Study provides new clues into causes of long COVID symptoms

Reposted from U of U Health.

A few months after the first case of COVID-19 was confirmed in the United States in early 2020, some people who appeared to have recovered from the SARS-CoV-2 viral infection began reporting that they had a constellation of persistent symptoms.

Soon after, these tenacious health problems, which included fatigue, memory loss, shortness of breath, and loss of the sense of smell and taste, were referred to as long COVID.

Since then, an estimated 14 million Americans who survived the virus have developed long COVID, according to an analysis conducted by The Washington Post in conjunction with Epic Systems, an electronic health records company, and the Kaiser Family Health Foundation. Of those, at least 3,500 people have died from long COVID complications, according to the Centers for Disease Control and Prevention (CDC).

While treatment at clinics that specialize in long COVID is available in most states, including at University of Utah Health, the underlying cause of the malady remains a mystery.

However, in a small study, U of U Health scientists recently detected a potentially important clue.

The scientists found that levels of a particular set of proteins that are crucial in controlling the growth and activity of immune system cells were almost undetectable among individuals who had long COVID. As a result, the researchers suspect that lungs and other organs are unable to fully heal and fend off other illnesses after being infected with SARS-CoV-2, the virus that causes COVID-19.

“It appears that the cells responsible for producing certain proteins called cytokines are not being stimulated to produce them where they are needed,” said Vicente Planelles, Ph.D., the study’s senior author and a professor of pathology at U of U Health.

“We propose that cells producing these cytokines are either immunologically exhausted or are possibly dying and are not there to be stimulated in the first place.”

The study, which was conceived and led by Elizabeth S.C.P. Williams, Ph.D., a former graduate student in Planelles’ lab, appears in the Journal of Clinical and Cellular Immunology. The finding could eventually lead to new treatments for long COVID, Planelles said.

Research leads to unexpected finding

Vicente Planelles, Ph.D., the study’s senior author and a professor of pathology at U of U Health.

Previous research by other scientists detected cytokines that are overactive in long COVID patients, which they suggest lead to prolonged inflammation and the onset of long COVID. Elevated cytokine levels and lingering inflammation are also associated other possible post-viral infections such as chronic fatigue syndrome. 

Like the earlier researchers, the U of U Health scientists suspected that abnormal and elevated levels of cytokines were a driving force behind long COVID. This was the main theory prompting their study.

To test this theory, Williams, Planelles, and colleagues analyzed blood samples from 12 women who had confirmed cases of long COVID and from 15 men and women who had either never had COVID-19 or had recovered from the infection without lingering symptoms.

To their surprise, they found that, compared with the healthy volunteers, individuals with long COVID had undetectable levels of two cytokines involved in repair of damaged tissue and a 70% decrease in another cytokine that promotes inflammation in body tissue.

“These results were surprising because better known post-viral syndromes caused by other viruses are thought to be triggered by an increase in cytokines that increase and prolong inflammation in the body,” Williams said.

Elizabeth S.C.P. Williams, Ph.D., a former graduate student in Planelles’ lab, conceived and led the study.

“The same sort of pro-inflammatory cytokine process was detected in early studies of long COVID as well,” Williams adds. “But in our study, we detect an opposite result––that the activity of at least four pro-inflammatory cytokines is diminished or nonexistent.”

Planelles, Williams, and colleagues theorize that the drop occurs because the immune cells responsible for producing these cytokines are exhausted during COVID-19 infection and no longer capable of secreting them.

As a result, damaged cells in the lungs and other organs can’t be properly repaired, even after the infection subsides. In turn, long COVID symptoms such as chest pain, shortness of breath, coughing, and fatigue solidify their grip.

“The damage done by the initial viral infection isn’t being healed properly,” postulates Williams, who is receiving post-doctoral training in hematology in another U of U Health lab. “Damaged tissue is a source of inflammation. If the damage persists, so will the inflammation, and you’ll continue to have symptoms.

