This website is intended for healthcare professionals only.
Take a look at a selection of our recent media coverage:
12th February 2024
An online rehabilitation programme can improve quality of life for adults with long Covid, a UK randomised controlled trial has found.
Researchers at the University of Warwick said it was the first high-quality evidence confirming the sustained clinical benefit and lack of harm with rehabilitation programmes for long Covid.
Those taking part in the eight-week REGAIN programme had weekly live online supervised, group exercise and psychological support sessions that they took part in from home.
Reporting the findings in the BMJ, the researchers said that at three months, 17% of the intervention group reported that their overall health was ‘much better now’ compared with 8% in the usual care group.
The study of 585 participants who were randomly assigned to the programme or a control group, which involved a one-off advice session, was also shown to be clinically effective at improving health related quality of life at one year.
Sustained improvements were seen in fatigue, anxiety, depression, pain, and other measures of general health, among participants, the researchers said.
Those taking part had an average age of 56 years and had all been hospitalised with Covid-19. They had all reported substantial ongoing physical and/or mental health problems more than three months after they were discharged.
National surveys have reported more than one million people in the UK report Covid-19 symptoms persisting for more than 12 weeks, with over 750,000 reporting ongoing symptoms more than two years after infection.
Debilitating symptoms can include fatigue, shortness of breath, cognitive dysfunction, pain, reduced physical capacity, and poor emotional wellbeing, all of which can profoundly affect quality of life.
Study leader Professor Gordon McGregor, professor of clinical exercise physiology and rehabilitation, at the University of Warwick, said: ‘There was no precedent for how best to treat people with long Covid.
‘We knew that centre-based NHS rehabilitation services did not have the capacity to support the numbers of people recovering from Covid-19, so alternative long-term strategies were needed.
He added that the REGAIN programme has the potential to reduce the chronic burden of Covid-19 and widen access to support. An economic evaluation of the study is also being undertaken.
‘Apart from the direct benefits for those concerned, improving the general health of people with long Covid can reduce demand on health and social care more widely and improve economic productivity,’ he said.
Dr Emily Fraser, consultant in respiratory medicine at Oxford University Hospitals NHS Foundation Trust, and clinical lead of a Post Covid clinic, said the study was not looking at a biomedical explanation for long Covid, which is proving difficult to pin down, but on what can practically be done to support patients.
‘A focus on rehabilitation and holistic care is essential for both management of symptom burden and supporting recovery of these patients, and group programmes that are online and accessible have been shown at our local level to be really beneficial.
‘Feeling supported, understood and reducing the sense of isolation that many patients have after hospital discharge is really important, alongside setting realistic expectations of recovery and what this looks like.’
But she pointed out a post-hospitalised group are demographically distinct from the community-managed post-Covid patients they see much more commonly.
It is ‘difficult to draw similarities to a female in their 40s who was previously healthy with a full-time job, three kids and an initial relatively mild acute illness’, she said, although rehab strategies should still be the focus.
A version of this article was originally published by our sister publication Pulse.
6th November 2023
Tens of thousands of people are suffering with long Covid symptoms more than a year after infection, say researchers who carried out the UKs largest study of the impact of the virus.
A survey of a quarter of a million people taking part in the REACT study found that while most people recover within 12 weeks, 7.5% of people had persistent symptoms for more three months and 5% reported symptoms lasting more than a year.
But people infected in the Omicron wave of the pandemic were 88% less likely to experience symptoms longer than four weeks after infection, compared to earlier wave, the study found, which could be due to immunity building up in the population and vaccination.
The new analysis, published in the journal Nature Communications, also highlighted how persistent symptoms of Covid-19 were related to worse mental health and quality of life.
Being female, already having more than one comorbidity, being from a deprived area, and being infected with an original strain of Covid-19 were all related with higher risk of symptoms lasting more than 12 weeks and longer recovery time in those with persistent symptoms, the researchers said.
The survey results – which were collected in towards the end of 2022 – show a snapshot of the continued impact of Covid-19 in the UK, the Imperial College London team noted.
Mild fatigue, difficulty thinking or concentrating and joint pains were the most common ongoing symptoms. But others reported loss or change of sense of smell or taste, shortness of breath, severe fatigue, chest tightness or pain, and poor memory.
Almost a third of people reporting symptoms at 12 weeks recovered within a year, the researchers found.
