Tag: long COVID

Large Study Reveals Risk Factors for Long COVID

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Early in the pandemic, many people who had SARS-Cov-2 infection or COVID began to report that they couldn’t shake off their symptoms even after a month or more – unusually long for a viral infection of the upper respiratory tract – or developed new, persistent symptoms soon after the infection cleared.

Although it’s still not clear what causes post-COVID conditions or “long COVID” (symptoms and conditions that develop, linger, or reoccur weeks or months after SARS-CoV-2 infection), a new study by researchers at Columbia University Vagelos College of Physicians and Surgeons confirms the high burden of long COVID and sheds light on who’s at greatest risk.

The study, published in JAMA Network, found that people with a milder infection – including those who were vaccinated against SARS-CoV-2 and those who were infected with an Omicron variant – were more likely to recover quickly.

Recovery time was similar for subsequent infections.

“Our study underscores the important role that vaccination against COVID has played, not just in reducing the severity of an infection but also in reducing the risk of long COVID,” says Elizabeth C. Oelsner, the study’s lead author and the Herbert Irving Associate Professor of Medicine.

Study details

The study involved over 4700 participants from the Collaborative Cohort of Cohorts for COVID 19 Research (C4R), who were asked to report their time to recovery after infection with SARS-CoV-2.

The study found that, between 2020 and early 2023, the median recovery time after SARS-CoV2-infection was 20 days, and more than one in five adults did not recover within three months.

Women and adults with pre-pandemic cardiovascular disease were less likely to recover within three months. Other pre-pandemic health conditions, including chronic kidney disease, diabetes, asthma, chronic lung disease, depressive symptoms, and a history of smoking, were linked to longer recovery times, but these associations were no longer significant after accounting for sex, cardiovascular disease, vaccination, and variant exposure.

“Although studies have suggested that many patients with long COVID experience mental health challenges, we did not find that depressive symptoms prior to SARS-CoV-2 infection were a major risk factor for long COVID.” 

Other groups disproportionately affected by long COVID were American Indian and Alaska Native participants, in whom severe infections and longer recovery times were more common.

“Our study clearly establishes that long COVID poses a substantial personal and societal burden,” says Oelsner. “By identifying who was likely to have experienced a lengthy recovery, we have a better understanding of who should be involved in ongoing studies of how to lessen or prevent the long-term effects of SARS-CoV-2 infection.”

Source: Columbia University Irving Medical Center

Scientists Discover Immune Key for Chronic Viral Infections

Colourised scanning electron micrograph of HIV (yellow) infecting a human T9 cell (blue). Credit: NIH

Australian researchers have discovered a previously unknown rogue immune cell that can cause poor antibody responses in chronic viral infections. The finding, published in the journal, Immunity, may lead to earlier intervention and possibly prevention of some types of viral infections such as HIV or hepatitis.

One of the remaining mysteries of the human immune system is why ‘memory’ B cells often only have a weak capacity to protect us from persistent infections.

In an answer to this, researchers from the Monash University Biomedicine Discovery Institute have now discovered that chronic viral infection induces a previously unknown immune B memory cell that does not produce high levels of antibodies.

Importantly the research team, led by Professor Kim Good-Jacobson and Dr Lucy Cooper, also determined the most effective time during the immune response for therapeutics such as anti-viral and anti-cancer drugs to better boost immune memory cell development.

“What we discovered was a previously unknown cell that is produced by chronic viral infection. We also determined that early intervention with therapeutics was the most effective to stop this type of memory cell being formed, whereas late intervention could not,” Professor Good-Jacobson said.

According to Dr Cooper, chronic viral infections have been known to alter our ability to form effective long-term protective antibody responses, but how that happens is unknown.

“In the future, this research may result in new therapeutic targets, with the aim to reduce the devastating effect of chronic infectious diseases on global health, specifically those that are not currently preventable by vaccines,” she said.

“Revealing this new immune memory cell type, and what genes it expresses, allows us to determine how we can target it therapeutically and whether that will lead to better antibody responses.”

The research team are also looking to see whether this population is a feature of long COVID, which results in some people having a reduced capacity to fight off the symptoms of COVID infection long after the virus has dissipated.

Source: Monash University

Overactive Complement System Causes Long Covid

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A new study from the University of Zurich (UZH) has revealed that the complement system plays an important role in Long Covid, a common sequela of SARS-CoV-2 infection. The findings, published in Science, show that the complement system ends up damaging tissue and blood cells even after the original infection has ended.

A significant proportion of individuals infected with SARS-CoV-2 develop long-lasting symptoms with a wide range of manifestations. The causes and disease mechanisms of Long Covid are still unknown, and there are no diagnostic tests or targeted treatments.

