Post-COVID Clinics / Long Haulers

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Re: Post-COVID Clinics / Long Haulers

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Doctors scramble to understand long Covid, but causes and prognosis are elusive

4/22/21


https://www.news-medical.net/news/20210 ... usive.aspx


One night in March 2020, Joy Wu felt like her heart was going to explode. She tried to get up and fell down. She didn't recognize friends' names in her list of phone contacts. Remembering how to dial 9-1-1 took "quite a bit of time," she recalled recently.

Wu, 38, didn't have a fever, cough or sore throat — the symptoms most associated with Covid-19 at the time — so doctors at the hospital told her she was having a panic attack. But later she developed those symptoms, along with difficulty breathing, fatigue and neurological issues.

Wu, of San Carlos, California, believes she had Covid — although, like many others who were unable to get tested early in the pandemic, she never got an official diagnosis. And, she said, its aftereffects continue to plague her.

Wu has struggled to get help from doctors, even those who take her symptoms seriously. “There’s no actual treatment,” she said, for people experiencing these lasting symptoms, often referred to as long Covid. When seeking help, “you’re basically a guinea pig at this point.”

For people suffering with lingering, debilitating symptoms months after a bout with Covid, pinning down a definition for long Covid may seem pointless. They just want relief.

"I don't care if it's Covid or some other illness," Wu said. "I want to get better."

But to public health experts, medical researchers and health care providers, understanding the causes, risk factors and spectrum of symptoms is vital.

"There's no single sign or lab test that can distinguish this syndrome from something else," said Dr. John Brooks, chief medical officer for the Centers for Disease Control and Prevention's Covid response. "Having something that we can use to define a [long-Covid] case is critical" for tracking how many people get it and how well they do, and to establish research criteria for clinical trials.

It's no easy task. There is no typical Covid "long hauler." After an infection, some people's initial symptoms don't abate, while other people develop entirely new symptoms that may affect multiple organs and systems. Studies have documented hundreds of lingering problems, but intense fatigue; chest pain; memory and concentration problems, often referred to as "brain fog"; shortness of breath; and a loss of taste and smell are common.

Having been hospitalized or placed on a ventilator isn't a reliable sign that someone will develop the condition. Many young, previously healthy people who had a mild initial infection are battling long Covid. Some people's symptoms drag on for months after their acute infection, while others' symptoms ebb and flow on a "corona coaster" of relapse and recovery.

In February, the National Institutes of Health announced a $1.15 billion, four-year initiative to study the causes and prevention of long Covid. The new research will bolster the growing number of studies that have already been published.

Younger and sicker


A year ago, when the novel coronavirus was surging through New York, Mount Sinai Health System created an app to monitor Covid patients at home, said David Putrino, the system's director of rehabilitation innovation. By early May it was apparent that roughly 10% of these non-hospitalized patients weren't getting better, he said. Many were younger and, until they got sick, healthier than the average Covid patient. And they were struggling with new symptoms they hadn't experienced in their original illness, such as heart palpitations and extreme fatigue.

An interdisciplinary team started to see these patients at what later became the Center for Post-Covid Care. Up to 30% of the patients have persistent symptoms that are a continuation of those they experienced when they were acutely ill, Putrino said. The other 70% tend to have novel symptoms that are specific to long Covid.

Mount Sinai's clinic, which manages the care of about 900 long Covid patients, is one of several dozen across the country devoted to Covid recovery, though the parameters for which patients they treat vary. Many involve multiple medical specialties, while others are dedicated to neurological or pulmonary symptoms or the aftereffects of ICU stays. Some require the patient to have a positive diagnostic or antibody test.

Putrino noted that some symptoms that Covid long haulers complain of are similar to those that affect people with "post-viral syndrome" who are recovering from serious infections like Ebola and Zika.

Such viral infections can cause severe inflammation and residual symptoms that last for months or years, said Dr. Steven Deeks, a professor of medicine at the University of California-San Francisco who is tracking people with long-Covid symptoms.

Other researchers have suggested that long Covid may actually encompass a number of separate syndromes, including post-intensive care syndrome, post-traumatic stress disorder or myalgic encephalomyelitis, sometimes called chronic fatigue syndrome. Still others note that some long Covid symptoms look like dysautonomia, a term for disorders of the autonomous nervous system, which regulates breathing and heart rate, among other things.

