Coronavirus and blood clots: Causes, effects and treatment

Authors: Nascimento Pinto MSN

The effects of Covid-19 on people are varied but city doctors have observed that there is a possibility of heart attacks, especially in youngsters. 

Some city experts say heart attacks after Covid-19 are caused due to the presence of blood clots in the body. However, others believe there is neither any scientific evidence to prove blood clot-related heart attacks occur due to Covid-19 nor that the virus causes disproportionally more heart attacks than otherwise. The jury is still out but the fact that heart attacks and blood clots and their presence in people who have suffered from Covid-19 is being discussed cannot be ignored.

Mid-day Online spoke to Dr Manish Hinduja, consultant-cardio thoracic and vascular surgery, Fortis Hospital and Dr Pravin Kahale, consultant, cardiology, Kokilaben Dhirubhai Ambani Hospital to understand more about the causes of blood clots and the effects post-Covid. They also shed light on the symptoms one must be aware of and the preventive measures but while taking expert advice.

What causes blood clots in people after they suffer from Covid-19?

Hinduja: In Covid, clots form in blood vessels because once the virus binds to ACE 2 receptors on blood vessel lining cells, it activates the release of clot-forming proteins. It is also sometimes due to hyperactive inflammation caused by the virus in the body.

Kahale: Any infection which damages the wall of the blood vessels increases the chances of clotting in the body and that is not particularly due to Covid, many infections can also lead to blood clots.

Do blood clots cause heart attacks in people who have suffered from Covid-19? What are the other complications that could occur due to these clots besides heart attacks?

Hinduja: Yes, clots if formed in blood vessels of the heart, can lead to heart attack. Clots can also cause stroke, pulmonary embolism, deep vein thrombosis in legs or arms, and kidney but rarely liver damage.

Kahale: Blood clots can occur due to multiple infections. There is no evidence of blood clot-related heart attacks due to Covid-19. Apart from leg veins called deep vein thrombosis, other complications that can occur are paralysis due to clots in the brain, and lung arteries.

Has there been an increase in the number of heart attacks due to blood clots or people coming with clots after suffering from Covid-19?

Hinduja: Definitely. There is an increase in the number of heart attacks after Covid infection (especially in the younger age group). 

Kahale: There is no evidence that Covid causes disproportionally more heart attacks.

What are the chances of the blood clots occurring? Do they appear more in any particular age group?

Hinduja: About 20-30 per cent of patients with Covid-19 infection needing ICU treatment, show features of blood clot formation within six months of infection. Although it is more common in elderly hospitalised patients, it is also seen in young patients who have no comorbidities.

Kahale: Blood clots in mild to moderate Covid cases are uncommon. In case of severe Covid, the chances of blood clots occurring are still less. There is no particular age which is more susceptible.

Which part of the body do the blood clots occur the most?

While Hinduja says blood clots occur in the lungs, heart and brain vessels, Kahale adds that they mostly occur in leg veins and lung circulation.

Can people avoid getting blood clots after Covid-19?

Hinduja: Yes, preventive treatment with blood thinners and early diagnosis is the key.

Kahale: A patient who has suffered from severe Covid-19 infection can take a blood thinner based on the need, and guidance of a doctor.

Are there any foods people can eat to prevent getting blood clots eventually causing heart attacks? Do they need to make lifestyle changes?

Hinduja: Staying active, avoiding smoking and reducing weight for obese patients can help in reducing the risk. Common foods like ginger, turmeric and garlic have been shown to have some blood thinning effects. However, their role in preventing Covid 19-related blood clots, is not well-documented.

Kahale: In terms of blood clotting due to Covid-19, there are no specific food or lifestyle changes required. The risk of developing blood clots for a patient suffering from severe Covid-19 is only a potential threat until a patient is Covid positive.

What are the signs or symptoms for people to realise they have a blood clot? Why should they be concerned?

Hinduja: There is sudden chest pain, swelling in arms or legs, drowsiness and weakness in limbs.

Kahale: Blood clots depend upon the area where the patient is affected. If it occurs in the lungs, it can cause breathlessness. If it is in the legs, then it can cause swelling of the legs; heart blood clots lead to a heart attack-like chest pain, and clots in the brain can cause paralysis or stroke.

Long COVID: which symptoms can be attributed to SARS-CoV-2 infection?

Authors: Christopher E Brightling Rachael A Evans Published:August 06, 2022DOI:https://doi.org/10.1016/S0140-6736(22)01385-X The Lancet

Mortality rates following SARS-CoV-2 infection have decreased as a consequence of public health policies, vaccination, and acute antiviral and anti-inflammatory therapies.1 However, in the wake of the pandemic, post-acute sequelae of COVID-19, or long COVID, has emerged: a chronic illness in people who have ongoing multidimensional symptomatology and disability weeks to years after the initial infection.2 Early reports of long COVID prevalence, summarized in a systematic review examining the frequency and variety of persistent symptoms after COVID-19, found that the median proportion of people who had at least one persistent symptom 60 days or more after diagnosis or at least 30 days after recovery from COVID-19 infection was 73%. 3 However, the estimated prevalence depends on the duration, population, and symptoms used to define long COVID. More recently, community-based studies have suggested a lower prevalence of persistent symptoms; 4 whereas among people who were hospitalised following COVID-19 infection, a high proportion do not fully recover (50–70%).56

The number of COVID-19 cases continues to rise and now exceeds 500 million worldwide.1 Consequently, the number of people with long COVID is similarly increasing. Indeed, the UK Office for National Statistics (ONS) survey up to May, 2022 estimated that 2 million people in the UK had self-reported long COVID. 8 Of these people, 72% reported having long COVID for at least 12 weeks, 42% for at least 1 year, and 19% for at least 2 years. Consistent with other studies, fatigue was the most common symptom in the ONS survey, followed by breathlessness, cough, and muscle ache.45678 Risk factors for long COVID are female sex, obesity, middle age (35–65 years), living in areas of greater socioeconomic deprivation, and the presence of another activity-limiting health condition.156 Importantly, health-care use is increased in those with long COVID, with increased general practitioner consultation rates.

How many of the symptoms currently attributed to long COVID actually represent pre-existent disease or are unrelated to COVID-19 is uncertain. Symptoms that were present before SARS-CoV-2 infection are often not recorded or assessed by recall. In The Lancet, Aranka V Ballering and colleagues 10  report the findings of a longitudinal cohort study conducted in the north of the Netherlands between April, 2020, and August, 2021, where 23 somatic symptoms were assessed using 24 repeated measurements in digital COVID-19 questionnaires. The study was embedded within the large, population-based Lifelines COVID-19 cohort. The main strengths of this study were that participants were their own control, with the pattern and severity of symptoms assessed before and 3–5 months after SARS-CoV-2 infection, and were also compared with a matched control group of COVID-19-negative participants. Of the 76 422 participants, 4231 (5·5%) had COVID-19 and were compared with 8462 matched controls. Participants had a mean age of 53·7 years (SD 12·9), 46 329 (60·8%) were female, and nearly all were of White ethnicity. The proportion of participants who had at least one core symptom of substantially increased severity to at least moderate was 21·4% (381 of 1782) in COVID-19-positive participants versus 8·7% (361 of 4130) in COVID-19-negative controls. Thus, this study found that core symptoms were attributed to COVID-19 in 12·7% of participants, or approximately one in eight. This is a major advance on previous long COVID prevalence estimates, as it includes a matched control group without SARS-CoV-2 infection and accounts for symptoms that were present before infection.

