Tag: covid

Categories : COVID Metabolic DisordersTags :

Diabetes Almost Doubles COVID Mortality Risk

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Diabetes - person measures blood glucose
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Compared to those without diabetes, the COVID mortality risk for people with diabetes is almost double, with almost three times the risk of being critically or severely ill, according to a review of research by researchers from the University of Aberdeen.

Fortunately, the review study, which is published in Endocrinology, Diabetes and Metabolism, also found that good management of the condition can mitigate against the risks.

Specifically, it was found that while diabetes presents a significant risk of severe illness and death with COVID, good glycaemic control in these patients can mitigate this risk.

The researchers reviewed findings from 158 studies, encompassing more than 270 000 participants from around the world to determine COVID’s impact on people with diabetes.

The pooled results showed that people with diabetes were 1.87 times more likely to die with COVID, 1.59 times more likely to be admitted to ICU, 1.44 times more likely to require ventilation, and 2.88 times more likely to be classed as severe or critical, when compared to patients without diabetes.

This is the first time a study has looked at the risks of COVID in patients with diabetes while factoring in the patients’ location and thereby highlighting potential healthcare resources available as well as possible ethnic differences and other societal factors.

Patients in China, Korea and the Middle East were found to be at higher risk of death than those from EU countries or the US. This, they suggested, may be the result of differences in healthcare systems and affordability of healthcare which may explain the finding that maintaining optimal glycaemic control, significantly reduces adverse outcomes in patients with diabetes and COVID.

Stavroula Kastora, who worked on the study explained: “We found that following a COVID infection, the risk of death for patients with diabetes was significantly increased in comparison to patients without diabetes.

“Equally, collective data from studies around the globe suggested that patients with diabetes had a significantly higher risk of requiring an intensive care admission and supplementary oxygen or being admitted in a critical condition in comparison to patients without diabetes.

“However, we found that the studies that reported patient data from the EU or US displayed less extreme differences between the patient groups. Ultimately, we have identified a disparity in COVID outcomes between the eastern and western world. We also show that good glycaemic control may be a protective factor in view of COVID-related deaths.

“In light of the ongoing pandemic, strengthening outpatient diabetes clinics, ensuring consistent follow up of patients with diabetes and optimising their glycaemic control could significantly increase the chances of survival following a COVID infection.”

Source: University of Aberdeen

Categories : Medical IndustryTags :

Storm on the Horizon for Life Insurance: Rising Prices and Long COVID

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Business data
Photo by Towfiqu barbhuiya on Unsplash

Coming out of 2021, Price Waterhouse-Cooper analysed major life insurers in a new report, and found that they were able to maintain their policy holder obligations and maintain their financial positions. However, uncertainty is growing as global commodity prices spike amid lackluster growth and COVID’s potential long-term impacts.

PwC analysed 2021 results for five major insurers:  Discovery, Liberty, Momentum Metropolitan Holdings Limited (MMH), Old Mutual, and Sanlam.

 Alsue du Preez, PwC Africa Insurance Leader, said that the results are presented in the context of rapidly changing circumstances in which insurers are conducting their businesses. “Significant shifts are still occurring, the latest being the invasion by Russia of Ukraine and flooding in KZN, impacting not only the economy but environmental and social conditions,” she said. “These factors, as well as ongoing shifts in customer expectations and needs, have the potential to continue to materially influence future performance.”

While the COVID pandemic in 2020 was unpredictable, the impact of the second and third waves in 2021 was underestimated by life insurers, the report noted. The year 2021 did however come with a realisation of just how complicated the variables are, bringing risk variance losses of R6.8bn.

Key indicators showed that profitability growth was subdued even pre-pandemic, with earnings growing in line with inflation. Value of New Business (VNB) margins – ie, profit from new policy signings – was trending downwards slightly. VNB was 2.7%–3.1% over the period 2011–2015 but decreased to 2.4% in 2018 and 2019. The VNB margin achieved in 2021 is lower still at 1.9%, but still an improvement from 2020’s result of 1.49%.

