A US study published in JAMA Network Open found that COVID was associated with a 4% increase in use of health care services across that country over the six months after initial infection.
Long COVID is known to affect some COVID patients long after symptoms of the acute infection had subsided. The typical clinical symptoms in long COVID are tiredness, dyspnoea, fatigue, brain fogginess, autonomic dysfunction, headache, persistent loss of smell or taste, cough, depression, low-grade fevers, palpitations, dizziness, muscle pain, and joint pains. This study showed that the greatest increase in encounters for these patients was in virtual visits, followed by emergency department visits.
“This study showed us that, in terms of the number of follow-up visits, a substantial amount of health care utilisation occurs in the six months following the acute stage of SARS-CoV-2 infection, which highlights the potential for COVID to exert an ongoing demand on health care organisations,” said epidemiologist Sara Y. Tartof, PhD, one of the study’s lead authors. “A 4% increase in encounters applied across a large population is a large number of visits associated with substantial cost. The absolute number is big. In this case, it was over 27 000 extra encounters among the eight health care organisations included in this study.”
Dr Tartof added: “On a broader scale, this study will help health care organisations develop their long-term strategic plans to meet patients’ needs following COVID infection.”
This study included patients of all ages from eight large integrated health care organizations across the US who completed a COVID diagnostic test between March 1 and November 1, 2020. Patients were matched on age, sex, race, ethnicity, site, and date of COVID test, and were followed for 6 months. The final matched study group consisted of 127 859 patients who tested positive for COVID-19 with an equal number testing negative.
Overall coronavirus infection was associated with a 4% increase in health care use over six months, predominantly for virtual encounters, followed by emergency department visits.
COVID-associated health care encounters for 18 conditions remained elevated 6 months from the acute stage of illness, with the largest increase in COVID-related utilisation including:
lingering COVID
alopecia, also known as hair loss
bronchitis
pulmonary embolism or deep vein thrombosis
difficulty breathing
In total, extra health care use associated with the effects of COVID infection consisted of 212.9 additional encounters per 1000 patients with COVID.
The study is one of the largest and most comprehensive studies of post-COVID utilisation among children under age 17.
COVID-positive children experienced increased health care use over six months for pulmonary embolism or deep vein thrombosis; irregular heartbeat; difficulty breathing; and ear, nose, and throat disorders.
“With complete data from all care settings across large integrated health care organisations, this study represents one of the largest and most comprehensive studies of post-COVID conditions to date,” said epidemiologist Debbie Malden, DPhil, another lead author.
Professor Resia Pretorius sounds rushed when Spotlight first tracks her down by phone at Heathrow Airport outside London. She is about to board a plane to South Africa after attending a conference, meetings, and symposia in the United Kingdom, all with the purpose of unravelling the complexity of long COVID and how to treat it.
There is no global consensus among researchers and clinicians on a definition for long COVID, there is no adequate diagnostic test for the debilitating condition, and the causes of patients progressing to long COVID are, at this stage, theoretical.
However, Pretorius who heads the Department of Physiological Science at the University of Stellenbosch remains upbeat. Her research group is the first to have reported evidence of inflammatory microclots in blood samples from individuals with long COVID, potentially solving an important piece of the long COVID puzzle.
She says scientific collaboration is intensifying to find answers to long COVID which affects 43% or 100 million people globally post-infection, according to a meta-analysis and systematic review.
Later speaking from Stellenbosch, Pretorius describes herself as a “lab person” who has been trying to find the cause of long COVID since 2020. “I have always been passionate about research. Now, I am working with clinicians and researchers in the UK, the USA, and other parts of the world. I am too worried to miss anything so I am at all of these meetings. There are 40 to 50 researchers globally who talk to each other regularly. We are going to crack this I know. We just have to.”
Causes of long COVID
As explained in a recent article in the journal Science, there are three leading theories scientists are pursuing in an attempt to decipher the effects of post-COVID-19 infection – which leads to an array of symptoms, including shortness of breath, fatigue, headaches, palpitations, and impairments in mental health and cognition or brain fog.