The pattern of symptomatology observed by Ballering and colleagues 0  was similar to previous reports, with fatigue and breathlessness among the most common symptoms, but other symptoms such as chest pain were more common in people who had COVID-19 than in COVID-19-negative controls. Ballering and colleagues10  propose a core symptom set to be considered as part of the case definition for long COVID. Although an agreed diagnostic core symptom set would inform clinical pathways and research, the study by Ballering and colleagues 10 did not fully consider the impact on mental health, it was conducted in one region in the Netherlands, and it did not include an ethnically diverse population; thus the concept of a core symptom set will require further validation. Importantly, the study by Ballering and colleagues 10  does not provide new mechanistic insights, which are key to uncovering new therapeutic targets. In other studies, clustering of patient-reported outcomes has identified different severity groups of long COVID and identified increased systemic inflammation in people with very severe long COVID.5, 6

 How patient-centred outcomes, together with biomarkers, can further refine long COVID diagnosis and inform precision medicine approaches warrants further consideration. Encouragingly, emerging data from other studies suggest that the proportion of newly infected people developing long COVID is reduced in people who have received vaccination before SARS-CoV-2 infection,11  and might be lower in people infected with the omicron variant than those infected with earlier variants.2

 Findings from the ONS survey suggested that vaccination following infection might reduce the symptom burden of long COVID after the first dose, with sustained improvement after a second dose13  Whether acute treatments for COVID-19 affect the likelihood of developing long COVID or its severity is unknown.

Current evidence supports the view that long COVID is common and can persist for at least 2 years after SARS-CoV-2 infection, although severe debilitating disease is present in a minority. The long COVID case definition needs to be further improved, potentially to describe different types of long COVID, of which better mechanistic understanding is crucial. This will lead to personalised multimodality treatments that can be implemented to manage the increasingly high number of people with long COVID.

CEB has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. RAE has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID. RAE holds a National Institute for Health and Care Research (NIHR) clinician scientist award CS-2016-16-020.

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9

Unraveling the Interplay of Omicron, Reinfections, and Long Covid

Authors:  Liz Szabo AUGUST 26, 2022 KHN

The latest covid-19 surge, caused by a shifting mix of quickly evolving omicron subvariants, appears to be waning, with cases and hospitalizations beginning to fall.

Like past covid waves, this one will leave a lingering imprint in the form of long covid, an ill-defined catchall term for a set of symptoms that can include debilitating fatigue, difficulty breathing, chest pain, and brain fog.

Although omicron infections are proving milder overall than those caused by last summer’s delta variant, omicron has also proved capable of triggering long-term symptoms and organ damage. But whether omicron causes long covid symptoms as often — and as severe — as previous variants is a matter of heated study.

Michael Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy, is among the researchers who say the far greater number of omicron infections compared with earlier variants signals the need to prepare for a significant boost in people with long covid. The U.S. has recorded nearly 38 million covid infections so far this year, as omicron has blanketed the nation. That’s about 40% of all infections reported since the start of the pandemic, according to the Johns Hopkins University Coronavirus Research Center.

Long covid “is a parallel pandemic that most people aren’t even thinking about,” said Akiko Iwasaki, a professor of immunobiology at Yale University. “I suspect there will be millions of people who acquire long covid after omicron infection.”

Scientists have just begun to compare variants head to head, with varying results. While one recent study in The Lancet suggests that omicron is less likely to cause long covid, another found the same rate of neurological problems after omicron and delta infections.

Estimates of the proportion of patients affected by long covid also vary, from 4% to 5% in triple-vaccinated adults to as many as 50% among the unvaccinated, based on differences in the populations studied. One reason for that broad range is that long covid has been defined in widely varying ways in different studies, ranging from self-reported fogginess for a few months after infection to a dangerously impaired inability to regulate pulse and blood pressure that may last years.

Even at the low end of those estimates, the sheer number of omicron infections this year would swell long-covid caseloads. “That’s exactly what we did find in the UK,” said Claire Steves, a professor of aging and health at King’s College in London and author of the Lancet study, which found patients have been 24% to 50% less likely to develop long covid during the omicron wave than during the delta wave. “Even though the risk of long covid is lower, because so many people have caught omicron, the absolute numbers with long covid went up,” Steves said.

recent study analyzing a patient database from the Veterans Health Administration found that reinfections dramatically increased the risk of serious health issues, even in people with mild symptoms. The study of more than 5.4 million VA patients, including more than 560,000 women, found that people reinfected with covid were twice as likely to die or have a heart attack as people infected only once. And they were far more likely to experience health problems of all kinds as of six months later, including trouble with their lungs, kidneys, and digestive system.

“We’re not saying a second infection is going to feel worse; we’re saying it adds to your risk,” said Dr. Ziyad Al-Aly, chief of research and education service at the Veterans Affairs St. Louis Health Care System.

Researchers say the study, published online but not yet peer-reviewed, should be interpreted with caution. Some noted that VA patients have unique characteristics, and tend to be older men with high rates of chronic conditions that increase the risks for long covid. They warned that the study’s findings cannot be extrapolated to the general population, which is younger and healthier overall.

“We need to validate these findings with other studies,” said Dr. Harlan Krumholz, director of the Yale New Haven Hospital Center for Outcomes Research and Evaluation. Still, he added, the VA study has some “disturbing implications.”

With an estimated 82% of Americans having been infected at least once with the coronavirus as of mid-July, most new cases now are reinfections, said Justin Lessler, a professor of epidemiology at the University of North Carolina Gillings School of Global Public Health.

Of course, people’s risk of reinfection depends not just on their immune system, but also on the precautions they’re taking, such as masking, getting booster shots, and avoiding crowds.

New Jersey salon owner Tee Hundley, 43, has had covid three times, twice before vaccines were widely available and again this summer, after she was fully vaccinated. She is still suffering the consequences.

After her second infection, she returned to work as a cosmetologist at her Jersey City salon but struggled with illness and shortness of breath for the next eight months, often feeling like she was “breathing through a straw.”

She was exhausted, and sometimes slow to find her words. While waxing a client’s eyebrows, “I would literally forget which eyebrow I was waxing,” Hundley said. “My brain was so slow.”

When she got a breakthrough infection in July, her symptoms were short-lived and milder: cough, runny nose, and fatigue. But the tightness in her chest remains.

“I feel like that’s something that will always be left over,” said Hundley, who warns friends with covid not to overexert. “You may not feel terrible, but inside of your body there is a war going on.”

