Very long Covid. Four versions of the origin of Post-Covid Syndrome (PCS) and its most dangerous consequences?

Several months after recovering from Covid-19, millions of people around the world are still unable to return to normal life. Some continue to experience shortness of breath, increased fatigue, and loss of smell and taste.

For others, coronavirus symptoms that previously disappeared suddenly reappear after a few weeks, sometimes accompanied by new symptoms. For some, Covid-19 evolves into a severe chronic disease affecting almost every organ.

Scientists and doctors of various specialties are trying to understand how and why 10-15% of those infected with the coronavirus develop “long COVID” (doctors call it PCS – “post-COVID syndrome”) – a disease that has no formal definition or established name. There are already calls in the USA to equate it with disability.

The Russian service of the BBC tells which versions seem most plausible to scientists today and tries to answer the question of what awaits patients, some of whom have not recovered for more than a year.

Polina T. of Moscow contracted Covid-19 in the fall of last year. When the first mild symptoms appeared in September, she mistook them for a cold and decided to rest for a few days – but just in case, she ordered a coronavirus test, which came back positive. Polina lost her sense of smell the day after she was diagnosed, when she “went to smell mustard in the morning and didn’t feel it. But all in all, she says, “the disease progressed very calmly – without high fever or any complications: I was just very weak, and my temperature was around 37.2”. The temperature did not go down for more than three weeks. During this time, Polina managed to take the test twice: the first one showed the presence of the virus in her body again, and the second one came out “clean”. Around the same time, her temperature returned to normal, but general weakness and increased fatigue persisted for another month after her official recovery. The lost sense of smell returned even later – around New Year’s.

Polina thought she had fully recovered, but her joy was short-lived: literally a few weeks later, strange things began to happen to her sense of smell. Familiar smells began to change into an extremely unpleasant odor that Polina herself describes as “a compost pit of fermented rotten vegetables. We explain quickly, simply, and clearly what happened, why it matters, and what happens next. The number of offers should remain: episodes. The end of the story: Podcast Advertising First it was paprika, then other products – meat, poultry, cauliflower – were infected with the stench, but the most unpleasant thing happened when a Muscovite woman began to perceive with the same disgust the smells of human bodies, both her own and those of others. This continues to this day, with no improvement observed – even though it’s been four months since January, and the tests stopped detecting the presence of the virus in Polina’s body in mid-October, more than seven months ago.

Polina’s story is a case that, while not the most common, is far from unique. Loss of sense of smell is one of the symptoms of “long COVID”, now well known to doctors and extensively described in the scientific literature. It is unpleasant, of course, but not fatal – and there is even hope for a full recovery.

However, after recovering from Covid-19, a patient may experience a variety of symptoms that fall under the description of Long Covid. This is how Ashley Nicole, a 35-year-old lawyer from Alberta, described her condition. “This morning, for the 255th time, I woke up with a blinding headache: everything seemed blurry before my eyes, so I could hardly see anything. It felt as if someone had stuffed broken glass down my throat, and my chest was so twisted that it took my breath away…” The tweet was published last December, although Ashley contracted the coronavirus in March, at the very beginning of the epidemic, and officially recovered in April 2020. However, the symptoms of the disease did not go away and are still present today, albeit slightly diminished. In addition to fatigue (one of the most common symptoms), over the past 14 months since the onset of the disease, Ashley has lost almost all of her hair, the skin on her hands has become hypersensitive as if burned, and her nails have become loose and darkened. These are all very rare, but also common symptoms of “long COVID”, which manifest themselves very individually in different patients and vary greatly in diversity.

The National Institute for Health in the United Kingdom suggests that post-COVID syndrome should be considered as “signs and symptoms that occur during or after an infection, with a clinical picture consistent with COVID-19, and persist for more than 12 weeks if they cannot be explained by any other alternative diagnosis”. The World Health Organization has been trying to compile a list of such “signs and symptoms” for several months now, but it is much more difficult than it seems at first glance.

Because Covid-19 is primarily transmitted through airborne droplets, we are accustomed to thinking of it as a respiratory disease: after entering the body through the nose or mouth, the virus affects the upper respiratory tract and then “descends” into the lungs. But a year ago, scientists found out that when the new virus enters the bloodstream from the nasopharynx, it quickly spreads throughout the body, hitting the most vulnerable organs. SARS-CoV-2 has been shown to be capable of disrupting the functioning of the nervous system, gastrointestinal tract, urinary and cardiovascular systems, and so on. Therefore, long-term complications of Covid-19 can occur almost anywhere.