One theory is that SARS-CoV-2 stubbornly persists in the body, even after the acute infection passes. Studies have shown that the virus lingers in a wide range of body sites, especially in the nerves and other tissues.
Another theory based on blood samples from COVID-19 patients reveals an immune system in disarray even eight months after first testing positive. The body’s cells do not appear to recover.
Images of micro clots as seen under an electron microscope. PHOTO: Supplied
The third, an area in which Pretorius has distinguished herself internationally, is that COVID-19 is not only a lung disease but significantly affects the vascular (blood flow) and coagulation (blood clotting) systems of the body.
A recent study published in the Cardiovascular Diabetology journal, conducted by Pretorius and colleagues, found that there is significant microclot formation in the blood of both acute COVID-19 and long COVID patients. A microclot is a blood clot that can only be seen through a microscope.
Pretorius explains that in a healthy person clots may form, for example, when you cut yourself. The main clotting protein is a molecule called fibrinogen. “When you’re healthy, it’s in solution. And then when you cut yourself, collagen is exposed, and a little gel called fibrin prevents you from bleeding out. In healthy individuals, the clots are then broken down by a process called fibrinolysis.
Blood samples from patients with long COVID have revealed high levels of various inflammatory molecules trapped in the microclots including fibrinogen and Alpha-2 antiplasmin – a molecule that prevents the breakdown of microclots.
The persistent blood clots essentially result in cells not getting enough oxygen in the tissues to sustain bodily functions. This, Pretorius says, may be central to numerous debilitating symptoms.
In healthy individuals, the body’s plasmin-antiplasmin system maintains a fine balance between blood clotting to prevent blood loss after an injury and fibrinolysis which prevents blood clots from forming.
With high levels of alpha(2)-antiplasmin in the blood of acute COVID-19 patients and individuals suffering from long COVID, the body’s ability to break down the clots is significantly undermined. The blood circulation becomes clogged up.
Microclots are generally not found in people who do not have long COVID. Pretorius says you can find them in some other conditions, such as diabetes, “but the difference is the number and the extreme presence of the clots with long COVID, that’s what’s making the difference,” she says.
Insoluble clots
Another difference is that the clots in long COVID are insoluble. When Pretorius tried to dissolve these clots using an enzyme called trypsin in her laboratory, they would not dissolve. They are resistant to fibrinolysis.
Initially, Pretorius was looking at acute COVID-19 infection. We received blood samples from ICU patients and we made blood smears and looked at them under a scanning electron microscope that can enlarge a sample hundreds of thousands of times. We then added a fluorescent dye or marker called Thioflavin T which lights up when there are misfolded proteins. This happens when, for example, the spike protein binds to the soluble fibrinogen molecule making it insoluble.
The SARS-CoV-2 virus is known to bind to ACE2 receptors and TMPRSS receptors which are found on platelets (blood cells that help with clotting). They are also found on the endothelium (the inner-most lining of the blood vessels). By binding to the platelets and the endothelium, the virus sets off a torrent of clotting causing vascular damage.
Pretorius says in early 2021, “I got a report from Harvard collaborators and others to say that patients do not fully recover post-infection and they referred to this as long COVID.
“I said let’s get the samples. We looked at the blood samples and lo and behold we found the clots and they were fully persistent. I was not surprised to find the clots in long COVID because I knew with acute COVID many people were dying because of clots in the lungs and shortness of breath. But, I did not know the extent to which they were present in long COVID.”
“When we did proteomics analysis on the sample, when we looked at the different molecules in the blood, I could not dissolve the sample with typical enzymes. I used a massively abrasive enzyme called Trypsin which dissolves any possible protein. But it could not dissolve these cells. The resilience of these clots, that they simply don’t get dissolved, surprised me,” Pretorius says.
Pretorius recalls that in 2020, several South African clinicians alerted others to COVID-19 not being a typical viral pneumonia but suggested it was also a vascular disease. “At that stage, it was massively controversial with many dismissing this idea saying it’s a virus that affects the lungs and that’s it,” she says.