Although each omicron subvariant has different mutations, they’re similar enough that people infected with one, such as BA.2, have relatively good protection against newer versions of omicron, such as BA.5. People sickened by earlier variants are far more vulnerable to BA.5.

Several studies have found that vaccination reduces the risk of long covid. But the measure of that protection varies by study, from as little as a 15% reduction in risk to a more than 50% decrease. A study published in July found the risk of long covid dropped with each dose people received.

For now, the only surefire way to prevent long covid is to avoid getting sick. That’s no easy task as the virus mutates and Americans have largely stopped masking in public places. Current vaccines are great at preventing severe illness but do not prevent the virus from jumping from one person to the next. Scientists are working on next-generation vaccines — “variant-proof” shots that would work on any version of the virus, as well as nasal sprays that might actually prevent spread. If they succeed, that could dramatically curb new cases of long covid.

“We need vaccines that reduce transmission,” Al-Aly said. “We need them yesterday.”

Could tiny blood clots cause long COVID’s puzzling symptoms?

Scientists debate evidence for a micro-clot hypothesis that has some people pursuing potentially risky treatments

Authors: Cassandra Willyard Nature 608, 662-664 (2022)doi: https://doi.org/10.1038/d41586-022-02286-7

When Lara Hawthorne, an illustrator in Bristol, UK, began developing strange symptoms after having COVID-19, she hoped that they weren’t due to the virus. Her initial illness had been mild. “I’ve been triple vaccinated. I felt quite protected,” she says. But months later, she was still sick with a variety of often debilitating symptoms: earaches, tinnitus, congestion, headaches, vertigo, heart palpitations, muscle pain and more. On some days, Hawthorne felt so weak that she could not get out of bed. When she finally saw her physician, the diagnosis was what she had been dreading: long COVID.

Unable to find relief, she became increasingly desperate. After reading an opinion piece in The Guardian newspaper about how blood clots might be to blame for long COVID symptoms, Hawthorne contacted a physician in Germany who is treating people with blood thinners and a procedure to filter the blood. She hasn’t heard back yet — rumour has it that people stay on the waiting list for months — but if she has the opportunity to head there for these unproven treatments, she probably will. “I don’t want to wait on my health when I’m feeling so dreadful,” she says.

Researchers are baffled by long COVID: hundreds of studies have tried to unpick its mechanism, without much success. Now some scientists, and an increasing number of people with the condition, have been lining up behind the as-yet-unproven hypothesis that tiny, persistent clots might be constricting blood flow to vital organs, resulting in the bizarre constellation of symptoms that people experience.

Heart disease after COVID: what the data say

Proponents of the idea (#teamclots, as they sometimes refer to themselves on Twitter) include Etheresia Pretorius, a physiologist at Stellenbosch University in South Africa, and Douglas Kell, a systems biologist at the University of Liverpool, UK, who led the first team to visualize micro-clots in the blood of people with long COVID. They say that the evidence implicating micro-clots is undeniable, and they want trials of the kinds of anticoagulant treatment that Hawthorne is considering. Pretorius penned the Guardian article that caught Hawthorne’s attention.

But many haematologists and COVID-19 researchers worry that enthusiasm for the clot hypothesis has outpaced the data. They want to see larger studies and stronger causal evidence. And they are concerned about people seeking out unproven, potentially risky treatments.

When it comes to long COVID, “we’ve now got little scattered of bits of evidence”, says Danny Altmann, an immunologist at Imperial College London. “We’re all scuttling to try and put it together in some kind of consensus. We’re so far away from that. It’s very unsatisfying.”

Cascade of clots

Pretorius and Kell met about a decade ago. Pretorius had been studying the role of iron in clotting and neglected to cite some of Kell’s research. When he reached out, they began chatting. “We had a Skype meeting and then we decided to work together,” Pretorius says. They observed odd, dense clots that resist breaking down for years in people with a variety of diseases. The research led them to develop the theory that some molecules — including iron, proteins or bits of bacterial cell wall — might trigger these abnormal clots.

Blood clotting is a complex process, but one of the key players is a cigar-shaped, soluble protein called fibrinogen, which flows freely in the bloodstream. When an injury occurs, cells release the enzyme thrombin, which cuts fibrinogen into an insoluble protein called fibrin. Strands of fibrin loop and criss-cross, creating a web that helps to form a clot and stop the bleeding.

Under a microscope, this web typically resembles “a nice plate of spaghetti”, Kell says. But the clots that the team has identified in many inflammatory conditions look different. They’re “horrible, gunky, dark”, Kell says, “such as you might get if you half-boiled the spaghetti and let it all stick together.” Research by Kell, Pretorius and their colleagues suggests that the fibrin has misfolded1, creating a gluey, ‘amyloid’ version of itself. It doesn’t take much misfolding to seed disaster, says Kell. “If the first one changes its conformation, all the others have to follow suit”, much like prions, the infectious misfolded proteins that cause conditions such as Creutzfeldt–Jakob disease.

Long-COVID treatments: why the world is still waiting

Pretorius first saw these strange, densely matted clots in the blood of people with a clotting disorder2, but she and Kell have since observed the phenomenon in a range of conditions1 — diabetes, Alzheimer’s disease and Parkinson’s disease, to name a few. But the idea never gained much traction, until now.

When the pandemic hit in 2020, Kell and Pretorius applied their methods almost immediately to people who had been infected with SARS-CoV-2. “We thought to look at clotting in COVID, because that is what we do,” Pretorius says. Their assay uses a special dye that fluoresces when it binds to amyloid proteins, including misfolded fibrin. Researchers can then visualize the glow under a microscope. The team compared plasma samples from 13 healthy volunteers, 15 people with COVID-19, 10 people with diabetes and 11 people with long COVID3. For both long COVID and acute COVID-19, Pretorius says, the clotting “was much more than we have previously found in diabetes or any other inflammatory disease”. In another study4, they looked at the blood of 80 people with long COVID and found micro-clots in all of the samples.

So far, Pretorius, Kell and their colleagues are the only group that has published results on micro-clots in people with long COVID.

But in unpublished work, Caroline Dalton, a neuroscientist at Sheffield Hallam University’s Biomolecular Sciences Research Centre, UK, has replicated the results. She and her colleagues used a slightly different method, involving an automated microscopy imaging scanner, to count the number of clots in blood. The team compared 3 groups of about 25 individuals: people who had never knowingly had COVID-19, those who had had COVID-19 and recovered, and people with long COVID. All three groups had micro-clots, but those who had never had COVID-19 tended to have fewer, smaller clots, and people with long COVID had a greater number of larger clots. The previously infected group fell in the middle. The team’s hypothesis is that SARS-CoV-2 infection creates a burst of micro-clots that go away over time. In individuals with long COVID, however, they seem to persist.

Dalton has also found that fatigue scores seem to correlate with micro-clot counts, at least in a few people. That, says Dalton, “increases confidence that we are measuring something that is mechanistically linked to the condition”.