Part of the immune system active for too long

A team of researchers led by Onur Boyman, professor of immunology at UZH and Director of the Department of Immunology at the University Hospital Zurich (USZ), has implicated the complement system. It is part of the innate immune system and normally helps to fight infections and eliminate damaged and infected body cells.

“In patients with Long Covid, the complement system no longer returns to its basal state, but remains activated and, thus, also damages healthy body cells,” says Boyman.

Continued activation of complement system damages tissue and blood cells

The researchers followed 113 COVID patients for up to one year after their acute SARS-CoV-2 infection and compared them with 39 healthy controls.

After six months, 40 patients had active Long Covid disease.

More than 6500 proteins in the blood of the study participants were analysed both during the acute infection and six months later.

“The analyses of which proteins were altered in Long Covid confirmed the excessive activity of the complement system. Patients with active Long Covid disease also had elevated blood levels indicating damage to various body cells, including red blood cells, platelets and blood vessels,” explains Carlo Cervia-Hasler, a postdoctoral researcher in Boyman’s team and first author of the study.

Bioinformatics recognises protein patterns

The measurable changes in blood proteins in active Long Covid indicate an interaction between proteins of the complement system, which are involved in blood clotting and the repair of tissue damage and inflammation.

In contrast, the blood levels of Long Covid patients who recovered from the disease returned to normal within six months.

Active Long Covid is therefore characterised by the protein pattern in the blood.

The blood markers were discovered using bioinformatics methods in collaboration with Karsten Borgwardt during his time as a professor at ETH Zurich.

“Our work not only lays the foundation for better diagnosis, but also supports clinical research into substances that could be used to regulate the complement system. This opens up new avenues for the development of more targeted therapies for patients with Long Covid,” Onur Boyman said.

Source: University of Zurich

Paxlovid does not Reduce Risk of Long COVID, Study Finds

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A recent has study found that Paxlovid (Nirmatrelvir-ritonavir) did not reduce the risk of developing long COVID for vaccinated, non-hospitalised individuals during their first COVID infection. The study also revealed a higher proportion of individuals with acute symptoms rebound and test-positivity than previously reported.

The study, by a team of researchers from UC San Francisco, is published in the Journal of Medical Virology.

Paxlovid treatment for acute COVID has been shown to be effective for high-risk unvaccinated individuals. But the effect of the treatment on long COVID risk, including whether it protects vaccinated people from getting long COVID, has been less clear.

The research team selected a group of vaccinated people from the UCSF Covid-19 Citizen Science study who had reported their first positive test for COVID-19 between March and August of 2022 and who were not hospitalised.

Some of these participants reported taking oral Paxlovid treatment during the acute phase of their COVID infection, while others did not.

In December of 2022, they were invited to answer a follow-up survey with questions about long COVID, COVID rebound symptoms and how long they continued to test positive.

Researchers found the two groups were similar. About 16% of those treated with Paxlovid had long COVID symptoms compared to 14% of those who were not treated with the medication.

Commonly reported symptoms included fatigue, shortness of breath, confusion, headache, and altered taste and smell.

Those who took Paxlovid and then went on to develop long COVID reported as many long COVID symptoms as those who were not treated with Paxlovid.

A small percentage of people developed severe long COVID, and those who had received Paxlovid were just as likely to have severe Long COVID symptoms as those who did not.

Among individuals who experienced symptomatic improvement during Paxlovid treatment, 21% reported rebound symptoms.

And among those with rebound symptoms, 10.8% reported one or more Long COVID symptom compared to 8.3% without rebound symptoms.

For participants who repeated antigen testing after testing negative and completing treatment, 25.7% reported rebound test positivity.

In total, 26.1% reported rebound symptoms or test positivity.

“We found a higher proportion with clinical rebound than previously reported but did not identify an effect of post-treatment rebound on long COVID symptoms,” said study first author Matthew Durstenfeld, MD, MAS, a cardiologist and UCSF assistant professor of Medicine.

“Our finding that Paxlovid treatment during acute infection is not associated with lower odds of long COVID surprised us, but it is consistent with two other rigorously conducted studies finding no difference in post-COVID conditions between 4 and 6 months after infection.”

The authors note that the study may have been impacted by limitations arising from its observational nature with researchers relying on patient self-reporting of treatment and Long COVID symptoms.

Source: University of California San Francisco Medical Center

Pre-existing Allergies Increase Risk of Experiencing Long COVID Symptoms

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In an analysis of published prospective studies of people of all ages with confirmed SARS-CoV-2 infection who were followed for at least 12 months, pre-existing allergic conditions were linked to higher risks of experiencing long-term symptoms associated with COVID, or ‘Long COVID’.  

