4 important questions about the long-term symptoms of COVID-19

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4 important questions about the long-term symptoms of COVID-19

4 important questions about the long-term symptoms of COVID-19. Scientists are beginning to gain insight into the long-term symptoms that affect some SARS-CoV-2 patients-but many mysteries are still unsolved.

When Claire Hastie fell ill in March last year, she tried to ignore it based on her previous experience with minor illnesses. At first, the symptoms were so mild that Hastie didn’t even notice that she was sick.

But within a week, the symptoms suddenly worsened. She has never been so uncomfortable. His chest was tight as if there was an elephant lying on his chest. Sometimes, she felt that she might die soon.

As a single mother of three children, Hastie said her “last words” to one of the children who happened to walk by the door of her room. Although a year has passed, her condition is not that serious, but she said that the symptoms have been there ever since.

Hastie has the so-called long-term COVID: a long-term illness that develops after being infected with SARS-CoV-2, the virus that causes COVID-19.

A survey of thousands of people revealed a wide range of symptoms, such as fatigue, dry cough, shortness of breath, headache and muscle aches. A team led by University College London neuroscientist Athena Akrami, who also has long-term symptoms of COVID, found 205 symptoms in a study of more than 3,500 people. By the 6th month, the most common symptoms are “fatigue, discomfort after exertion, and cognitive dysfunction”. These symptoms sometimes go up and down, and sometimes you think that you are about to heal, and the symptoms reappear as a result.

In the first few months of the pandemic, the idea that the virus could cause chronic disease was ignored in the desperate struggle to deal with acute cases. But Hastie soon realized that she was not the only person suffering from this disease. In May 2020, she opened a Facebook group for people who have been suffering from COVID for a long time. Today, it has more than 40,000 members and collaborates with research groups working on this disease—Hastie sometimes appears as a co-author of the paper.

At the same time, the long-term COVID has changed from a largely neglected field to a public health problem. In January of this year, the WHO revised its COVID-19 treatment guidelines to include a recommendation that all long-term COVID patients should receive follow-up care.

Funding agencies are also paying attention. On February 23, NIH announced that it would spend US$1.15 billion in long-term COVID research within 4 years, which it called “post-acute sequelae of COVID-19 (PASC).” In the United Kingdom, the National Institute for Health Research (NIHR) announced in February that it would invest 18.5 million pounds (US$25.8 million) to fund four long-term COVID studies-and in the following month, increase in this area 20 million pounds of investment. The UK BioBank plans to send self-test kits to all its 500,000 participants so that it can identify those with SARS-CoV-2 antibodies and invite them to conduct further research.

As the number of confirmed COVID cases worldwide exceeds 170 million, millions of people may experience persistent symptoms and urgently need to know how long-term COVID will affect their future health. In this article, the journal Nature looks at four key questions about long-term COVID that scientists are studying.

1. How many people suffer from long-term COVID-19, and who is most at risk?

As a result of a series of investigations, people have become more and more aware of the overall long-term COVID epidemic-but it is not certain who is at the greatest risk and why it only affects some people.

Most early prevalence studies only focus on people hospitalized with acute COVID-19. Ani Nalbandian, a cardiologist at Columbia University Irving Medical Center in New York, and others compiled nine such studies and published a review on March 22. They found that 32.6% to 87.4% of patients reported that at least one symptom persisted after a few months.

But most patients with COVID-19 have symptoms that are not mild enough to be hospitalized. The best way to assess the long-term prevalence of COVID is to follow a representative population who has tested positive for the virus. The Office for National Statistics (ONS) has done just that, by tracking more than 20,000 people who have tested positive since April 2020 (Figure: Uncertain endpoint). In the latest analysis published on April 1, ONS found that 13.7% of people still report symptoms after at least 12 weeks (there is no widely agreed definition for long-term COVID, but ONS believes that long-term symptoms of COVID-19 will last for more than 4 weeks).

Akrami believes that this is the best estimate so far. While studying the original topic-neuroscience-she is also committed to studying the long-term COVID-19.

In other words, more than one in ten people infected with SARS-CoV-2 will develop long-term COVID. If the prevalence rate in the UK is applied elsewhere, there will be more than 16 million long-term COVID-19 patients worldwide.

This condition seems to be more common in women than men. In another ONS analysis, 23% of women and 19% of men still had symptoms 5 weeks after infection. Rachael Evans, a clinical scientist at the University of Leicester in the United Kingdom and a member of the Post-Hospitalisation COVID-19 study (PHOSP-COVID), pointed out that this is “astonishing.” “If you are a male and are infected with COVID, you are more likely to go to the hospital and more likely to die, but you may also survive. Compared with this, women are more likely to have persistent symptoms.

There is also a unique age distribution. According to data from the UK National Bureau of Statistics, middle-aged people are more likely to develop long-term COVID: People between 35 and 49 years old have a 25.6% chance of still having symptoms at 5 weeks. This is less common among young and elderly people-although Evans reminded that the latter’s findings may be due to “survivor bias”, because too many elderly people with COVID-19 have died.