The present value of new business premiums (PVNBP), which is the present value of total confirmed premiums that will be received from present to future, increased by 13% from 2019, but this could not offset the fall in margins compared with pre-pandemic levels. 

The report paints a grim picture for economic growth. Stifled GDP growth – with a per capita GDO fall of 4.2% – has been compounded by Russia’s invasion of Ukraine, with supply chain disruptions and knock-on global price increases. 

“Given the consequent higher inflation, weaker external demand and an unreliable power supply (the country’s largest growth inhibitor), we now forecast a real GDP growth rate of 2.0% this year (from 2.3% previously) with continued downside risk,” du Preez said. “Alongside this, weaker economic outlook provides even greater concern about the speed of the country’s jobs recovery. There is little scope for South Africa’s unemployment rate to improve this year if local business sentiment is weighed down by these factors.” 

Pressure on low/medium income households will impact their ability to afford new or existing insurance products

Increasing living costs will adversely impact all households during 2022, though this will impact the various income groups differently. 

“Middle to higher income groups are re-evaluating their discretionary spending patterns and are either ‘buying down’ or reducing insurance and savings products,” du Preez said. “On the other hand, households in the lower to lower-middle income categories will struggle to sustain their monthly basket of goods purchases. Given increased costs of necessities, these households will need to carefully consider the affordability of other discretionary monthly expenses, including insurance products.”

More than half of the income of low-income households goes on food and non-alcoholic beverages, which will be impacted by increasing commodity prices.

As we now proceed out of the rollercoaster that was 2021, a fair amount of uncertainty lingers in the industry. Talk is now moving more towards whether cost savings insurance entities achieved during the lockdown will be sustainable, as well as what allowance should be made for COVID’s impacts on long term mortality and long-COVID. 

Moving out of the rollercoaster of 2021, there is still significant uncertainty in the industry, with discussion over whether insurance companies will sustain their cost savings made during lockdown. Another question is how COVID will impact the industry in terms of mortality and long COVID.

The major life insurers’ Stronger performances in FY21 showed sustained strength in operational and capital management, and the relative benefits of diversification amongst their business portfolios. “The post-COVID financial ‘recovery’ is pleasing to see, but the pre-COVID comparison, coupled with the difficult macro-economic backdrop into the medium term, demonstrates the need for insurers to continue to innovate and invest on multiple fronts,” du Preez said. 

Categories : COVIDTags : 1 Comment

Excess Deaths from COVID Nearly 15 Million – WHO

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Source: Pixabay CC0

The World Health Organization (WHO) estimates that the full death toll associated directly or indirectly with the COVID pandemic (described as “excess mortality”) was approximately 14.9 million, with a range of 13.3 million to 16.6 million.  

“These sobering data not only point to the impact of the pandemic but also to the need for all countries to invest in more resilient health systems that can sustain essential health services during crises, including stronger health information systems,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “WHO is committed to working with all countries to strengthen their health information systems to generate better data for better decisions and better outcomes.”

Excess mortality is calculated as the difference between the number of deaths that have occurred and the number that would be expected in the absence of the pandemic based on data from earlier years. 

Excess mortality includes deaths directly associated with COVID (due to the disease) or indirectly (due to the pandemic’s impact on health systems and society). Deaths linked indirectly to COVID are attributable to other health conditions for which people were unable to access prevention and treatment because health systems were overburdened by the pandemic. Excess death numbers can be influenced also by deaths averted during the pandemic due to lower risks of certain events, such as car accidents or occupational injuries. 

The estimate for a 24-month period (2020 and 2021) finds that the excess deaths (84%) are largely concentrated in South-East Asia, Europe, and the Americas. Some 68% of excess deaths are concentrated in just 10 countries globally. Middle-income countries account for 81% of the 14.9 million excess deaths (53% in lower-middle-income countries and 28% in upper-middle-income countries) over the 24-month period, with high-income and low-income countries each accounting for 15% and 4%, respectively. 

