Observatory and Fast Facts

Dec. 22, 2021

Severe COVID tied to high risk of death, mostly by other causes, within year

Survivors of severe COVID-19 — especially those younger than 65 years — may be at more than twice the risk of dying within the next year than those who had mild or moderate illness or were never infected, finds a study in Frontiers in Medicine, according to a news release from the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota.

Another finding of the analysis of electronic health records of 13,638 patients who tested positive or negative for COVID-19 is that only 20% of those who had severe COVID-19 (requiring hospitalization) and died did so because of complications of their infection, such as abnormal blood clotting, respiratory failure, or cardiovascular problems. Rather, 80% were due to different reasons typically considered unrelated to COVID-19.

Of all patients, 178 had severe COVID-19, while 246 were mildly or moderately ill, and the rest tested negative. Among all patients, 2,686 died within 12 months of their COVID-19 diagnosis.

Relative to uninfected patients, those recovered from severe COVID-19 younger than 65 years had a 233% increased risk of dying in the next year. The increased risk was greater than that of survivors of severe COVID-19 who were 65 years or older.

The finding that most deaths were not due to COVID-19 complications suggests that the health of these patients had declined since their initial diagnosis, leaving them susceptible to different medical conditions.

COVID-19 infection rewires immunity “pathways” in pregnant mothers, affecting newborns’ immune systems

New UCLA-led research finds that severe COVID-19 illness during pregnancy triggers an inflammatory “cascade” that may lead to damage associated with the disease — and which, in turn, may alter the infants’ own immune system, according to a news release.

The findings, published in Cell Reports Medicine, may explain why COVID-19 during pregnancy can cause severe, damaging disease, said Karin Nielsen, Professor of Pediatrics in the Division of Infectious Diseases at the UCLA David Geffen School of Medicine. These findings also demonstrate the impact COVID-19 can have on infants born to women who had the infection during pregnancy, even when the infants are not infected with the virus.

The researchers focused on cellular proteins called cytokines, which are important components of the immune system. Chemokines are a type of cytokine that guide white blood cells to the site in need of repair. Levels of these proteins are in balance in healthy bodies, but in the presence of COVID-19, some cytokines are triggered, and others silenced in a process called upregulation or downregulation.

The researchers tested 93 mothers infected with COVID-19 and 45 of their infants at day 1 that were exposed in the womb using next generation sequencing (NGS)-based Olink proteomic profiling. This NGS technology enabled screening of nearly 1,500 cytokines, thus identifying alterations in immune system proteins and pathways.

They found that severe COVID-19 appears to rewire the immune systems in mothers and their newborns. In mothers with severe disease, COVID-19 upregulated and downregulated specific cytokines during pregnancy and delivery. These inflammatory “pathways,” as they are called, are associated with liver and heart disease. In addition, infants born to mothers with severe COVID-19 had inflammatory profiles, identified by the presence of specific cytokines and chemokines, which were different from those normally found in newborns.

These altered cytokine levels are usually present in infants with respiratory problems and, in some cases, poor neurodevelopment. The researchers did not find these immune alterations in infants born to mothers who were infected but asymptomatic or who had mild to moderate COVID-19 disease.

Study shows COVID-19-related brain complications

A multi-institutional international study on brain complications of COVID-19 has found that approximately one in 100 patients hospitalized with COVID-19 will likely develop complications of the central nervous system. These can include stroke, hemorrhage, and other potentially fatal complications, according to a news release from the Radiological Society of North America (RSNA).

“Much has been written about the overall pulmonary problems related to COVID-19, but we do not often talk about the other organs that can be affected,” said Scott H. Faro, MD, FASFNR, Professor of Radiology and Neurology and Director of the Division of Neuroradiology/Head & Neck Imaging at Thomas Jefferson University in Philadelphia.

To derive a more complete picture, Faro and his colleagues analyzed nearly 40,000 cases of hospitalized COVID-19 positive patients from seven U.S. and four western European university hospitals. The patients had been admitted between September 2019 and June 2020. Their average age was 66 years old, and there were twice as many men as women.

The most common cause of admission was confusion and altered mental status, followed by fever. Many of the patients had comorbidities like hypertension, cardiac disease, and diabetes.

There were 442 acute neuroimaging findings that were most likely associated with the viral infection. The overall incidence of central nervous system complications in this large patient group was 1.2%.