Although long-term COVID is less common among young people, this does not mean that it does not exist. Even for children aged 2-11, the National Bureau of Statistics estimates that 9.8% of people who test positive for the virus will still have symptoms after at least 5 weeks, which reinforces the recommendations of other studies that children may be chronically infected with COVID. However, some medical professionals have played down this idea. Sammie Mcfarland, founder of the British support organization Long Covid Kids, said that people still do not believe that children will also have long-term COVID-19. Their symptoms are often ignored.

However, age and gender are very effective in identifying people at risk. A paper published in March proposed a model that uses only a person’s age, gender, and the number of symptoms reported in the first week to successfully predict whether a person will be infected with COVID for a long time.

Nevertheless, there are still many uncertainties. In particular, if about 10% of SARS-CoV-2 infected people have long-term COVID-as the ONS data indicates-then why is that 10%?

Uncertain end

OFFICE FOR NATIONAL STATISTICS tracked more than 2000 people infected by COVID-19 to check how long their symptoms las. ONS definites” Long-term COVID” as COVID-19 symptoms lasting more than 4 weeks

4 important questions about the long-term symptoms of COVID-19

2. What is the potential biology of long-term COVID?

Although researchers have thoroughly investigated the various symptoms of long-term COVID, there is no clear explanation yet. Hastie pointed out that we need people to pay attention to these mechanisms. This is not easy: research shows that many people with chronic COVID have problems with multiple organs, which suggests that this is a multi-system disease.

Evans said it seems unlikely that the virus itself is still working. Most studies have shown that the body has almost cleared the virus after a few weeks, so he very much suspects that this may not be a direct consequence of the virus infection.

However, there is evidence that fragments of the virus, such as protein molecules, can last for months. In this case, even if they cannot infect cells, they may damage the body in some way.

Another possibility is that the prolonged COVID is caused by the immune system getting out of control and attacking other parts of the body. In other words, the long-term COVID may be an autoimmune disease. Steven Deeks, a doctor and infectious disease researcher at the University of California, San Francisco, pointed out that SARS-CoV-2 is like a nuclear bomb as far as the immune system is concerned. It will only blow up everything. Some of these immune changes may persist-as seen in the consequences of other viral infections (see question 3).

Nevertheless, it is too early to say which hypothesis is correct, and each hypothesis may be correct for different people: preliminary data suggests that long-term COVID may combine several diseases into one.

Some researchers are taking the next step, hoping to uncover the mystery of biology. PHOSP-COVID has recruited more than 1,000 British patients and collected blood samples to look for evidence of inflammation, cardiovascular problems and other changes. Similarly, Deeks helped recruit nearly 300 COVID-19 patients, followed up every 4 months thereafter, and provided blood and saliva samples. According to Deeks, they have a huge specimen library and are studying the results of inflammation, changes in the blood coagulation system, and evidence of the continued existence of the virus. The team found changes in the levels of cytokines (molecules that help regulate the immune response) in the blood of people infected with COVID-19, indicating that the immune system is indeed out of balance, and protein markers also indicate neuronal dysfunction.

Evans said that a better understanding of the underlying biological mechanisms will point the way for treatments and drugs. But it seems unlikely that there will be a single, concise explanation for the long-term COVID. Most researchers now suspect that there are several mechanisms at work, so the long-term COVID of one person may be very different from that of another person. Last October, a review published by NIHR raised the possibility that long-term COVID symptoms “may be due to many different syndromes.” Deeks pointed out that now the problem has become very complicated, and there is no fixed clinical phenotype. There are different tastes, different clusters. They may all have different mechanisms. His team plans to use machine learning to calculate how many types of long-term coronaviruses are and the differences between them.

Evans and her PHOSP-COVID colleagues tried this in a preprint released on March 25. They studied 1,077 COVID-19 patients, and the symptoms recorded included physical disorders, mental health difficulties such as anxiety, and cognitive disorders in areas such as memory and language. The researchers also recorded basic information such as age and gender, as well as biochemical data such as C-reactive protein levels (a measure of inflammation). The team then used a mathematical tool called cluster analysis to see if there were groups of identifiable patients with similar characteristics.

Evans and others believe that if you have severe acute lung injury and multiple organ failure, then these people will have persistent pathology. But the study found that there is almost no relationship between the severity of the acute phase or the degree of organ damage and the severity of long-term COVID.

The actual situation is more complicated. The analysis identified four groups of long-term COVID patients with obvious symptoms. Three of the groups have varying degrees of mental health and physical impairment, but little or no cognitive impairment. The fourth group showed only moderate mental health and physical impairment, but had obvious cognitive problems.

Evans emphasized that there are big differences in the degree of cognitive impairment, although this study did not reveal the underlying mechanism. But this is definitely the first step.