Professor Paul Elliott, chair of epidemiology and public health medicine at Imperial College London, said: ‘We find that the variant of SARS-CoV-2 people are infected with, the initial severity of their symptoms, and whether they have pre-existing health conditions all have an impact on whether they will develop lasting symptoms.’
Study lead Dr Christina Atchison, principal clinical academic fellow within the School of Public Health at Imperial College London, said while the landscape has changed considerably since the early peak of the Covid-19 pandemic, this analysis shows that a proportion of adults are still experiencing lasting symptoms.
‘Importantly, we find that compared to wild type virus, those infected when Omicron was dominant were far less likely to report symptoms lasting beyond 12 weeks,‘ she said. ‘This may reflect the changing levels of immunity in the population from previous exposure to the virus and vaccination.’
The team is now doing detailed interviews with some of those affected with ongoing symptoms to further understand the variation in people’s experiences and the impact on their everyday lives as well as the broader longer-term impact of the pandemic on health and wellbeing of those who took part in REACT.
This article was originally published by our sister publication Pulse.
12th October 2023
‘Long colds’ with similar respiratory impact as long Covid may be an ‘underestimated’ issue, a new study has concluded.
By analysing 16 potential long Covid symptoms in participants from a UK population-based study, researchers found that a previous Covid infection was ‘associated with increased prevalence and severity of a wide range of symptoms’.
In particular, participants with a previous Covid infection had increased odds of problems with taste or smell and lightheadedness or dizziness compared with participants who had previous non-Covid acute respiratory infections (ARIs).
However, they also found ‘increased burden of many symptoms’ among those who had non-Covid ARIs when compared with those who had no previous infections.
The authors therefore suggested there could be ‘long-lasting health impacts from other respiratory infections that are going unrecognised’.
Using the COVIDENCE UK study, the researchers looked at data reported between January and February 2021 by over 10,000 participants who were unvaccinated against Covid.
Their findings said: ‘Participants with SARS-CoV-2 infection had increased odds of problems with taste/smell (odds ratio 19.74, 95% CI 10.53–37.00) and lightheadedness or dizziness (1.74, 1.18–2.56) compared with participants with non-Covid-19 ARIs.’
But for other symptoms, there was ‘little difference’ between those with previous Covid infections and those with other infections.
While the researchers suggested that long-term symptoms following ARIs could be similar to long Covid, they highlighted that their study does not show whether these symptoms have a similar duration.
The findings also indicated that coughing, problems with taste or smell and dyspnoea may be the first symptoms to show improvement following a Covid infection, since there was a lower symptom burden among participants who had been infected more than 12 weeks prior.
Both long Covid and post-ARI symptoms are likely under-reported, and, for the latter, an ‘alternative diagnosis’ may be needed, according to the authors.
They said: ‘Importantly, less than a quarter of our participants with previous SARS-CoV-2 infection had ever reported long Covid – including half of participants with the most severe symptoms – suggesting that some people with ongoing symptoms may not be ascribing these symptoms to the infection, or may not consider their symptoms serious enough to qualify as long Covid.
‘This could exacerbate under-reporting of the condition, likely impacting the healthcare resources made available to people with long-term sequelae.
‘A lack of awareness of post-acute sequelae of other ARIs – or even the lack of a common term, like “long Covid” – is likely to contribute to under-reporting as well.’
The authors highlighted the need for future research to enable diagnosis of both long Covid and other post-ARI symptoms so that all patients get the support they need.
Professor Paul Harrison, professor of psychiatry at the University of Oxford, said the study ‘supports previous findings that long-term symptoms are common after respiratory infections in general’ and not just after Covid.
He added: ‘However, Covid-19 infection was associated with a higher risk of several complaints, including memory problems, suggesting that ‘brain fog’ may be particularly related to the SARS-CoV-2 virus.’
Professor Peter Openshaw, professor of experimental medicine at Imperial College London, said: ‘The study is important in showing that recovery from ARI may be slow regardless of cause, that people should expect a slow return to normality and not expect to immediately return to full activities immediately after an ARI from whatever cause.
‘The study does not show how many of those suffering from ARI go on to develop longer term debility.’
This story was originally published by our sister publication Pulse.
27th September 2023
The benefits of ensitrelvir use in patients with symptoms of long Covid and as a second-line treatment option for those hospitalised with Covid-19, have been presented at the recent European Scientific Working Group on Influenza and other Acute Respiratory Viruses’ (ESWI) Influenza Conference.
