Tag: long COVID

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Long COVID Brain Fog Far More Common in US than India, Other Nations

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Large study of patients in the US, Colombia, Nigeria and India finds symptom burden highest in high-income countries

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Patients with long COVID-19 in the US report far higher rates of brain fog, depression and cognitive symptoms than patients in countries such as India and Nigeria, according to a large international study led by Northwestern Medicine.

The authors note that higher reported symptom burden in the US may reflect lower stigma and greater access to neurological and mental health care, rather than more severe disease.

The study, the first cross-continental comparison of long COVID neurological manifestations, tracked more than 3100 adults with long COVID evaluated at academic medical centres in Chicago; Medellín, Colombia; Lagos, Nigeria; and Jaipur, India.

Among patients who were not hospitalised during their COVID infections (the majority in the study), 86% in the US reported brain fog, compared with only 63% in Nigeria, 62% in Colombia and 15% in India. Rates of psychological distress showed a similar pattern: Nearly 75% of non-hospitalised patients in the US reported symptoms of depression or anxiety, compared with only 40% in Colombia and fewer than 20% in Nigeria and India.

“It is culturally accepted in the US and Colombia to talk about mental health and cognitive issues, whereas that is not the case in Nigeria and India,” said Dr Igor Koralnik, senior study author and chief of neuro-infectious disease and global neurology at Northwestern University Feinberg School of Medicine.

“Cultural denial of mood disorder symptoms as well as a combination of stigma, misperceptions, religiosity and belief systems, and lack of health literacy may contribute to biased reporting. This may be compounded by a dearth of mental health providers and perceived treatment options in those countries.”

The study was published in Frontiers in Human Neuroscience.

Additional key findings

  •        Brain fog, fatigue, myalgia (muscle pain), headache, dizziness and sensory disturbances (such as numbness or tingling) were the most common neurological symptoms across all countries
  •        Insomnia was reported by nearly 60% of non-hospitalised US patients, compared with roughly one-third or fewer of patients in Colombia, Nigeria and India
  •        Statistical clustering showed clear separation between high- and upper-middle-income (US, Colombia) and lower-middle-income (Nigeria, India) countries

Building on this work, Koralnik and his international collaborators are now studying cognitive rehabilitation treatments for long COVID brain fog in Colombia and Nigeria, using the same protocols developed for patients treated at the Shirley Ryan AbilityLab in Chicago.

By Ben Schamisso

Source: Northwestern University

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Study Tracks Physical and Cognitive Impairments Associated with Long COVID

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Researchers following nearly 1000 people with post-COVID-19 syndrome found few changes to their symptoms in the second year of illness

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Two-thirds of people with post-COVID-19 syndrome have persistent, objective symptoms – including reduced physical exercise capacity and reduced cognitive test performances – for a year or more, with no major changes in symptom clusters during the second year of their illness, according to a new study published January 23rd in the open-access journal PLOS Medicine by Winfried Kern of Freiburg University, Germany, and colleagues.

Self-reported health problems following SARS-CoV-2 infection have commonly been described and may persist for months. However, the long-term prognosis of post-COVID-19 syndrome (PCS) is unknown.

In the new study, researchers studied 982 people aged 18 to 65 who had previously been identified as having PCS, as well as 576 controls. All participants visited one of several university health centers in southwestern Germany for comprehensive assessments, including neurocognitive, cardiopulmonary exercise, and laboratory testing.

The predominant symptom clusters among people with PCS were fatigue/exhaustion, neurocognitive disturbances, chest symptoms/breathlessness, and anxiety/depression/sleep problems. Nearly 68% of people who originally reported PCS still struggled with symptoms in the second year. Exercise intolerance with post-exertional malaise was reported by 35.6% of people with persistent PCS, and these people had worse outcomes and more severe symptoms. People with lower educational attainment, obesity, or more severe illness during the initial COVID-19 infection were also at higher risk of prolonged symptoms.

