Could long COVID represent new global health crisis?

Prolonged physical, mental, and neurological symptoms have affected children as much as adults, including many who had mild reactions when they were infected with the coronavirus

Unlike other common infections, such as Influenza, COVID-19 intrigues researchers and physicians regarding the effects it causes after the infection. As our understanding of the disease increased, the possibility that people, even cured, could be left with long-term sequelae became evident. The expectation was that the symptoms would disappear with the improvement of the clinical condition of those affected, however, despite the majority of patients showing complete recovery, a portion may experience persistent symptoms after infection, which cause physical and emotional damage, giving rise to a name for this type of contamination with post-infection damage: long COVID. The expression that designates this phenomenon, refers to situations that go beyond twelve weeks and covers a wide range of symptoms. The most common, apparently, have to do with fatigue and breathing difficulties. There is also mentions of cardiac sequelae and mental fog (brain fog).

Professor Dr. Danny Altmann, from the Department of Immunology and Inflammation at London Imperial College explains that patient groups now define hundreds of symptoms in various combinations. For him, an important point is that studies around the world present very similar hierarchies of symptoms. “Almost at the top of the list is fatigue, shortness of breath, chest/heart pain, brain fog. But with the large number of studies in progress around the world, the list will grow longer”, he alerts.

In the search for answers to explain the long COVID, researchers in the United States have developed a new theory. According to them, the cause of the symptoms may have nothing to do with the coronavirus, but with another virus, the Epstein-Barr (EBV), responsible for one of the most common viral infections in the world, mononucleosis (known as the kissing disease ), and has flu-like symptoms. The study entitled Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation was published in the scientific journal Pathogens. According to the study, more than 73% of patients with COVID who had prolonged symptoms were also positive for reinfection with EBV, which is inactive in the body and can be reactivated in periods of psychological stress.

Meanwhile, scientists at the RCSI University of Medicine and Health Sciences in Ireland have released a new study titled “Persistent Endotheliopathy in the Pathogenesis of Long COVID Syndrome”, published in the Journal of Thrombosis and Haemostasis. To conduct the study, the team examined 50 patients with symptoms of long COVID to understand whether abnormal blood clotting could be involved. The researchers found that the clotting markers were significantly elevated in the patients blood compared to healthy people, while the inflammation markers returned to normal. For them, the difference between the markers of coagulation and inflammation indicate that blood clots may be related to symptoms of long COVID.

Other scientists also detect one more likely complication of long COVID: cognitive problems that impair memory, reasoning, and problem-solving ability. In the United States, for example, many children preparing to return to school struggle to recover from persistent physical, neurological and psychiatric symptoms after being infected with the coronavirus. In the UK there is a large cohort of children with long COVID.

Expand understanding of post-COVID syndrome

Asked why it is so difficult to definitively diagnose long COVID, Dr. Altmann points out that at the moment, most countries do not have a clinical definition, so the diagnosis is necessarily made by the patients report. This, in turn, can fuel a complicated situation, in which the condition can only be reported by the patient, although what was reported becomes a term used by cynics to undermine the existence of the condition, he ponders. For Dr. Altmann, formal clinical definitions are needed (time since onset of acute illness, number of symptoms, etc.), also ideally supported by blood tests for biomarkers.

And how are we going to discover the long-term effects of long COVID if there are currently no tests to diagnose it? “The answer seems obvious, there needs to be a much greater awareness of the definition among general practitioners. That is, you can encode it in national health record databases, even if you dont have a blood test,” emphasizes Dr. Altmann, who is currently studying whether there is blood similarity between people who suffer from long COVID. He and his team  analyze the range of antibodies in the blood of patients who have been hospitalized, people who have not been hospitalized and also those who have not even been able to access a PCR test, to find out which parts of the human proteome, the human protein antigens, respond so that they understand how this test can be performed, in order to make something accessible and able to provide the necessary diagnosis. “We hope to discover a biosignature in the blood that can form a test, but also inform which therapies are useful”, he says. Click here to learn more.

Regarding the evidence that long COVID may predispose to other health conditions, Dr. Altmann reveals that some patients are concerned that there may be implications, such as for long-term neurocognitive function, but its too early to tell. Others are concerned about outbreaks of other autoimmune diseases such as diabetes, vasculitis and arthritis. Asked if it is possible to avoid the effects of long COVID, Dr. Altmann is categorical in stating that this is the big question and the reason why detailed mechanistic studies based on prospective analyses are needed. “Obviously, if we know the risk factors it is possible to proactively treat. Candidates would be antivirals or anti-inflammatory drugs, but we need the studies”, he emphasizes.

Can the emergence of new variants have a distinct impact on long COVID? Dr. Altmann acknowledges that this is a great question, unfortunately for the most part still unknown. He clarifies that many aspects of the variant biology are different, so there may well be differences in terms of long COVID. “The point about long COVID is that you tell the story in real time and you dont know the long-term prospects”, he adds. With regard to vaccines, he said, it is still too early to say whether they have an impact on long COVID or if they are limiting it in some way. But the simplest and most obvious point, however, is that getting the vaccine results in fewer infections and fewer infections mean fewer long COVID.

Studies estimate that long COVID can affect from 10% to 30% of adults infected with the coronavirus. Despite the significant percentage of people with long COVID, limited evidence on the problem and lack of diagnostic tools, the number of patients that continues to grow could represent a new global health crisis and demonstrates the enormous challenge to be faced by health systems. “It is very important that all affected countries prepare themselves; if long COVID accounts for 10 to 20% of all those infected, perhaps for the next four or five years, the implications will be huge: for health care delivery, number of clinics, doctors and nurses. The only way to prepare for this is to have some accurate numbers and then put enough government money into it. In some aspects, Brazil is ahead of the world, having taken this path with chikungunya, concludes Dr. Altmann.