The analysis, which is published in Clinical & Experimental Allergy, identified 13 relevant studies (with a total of 9 967 participants) published between January 1, 2020 and January 19, 2023.

Although the data as a whole from the studies suggested that individuals with asthma or rhinitis might be at increased risk of long COVID after SARS-CoV-2 infection, the evidence for these associations was very uncertain. Therefore, more robust epidemiological research is needed to clarify the role of allergy in the development of Long COVID.

“We need a better, harmonised definition of what is considered Long COVID for epidemiological studies of this sort. Regardless we will be updating our analysis once further studies have been published in the next few months,” said corresponding author Christian Apfelbacher, PhD, of the Institute of Social Medicine and Health Systems Research, in Germany.

Source: Wiley

Not Just ‘Long COVID’: Researchers Find ‘Long Colds’

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A new study from Queen Mary University of London, published in The Lancet’s EClinicalMedicine, has found that people may experience long-term symptoms, termed ‘long colds’, after non-COVID acute respiratory infections.

The ‘long cold’s’ most common symptoms included coughing, stomach pain, and diarrhoea more than four weeks after the initial infection. While the severity of an illness appears to be a key driver of risk of long-term symptoms, just why some people suffer extended symptoms while others do not is a focus of further research.

The findings suggest that there may be long-lasting health impacts following non-COVID acute respiratory infections such as colds, influenza, or pneumonia, that are currently going unrecognised. However, the researchers do not yet have evidence suggesting that the symptoms have the same severity or duration as long COVID.

The research compared the prevalence and severity of long-term symptoms after an episode of COVID versus an episode of another acute respiratory infection that tested negative for COVID. Those recovering from COVID were more likely to experience light-headedness or dizziness and problems with taste and smell compared to those who had a non-COVID respiratory infection.

While long COVID is now a recognised condition, there have been few studies comparing long-term symptoms following SARS-CoV-2 coronavirus infection versus other respiratory infections.

The study is the latest output from COVIDENCE UK, Queen Mary University of London’s national study of COVID, launched back in 2020 and still in follow-up, with over 19 000 participants enrolled. This study analysed data from 10 171 UK adults, with responses collected via questionnaires and statistical analysis carried out to identify symptom clusters.

Giulia Vivaldi, researcher on COVIDENCE UK from Queen Mary University of London and the lead author of the study, said: “Our findings shine a light not only on the impact of long COVID on people’s lives, but also other respiratory infections. A lack of awareness – or even the lack of a common term – prevents both reporting and diagnosis of these conditions.

“As research into long COVID continues, we need to take the opportunity to investigate and consider the lasting effects of other acute respiratory infections.

“These ‘long’ infections are so difficult to diagnose and treat primarily because of a lack of diagnostic tests and there being so many possible symptoms. There have been more than 200 investigated for long COVID alone.”

Source: Queen Mary University of London

Study Explains a Link between COVID and Increased Cardiovascular Risk

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A study published in the journal Nature Cardiovascular Research shows that SARS-CoV-2 can directly infect the arteries of the heart and cause the fatty plaque inside arteries to become highly inflamed, increasing the risk of heart attack and stroke. The findings may help explain why certain people who get COVID have a greater chance of developing cardiovascular disease, or if they already have it, develop more heart-related complications.

In the National Institutes of Health (NIH)-funded study, researchers focused on older people with atherosclerotic plaque, who died from COVID. However, because the researchers found the virus infects and replicates in the arteries no matter the levels of plaque, the findings could have broader implications for anybody who gets COVID.

“Since the early days of the pandemic, we have known that people who had COVID have an increased risk for cardiovascular disease or stroke up to one year after infection,” said Michelle Olive, PhD, acting associate director of the Basic and Early Translational Research Program at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH. “We believe we have uncovered one of the reasons why.”

Though previous studies have shown that SARS-CoV-2 can directly infect tissues such as the brain and lungs, less was known about its effect on the coronary arteries. Researchers knew that after the virus reaches the cells, the body’s immune system sends in macrophages to help clear the virus. In the arteries, macrophages also help remove cholesterol, and when they become overloaded with cholesterol, they morph into a specialised type of cell called foam cells.

The researchers thought that if SARS-CoV-2 could directly infect arterial cells, the macrophages that normally are turned loose might increase inflammation in the existing plaque, explained Chiara Giannarelli, MD, PhD, associate professor in the departments of medicine and pathology at New York University’s Grossman School of Medicine and senior author on the study. To test their theory, Giannarelli and her team took tissue from the coronary arteries and plaque of people who had died from COVID and confirmed the virus was in those tissues. Then they took arterial and plaque cells – including macrophages and foam cells – from healthy patients and infected them with SARS-CoV-2 in a lab dish. They found that the virus had also infected those cells and tissues.

