Tag: 28/4/21

Earlier, Improved MRI Detects ‘Broken-heart’ Syndrome

A new study from Karolinska Institutet in Sweden suggests that early magnetic resonance imaging (MRI) of the heart can greatly increase the rate of diagnosis of broken-heart syndrome, which can happen when there is no obvious cause in the coronary artery. 

Myocardial infarction is typically caused by a blockage of the coronary artery by a blood clot. However, in up to 10% of all myocardial infarctions, no obvious cause in the coronary artery is found, and so the working diagnosis MINOCA (myocardial infarction with non-obstructive coronary arteries) is given, which can subsequently lead to one of several diagnoses.

Most of these patients are women, many of whom are diagnosed with takotsubo cardiomyopathy (broken-heart syndrome), characterised by reduced heart function that is likely stress-related, presenting the same symptoms as a standard heart attack.

“Around 80 to 90% of broken-heart sufferers are women, and the disease is associated with mental stress,” said principal investigator Per Tornvall, senior physician and professor at the Department of Clinical Science and Education, Stockholm South General Hospital, Karolinska Institutet. “There also seems to be a link to hypersensitivity towards stress caused by low estrogen levels. Unfortunately, research on the investigation and treatment of myocardial infarction is often done on men, while female heart disease is less studied.”

In a prior study with 150 patients, cardiovascular magnetic resonance (CMR) is often done when examining patients with MINOCA. CMR conducted approximately 10 days after onset can result in a diagnosis in under half the patients, normally takotsubo or myocarditis (inflammation of the heart muscle), Now, the same researchers have tested a new, more sensitive CMR technique two to four days after onset on a comparable group of 148 patients. They found that 77% of the patients could be diagnosed: 35% of takotsubo and 17% of myocardial inflammation, compared with 19 and 7%, respectively, in the first study.

“We don’t know how much effect the improved CMR technique has, but the results suggest that with early examination more patients can get a correct diagnosis and therefore the right treatment,” says Professor Tornvall. “The next step is for us to develop the CMR examination with pharmacological stress of the heart. This will enable us to study the smallest of the blood vessels and hopefully find a cause for the 23% who received no diagnosis.”

Source: Medical Xpress

Journal information: Peder Sörensson et al. Early Comprehensive Cardiovascular Magnetic Resonance Imaging in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries, JACC: Cardiovascular Imaging (2021). DOI: 10.1016/j.jcmg.2021.02.021

Treatment of Lingering COVID Pain is Challenging

The treatment of pain in recovered COVID patients poses unique challenges, said a pain expert presenting at the American Academy of Pain Medicine virtual meeting.

“A lot of these patients are going to need rehabilitation” or physical therapy, noted Natalie Strand, MD, of the Mayo Clinic in Scottsdale, Arizona, at the meeting. “There can be quite a bit of deconditioning that occurs, especially after a prolonged ICU stay. Neuropathic pain is also quite common.”

Post-COVID neuropathy may be viral or else possibly related to patient positioning, including prone positioning. Some patients “may need short-term opioids or gabapentinoids and they may experience aggravation of prior underlying pain, either due to direct physical causes or to the increase in anxiety and depression that can accompany a COVID infection,” Dr Strand said.

A study that followed 143 patients two months after acute COVID showed a high proportion reported persistent symptoms — including fatigue (53%), joint pain, (27%) and chest pain (22%) — that often results in patients going to a pain clinic for care, she noted.

Persistent pain remains prevalent, following any ICU admission, ranging from 28% to 77%, according to Dr Strand.

Chronic neuropathic pain after a COVID patient’s ICU stay can include muscle pain related to joint contractures or muscle atrophy, and pain due to critical illness myopathy or polyneuropathy. In addition, peripheral nerve injuries have been associated with prone positioning for COVID–related acute respiratory distress syndrome, Dr Strand added. Complications from traumatic procedures like placement of chest tubes or tracheotomy can also cause chronic neuropathic pain.

Dr Strand noted that pain can persist after discharge of COVID patients, as indicated by follow-ups. In China, three-quarters of patients previously hospitalised with COVID continued to report at least one symptom 6 months later, with fatigue or muscle weakness by far the most common symptoms (63%). “Compared with 2-month follow up, 6 months later we see the same trends,” she pointed out.

In that study, “13% of the patients who did not develop an acute renal injury during their hospital stay and presented with normal renal function exhibited a decline in GFR at follow up,” Dr Strand noted. This may signal caution about using NSAIDS to manage pain in some patients, she said: “Normal renal function at discharge does not necessarily mean it will remain this way 6 months afterwards.”

