Tag: long COVID

Long COVID Risk only Slightly Lower after Vaccination

Man wearing mask with headache
Source: Usman Yousaf on Unsplash

Vaccination only reduces the risk of long COVID after infection by only about 15%, according to a study of more than 13 million people published in Nature Medicine. That’s the largest cohort that has yet been used to examine how much vaccines protect against the condition, but it is unlikely to end the uncertainty as other studies have produced conflicting results.

Studying long COVID has been challenging not least because of how hard it is to define from its constellation of symptoms. Even its prevalence has been hard to determine, with some studies suggesting it occurs in 30% of people after COVID infections. But nephrologist Ziyad Al-Aly and colleagues conducted a study of about 4.5 million people treated at US Department of Veterans Affairs (VA) hospitals, and the findings suggested that the number is 7% overall and lower than that for those who were not hospitalised.

Another mystery has been whether long COVID is less likely to occur after a breakthrough infection. But Al-Aly’s team now looked at VA health records from January to December 2021, including those of about 34 000 vaccinated people who had breakthrough SARS-CoV-2 infections, 113 000 people who had been infected but not vaccinated and more than 13 million people who had not been infected.

These results indicated only 15% a reduction of Long COVID in vaccinated individuals, a marked contrast to previous, smaller studies which suggested much higher protection rates. It’s also a departure from another large study, which used self-reported data from 1.2 million UK smartphone users and found that vaccination halved the risk of long COVID.

The authors of the latest study also compared symptoms such as brain fog and fatigue in vaccinated and unvaccinated people for up to six months after they tested positive for SARS-CoV-2. The team found no difference in type or severity of symptoms between those who had been vaccinated and those who had not. “Those same fingerprints we see in people who have breakthrough infections,” Al-Aly said.

In the US alone there have been over 83 million COVID infections, he noted. If even a small percentage of those turn into long COVID, “that’s a staggeringly high number of people affected by a disease that remains mysterious”.

Such limited protection means putting vulnerable people such as the immunocompromised at risk if measures such as masking are withdrawn. “We’re literally solely reliant, now almost exclusively, on the vaccine to protect us and to protect the public,” said Al-Aly. “Now we’re saying it’s only going to protect you 15%. You remain vulnerable, and extraordinarily so.”

“Generally speaking, this is horrifying,” said David Putrino, a physical therapist at Mount Sinai Health System in New York City who studies long COVID. While he praises the study, he notes that it is limited because it does not break the data down by key factors, such as medical history. “These are very important questions we need answers to,” Putrino says. “We don’t have any really well constructed studies just yet.”

Steven Deeks, an HIV researcher at the University of California, San Francisco, points out that the study includes no data from people infected during the period when the Omicron variant was causing the majority of infections. “We have no data on whether Omicron causes long COVID,” he says. The findings, he adds, “apply to a pandemic that has changed dramatically”.

Deeks added, that the results do highlight the need for more research on long COVID, and for accelerated development of therapies. “We don’t have a definition, we don’t have a biomarker, we don’t have an imaging test, a mechanism or a treatment,” he said. “We just have questions.”

Source: Nature

Long COVID Cognitive Impairment More Widespread than Thought

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Scientists following COVID patients up to 12 months after diagnosis have found that mild cognitive impairment is common even after mild to moderate COVID. The study results, currently in preprint on the medRxiv server awaiting peer review, suggest that cognitive impairment, though barely noticeable, may affect large portions of the global population.

The finding comes as the US Centers for Disease Control reported that up to 1 in 5 Americans experienced at least one symptom that could be attributable to Long COVID.

SARS-CoV-2 is believed to cause lasting cognitive impairment in some cases, though the exact nature of it was not clear. Severe COVID cases risk damage through hypoxia, stroke, as well as the immune and inflammatory response to SARS-CoV-2. Mild to moderate COVID cases are still at risk of brain dysfunction, and cognitive deficits, providing a window into the potential mechanisms of brain injury without the confounding role of severe disease and its complications. Given the large numbers of people who had mild to moderate COVID disease, there would be significant implications for public health.

