Interim data from early US COVID-19 hotspot show mortality of disease were not associated with race/ethnicity

A study of interim data from two hospitals in an early US COVID-19 hotspot, to be presented at the ESCMID Conference on Coronavirus Disease (ECCVID, held online 23-25 September), shows that race and ethnicity were not significantly associated with higher in-hospital COVID-19 mortality, and that rates of moderate, severe, and critical forms of COVID-19 were similar between racial and ethnic groups.

The study, by Dr. Daniel Chastain (University Of Georgia College Of Pharmacy, Albany, GA, U.S.) and colleagues included data from adult patients hospitalised between March 10 and and May 22 with COVID-19, defined by laboratory-detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, in Southwest Georgia.

The authors compared severity of illness categories on presentation to the hospital between patients from different racial and ethnic groups based on criteria from the US National Institutes of Health (NIH) COVID-19 treatment guidelines. They also studied outcomes including comorbidities, laboratory values, vital signs, and in-hospital mortality.

A total of 164 randomly selected non-consecutive patients were included with a median age of 61.5 years. These consisted of 119 African American patients, 36 Caucasian patients, and 9 Latinx patients. Thus the majority were African American (73%) and 51% were female. Rates of moderate, severe, and critical COVID-19 did not significantly differ between African American (9%, 56%, and 35%), Caucasian (0%, 69%, and 31%), and Latinx patients (0%, 56%, and 44%). In-hospital mortality was not statistically significantly different between groups but was highest among Caucasians (31%) followed by Latinx (22%) and African Americans (16%).

Caucasian patients had significantly higher Charlson comorbidity index scores (meaning more underlying conditions) (4.5) compared to African American (4) and Latinx (2) patients, while median BMI was significantly higher in African Americans (33.7 kg/m2) than in Caucasians (26.9) or Latinx patients (25.9).

Duration of time from symptom onset to admission was similar between groups, whereas median temperature on admission was significantly higher in African Americans (38.3C) than in Caucasians (37.9) or Latinx patients (37.8)

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Risk gene for Alzheimer’s has early effects on the brain

A genetic predisposition to late-onset Alzheimer’s disease affects how the brains of young adults cope with certain memory tasks. Researchers from the German Center for Neurodegenerative Diseases (DZNE) and the Ruhr-Universität Bochum report on this in the scientific journal Current Biology. Their findings are based on studies with magnetic resonance imaging in individuals at the age of about 20 years. The scientists suspect that the observed effects could be related to very early disease processes.

The causes for Alzheimer’s in old age are only poorly understood. It is believed that the disease is caused by an unfavorable interaction of lifestyle, external factors and genetic risks. The greatest genetic risk factor for late-onset Alzheimer’s disease stems from inherited mutations affecting “Apolipoprotein E” (ApoE), a protein relevant for fat metabolism and neurons. Three variants of the ApoE gene are known. The most common form is associated with an average risk for Alzheimer’s. One of the two rarer variants stands for an increased risk, and the other for a reduced risk.

“We were interested in finding out whether and how the different gene variants affect brain function. That is why we examined the brains of young adults in the scanner while they had to solve a task that challenged their memory,” explained Dr. Hweeling Lee, who led the current study at the DZNE in Bonn.

Distinguishing similar events

The group of study participants comprised of 82 young men and women. They were on average 20 years old, and all of them were university students considered to be cognitively healthy. According to their genotype for ApoE, 33 of them had an average, 34 an increased and 15 a reduced risk of developing Alzheimer’s disease at a late age. During the study in the brain scanner, all individuals were presented with more than 150 successive images displayed on a monitor. These were everyday objects such as a hammer, a pineapple or a cat. Some pictures were repeated after a while, but sometimes the position of the displayed objects on the screen had changed. The study participants had to identify whether an object was “new” or had been shown before—and if so, whether its position had shifted.

“We tested the ability to distinguish similar events from one another. This is called pattern separation,” said Hweeling Lee. “In everyday life, for example, it’s a matter of remembering whether a key has been placed in the left or right drawer of a dresser, or where the car was parked in a parking garage. We simulated such situations in a simplified way by changing the position of the depicted objects.”

