February | 2022 | COVID-19 CENTRAL @THEU

Can salivary glands infected with COVID-19 increase risk for relapse or reinfection?

February 28, 2022

University of Utah Health scientists are leading an effort to determine if salivary glands infected with the virus that causes COVID-19 could diminish a person’s long-term immunity to the disease after being immunized or after recovering from the illness.

The investigation, supported by a two-year grant from the National Institutes of Health, will explore whether salivary glands that have SARS-CoV-2 can lessen the body’s ability to make antibodies that would protect it against reinfection by the virus.

A graphic drawing of a person with inflamed salivary glands injected with viruses.

A person with viral inflammation of the salivary glands. Vector illustration of sialolithiasis. Photo credit: Getty Images

Viruses like SARS-CoV-2 are commonly found in salivary glands. How SARS-CoV-2 gets there, though, is still a mystery. Typically, viruses can enter the salivary glands through the moist inner lining of the oral cavity, called mucosa, or travel there via the bloodstream, says Melodie Weller, Ph.D., an assistant professor of dentistry who is leading the new study.

Like some other parts of the body, the salivary glands have what is known as “immune privilege,” meaning that even though they are infected, the immune system may not effectively clear pathogens within the glands. As a result, the salivary glands can be a lingering repository for viruses such as SARS-CoV-2 and other viruses.

Proteins that we are exposed to in our digestive tract can trigger what is called “oral tolerance.” As a result, our immune system won’t produce antibodies to these proteins, such as those in the foods that we eat, Weller says. However, because viruses contain proteins, they too may be overlooked by the immune system in the gastrointestinal tract.

“If viral proteins are released into the saliva––and we swallow a lot of saliva every day––then they may have the capacity to decrease our ability to make antibodies,” Weller says. “That can have an impact on how long immunity will last. So, the better we can understand the role of SARS-CoV-2 in the salivary glands, the better we’ll understand how reinfection and breakthrough infections after immunization are occurring during this pandemic.”

The researchers suspect that SARS-CoV-2 released from the salivary glands may inhibit the production of antibodies—and, as a result, increase the risk of relapse or reinfection. They also could limit the long-term effectiveness of vaccines.

Weller and colleagues are testing this hypothesis in mice, expressing SARS-CoV-2 viral proteins in the salivary glands. They plan to vaccinate these animals to see how they respond.

“If they’re getting viral protein exposure in the gut through swallowing saliva, then we will likely see a decrease in immunity or a decrease in the duration of the immune response,” Weller says.

Study: in much of the U.S., virtual school did not lower COVID-19 case rates in surrounding communities

February 28, 2022

Analysis shows no difference in COVID-19 rates between U.S. counties where school was held in-person and those that had virtual school, except in the South

Since March 2020, parents, educators, and politicians have debated whether to send children to school in person during the COVID-19 pandemic. New research suggests that in most regions, with the exception of the South, opening schools for in-person learning was not associated with an increase in COVID-19 case rates in the community. The results of the nationwide study, published in Nature Medicine, included 895 school districts across the United States.

“The results suggest it is possible for schools to operate safely and in-person without increasing case rates in the community,” says Richard Nelson, Ph.D., associate professor of epidemiology at University of Utah Health and co-senior author with Westyn Branch-Elliman, M.D., of the VA Boston Healthcare System. “But the flip side is true, too. In some areas, in-person school did appear to be a source of community spread.”

The researchers analyzed data gathered during the 12 weeks from July to September 2020 by region, and categorized them as the Northeast, Midwest, South, and Mountain West. The Pacific West was not included because nearly all public schools were virtual. The study found that:

In every region analyzed, COVID-19 cases increased during the weeks following the start of school.
The South was the only region where case rates were higher in counties with in-person or hybrid school as compared to counties with virtual learning, after controlling for other contributing factors.
In all other regions, community case rates during the period following school opening were similar regardless of whether school was virtual, hybrid, or in-person.

“We know that cases increased substantially last fall throughout the country,” Nelson says. “In some areas of the country, school mode was a contributing factor to those increasing rates, whereas in other areas it was not.”

“The results suggest it is possible for schools to operate safely and in-person without increasing case rates in the community. But the flip side is true, too.”

In the South, which included 191 counties from Delaware to Texas, traditional in-person school was associated with an increase in community cases of COVID-19 beginning two weeks after the school reopened. The increase was chiefly among people between the ages of 0-9, or 20 and older. Data were not available for stratification that would allow the scientists to analyze impacts on different school-age groups (e.g. elementary, middle, and high school).