To assess the effects of the disease, the researchers studied 128 SARS-CoV-2 positive patients, assessing cognition and olfaction at set intervals after COVID diagnosis, along with lung capacity and blood biomarkers including the kynurenine pathway (KP).

After correcting for demographics, mild to moderate cognitive impairment was present in 26% on year post diagnosis, respectively. Overall cognitive performance declined mildly, but was statistically significant. KP metabolites quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine were significantly associated with cognitive decline.

“The immune system reacts first with the virus … tries to basically get rid of the virus,” she said to ABC News. “Then it goes a little bit into overdrive and this overdrive does not fully calm down.”

The KP pathway was seen to be disturbed similarly to the way inflammation is caused by viruses such as HIV.

“I think we’re seeing something a bit akin here, where this low level of inflammation is more and more understood as being able to traffic to the brain, or even being within the brain and affecting those regions of the brain where we process information that demand speed, extra attention and extra cognitive demands,” she explained.

Dr Cysique emphasises that the cognitive decline recorded among most participants in the study is mild and they may not even notice it.

The researchers suggested that as a unique biomarker, the KP offers a potential therapeutic target for COVID-related cognitive impairment.

Females ‘Significantly’ More Likely to Experience Long COVID

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A new study published in Current Medical Research and Opinion has revealed that females are “significantly” more likely to suffer from Long COVID than males and will experience substantially different symptoms.

Long COVID is a syndrome in which complications persist more than four weeks after the initial infection of COVID, sometimes for many months.

In a review of studies, researchers observed females with Long COVID are presenting with a variety of symptoms including ear, nose, and throat issues; mood, neurological, skin, gastrointestinal and rheumatological disorders; as well as fatigue.

Male patients, however, were more likely to experience endocrine disorders such as diabetes and kidney disorders.

“Knowledge about fundamental sex differences underpinning the clinical manifestations, disease progression, and health outcomes of COVID is crucial for the identification and rational design of effective therapies and public health interventions that are inclusive of and sensitive to the potential differential treatment needs of both sexes,” the authors explained.

“Differences in immune system function between females and males could be an important driver of sex differences in Long COVID syndrome. Females mount more rapid and robust innate and adaptive immune responses, which can protect them from initial infection and severity. However, this same difference can render females more vulnerable to prolonged autoimmune-related diseases.”

In their review, researchers gathered a total sample size amounting to 1 393 355 unique individuals.

While the number of participants sounds large, only 35 of the 640 634 total articles in the literature provided sex disaggregated data in sufficient details about symptoms and sequalae of COVID disease to understand how females and males experience the disease differently.

The findings showed that, with the initial onset of COVID, female patients were far more likely to experience mood disorders such as depression, ear, nose, and throat symptoms, musculoskeletal pain, and respiratory symptoms. Male patients, on the other hand, were more likely to suffer from renal disorders.

The authors note that this synthesis of the available literature is among the few to break down the specific health conditions that occur as a result of COVID-related illness by sex. Plenty of studies have examined sex differences in hospitalisation, ICU admission, ventilation support, and mortality. But the research on the specific conditions that are caused by the virus, and its long-term damage to the body, have been understudied when it comes to sex.

“Sex differences in outcomes have been reported during previous coronavirus outbreaks,” the authors added. “Therefore, differences in outcomes between females and males infected with SARS-CoV-2 could have been anticipated. Unfortunately, most studies did not evaluate or report granular data by sex, which limited sex-specific clinical insights that may be impacting treatment.” Ideally, sex disaggregated data should be made available even if it was not the researcher’s primary objective, so other interested researchers can use the data to explore important differences between the sexes.

Greater occupational exposure through traditionally female-dominated jobs may may complicate interpretation the COVID sequelae.

Source: EurekAlert!

Substantially Lower Long COVID Risk from Omicron Infection

SARS-CoV-2 infecting a human cell
Infected cell covered with SARS-CoV-2 viruses. Source: NIAID

Findings from a new study reported in The Lancet has found the risks of developing long COVID are greatly reduced (by ~50% to 75%) as a result of Omicron infection compared to Delta infection.

The study, the first of its kind to report on long COVID risk associated with Omicron, highlights the speed with which app-based health surveillance can provide insights. These have further been shown to be consistent and replicable.

