Assoc. Dr. Stoyan Ivanov, MD: Almost half of people with covid-pneumonia develop pulmonary fibrosis

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Assoc. Dr. Stoyan Ivanov, MD: Almost half of people with covid-pneumonia develop pulmonary fibrosis
Assoc. Dr. Stoyan Ivanov, MD: Almost half of people with covid-pneumonia develop pulmonary fibrosis
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Assoc. Dr. Stoyan Ivanov, MD, is a specialist in internal medicine, pneumology and phthisiology, works in the city of Sofia. He has over 40 years of experience and expertise in the field of sarcoidosis. Conducts preventive examinations, diagnostics, treatment and appointment of therapy for diseases of the respiratory system.

He is the author of more than 180 scientific works and three monographs: "Hypersensitive pneumonitis", "Sarcoidosis and other granulomatoses" and "Diffuse pulmonary fibrosis". He was the editor-in-chief of the journal Pneumology and Phthisiatry. He was selected in the survey of "Darik Radio" to participate in the ranking "The best doctors in Bulgaria", in the field of pneumology and phthisiology.

Assoc. Ivanov graduated from the Medical University, Sofia, in 1975. He obtained speci alties in internal medicine and pneumology and phthisiology in 1984 and 1986. In 1983 he obtained the scientific and educational degree "Doctor", and in 1988 he obtained his habilitation as an associate professor. He specialized in lung diseases in Berlin and Germany.

Participated in the creation of the scientific school on diffuse parenchymal lung diseases. Participates in numerous national congresses and seminars in the speci alty.

In 1976, Assoc. Professor Ivanov was elected as an assistant at the Institute of Pneumology and Phthisiology at the Medical University - Sofia. In 1988, he became the head of the Second Clinic of the St. Sofia General Hospital at the Sofia University, which he led until 2018. Prof. Ivanov was a National Consultant on Pulmonary Diseases at the Ministry of He alth. At the moment, he is part of the team of specialists at "Vita" Medical Center, Sofia.

In the course of the coronavirus pandemic, it turned out that about 30% of the sick, especially those with covid-pneumonia, developed some degree of mental disorders - anxiety, depression, panic attacks, etc. This is mainly due to the fact that many patients associate the disease of fibrosis with something residual, irreversible and final stage in the development of an inflammatory process. What is pulmonary fibrosis and is it really an irreversible and incurable disease, we talk to associate professor Dr. Stoyan Ivanov, specialist in internal medicine, pneumology and phthisiology.

Prof. Ivanov, as a specialist with extensive experience in the follow-up and diagnosis of patients with pulmonary fibrosis, is such a diagnosis a possible aggravating factor for the development of high anxiety in such patients?

- The question we are asked is - if there is a description of fibrosis in the X-ray and the modern computed tomography (CT) in almost half of the patients who have recovered from covid-pneumonia, the outcome is only bad? It is necessary to emphasize that the term fibrosis is also present in the descriptions of histopathologists and clinicians, and they put different content into it.

For example, to histopathologists, the term fibrosis means the presence of fibroblastic proliferation in the lungs, which can develop into non-resorbable scars, but not necessarily in all cases. For imaging specialists, changes of the type of fine reticular shadows (reticularization), traction bronchiectasis and particularly characteristic prominent micro- and macrocystic changes, of the "honeycomb" type, are most often described as fibrotic. Such changes may not be visible in the initial stages on standard radiography, and this is best seen on high-resolution computed tomography (HRCT).

For the clinician, the diagnosis of pulmonary fibrosis requires a multidisciplinary discussion, as the pathway to fibrosis, as well as the outcome, is different in different diseases. Thus, fibrosis can be viewed as a dynamic process with both good and bad outcomes possible.

What is more special about post-covid-pulmonary fibrosis?

- More particularly, knowledge about fibrogenesis in post-covid-pulmonary fibrosis is still insufficient. It is difficult to make a longer-term prediction about its ultimate evolution. Moreover, the spectrum of disease manifestations greatly varies from asymptomatic cases, to moderately severe and critically severe, with acute respiratory distress syndrome (ARDS). But there is a lack of clarity about the long-term consequences.

For example, with the same clinical and X-ray manifestations, the final outcome is different - in one third of the patients with changes in fibrosis, after 120 days a spontaneous reverse development of the process occurred. This leads us to believe that there is probably a different genetic predisposition to the disease itself - fibrosis.