When they looked at objective measures of health and cognition, the team found that people with persistent PCS had significant reductions in handgrip strength, maximal oxygen consumption, and ventilatory efficiency. Patients with persistent PCS and post-exertional malaise scored lower than control patients on cognitive tests measuring memory, attention, and processing speed; however, the researchers point out that they had no data on cognition before acute COVID-19 infection. The team was not able to identify differences in cardiac function or laboratory values, including tests of viral persistence.

“The results call for the inclusion of cognitive and exercise testing in the clinical evaluation and monitoring of patients with suspected PCS,” the authors say. “Observational studies with longer follow-up are urgently needed to evaluate factors for improvement and non-recovery from PCS.”

The authors add, “Grave symptoms with mental and physical exercise dysfunction, but no laboratory markers in Long Covid/post-Covid syndrome.”

Provided by PLOS

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Persistent Infection could Explain Some Long COVID Cases

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A persistent infection could explain why some people experience long COVID symptoms, according to a new study led by researchers at Brigham and Women’s Hospital. The team found evidence of persistent infection in 43% of participants with cardiopulmonary, musculoskeletal or neurologic symptoms of long COVID. The results are published in Clinical Microbiology and Infection.

“If we can identify a subset of people who have persistent viral symptoms because of a reservoir of virus in the body, we may be able to treat them with antivirals to alleviate their symptoms,” said lead author Zoe Swank, PhD, a postdoctoral research fellow in the Department of Pathology at Brigham and Women’s Hospital.

The study analysed 1569 blood samples collected from 706 people, including 392 participants from the National Institutes of Health-supported Researching COVID to Enhance Recovery (RECOVER) Initiative,  who had previously tested positive for a COVID infection. With a highly sensitive test they developed, researchers looked for whole and partial proteins from the SARS-CoV-2 virus. They also analysed data from the participants’ long COVID symptoms, using electronic medical chart information or surveys that were gathered at the same time as the blood samples were taken.

Compared to people who didn’t report long COVID symptoms, those who reported persisting symptoms many organ systems were approximately twice as likely to have SARS-CoV-2 proteins circulating in their blood. The research team was able to detect the spike protein and other components of the SARS-CoV-2 virus using Simoa, an ultrasensitive test for detecting single molecules. Commonly reported long COVID symptoms included fatigue, brain fog, muscle pain, joint pain, back pain, headache, sleep disturbance, loss of smell or taste, and gastrointestinal symptoms.

Specifically, 43% of those with long COVID symptoms affecting three major systems in the body, including cardiopulmonary, musculoskeletal, and neurologic systems, tested positive for viral proteins within 1 to 14 months of their positive COVID test. But only 21% of those who didn’t report any long COVID symptoms tested positive for the SARS-CoV-2 biomarkers in this same period.

It’s possible that a persistent infection explains some – but not all – of the long COVID sufferers’ symptoms. If this is the case, testing and treatment could aid in identifying patients who may benefit from treatments such as antiviral medications.

A Condition with More Than One Cause

One of the questions raised by the study is why more than half of patients with wide-ranging long COVID symptoms tested negative for persistent viral proteins.

“This finding suggests there is likely more than one cause of long COVID,” said David Walt, PhD, a professor of Pathology at Brigham and Women’s Hospital and Principal Investigator on the study. “For example, another possible cause of long-COVID symptoms could be that the virus harms the immune system, causing immune dysfunction to continue after the virus is cleared.”

To better understand whether an ongoing infection is behind some people’s long COVID symptoms, Swank, Walt and other researchers are currently conducting follow-up studies. They’re analyzing blood samples and symptom data in larger groups of patients, including people of wide age ranges and those with compromised immune symptoms. This way, they can also see if some people are more likely to have persistent virus in the body.

“There is still a lot that we don’t know about how this virus affects people,” said David C. Goff, MD, PhD, a senior scientific program director for the RECOVER Observational Consortium Steering Committee and director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH. “These types of studies are critical to help investigators better understand the mechanisms underlying long COVID – which will help bring us closer to identifying the right targets for treatment.”

Goff added that these results also support ongoing efforts to study antiviral treatments.  