Pretorius says this was despite papers published overseas in 2020 that concluded COVID-19 was also a vascular disease. “It was made controversial in South Africa but it is now widely accepted that COVID-19 also affects clotting as well as the body’s vasculature (network of blood vessels).”
Pretorius says, “Although the microclot is a theory, it encompasses all of the other suggested causes of long COVID because the spike protein itself can trigger microclots. We have submitted a paper, looking at many more blood samples, where we found inflammatory molecules trapped inside the blood clots which do not break down. We also found antibodies so the theories about immune abnormalities, persistent virus, and microclots are intertwined. All of these can cause organ damage. So if you look at it from a systems biology approach, all of these are valid.”
Many are told that their symptoms are possibly psychological, all in their head, and they are told to get some rest and to stop stressing. Meanwhile, the patients are very ill
Diagnostics
Pretorius says there are no general pathology tests readily available to diagnose people with long COVID.
“People that are desperately ill – bedridden or in wheelchairs – are often given generalised blood tests. They are told that their pathology test results are within normal to healthy ranges. Many are told that their symptoms are possibly psychological, all in their head, and they are told to get some rest and to stop stressing. Meanwhile, the patients are very ill,” she says.
Pretorius says the main reason the traditional laboratory tests do not pick up any of the inflammatory molecules is that they are trapped inside the insoluble microclots. A typical pathology test looks at the soluble content of the blood, so if the molecules are trapped they will be missed.
“We patented a long COVID test which is just a simple microscopy test that is a useable diagnostic method to see if microclots are present,” Pretorius says.
Microscopy methods are not readily available at pathology laboratories. However, Pretorius says, “We have crowd-funded and received funding from the Polybio Research Foundation in America to buy a flow cytometer for our blood lab to develop a flow cytometry method that can be used in the typical pathology labs. So we hope to have a diagnostic that will be readily available in a couple of months.”
Treatment
Pretorius says colleagues in the United Kingdom have already designed two randomised controlled trials to independently test both coagulation therapy (CLOTT-UK) and Apheresis (CLOTT-Apheresis trial ) in which microclots and inflammatory molecules are filtered out in a dialysis-type treatment. These trials will study whether anticoagulants and Apheresis give long-lasting relief of symptoms. These trials are being planned and researchers are waiting for ethics approval.
In addition, colleagues from the University of Sheffield Hallam and from the University of Manchester have independently set up microclot testing in their labs and they are planning to publish their UK cohort results soon. They are also correlating long COVID severity to microclot presence, says Pretorius.
“It’s been quite a ride. Seeing the devastation of long COVID, I realise why I decided not to be a clinician… handling and hearing all the issues is just so sad,” says Pretorius.
But, she remains determined to help “crack” long COVID.
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.”
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.
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.
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.
Participants were selected on a positive COVID test after SARS-CoV-2 after vaccination, at least one log per week in the app for at least 28 days after testing positive, and no previous SARS-CoV-2 infections before vaccination. The researchers identified 56 003 UK adults first testing positive between Dec 20, 2021, and March 9, 2022, when the Omicron variant became dominant. Similarly, researchers identified 41 361 UK adult cases first testing positive between June 1, 2021, and Nov 27, 2021, during the period of Delta dominance.
Both symptomatic and asymptomatic infections were considered, and, for the Omicron period, only participants testing positive before Feb 10, 2022, were included, to ensure all participants had at least 28 days for symptom reporting after testing positive. The researchers adjusted for socioeconomic deprivation and other factors.
In both periods, female participation was higher than male participation (55% for Omicron and 59% for Delta cases). Delta and Omicron cases had similar age (mean age 53 years) and prevalence of comorbidities (around 19%). Among Omicron cases, 2501 (4.5%) of 56 003 people experienced long COVID and, among Delta cases, 4469 (10.8%) of 41 361 people experienced long COVID. Cases were stratified by time from vaccination to first infection. They found that, for all vaccine timings, Omicron cases were less likely to experience long COVID, with an odds ratio ranging from 0.24 to 0.50.
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.
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.”
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.
“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.
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.”
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.
