St Petersburg University scientists: a fifth of patients who have recovered from COVID-19 have long Covid

The International Congress was organised by St Petersburg University and Ariel University (Israel) and supported by a grant from the Government of the Russian Federation for state support of research headed by leading scientists, contract No 14.W03.31.0009.

After immunology emerged as a science and especially when the first vaccines were developed, we inclined to regard epidemics as a thing of the past and the risk of another pandemic like the 1918 Spanish flu seemed to be negligible. ‘Yet, as the German philosopher Karl Robert Eduard von Hartmann put it, no matter how medicine has progressed, no matter how many remedies have been found, diseases evolve. New diseases appear and will appear, and they will always be one step ahead of medicine', said Leonid Churilov, Deputy Head of the Laboratory of the Mosaic of Autoimmunity, Head of the Department of Pathology at St Petersburg University, and Co-President of the Congress.

In early 2020, one step ahead of medicine was SARS-CoV-2, the coronavirus that changed our world. Although progress has been made in Coronavirus treatments and prevention, the pandemic is still underway. This means that we 'must use what modern medicine has achieved to shape a better future for all of us' said Professor Albert Pinhasov, Rector of Ariel University.  As of November 2021, more than 262 million people were infected worldwide, more than five million died. Yehuda Shoenfeld is Head of the Laboratory of the Mosaic of Autoimmunity at St Petersburg University, President of Ariel University, Member of the Israeli Academy of Sciences and Humanities. He characterised the causative agent of the new coronavirus infection as an 'autoimmunity virus', largely due to the nature of complications arising from COVID-19.

Among the reasons behind the high mortality rate from COVID-19 is a cytokine storm, the congress participants agreed. This is severe immune reaction to inflections in which the body releases too many cytokines.  The inflammatory cytokines start ‘storming’ out of control and are present in the blood at higher-than-normal amounts. They choke blood flow, cause breathing difficulty, and limit gas exchange in lungs. Blood clots form throughout the body. The lining inside of blood vessels becomes sticky. This leads to hypoxia and multiple-organ failure. In medicine, it is generally referred to as 'toxic-infectious shock'. When the immune system reacts to a pathogen, antibodies are released. These are special signalling molecules for transferring information from one cell to another, recognising and binding antigens. Among them are also autoantibodies to the body's own antigens. In small quantities, they are safe, help regulate the body’s vital activity, and eliminate tissue breakdown products. When they become too abundant, they start attacking healthy cells, damaging lung and causing multiple-organ failure. This increase in autoimmunity to a disease-causing level is facilitated by the 'mimicry' of the virus, with its protein fragments similar to our own, and a huge amount of cytokines in the blood.

The cytokine storm is not a new phenomenon in medicine. It may be associated with sepsis, for example. Yet scientists are far from being able to be unanimous in explaining why in some patients with coronavirus it is like a real tsunami and leads to serious failures or death, while other patients manage to avoid it

Among possible reasons is genetic predisposition. On the one hand, if you have a strong immune system, your immune system protects your body against viruses. On the other hand, once the immune system gets out of control, it can be fatal.

Another cause of complications in COVID-19 is hyperferritinemia. High ferritin levels can activate macrophages, i.e. nonspecific immune cells that are involved in transmitting inflammation and specific immune responses. When activated, some macrophages begin to release cytokines that can trigger cytokine storm.

Although the pandemic has been raging for almost two years, the treatment of COVID-19 and long Covid is still symptomatic, the participants of the congress said. To ensure effective treatment, doctors need to find a way to predict the disease severity. This is the key to understanding which patients will recover fast and which patients will have severe or critical cases.

Among the reasons behind a severe course of the disease is a special expression of angiotensin-converting enzyme 2 (ACE2). It is an enzyme that normally plays a positive role in our body. The SARS-CoV-2 virus binds to ACE2 prior to entry and infection of cells. Hence, ACE2 acts as a cellular doorway to organs, causing failure of the heart, kidneys, gastrointestinal tract, adrenal and thyroid glands, and gonads. The number of ACE2 on certain cells can indicate the target of the virus and determine the damage to organs and tissues. In this regard, doctors can make right treatment decisions and reduce the devastating effects of coronavirus disease.

In infectious diseases, immune system fights a pathogen. If it is incorrectly targeted or insufficiently regulated, it attacks healthy tissues, causing autoimmune or autoinflammatory diseases. In other words, the body attacks and damages its own tissues and organs. Among such conditions are: rheumatoid arthritis; systemic lupus erythematosus; scleroderma; Guillain-Barre syndrome; Kawasaki disease; insulin-dependent diabetes mellitus; thyroiditis; diffuse toxic goiter; chronic adrenal insufficiency; some forms of encephalitis; myocarditis; gastritis; pancreatitis; and colitis to name just a few. Even anosmia, i.e. loss of sense of smell that is so widespread in COVID-19 and in some other diseases, can be autoimmune, the scientists say.

In September 2021, St Petersburg University’s Laboratory of the Mosaic of Autoimmunity and the Pirogov Clinic of High Medical Technologies opened the Centre for the Study of Autoimmune Diseases and the Effects of the New Coronavirus Disease. The Centre has no rivals in Russia or abroad. It is set to conduct research on long Covid and treat patients with similar symptoms. Among them are: fatigue which cannot be relieved by sleep and rest; shortness of breath; cognitive dysfunction; so-called fog in the head; tachycardia and arrhythmias; sleep disturbances; and musculoskeletal and joint pain to name just a few.

Another challenge, as observed by doctors worldwide, is post-Covid mental health complications.

Patients may feel suppressed, have depression or chronic fatigue syndrome accompanied by fibromyalgia and immune dysfunction. Previously, very similar symptoms were observed in people: after infections of the herpes group viruses; during living and long-term regular stay in rooms where the microenvironment is saturated with compounds of an antigenic and immunostimulating nature ('syndrome of unhealthy buildings'); and after exposure to complex antigenic, toxic and immunostimulating effects as in the USA army soldiers who participated in Operation Desert Storm in the early 1990s (Gulf War syndrome). Scientists believe that although all these clusters of symptoms have different causes, they develop in the same way. Over-activated immune system leads to autoimmune damage to organs and relationship between immune system and neuroendocrine system.

When the pandemic started, the World Health Organization (WHO) was sceptical about patients reporting that after recovery they felt unwell, had chronic fatigue, memory loss, and attention loss.  Later, due to the active position of patients, WHO officially recognised long Covid and included it in the International Classification of Diseases.

Varvara Riabkova, Assistant Researcher in the Laboratory of the Mosaic of Autoimmunity, employee of the Centre for the Study of Long Covid at St Petersburg University

As a result, doctors can make such a diagnosis and start relevant treatment of long Covid. The number of patients with long Covid, according to the researchers, is now approaching 20% ​​of the total number of those who have had the new coronavirus disease. Yet determining whether a patient has long Covid or not, it is necessary to exclude alternative causes of similar symptoms.

The Centre for the Study of Long Covid as part of the Clinic of High Medical Technologies at St Petersburg University is set to develop an individual treatment scheme based on a multidisciplinary approach. You can get advice from doctors of different specialties. The Centre also aims to develop diagnostics protocols, treatment and rehabilitation schemes for patient with long Covid, said Natalia Gavrilova, a researcher at the Laboratory of the Mosaic of Autoimmunity and an employee of the Centre for the Study of Long Covid. Although the Centre is located in St Petersburg, it is open for residents living in St Petersburg and from other regions. The Centre offers services online.