The researchers controlled for local policies, including closings of workplaces and public transportation, canceling of public events, COVID testing and contact tracing policies, and mask requirements.

However, because people follow policies imperfectly, another important piece of data the researchers considered was community mobility. This is data collected from Google location history that reflects how much people are actually moving around the community in four categories: residences, workplaces, grocery/pharmacy, and retail/recreation locations.

In communities where people are moving around more, there is more social interaction outside of school and thus more opportunity for infection to spread, Nelson explains. “Traditional school in an area where there’s lots of movement looks different than traditional school where there’s not much movement in the community, in terms of case rates,” Nelson says. “For this reason, it is important to take community-level mobility into account when evaluating the impact that schools had on cases.”

Together, the data suggest that the impact of traditional and hybrid school on community spread varied throughout the country, Nelson says. Further investigation into factors that may have contributed to community spread in the South could help determine the most effective mitigation measures for in-person school.

Branch-Elliman explains that it’s possible that regional differences in community-level and in-school mitigation strategies, or other factors such as environmental conditions, may have played a role. “It is important to appreciate that schools are not islands,” Branch-Elliman says. “They exist as part of a broader community network.”

At the time the study data were collected, vaccinations were not available and the Delta variant had not yet emerged in the U.S. Additional research will also need to investigate how these factors affect the spread of COVID-19.

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The research was published as “The Impact of School Opening Model on SARS-CoV-2 Community Incidence and Mortality” and was supported by the National Institutes of Health.

Additional centers that participated in the study include Binghamton University, Boston University School of Medicine, Brown University, Beth Israel Deaconess Medical Center, Iowa City VA Health Care System, University of Iowa, VA Salt Lake City Health Care System, and Harvard Medical School

U of U Health leads national studies of “long covid” in adults and during pregnancy

February 28, 2022

University of Utah Health scientists are on the leading edge of a pair of large studies investigating the long-term effects of COVID-19. The nationwide studies, supported by the National Institutes of Health, will attempt to answer key questions about the lingering effects of the viral disorder on pregnant individuals and their infants, as well as why some people develop post-acute sequelae of SARS-CoV-2 (PASC), including “long COVID,” and others don’t.

PASC affects up to 30% of COVID-19 patients, causing a host of lingering and potentially serious symptoms. These include fatigue, breathing difficulties, memory problems, chest pain, and fast or pounding heart. The two groups are part of a larger NIH initiative, “Researching COVID to Enhance Recovery” (RECOVER) Initiative, which seeks to understand, prevent, and treat PASC.

Torri D. Metz, M.D., a University of Utah maternal-fetal medicine specialist. Photo credit: Charlie Ehlert

Assessing COVID-19’s impact on pregnancy, newborns

Among the vital but still unanswered questions about COVID-19 and PASC is what influence the disease may have on pregnant individuals and their infants.

“We really don’t understand right now what the long-term consequences are of getting COVID-19 in pregnancy,” says T orri D. Metz, MD, MS, a maternal-fetal medicine subspecialist and associate professor at U of U Health who is leading a multi-center effort seeking answers to this question.

Rachel Hess, M.D., co-director of the Utah Clinical and Translational Science Institute (CTSI). Photo credit: Charlie Ehlert

Previous research suggests that pregnant individuals who have severe COVID-19 are three times more likely to receive intensive care and twice as likely to die of the disease than those who aren’t pregnant. While transmission of the virus from mother to child during pregnancy is rare, up to 3% of babies born to women with COVID-19 test positive for the virus after birth.

“It’s possible that the disease may be different in pregnant women because their immune systems function a bit differently than in non-pregnant women,” Metz says. “In terms of offspring, we know how important the in-utero environment is for babies, and we’re concerned that the inflammatory process that occurs when patients who are pregnant get COVID-19 may affect the babies in utero and after they are born.”

Over the next four years, Metz and her colleagues from 12 other medical institutions nationwide involved in the Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units (MFMU) Network will track the health of about 1,500 women who had COVID-19 during pregnancy and their children who were born in the following days, weeks, or months. They will also track the health of about 250 women who did not get COVID-19 during pregnancy and their offspring.

In particular, the researchers will be looking for any impairments in cognitive development or cardiovascular complications among the children as they grow. They will also compare the long-term effects of PASC on the mothers who had COVID-19 during pregnancy versus pregnant individuals who were uninfected.

Sorting out why some people get ‘Long COVID’

Rachel Hess, M.D., co-director of the Utah Clinical and Translational Science Institute (CTSI), leads an effort by the Mountain States PASC Consortium (MSPC), a coalition of five health care systems in Utah, Colorado, and New Mexico. The group will compare COVID-19 patients who have or have had PASC with those who had COVID-19 but did not develop long-term symptoms.