Additionally, the researchers found that when they compared the infection rates of SARS-CoV-2, they showed that the virus infects macrophages at a higher rate than other arterial cells. Cholesterol-laden foam cells were the most susceptible to infection and unable to readily clear the virus. This suggested that foam cells might act as a reservoir of SARS-CoV-2 in the atherosclerotic plaque. Having more build-up of plaque, and thus a greater number of foam cells, could increase the severity or persistence of COVID.

The researchers then looked at the predicted inflammation in the plaque after infecting it with the virus. They observed the release of inflammatory cytokines, also known to promote the formation of even more plaque. The cytokines were released by infected macrophages and foam cells. The researchers said this may help explain why people who have underlying plaque buildup and then get COVID may have cardiovascular complications long after getting the infection.  

“This study is incredibly important as it adds to the larger body of work to better understand COVID,” said Olive. “This is just one more study that demonstrates how the virus both infects and causes inflammation in many cells and tissues throughout the body. Ultimately, this is information that will inform future research on both acute and Long COVID.”

Though the findings conclusively show that SARS-CoV-2 can infect and replicate in the macrophages of plaques and arterial cells, they are only relevant to the original strains of SARS-CoV-2 that circulated in New York City between May 2020 and May 2021. The study was conducted in a small cohort of older individuals, all of whom had atherosclerosis and other medical conditions; therefore, the results cannot be generalised to younger, healthy individuals.

Source: National Institutes of Health

‘Long COVID’ Risks are Inflated by Flawed Research, Reviewers Find

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‘Long COVID’ is a mysterious constellation of symptoms associated with having recovered from COVID infection – but how many cases represent a true condition, and how many fall under a poorly-defined umbrella of currently known ones? Overly broad definitions, a lack of appropriate, or any, comparison groups, among other things, in studies looking at the epidemiology of the condition have distorted the risks, say the authors of a review published in BMJ Evidence-based Medicine.

This is further compounded by inclusion of poorly conducted studies into systematic reviews and pooled data analyses that end up overstating the risk yet again, they add. 

Likely consequences include increased public anxiety and healthcare spend; misdiagnoses; and diversion of funds from those who really do have other long term conditions secondary to COVID infection, suggest the researchers.

Many after-effects of COVID infection include post-ICU syndrome, which is a constellation of health issues that are present when the patient is in intensive care and which persist after discharge home, and shortness of breath following pneumonia. The trouble is that these are common to many upper respiratory viruses, the researchers point out.

None of the working definitions of ‘long COVID’ used by influential health bodies, such as the US Centers for Disease Control and Prevention, the World Health Organization, the UK National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), and the Royal College of General Practitioners requires a causal link between SARS-CoV2 and a range of symptoms. 

Not only should comparator (control) groups be included in ‘long COVID’ studies, when they often aren’t, but they should also be properly matched to cases, ideally by age, sex, geography, socioeconomic status and, if possible, underlying health and health behaviours, which they rarely are, say the researchers.

During the early stages of the pandemic, when SARS-CoV-2 testing wasn’t widely available, studies were more likely to include a non-representative sample of SARS-CoV-2-positive patients by including fewer patients with mild or no symptoms.

This is known as sampling bias, which occurs when certain members of a population have a higher probability of being included in a study sample than others, potentially limiting the generalisability of a study’s findings, explain the researchers.

“Our analysis indicates that, in addition to including appropriately matched controls, there is a need for better case definitions and more stringent [‘long COVID’] criteria, which should include continuous symptoms after confirmed SARS-CoV-2 infection and take into consideration baseline characteristics, including physical and mental health, which may contribute to an individual’s post COVID experience, “ they write, adding that the umbrella term ‘long COVID’ should be jettisoned in favour of different terms for specific after effects.

While the results of high quality population studies on ‘long COVID’ in adults and children have been reassuring, they point out,  the body of research “is replete with studies with critical biases” they add, setting out common pitfalls.

“Ultimately, biomedicine must seek to aid all people who are suffering. In order to do so, the best scientific methods and analysis must be applied. Inappropriate definitions and flawed methods do not serve those whom medicine seeks to help,” they insist.

“Improving standards of evidence generation is the ideal method to take long COVID seriously, improve outcomes, and avoid the risks of misdiagnosis and inappropriate treatment,” they include.

Source: EurekAlert!