There may be a relationship with the SARS-CoV-2 virus and chronic neuropathic pain, Strand observed. In a recent article in Pain Reports, “the authors concluded it could be direct or indirect effects of the virus on the nervous system that can cause neuropathic pain,” she noted. “We know that there are neuropathic symptoms involved with the famous loss of taste and loss of smell with presentation,” she continued. “But also in the acute phase, we commonly see headache, dizziness, muscle pain, ataxia, and in hospitalized patients we see stroke, meningitis, encephalitis, and autoimmune disorders like Guillain-Barré syndrome and acute disseminated encephalomyelitis.”

Psychological stressors can also be related to the emergence of chronic pain, added Dr Strand. “Anxiety and depression often follows COVID-19 infection,” she said. “It may be wise to screen our patients for anxiety and depression after infection to see if we can further control these components to help manage their pain overall.”

Source: MedPage Today

Presentation information: Strand NH “Treating the COVID-Recovered Patient: An Evolving Understanding” AAPM 2021.

Girls at Almost Double The Risk of Concussion in American Football

In high school American football, girls are at nearly double the risk of concussion compared to boys, according to a new study. Girls are also less likely to be removed from play and take longer to recover from the injury than their male counterparts.

Researchers at the University of Pennsylvania and Michigan State University along with Prof Willie Stewart, Honorary Professor at the University of Glasgow reviewed three years of injury data for a population of around 40 000 female high school American footballers in the Michigan High School Athletic Association, comparing them to a similar number of their male counterparts.

They found that, as seen in previous studies, the risk of sports related concussion among female footballers was 1.88 times higher than among males. The researchers also identified several sex-associated differences in sports concussion mechanism and management. This provides new insight into this kind of injury in this demographic. 

Male footballers tended to be injured in collisions with another player and were 1.5 times more likely than females to be removed from play on the day of injury. Female footballers were most often injured from impacts involving equipment, such as the ball or a goalpost, and also took on two days longer on average to recover from injury and return to play. A recent study however showed no differences for concussion recovery time among male and female college athletes, but there could be differences depending on the type of sport.

These sex-associated differences among teenage athletes in mechanism of injury and in management and outcomes of concussion raise the question of whether sports should consider the adoption of sex specific approaches to both participation and concussion management.

Lead author Dr Abigail Bretzin, postdoctoral fellow and certified athletic trainer at the University of Pennsylvania, said: “This is the first study to look in this detail at sex-associated differences in concussion management and outcomes in teenage footballers. Our findings add to research showing that female athletes are at increased concussion risk compared to male athletes, and highlight the importance of sex-specific research in this field.”

Senior author Prof Stewart, said: “Given we know the importance of immediate removal from play for any athlete with suspected concussion, it is notable that “if in doubt, sit them out” appears more likely to happen for boys than girls. This, together with the finding that mechanism of injury appears different between boys and girls, suggests that there might be value in sex-specific approaches to concussion education and management in this age group.”

Source: Medical Xpress

Journal information: Abigail C. Bretzin et al. Association of Sex With Adolescent Soccer Concussion Incidence and Characteristics, JAMA Network Open (2021). DOI: 10.1001/jamanetworkopen.2021.8191

Trump Encouraged to Urge Followers to Take Vaccine

As US polls show that half of Republicans voters are reluctant to get a COVID vaccine, two former senior Trump administration officials have said that former US President Donald Trump is being encouraged to urge his followers to get the jab. 

The officials stressed that herd immunity could be threatened by Republican vaccine hesitancy, and that Trump’s followers will listen to him and him alone.

“Vaccines are widely regarded as one of Trump’s greatest accomplishments, and Trump understands that this legacy is at risk because half of his supporters are not taking the vaccine,” one of the officials told CNN. “It’s just not clear yet if he understands that he’s the only one who can fix this.”

The other official concurred. “In Trump country, if you want to call it that, there are still significant numbers of people who aren’t sure [COVID] is a real thing, despite folks getting sick, and there are lots of suspicions about the vaccine,” the source said. “They have literally said to me, ‘I want to hear from the president about this.’ I don’t think they’re going to listen to anyone else.”

Trump told Fox News last week that he would make a “commercial” about the vaccine, but did not make a firm commitment.
However, a person close to Trump disagreed he should take this approach. “He shouldn’t be pushing these vaccines. His posse isn’t exactly vaccine-approving and it could backfire,” the person said.

