Month: January 2023

New COVID-19 antibody test helps keep track of immunity to variants

January 26, 2023

Original story at U of U Health.

The experts agree — the pandemic is not over. Infections are ticking up again, fueled by new variants our immune systems are ill prepared for.

That’s according to a study which found that the antibodies generated in people who were vaccinated and/or recovered from COVID-19 prior to 2022 failed to neutralize the variants circulating today.

The study was led by Shawn Owen, PhD, an assistant professor of pharmaceutics and pharmaceutical chemistry at University of Utah Health and Igor Stagljar, PhD, a professor of biochemistry and molecular genetics, at the University of Toronto’s Temerty Faculty of Medicine.

The journal Nature Communications published their findings.

The researchers say the antibody test they developed to measure immunity in the study’s participants will be a valuable tool for deciding who needs a booster and when, which will help save lives and avoid future lockdowns.

“As the pandemic stretches on, we need ways to determine if people are protected from infection or reinfection,” Owen says. “Our assay can help monitor the level of immunity a person has after they’ve been vaccinated or infected. It can also reveal the level of protection against new variants which can help guide decisions about when to get a booster or if a new vaccine is needed.”

Many antibody tests have been developed over the past two years. But only a few authorized tests are designed to monitor neutralizing antibodies, which coat the viral spike protein so that it can no longer bind its receptor and enter cells.

It’s an important distinction, as only a fraction of all Sars-CoV-2 antibodies generated during infection are neutralizing. And while most vaccines were specifically designed to produce neutralizing antibodies, it’s not clear how much protection they give against variants

“The truth is we don’t yet know how frequent our shots should be to prevent infection,” Stagljar says. “To answer these questions, we need rapid, inexpensive and quantitative tests that specifically measure Sars-CoV-2 neutralizing antibodies, which are the ones that prevent infection.”

To meet this need, the research team developed Neu-SATiN, which stands for Neutralization Serological Assay. The effort was was spearheaded by Sun Jin Kim, a postdoctoral fellow in Owen’s lab and Zhong Yao, a senior research associate in Stagljar’s lab, who are the co-first authors on the paper.

The method is as accurate as, but faster and cheaper than, the current gold standard assay, and it can be quickly adapted for new variants as they emerge, according to the researchers.

“The biggest advantage of Neu-SATiN over other surrogate assays is the modularity,” Kim says. “Each of the Neu-SATiN’s assay components are genetically engineered and recombinantly expressed making them relatively easy to modify and produce. This enables Neu-SATiN to be a truly “mix-and-read” assay.”

The pin prick test is powered by the fluorescent luciferase protein from a deep-water shrimp. It measures the ability of the viral spike protein to bind the human ACE2 receptor, each of which is attached to a luciferase fragment.

The binding brings the luciferase pieces into proximity so that they reconstitute a full-length protein, which gives off a glow of light that is captured by instrumentation. When patient blood sample is added into the mixture, the neutralizing antibodies will bind the spike protein, preventing it from contacting ACE2. Luciferase remains in pieces, with an accompanying drop in light signal.

The plug and play method can be adapted to different variants within a couple of weeks by engineering variant mutations into the spike protein.

The researchers applied Neu-SATiN to blood samples collected from 63 patients with different histories of COVID-19 infection and vaccination up to November 2021. Their antibody neutralizing capacity was assessed against the original Wuhan strain and the variants, Alpha, Beta, Gamma, Delta and Omicron.

The neutralizing antibodies were found to last about three to four months. At that time, their levels dropped by about 70 per cent irrespective of infection or vaccination status. Hybrid immunity, acquired through both infection and vaccination, produced higher antibody levels at first, but also dropped significantly four months later.

Most worryingly, infection and/or vaccination provided good protection against the previous variants, but not Omicron, or its sub-variants, BA.4 and BA.5.

The researchers stress that vaccines still confer significant protection from severe disease and death. However, that the findings from Owen’s team and others call for vigilance in the coming period, given that the more transmissible BA.4 and BA.5 sub-variants can escape immunity acquired from earlier infections with Omicron. as attested by rising reinfections.

Moving forward, the researchers hope to expand its availability.