Long COVID’s ‘Blue Legs’ Syndrome in Need of Greater Awareness

An unusual case of a Long Covid patient’s legs turning blue after 10 minutes of standing highlights the need for greater awareness of this symptom among people with the condition, according to new research published in the Lancet.

The paper, authored by Dr Manoj Sivan at the University of Leeds, focuses on the case of one 33-year man who developed with acrocyanosis – venous pooling of blood in the legs.

A minute after standing, the patient’s legs began to redden and became increasingly blue over time, with veins becoming more prominent. After 10 minutes the colour was much more pronounced, with the patient describing a heavy, itchy sensation in his legs. His original colour returned two minutes after he returned to a non-standing position.

The patient said he had started to experience the discolouration since his COVID-19 infection. He was diagnosed with postural orthostatic tachycardia syndrome (POTS), a condition that causes an abnormal increase in heart rate on standing.

Dr Sivan, Associate Clinical Professor and Honorary Consultant in Rehabilitation Medicine in the University of Leeds’ School of Medicine, said: “This was a striking case of acrocyanosis in a patient who had not experienced it before his COVID-19 infection.

“Patients experiencing this may not be aware that it can be a symptom of Long Covid and dysautonomia and may feel concerned about what they are seeing. Similarly, clinicians may not be aware of the link between acrocyanosis and Long Covid.

“We need to ensure that there is more awareness of dysautonomia in Long Covid so that clinicians have the tools they need to manage patients appropriately.”

Long Covid affects multiple systems in the body and has an array of symptoms, affecting patients’ ability to perform daily activities. The condition also affects the autonomic nervous system, which is responsible for regulating blood pressure and heart rate.

Acrocyanosis has previously been observed in children with dysfunction of the autonomic nervous system (dysautonomia), a common symptom of post-viral syndromes.

Previous research by Dr Sivan’s team has shown that both dysautonomia and POTS frequently develop in people with Long Covid.

Dysautonomia is also seen in a number of other long-term conditions such as Fibromyalgia and Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome or ME.

Dr Sivan said: “We need more awareness about dysautonomia in long term conditions; more effective assessment and management approaches, and further research into the syndrome. This will enable both patients and clinicians to better manage these conditions.”

The research is the latest work by the team in the field of autonomic medicine. Other developments include a home test for people with symptoms of autonomic dysfunction in conditions such as long COVID, chronic fatigue syndrome, fibromyalgia, and diabetes 1 and 2, where people experience dizziness or blackouts.

Source: University of Leeds

Cognitive Impairment Persists Two Years after COVID Infection

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Researchers from King’s College London have found that people with longer-term COVID symptoms including brain fog showed reduced performance in tasks testing different mental processes – up to two years after infection with the virus, according to results published in the journal eClinicalMedicine.

Researchers examined whether COVID infection affected performance in two rounds of online cognitive testing that took place in 2021 and 2022. Data was collected for over 3000 participants of the COVID Symptom Study Biobank study, across 12 tasks that tested memory, attention, reasoning, processing speed and motor control.

The participants whose test scores were most affected by COVID were those who had experienced symptoms related to the virus for 12 weeks or more. In these people, the effect of COVID on test accuracy was comparable in size to the effect of a 10-year increase in age.

There was no significant improvement in these test scores between the two rounds of testing, which took place nine months apart. By the second round of testing, the average time since participants’ initial COVID infection was almost two years.

The researchers then separated participants by whether they felt fully recovered following COVID infection. People who felt fully recovered after COVID infection performed similarly to those who had not had the virus at all. In contrast, participants who did not feel fully recovered after infection had lower task accuracy scores on average.

Lead author Dr Nathan Cheetham, a Senior Postdoctoral Data Scientist at King’s College London said:

“Our findings suggest that, for people who were living with long-term symptoms after having COVID, the effects of the coronavirus on mental processes such as the ability to recall words and shapes are still detectable at an average of almost two years since their initial infection.

“However, the result that COVID had no effect on performance in our tests for people who felt fully recovered, even if they’d had symptoms for several months and could be considered as experiencing ‘long COVID’, was good news. This study shows the need to monitor those people whose brain function is most affected by COVID-19, to see how their cognitive symptoms continue to develop and provide support towards recovery.”

Professor Claire Steves, a Professor of Ageing and Health at King’s College London, added:

“We used sensitive tests to measure speed and accuracy across a range of brain challenges. This study shows that some individuals have measurable changes in these tests after COVID-19 going on for nearly two years. The fact remains that two years on from their first infection, some people don’t feel fully recovered and their lives continue to be impacted by the long-term effects of the coronavirus. We need more work to understand why this is the case and what can be done to help.”

Source: King’s College London