All the living former presidents save for Trump, and their wives, appeared in an ad campaign started last month encouraging vaccination – though Trump’s team denied he was approached to participate. This was because the team that organised the PSA did not think it was likely he would participate, according to a source close to that project.

In the Fox interview, Trump said, “I encourage them to take it. I do,” referring to his supporters, but has only spoken out a few times about vaccination.

Fifty-four percent of Republicans are either hesitant about or opposed to getting a COVID vaccine, according to a March survey by the Kaiser Family Foundation, and 29% said they would not get a vaccine under any circumstances.

The number of people 18 and over with at least one vaccine dose, the top 10 states are all states President Joe Biden won last November. Trump won 9 out of the bottom 10 states for vaccination.

A third former Trump official confided that as early as last summer, there were already concerns over Republican vaccine refusal.

“On Facebook I saw a ton of hesitancy for that group — just insane amounts of hesitancy already and we knew it was just going to get worse,” the official said.

That official said Trump ally Michael Caputo briefly mentioned to Trump last fall that it would be good for the president to do a vaccine PSA after the election.

One of the other former officials noted that recently, Caputo “in particular has been active in discussing” the possibility of doing a PSA with the Trump team.

“Michael takes this very seriously and sees this as a big public health problem,” said the source. “His stepping out, because he’s so connected to the president, is really going to be forceful and incredibly helpful.”

Mr Caputo served as assistant secretary for public affairs at the US Department of Health and Human Services, leaving after being diagnosed with throat cancer and a rant at heath scientists saying they were undermining Trump.

Mr Caputo confirmed to CNN that he met with Trump and the two men “spoke about vaccine hesitancy and what can be done about it.”

Trump’s final year in office will define his legacy, according to historians, which was marred by the failure to contain COVID and his incitement of a mob that stormed the US Capitol.

The former  officials said they don’t want to see the vaccine development that Trump pushed undone by vaccine hesitancy, including among his own supporters.

“I see Operation Warp Speed tipping towards failure, and it really concerns me,” one of the senior officials warned. “If we don’t move half those people into the vaccinated column, we’re most likely not going to reach community immunity, and if we don’t reach it, then the president’s vaccine legacy is dead.”

The other senior official said Trump supporters would respond positively to the former president “taking ownership of Operation Warp Speed” and mentioning that he and his wife were both vaccinated.

“He could talk about how [vaccine uptake] is the way to get the country back to where it needs to be economically and socially, using his language that he uses with his supporters. I think that would be really powerful,” said the source.

Source: CNN

‘Nanotraps’ Capture COVID Virus and Prevent Infection

Researchers have developed an entirely new treatment for COVID: ‘Nanotraps’ that capture the viruses inside the body, allowing the immune systems to destroy them

The “Nanotraps” mimick the human cells the virus normally attaches to, and bind it to their surface, keeping the virus from reaching other cells and target it for destruction by the immune system. It is possible that Nanotraps could be used on SARS-CoV-2 variants, and could be administered as a nasal spray.

“Since the pandemic began, our research team has been developing this new way to treat COVID-19,” said Assistant Professor Jun Huang, whose lab led the research. “We have done rigorous testing to prove that these Nanotraps work, and we are excited about their potential.”

Postdoc Min Chen and graduate student Jill Rosenberg targeted the spike mechanism that SARS-CoV-2 uses to lock onto ACE2 proteins on human cells.

To create a trap that would bind to the virus in the same way, they designed nanoparticles with a high density of ACE2 proteins on their surface. Other nanoparticles were designed with neutralising antibodies on their surfaces.

ACE2 proteins and neutralising antibodies have both been used in COVID treatments, but by mounting them onto nanoparticles, a much more effective and robust means for trapping the virus was created.

The nanoparticles are smaller than cells, 500 nanometres in diameter, allowing them to reach deep inside tissue and trap the virus.

No evidence of toxicity was seen in tests with mice, and they then tested the Nanotraps against a non-replicating virus called a pseudovirus in human lung cells in tissue culture plates and saw that they completely prevented viral entry into the cells.

 When the nanoparticle binds to the virus (about 10 minutes after injection), it chemically signalled macrophages to engulf and destroy the nanoparticle and the attached virus. Macrophages normally engulf nanoparticles, so this merely sped up the process.

Testing the Nanotraps on a pair of donated lungs kept alive with a ventilator, they found that they completely prevented infection.