The estimates confirm that the global death toll was higher for men than for women (57% male, 43% female) and higher among older adults. A better picture of COVID mortality data comes from excess deaths per 100 000 instead of mortality counts, which can seem skewed due to population size.

“Measurement of excess mortality is an essential component to understand the impact of the pandemic. Shifts in mortality trends provide decision-makers information to guide policies to reduce mortality and effectively prevent future crises. Because of limited investments in data systems in many countries, the true extent of excess mortality often remains hidden,” said Dr Samira Asma, Assistant Director-General for Data, Analytics and Delivery at WHO. “These new estimates use the best available data and have been produced using a robust methodology and a completely transparent approach.”

The production of these estimates is a result of a global collaboration supported by the work of the Technical Advisory Group for COVID-19 Mortality Assessment and country consultations. 

Source: World Health Organization

Categories : Diseases, Syndromes and ConditionsTags :

Gene Mutation in Young Girl May Finally Yield Lupus Treatment

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Facial rash characteristic of lupus. Credit: Statpearls

A study published in Nature has identified mutations in an X chromosome gene that senses viral RNA, as a cause of the autoimmune disease lupus, a finding which may explain why the disease is far more common in females, and which might lead to new treatments.

In the study, whole genome sequencing was performed on the DNA of a Spanish child named Gabriela, who was diagnosed with severe lupus at age 7. Such a severe case with early onset of symptoms is rare and suggests a single genetic cause.

In their genetic analysis, the researchers discovered a single point mutation in the TLR7 gene. Referrals from other institutions, they were able to identify other cases of severe lupus where this gene was also mutated.

To confirm that the mutation causes lupus, the team inserted the gene into mice, which went on to develop the disease and showed similar symptoms. The mouse model and the mutation were both named ‘kika’ by Gabriela, the young girl central to this discovery.

Carola Vinuesa, senior author and principal investigator said: “It has been a huge challenge to find effective treatments for lupus, and the immune-suppressors currently being used can have serious side effects and leave patients more susceptible to infection. There has only been a single new treatment approved by the FDA in about the last 60 years.

“This is the first time a TLR7 mutation has been shown to cause lupus, providing clear evidence of one way this disease can arise.”

Professor Nan Shen, co-director of CACPI adds: “While it may only be a small number of people with lupus who have variants in TLR7 itself, we do know that many patients have signs of overactivity in the TLR7 pathway. By confirming a causal link between the gene mutation and the disease, we can start to search for more effective treatments.”

The mutation identified by the researchers makes TLR7 protein bind more readily guanosine and become more active. This in turn increases the sensitivity of the immune cell, making it more likely to incorrectly target healthy tissue.

Interestingly, other studies have shown mutations that cause TLR7 to become less active are associated with some cases of severe COVID infection, highlighting the delicate balance of a healthy immune system.

The findings could also explain why lupus is 10 times more common in females than in males. Because TLR7 is located on the X chromosome, females have two copies of the gene while males have one. Usually, in females one of the X chromosomes is inactive, but in this section of the chromosome, silencing of the second copy is often incomplete. This means females with a mutation in this gene can have two functioning copies.

Study co-author Dr Carmen de Lucas Collantes, said: “Identification of TLR7 as the cause of lupus in this unusually severe case ended a diagnostic odyssey and brings hope for more targeted therapies for Gabriela and other lupus patients likely to benefit from this discovery.”

Gabriela, now a teenager, remains in touch with the research team. She said, “I hope this finding will give hope to people with lupus and make them feel they are not alone in fighting this battle. Hopefully the research can continue and end up in a specific treatment that can benefit so many lupus warriors who suffer from this disease.”