In many ways, long COVID resembles another disease that has defied explanation: chronic fatigue syndrome, also known as myalgic encephalomyelitis (ME/CFS). Maureen Hanson, who directs the US National Institutes of Health (NIH) ME/CFS Collaborative Research Center at Cornell University in Ithaca, New York, says that Pretorius and Kell’s research has renewed interest in a 1980s-era hypothesis about abnormal clots contributing to symptoms. Pretorius, Kell and colleagues found amyloid clots in the blood of people with ME/CFS, but the amount was much lower than what they’ve found in people with long COVID5. So clotting is probably only a partial explanation for ME/CFS, Pretorius says.

Micro-clot mysteries

Where these micro-clots come from isn’t entirely clear. But Pretorius and Kell think that the spike protein, which SARS-CoV-2 uses to enter cells, might be the trigger in people with long COVID. When they added the spike protein to plasma from healthy volunteers in the laboratory, that alone was enough to prompt formation of these abnormal clots6.

Bits of evidence hint that the protein might be involved. In a preprint7 posted in June, researchers from Harvard University in Boston, Massachusetts, reported finding the spike protein in the blood of people with long COVID. Another paper8 from a Swedish group showed that certain peptides in the spike can form amyloid strands on their own, at least in a test tube. It’s possible that these misfolded strands provide a kind of template, says Sofie Nyström, a protein chemist at Linköping University in Sweden and an author of the paper.

Micrographs of platelet poor plasma of a healthy volunteer showing few microclots,and post-COVID-19 infection showing microclots
Micro-clots (green) in a study participant before SARS-CoV-2 infection (left four panels) and in the same person after they developed long COVID (right four panels).Credit: E. Pretorius et al./Cardiovasc. Diabetol. (CC BY 4.0)

A California-based group found that fibrin can actually bind to the spike. In a 2021 preprint9, it reported that when the two proteins bind, fibrin ramps up inflammation and forms clots that are harder to degrade. But how all these puzzle pieces fit together isn’t yet clear.

If the spike protein is the trigger for abnormal clots, that raises the question of whether COVID-19 vaccines, which contain the spike or instructions for making it, can induce them as well. There’s currently no direct evidence implicating spike from vaccines in forming clots, but Pretorius and Kell have received a grant from the South African Medical Research Council to study the issue. (Rare clotting events associated with the Oxford–AstraZeneca vaccine are thought to happen through a different mechanism (Nature 596, 479–481; 2021).)

Raising safety concerns about the vaccines can be uncomfortable, says Per Hammarström, a protein chemist at Linköping University and Nyström’s co-author. “We don’t want to be over-alarmist, but at the same time, if this is a medical issue, at least in certain people, we have to address that.” Gregory Poland, director of the Mayo Clinic’s vaccine research group in Rochester, Minnesota, agrees that it’s an important discussion. “My guess is that spike and the virus will turn out to have a pretty impressive list of pathophysiologies,” he says. “How much of that may or may not be true for the vaccine, I don’t know.”

Dearth of data

Many researchers find it plausible and intriguing that micro-clots could be contributing to long COVID. And the hypothesis does seem to fit with other data that have emerged on clotting. Researchers already know that people with COVID-19, especially severe disease, are more likely to develop clots. The virus can infect cells lining the body’s 100,000 kilometres of blood vessels, causing inflammation and damage that triggers clotting.

Those clots can have physiological effects. Danny Jonigk, a pathologist at Hanover Medical School in Germany, and his colleagues looked at tissue samples from people who died of COVID-19. They found micro-clots and saw that the capillaries had split, forming new branches to try to keep oxygen-rich blood flowing10. The downside was that the branching introduces turbulence into the flow that can give rise to fresh clots.

How common is long COVID? Why studies give different answers

Several other labs have found signs that, in some people, this tendency towards clotting persists months after the initial infection. James O’Donnell, a haematologist and clotting specialist at Trinity College Dublin, and his colleagues found11 that about 25% of people who are recovering from COVID-19 have signs of increased clotting that are “quite marked and unusual”, he says.

What is less clear is whether this abnormal clotting response is actually to blame for any of the symptoms of long COVID, “or is it just, you know, another unusual phenomenon associated with COVID?” O’Donnell says.

Alex Spyropoulos, a haematologist at the Feinstein Institutes for Medical Research in New York City, says the micro-clot hypothesis presents “a very elegant mechanism”. But he argues that much more work is needed to tie the lab markers to clinical symptoms. “What’s a little bit disturbing is that these authors and others make huge leaps of faith,” Spyropoulos says.

Jeffrey Weitz, a haematologist and clotting specialist at McMaster University in Hamilton, Canada, points out that the method Pretorius’s team is using to identify micro-clots “isn’t a standard technique at all”. He adds: “I’d like to see confirmation from other investigators.” Micro-clots are difficult to detect. Pathologists can spot them in tissue samples, but haematologists tend to look for markers of abnormal clotting rather than the clots themselves.

Other, larger studies of long COVID have failed to find signs of clotting. Michael Sneller, an infectious-disease specialist, and his colleagues at the NIH in Bethesda, Maryland, thoroughly examined 189 people who had been infected with SARS-CoV-2, some with lingering symptoms and some without, and 120 controls12. They did not specifically look for micro-clots. But if micro-clots had been clogging the capillaries, Sneller says, they should have seen some evidence — tissue damage in capillary-rich organs such as the lungs and kidneys, for example. Micro-clots might also damage red blood cells, leading to anaemia. But Sneller and his colleagues found no signs of this in any of the lab tests.

The four most urgent questions about long COVID

Kell and Pretorius argue that just because this study didn’t find any evidence of micro-clots doesn’t mean they aren’t there. One of the key issues with long COVID is that “every single test comes back within the normal ranges”, Pretorius says. “You have desperately ill patients with no diagnostic method.” She hopes that other researchers will read their papers and attempt to replicate their results. “Then we can have a discussion,” she says. The ultimate causal proof, she adds, would be people with long COVID feeling better after receiving anticoagulant therapies.

There is some limited evidence of this. In an early version of a preprint, posted in December 2021, Kell, Pretorius and other researchers, including physician Gert Jacobus Laubscher at Stellenbosch University, reported that 24 people who had long COVID and were treated with a combination of two antiplatelet therapies and an anticoagulant experienced some relief13. Participants reported that their main symptoms resolved and that they became less fatigued. They also had fewer micro-clots. Pretorius and Kell are working to gather more data before they try to formally publish these results. But other physicians are already using these medications to treat people with long COVID. Some are even offering a dialysis-like procedure that filters fibrinogen and other inflammatory molecules from the blood. To O’Donnell, such treatment feels premature. He accepts that some people with long COVID are prone to clots, but leaping from a single small study to treating a vast number of people is “just not going to wash in 2022 in my book”, he says. Sneller agrees. “Anticoagulating somebody is not a benign thing. You basically are interfering with the blood’s ability to clot,” he says, which could make even minor injuries life-threatening.

