

COVID-19 vaccine effectiveness dips, but remains potent deterrent

November 2, 2021

COVID-19 vaccines remain effective, but their potency has diminished in recent months, according to a nationwide study at eight sites, including Salt Lake City, Utah.

Scientists calculated vaccine effectiveness to be 80% in a large group of fully vaccinated frontline workers between December 2020 and August 2021, compared to 91% in earlier surveys. The estimates were based on COVID-19 RT-PCR testing and did not measure whether there were changes in efficacy in protecting against severe disease, including hospitalization and death.

The authors say one reason for the change could be waning immunity, a decrease in the strength over time of the body’s vaccine-activated defenses against the virus. The difference may also reflect the fact that the vaccines are not as effective against the highly contagious Delta variant of the SARS-CoV-2 virus, which since June 2021, has become the most common cause of COVID-19 in the U.S.

“The vaccines are still helping save lives and keep people from getting sick despite a slight diminishing return over many months,” explains Matthew Thiese, Ph.D., associate professor at the University of Utah Rocky Mountain Center for Occupational and Environmental Health (RMCOEH). “These data, combined with other data, demonstrate that vaccinated people are much less likely to get COVID-19 and are much less likely to be hospitalized.” Thiese is co-investigator and RMCOEH assistant professor Sarang Yoon, D.O., is primary investigator of the HEROES-RECOVER (Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel) study site in Utah.

The study published on August 24 in the Morbidity Mortality Weekly Report (MMWR) from the Centers for Disease Control and Prevention (CDC). Additional study sites in the HEROES-RECOVER network are Phoenix, Tucson, and other areas in Arizona; Miami, Florida; Portland, Oregon; Duluth, Minnesota; and Temple, Texas.

The network followed 4,136 health care personnel, first responders, and essential workers who had not previously had COVID-19. Study participants submitted samples for RT-PCR testing on a weekly basis and 2,976 participants were fully vaccinated within the study period, receiving either the Pfizer-BioNtech (65%), Moderna (33%), or Johnson & Johnson (2%) vaccines. Test results from these groups between December 14, 2020, to August 14, 2021, show that:

Among unvaccinated study participants, 194 infections occurred in 181,357 person-days (combined total of number of days of testing for this group).
Among fully vaccinated participants, 34 infections occurred in 454,832 person-days.

During that time period, the vaccines were 80% effective for all fully vaccinated study participants, but preliminary data indicate that vaccines may wane in intensity over time with lower effectiveness after five or more months following full vaccination. In addition, the vaccines appeared to be less effective during the last 43 days of the study period when Delta became the predominant virus variant. However, because sample sizes were small, these results were not statistically significant. These trends will be investigated further in future studies.

“These data show that the vaccine is still quite effective against the different strains of COVID-19, including the Delta variant,” Thiese says. “The protection people get from the vaccine is keeping people from getting COVID-19 at a ratio of 14 to 1. As these data continue to come in, they are going to help chart recommendations for masking, social distancing, and booster shots.”

5 ways U scientists are addressing COVID-19

November 2, 2021

As COVID-19, the disease caused by the new coronavirus, spreads across the globe, University of Utah scientists are stepping up to the plate to address the numerous unanswered questions emerging in its wake. Sound science that informs how the novel virus came to be, how it behaves, and how it spreads will be invaluable for developing and implementing strategies to defeat it.

Within a few short weeks, more than a dozen new research studies have popped up across the U — from physics to biochemistry to bioengineering — and many more are in the works. The U’s Immunology, Inflammation, and Infectious Disease Initiative quickly assembled support for these new efforts with a virtual meeting that attracted 207 participants, and in collaboragtion with the Vice President for Research, funding for COVID-19 research. While projects at the U vary in approach, they share a common goal: to create a brighter future for all of us.

We describe five of them here.

Do changes in temperature and humidity affect the new coronavirus?

One of the biggest unknowns about the coronavirus is how changing seasons will affect its spread. Researchers from the Department of Physics & Astronomy received grant funding to answer this question. The physicists will create individual synthetic coronavirus particles without a genome, making the virus incapable of infection or replication. The researchers will test how the structure of the coronavirus withstands changes in humidity and temperature, and under what conditions the virus falls apart.

-Lead scientists: Michael Vershinin, PhD, Saveez Saffarian, PhD, Physics and Astronomy

A drug to block infection

One thing we really need is a medicine that prevents or treats COVID-19. Biochemists at U of U Health are working toward that goal by repurposing a strategy they developed against another infectious disease, HIV. Their trick is to build mirror images of pieces of proteins, called D-peptides. These little chemicals are designed to jam the infection process; because D-peptides aren’t found in nature, they aren’t degraded by the body. This could mean that one dose could last a long time, simplifying treatment and lowering cost. Getting new drugs approved can be a lengthy process, so this approach may not help with the current outbreak. That’s why the scientists are simultaneously creating a broad inhibitor that could be effective against other new coronaviruses.

-Lead scientists: Debra Eckert, PhD, Christopher Hill, DPhil, Michael, Kay, PhD, Biochemistry

Origins of the new coronavirus, SARS-CoV-2

Bats are rife with coronaviruses, most of which are likely harmless to people. Scientists have found that these viruses can exchange pieces of genetic information with each other, giving rise to viruses that cause outbreaks in humans. To identify the role these exchanges may have played in the origin of SARS-CoV-2, researchers in the Department of Human Genetics are scouring the virus’ genome to find regions that have changed recently. This can determine whether genetic exchange could have empowered the virus to infect us and evade our immune defenses. Understanding how docile viruses turn deadly could one day inspire new ideas to stop them.

-Lead scientists:Stephen Goldstein, PhD, Nels Elde, PhD, Human Genetics

Who should be tested for COVID-19?

A limited number of COVID-19 tests are available due to international shortages of supplies to make them. In this situation, it is best to reserve testing for individuals who are most at risk for having the disease and developing severe symptoms. But who are they? Using mathematical models of disease spread and clinical data from those who have already been tested, infectious disease physicians are developing an online calculator. Plug in medical data and out comes a score indicating the likelihood that the patient will test positive. If the score is high, she should be tested. If the score is low, she can monitor symptoms at home (calling in if they change), potentially preserving a precious test.

-Lead scientist: Daniel Leung, MD, MSc, Infectious Disease

Projecting a better future

If we could see that the future looks dire, we might be able to strategize ways to change it. Epidemiologists are creating models based on what is known about transmission of the new coronavirus and combining them with census data. The result? An indication of when the disease might enter different parts of the country, along with an expected number of cases. With this virtual world, scientists can then determine how outcomes might change when people take precautions, like physical distancing. Scientists are also developing hospital-specific scenarios to anticipate needs for beds, masks, ventilators, and other precious items in limited supply. With these data, the hope is to shift the future from ominous to optimistic.

-Lead scientist: Lindsay Keegan, PhD, Epidemiology