The researchers are now investigating the repurposing of existing treatments which target the TLR7 gene. By targeting this gene, they hope to be able to also help patients with related conditions.

Carola added: “There are other systemic autoimmune diseases, like rheumatoid arthritis and dermatomyositis, which fit within the same broad family as lupus. TLR7 may also play a role in these conditions.”

Source: Francis Crick Institute

Categories : COVIDTags :

Home Pulse Oximeters in COVID no Better Than Just Asking

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Self-measurement of oxygen levels with pulse oximeters is no better than just regularly asking patients with COVID if they are short of breath, according to new research published in the New England Journal of Medicine. Pulse oximeters have often been applied because of concerns that patients might not notice their blood oxygen levels sliding dangerously. 

However, people in Penn Medicine’s COVID Watch programme, which monitors patients recovering at home via automated text messaging, had the same outcomes whether they used oxygen-measuring devices or not.

“Compared to remotely monitoring shortness of breath with simple automated check-ins, we showed that the addition of pulse oximetry did not save more lives or keep more people out of the hospital,” said the study’s co-lead author, Anna Morgan, MD, medical director of the COVID Watch program and an assistant professor of General Internal Medicine. “And having a pulse oximeter didn’t even make patients feel less anxious.”

The COVID Watch was launched in March 2020 to remotely monitor COVID patients at home, with 28 500 people enrolled to date. Twice a day for two weeks, text messages were automatically sent to these patients asking how they felt and if they were having difficulty breathing. If patients indicated dyspnoea, the programme would alert a nurse to make contact and arrange care.

“The programme made it easy to identify the sickest patients who needed the hospital, and keep the others at home safely,” said David Asch, MD, executive director of the Center for Health Care Innovation and a professor of Medicine, Medical Ethics and Health Policy. “The programme was associated with a 68 percent reduction in mortality, saving a life approximately every three days during peak enrollment early in the pandemic.”

However it was not known if monitoring blood oxygen would help.

“Early in the pandemic, there was a prevalent theory that oxygen levels in the blood dropped before a COVID patient became symptomatic and short of breath,” said study co-lead author Kathleen Lee, MD. “Detecting this earlier with a home pulse oximeter might provide an opportunity to get patients who are on the cusp of deteriorating to the hospital faster and initiate time-sensitive therapies to improve outcomes.”

The use of pulse oximeters was so intuitively appealing that the process got adopted even before this trial, the first randomised trial to test whether it actually worked.

“Several health systems, and even states like Vermont and countries like the United Kingdom, have integrated pulse oximetry into the routine home management of patients with COVID, but there’s been scant evidence to show this strategy makes a difference,” said the research project’s principal investigator M. Kit Delgado, MD.

In this study, more than 2000 patients enrolled in COVID Watch between Nov. 29, 2020, and Feb. 5, 2021, were randomised to receive standard COVID Watch care or the same program with the addition of a pulse oximeter.

However, no statistical difference was seen in the main study measure, the average number of days enrolled patients spent alive and out of the hospital in the 30 days after they were enrolled. For patients with pulse oximeters, the measure was 29.4 days; for those without, it was 29.5, with no difference across racial liines. This was important as black patients are known to have had worse COVID outcomes and concerns had been raised about the accuracy of pulse oximeters in people with darker skin.
The researchers cautioned that the study focused on pulse oximeters in established programme of remote monitoring, and patients don’t have access to a system like COVID Watch or on-call clinicians, self-monitoring with pulse oximeters may still be a reasonable approach until there is evidence to the contrary.

“Overall, these findings suggest that a low-tech approach for remote monitoring systems based on symptoms is just as good as a more expensive one using additional devices. Automated text messaging is a great way for health systems to enable a small team of on-call nurses to manage large populations of patients with COVID,” said co-principal investigator, Krisda Chaiyachati, MD. “There are a lot of other medical conditions where the same kind of approach might really help.”