Kell says he’s tired of waiting for a consensus on how to treat long COVID. “These people are in terrible pain. They are desperately unwell,” he says. Altmann understands that frustration. He gets e-mails almost daily, asking: “Where are the drug trials? Why does it take so long?” But even in the midst of a pandemic, he argues, researchers have to follow the process. “I’m not rubbishing anybody’s data. I’m just saying we’re not there yet,” he says. “Let’s join up the dots and do this properly.”

References

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New study suggests covid increases risks of brain disorders

Authors: Frances Stead Sellers Fri, August 19, 2022  Washington Post

A study published this week in the Lancet Psychiatry showed increased risks of some brain disorders two years after infection with the coronavirus, shedding new light on the long-term neurological and psychiatric aspects of the virus.

The analysis, conducted by researchers at the University of Oxford and drawing on health records data from more than 1 million people around the world, found that while the risks of many common psychiatric disorders returned to normal within a couple of months, people remained at increased risk for dementia, epilepsy, psychosis and cognitive deficit (or brain fog) two years after contracting covid. Adults appeared to be at particular risk of lasting brain fog, a common complaint among coronavirus survivors.

The study was a mix of good and bad news findings, said Paul Harrison, a professor of psychiatry at the University of Oxford and the senior author of the study. Among the reassuring aspects was the quick resolution of symptoms such as depression and anxiety.

“I was surprised and relieved by how quickly the psychiatric sequelae subsided,” Harrison said.

David Putrino, director of rehabilitation innovation at Mount Sinai Health System in New York, who has been studying the lasting impacts of the coronavirus since early in the pandemic, said the study revealed some very troubling outcomes.

“It allows us to see without a doubt the emergence of significant neuropsychiatric sequelae in individuals that had covid and far more frequently than those who did not,” he said.

Because it focused only on the neurological and psychiatric effects of the coronavirus, the study authors and others emphasized that it is not strictly long-covid research.

“It would be overstepping and unscientific to make the immediate assumption that everybody in the [study] cohort had long covid,” Putrino said. But the study, he said, “does inform long-covid research.”

Between 7 million and 23 million people in the United States have long covid, according to recent government estimates – a catchall term for a wide range of symptoms including fatigue, breathlessness and anxiety that persist weeks and months after the acute infection has subsided. Those numbers are expected to rise as the coronavirus settles in as an endemic disease.

The study was led by Maxime Taquet, a senior research fellow at the University of Oxford who specializes in using big data to shed light on psychiatric disorders.

The researchers matched almost 1.3 million patients with a diagnosis of covid-19 between Jan. 20, 2020, and April 13, 2022, with an equal number of patients who had other respiratory diseases during the pandemic. The data, provided by electronic health records network TriNetX, came largely from the United States but also included data from Australia, Britain, Spain, Bulgaria, India, Malaysia and Taiwan.

The study group, which included 185,000 children and 242,000 older adults, revealed that risks differed according to age groups, with people age 65 and older at greatest risk of lasting neuropsychiatric affects.

For people between the ages of 18 and 64, a particularly significant increased risk was of persistent brain fog, affecting 6.4 percent of people who had had covid compared with 5.5 percent in the control group.

Six months after infection, children were not found to be at increased risk of mood disorders, although they remained at increased risk of brain fog, insomnia, stroke and epilepsy. None of those affects were permanent for children. With epilepsy, which is extremely rare, the increased risk was larger.

The study found that 4.5 percent of older people developed dementia in the two years after infection, compared with 3.3 percent of the control group. That 1.2-point increase in a diagnosis as damaging as dementia is particularly worrisome, the researchers said.

The study’s reliance on a trove of de-identified electronic health data raised some cautions, particularly during the tumultuous time of the pandemic. Tracking long-term outcomes may be hard when patients may have sought care through many different health systems, including some outside the TriNetX network.

“I personally find it impossible to judge the validity of the data or the conclusions when the data source is shrouded in mystery and the sources of the data are kept secret by legal agreement,” said Harlan Krumholz, a Yale scientist who has developed an online platform where patients can enter their own health data.

Taquet said the researchers used several means of assessing the data, including making sure it reflected what is already known about the pandemic, such as the drop in death rates during the omicron wave.

Also, Taquet said, “the validity of data is not going to be better than validity of diagnosis. If clinicians make mistakes, we will make the same mistakes.”

The study follows earlier research from the same group, which reported last year that a third of covid patients experienced mood disorders, strokes or dementia six months after infection with the coronavirus.

While cautioning that it is impossible to make full comparisons among the effects of recent variants, including omicron and its subvariants, which are currently driving infections, and those that were prevalent a year or more ago, the researchers outlined some initial findings: Even though omicron caused less severe immediate symptoms, the longer-term neurological and psychiatric outcomes appeared similar to the delta waves, indicating that the burden on the world’s health-care systems might continue even with less-severe variants.

Hannah Davis, a co-founder of the Patient-Led Research Collaborative, which studies long covid, said that finding was meaningful. “It goes against the narrative that omicron is more mild for long covid, which is not based on science,” Davis said.

“We see this all the time,” Putrino said. “The general conversation keeps leaving out long covid. The severity of initial infection doesn’t matter when we talk about long-term sequalae.

What, Exactly, Is ‘Paxlovid Mouth’ and How Do You Get Rid of It?

The Covid-19 antiviral drug can leave a foul taste. The afflicted are scouring for remedies online.

Authors: Alex Janin Aug. 16, 2022 Wall Street Journal

Jeanette Witten recently rummaged through her pantry for Red Hots, the cinnamon-flavored candy.

The 56-year-old in Montclair, N.J., was looking for a reprieve from a persistent residual taste—“like your mouth is just clenched around a grapefruit rind”—that came after she took Paxlovid, Pfizer’s antiviral drug to treat Covid-19. 

Ms. Witten is one of many people who have scouted remedies for what is informally known as Paxlovid mouth, a taste that can linger for as long as you take the drug. Patients who have taken Paxlovid have described it as sun-baked trash-bag liquid, a mouthful of dirty pennies and rotten soymilk. They have tried to erase the taste with salves from cinnamon to milk to pineapple. They are also trading strategies online. 

Pfizer spokesperson acknowledged the side effect, called dysgeusia, and pointed to a study that found the symptom occurred 5.6% of the time people took the drug. The study was funded by Pfizer and published in the New England Journal of Medicine. The company said most patients’ dysgeusia symptoms were mild.

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The culprit is likely ritonavir, a part of the drug that is used to boost levels of antiviral medicines, doctors say. Ritonavir has a known association with dysgeusia. It is a small price to pay given the nearly 90% reduction in hospitalization and death among those at risk for severe disease from Covid-19, say doctors and people who have taken the medication. 

But it’s still hard for many patients to stomach.