A major strength of the study was the ability to log a wide range of symptoms with the app. Limitations of the self-reported data include no direct testing of infectious variants (here assumed from national data) and no objective measures of illness duration. There was insufficient data to estimate the odds of long COVID in unvaccinated individuals. Finally, to enable swift reporting, the period of assessment of omicron cases was slightly shorter than for the delta variant, and assessment of longer durations of long COVID (eg, >12 weeks) was not possible.

In this case-control observational study, the researchers took self-reported data from the COVID Symptom Study app.

However, the researchers noted that the the absolute number of people with long COVID at a certain time depends on the pandemic curve. Considering the UK Omicron peak of more than 350 000 new symptomatic COVID cases per day estimated on March 26, 2022, by the ZOE app model, with 4% of cases being long COVID, future numbers with long COVID will inevitably rise.

Source: The Lancet

Steroids after Severe COVID Reduces One-year Mortality by 51%

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Researchers have shown that severe inflammation during hospitalisation for COVID increases post-recovery mortality risk by 61% – but this risk is reduced again by 51% if anti-inflammatory steroids are prescribed upon discharge. We need to think of COVID as a potentially chronic disease that requires long-term management, argue the authors, whose results are published in Frontiers in Medicine.

Evidence continues to gather that ‘long COVID’, that is, continued negative health impacts months after apparent recovery from severe COVID, is an important risk for some patients. For example, researchers showed last December that hospitalised patients who seemingly recovered from severe COVID run more than double the risk of dying within the next year, compared to those with only mild COVID or who never had COVID.

Now, the same research team shows that among patients hospitalised for COVID who seemingly recovered, severe systemic inflammation during their hospitalisation is a risk factor for death within one year.

“Here we show that the stronger the inflammation during the initial hospitalisation, the greater the probability that the patient will die within 12 months after seemingly ‘recovering’ from COVID.”

Professor Arch G Mainous III

“COVID is known to create inflammation, particularly during the first, acute episode. Our study is the first to examine the relationship between inflammation during hospitalisation for COVID and mortality after the patient has ‘recovered’,” said first author Professor Arch G Mainous III at the University of Florida Gainesville.

“Here we show that the stronger the inflammation during the initial hospitalisation, the greater the probability that the patient will die within 12 months after seemingly ‘recovering’ from COVID.”

Prof Mainous and colleagues analysed electronic health records of 1207 adults hospitalised with COVID in 2020 or 2021 within the University of Florida health system, with at least a one year follow-up after discharge. As a proxy for the severity of systemic inflammation during hospitalisation, they used a common and validated measure: C-reactive protein (CRP), secreted by the liver in response to a signal by active immune cells.

Widespread inflammation in the body

As expected, the blood concentration of CRP during hospitalisation was strongly correlated with the severity of COVID: 59.4mg/L for patients not needing supplemental oxygen, 126.9 mg/L for those who needed extra oxygen without mechanical ventilation, and 201.2 mg/L for the most severe cases, who required ventilation through a ventilator or through ECMO.

After correcting for risk factors, patients with the highest CRP concentration measured their during their hospital stay had a 61% greater risk of all-cause mortality within one year of discharge than patients with the lowest CRP concentration.

Prof Mainous said: “Many infectious diseases are accompanied by an increase in inflammation. Most times the inflammation is focused or specific to where the infection is. COVID is different because it creates inflammation in many places besides the airways, for example in the heart, brain, and kidneys. High degrees of inflammation can lead to tissue damage.”

Importantly, the authors showed that the increased all-cause mortality risk associated with severe inflammation was reduced again by 51% if the patient was prescribed anti-inflammatory steroids after their hospitalisation.

These results mean that the severity of inflammation during hospitalisation for COVID can predict the risk of subsequent serious health problems, including death, from ‘long COVID’. They also imply that current recommendations for best practice may need to be changed, to include more widespread prescription of orally taken steroids to COVID patients upon their discharge.

COVID as a chronic disease?

The authors propose that COVID should be seen as a potentially chronic disease.