Source: University of Pennsylvania School of Medicine

Categories : COVID Obstetrics & GynaecologyTags :

Caesarean and Induced Deliveries Fell During Pandemic

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During the first few months of the COVID pandemic, premature births from caesarean and induced deliveries fell by 6.5% – and remained consistently lower throughout, according to research reported in the journal Pediatrics. This is likely a result of fewer prenatal visits due to lockdown and social distancing rules, the researchers suggested, and call into question how many such interventions are necessary.   

The study, the first to examine pandemic-era birth data at scale, raises questions about medical interventions in pregnancy and whether some decisions by doctors may result in unnecessary preterm deliveries, according to Assistant Professor Daniel Dench, the paper’s lead author.

“While much more research needs to be done, including understanding how these changes affected fetal deaths and how doctors triaged patient care by risk category during the pandemic, these are significant findings that should spark discussion in the medical community,” A/Prof Dench said.

In effect, the study begins to answer a question that never could have been resolved in a traditional experiment: What would happen to the rate of premature C-sections and induced deliveries if women didn’t see doctors as often, especially in person, during pregnancy?

Doing such a study would be unethical, but lockdown had a side effect of reducing prenatal care visits by more than a third, according to one analysis. That gave A/Prof Dench and colleagues an opportunity to evaluate the impacts, after all.

The researchers took records of nearly 39 million US births from 2010 to 2020, and compared them to expected premature births (born before 37 weeks) from March to December 2020. 

The researchers found that in March 2020, when lockdowns began in the US, preterm births from C-sections or induced deliveries immediately fell from the forecasted number by 0.4%. From March 2020 to December 2020, the number remained on average 0.35% below the predicted values. That translates to 350 fewer preterm C-sections and induced deliveries per 100 000 live births, or 10 000 fewer overall.

Before the pandemic, the number of preterm C-sections and induced deliveries had been rising. Spontaneous preterm births also fell by a small percentage in the first months of the pandemic, but much less than births involving those two factors. The number of full-term caesarean and induced deliveries increased.

“If you look at 1000 births in a single hospital, or even at 30 000 births across a hospital system, you wouldn’t be able to see the drop as clearly,” said A/Prof Dench. “The drop we detected is a huge change, but you might miss it in a small sample.”  

The researchers also corrected for seasonality, for example, preterm births are higher on average in February than in March, which helped them get a clearer picture of the data.

The research comes with caveats. Up to half of all preterm C-sections and induced deliveries are due to a ruptured membrane, which is a spontaneous cause. But in the data Dench and his team used, it’s impossible to distinguish these C-sections from the ones caused by doctors’ interventions. So, Dench and co-authors are seeking more detailed data to get a clearer picture of preterm deliveries.

Still, these findings are significant because the causes for preterm births are not always known.

“However, we know for certain that doctors’ interventions cause preterm delivery, and for good reason most of the time,” A/Prof Dench said. “So, when I saw the change in preterm births, I thought, if anything changed preterm delivery, it probably had to be some change in how doctors were treating patients.”

The researchers’ findings raise a critical question: Was the pre-pandemic level of doctor intervention necessary?

“It’s really about, how does this affect foetal health?” said A/Prof Dench. “Did doctors miss some false positives – did they just not deliver the babies that would have survived anyway? Or did they miss some babies that would die in the womb without intervention?”  

A/Prof Dench plans to use foetal death records from March 2020 to December 2020 to answer this question. If he finds no change in foetal deaths at the same time as the drop in preterm births, that could point to “false positives” in doctor intervention that can be avoided in the future. Learning which pregnancies required care during the pandemic and which ones didn’t could help doctors avoid unnecessary interventions in the future.  

“This is just the start of what I think will be an important line of research,” A/Prof Dench said.