“Long COVID affects different organs, so it’s clearly a multidisciplinary problem,” agrees Maria Van Kerkhove, the WHO’s senior technical specialist in the fight against the Covid-19 pandemic. According to Maria, she has met with many patients over the past year who have complained of prolonged illness and have asked the WHO to at least publicly acknowledge that long COVID is real – that the syndrome actually exists and is not a figment of the imagination of those who have recovered. And on this issue, the WHO’s position is clear. “We know this is a real problem,” Van Kerkhove assured a BBC correspondent. “We know that long COVID affects different organs. What we are trying to do now is to organize a systematic collection of data in order to develop treatment protocols, rehabilitation protocols, so that everyone, no matter where they are in the world, can get the help they need.”

So far, Maria Van Kerkhov says, one thing is absolutely clear: “This is indeed a dangerous virus […] Even if a person has COVID relatively easily and recovers relatively quickly, it can have extremely unpleasant long-term consequences. Their words are backed up by statistics. According to the UK Office for National Statistics, nearly one in seven patients diagnosed with Covid-19 have symptoms of the coronavirus for at least three months. Considering that as of March of this year, the number of confirmed cases worldwide has exceeded 110 million, it is reasonable to assume that at least 15 million people today may be experiencing some degree of symptoms and signs of “long COVID”.

Given the problems with counting and testing for the virus in different countries and at different stages of the pandemic, this number could be even higher. In the UK alone, by the end of February this year, nearly 500,000 people complained that they had not been free of post-COVID symptoms for at least six months. And that half a million, by definition, does not include patients from the second wave that began in the country in October. Francis Collins, head of the National Institutes of Health in the United States, estimated in late April that 3 million Americans already have chronic health problems caused by Covid-19. “This is such a huge problem for the health of the nation that it is hard to overestimate,” he said.

At the same time, experts pay special attention to an interesting fact: the overwhelming majority of patients who develop post-COVID syndrome (90%) had no underlying chronic diseases before infection, which usually complicates the infection, and they experienced COVID-19 itself in a relatively mild form – and even if they sought medical attention, they did not need to be hospitalized. So they did not expect the virus to come back in a few months.

In general, the symptoms of Covid-19 last for several months in relatively young patients (the average age of people with long Covid symptoms is 40 years), and among them there are significantly more women than men (70-80%). So what are these symptoms – is there at least a rough list of them? Yes and no.

The majority of serious studies that have been reviewed by the scientific community are not large enough and at best describe a hundred people with MS. The largest research in this area to date is an online survey conducted last fall by British and American scientists in collaboration with a group of activists who are COVID-19 patients themselves. Nearly 3800 people took part, listing 205 different manifestations of the disease. According to the respondents, one-third of the symptoms had bothered them for at least six months.

The format of Internet surveys implies a rather biased sample. And, of course, patients’ perceptions of their own symptoms are less reliable than laboratory tests. Therefore, the results of such studies should be treated with caution. However, the survey results can provide a general understanding of patients’ well-being, as well as when and in what combination symptoms occur and how long they last.

The majority of survey respondents listed a variety of symptoms they experienced, but the most debilitating long-term manifestations of the disease were usually described as severe breathlessness, incredible fatigue, post-exertional malaise, or brain fog. The authors of the study pay special attention to chronic fatigue syndrome. Most of the patients observed experienced an incredible weakness that made it difficult for them to get out of bed. Six months after infection, three-quarters of those who still had symptoms (i.e., had developed chronic fatigue syndrome) still complained of a catastrophic lack of energy. To the point where even the simplest daily tasks, such as getting dressed, eating breakfast, or going to the bathroom, left them so exhausted that they required complete rest. “You feel like you’ve just been hit by a truck and left on the side of the road to die – so you can’t speak or move,” says Shannon Riley, one of the “Long Covid” patients.

Many experts are concerned that one of the most common symptoms of PCS is a disruption of cognitive function, including impaired consciousness, which is more characteristic of mental disorders that usually develop at a much older age. Many patients described problems with concentration and an inability to sustain attention, difficulty solving simple tasks, or making decisions. These problems began in the first week of illness and increased over the course of three months. However, even after six months, if the symptoms have not completely disappeared, about one in two respondents complains of some degree of mental fog.