Long-term symptoms 23 months after SARS-CoV-2 infection

Authors: Shanet Susan Alex Aug 2 2022 Medical Life Sciences News

In a recent article posted to Open Forum Infectious Diseases, scientists analyzed coronavirus disease 2019 (COVID-19) symptoms lasting 23 months after the infection.

Background

More than 572 million confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases globally were reported over two and a half years into the COVID-19 pandemic. In addition, there are likely many more undetected COVID-19 cases. Meanwhile, numerous studies have shown that the long-lasting impacts of COVID-19, also known as long COVID, could significantly influence the global public health and healthcare burden. Nonetheless, the length of long COVID is still unknown, given most studies indicate that patients still have identifiable signs and symptoms at the time of their last evaluation about 12 months following infection.

In a prospective cohort of 180 mostly non-hospitalized cases, the present study’s authors have previously detailed the prevalence of symptoms four months following SARS-CoV-2 infection, with more than half of the subjects experiencing persistent symptoms.

About the study

In the current prospective research, the scientists investigated the same study population they assessed earlier for four months for long-term COVID-19 symptoms for 23 months post-SARS-CoV-2 infection. 

The team invited all patients with confirmed COVID-19 in the Faroe Islands between March 2020 and April 2020 to participate in the study. Further, 180 subjects were interviewed via phone, and a validated questionnaire was used to evaluate their symptoms. Moreover, all study volunteers submitted informed consent before enrolling. The last follow-up was performed 19 to 23 months after illness onset, from November 2021 to January 2022.

The researchers asked questions on memory, recovery, and concentration only at the last follow-up since the chronic neurological effects of COVID-19 were unknown at the start of the SARS-CoV-2 pandemic. They also interrogated the participants regarding concentration and memory problems before COVID-19.

Results

Overall, the study results showed that above one-third of COVID-19 patients from the spring of 2020 reported still having symptoms over two years following the acute infection. However, 76% of volunteers claimed full recovery, even some with at least one SARS-CoV-2 symptom during follow-up. Some people with chronic COVID-19 symptoms reported feeling complete recovery, whereas 2% reported feeling no recovery, and 22% reported no full recovery.

Long COVID study looks at why some can’t shake dizziness, fatigue and more

Authors: Helena Oliviero, The Atlanta Journal-Constitution

Georgia residents among thousands needed for a massive study to discover how the virus causes lingering symptoms.

Back in the summer of 2020, when the pandemic was still new and hospitals were overflowing, Emory Healthcare opened a facility to treat a perplexing group of COVID-19 survivors.

The patients had withstood the virus’s initial onslaught but couldn’t shake some of the symptoms.

At the time, Dr. Alex Truong thought the long COVID clinic might be needed for a year, maybe two.

But long COVID — a mysterious constellation of ailments that can go on for many weeks or months — has become a bigger problem than Truong could have ever imagined.

In the U.S. alone, 1 in 5 of the adults stricken with COVID-19 have developed conditions that could be considered long COVID, according to a recent study by the Centers for Disease Control and Prevention. Symptoms range from brain fog and unrelenting fatigue to gastric and cardiac issues. Among those 65 and older, the estimates are even higher — 1 in 4.

That translates into millions of Americans and more than 300,000 Georgians.

Other estimates vary wildly. There is no test for long COVID. No official statistics exist.

Clinicians at the Emory clinic have treated more than 1,000 COVID survivors. There’s now a four-month waiting list to be seen at the clinic.ExploreComplete coverage of COVID-19 in Georgia

“It’s been shocking,” said Truong, who is co-director of the clinic,located at Emory University Hospital Midtown. “I’ve never seen, with other infections, such widespread, all-over-the-body symptoms for this long.”

COVID can wreak havoc on a person’s body and damage organs – the lungs, heart, kidneys and liver. Experts worry that people who are infected multiple times have increased chances of developing long COVID.

How is long COVID defined?

A recent CDC study says that 1 in 5 of U.S. adults stricken with COVID-19 have developed conditions that could be considered long COVID, which the agency defines as symptoms lasting at least four weeks after infection.

The CDC says the following symptoms are the most common for this complex and poorly understood condition:

  • Tiredness or fatigue that interferes with daily life
  • Difficulty breathing, shortness of breath, chest pain
  • Difficulty thinking or concentrating (sometimes referred to as “brain fog”)
  • Headache
  • Sleep problems
  • Anxiety
  • Digestive issues
  • Joint or muscle pain

“With COVID, we tend to think about the hospitalizations and deaths, and then we kind of stop there sometimes,” said Dr. Tiffany Walker, who has treated long COVID patients at Grady Memorial Hospital. “I don’t want to paint the picture of everybody’s debilitated, but some people are, and it’s people that don’t expect it. The times that people have cried in my office because they’re just so overwhelmed is like more than anything I’ve experienced before in clinical practice.”

Walker now leads a long COVID study at Grady, which is part of a massive National Institutes of Health effort to find the connection between seemingly unrelated symptoms that have afflicted patients and confounded physicians.

Scientists still do not know how the virus triggers such a wide range of problems, from minor to incapacitating, or why issues emerge in some patients but not in others, or what exactly the risk factors are for developing them.

What’s more, there is no specific treatment for longCOVID. Instead, the current approach is to deal with each symptom individually.

It’s often hard to offer satisfying answers to patients. “It’s just very upsetting and really challenging,” Walker said. “As a physician, you really want to be able to provide a prognosis at least, at a minimum to be able to express to them, this is what you can expect.”

But doctors “don’t know enough to know what the course is going to be and who’s going to get better and who isn’t, and you don’t know enough about how to treat those that aren’t getting better,” she said.

And the world’s leading health organizations don’t even have a standard definition of what constitutes long COVID, Truong said. The CDC defines long COVID, which it calls Post-COVID Conditions, as symptoms lasting four weeks or longer after infection. The World Health Organization says people cross over into long COVID after symptoms persist for at least three months.

In 2021, 60% of patients at the Emory and Grady long COVID clinics enrolled in a study aimed at gathering more information on the illness. At the time of their enrollment, patients had already been dealing with COVID symptoms for an average of 107 days.

Even people who have mild or asymptomatic COVID-19 infections can have new health problems crop up months after they’ve tested negative.

Remaining vigilant

The CDC’s study evaluated electronic medical records for nearly 2 million people. The agency compared those who had been infected with the coronavirus and those who had not. The analysis found 38% percent of the COVID patients developed one or more new health problems, compared to 16% percent of the non-COVID patients. The health problems of about 21% of the younger COVID patients in the study, those ages 18 to 64, and nearly 27% of the older people, 65 and up, could be attributed to long COVID. The study did not look at vaccination status.

A growing number of studies suggest that getting a COVID vaccine can reduce — though not eliminate — the risk of longer-term symptoms.

Some experts think that today’s omicron strains pose a lower risk for long COVID than previous variants. But they caution: Even if omicron is less likely to cause long-lasting symptoms, particularly for people who have been vaccinated, the actual number of long COVID sufferers will still grow due to the high infection rate.