Source: Georgia Institute of Technology

Categories : COVIDTags :

Increased Risk of DVT, Pulmonary Embolism, and Bleeding after COVID

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3D illustration of a thrombus. Credit: Mecder, CC BY-SA 4.0, via Wikimedia Commons

There is an increased risk of developing deep vein thrombosis (DVT) for six months after a COVID, a study published in the BMJ suggests, as well as increased risk of pulmonary embolism and bleeding for shorter periods. The risk was particularly evelated for those with severe COVID as well as those infected during the first wave.

This highlights the importance of COVID vaccination, the researchers said. While there has been concern over the risk of blood clots after vaccination, the risk is far smaller, according to a large study last year.

It had previously been observed that people who had COVID had an increased risk of blood clots, and the researchers wanted to find out when that risk returns to normal levels.

The researchers tracked the health of just over one million people in Sweden who tested positive for COVID between February 2020 and May 2021 in Sweden, comparing them against four million people age- and sex-matched non-infected individuals.

Adjusting for confounding factors such as comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event, the researchers found an increased risk of:

  • first DVT, for up to three months
  • first pulmonary embolism, for up to six months
  • first bleeding event, such as a stroke, for up to two months

Comparing blood clot risk after COVID to the normal level of risk, the results showed that:

  • four in every 10 000 COVID patients developed DVT compared with one in every 10 000 non-infected individuals
  • about 17 in every 10,000 COVID patients had a blood clot in the lung compared with fewer than one in every 10,000  non-infected individuals

The authors wrote that the increased risk of blood clots was higher in the first wave than later waves, probably because treatments improved during the pandemic and older patients were starting to be vaccinated by the second wave.

Pulmonary embolism risk in people with severe COVID was 290 times greater than normal, and seven times higher than normal after mild COVID. However, there was no increase in bleeding risk in mild cases.

“For unvaccinated individuals, that’s a really good reason to get a vaccine – the risk is so much higher than the risk from vaccines,” said principal study investigator Anne-Marie Fors Connolly, from Umea University in Sweden.
While COVID’s causing the blood clots cannot be proven in this study, the researchers have a number of theories on the mechanism. It could be the direct effect of the virus on the layer of cells which line blood vessels, an exaggerated inflammatory response to the virus, or the body making blood clots at inappropriate times.

Though vaccines are very effective against severe COVID, but less so against infection, especially with the Omicron variant. This means repeat symptomatic infections are commonplace.

Source: BBC News

Categories : COVID Healthcare Politics and RegulationsTags :

After More than Two Years, SA’s State of Disaster Finally Ends

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Image by Quicknews

More than two years since the start of the COVID pandemic. President Cyril Ramaphosa on Monday evening (4 April) announced the repeal of South Africa’s national state of disaster. A transition to new regulations to manage the pandemic will take place in coming weeks.

However, the end of the state of emergency had already been extended, a decision met with much criticism. Its end had long been called for, including experts such as Professor Shabir Madhi of Wits University.

Speaking about the extension in January, Prof Madhi told the Daily Maverick that the state of disaster regulations “have done very little when it comes to protecting people from being infected, because, had it had any impact, we wouldn’t have had 70% of the population infected with the virus at least once since the start of the pandemic.”

In the announcement, President Ramaphosa said the state of disaster and associated lockdown restrictions had been needed to properly deal with the COVID pandemic.

The state of disaster also allowed the establishment of the COVID TERs scheme, the R350 social relief of distress grant, the extension of driving licences and other necessary changes.

President Ramaphosa stated that the state of disaster and its powers were always ‘temporary and limited’, with the country now entering a new phase in the pandemic. While SARS-CoV-2 continues to circulate in the country, experience had already shown early in the fourth wave that the Omicron variant has decoupled COVID infection from rates of hospitalisation or deaths.

“Going forward, the pandemic will be managed in terms of the National Health Act. The draft Health Regulations have been published for public comment. Once the period for public comment closes on the 16th of April 2022 and the comments have been considered, the new regulations will be finalised and promulgated.