Whatever "long Covid" ultimately comes to mean, it continues to surprise medical experts. If someone has a serious bout of pneumonia, an infection that inflames the air sacs in the lungs, it's not surprising if they have a bad cough for a few months as their body slowly heals, said Brooks, of the CDC.

But with a Covid infection, sometimes that cough doesn't go away for many months, and along with it someone might have brain fog. Another might develop encephalitis, a swelling of the brain.

"This is not a cluster [of symptoms] that we see after a typical viral respiratory infection," Brooks said.

A push by patients

There are several working theories about what causes long Covid.

Some studies suggest that the virus or remnants of it may lurk in the body and continue to stimulate the immune system. Or the virus may have been cleared, but "the immune system keeps fighting against a perceived enemy, because it hasn't gotten the word that the war is over," said Dr. Michael Saag, a professor of medicine and infectious diseases at the University of Alabama-Birmingham who participated in a two-day workshop sponsored by NIH in December. Or tissues may have been damaged during the initial immune response, causing long-term symptoms.

Despite the imprimatur of respected researchers and public health experts, skeptics remain. Some doctors complain that the diagnosis is being propelled by interest groups rather than science. Others compare it to other chronic conditions, like fibromyalgia, for which there are no definitive diagnostic tests. Some suggest it is a psychosomatic illness.

Patients and their advocates played a crucial role in drawing attention to and gaining acceptance of long Covid.

After contracting Covid in March 2020, Diana Berrent started Survivor Corps as a Facebook support group; it has grown into a broader advocacy organization for Covid patients, with more than 150,000 members.

"Most of the people who we see suffering from long-term Covid were not the ones who were in the hospital and on ventilators," Berrent said. "These are people who mostly had what I had — what I call the 'Tylenol and Gatorade' variety of Covid," which they coped with at home.

Much like patients with myalgic encephalomyelitis/chronic fatigue syndrome, people with long Covid say finding supportive medical providers is a problem, said Emily Taylor, director of advocacy and community relations at the group Solve M.E. It recently co-founded the Long Covid Alliance with 21 other organizations to draw attention to post-viral illnesses.

Long Covid presents an opportunity to find answers not only for long Covid but also for a range of conditions that have struggled for research dollars and support.

"The post-viral research community is all coming together now to address Covid," Taylor said. "Frankly, there's no other option."
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Re: Post-COVID Clinics / Long Haulers

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COVID-19 survivors have increased risk of death for at least six months

4/23/21


https://www.news-medical.net/news/20210 ... onths.aspx


As the COVID-19 pandemic has progressed, it has become clear that many survivors -; even those who had mild cases -; continue to manage a variety of health problems long after the initial infection should have resolved.

In what is believed to be the largest comprehensive study of long COVID-19 to date, researchers at Washington University School of Medicine in St. Louis showed that COVID-19 survivors -; including those not sick enough to be hospitalized -; have an increased risk of death in the six months following diagnosis with the virus.

The researchers also have catalogued the numerous diseases associated with COVID-19, providing a big-picture overview of the long-term complications of COVID-19 and revealing the massive burden this disease is likely to place on the world's population in the coming years.

The study, involving more than 87,000 COVID-19 patients and nearly 5 million control patients in a federal database, appears online April 22 in the journal Nature.

" Our study demonstrates that up to six months after diagnosis, the risk of death following even a mild case of COVID-19 is not trivial and increases with disease severity. It is not an exaggeration to say that long COVID-19 -; the long-term health consequences of COVID-19 -; is America's next big health crisis. Given that more than 30 million Americans have been infected with this virus, and given that the burden of long COVID-19 is substantial, the lingering effects of this disease will reverberate for many years and even decades. Physicians must be vigilant in evaluating people who have had COVID-19. These patients will need integrated, multidisciplinary care."

- Ziyad Al-Aly, MD, Study Senior Author and Assistant Professor of Medicine, Washington University in St. Louis

In the new study, the researchers were able to calculate the potential scale of the problems first glimpsed from anecdotal accounts and smaller studies that hinted at the wide-ranging side effects of surviving COVID-19, from breathing problems and irregular heart rhythms to mental health issues and hair loss.