“We are working with a few companies to assess the efficacy of their vaccine candidates against Omicron and also negotiating a license with another company to commercialize the assay,” Owen says.

The research was supported with funding from the Office of the Vice President for Research and the 3i Initiative at the University of Utah, and the Toronto COVID-19 Action Fund.

Earliest cases of COVID-19 traced to market in Wuhan, China

January 26, 2023

Original story at U of U Health.

An international team of 18 researchers, including a scientist at University of Utah Health, have determined that the earliest cases of COVID-19 in humans arose at a wholesale fish market in Wuhan, China, in December 2019. They linked these cases to bats, foxes and other live mammals infected with the virus sold in the market either for consumption as meat or for their fur.

The finding, published in the July 26, 2022, issue of Science, aligns with early reports, later dismissed by senior Chinese officials, that live animals sold at the Huanan Seafood Wholesale Market were the likely source of the pandemic that has claimed at least 6.4 million lives since it first emerged in China nearly three years ago.

“These are the most compelling and most detailed studies of what happened in Wuhan in the earliest stages of what would become the COVID-19 pandemic,” says Stephen Goldstein, Ph.D., a co-author of the study led by senior author Kristian Anderson, Ph.D., from the Scripps Research Institute in La Jolla and first author Michael Worobey, Ph.D., from the University of Arizona. Goldstein is a postdoctoral scientist in the department of Human Genetics at U of U Health. “We have convincingly shown that the wild animal sales at the Huanan Market in Wuhan are implicated in the first human cases of the disease.”

Among the study’s key findings:

  • The emergence of SARS-CoV-2, the virus that causes COVID-19, can likely be traced to one or more of the 10 to 15 stalls in the market that sold rats, porcupines, badgers, hares, foxes, hedgehogs, marmots, and Chinese muntjac (a small deer). Health officials and researchers detected SARS-CoV-2 on animal cages, carts, and drainage grates in these venues.
  • The only areas where the virus was spreading in December 2019 were in neighborhoods within a half-mile of the market. Previously, some researchers had suggested that the virus was brought into the market from elsewhere in the city and spread among its patrons. Instead, the new findings strongly suggest that the virus originated in the market via live animal sales, and slowly spreading from there into nearby neighborhoods and then the city at large.
  • Two variants of the SARS-CoV-2 virus were detected at the market. That suggests both variants originated independently at the market and helps confirm the researchers’ hypothesis that early spread of the infection began there. If the virus originated elsewhere, it’s more likely that only a single variant would have been found.

The researchers say that moving forward, public officials should seek better understanding of the wildlife trade in China and elsewhere and promote more comprehensive testing of live animals sold in markets to lower the risk of future pandemics.

In a press conference, Stephen Goldstein, PhD, explains and answers questions about the study.

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The research published as “The Huanan Seafood Wholesale Market in Wuhan Was the Early Epicenter of the COVID-19 Pandemic” in Science on July 26, 2022.

 

Gun injuries in children spiked during the pandemic

January 26, 2023

Original story at U of U Health.

Gun injuries in kids surged during the COVID-19 pandemic, with a 50% increase compared to previous years. Data from children’s hospitals showed there were 2,759 firearm injuries among children between April 2020 to December 2021 compared to 1,815 injuries during the same time period in 2018 and 2019. Researchers at University of Utah Health carried out the analysis, which published as a research letter in JAMA Pediatrics. 

“Firearm injuries are the leading cause of death for children and adolescents in the United States. This is a heart-breaking statistic,” Stephanie Iantorno, M.D. told Healio. She is lead author of the study and a surgical resident at the Spencer Fox Eccles School of Medicine at the University of Utah. Katie Russell, M.D., an assistant professor in the Department of Surgery, was the study’s senior author. “During the pandemic, there were significantly more firearm injuries seen at children’s hospitals across the country, and that is pretty alarming,” says Iantorno.

Closer analysis revealed that a disproportionate number of Black children and children with public insurance were injured by guns during that time compared to previous years. “Pandemic conditions exacerbated many structural inequities that contribute to health disparities, and our findings may reflect the disparities that some minoritized children experienced during the study period,” the study’s authors wrote.

The results came from statistical analysis of the Pediatric Health Information System (PHIS) database with information from 49 children’s hospitals across the U.S. and does not account for transfers from other hospitals.