Further studies needed

The researchers found no significant differences between healthy men and women in 12 of the 13 cytokines measured. Compared to healthy women in the study, females with long COVID had similar reductions in cytokine activity as in the original analysis, which included both men and women.

The findings are based on a small sample size and should be replicated in a larger study, Planelles said. The study also did not determine if different strains of SARS-CoV2 had any influence on cytokines, nor did it account for possible regional differences in causes of long COVID.

“This study was conducted in Utah, a very specific area of the country,” Planelles said. “Perhaps in other geographical areas there may be other mechanisms leading to onset of long COVID. So, this could be one of the ways, but perhaps not the only way, that could lead to this persistent problem.”

In fact, Planelles notes that other scientists are looking at many different ways that autoimmunity, damaged tissue, or tiny blood clots can contribute to the onset of long COVID. In theory, these problems can arise independently or interact with each other to provoke lingering symptoms.


This work was supported by the University of Utah Inflammation, Immunology, and Infectious Diseases (3i) Initiative’s Emerging Infectious Diseases Fellowship (recipient, ESCPW) and by a seed grant from the University of Utah Vice President for Research and the Immunology, Inflammation, and Infectious Disease Initiative (recipient, VP). VP and MC were supported by NIH GRANT 5R01-AI143567.

Gun injuries in children spiked during the pandemic

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.

# # #

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.

Study: covid may increase risk of stroke in kids

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.


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.”

Research on long COVID in Utah

While most people who have had COVID-19 recover within a few weeks, as many as 1 in 3 people experience long term side effects of the disease. This is called “Long COVID.” Researchers are grappling with the unknowns of Long COVID: Why does it happen? Who does it happen to? How can we help those who have it?

Learn how researchers at University of Utah Health leverage a global crisis to make a tangible impact on lives in Utah and beyond.

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

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 Torri 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.

Headshot of

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.

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

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

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 Torri 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.

COVID-19 complications more likely in Black and Native American populations

Black people and Native Americans with health problems prior to contracting COVID-19 are more likely to have longer hospital stays, require treatment with a ventilator and have a higher risk of death than White people who have similar preexisting conditions, according to a new nationwide study led by University of Utah Health scientists.

The researchers say these results refute the notion that Black, Indigenous and People of Color are at greater risk of COVID-19 complications because they have one or more previous illnesses or diseases.

“Our findings contest arguments that Blacks and other racial and ethnic minorities are dying from COVID-19 at higher rates than their White counterparts because they have more comorbidities,” says Fares Qeadan, an assistant professor of biostatistics in the Division of Public Health and lead author of the study. “In fact, when we compared Blacks, Native Americans and Whites who had the same number of prior conditions, Blacks and Native Americans were still at higher risk of dying or being put on a ventilator.”

The study appears in Scientific Reports.

Preexisting conditions such as cancer, heart disease and obesity could be driving factors in higher risks for hospitalization, need for ventilation and death due to COVID-19, according to the Centers for Disease Control and Prevention. Blacks, Latinos and Native Americans all tend to also have more preexisting conditions than Whites. As a result, some researchers have suggested this could account for the higher rate—up to 3.7 times greater—of hospitalization and other COVID-19 complications among these racial and ethnic minority groups compared to Whites.

However, few studies have scrutinized whether populations with health disparities that have similar types of preexisting conditions as Whites have the same risk of COVID-19 complications. To address this concern, Qeadan and colleagues examined more than 52,000 medical records of patients who were diagnosed or who had tested positive for COVID-19.

Using a computerized analytical tool called the Elixhauser comorbidity index (ECI), they identified 31 common preexisting conditions that could contribute to COVID-19 complications. Each patient received a comorbidity score based on disease history and was then compared to patients with similar scores. This apples-to-apples approach, as well as multi-level regression models, allowed the researchers to more precisely identify differences in COVID comorbidities among racial and ethnic groups.