"This study differs from others that have looked at long COVID-19 because, rather than focusing on just the neurologic or cardiovascular complications, for example, we took a broad view and used the vast databases of the Veterans Health Administration (VHA) to comprehensively catalog all diseases that may be attributable to COVID-19," said Al-Aly, also director of the Clinical Epidemiology Center and chief of the Research and Education Service at the Veterans Affairs St. Louis Health Care System.

The investigators showed that, after surviving the initial infection (beyond the first 30 days of illness), COVID-19 survivors had an almost 60% increased risk of death over the following six months compared with the general population.

At the six-month mark, excess deaths among all COVID-19 survivors were estimated at eight people per 1,000 patients. Among patients who were ill enough to be hospitalized with COVID-19 and who survived beyond the first 30 days of illness, there were 29 excess deaths per 1,000 patients over the following six months.

"These later deaths due to long-term complications of the infection are not necessarily recorded as deaths due to COVID-19," Al-Aly said. "As far as total pandemic death toll, these numbers suggest that the deaths we're counting due to the immediate viral infection are only the tip of the iceberg."

The researchers analyzed data from the national health-care databases of the U.S. Department of Veterans Affairs. The dataset included 73,435 VHA patients with confirmed COVID-19 but who were not hospitalized and, for comparison, almost 5 million VHA patients who did not have a COVID-19 diagnosis and were not hospitalized during this time frame. The veterans in the study were primarily men (almost 88%), but the large sample size meant that the study still included 8,880 women with confirmed cases.

To help understand the long-term effects of more severe COVID-19, the researchers harnessed VHA data to conduct a separate analysis of 13,654 patients hospitalized with COVID-19 compared with 13,997 patients hospitalized with seasonal flu. All patients survived at least 30 days after hospital admission, and the analysis included six months of follow-up data.

The researchers confirmed that, despite being initially a respiratory virus, long COVID-19 can affect nearly every organ system in the body. Evaluating 379 diagnoses of diseases possibly related to COVID-19, 380 classes of medications prescribed and 62 laboratory tests administered, the researchers identified newly diagnosed major health issues that persisted in COVID-19 patients over at least six months and that affected nearly every organ and regulatory system in the body, including:

Respiratory system: persistent cough, shortness of breath and low oxygen levels in the blood.
Nervous system: stroke, headaches, memory problems and problems with senses of taste and smell.
Mental health: anxiety, depression, sleep problems and substance abuse.
Metabolism: new onset of diabetes, obesity and high cholesterol.
Cardiovascular system: acute coronary disease, heart failure, heart palpitations and irregular heart rhythms.
Gastrointestinal system: constipation, diarrhea and acid reflux.
Kidney: acute kidney injury and chronic kidney disease that can, in severe cases, require dialysis.
Coagulation regulation: blood clots in the legs and lungs.
Skin: rash and hair loss.
Musculoskeletal system: joint pain and muscle weakness.
General health: malaise, fatigue and anemia.

While no survivor suffered from all of these problems, many developed a cluster of several issues that have a significant impact on health and quality of life.

Among hospitalized patients, those who had COVID-19 fared considerably worse than those who had influenza, according to the analysis. COVID-19 survivors had a 50% increased risk of death compared with flu survivors, with about 29 excess deaths per 1,000 patients at six months. Survivors of COVID-19 also had a substantially higher risk of long-term medical problems.

"Compared with flu, COVID-19 showed remarkably higher burden of disease, both in the magnitude of risk and the breadth of organ system involvement," Al-Aly said. "Long COVID-19 is more than a typical postviral syndrome. The size of the risk of disease and death and the extent of organ system involvement is far higher than what we see with other respiratory viruses, such as influenza."

In addition, the researchers found that the health risks from surviving COVID-19 increased with the severity of disease, with hospitalized patients who required intensive care being at highest risk of long COVID-19 complications and death.

"Some of these problems may improve with time -; for example, shortness of breath and cough may get better -; and some problems may get worse," Al-Aly added. "We will continue following these patients to help us understand the ongoing impacts of the virus beyond the first six months after infection. We're only a little over a year into this pandemic, so there may be consequences of long COVID-19 that are not yet visible."

In future analyses of these same datasets, Al-Aly and his colleagues also plan to look at whether patients fared differently based on age, race and gender to gain a deeper understanding of the risk of death in people with long COVID-19.