The authors note that understanding the context of gun injuries in children may inform approaches for prevention and prepare health systems to provide the best care in such circumstances.

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In addition to Iantorno and Russell, the study’s coauthors are Robert Swendiman, M.D., and Brian Bucher, M.D.

The research was supported by the University of Utah, Intermountain Healthcare, and the Agency for Healthcare Research and Quality and published as “Surge in Pediatric Firearm Injuries Presenting to US Children’s Hospitals During the COVID-19 Pandemic.

More than 40% of Americans misled others about having COVID-19 and use of precautions

January 26, 2023

Original story at U of U Health.

Four of 10 Americans surveyed report that they were often less than truthful about whether they had COVID-19 and/or didn’t comply with many of the disease’s preventive measures during the height of the pandemic, according to a new nationwide study led in part by University of Utah Health scientists. The most common reasons were wanting to feel normal and exercise personal freedom.

The study, which appears in the Oct. 10, 2022, issue of JAMA Network Open, raises concerns about how reluctance to accurately report health status and adherence to masking, social distancing, and other public health measures could potentially lengthen the current COVID-19 pandemic or promote the spread of other infectious diseases in the future, according to Angela Fagerlin, Ph.D., senior author of the study and chair of the Department of Population Health Sciences at U of U Health.

“COVID-19 safety measures can certainly be burdensome, but they work,” says Andrea Gurmankin Levy, Ph.D., a professor of social sciences at Middlesex Community College in Connecticut. As co-lead author of the study, she worked in collaboration with Fagerlin and other scientists at U of U Heath as well as researchers elsewhere in the United States.

“When people are dishonest about their COVID-19 status or what precautions they are taking, it can increase the spread of disease in their community.” Levy says. “For some people, particularly before we had COVID vaccines, that can mean death.”

The researchers decided to assess how truthful Americans were being about their COVID-19 disease status and/or compliance with COVID-19 preventive measures after they noticed several media stories about people who were dishonest about their vaccination status, Fagerlin says.

University of Utah Health scientists Angela Fagerlin, Ph.D., and Alistair Thorpe, Ph.D., led a study about how and why some people were less than truthful about their COVID-19 status.

In the survey, conducted in December 2021, more than 1,700 people from across the country were asked to reveal whether they had ever misrepresented their COVID-19 status, vaccination status, or told others that they were following public health measures when they actually weren’t. The sample size is far larger and asked about a broader range of behaviors than previous studies on this topic, according to Fagerlin, who is also a research scientist at the Veteran Affairs Salt Lake City Healthcare System.

Screening questions allowed the health service researchers and psychologists who designed the study to evenly divide the participants: one-third who had had COVID-19, one-third who had not had COVID-19 and were vaccinated, and one-third who had not had COVID-19 and were unvaccinated.

Based on a list of nine behaviors, 721 respondents (42%) reported that they had misrepresented COVID-19 status or failed to follow public health recommendations. Some of the most common incidents were:

  • Breaking quarantine rules
  • Telling someone they were with, or were about to see, that they were taking more COVID-19 precautions than they actually were
  • Not mentioning that they might have had, or knew that they had, COVID-19 when entering a doctor’s office
  • Telling someone they were vaccinated when they weren’t
  • Saying they weren’t vaccinated when they actually were

All age groups younger than 60 years and those who had a greater distrust of science were more likely to engage in misrepresentation and/or misrepresentation than others. About 60% of respondents said that they had sought a doctor’s advice for COVID-19 prevention or treatment.

 However, the researchers found no association between COVID-19 misrepresentation and political beliefs, political party affiliation, or religion.

“Some individuals may think if they fib about their COVID-19 status once or twice, it’s not a big deal,” Fagerlin says. “But if, as our study suggests, nearly half of us are doing it, that’s a significant problem that contributes to prolonging the pandemic.”

Among the reasons respondents gave for misrepresentation were:

  • I didn’t think COVID-19 was real, or it was no big deal
  • It’s no one else’s business
  • I didn’t feel sick
  • I was following the advice of a celebrity or other public figure
  • I couldn’t miss work to stay home

Among the study’s limitations, the researchers could not determine if respondents honestly answered survey questions, opening the possibility that their findings underestimated how commonly people misrepresented their health status.