“My biggest hope for the MSPC study is that we can develop a better understanding of why some people are experiencing really debilitating PASC symptoms and eventually help them get back to normal—or as close to it as possible,” Hess says.

The consortium plans to recruit more than 900 adults, 18 and older, for the study, including a diverse set of volunteers from Hispanic, Native American, and rural populations within the Mountain West region.

“Because this is such a new syndrome, determining what is different about people who develop PASC as a result of having COVID-19 is an important task,” Hess says. “This study could help us better define what this syndrome is and improve our understanding of its biological basis.”

The MSPC study includes patients who have been newly diagnosed with COVID-19, as well as those who had COVID-19 throughout the pandemic. Others who have not been infected with SARS CoV-2, the virus that causes COVID-19, will be recruited as a control group.

“Tracking individuals who currently have COVID-19 could help us determine if there are any patterns early in the disease that lead some patients to develop PASC later on,” Hess says.

Young people recover quickly from rare myocarditis side effect of COVID-19 vaccine

February 28, 2022

Adapted with permission from the American Heart Association.

Most young people under the age of 21 who developed suspected COVID-19 vaccine-related heart muscle inflammation known as myocarditis had mild symptoms that improved quickly, according to new research published today in the American Heart Association’s flagship journal Circulation.

Myocarditis is a rare but serious condition that causes inflammation of the heart muscle. It can weaken the heart and affect the heart’s electrical system, which keeps the heart pumping regularly. It is most often the result of an infection and/or inflammation caused by a virus.

Using data from 26 pediatric medical centers across the United States and Canada, researchers reviewed the medical records of patients younger than 21 who showed symptoms, lab results or imaging findings indicating myocarditis within one month of receiving a COVID-19 vaccination, prior to July 4, 2021. Cases of suspected vaccine-associated myocarditis were categorized as “probable” or “confirmed” using CDC definitions.

Of the 139 teens and young adults, ranging from 12 to 20 years of age, researchers identified and evaluated:

Most patients were white (66.2%), nine out of 10 (90.6%) were male and median age was 15.8 years.
Nearly every case (97.8%) followed an mRNA vaccine, and 91.4% occurred after the second vaccine dose.
Onset of symptoms occurred at a median of 2 days following vaccine administration.
Chest pain was the most common symptom (99,3%); fever and shortness of breath each occurred in 30.9% and 27.3% of patients, respectively.
About one in five patients (18.7%) was admitted to intensive care, but there were no deaths. Most patients were hospitalized for two or three days.
More than three-fourths (77.3%) of patients who received a cardiac MRI showed evidence of inflammation of or injury to the heart muscle.
Nearly 18.7% had at least mildly decreased left ventricular function (squeeze of the heart) at presentation, but heart function had returned to normal in all who returned for follow-up.

“These data suggest that most cases of suspected COVID-19 vaccine-related myocarditis in people younger than 21 are mild and resolve quickly,” said the study’s first author, Dongngan T. Truong, M.D., an associate professor of pediatrics in the division of cardiology at University of Utah Health and a pediatric cardiologist at Intermountain Primary Children’s Hospital in Salt Lake City. “We were very happy to see that type of recovery. However, we are awaiting further studies to better understand the long-term outcomes of patients who have had COVID-19 vaccination-related myocarditis. We also need to study the risk factors and mechanisms for this rare complication.”

Researchers say future studies should follow patients who have suffered vaccine-associated myocarditis over a longer term, since this study examined only the immediate course of patients and lacks follow-up data. Additionally, there are several important limitations to consider. The study design did not allow scientists to estimate the percentage of those who received the vaccine and who developed this rare complication, nor did it allow for a risk/benefit ratio examination. The patients included in this study were also evaluated at academic medical centers and may have been more seriously ill than other cases found in a community.

“It is important for health care professionals and the public to have information about early signs, symptoms and the time course of recovery of myocarditis, particularly as these vaccines become more widely available to children,” Truong said. “Studies to determine long-term outcomes in those who have had myocarditis after COVID-19 vaccination are also planned.”

COVID-19 linked to serious health complications during pregnancy

February 28, 2022

Pregnant individuals infected with SARS-CoV-2, the virus that causes COVID-19, are about 40% more likely to develop serious complications or die during pregnancy than those who aren’t infected with the virus, according to a nationwide study led by a University of Utah Health obstetrician.

The researchers concluded that the severity of COVID-19 symptoms is a key indicator of heightened risk of pregnancy complications. This was particularly evident among the most severely ill people, who were three times more likely to develop pregnancy complications than those who tested negative or who were less affected by the disease.