Source:

Washington University in St. Louis

Journal reference:


Al-Aly, Z., et al. (2021) High-dimensional characterization of post-acute sequalae of COVID-19. Nature. doi.org/10.1038/s41586-021-03553-9.
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Re: Post-COVID Clinics / Long Haulers

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Doctors More Likely to Prescribe Opioids to Covid ‘Long Haulers,’ Raising Addiction Fears

4/28/21


https://khn.org/news/article/doctors-mo ... ion-fears/


Covid survivors are at risk from a possible second pandemic, this time of opioid addiction, given the high rate of painkillers being prescribed to these patients, health experts say.

A new study in Nature found alarmingly high rates of opioid use among covid survivors with lingering symptoms at Veterans Health Administration facilities. About 10% of covid survivors develop “long covid,” struggling with often disabling health problems even six months or longer after a diagnosis.

For every 1,000 long-covid patients, known as “long haulers,” who were treated at a Veterans Affairs facility, doctors wrote nine more prescriptions for opioids than they otherwise would have, along with 22 additional prescriptions for benzodiazepines, which include Xanax and other addictive pills used to treat anxiety.

Although previous studies have found many covid survivors experience persistent health problems, the new article is the first to show they’re using more addictive medications, said Dr. Ziyad Al-Aly, the paper’s lead author.

He’s concerned that even an apparently small increase in the inappropriate use of addictive pain pills will lead to a resurgence of the prescription opioid crisis, given the large number of covid survivors. More than 3 million of the 31 million Americans infected with covid develop long-term symptoms, which can include fatigue, shortness of breath, depression, anxiety and memory problems known as “brain fog.”

The new study also found many patients have significant muscle and bone pain.

The frequent use of opioids was surprising, given concerns about their potential for addiction, said Al-Aly, chief of research and education service at the VA St. Louis Health Care System.

“Physicians now are supposed to shy away from prescribing opioids,” said Al-Aly, who studied more than 73,000 patients in the VA system. When Al-Aly saw the number of opioids prescriptions, he said, he thought to himself, “Is this really happening all over again?”

Doctors need to act now, before “it’s too late to do something,” Al-Aly said. “We must act now and ensure that people are getting the care they need. We do not want this to balloon into a suicide crisis or another opioid epidemic.”

As more doctors became aware of their addictive potential, new opioid prescriptions fell, by more than half since 2012. But U.S. doctors still prescribe far more of the drugs — which include OxyContin, Vicodin and codeine — than physicians in other countries, said Dr. Andrew Kolodny, medical director of opioid policy research at Brandeis University.

Some patients who became addicted to prescription painkillers switched to heroin, either because it was cheaper or because they could no longer obtain opioids from their doctors. Overdose deaths surged in recent years as drug dealers began spiking heroin with a powerful synthetic opioid called fentanyl.

More than 88,000 Americans died from overdoses during the 12 months ending in August 2020, according to the Centers for Disease Control and Prevention. Health experts now advise doctors to avoid prescribing opioids for long periods.

The new study “suggests to me that many clinicians still don’t get it,” Kolodny said. “Many clinicians are under the false impression that opioids are appropriate for chronic pain patients.”

Hospitalized covid patients often receive a lot of medication to control pain and anxiety, especially in intensive care units, said Dr. Greg Martin, president of the Society of Critical Care Medicine. Patients placed on ventilators, for example, are often sedated to make them more comfortable.

Martin said he’s concerned by the study’s findings, which suggest patients are unnecessarily continuing medications after leaving the hospital.

“I worry that covid-19 patients, especially those who are severely and critically ill, receive a lot of medications during the hospitalization, and because they have persistent symptoms, the medications are continued after hospital discharge,” Martin said.

While some covid patients are experiencing muscle and bone pain for the first time, others say the illness has intensified their preexisting pain.

Rachael Sunshine Burnett has suffered from chronic pain in her back and feet for 20 years, ever since an accident at a warehouse where she once worked. But Burnett, who first was diagnosed with covid in April 2020, said the pain soon became 10 times worse and spread to the area between her shoulders and spine. Although she was already taking long-acting OxyContin twice a day, her doctor prescribed an additional opioid called oxycodone, which relieves pain immediately. She was reinfected with covid in December.

“It’s been a horrible, horrible year,” said Burnett, 43, of Coxsackie, New York.