Ensitrelvir is an oral antiviral drug for Covid-19 manufactured by Shionogi, which is currently approved under the emergency regulatory approval system in Japan. The drug inhibits 3CL protease, an enzyme that is essential for the replication of the virus.
The first study presented at the ESWI Influenza Conference was an exploratory analysis of the Phase 3 part of the pivotal SCORPIO-SR trial. Conducted in Japan, South Korea and Vietnam, the researchers found that ensitrelvir may reduce the risk of a number of persistent and new late-onset symptoms associated with long Covid over one year.
Long Covid was analysed based on a patient-reported questionnaire at three, six and 12 months from the first date of treatment. The researchers defined long Covid by patient reports of ‘not having returned to pre-Covid health’ and having at least one (mild or more severe) symptom out of 27 possible symptoms.
The use of ensitrelvir at doses of 125 mg and 250 mg, showed a numerical relative risk reduction of 25% and 26% respectively when compared to the placebo for 27 long Covid symptoms at one year. A similar trend in risk reduction was observed at three and six months.
Furthermore, in subgroup analyses, there was a greater risk reduction in patients with a body mass index of ≥25 kg/m2 as well as in those with a median or higher symptom score at the start of treatment.
These results suggest that early treatment of Covid-19 with ensitrelvir could reduce the risk of a number of persistent and new late-onset symptoms associated with long Covid.
Dr Andreas Karas, vice president, medical affairs, Shionogi Europe, said: ‘As Covid-19 remains endemic, persisting symptoms continue to adversely affect millions of people worldwide. We’re pursuing further research to substantiate the potential of ensitrelvir as a treatment option for acute Covid-19 infection and whether this can prevent the long-term effects the virus can cause.
‘We look forward to sharing the results at ESWI and to hearing from the community as we advance our global ensitrelvir clinical development program.‘
In the second study presented at the ESWI Influenza Conference, researchers suggested that for hospitalised patients with Covid-19 and significant co-morbidities who failed to respond to remdesivir as the first-line treatment, ensitrelvir could serve as an alternative treatment.
The small, real-world study from Japan, conducted at the Rinku General Medical Centre, included 21 high-risk hospitalised patients with Covid-19 infections who failed to respond to a three-day course of remdesivir.
These patients, who had either a mild or moderate severity infection and of whom a third (33.3%) had co-morbidities, then received five days of treatment with ensitrelvir 125 mg.
After five days of treatment, all 21 patients showed clinical improvement. Furthermore, no deaths or drug-related adverse events were observed at day 28, but one person later died in the hospital at day 59.
Masaya Yamato, an investigator on these trials and director of the Infectious Diseases Center at Rinku General Medical Center in Osaka, Japan, said: ‘While certain treatments are available for high-risk people with Covid-19 to reduce the risk of becoming seriously ill, additional treatment options are needed. These results indicate the potential for ensitrelvir to help address these needs.‘
Ensitrelvir remains an investigational drug outside of Japan. In April 2023, the FDA in the US recently granted fast track designation to the drug for Covid-19. This process is designed to facilitate the development and expedite the review of potential new therapies that treat serious conditions and fulfil an unmet medical need.
12th June 2023
Metformin use by overweight or obese patients reduces the risk of developing long Covid by around 41%, according to the findings of a recent randomised, placebo-controlled trial.
Published in The Lancet Infectious Diseases, the study followed up on previous research which sought to determine whether the use of metformin, ivermectin or fluvoxamine prevented the primary outcome. These were the occurrence of hypoxemia, an emergency department visit, hospitalisation, or death associated with Covid-19. The researchers concluded that none of three drugs reduced the primary outcome.
For the follow-up study, the same researchers followed a subgroup of patients for 300 days to assess if any of the drugs would prevent long Covid. The participants were adults aged 30-85 years with overweight or obesity and with Covid symptoms for less than seven days. In the original trial, metformin was titrated up to a dose of 1,500 mg daily and the subsequent development of long Covid was physician diagnosed. The design of the original trial enabled a comparison of metformin use with a matching placebo and the findings of the current study largely relate to metformin.
A total of 1,126 participants, 564 assigned to metformin and the remainder to matched placebo were included in the analysis. Overall, 8.3% of the cohort had developed long Covid by day 300.