High-resolution through modern technology

Simultaneously to this experiment, the brain activity of the volunteers was recorded using a technique called “functional magnetic resonance imaging”. Focus was on the hippocampus, an area only a few cubic centimeters in size, which can be found once in each brain hemisphere. The hippocampus is considered the switchboard of memory. It also belongs to those sections of the brain in which first damages occur in Alzheimer’s disease.

When measuring brain activity, the scanner was able to show its full potential: It was an “ultra-high field tomograph” with a magnetic field strength of seven Tesla. Such devices can achieve a better resolution than brain scanners usually used in medical examinations. This enabled the researchers to record brain activity in various sub-fields of the hippocampus with high precision. “Up to now, there were no comparable studies with such level of detail in ApoE genotyped participants. This is a unique feature of our research,” said Hweeling Lee.

No differences in memory performance

There were no differences between the three groups of subjects with regard to their ability for pattern separation. “All study participants performed similarly well in the memory test. It did not matter whether they had an increased, reduced or average risk for Alzheimer’s disease. Such results are certainly to be expected in young healthy people,” said Nikolai Axmacher, Professor of Neuropsychology at the Ruhr-Universität Bochum, who was also involved in the current study. “However, there were differences in brain activity. The different groups of study participants activated the various subfields of the hippocampus in different ways and to varying degrees. Their brains thus reacted differently to the memory task. In fact, we saw differences in brain activation not only between people with average and increased risk, but also between individuals with average and reduced risk.”

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Genetic mutations may be linked to infertility, early menopause

A new study from Washington University School of Medicine in St. Louis identifies a specific gene’s previously unknown role in fertility. When the gene is missing in fruit flies, roundworms, zebrafish and mice, the animals are infertile or lose their fertility unusually early but appear otherwise healthy. Analyzing genetic data in people, the researchers found an association between mutations in this gene and early menopause.

The study appears Aug. 28 in the journal Science Advances.

The human gene—called nuclear envelope membrane protein 1 (NEMP1)—is not widely studied. In animals, mutations in the equivalent gene had been linked to impaired eye development in frogs.

The researchers who made the new discovery were not trying to study fertility at all. Rather, they were using genetic techniques to find genes involved with eye development in the early embryos of fruit flies.

“We blocked some gene expression in fruit flies but found that their eyes were fine,” said senior author Helen McNeill, Ph.D., the Larry J. Shapiro and Carol-Ann Uetake-Shapiro Professor and a BJC Investigator at the School of Medicine. “So, we started trying to figure out what other problems these animals might have. They appeared healthy, but to our surprise, it turned out they were completely sterile. We found they had substantially defective reproductive organs.”

Though it varied a bit by species, males and females both had fertility problems when missing this gene. And in females, the researchers found that the envelope that contains the egg’s nucleus—the vital compartment that holds half of an organism’s chromosomes—looked like a floppy balloon.

“This gene is expressed throughout the body, but we didn’t see this floppy balloon structure in the nuclei of any other cells,” said McNeill, also a professor of developmental biology. “That was a hint we’d stumbled across a gene that has a specific role in fertility. We saw the impact first in flies, but we knew the proteins are shared across species. With a group of wonderful collaborators, we also knocked this gene out in worms, zebrafish and mice. It’s so exciting to see that this protein that is present in many cells throughout the body has such a specific role in fertility. It’s not a huge leap to suspect it has a role in people as well.”

To study this floppy balloon-like nuclear envelope, the researchers used a technique called atomic force microscopy to poke a needle into the cells, first penetrating the outer membrane and then the nucleus’s membrane. The amount of force required to penetrate the membranes gives scientists a measure of their stiffness. While the outer membrane was of normal stiffness, the nucleus’s membrane was much softer.

“It’s interesting to ask whether stiffness of the nuclear envelope of the egg is also important for fertility in people,” McNeill said. “We know there are variants in this gene associated with early menopause. And when we studied this defect in mice, we see that their ovaries have lost the pool of egg cells that they’re born with, which determines fertility over the lifespan. So, this finding provides a potential explanation for why women with mutations in this gene might have early menopause. When you lose your stock of eggs, you go into menopause.”