“This study goes a long way toward showing us what concerns people have about the public health measures implemented in response to the pandemic and how likely they are to be honest in the face of a global crisis,” says Alistair Thorpe, Ph.D., co-first author and a post-doctoral researcher in the Department of Population Health Sciences at U of U Health. “Knowing that will help us better prepare for the next wave of worldwide illness.”

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In addition to Fagerlin and Thorpe, University of Utah Health researchers Holly Shoemaker, Frank A. Drews, Jorie M. Butler, and Vanessa Stevens contributed to this study. Other participating institutions include Middlesex Community College in Middletown, Connecticut; University of Colorado School of Medicine, Aurora; Veterans Affairs Denver Center for Innovation; University of Iowa School of Medicine, Iowa City; Salt Lake City VA Informatics Decision-Enhancement and Analytic Sciences (IDEAS) Center for Innovation; VA Salt Lake City Health Care System; and the American Heart Association.

The study, “Misrepresentation and Nonadherence Regarding COVID-19 Public Health Measures,” appears in the Oct. 10, 2022, issue of JAMA Network Open. It was supported by the Jon M. Huntsman Presidential Endowment and an American Heart Association Children’s Strategically Focused Research Network Fellowship.

MRNA vaccines significantly reduce severity of Delta, Omicron COVID-19 infections

January 26, 2023

Original story at U of U Health.

People who have received two or three doses of an mRNA COVID-19 vaccine are significantly more likely to have milder illnesses if infected with the Delta or Omicron coronavirus variants than those who are unvaccinated, according to a nationwide study involving a team of University of Utah researchers.

The study, which examined health care personnel, first responders and other frontline workers in Utah and five other states, builds on previous research that indicates mRNA vaccines provide protection against severe health outcomes associated with COVID-19 despite the variants’ increased transmissibility. 

“It’s encouraging that the mRNA vaccines hold up rather well against these variants,” said Sarang Yoon, D.O., a study co-author who leads the Utah portion of the research and is part of the Rocky Mountain Center for Occupational and Environmental Health, a partnership between the University of Utah and Weber State University. “We know that breakthrough cases are more likely with Delta and Omicron than the initial strain, but the vaccines still do a good job of limiting the severity of the infection.”

The study was published Tuesday in the Journal of the American Medical Association (JAMA). It is the latest of several peer-reviewed papers resulting from the nationwide HEROES-RECOVER project funded by the U.S. Centers for Disease Control and Prevention. 

Researchers examined 1,199 participants who developed COVID-19 infections. Of the participants, 24% were infected with Delta and 62% contracted Omicron, while 14% had the original virus strain. 

Delta highlights:

  • Participants who had received two vaccine doses were significantly less likely to be symptomatic than those who were unvaccinated (77.8% vs. 96.1%)
  • Symptomatic participants with a third dose were far less likely to experience fever or chills than those who were unvaccinated (38.5% vs. 84.9%) and experienced symptoms for an average of six fewer days (10.2 days vs. 16.4 days)

Omicron highlights:

  • The risk of symptomatic infection was similar between participants with two vaccine doses and those who were unvaccinated, while those with three doses experienced a higher risk than the unvaccinated (88.4% vs. 79.4%)
  • Symptomatic participants with three doses were significantly less likely to experience fever or chills (51.5% vs 79%) or seek medical care (14.6% vs 24.7%) than the unvaccinated

The authors noted that, while the study is among the largest of its kind examining COVID-19 vaccines over time and across variants, grouping participants by variant and vaccine status resulted in some combinations with relatively few people, affecting the precision of the findings. They also indicated that the study was not able to account for all factors influencing COVID-19 severity, which may skew the results. There were also results the authors characterized as “unexpected” among participants who received three doses and had symptomatic Omicron infections.

Researchers gathered data between Dec. 14, 2020, and April 19, 2022. Participants submitted self-collected nasal swabs weekly regardless of COVID-19 symptoms, as well as at the beginning of experiencing signs of illness. Participants were excluded from the study if they had infections before the study start date, or if their infections occurred: sooner than 14 days after their second vaccine dose, sooner than seven days after their third dose or more than 149 days after their third dose. 