Specifically, compared with Whites, Blacks who had similar comorbidity scores had:

  • Longer hospital stays (1.22 days vs. 1.07 days)
  • Were more likely to be ventilator-dependent (85% more when the comorbidity score is low and 23% more when the score is high)
  • Were more likely to die (47% more when the comorbidity score is low and 13% more when the score is high)

Compared with Whites, Native Americans with similar comorbidity scores had:

  • Longer hospital stays (1.42 days vs. 1.07 days)
  • Higher odds of ventilator dependence across all comorbidity scores and
  • Higher odds of death (234% higher when the comorbidity score is low and 169% higher when the score is elevated)

The researchers note that their study only included patients who sought treatment for COVID-19. As a result, medically underserved and minority populations without health insurance may be underrepresented in this research. Differences in medical record coding within and between health care facilities also could have influenced these results.

“We hope the results of this study will help us better understand what’s going on in medical care that creates these disproportionalities,” says Elizabeth VanSant-Webb, a study co-author and project manager at the Sorenson Impact Center at University of Utah. “Hopefully, this will lead to better interventions to close the health care gap in this country.”

Moving forward, the researchers plan to potentially conduct a qualitative study to better explore patients’ experiences, provider behavior and hospital practices that may have contributed to these disparities.

“Our study did not explicitly examine the influence of social determinants of health such as structural racism, which could have contributed to the inequities we found,” says Charles R. Rogers, an assistant professor of Public Health and senior author of the study. “Decades before the pandemic, the value based on an individual simply because of the color of their skin has likely contributed to both poor health outcomes and health care access at alarmingly high rates for communities of color and warrants further investigation.”

The study, “Racial Disparities in COVID-19 Outcomes Exist Despite Comparable Elixhauser Comorbidity Indices between Blacks, Hispanics, Native Americans, and Whites,” appears in Scientific Reports. The V Foundation for Cancer Research, 5 for the Fight, Huntsman Cancer Institute and the National Cancer Institute partly supported the study financially. The content does not necessarily represent the official views of any of these entities and is solely the responsibility of the research team.

Evidence suggests COVID-19 isn’t sexually transmitted

COVID-19 is unlikely to be spread through semen, according to University of Utah Health scientists who participated in an international study of Chinese men who recently had the disease. The researchers found no evidence of the virus that causes COVID-19 in the semen or testes of the men.

The study was not comprehensive enough to fully rule out the possibility that the disease could be sexually transmitted. However, the chances of it occurring, based on this limited finding, appear to be remote.

“The fact that in this small, preliminary study that it appears the virus that causes COVID-19 doesn’t show up in the testes or semen could be an important finding,” says James M. Hotaling, M.D., a co-author of the study and a U of U Health associate professor of urology specializing in male fertility. “If a disease like COVID-19 were sexually transmittable that would have major implications for disease prevention and could have serious consequences for a man’s long-term reproductive health.”

The study appears in Fertility & Sterility, a peer-reviewed journal published by the American Society of Reproductive Medicine.

The international team of researchers from China and the United States launched the study in response to concerns that SARS-CoV-2, the virus that causes COVID-19, could be sexually transmitted like Ebola, Zika and other emerging viral pathogens. To find out, they collected semen samples from 34 Chinese men one month (on average) after they were diagnosed with mild to moderate cases of COVID-19. Laboratory tests did not detect SARS-CoV-2 in any of the semen samples.

But just because the virus wasn’t present in the existing semen didn’t necessary rule out that it hadn’t entered the testes where sperm cells are formed.

“If the virus is in the testes but not the sperm it can’t be sexually transmitted,” says Jingtao Guo, Ph.D., a postdoctoral scientist at the Huntsman Cancer Institute at the University of Utah who also co-authored the study. “But if it is in the testes, it can cause long-term damage to semen and sperm production.”

To sort this part of the puzzle out, the researchers analyzed a dataset generated from a single cell mRNA atlas from healthy young organ donors that was available from prior work. This atlas allows them to examine mRNA, the genetic material used to make proteins, in any single testicular cell. In this case, scientist used it to examine the expression of a pair of genes associated with SARS-CoV-2. These two genes, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) act as receptors, allowing SARS-CoV2 to penetrate cells and replicate. In order for the virus to access cells effectively, both receptors must be present in the same cell.