Doctors should recognize that pain can be a part of long covid, Martin said. “We need to find the proper non-narcotic treatment for it, just like we do with other forms of chronic pain,” he said.

The CDC recommends a number of alternatives to opioids — from physical therapy to biofeedback, over-the-counter anti-inflammatories, antidepressants and anti-seizure drugs that also relieve nerve pain.

The country also needs an overall strategy to cope with the wave of post-covid complications, Al-Aly said

“It’s better to be prepared than to be caught off guard years from now, when doctors realize … ‘Oh, we have a resurgence in opioids,’” Al-Aly said.

Al-Aly noted that his study may not capture the full complexity of post-covid patient needs. Although women make up the majority of long-covid patients in most studies, most patients in the VA system are men.

The study of VA patients makes it “abundantly clear that we are not prepared to meet the needs of 3 million Americans with long covid,” said Dr. Eric Topol, founder and director of the Scripps Research Translational Institute. “We desperately need an intervention that will effectively treat these individuals.”

Al-Aly said covid survivors may need care for years.

“That’s going to be a huge, significant burden on the health care system,” Al-Aly said. “Long covid will reverberate in the health system for years or even decades to come.”
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Re: Post-COVID Clinics / Long Haulers

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Long COVID also affects children, study finds

4/28/21

https://www.news-medical.net/news/20210 ... finds.aspx


Older children and children with allergies or asthma were found to have greater odds of having persistent symptoms even months after recovery.

With the COVID-19 pandemic continuing to affect many parts of the globe, our understanding of the short-term and acute effects of the disease has been growing, but its consequences on long-term health are still poorly known. Some studies report individuals with symptoms such as fatigue, muscle weakness, and breathlessness six months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These long-term effects are known as Long COVID.

Although children are at lower risk for severe COVID-19, they still have many different symptoms. Some data suggests up to a third of hospitalized children required intensive care, with some children showing multi-organ failure requiring support to breathe. A few children develop a severe condition a few weeks after recovery called multisystem inflammatory syndrome in children (MIS-C).

Data on the long-term effects of severe COVID-19 in children is still limited to small studies. But, these show that more than half the children have at least one symptom that persists even after four months of infection.

In a new study published on the medRxiv* preprint server, researchers followed hospitalized children after discharge to understand the effect of COVID-19 over the long term.

Following hospitalized children after recovery

The researchers studied children admitted to the Z.A. Bashlyaeva Children’s Municipal Clinical Hospital in Moscow between April and August 2020. The team followed up with the parents of these children in February 2021 to complete a survey.

From the hospital medical records, the team obtained information such as demographics, symptoms, co-morbidities, care at the hospital, clinical outcomes. Using the follow-up survey, the team obtained information on persistent symptoms and the children's general physical and psychosocial well-being compared to before COVID-19.

Of the 836 children admitted to the hospital and with accurate contact information, the researchers were able to conduct a follow-up survey of 518 children. The median age of the children was about 10 years,.

The most common pre-existing condition was a food allergy, followed by allergic rhinitis and asthma, gastrointestinal problems, eczema, and neurological problems. About 37% of the children had pneumonia during their stay in the hospital, and about 2.7% had severe disease.

During the follow-up, about one-fourth of the children reported at least one persistent symptom. The most common were fatigue, followed by insomnia. They also reported changed smell and headaches. Most symptoms decreased over time, but sleep disturbances and headaches did not change. This could be related more to psychological mechanisms rather than virus effects. Some symptoms such as fatigue and sleep issues were seen together.

Wellness scores for children with persistent symptoms were much lower than the scores before COVID-19, while children with no long-term symptoms did not report any changes in wellness. Other changes such as decreased appetite, increased sleep, and reduced physical activity were reported to be because of COVID-19. About one in twenty parents attributed changes to COVID-19.

Risk factors for long COVID

Older children, above 6 years, had greater odds of persistent symptoms than children less that 2 years old. In adults also, the risk for long COVID-19 symptoms has been seen to increase with age. Another predictor for long-term symptoms was allergic diseases. This is also similar to what is seen in adults. Studies have reported long COVID in people with asthma. Some reports suggest COVID-19 consequences may be related to mast cell activation, seen in allergic diseases, which may be responsible for long-term consequences of COVID-19.