The cumulative incidence of long Covid was 6.3% in the metformin group, but 10.4% (7.8-12.9) in those who received placebo (Hazard ratio, HR = 0.59, 95% CI 0.39 – 0.89 p = 0.012). In practice therefore, use of metformin reduced the absolute risk of developing long Covid by 4.1%. In other words, 24 people would need to take metformin to prevent one case of long Covid.
In the subgroup there were some interesting observations. The reduction in the risk of developing long Covid from using metformin was only significant if given less than three days from symptom onset (HR = 0.37, 95% CI 0.15 – 0.95). Similarly, the effect was also only significant in patients under 45 years of age, women and those with a body mass index greater than 30. Furthermore, metformin had no significant effect among those vaccinated against Covid-19.
Despite the positive findings, the researchers do acknowledge some limitations. Firstly, it is unclear if their findings would be generalisable to adults of a normal weight. Secondly, with a largely white population, whether metformin would still be effective for different ethnicities is unclear.
8th June 2023
A recent study showing that patients with long Covid had reduced vitamin D levels, raises the possibility that supplementing with the vitamin to ensure adequate levels may protect against this post-infection sequela. Rod Tucker considers the evidence.
A recent observational study published in The Journal of Clinical Endocrinology & Metabolism (JCEM), found that among patients initially hospitalised with Covid-19, those who developed long Covid had significantly lower vitamin D levels than a group of matched controls without the condition six months later.
This suggests that supplementing with the vitamin could help mitigate long Covid. Nevertheless, in order to prevent long Covid (also referred to as post-Covid condition), vitamin D should also have a role in protecting against infection with the virus in the first place.
With more than three years having passed since the start of the pandemic, is there now convincing evidence that supplementing with vitamin D reduces the risk of infection with Covid-19 virus and therefore the risk of long Covid?
The role of vitamin D in protecting against viral infections has been known for some time. In 2013, a systematic review of 11 placebo-controlled trials found that vitamin D had a protective effect against respiratory tract infections and these findings were confirmed in an update review from 2021.
Following the emergence of the Covid-19 virus, there was renewed interest in these findings, given how Covid-19 was perceived as a respiratory pathogen. Additionally, further support for the potential role of vitamin D came from observational studies demonstrating an inverse relationship between serum 25-hydroxyvitamin D concentrations and the incidence or severity of Covid-19 and how low serum vitamin D levels represented an independent risk factor for both Covid-19 infection and hospitalisation.
Given the relationship between low serum vitamin D levels and Covid-19, could supplementing with the vitamin reduce the risk of infection? The answer it seems, is only maybe. The available evidence is somewhat mixed though one study sounded a note of caution, suggesting how supplementing with the vitamin was potentially harmful.
This caution arose from an Italian study, undertaken in Lombardy during the early part of the pandemic, among those hospitalised with Covid-19. It observed that in patients previously taking taking vitamin D supplements, there was a trend towards higher mortality. As this was an observational study, the evidence was potentially unreliable. The real proof could only be derived from a randomised trial.
Fortunately, one such trial in a group of front-line healthcare workers with suboptimal vitamin D levels, found a significantly lower risk of infection among those supplementing with vitamin D. In contrast, however, a test-and-treat study in patients with suboptimal vitamin D levels, concluded that treatment with the vitamin was not associated with a reduction in the risk of Covid-19 infection.
Other work showed how giving patients hospitalised Covid-19 a vitamin D boost had no effect on their length of hospital stay, but the use of vitamin D did reduce the risk of death and intensive care unit (ICU) admission. More recently, a Spanish study comparing cholecalciferol or calcifediol supplementation, observed how both were associated with a lower risk of infection, less severe infection and a lower risk of death but only where serum vitamin D levels exceeded 30 ng/ml.
Although not definitive, it seems that vitamin D may well offer some protection against infection with Covid-19 and the subsequent adverse health outcomes such as ICU admission. But does vitamin D also exert a protective role against the development of long Covid and would supplementation help, particularly those with low serum levels?
Unfortunately, the answer is far from clear, but the available data does not seem to hold much promise. For instance, in one analysis of those with long Covid, characterised predominately by fatigue and reduced exercise tolerance, the authors concluded that these symptoms were independent of vitamin D levels. Other work has also failed to identify any relationship between vitamin D deficiency and post-Covid symptoms.
Part of the problem is that the risk factors for developing long Covid are less well defined than for infection. Long Covid is associated with a myriad of both physical and mental symptoms that negatively impact on quality of life. It has even been suggested that many long Covid symptoms are not directly due to the virus itself, but that the Covid virus is able to reactivate the Epstein-Barr virus.