They also collaborated with researchers at Argonne National Laboratory to test the Nanotraps with a live virus (rather than a pseudovirus) in an in vitro system. They found a 10 times better performance than with neutralising antibodies or ACE2 inhibitor.

The researchers plan further tests, including live virus and its variants.

“That’s what is so powerful about this Nanotrap,” Rosenberg said. “It’s easily modulated. We can switch out different antibodies or proteins or target different immune cells, based on what we need with new variants.”

Storage is simple, as the Nanotraps can be kept in a standard freezer, and administration is simple, using a nasal spray. The researchers said it is also possible to serve as a vaccine by optimisation of the Nanotrap formulation.

Source: Phys.Org

Journal information: Min Chen et al, Nanotraps for the containment and clearance of SARS-CoV-2, Matter (2021). DOI: 10.1016/j.matt.2021.04.005

Loss of Smell and Taste in COVID Explained

Cut lemon. Photo by Karolina Grabowska from Pexels

New research awaiting peer review uncovers why the loss of sense of taste is one of the symptoms of COVID infection.  New research has found that taste receptors have ACE2 and are also at risk for SARS-CoV-2 invasion.

Understanding the presence of viral infection in taste buds could help treat people with ‘long COVID’ who could continue to experience changes in or loss of taste months after the initial infection.

SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) enzyme attached to the membranes of cells as their point of entry. ACE2 enzymes are present all over the body, especially in the lungs and nose, coinciding with COVID’s early symptoms of loss of smell and difficulty breathing. Loss of taste is another early COVID infection sign, although the mechanism behind this is unclear. 

“By demonstrating the co-localization of SARS-CoV-2 virus, Type II taste cell marker, and the viral receptor ACE2, we show evidence for replication of this virus within taste buds that could account for acute taste changes during active COVID-19,” wrote the authors. “This work also shows that the proliferation of the taste stem cells in recovering patients may take weeks to return to their pre-COVID-19 state, providing a hypothesis for more chronic disruption of taste sensation, reports of which are now appearing in the medical literature.”

Source: Wikimedia. CC0 Creative Commons
Diagram of the tongue. The fungiform papillae is located near the centre of the tongue.

ACE2 is present on Type II taste bud cells on the tongue. There are three cranial nerves (CN VII, IX and X) that are involved in relaying taste information to the central nervous system. Taste is first discriminated in taste receptor cells (TRCs) within taste buds located in circumvallate (CVP), foliate (FLP) and fungiform papillae (FP) in the tongue. Three defined TRCs relay five basic tastes. Stem cells around the taste bud receive signals from taste cells, prompting differentiation into a replacement TRC. 

The researchers identified 5000 to 10 000 taste buds, with almost half located at the base of the tongue called circumvallate papillae. ACE2 was found to be coexpressed with phospholipase C β2 used in the signaling of type II taste receptor cells. Taste receptor cells in the back of the tongue, a region known as fungiform pallipae, also had ACE2 receptors, providing further evidence of a viral entry point for SARS-CoV-2.

“Replication of virus can likely then occur undisturbed and allow for transmission from the taste bud into circulation, and locally infect lingual and salivary gland epithelium, oral mucosa and larynx and even on into the lungs,”

Case Studies of Altered Taste During and After COVID Infection

A 45-year old woman with COVID and controlled hypertension reported changes in her sense of taste, including not being able to taste the sweetness from chocolate and describing curry as ‘white’ and her tongue was enlarged and redder around the fusiform pallipae.

SARS-CoV-2 RNA was found in samples taken from that area, specifically in PLCB2 positive cells. The virus was also found in the lamina propria with disruptions in the stem cell layer. Symptoms improved after six weeks, along with taste perception.

A 63-year-old man with no preexisting conditions had donated samples of his fusiform pallipae in 2019, and more samples were taken six weeks after testing positive for COVID. He experienced several long COVID symptoms, including mild loss of taste — coffee tasted like mud, and he could not taste chocolate. The virus was not present in samples of his fusiform pallipae 10 weeks after infection. However, he had altered changes to the stem cell layer of the tongue compared to the 2019 samples.

The researchers suggested that stem cell impairments may affect taste bud cell turnover and could contribute to the delayed return of sense of taste.

Source: News-Medical.Net

Journal information: Doyle ME, et al. Human Taste Cells Express ACE2: a Portal for SARS-CoV-2 Infection. bioRxiv, 2021. doi: https://doi.org/10.1101/2021.04.21.440680
https://www.biorxiv.org/content/10.1101/2021.04.21.440680v1