“Since the requirements for the National State of Disaster to be declared in terms of the Disaster Management Act are no longer met, Cabinet has decided to terminate the National State of Disaster with effect from midnight tonight.”

President Ramaphosa said certain provisional regulations will remain in place for a further 30 days to ensure a smooth handover to the new regulations under the National Health Act.

The transitional measure which will automatically lapse after 30 days include:

  • Wearing face masks must continue to be worn in an indoor public space.
  • Gatherings will continue to be restricted in size. Indoor and outdoor venues can accept 50% of capacity subject to vaccination or a COVID test. Gatherings of 1000 people indoors and 2000 people outdoors are permitted for the unvaccinated.
  • Travellers entering South Africa will need to show proof of vaccination or proof of a negative test.
  • The R350 SRD grant will remain in place, with the Department of Social Development finalising separate regulations allowing it to continue.
  • The grace period for driving licence extensions remain in place.

All other regulations fall away from midnight and the COVID alert levels will no longer apply, President Ramaphosa said. The no-fault vaccination compensation scheme will also continue operating.

Source: BusinessTech

Categories : Cardiovascular Disease COVIDTags :

Possible Cause of COVID Arrhythmias Discovered

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Anatomical model of a human heart
Photo by Robina Weermeijer on Unsplash

The SARS-CoV-2 virus can infect cardiac pacemaker cells, causing the cells to undergo self-destruct by ferroptosis according to a preclinical study reported in Circulation Research. This may explain the heart arrhythmias that are commonly observed in COVID patients.

In the study, the researchers used an animal model as well as human stem cell-derived pacemaker cells to show that SARS-CoV-2 can readily infect pacemaker cells and trigger a process called ferroptosis, where cells self-destruct, releasing damaging reactive oxygen molecules.

“This is a surprising and apparently unique vulnerability of these cells — we looked at a variety of other human cell types that can be infected by SARS-CoV-2, including even heart muscle cells, but found signs of ferroptosis only in the pacemaker cells,” said study co-senior author Professor Shuibing Chen.

Arrhythmias, including tachycardia and bradycardia, has been observed in some COVID patients, and multiple studies link these arrhythmias to worse COVID outcomes. But how the coronavirus caused these remained unclear.

In the new study, the researchers examined golden hamsters (one of the only lab animals that reliably develops COVID-like signs from SARS-CoV-2 infection) and found evidence that following nasal exposure, the virus can infect the sinoatrial node, which is the natural cardiac pacemaker.

The researchers then induced human embryonic stem cells to mature into cells closely resembling sinoatrial node cells. They showed that these induced human pacemaker cells can be infected by SARS-CoV-2 as they express ACE2 receptors. Large increases in inflammatory immune gene activity were also seen in the infected cells.

The team’s most surprising finding, however, was that the pacemaker cells, in response to the stress of infection, showed clear signs of a cellular self-destruct process called ferroptosis, which involves accumulation of iron and the runaway production of reactive oxygen molecules. The scientists were able to reverse these signs in the cells using compounds that are known to bind iron and inhibit ferroptosis.

“This finding suggests that some of the cardiac arrhythmias detected in COVID patients could be caused by ferroptosis damage to the sinoatrial node,” said co-senior author Dr Robert Schwartz

While COVID patients could in principle be treated with ferroptosis inhibitors specifically to protect sinoatrial node cells, antiviral drugs that block the effects of SARS-CoV-2 infection in all cell types would be preferable, the researchers said.

The researchers plan to continue to use their cell and animal models to investigate sinoatrial node damage in COVID and other settings.

“There are other human sinoatrial arrhythmia syndromes we could model with our platform,” said co-senior author Dr. Todd Evans. “And, although physicians currently can use an artificial electronic pacemaker to replace the function of a damaged sinoatrial node, there’s the potential here to use sinoatrial cells such as we’ve developed as an alternative, cell-based pacemaker therapy.”