While supplementing with vitamin D may well help to reduce the risk of developing a Covid-19 infection and the subsequent Covid-related adverse outcomes, the role of the vitamin in long Covid is more uncertain. Although the recent JCEM study highlighted that low vitamin D levels were associated with long Covid, there is an urgent need for randomised trials to explore the possible value of supplementing with the vitamin as a means of attenuating this debilitating post-infection sequela.
11th May 2023
Fergus Gleeson has long held an interest in MRI scanning techniques that use hyperpolarised xenon – an odourless gas – to detect early-stage lung disease. Here, he discusses his interest in xenon, how the gas works in practice and his latest research findings in relation to long-Covid.
In 2020, Fergus Gleeson, professor of radiology at Oxford University and consultant radiologist at Oxford University Hospitals NHS Foundation Trust, turned his attention to a small study of post-Covid patients. They were experiencing breathlessness several months after being discharged from hospital, despite CT scans that appeared to show their lungs were normal.
The findings from this small study prompted Professor Gleeson to widen the research to investigate possible lung damage in non-hospitalised, post-Covid patients who continue to experience breathlessness many months after infection.
He is the principal investigator of the EXPLAIN study, one of 19 projects to receive nearly £40m from the National Institute for Health Research to improve understanding of long-Covid, from diagnosis and treatment through to rehabilitation and recovery.
I’ve worked in the xenon field since 2007/08 to identify patients with obstructive lung disease and interstitial lung disease, as have other researchers, including Professor Jim Wild, who is the head of imaging and NIHR research professor of magnetic resonance at the University of Sheffield. [Indeed, Wild pioneered the method, development and applications of hyperpolarised xenon MRI used in the EXPLAIN study.]
Xenon is unique in its ability to measure gas transfer in the lungs. The MRI scanner is programmed to detect signal from polarised xenon. The oxygen in the normal air we breathe isn’t used because it does not give enough MRI signal. Xenon behaves just like oxygen, so radiologists can use it to observe how it moves from the lungs into the blood stream and highlight any areas where it is not flowing well between the airways, gas exchange membranes and capillaries in the lungs.
The patient lies in an MRI scanner on a magnet with a vest like coil around their chest and breathes in one litre of inert gas xenon through a plastic straw. It is possible to watch the physiology of a patient’s lungs in real time and see where the xenon might be held up, how fast it moves, whether it gets to the alveoli and from this assess how well the exchange of oxygen and carbon dioxide happens in the blood. The degree of gas exchange is colour coded with areas of more damaged lungs being darker or a different colour to areas with normal exchange.
The scan times may be very short, for example a single sequence may only require the patient to breathe in and hold their breath for 14-20 seconds. There’s no radiation exposure so it can be repeated over time to see whether the changes to the lungs improve. If the research proves to be clinically useful, the equipment could be set up in multiple regional centres in a relatively short space of time. All that is needed is a cylinder of xenon and the polariser – which is about the size of a large chest of drawers. The MRI scanner would also need to be modified to detect the signal from the xenon gas.
Ours is located in the radiology department at the Churchill Hospital in Oxford. There’s one in Sheffield University’s imaging department, one is being installed at University College Hospital London and one at Manchester University. There’s also a couple in Denmark, two in Germany, several in the United States and at least one in Canada.
Some people were complaining of persistent breathlessness and fatigue for many months after the Covid-19 infection, so we conducted a small study on patients aged between 19 and 69. None of them required intensive care or ventilation, and standard CT scans showed no significant lung damage. The hyperpolarised xenon MRI scans revealed signs of lung damage for a number of the patients who were reporting breathlessness.
We then broadened the study out to include non-hospitalised individuals who had tested positive for Covid-19 across a range of age groups. Now, there are many different arms of the study and we’re working with three other hospital sites: Sheffield, Manchester and Cardiff. Hundreds of thousands of people in the UK continue to experience symptoms months after having Covid-19, with breathlessness one of the most commonly reported symptoms.
We hope to identify what’s causing patients with long-Covid breathlessness and essentially give them answers as to how long they might have these abnormalities and whether they’ll get better.