The SARS-CoV-2 blood test developed by Brigham and Women’s researchers is also currently being used in a national study, called RECOVER-VITAL, that is testing whether an antiviral drug helps patients recover from long COVID. The RECOVER-VITAL trial will test the patients’ blood before and after treatment with an antiviral to see if treatment eliminates persistent viral proteins in the blood.

The idea that a virus can stay in the body and cause ongoing symptoms months after an infection isn’t unique to COVID. “Other viruses are associated with similar post-acute syndromes,” said Swank. She noted animal studies have found Ebola and Zika proteins in tissues post-infection, and these viruses have also been associated with post-infection illness.

Source: Brigham and Women’s Hospital

Categories : COVID NeurologyTags :

Higher Doses of Lithium might Relieve Long COVID, Research Suggests

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A small University at Buffalo clinical trial has found that at low doses, lithium aspartate is ineffective in treating the fatigue and brain fog that is often a persistent feature of long COVID; however, a supplemental dose-finding study found some evidence that higher doses may be effective.

Published in JAMA Network Open, the study was led by Thomas J. Guttuso, Jr., MD, professor of neurology in the Jacobs School of Medicine and Biomedical Sciences at UB and a physician with UBMD Neurology.

“It’s a negative study with a positive twist,” Guttuso concludes.

Because long COVID is believed to stem from chronic inflammation and lithium has known anti-inflammatory actions, Guttuso had recommended that a patient of his try low-dose lithium for persistent long COVID symptoms. He was surprised when this patient reported a near full resolution of fatigue and brain fog within a few days of initiating lithium aspartate at 5mg a day.

Relief from symptoms

Based on this single case, Guttuso became interested in lithium aspartate as a potential treatment for long COVID and recommended it to other such patients.

According to Guttuso, 9 of 10 long COVID patients he treated with lithium aspartate 5-15mg a day saw very good benefit in terms of improvements to their fatigue and brain fog symptoms.

“Based on those nine patients, I had high hopes that we would see an effect from this randomized controlled trial,” says Guttuso. “But that’s the nature of research. Sometimes you are unpleasantly surprised.”

The randomised controlled trial showed no benefit from 10-15mg a day of lithium aspartate compared to patients receiving a placebo.

After one patient from the study subsequently increased the lithium aspartate dosage to 40mg a day and experienced a marked reduction in fatigue and brain fog symptoms, Guttuso decided to then conduct a dose-finding study designed to explore if a higher dose of lithium aspartate may be effective.

The three participants who completed the dose-finding study reported greater declines in fatigue and brain fog with the higher dose of 40-45mg per day. This was especially true in the two patients with blood lithium concentrations of 0.18 and 0.49mmol/L compared to one patient with a level of 0.10mmol/L who saw partial improvements.

“This is a very small number of patients, so these findings can only be seen as preliminary,” says Guttuso. “Perhaps achieving higher blood levels of lithium may provide improvements to fatigue and brain fog in long COVID.”

Dosage may be too low

He notes that it is possible the randomized controlled trial was ineffective because the dose of lithium aspartate that was used was too low.

“The take-home message is that very low dose lithium aspartate, 10-15 milligrams a day, is ineffective in treating the fatigue and brain fog of long COVID,” says Guttuso. “Perhaps we need to do another randomised controlled trial that uses higher lithium aspartate dosages that achieve blood lithium levels of 0.18-0.50mmol/L to determine if they could be effective.”

An estimated 17 million people have long COVID in the US, and worldwide the number is estimated at 65 million.

“There currently are no evidence-based therapies for long COVID,” says Guttuso. He hopes that the National Institutes of Health will view lithium as worth studying through a trial with higher dosages; the NIH is allocating an additional $500 million to study long COVID therapies that appear to be promising.

Guttuso adds that if a subsequent randomised controlled trial finds that higher dosages of lithium aspartate are effective, long COVID patients would still need to discuss taking it with their health care providers; in addition, he says, if they do begin taking it at higher dosages, blood lithium levels should be monitored.

Source: University at Buffalo

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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

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Scientists Discover Immune Key for Chronic Viral Infections

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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

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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

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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

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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

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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