Source: Weill Cornell Medicine

Categories : COVID Respiratory DiseasesTags :

Why People with Asthma are Less Vulnerable to COVID

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Researchers have revealed biological reasons for how disease progression happens and why a certain population of asthma patients are less susceptible to severe COVID.

This research, published in PNAS, shows the importance of the well-known cytokine interleukin-13 (IL-13) in protecting cells against SARS-CoV-2, something which helps explain why people with allergic asthma fare better than the general population despite having a chronic lung condition. However, the same cannot be said for individuals with other diseases, such as chronic obstructive pulmonary disease (COPD) or emphysema, who are at very high risk of severe COVID.

“We knew there had to be a bio-mechanistic reason why people with allergic asthma seemed more protected from severe disease,” said Assistant Professor Camille Ehre, PhD, senior author of the paper. “Our research team discovered a number of significant cellular changes, particularly due to IL-13, leading us to conclude that IL-13 plays a unique role in defence against SARS-CoV-2 infection in certain patient populations.”

Although cytokines like IL-13 cannot be used as therapies because they trigger inflammation, it is important to understand natural molecular pathways that cells use to protect themselves from pathogen invasion, as these studies have the potential to reveal new therapeutic targets.

Many health factors increase a person’s risk of severe COVID, but during the pandemic, epidemiologists found that people with allergic asthma were less susceptible to severe disease.

“These are patients with asthma caused by allergens, such as mould, pollen, and dander,” said A/Prof Ehre. “To find out why they are less susceptible, we investigated specific cellular mechanisms in primary human airway epithelial cell cultures.”

Genetic analysis human airway cell cultures infected with SARS-CoV-2 revealed that the expression of ACE2 governed which cell types were infected and their viral load.

Electron microscopy (EM) identified an intense exodus of virus from infected ciliated cells, which move mucus along the airway surface. EM also revealed severe cytopathogenesis – changes inside human cells due to viral infection. And these changes culminating in ciliated cells (packed with virions) shedding away from the airway surface.

“This shedding is what provides a large viral reservoir for spread and transmission of SARS-CoV-2,” A/Prof Ehre said. “It also seems to increase the potential for infected cells to relocate to deeper lung tissue.”

Further experiments on infected airway cells revealed that a major mucus protein called MUC5AC was depleted inside cells, likely because the proteins were secreted to try to trap invading viruses. But the virus load kept increasing because the cells tasked with producing MUC5AC were overwhelmed in the face of a rampant viral infection.

The researchers knew from epidemiological studies that allergic asthma patients—known to overproduce MUC5AC—were less susceptible to severe COVID. A/Prof Ehre and colleagues also knew the cytokine IL-13 increased MUC5AC secretion in the lungs when asthma patients faced an allergen.

The scientists decided to mimic asthmatic airways by treating human airway cells with IL-13. They then measured viral titres, viral mRNA, the rate of infected cell shedding, and the overall number of infected cells. Each one was significantly decreased. They found this remained true even when mucus was removed from the cultures, suggesting other factors were involved in the protective effects of IL-13 against SARS-CoV-2.

Bulk RNA-sequencing analyses revealed that IL-13 upregulated genes that control glycoprotein synthesis, ion transport, and antiviral processes – all of which are important in airway immune defence. They also showed that IL-13 reduced the expression of the viral receptor, ACE2, as well as reducing the amount of virus inside cells and cell-to-cell viral transmission.

Taken together, these findings indicate that IL-13 significantly affected viral entry into cells, replication inside cells, and spread of virus, thus limiting the virus’s ability to find its way deeper into the airways to trigger severe disease.

“We think this research further shows how important it is to treat SARS-CoV-2 infection as early as possible,” A/Prof Ehre said. “And it shows just how important specific mechanisms involving ACE2 and IL-13 are, as we try our best to protect patients from developing severe infections.”

Source: University of North Carolina Health Care