Since the study is based on the ISARIC COVID-19 Health and Wellbeing Follow-Up Survey for Children, it will help compare with other such future studies. The large sample size and the longest time of follow-up to date is another strength of the study.

The authors do note some limitations. The study was based only on children in Moscow and included only hospitalized children, which is not a very representative population. Only parents or caregivers of the children were interviewed for the follow-up survey and there could be a recall bias risk. Further studies are needed to help better understand the long-term effects of COVID-19 in children and how the risk factors play a role.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Risk factors for long covid in previously hospitalised children using the ISARIC Global follow-up protocol: A prospective cohort study, Ismail M Osmanov, Ekaterina Spiridonova, Polina Bobkova, Aysylu Gamirova, Anastasia Shikhaleva, Margarita Andreeva, Oleg Blyuss, Yasmin El-Taravi, Audrey DunnGalvin, Pasquale Comberiati, Diego G Peroni, Christian Apfelbacher, Jon Genuneit, Lyudmila Mazankova, Alexandra Miroshina, Evgeniya Chistyakova, Elmira Samitova, Svetlana Borzakova, Elena Bondarenko, Anatoliy A Korsunskiy, Irina Konova, Sarah Wulf Hanson, Gail Carson, Louise Sigfrid, Janet T Scott, Matthew Greenhawt, Elizabeth A Whittaker, Elena Garralda, Olivia Swann, Danilo Buonsenso, Dasha E Nicholls, Frances Simpson, Christina Jones, Malcolm G Semple, John O Warner, Theo Vos, Piero Olliaro, Daniel Munblit, Sechenov StopCOVID Research Team medRxiv 2021.04.26.21256110; doi: https://doi.org/10.1101/2021.04.26.21256110, ​https://www.medrxiv.org/content/10.1101 ... 21256110v1
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Re: Post-COVID Clinics / Long Haulers

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Risk factors for long COVID-19 in children

4/29/21

https://www.news-medical.net/news/20210 ... ldren.aspx


After more than a year of the coronavirus disease 2019 (COVID-19) pandemic, it has become clear that children are less susceptible to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in terms of the number of infections and the severity of illness.

However, some children do develop severe disease as well as a host of long-term complications or sequelae. A new study, released as a preprint on the medRxiv* server, describes the risk factors and outcomes of such “long COVID-19” in a cohort of children who were hospitalized with COVID-19.

Earlier studies show that COVID-19 is associated with both immediate and long-term health issues. However, such studies in children and adolescents are few, except for some small case and cohort studies.

These show that over 50% of these children have one or more symptoms at four months after acute COVID-19. A recent Australian study contradicts these figures, indicating that less than a tenth of children are symptomatic at 3-6 months after infection. However, these children were mostly young (median age of 3 years), and the disease was mostly mild.

Study aims

The current study aimed to evaluate the clinical features and other variables in children, to pick out the relevant risk factors for the development of long COVID-19 in children.

Among children hospitalized with COVID-19, one in three patients will require admission to the intensive care unit (ICU). Many of these children will require some form of respiratory support, and some will show signs of organ failure in one or more organs.

A peculiar complication of pediatric COVID-19 is the multisystem inflammatory syndrome in children (MIS-C), typically seen a few weeks after the acute phase. In order to capture this condition, among others, the researchers used the protocol published by the pediatric COVID-19 working group of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC).

Study details

The current study included about 520 children, with a median age of 10 years. Both boys and girls were included in almost equal proportions. The follow-up continued for a median of almost nine months.

Of these children, over half had no underlying illnesses.

Among the rest (45%), the largest number had food allergies (13%), while one in ten had allergic rhinitis, and the same proportion had asthma. Almost the same number had gastrointestinal problems, eczema and neurological problems.

While 37% had pneumonia while in hospital, less than 3% had breathing problems severe enough to warrant ventilation or intensive care unit (ICU) admission.

What were the findings?


The study shows that almost one in four children were still symptomatic even months after hospitalization, and the involvement of multiple systems was observed in a tenth of the cohort.

Fatigue was present in 16% of children at discharge, but fell over time, as seen above. Similarly, anosmia was reported in 9%, ageusia or dysgeusia in 6%, and respiratory difficulty in 4%. These symptoms decreased in frequency over time, to 5%, 4% and 1%, respectively.