“When someone has a cold or even pneumonia, we usually think of the illness being over once the patient recovers. This is different from a chronic disease, like congestive heart failure or diabetes, which continue to affect patients after an acute episode. We may similarly need to start thinking of COVID as having ongoing effects in many parts of the body after patients have recovered from the initial episode,” said Prof Mainous.

“Once we recognise the importance of ‘long Covid’ after seeming ‘recovery’, we need to focus on treatments to prevent later problems, such as strokes, brain dysfunction, and especially premature death.”

Source: Frontiers

Long COVID May be Due to Suppressed Immune System

Man wearing mask with headache
Source: Usman Yousaf on Unsplash

Scientists studying the effect of the monoclonal antibody Leronlimab on long COVID may have found a surprising clue to the baffling syndrome, one that contradicts their initial hypothesis. The cause may be down to an abnormally suppressed immune system, and not a persistently hyperactive one as they initially suspected.

The study was published in Clinical Infectious Diseases.

“While this was a small pilot study, it does suggest that some people with long COVID may actually have under-active immune systems after recovering from COVID, which means that boosting immunity in those individuals could be a treatment,” said senior author Professor Otto Yang.

COVID is known to be caused by hyperactive immune responses against SARS-CoV-2 resulting in damage to lungs and other organs, and sometimes a cytokine storm that overwhelms the individual, which could lead to severe illness and death.

For some who recover from COVID, various symptoms can persist for months, such as fatigue, mental haziness, and shortness of breath. Classified as long COVID, a limited understanding of the causes makes it difficult to develop treatments.

One suggested possibility is that persistence of immune hyperactivity after COVID is a major contributor. The researchers therefore ran a small exploratory trial of Leronlimab, an antibody that attaches to an immune receptor called CCR5 that is involved in inflammation, on 55 people with the syndrome. Leronlimab was originally being developed as an HIV treatment.

Participants were randomised to receiving either weekly injections of the antibody or a saline placebo for eight weeks, and changes in 24 symptoms associated with long COVID were tracked, including loss of smell and taste, muscle and joint pain, and brain fog.

Originally, the researchers believed that blocking CCR5 would calm an overactive immune system after COVID infection. Indeed, preliminary results from an earlier trial appeared to show an improvement with Leronlimab.

“But we found just the opposite,” Prof Yang said. “Patients who improved were those who started with low CCR5 on their T cells, suggesting their immune system was less active than normal, and levels of CCR5 actually increased in people who improved. This leads to the new hypothesis that long COVID in some persons is related to the immune system being suppressed and not hyperactive, and that while blocking its activity, the antibody can stabilize CCR5 expression on the cell surface leading to upregulation of other immune receptors or functions.”

The findings, the researchers wrote, “suggests a complex role for CCR5 in balancing inflammatory and anti-inflammatory effects, eg through T regulatory cells,” although the results need to be confirmed in a larger, more definitive study.

Source: University of California – Los Angeles Health Sciences

About 30% of COVID Patients Develop Long COVID

Woman holding her chest
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A new study published in Journal of General Internal Medicine found that 30% of people treated for COVID developed ‘Long COVID’. Risk of Long COVID was greater in people with a history of hospitalisation, diabetes, and higher BMI; and less in organ transplant recipients and those not on private health insurance. Surprisingly, ethnicity, older age, and socioeconomic status were not linked to the syndrome despite the link to greater risk of severe illness and mortality.

Of the 309 people with long COVID studied, the most persistent symptoms were fatigue and shortness of breath (31% and 15%, respectively) in hospitalised persons, and loss of sense of smell (16%) in outpatients.

The incidence and risk factors of Long COVID, and even how to define the syndrome, have remained unclear throughout the pandemic. The researchers sought evaluate its association with demographics and clinical characteristics in order to devise the most effective treatments.

The study examined 1038 people enrolled in the UCLA COVID Ambulatory Program from April 2020 to February 2021. Of those, 309 developed Long COVID, determined by them reporting persistent symptoms on questionnaires 60 or 90 days after infection or hospitalisation.

Potential weaknesses in the study include the subjective nature of how patients rated their symptoms, the limited number of symptoms the researchers evaluated, and limited information about patients’ pre-existing conditions.