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Other co-authors associated with the University of Utah and Rocky Mountain Center for Occupational and Environmental Health include Kurt Hegmann, M.D.; Matthew Thiese, P.h.D; Andrew Phillips, M.D.; Jenna Praggastis, B.S.; and Matthew Bruner, B.S.

Study: covid may increase risk of stroke in kids

January 26, 2023

Overall risk is low but real, data suggests.

Children may be at increased risk of stroke after COVID-19 infection, according to a new study published this week in the journal Pediatric Neurology.

“It may be that hyper-immune response that comes later that’s causing kids to clot,” said MaryGlen J. Vielleux, M.D., a pediatric neurology resident at University of Utah Health and lead author of the study. “Overall, kids have a relatively low risk for stroke, but there is a rare but real risk after COVID.”

Though previous research has shown that adults with COVID are at higher risk of stroke, that link has not previously been made with children. That may in part be because kids who do experience strokes generally have better medical outcomes than adults.

At the beginning of 2021, pediatric neurologists in Salt Lake City began to notice what appeared to be a growing number of stroke patients. These were kids who were seemingly healthy before experiencing a stroke.

They wondered whether this was a true increase and how it might compare to stroke numbers historically. They also wanted to know whether the apparent increase had any connection to the peak in COVID cases a few months before a rise in Multisystem Inflammatory Syndrome in Children (MIS-C).

“If we see one kid with a stroke a month, that would be pretty typical,” said Joshua L. Bonkowsky, M.D., Ph.D., and Chief of the Division of Pediatric Neurology at U of U Health and Intermountain Primary Children’s Hospital. “We were seeing three cases a week for multiple weeks in a row.”

By reviewing medical charts and diagnosis codes, researchers were able to identify 16 patients at the hospital who had an ischemic stroke between March 2020 and June 2021. Most of those took place between February and May 2021, shortly after the surge of COVID pediatric cases in the Mountain West region.

Of those tested for COVID antibodies, nearly half tested positive. None of the 16 had been severely sick with the virus and some had been asymptomatic. Five patients were not tested for past COVID infection, a limitation of the study.

“Overall, kids have a relatively low risk for stroke, but there is a rare but real risk after COVID.”

Pediatric stroke is very rare, so it is difficult to do a large study even at a major regional institution.

The new data did show that the overall number of strokes was significantly higher than what had been seen historically at Intermountain Primary Children’s Hospital. Over the past five years, the number of children with strokes of uncertain origins had averaged around 4 per year.  In the first six months of 2021, the hospital cared for 13 kids with a stroke of unknown origins.

Primary Children’s Hospital serves children from multiple states in the Mountain West. Any child in the region who has a stroke receives treatment at the hospital. That gives clinicians a unique ability to get a comprehensive snapshot of certain medical conditions such as stroke.

The study’s results are in contrast to the findings of a 2021 international study of children early in the pandemic that suggested COVID did not cause an increased risk of stroke in children.

The new study also showed that the risk of stroke is independent of whether or not the patient has Multisystem Inflammatory Syndrome in Children (MIS-C), a known complication of COVID. Only three of the patients had confirmed cases of MIS-C.

Analysis shows a rise in pediatric stroke cases after a surge in cases of COVID-19 suggesting that COVID-19 increases stroke risk. Stroke was not associated with MIS-C.

Of the 16 kids studied, most had few lingering impacts from their stroke by the time they left the hospital

Researchers hope this new study highlights the need for early evaluation of neurologic symptoms in children to rule out the possibility of stroke. Children often do not display the symptoms commonly associated with stroke in adults.

Children may have weakness on one side of the body but can often have an altered mental state or difficulty walking.

The data show that even kids who were asymptomatic from COVID could go on to experience a serious complication like stroke, said Vielleux.

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In addition to Vielleux and Bonkowsky, the study’s co-authors are Shanna Swartwood, M.D., Dan Nguyen, M.D., Karen E. James, M.D., from the Spencer Fox Eccles School of Medicine at the University of Utah and Bree Barbeau, M.P.H. from the Utah Department of Health. The research published as “SARS-CoV-2 Infection and Increased Risk for Pediatric Stroke.”