“We already knew that pregnant people are at higher risk for the complications of COVID-19 itself,” says T orri D. Metz, MD, MS, a maternal-fetal medicine specialist and associate professor of obstetrics and gynecology at U of U Health who led the multi-center effort. “Our research is among the first to find that infection with SARS-CoV-2 can elevate the risk of serious consequences related to progression of common pregnancy complications such as developing high blood pressure, having postpartum bleeding, or acquiring an infection other than SARS. This is why we need to make sure pregnant individuals are vaccinated.”

Torri D. Metz, M.D., a University of Utah maternal-fetal medicine specialist. Photo credit: Charlie Ehlert

The study appears in the February 7, 2022, issue of JAMA.

The researchers analyzed electronic medical records of 14,104 pregnant individuals treated at 17 medical centers nationwide that participate in the Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units (MFMU) Network between March 1, 2020, and December 31, 2020.

About 2,350 of these individuals tested positive for SARS-CoV-2 during pregnancy or within six weeks of delivery. More than 13% of those who tested positive developed pregnancy complications during the study compared to 9% of those who tested negative. All five of the maternal deaths occurred in the SARS-CoV-2 positive group. In addition, the researchers found that:

Complications were more prevalent with moderate to severe COVID-19.

Compared to those who had mild (flu-like) symptoms or were asymptomatic, pregnant individuals who had moderate or severe symptoms, requiring treatment with supplemental oxygen or ICU care, were about three times (26.1% vs. 9.2%) more likely to have serious pregnancy complications.

These problems included eclampsia, severe high blood pressure, kidney failure and other end organ damage caused by high blood pressure, sepsis from infections other than SARS-CoV-2, and endometritis requiring prolonged administration of intravenous antibiotics.

Premature birth was more likely in infected individuals.

SARS-CoV-2 infection was significantly associated with premature birth and NICU admission. However, maternal SARS-CoV-2 was not associated with any other adverse outcomes among newborns. In fact, only 1.2% of newborns tested positive for the virus before discharge.

People with certain characteristics were more likely to have complications.

Individuals who tested positive and subsequently developed pregnancy complications were more likely to have a body mass index (BMI) of 30 or higher and identify as Hispanic or Black. These findings are consistent with other demographic findings among non-pregnant individuals infected with the virus, Metz says.

Pregnant individuals who had moderate or severe COVID-19 symptoms were also at significantly higher risk of cesarean birth (45.4% vs. 32.4%) than those without SARS-CoV-2. However, cesarean birth rates were similar among those who had mild symptoms or were asymptomatic compared with those without SARS-CoV-2.

“Some pregnant individuals who have COVID-19 are just too sick for us to attempt a vaginal birth,” Metz says. “In certain circumstances, such as the onset of preeclampsia, the fetus is also far less likely to tolerate it.”

Among the study’s limitations is that 80% of the SARS-CoV-2 infections were detected in the third trimester, hampering efforts to evaluate the effects of the virus on complications early in pregnancy.

The study was also conducted prior to the widespread availability of mRNA vaccines. However, Metz says, the new findings bolster the scientific rationale behind efforts to get individuals who are pregnant, or considering having a child, vaccinated.

“The complications of pregnancy we observed were mostly in people who had moderate to severe symptoms of COVID-19,” Metz says. “We know from other studies that vaccination prevents the most severe symptoms of the disease. So, this is just another piece of the puzzle that should encourage pregnant people to get vaccinated.”

The study, “Association of SARS-CoV-2 Infection with Serious Maternal Morbidity and Mortality from Obstetric Complications,” appears in the February 7, 2022 issue of JAMA. It was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Center for Advancing Translational Sciences.

In addition to U of U Health, institutions participating in this study include George Washington University, University of Alabama, Northwestern University, Brown University, University of Texas Medical Branch, University of Pittsburgh, Case Western University, University of North Carolina, The Ohio State University, Columbia University, University of Pennsylvania, the University of Texas Health Sciences Center-Houston, and the University of Texas-Austin.

Conflicts of Interest: Torri D. Metz received personal fees and grants from Pfizer as well as grants from Gestvision; Brenna L. Hughes received personal fees from Merck; Hyagriv N. Simihan is an LLC co-founder of Naima Health and received personal fees from UptoDate outside of the current study; Alan T. N. Tita received grants from Pfizer; Maged Costantine reported a relationship with Baxter International, Momenta Pharmaxeuticals, Progenity, AMAG Pharmaceuticals, and ObsEva. No other authors report any conflict of interest.