When the scientists examined the dataset, they found that genes encoding these two proteins were only found in four of the 6,500 testicular cells, suggesting that SARS-CoV-2 is unlikely to invade human testicular cells, Guo says

Despite these findings, the researchers acknowledge that their study has several important limitations including a small sample size and the fact that none of the donors had been severely ill with COVID-19.

“It could be that a man who is critically ill with COVID-19 might have a higher viral load, which could lead to a greater likelihood of infecting the semen. We just don’t have the answer to that right now,” Hotaling says. “But knowing that we didn’t find that kind of activity among the patients in this study who were recovering from mild to moderate forms of the disease is reassuring.”

However, Hotaling warns that intimate contact can still increase the risk of spreading the disease through coughing, sneezing and kissing. In addition, some infected people are asymptomatic and can appear healthy, even as they pass the virus along to others.

In addition to Drs. Hotaling and Guo, other U of U Health researchers involved in this study titled, “No Evidence of SARS-CoV-2 in Semen of Males Recovering from COVID-19,” were Darshan  Patel, MD, and Adam Spivak, MD. The research was supported by the National Natural Science Foundation of China and the Huazhong University of Science & Technology.

See original press release here.

Amniotic fluid could reduce symptoms, long-term risks of COVID-19

Amniotic fluid, the clear liquid that helps nourish and protect fetuses before birth, isn’t just for babies. In fact, for nearly 100 years, doctors have used the mixture to help heal skin wounds, burns, and leg ulcers as well as provide protection for surgical adhesions.

Now, in a first-of-its-kind effort, University of Utah Health researchers are investigating whether human amniotic fluid (HAF) can reduce lung inflammation caused by COVID-19 and promote the recovery of patients who have contracted the disease.

“If successful, our research could shorten or mitigate the intensity of COVID-19 and have a lot of downstream effects including reducing the need for critical care, improving patient outcomes, and getting them home faster,” says Craig Selzman, MD, the study’s senior investigator and chief of U of U Health’s Division of Cardiothoracic Surgery.

Selzman and his colleagues first became interested in amniotic fluid as a possible treatment for COVID-19 after reading about a small study conducted in China. The study found that four pregnant women who were ill with the virus gave birth to healthy babies who didn’t have any covid-19 symptoms.

Intrigued, Selzman’s team, working in conjunction with the School of Medicine’s Cell Therapy and Regenerative Medicine program, treated 10 COVID-19 patients with HAF. Preliminary results in this small group suggest there was a 40% reduction of inflammation in some patients’ lungs. This reduction was measured by changes in C-reactive protein (CRP), a substance produced in the liver that is considered a biomarker of body’s inflammatory response.

“Theoretically, amniotic fluid is probably halting the progression of the disease by impeding its ability to cause inflammatory responses in the heart, lungs and other organs,” Selzman says.

But why HAF, which is composed of a mixture of electrolytes (salts), proteins, carbohydrates, lipids and urea, triggered this effect still isn’t clear and will required additional study.

In the meantime, Selzman and his colleagues are getting ready to conduct a phase 2 clinical trial involving 60 COVID-19 patients with varying severity of the illness. Half will receive HAF treatment; the other 30 will get standard care.

In addition to monitoring the patients for acute symptoms, the researchers hope HAF treatment will diminish the risk that these patients will develop pulmonary fibrosis (scarring and stiffening of the lungs) and other chronic respiratory conditions.

“If we can halt this inflammatory process early on, we could actually prevent the onset of advance lung disease in the months and years ahead,” Selzman says. “So, it’s not just trying to get people better right now. It’s also trying to stave off what could be long-term consequences of this viral infection.”

This research is supported, in part, by the University of Utah’s Immunology, Inflammation & Infectious Disease Initiative (3i) See original press release here.