We’re using hyperpolarised xenon MRI scans to investigate possible lung damage in long-Covid patients who have not been hospitalised with Covid-19 but who continue to experience breathlessness. The full study will recruit around 400 participants following on from our two initial pilot studies. The EXPLAIN study will include:
We detected significantly impaired gas transfer from the lungs to the bloodstream in long-Covid patients when other tests were normal. These patients had never been in hospital, did not have an acute severe illness when they had their Covid-19 infection, and some had experienced symptoms for a year after contracting it. The important questions that now need answering are how many patients with long-Covid will have abnormal scans, what the significance of the abnormality we’ve detected is, what the cause of the abnormality is and what its longer-term consequences will be. Once we understand the mechanisms driving these symptoms, we will be better placed to develop more effective treatments.
We need to complete recruitment and analyse the data, so we have some way to go before fully understanding the nature of the lung impairment that follows Covid-19 infection. However, the clinical-academic collaboration in EXPLAIN and other studies funded by NIHR are fundamental steps towards understanding the biological basis of long-Covid. This, in turn, will help us to develop more effective therapies.
14th October 2022
A Scottish study has found that 18 months after a symptomatic COVID-19 infection, 11% of patients reported being still not being fully recovered with just over half (51%) stating that they were only partially recovered.
Long covid is now referred to by the World Health Organisation as post COVID-19 and defined as a condition that occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis. While this definition considers the persistence of symptoms for longer than two months, a meta-analysis of 18 studies which included 8,591 COVID-19 survivors with post-COVID symptoms persisting for at least 12 months, found that fatigue/weakness, dyspnoea, arthromyalgia, depression/anxiety, memory loss/concentration difficulties and insomnia were the most prevalent symptoms at one-year follow-up. However, in the meta-analysis, the majority of the included studies (13) were from hospitalised patients and the sample sizes varied from 51 to 2433 with a median of 146.
For the present study, researchers included patients with all levels of disease severity, those with both asymptomatic and symptomatic infections and included a comparator group of individuals who reported never being infected with the virus. Data were collected from the Long-CISS study, and which invited everyone over 16 years of age in Scotland with a positive PCR test for COVID-19 to participate. The study also included with a comparison group of non-infected individuals and PCR positive individuals were matched 3:1 with non-infected individuals based on age, sex and area-based socioeconomic deprivation quintile. The data were collected via an on-line questionnaire, and which was repeated 6, 12 and 18 months after individual’s infection to assess the extent to which they had recovered. The questionnaire assessed 26 symptoms, limitations across 7 activities of daily living and health-related quality of life, hospitalisations and assessed recovery as full, partial or none (i.e., not recovered).
Participants not recovered during follow-up
A total of 96,238 individuals with a median age of 45 years (60.9% female) were included in the study, of whom, 31,486 had symptomatic COVID-19, 1,795 an asymptomatic infection and 62,957 who had never been infected.
A total of 3,744 individuals provided data on their recovery status at 6 and 12 months and after 6 months, 8% reported that they had not recovered and this figure was unchanged at 12 months. In addition, 45% and 46% stated that they were fully recovered at 6 and 12 months respectively. Interestingly, a similar proportion reported being only partially recovered at 6 and 12 months (47% and 46% respectively). Only 197 individuals provided data at 12 and 18 months and of these, 11% reported being not recovered at both time points, whereas a slightly higher proportion (51%) stated that they were partially recovered at 12 and 18 months.
Individuals who reported being symptomatic reported a significantly higher risk of impairment of 6 of the 7 daily living activities including walking/getting around (odds ratio, OR = 1.80, 95% CI 1.73 – 1.88, p < 0.001) and exercise or sport (OR = 2.34) and housework or chores (OR = 1.97). Symptomatic participants also reported a number of symptoms on follow-up, of which the highest were changes in taste and smell.
Factors associated with a lack of complete recovery were more severe initial infection, white ethnicity and pre-existing health conditions.
The authors concluded that 6 – 18 months following symptomatic infection with COVID-19, adults were at greater risk of a diverse range of symptoms and a negative impact on daily activities that could not be explained by confounding.
Citation
Hastie CE et al. Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study Nat Commun 2022
2nd August 2022
The World Health Organization uses the term post COVID-19 conditions (i.e., long COVID), to define a condition that occurs among ‘individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis.
To date, the currently available literature on long covid relates to the symptoms developed in adults, although one recent analysis that specifically focused on children and young people and who were followed-up for a median of 125 days, observed a range of symptoms including a higher incidence of diarrhoea and fatigue.
Nevertheless, the complete range and frequency of long Covid symptoms that develop in children and adolescents remains unclear and was the subject of the current study by the Mexican and US team.