McNeill and her colleagues suspect that the nuclear envelope has to find a balance between being pliant enough to allow the chromosomes to align as they should for reproductive purposes but stiff enough to protect them from the ovary’s stressful environment. With age, ovaries develop strands of collagen with potential to create mechanical stress not present in embryonic ovaries.

“If you have a softer nucleus, maybe it can’t handle that environment,” McNeill said. “This could be the cue that triggers the death of eggs. We don’t know yet, but we’re planning studies to address this question.”

Over the course of these studies, McNeill said they found only one other problem with the mice missing this specific gene: They were anemic, meaning they lacked red blood cells.

“Normal adult red blood cells lack a nucleus,” McNeill said. “There’s a stage when the nuclear envelope has to condense and get expelled from the young red blood cell as it develops in the bone marrow. The red blood cells in these mice aren’t doing this properly and die at this stage. With a floppy nuclear envelope, we think young red blood cells are not surviving in another mechanically stressful situation.”

The researchers would like to investigate whether women with fertility problems have mutations in NEMP1. To help establish whether such a link is causal, they have developed human embryonic stem cells that, using CRISPR gene-editing technology, were given specific mutations in NEMP1 listed in genetic databases as associated with infertility.

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Early government intervention is key to reducing the spread of COVID-19

Early and strict governmental intervention is a key factor in reducing the spread of COVID-19 cases. That’s the conclusion reached by a team of researchers comparing outbreaks of the novel coronavirus between the Chinese province of Hunan and Italy in a new paper published in Frontiers in Medicine.

While Hunan and Italy are similar in population size—about 60-70 million people each—the scope of the epidemic in each location has differed dramatically. At time of publication, Italy has the second-most confirmed deaths after the United States and ranks third in total confirmed infections, according to the Johns Hopkins University Coronavirus Resource Center. There are just over 1,000 confirmed cases in Hunan.

The research team, based in China, used data from the John Hopkins database through April 2 to map infection trends in both Hunan and Italy. They modified a standard mathematical model known as a susceptible-infected-removed (SIR) model to account for the effects of different epidemic prevention measures at different periods in time.

“It should be noted that in actual situations, the speed of transmission can be changed through many interventions, such as personal protective measures, community-level isolation and city blockade,” said lead author Dr. Wangping Jia with the Chinese PLA General Hospital in Beijing.

The paper’s extended SIR (eSIR) model found that under current measures there could be a total of 3,369 (the mean in a possible range of 840-8,013) infected cases in Hunan, with the endpoint of the epidemic having already occurred around March 3. In contrast, total infected cases in Italy are projected to be 182,051 (the mean in a possible range of 116,114-274,378) with an end date around August 6.

The authors speculated that the disparate trends could be due to a couple of reasons. For instance, Italy may not have implemented preventive measures soon enough, as the eSIR model demonstrated that taking action earlier in the case of Hunan drastically reduced infection rates.

The authors noted that “from China’s experience, various control measures, including the early detection and isolation of individuals with symptoms, traffic restrictions, medical tracking, and entry or exit screening, can well prevent the further spread of COVID-19.”

The paper did not specifically address mortality rates because a number of factors can affect these predictions, according to Jia, such as bed capacity of intensive care units, as well as a patient’s age, sex and any underlying health conditions such as cardiovascular disease, hypertension and diabetes.

“Accurate patient-specific data are urgent needs for the prediction of the total deaths,” he said.

The Italian government recently announced it would begin to ease lockdown measures beginning May 4—three months earlier than the eSIR model advises.

“We think it is too early to ease restrictions starting around May 4,” Jia said. “The potential second wave may come if restrictions are eased three months earlier. Italy is not in the end period of the COVID-19 epidemic.”

The authors concede that the current study has several limitations. First, due to the limited amount of testing, it’s likely the number of infected people in Italy and elsewhere is higher than the official count. The eSIR model does not incorporate the disease’s incubation period, which could make it less accurate. And there may be other factors that could throw off the estimate, such as the influence of “super spreaders” of the disease on a population.

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