“This study illustrates the need to follow diverse patient populations longitudinally to understand the Long COVID disease trajectory and evaluate how individual factors such as pre-existing co-morbidities, sociodemographic factors, vaccination status and virus variant type affect type and persistence of Long COVID symptoms,” said Dr Sun Yoo, health sciences assistant clinical professor at UCLA. “Studying outcomes in a single health system can minimise variation in quality of medical care. Our study also raises questions such as: Why were patients with commercial insurance twice as likely to develop Long COVID than patients insured through Medicaid? Because persistent symptoms can be subjective in nature, we need better tools to accurately diagnose Long COVID and to differentiate it from exacerbations of other emerging or chronic conditions. Finally, we need to ensure equitable access to outpatient Long COVID care.”

Source: University of California – Los Angeles Health Sciences

Almost a Third of Older Adults Develop New Condition after COVID

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Almost a third of older adults infected with COVID in 2020 developed at least one new condition requiring medical attention in the months after initial infection, compared to only a fifth who were not infected, according to a study published by The BMJ.

Conditions involved a range of major organs and systems, including the heart, kidneys, lungs and liver as well as mental health complications. Some studies now examine the frequency and severity of sequelae after COVID infection, but few have described the excess risk of new conditions triggered by COVID infection in adults 65 and older.

Researchers used US health insurance records to identify 133 366 individuals aged 65 or older in 2020 who were diagnosed with COVID before 1 April 2020. Three (non-COVID) comparison groups were matched: from 2020, 2019, and a group diagnosed with viral lower respiratory tract illness.

The researchers then recorded any persistent or new conditions starting 21 days after a COVID diagnosis (the post-acute period) and calculated the excess risk for conditions triggered by COVID over several months based on age, race, sex, and whether patients were hospitalised with COVID.

The results show that among individuals diagnosed with COVID9 in 2020, 32% sought medical attention in the post-acute period for one or more new or persistent conditions, which was 11% higher than the 2020 comparison group.

Compared with the 2020 comparison group, COVID patients were at increased risk of developing a range of conditions including respiratory failure (an extra 7.55 per 100 people), fatigue (+5.66 per 100), high blood pressure (+4.43 per 100), and mental health diagnoses (+2.5 per 100). Similar findings were found for the 2019 comparison group.

However, compared with the group with viral lower respiratory tract illness, only respiratory failure, dementia, and fatigue showed increased risk differences of 2.39, 0.71, and 0.18 per 100 people with COVID, respectively.

Individuals hospitalised with COVID had a markedly increased risk for nearly all conditions. The risk of several conditions was also increased for men, for those of black race, and for those aged 75 and older.

Limitations include being an observational study – however, the authors warn that the number survivors with sequelae will continue to grow.

“These findings further highlight the wide range of important sequelae after acute infection with the SARS-CoV-2 virus,” they write. “Understanding the magnitude of risk for the most important clinical sequelae might enhance their diagnosis and the management of individuals with sequelae after acute SARS-CoV-2 infection.”

“Also, our results can help providers and other key stakeholders anticipate the scale of future health complications and improve planning for the use of healthcare resources,” they conclude.

Source: The BMJ

COVID is Turning Some Children into ‘Fussy Eaters’

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More and more children could be turning into ‘fussy eaters’ after a bout of COVID, according to smell experts at the University of East Anglia and Fifth Sense, a charity for people affected by smell and taste disorders.

This is because they may be suffering parosmia – a symptom where people experience strange and often unpleasant smell distortions. Once-loved foods like chicken may taste like petrol, for example, making it hard for children to eat those foods and maintain a healthy diet – or even take in enough calories to maintain their weight.

Together, Fifth Sense and leading smell expert Professor Carl Philpott from University of East Anglia, are launching guidance to help parents and healthcare professionals better recognise the disorder.

Prof Carl Philpott said: ”Parosmia is thought to be a product of having less smell receptors working which leads to only being able to pick up some of the components of a smell mixture. It’s a bit like Eric Morecambe famously said to Andre Previn – ‘it’s all the right notes but not necessarily in the right order’.