Insomnia persisted at the same level (7.5%), as did headaches (4.5%) and hair loss (4%), over 6-7 months.

The most common symptom reported at the end of the follow-up period was tiredness, followed by sleep disturbances, anosmia, and headache. Fatigue was present in a tenth of the cohort, while the others were reported in 3-5% of the children.

Symptoms involving the neurological, cardiovascular, respiratory and those involving the muscles and the skeleton, were each reported in 2-3% of children. About one in ten had more than one symptom persisting at the end of the follow-up period.

The symptoms that most commonly occurred together included fatigue and sleep disturbances, in 2%. Almost the same number had tiredness with sensory deficits. About 3% had persistent symptoms of more than two different types.

The emotional and behavioral changes reported to be due to the illness were reduced eating, less or more sleep, increased inactivity, and emotional dampening in roughly 5% of affected children. Tiredness, insomnia and sensory issues were the most frequently reported persistent symptoms.

Risk factors

The findings also show that children less than two years of age were less likely to have persistent symptoms. Those aged 6-18 years had 2.7 times higher odds of long COVID-19, compared to those below 2 years.

Children with a history of allergic disease had 1.7 times higher odds of delayed resolution. This may be linked to the immunological bias towards T helper 2 (Th2) cell response

For children with more than one persistent symptom, the odds were 2.5 times higher for those aged 6-11 years, and 3.2 times higher among 12-18 years, relative to those younger than 2 years.

The relatively high prevalence of at least one persistent symptom of long COVID-19 in this group indicates that age is a risk factor.

What are the implications for children’s health?

The current study is the largest cohort study of children who had been hospitalized with acute COVID-19, including a long follow-up period. It shows that children with persistent symptoms were less well compared to their health before they contracted the infection.

A tenth of the children had two or more persistent symptoms, with older children being at higher risk. Despite a waning prevalence of most symptoms reported at admission, a significant minority failed to show a complete return to normal health.

The reasons why headache and insomnia fail to exhibit a reduced prevalence over time may be psychological, suggest the researchers. The duration of persistent symptoms should be assessed in all such studies, to evaluate their importance and the need for interventions at the time of follow-up.

The identification of specific risk factors should drive further research into the factors that drive long COVID-19 in this patient group, both to validate these findings in controlled studies, and to develop guidelines for intervention, to optimize the clinical outcomes.

Moreover, it emphasizes the need for long-term monitoring of these children after their discharge.

" Future work should to be multidisciplinary, prospective, with a control cohort, repeated sampling and with an ability for children to report their health and wellbeing themselves, accompanied by biological sample collection.”

This will help understand the mechanism of long COVID-19, and its association with other risk factors, as well as therapeutic avenues.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Osmanov, I. M. et al. (2021). Risk factors for long covid in previously hospitalised children using the ISARIC Global follow-up protocol: A prospective cohort study. medRxiv preprint. doi: https://doi.org/10.1101/2021.04.26.21256110, https://www.medrxiv.org/content/10.1101 ... 21256110v1
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Re: Post-COVID Clinics / Long Haulers

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Most long COVID-19 sequelae affect people under 65, finds study

5/3/21


https://www.news-medical.net/news/20210 ... study.aspx


As hundreds of thousands of people continue to become infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to coronavirus disease 2019 (COVID-19), a significant minority will develop severe disease, and about 1% will die. However, many more who recover from the acute infection will have persistent symptoms and debility. This sequalae, encompassing a range of different post-viral complications, has come to be known as “long covid.”

A new study, released as a preprint on the medRxiv* server, discusses the typical symptoms and signs of this syndrome, with the intention of improving the specificity of detection and reporting.

Possible post-acute sequelae

Many symptoms have been recorded in the post-acute stage (post-acute sequelae of COVID-19, PASC), including tiredness, breathing difficulty, chest pain and cough; anxiety, depression and post-traumatic stress disorder, among emotional and mental disorders; neurocognitive symptoms such as poor memory and concentration.

These may last for weeks or months; however, all may not be the direct result of COVID-19.

Since many earlier studies on this syndrome have been based on small numbers of confirmed and often hospitalized-discharged COVID-19 patients, and since they rely on self-reported symptoms and outcomes, they may be subject to some potential biases.

Study aim

The current study aimed at analyzing newly diagnosed symptoms and conditions in a large number of patients, irrespective of their COVID-19 history, in order to help disentangle those conditions that are truly associated with the acute infection.