The most common complication was ischemic stroke, with an incidence of 6.2%, followed by intracranial hemorrhage (3.72%) and encephalitis (0.47%), an inflammation of the brain.

The researchers also discovered a small percentage of unusual findings, such as acute disseminating encephalomyelitis, an inflammation of the brain and spinal cord, and posterior reversible encephalopathy syndrome, a syndrome that mimics many of the symptoms of a stroke.

Diverse genome sequences provide a tool for studying heart disease risk

In a large-scale study of people from diverse ancestries, researchers narrowed down the number of genomic variants that are strongly associated with blood lipid levels and generated a polygenic risk score to predict elevated low-density lipoprotein cholesterol levels, a major risk factor for heart disease, according to a news release from the National Institutes of Health (NIH).

The study, published in the journal Nature, was led by the Global Lipids Genetics Consortium. The authors include researchers at the National Human Genome Research Institute (NHGRI), part of NIH.

Lipids are fat-like substances that can be found in blood and body tissues. They come in two major forms - cholesterol and triglycerides. Humans need a certain amount of lipids in the body for normal function, but elevated lipid levels may increase the risk of developing a heart condition. Polygenic risk scores provide an estimate of an individual’s risk for specific diseases, based on their DNA changes related to those diseases.

“Finding the set of genomic variants that are important for this trait is key for us to understand the biology and identify new drug targets,” said Cristen Willer, PhD, Professor of Human Genetics at the University of Michigan. “These genomic variants then inform how well polygenic risk scores work to determine risk for such diseases.”

Since the field’s inception, the genomics community has performed over 6,000 studies looking at the association of specific genomic variants and cardiovascular disease. However, the design of these studies overwhelmingly included individuals from European ancestral populations.

To address this issue, researchers accumulated data from 201 previous genome-wide association studies, including about 1.65 million individuals from five ancestral groups: African, East Asian, European, Hispanic, and South Asian. About 1.32 million of those studies were from European ancestry, and the remaining 350,000 were non-European. The studies contained data on blood levels of the different classes of cholesterol and triglycerides.

The research group calculated the polygenic risk scores using data from each of the different ancestral groups, either separately or all together. Then, they tested the risk scores in a diverse set of studies, including Africans enrolled from Ghana, Kenya, and Nigeria as part of the Africa America Diabetes Mellitus study.

The results showed a polygenic risk score that includes diverse genomic data is much more predictive of whether a person of any ancestry will have elevated low-density lipoprotein cholesterol levels than a score that only includes European genomic data. 

Pathologists find evidence of pre-existing chronic lung disease in people with long COVID

Researchers at University of Michigan Health, part of Michigan Medicine, are examining lung biopsies from patients living with persistent respiratory symptoms, such as shortness of breath, to help better define the pattern of damage associated with COVID-19. Their work has led to a surprising finding: some patients’ symptoms could be due to damage that existed before getting COVID-19, according to a news release from the academic medical center.

Jeffrey Myers, MD, Professor of Anatomic Pathology, along with Kristine E. Konopka, MD, Associate Professor of Thoracic Pathology, and their Department of Pathology team, examined lung biopsies from 18 living patients who had ongoing respiratory symptoms or abnormal CT scans after recovering from COVID-19. Five patients were reported to have lung disease prior to their COVID-19 diagnosis. Fourteen patients had what is known as ground glass opacities on radiological scans, areas of the lungs that appear as a cloudy gray color as opposed to the dark color of normal air-filled lungs, on a chest X-ray or CT scan.

The most common finding in this set of patients was a condition known to pathologists as usual interstitial pneumonia, or UIP, also known clinically as idiopathic pulmonary fibrosis, or IPF, a well-studied chronic lung disease. IPF is the most common type of pulmonary fibrosis and causes scarring and stiffening of the lungs.

UIP/IPF is a progressive disease that gets worse with time and an infection, such as with SARS-CoV-2, can lead to accelerated illness or even death, what is known as an acute exacerbation of IPF, explained Myers. “SARS-CoV-2 comes along and does to the lung, from a pathology perspective, exactly what happens with an acute exacerbation.”

Biopsies from these patients show evidence of the underlying pre-existing lung scarring with, layered on top, evidence of diffuse alveolar damage, a pattern of lung tissue damage commonly seen in patients with acute respiratory distress syndrome of any cause.