He said that as COVID swept through classrooms in the UK, there has been a growing awareness that it is affecting children too. “In many cases the condition is putting children off their food, and many may be finding it difficult to eat at all.

“It’s something that until now hasn’t really been recognised by medical professionals, who just think the kids are being difficult eaters without realising the underlying problem. For Prof Philpott, he is seeing teenage patients with parosmia for the first time in his career.

Fifth Sense Chair and founder Duncan Boak said: “We’re hearing anecdotal evidence that children are really struggling with their food after covid.

“If children are suffering smell distortions – and food smells and tastes disgusting – it’s going to be really hard for them to eat the foods they once loved.

“We’ve heard from some parents whose children are suffering nutritional problems and have lost weight, but doctors have put this down to just fussy eating. We’re really keen to share more information on this issue with the healthcare profession so they’re aware that there is a wider problem here.”

Together with Prof Philpott, Fifth Sense have put together guidance for parents and healthcare providers to help recognition and understanding of the problem.

The guidance shows that children should be listened to and believed. Parents can help by keeping a food diary noting those that are safe and those that are triggers.

“Establishing what the triggers are and what tastes ok is really important,” said Prof Philpott.

“There are lots of common triggers – for example cooking meat and onions or garlic and the smell of fresh coffee brewing, but these can vary from child to child.

“Parents and healthcare professionals should encourage children to try different foods with less strong flavours such as pasta, bananas, or mild cheese – to see what they can cope with or enjoy.

“Vanilla or flavour-free protein and vitamin milkshakes can help children get the nutrients they need without the taste. And it may sound obvious, but children could use a soft nose clip or hold their nose while eating to help them block out the flavours.”

Smell training’ has emerged as a simple and side-effect free treatment option for various causes of smell loss, and is a final option to consider.

Prof Philpott said: “Smell training involves sniffing at least four different odours – for example eucalyptus, lemon, rose, cinnamon, chocolate, coffee, or lavender – twice a day every day for several months.

“Children should use smells that they are familiar with and are not parosmia triggers. In younger children this might not be helpful, but in teenagers this might be something they can tolerate.”

Source: University of East Anglia

Over 50s Have Greater Risk of Reduced Mobility after COVID

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Adults over 50 with mild or moderate COVID have increased risk of worsening mobility and physical function, even if hospitalisation is not required to treat the virus, new research has found.

The study, published in JAMA Network Open, highlights the burden of COVID among middle-aged and older adults who are not hospitalised, and suggests that even those who experienced even mild COVID have lasting, troublesome symptoms.

Researchers surveyed more than 24 000 people over the age of 50 from across Canada during the initial phase of the lockdown in 2020 to determine the effect of a COVID diagnosis on their mobility. 

The team looked at mobility issues including difficulty getting up from sitting in a chair, ability to walk up and down stairs without assistance and walking two to three neighbourhood blocks, as well as changes in participants’ ability to move around the home, engage in housework and physical activity.

“We found that even those with mild and moderate illness due to COVID experienced adverse changes in mobility and physical function compared to individuals without COVID,” said co-author Professor Susan Kirkland.

“These findings are worth noting because they indicate that the negative effects of COVID are much broader and impact a wider range of older adults than those who are hospitalised for COVID.”

Participants with COVID had nearly double the odds of worsening mobility and physical function, although most had mild or moderate symptoms. Of the 2748 individuals with confirmed, probable or suspected COVID, 94% were not hospitalised.

Individuals with confirmed or probable COVID had double the odds of worsening ability to engage in household activities and participate in physical activity than those without COVID. Similar results were found for those with suspected COVID.

“Our results showed there was a higher risk for mobility problems in people who were older, had lower income, those with three or more chronic conditions, low physical activity and poorer nutrition,” said co-author, assistant professor Marla Beauchamp.

“However, those factors alone did not account for the mobility problems we observed among people with COVID. Rehabilitation strategies need to be developed for adults who avoid hospitalisation due to COVID but still need support to restore their mobility and physical function.”

The researchers concluded that there is a need to further understand the long-term impacts of COVID and consider “the development and implementation of effective intervention and management approaches to address any persistent deficits in mobility and functioning among those living in the community.”

Source: Dalhousie University