The study was retrospective in design, with over 57,000 patients, all of whom had undergone the gold standard reverse transcriptase-polymerase chain reaction (RT PCR) test for the virus.

The analysis was performed with the help of a computational model called MLHO that was designed to reveal associations using electronic health records (EHR), and that has been shown to be useful in the evaluation of this condition.

All these symptoms were recorded in the EHR at two or more months from the performance of a COVID-19 test in patients not hospitalized with the infection at any time, and who were still alive, and had two entries in their EHR, six months apart or more, within three years before the test. This was to make sure these patients would probably be captured by the study center.

Of the 57,000 patients, about a fifth of them were positive for the virus (around 11,400).

The findings


The researchers found new symptoms reported between 3-6 months, and 6-9 months, respectively, following the COVID-19 test, in both patients who tested negative and those with positive results. This yielded 28 positive associations with a history of SARS-CoV-2 infection, in groups varying by age and sex and by time.

Seven of the phenotypes had over 97% confidence for a history of COVID-19.

Early PASC


Between 3-6 months, alopecia was 3.5 times more likely overall, as well as in women under 65 years. In women over 65 years, the odds of alopecia in this period were over four-fold higher. The risk was not increased between 6-9 months.

Non-specific chest pain was also present at a higher frequency between 3-6 months overall, with 35% higher odds but more than 2.5-fold higher odds in the group of women under 65.

Men who were 65 years or more had 1.8-fold higher odds of edema, while those under 65 showed 2.6-fold higher odds of proteinuria, within 3-6 months.

In women aged 65 and over, within 3-6 months, gallstones (three-fold higher odds) and dementias (2.5-fold increase) were observed to be associated with a history of COVID-19, as well as twice the odds of Paget’s disease or other bone conditions, more in men.

Later PASC

In the later time period, nail disease was found to be associated with a history of prior COVID-19 in men 65 years or more.

Similarly, in the later time period, women of 65 or over had twice as high odds of anxiety disorders and dizziness. Those younger than this had two-fold higher odds of menstrual disturbances.

A less strong association was seen with acute-angle glaucoma in men under 65 at 6-9 months after diagnosis, at four-fold the odds.

Both time periods

Altered taste and smell were found to be twice as likely in both time periods, with women under 65 showing 2.5-fold higher odds.

Other less robust associations with previous COVID-19 were seen, such as chronic fatigue syndrome, especially in women and those under 65 years, in both time periods. Patients under 65 also had over two-fold higher odds of conjunctival disorders.

What are the conclusions?

These findings suggest that some of the previously identified post sequelae of COVID-19 may not be accurate and that most of the PASC are observed in patients under 65 years of age.”

Earlier studies have shown that PASC includes alopecia, anosmia and dysgeusia, and non-specific chest pain. The current study confirms them, and shows these to be early sequelae.

The findings also show Paget’s disease as an association with prior COVID-19. This will require further work for validation. Chronic fatigue syndrome is also an important association in those with a history of this infection.

Nail disease was strongly associated with a history of COVID-19, at 3.5-fold higher risk. This includes leukonychia, onycholysis, Beau’s lines and mee’s lines. These are markers of general ill-health, being associated with kidney and liver disease as well as infections. However, Beau’s lines seem to show a specific association with COVID-19.

The researchers consider this to be a possibly common PASC, and probably the result of the widespread inflammation and, in many cases, kidney damage caused by COVID-19.

Similarly, proteinuria in young patients associated with a positive history of this infection seems to indicate that the renal damage is not so short-lived as previously thought. Acute glaucoma should also be considered as a potential PASC, according to this study.

The approach used in this study was designed to prevent a plethora of false associations along with more flexible criteria for identification of PASC than the standard phenome-wide association study (PheWAS).

In future work, hospitalized patients should also be included. EHR data is abundantly available, “providing exceptional opportunities for instrumenting healthcare systems to study evolving pandemic byproducts.”

*Important Notice


medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:


Estiri, H. et al. (2021). Evolving Phenotypes of non-hospitalized Patients that Indicate Long Covid. medRxiv preprint. doi: https://doi.org/10.1101/2021.04.25.21255923, https://www.medrxiv.org/content/10.1101 ... 21255923v1
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