3. What is the relationship between long-term COVID and other post-infection syndromes?

Some scientists are not surprised by the long-term COVID. Anthony Komaroff, a physician at Harvard Medical School in Boston, Boston, said that scientific literature over 100 years ago reported the persistence of symptoms after infection.

He pointed out this fact in a webinar organized by MEAction in March. Located in Santa Monica, California, MEAction is dedicated to raising awareness of myalgic encephalitis (also known as chronic fatigue syndrome (ME/CFS)). People suffering from this debilitating disease will be exhausted even after performing light activities, and they will also experience headaches and other symptoms at the same time. For a long time, because there is no clear biological basis, ME/CFS is often rejected by some medical professionals.

It is not uncommon for infections to cause long-term symptoms. A study of 253 people diagnosed with certain viral or bacterial infections found that after 6 months, 12% reported persistent symptoms, including “disabling fatigue, musculoskeletal pain, neurological recognition Knowing difficulties and emotional disorders”. This percentage is surprisingly similar to the long-term COVID prevalence observed in the United Kingdom by the National Bureau of Statistics.

According to Komaroff and his colleagues, Lucinda Bateman, founder of the Bateman Horne Center in Salt Lake City, Utah, and a researcher who specializes in ME/CFS11, some long-term COVID patients may be eligible for ME/CFS. Diagnostic criteria. But there seems to be a difference: For example, people with chronic COVID are more likely to report shortness of breath than people with ME/CFS. In addition, if the long-term COVID is finally subdivided into multiple syndromes, this will further complicate the comparison between it and ME/CFS.

University of Southampton public health researcher Nisreen Alwan pointed out that so far, he has refused to say that long-term COVID is ME/CFS, because he really thinks it is a general term, and that long-term COVID actually encompasses a lot of symptoms. Deeks agrees with many people. He thinks everyone needs to be a little agnostic now, don’t make too many assumptions, and don’t put all these different syndromes in the same bucket. However, many people do agree that these two diseases can be effectively studied at the same time. Alwan believes that there should be an alliance. Some researchers are already planning to collaborate. For example, a major study called DecodeME aims to recruit 20,000 people to find genetic factors that cause ME/CFS. Evans pointed out that PHOSP-COVID will share data with DecodeME.

Akrami really hopes that the long-term research on COVID-19 will provide some inspiration for other diseases after infection.

Hastie hopes more bluntly not to waste a good crisis.

4. What can we do for long-term COVID-19 patients?

Currently, the options are quite limited because people know very little about this disease.

Some countries are opening clinics for long-term COVID patients. In Germany, a company called MEDIAN has begun accepting long-term COVID patients in some of its private rehabilitation clinics. In England, the National Health Service provided £10 million to a network of 69 clinics: these clinics have begun to assess and help people with this disease.

Hastie said this is the first step that is welcome, but there are few evidence-based treatments. More and more people believe that a multidisciplinary team is needed because long-term COVID will affect many parts of the body. Akrami reminded that, on average, everyone has 16 or 17 symptoms, and clinics usually don’t have such a team.

Most of the challenges will be social and political because people with chronic COVID must rest, usually for several months at a time, and they need support in doing so. Hastie believes that their condition “needs to be treated as a disability.”

In terms of drugs, a small number of drugs are being tested. PureTech Health, a biotechnology company based in Boston, Massachusetts, announced in December last year that it was starting clinical trials of its anti-fibrosis and anti-inflammatory agent deupirfenidone, and it is expected to obtain results in the second half of 2021. In the UK, Charlotte Summers, an intensive care specialist at the University of Cambridge, and others initiated a study called HEAL-COVID to prevent the occurrence of long-term COVID. Participants hospitalized with COVID-19 will take one of two drugs after discharge: apixaban, an anticoagulant that may reduce the risk of dangerous blood clots; and atorvastatin, an anti-inflammatory drug. In the United States, NIH is funding an existing drug trial that patients with mild COVID-19 can use at home. Participants will be followed for 90 days to test the drug’s effect on long-term symptoms.

Finally, there is the question of what role the COVID-19 vaccine might play. Although many of them can prevent death and serious illness, scientists do not yet know whether they can prevent long-term COVID.

How does the vaccine affect people who already have long-term COVID symptoms? A UK survey of more than 800 long-term COVID patients (not yet peer-reviewed) reported in May that 57% of people’s symptoms have improved overall, 24% have no changes, and 19% are in the first place. The condition worsened after the vaccine was administered. In April, Akrami’s team launched a systematic survey to reveal more information, “People need to be vaccinated to escape the pandemic, but we need to address their concerns about whether the vaccine is helpful, harmless or harmful” .

Similarly, Akiko Iwasaki, an immunobiologist at Yale University in New Haven, Connecticut, is recruiting unvaccinated long-term COVID patients and tracking their body’s response to the vaccine. Her hypothesis is that vaccines can improve symptoms by eliminating any viruses or viral residues left in the body, or by rebalancing the immune system.

People with chronic COVID just want something useful. Hastie said that they just want to know how to get better.

(source:internet, reference only)

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