At the same time, scientists are absolutely certain that in addition to fatigue, respiratory problems, and cognitive impairment, CCS can have a variety of other side effects – sometimes completely unexpected. For example, while we learned last spring that one of the characteristic symptoms of Covid-19 is a temporary loss of smell (anosmia), patients who have already recovered from coronavirus are now increasingly reporting a disruption in the normal functioning of olfactory receptors (parosmia) – when the most familiar things suddenly start to smell like sewage, rotten fish, or burnt plastic. This is the diagnosis that Moscow resident Polina T. should have received in January: “When I went to the doctor with a complaint of distorted smells, he told me that it was a very common problem related to COVID-19 and that it would probably go away on its own.” Professor Nirval Kumar, head of the British Association of ENT Doctors, also assured journalists that parosmia is a reversible disorder of smell that eventually goes away on its own, although this process can be accelerated with the help of special therapy.

In April, academician Alexander Chuchalin, who heads the Russian Respiratory Society, reported that doctors have begun diagnosing a condition called “post-COVID myocarditis” in patients with long COVID. According to him, in addition to mild symptoms, the virus also affects the heart muscle.

In addition, Chuchalin explained that Covid-19 can induce fibrosis (i.e., scarring) not only in the lungs, but also in any organ that the virus has reached. This occurs when the patient’s immune system fails to deal with the infection and essentially “encases” the virus, turning the functioning cells of the liver, kidneys, pancreas, spleen, or other organs into connective tissue. The virus has also been shown to sometimes cause blood clotting problems and increase the risk of thrombosis. In the long term, this could lead to unexpected symptoms in some patients. In particular, cases of tooth loosening and hair loss in coronavirus patients have been described in medical journals. According to doctors, changes in the blood vessels may have led to impaired blood circulation in the gums or around the hair follicles. Moreover, Covid-19 is by no means the first or only disease to cause such unpleasant and varied long-term consequences, says Amy Proal, head of the scientific department at the PolyBio research fund, which specializes in the study of autoimmune diseases.

In an interview with the BBC, Dr. Proal listed four possible reasons for “long COVID”. First, during the acute phase of coronavirus infection, the coronavirus causes severe damage to any organ, such as the fibrosis mentioned above. When the acute phase subsides, the affected organ may not always be able to fully recover its functions, meaning that Covid-19 actually provokes a virus-unrelated chronic condition. Second, although the PCR tests cannot detect the virus, the virus does not completely leave the patient’s body and remains in one or another organ (“reservoir”) – for example, in liver tissue or the central nervous system.

In such cases, the presence of the virus itself can cause chronic symptoms by interfering with the normal functioning of the organ. Such cases have been described in patients with Zika or Ebola viruses.

Third, the coronavirus Sars-Cov-2 disrupts the immune system settings that are established from childhood and disrupts the signals of interferon proteins that restrain other viruses that are constantly present in our bodies, as a result of which these other viruses become activated and begin to actively replicate. For example, according to Dr. Pearl, several studies have already been conducted during the pandemic showing reactivation of herpes viruses in coronavirus patients. “But we are not sterile: trillions of microorganisms – bacteria and viruses – live in our bodies,” she explains. “It is logical to assume that in conditions of weakened immunity due to the coronavirus, the usual balance is disturbed – and as a result, whole colonies of these microorganisms begin to go out of control, causing some chronic symptoms. Such cases [in COVID patients] have also been documented in several studies.”

And finally, the fourth possible reason is explained by genetics, if, by chance, the coronavirus actually comes into conflict with the patient’s DNA, turning Covid-19 into a chronic autoimmune disease. This happens when one of the proteins produced in the patient’s body is similar in shape and size to the virus protein. This phenomenon is known as “molecular mimicry,” and even if the two protein molecules have almost nothing in common in terms of composition, such a coincidence can be enough. The body’s aggressive immune response to the infection will inevitably destroy the patient’s own cells that produce the necessary proteins. All of the above explanations, Dr. Proal clarifies, are not mutually exclusive and may occur in any combination in a given patient with PCS.

Before answering the question of whether patients who have been experiencing uncomfortable symptoms for more than a year should wait for full recovery, Amy Proal pauses. “I think… I think the patients will get better,” she finally replies. “Yes, I am optimistic.”

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