It’s often hard to determine whether health problems that emerge after a case of COVID are truly triggered by the virus.

Lead Nurse Practitioner Lori Reed, who works at the Piedmont Pulmonary COVID Recovery clinic, said some patients dealing with preexisting conditions may be more aware of them after coronavirus infections. That means it’s important for clinicians to obtain thorough medical histories to pinpoint when symptoms, such as dizziness, memory loss and headaches, started and when they worsened, she said.

“One that comes up all the time is asthma because asthma can develop at any point in life,” Reed said. “We know, historically, viral illnesses can cause asthma onset, so COVID can cause asthma onset. But, with women, hormonal changes and menopause can also cause onset.”

Reed recommends patients see a doctor after a COVID infection to rule out COVID-related damage to the body, and she urges people to remain vigilant of any sign of new problems.ExploreFrom November: Georgia long-COVID patients fight for benefits, legitimacy

“Pay attention to subtle things that some people may write off,” she said. “Talk to your doctor about brain fog or things like, ‘I just forgot what I was going to make for dinner,’ or ‘You know, that bill came in, and I forgot to pay for it.’”

At long COVID clinics, a team of specialists — cardiologists, pulmonologists, neurologists, psychiatrists and others — work together to treat patients. Often, the patients undergo a comprehensive evaluation, including a series of lab tests and imaging tests, to rule out other undiagnosed medical conditions.

Lacking established therapies for long COVID symptoms, doctors often rely on approaches that have been used for other ailments with similar symptoms.

“It’s been shocking. I’ve never seen, with other infections, such widespread, all-over-the-body symptoms for this long.”

– Dr. Alex Truong, co-director of Emory Healthcare’s post-COVID clinic

Neurological stimulants such as Adderall have shown to be effective at improving energy and focus. Albuterol, an inhaled medicine frequently used to treat asthma, can improve breathing. Other medications, physical therapy and cognitive programs also can be helpful.

“I would say to people who get COVID, you didn’t ask to get COVID, and you don’t deserve to fall ill and not have answers,” said Reed. “Reach out to somebody to at least be seen and evaluated because we can do things to get you feeling better. If we can’t reverse the long-term consequences, we can at least improve your quality of life.”

A high-stakes undertaking

Close to 1,000 people in Georgia — and at least 17,000 adults across the country — are being recruited for the massive NIH study called Researching COVID to Enhance Recovery (RECOVER). Its goal is to answer fundamental questions about exactly how the virus causes long COVID, which ultimately could lead to better, more tailored treatments.

The study sites in Atlanta — Emory Hope Clinic, Grady, Morehouse School of Medicine, the Atlanta Veterans Affairs Healthcare System and Kaiser Permanente of Georgia — will work together and are slated to receive a total of about$20 million over four years for the high-stakes undertaking.

The NIH study

The Atlanta sites for the NIH are still actively recruiting patients who have had COVID-19 in the past 30 days, as well as those who have never been infected. Click here for more information.

Walker, from Grady, said clinicians have been working to recruit a diverse group of adults, and are seeking three categories of participants: those who have COVID right now, those with long COVID, and others who have never had COVID. Finding people who have never had the illness is getting increasingly difficult with an ever-changing virus and continued waves of infections.

Plenty of theories have formed around long COVID. Some researchers think people suffer prolonged symptoms because they have never really shaken COVID-19, though they think they have. Instead, the virus is still hiding in their bodies, damaging nerves and other organs. Other research suggeststhe virus may be gone, but it causes the immune system to go haywire and attack the body.

There’s also research that indicates certain medical conditions may play a role in who develops long COVID, such as Type 2 diabetes, or a reactivation of Epstein-Barr virus, which infects most people when they are young.

‘A monster’

In July 2020, Latoshia Allen Perrymond fell ill with COVID. Within a week, the 52-year-old Stone Mountain woman was struggling to catch her breath. She ended up hospitalized — for four months.

Though she survived, COVID damaged her heart and lungs. She said she’s been struggling mightily ever since. Dependent on oxygen around the clock, the former caregiver now relies on family members to help care for her.

She can no longer go on walks with her husband or cook big meals, or even sleep lying flat.

In late March, she eagerly joined the NIH study at Grady.

Like other participants in the NIH RECOVER study, she’s undergoing physical assessments.

“I feel good about the study because it means that I’m part of the answers,” she said. “I’m willing to do whatever they need because this COVID and long COVD is a monster and it’s still creepy. I’m learning to live with this new norm for me, but I hope that I can get better.”

Doctors are also eager for more answers.

“My hope is to find a pathology that unifies all of these symptoms,” said Truong. “My hope is, as the pandemic progresses, the variants become less virulent and less likely to cause long haul issues, and more and more patients are getting vaccinated. I hope we learn from this pandemic so that, when the next pandemic comes, we are a lot smarter, a lot more nimble in our approach, and more aware of the long haul issues.”

For now, the best way to try to avoid long COVID is to try to avoid the virus, Truong said. Get vaccinated and boosted and wear masks – especially indoors around crowds of people.

“It’s as simple as that,” he said. “But, unfortunately, I don’t think people want to hear it.”

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Who’ll Get Long COVID? Just a Look at a Patient Gives Clues

Authors: Dennis Thompson Jul 19, 2022 The Indiana Gazette

ometimes just looking at a person can give clues to their likelihood of developing long COVID after a bout with the virus.

For example, obese people are five times more likely to suffer long COVID symptoms that persist at least three months after their infection clears, a major new U.S. study finds.

Another risk factor: Experiencing hair loss during COVID-19 illness, the same study found.

Headache and sore throat during infection also greatly increase a person’s risk of long-haul symptoms, the researchers added.

However, the results also showed that other risk factors for COVID-19 infection do not necessarily mean a person will develop long COVID, noted senior researcher Eileen Crimmins, chair of gerontology for the University of Southern California and director of the USC/UCLA Center on Biodemography and Population Health.

“What’s somewhat more interesting are the things that didn’t matter,” Crimmins said. “Gender didn’t predict long COVID. Race/ethnicity didn’t predict long COVID. And having conditions like hypertension [high blood pressure], heart disease, cancer, they didn’t predict long COVID.”

Overall, 23% of people infected with COVID-19 can be expected to develop long-haul symptoms, regardless of whether their infection was severe enough to require hospitalization, Crimmins and her colleagues reported. The study was published online recently in the journal Scientific Reports.

The World Health Organization defines long COVID as symptoms that last 12 weeks or longer after the initial infection has cleared, the researchers said.

“A significant number of people may have trouble working, taking care of their families, doing the things they need to do day-to-day because they’ve had the condition,” Crimmins said. “So, it’s not a nothing disease.”

These numbers are based on the Understanding America Study COVID-19 National Panel, an ongoing regular survey of more than 8,400 U.S. adults.

Starting every two weeks in March 2020, panel members were asked to fill out a questionnaire detailing their health status and any symptoms they might be having.