The researchers looked for any type of study that included children and discussed long COVID, which they defined as the presence of one or more symptoms for longer than 4 weeks after the acute infection.
Children and long covid
The search identified a total of 21 eligible studies with 80,071 children and adolescents and which were included in the meta-analyses. The number of patients in each of the studies ranged from 53 to 57,763 and the participant ages from 0 to 18 years and the authors identified more than 40 long-term clinical manifestations of long Covid.
The overall prevalence of long Covid in children and adolescents was 25.2% (95% CI 18.2 –33.0) although among children who had been hospitalised, this increased to 29.2% (95% CI 17.8–41.9).
A wide range of symptoms were detected, with the most common (16.5%) being mood symptoms (e.g., sadness, tension, anger, depression, and anxiety) fatigue (9.7%), sleep disorders (8.4%) which encompassed insomnia, hypersomnia, and poor sleep quality. Other symptoms included headache (7.8%) and respiratory symptoms (7.6%).
The authors calculated that in comparison to controls, children with long COVID had a higher risk of persistent dyspnoea (OR 2.69, 95% CI 2.3 – 3.1), anosmia/ageusia (OR 10.7, 95% CI 2.5 – 46.0), and/or fever (OR 2.2, 95% CI 1.2 – 4.1).
Based on their findings, they concluded that the results of the meta-analysis supported the continued monitoring of the impact of long Covid on children and adolescents.
Citation
Lopez-Leon S et al. Long-COVID in children and adolescents: a systematic review and meta-analysis Sci Rep 2022
8th July 2022
The continued presence of spike protein in patients with long COVID may be responsible for their persistent symptoms and serve as a biomarker for the condition according to a small scale study by researchers from Boston, US.
Although many millions of people who have been infected with COVID-19 make a full recovery, for some, symptoms may continue and they develop a wide range of persistent symptoms that fail to resolve over the course of many months. Such patients are diagnosed with long COVID or post-acute sequelae of COVID-19 (PASC).
The World Health Organization have described what it terms ‘post COVID-19 condition’ defined as occurring in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis.
The cause of PASC remains to be determined although many theories have been proposed including tissue persistence of viral antigen, systemic and tissue localised inflammatory responses, reactivation of human herpesviruses (e.g., Epstein-Barr virus), alterations in the gut microbiome, issues related to clotting, and the interplay between SARS-CoV-2-specific and auto-reactive immunity.
Nevertheless, untangling the complex biology involved may be assisted through the identification of biomarkers in those with PASC.
In the present study, the US team analysed plasma samples from patients with PASC and for comparative purposes those who had been infected with COVID-19 but made a full recovery. The researchers measured the levels of three antigens: the S1 subunit of spike, full length spike protein and nucleocapsid (N).
Spike protein levels in PASC
The study included a sample of 37 PASC patients with a median age of 46 years (81% female) and 26 (median age 63, 38% female) without PASC.
For the PASC patients, blood samples were collected two or more times up to 12 months after their initial PCR confirmed COVID-19 infection. Blood samples were collected from individuals who had COVID-19 but not PASC, up to five months post-diagnosis.
The team were able to detect either S1, full length spike protein or N in roughly 65% of PASC patients at any given point in time, several months post-COVID-19. For the 3 antigens however, spike protein was detected in 60% of PASC patients, whereas S1 was detected to a lesser extent and N only in a single patient at different time points. Spike protein was undetectable in those who had fully recovered from COVID-19 although both S1 and N were found.
In cases where PASC patients had blood samples collected a multiple time points, all three antigens could be detected several months after the acute infection, although spike protein was detected most often over time.
Commenting on these results, the authors noted how circulating levels of spike protein in the majority of PASC patients but none of those without PASC was compelling. Given that only two patients with PASC had been hospitalised, these results suggested the continued presence of spike protein was associated with COVID-19 infection per se rather than the severity of infection.
The authors added that detection of spike protein was likely to indicate that PASC is associated with a reservoir of active virus and which persisted in the body.
The authors concluded that spike protein could potentially serve as a biomarker for PASC although further studies with larger patient cohorts were required to confirm these findings.
Citation
Swank Z et al. Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae MedRxiv 2022
Download Hospital Healthcare Europe free app
© Cogora 2024
Cogora Limited. 1 Giltspur Street, London EC1A 9DD
Registered in the United Kingdom. Reg. No. 2147432