During the following year, about 10% of total participants reported that they’d been diagnosed with or tested positive for COVID-19.

The researchers focused in on 308 people who had COVID-19 and had reported their health status and symptoms before, during, and at least three months after their initial diagnosis.

What factors influenced the odds of long COVID the most? Obesity increased a person’s risk of long COVID by nearly five and a half times, the results showed. Other prominent risk factors included hair loss during infection, which increased sevenfold the risk of long COVID. Headache and sore throat each increased a person’s risk by more than three times.

It’s likely that obesity and hair loss are both tied to the amount of inflammation a person suffers during their COVID-19 infection, which can wreak havoc on their body’s organs, explained Dr. William Schaffner, medical director of the National Foundation for Infectious Diseases.

“Perhaps obesity allows that inflammation to persist for a longer period of time, therefore resulting in symptoms,” Schaffner said. “Hair loss is kind of new to me, but that’s obviously going to be some sort of symptom that relates somehow to inflammation.”

Surprisingly, age, gender, race, education, smoking, and preexisting health conditions like diabetes or asthma didn’t appear to influence the risk of long COVID.

The most common symptoms people developed during COVID that persisted months later included:

  • Headache (22%)
  • Runny or stuffy nose (19%)
  • Abdominal discomfort (18%)
  • Fatigue (17%)
  • Diarrhea (13%)

The study did not find other symptoms that have been commonly reported by long COVID-19 patients, including brain fog and joint pain, Schaffner noted.

“So there are some things that reinforce what’s in the literature and some other things that are a little different,” Schaffner said.

Despite that, Schaffner praised the study as a “noteworthy addition to the literature” that should help the many long COVID centers that have opened up around the country to deal with this phenomenon.

“The main thing I take away from this is that long COVID is not unusual. In fact, it’s rather common,” Schaffner said. “It’s persistent and it will require a great deal of medical attention going forward. A lot of medical resources will have to be devoted to this, and those resources will largely be outside the hospital, including supportive care, physical therapy and even some psychological support for these patients.”

Crimmins added it could take years, and even decades, to fully understand the long-term effects of COVID-19.

Research into the 1918 influenza pandemic found that fetuses in utero when moms caught the flu had a 25% higher risk of heart disease by the time they were in their 70s, Crimmins noted.

“There are things that may happen in this population to their underlying health that may not be immediately obvious, but could have relatively significant long-term effects,” Crimmins said of long COVID patients.

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Even mild Covid is linked to brain damage, scans show

The new British research is the first to reveal striking differences in areas of the brain based on scans taken before and after a coronavirus infection.

Authors: Benjamin Ryan Posted July 2022, From NBX News

During at least the first few months following a coronavirus infection, even mild cases of Covid-19 are associated with subtle tissue damage and accelerated losses in brain regions tied to the sense of smell, as well as a small loss in the brain’s overall volume, a new British study finds. Having mild Covid is also associated with a cognitive function deficit.

These are the striking findings of the new study led by University of Oxford investigators, one that leading Covid researchers consider particularly important because it is the first study of the disease’s potential impact on the brain that is based on brain scans taken both before and after participants contracted the coronavirus.

“This study design overcomes some of the major limitations of most brain-related studies of Covid-19 to date, which rely on analysis and interpretation at a single time point in people who had Covid-19,” said Dr. Serena S. Spudich, a neurologist at the Yale University School of Medicine, who was not involved in the research.

The research, which was published Monday in Nature, also stands out because the lion’s share of its participants apparently had mild Covid — by far, the most common outcome of coronavirus infections. Most of the brain-related studies in this field have focused on those with moderate to severe Covid.

Gwenaëlle Douaud, an associate professor at the Nuffield Department of Clinical Neurosciences at Oxford and the paper’s lead author, said that the excess loss of brain volume she and her colleagues observed in brain scans of hundreds of British individuals is equivalent to at least one extra year of normal aging.

“It is brain damage, but it is possible that it is reversible,” she said. “But it is still relatively scary because it was in mildly infected people.”

Douaud and her team relied on a rich data source: the United Kingdom Biobank. Before the Covid pandemic began, this mammoth database already had on hand tens of thousands of brain MRIs of people in Britain, along with responses to surveys about their diets and lifestyles and results from cognitive function tests.

The investigators focused on 401 people between 51 and 81 years old who had tested positive for Covid according to clinical data linked to the Biobank study. They were invited back for a second brain scan, which they received an average of about five months after contracting the coronavirus. Covid was apparently mild in the vast majority of these participants; only 15 of them were hospitalized with the disease.

The researchers compared these pairs of scans to those of a control group of 384 U.K. Biobank participants who had not tested positive for Covid and were matched according to the Covid-positive group’s rates of obesity, blood pressure, smoking and diabetes, as well as their socioeconomic status, age and sex.

Between the pairs of MRIs, which were separated by an average of about three years, the researchers observed a striking trend among those who had Covid: a greater loss of what’s known as gray matter in the brain, as well as a higher rate of abnormalities in the brain tissue. Gray matter, which appears gray on certain brain scans, is comprised of various cells, including neurons.

It would be normal for adults within the study’s age range to lose a small amount of brain tissue after three years of aging, the researchers note. But compared with the control group, those who had Covid experienced an additional 0.2 percent to 2 percent loss of brain tissue in regions which are mostly associated with the sense of smell — specifically, in the parahippocampal gyrus, the orbitofrontal cortex and the insula.

The overall brain volume in people with Covid declined by an extra 0.3 percent over those without the disease.

Older participants experienced all these excess brain-related declines more profoundly.

The study offers no indication whether a Covid vaccination would mitigate the risk of such changes. The participants tested positive for the disease between March 2020 and April 2021, before the vaccines were widely available in the U.K.

On cognitive function tests, those who had Covid demonstrated a slower ability to process information and had lower marks on what’s known as executive function, which is an umbrella measure of the brain’s ability to manage complex tasks. Again, these Covid-linked deficits were more pronounced among older individuals.

Dr. Avindra Nath, clinical director of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, said that these findings “have long-term implications, since we would be concerned about the possibility of similar cognitive dysfunction in a large population worldwide.”

“It needs to be determined if these patients could further deteriorate over a period of time,” he said.

The investigators had no access to data on any Covid-related symptoms the participants may have experienced. So they don’t know if the participants actually lost their sense of smell or have experienced long-term symptoms in the disease’s wake. Some likely had asymptomatic cases.

That said, the loss of smell was particularly prevalent among those infected with the coronavirus during the first two major waves of the pandemic. And when particular regions of the brain go unused, they are inclined to atrophy. Nevertheless, the study’s authors don’t know whether the coronavirus caused a loss of smell through a nonbrain-based mechanism and this, in turn, prompted the brain damage, or if possibly the brain damage caused the loss of smell.

How long do Covid brain changes last?

A study published in Cell in February found that a coronavirus infection of various cells in the nasal cavity gives rise to inflammation that inhibits the functioning of smell-receptor proteins on nerve cells, leading to smell loss.