Post-covid-pulmonary fibrosis can be said to appear as a result of the actions of the virus on the one hand, and on the other - the impact on the lung of those trying to protect us, immune-mediated mechanisms unlocked by the cytokine storm'. This leads to epithelial and endothelial damage, with subsequent accumulation of fibroblasts, myofibroblasts and intense collagen deposition.

Parallel to these processes, there is another pathogenetic manifestation of vasculitis, with accompanying coagulopathy, manifested by thrombosis and bleeding. Ultimately, these processes lead to post-covid pulmonary fibrosis.

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Assoc. Dr. Stoyan Ivanov

Can certain risk factors be identified at this stage that contribute to the development of post-covid-pulmonary fibrosis?

- Based on the thousands of covid-pneumonia patients, the WHO found that in about 40% of patients, the subsequent development of post-covid syndrome and persistent manifestations of chronic respiratory symptoms.

In the beginning, while there was not enough accumulated data, and perhaps speculatively, the longer-term course of the disease was accepted as the main risk factor for the development of post-covid-pulmonary fibrosis. But subsequently, newer knowledge relates the development of fibrosis mainly to the severity of the disease process.

This severity occurs as a consequence of the acute respiratory distress syndrome (ARDS) that has developed. Especially when it is more prolonged, it leads to impaired alveolar epithelization, fibroblast activation, collagen deposition and disruption of normal lung architecture.

One third of those who develop acute respiratory distress syndrome also get post-covid-pulmonary fibrosis. As a concomitant risk factor, the use of non-invasive and invasive ventilation in some patients with ARDS is indicated, in which it is possible to develop ventilator-induced lung damage, with subsequent pulmonary fibrosis.

Another significant risk factor for the development of fibrosis is advanced age, especially if there is concomitant heart disease and diabetes. Although to a lesser extent, post-covid-pulmonary fibrosis can also develop in people at a younger age. Even those with mild clinical manifestations can develop massive lung changes. Asymptomatic cases have been described of people who were contacts but with high antibodies who subsequently developed post-covid pulmonary fibrosis.

In the initial stage, the patients may not have any particular complaints, but if the process progresses, shortness of breath appears during light physical efforts, accompanied by an inconstant dry cough. It is possible that at this initial stage, the initial fibrotic changes may not be detected on the standard lung X-ray taken.

In such cases, the tool of choice for diagnosis is high-resolution computed tomography (HRCT). In half of the patients, there are also functional disorders during spirometry, with determination of diffusion capacity. Rarely, lung biopsy may be necessary in progressive and atypical cases.

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With what other progressive and fibrosing lung diseases is it necessary to differentiate post-covid-pulmonary fibrosis?

- It is important to investigate whether, before the covid disease, the patient did not have any previous fibrosing diseases, such as some of the connective tissue diseases. For example, in 90% of patients with systemic sclerosis, manifestations of pulmonary fibrosis can be observed. The same are reported in 30% of patients with rheumatoid arthritis and in 60% of cases with mixed connective tissue disease.

In these cases, an important test is a set of antibodies that are strictly specific. Meanwhile, these diseases must be differentiated from fibromyalgia (psychogenic rheumatism), which is characterized by muscle and joint pain and chronic fatigue.

Among the environmental factors occurring with fibrosing lung changes are pneumoconiosis and hypersensitivity pneumonitis. Among the drugs with a fibrosing effect are: cordarone, methotrexate, bleomycin and monoclonal antibodies. Differentiation from idiopathic pulmonary fibrosis (IPF), which is the most common in the elderly population and carries a poor prognosis, is most important.

With her, the average life expectancy after diagnosis is 2.5-3.5 years. It has two characteristic physical symptoms – drumsticks and inspiratory ringing rales in the lung bases. In this clinical unit, the most widely tested and conditionally recommended for treatment are two antifibrotic drugs approved in Europe and in our country, respectively.

Is there currently evidence of a possible causal treatment for covid-pulmonary fibrosis?

- Various treatment strategies continue to be tested. So far, there is no evidence that the used antiviral medications lead to a reduction in the likelihood of developing pulmonary fibrosis. Long-term low-dose corticotherapy also does not prevent the development of fibrosis.

Of the antifibrotic medications approved in our country - Pirfenidon (Esbriet) and Nintedanib (Ofeu) are of conditional benefit in idiopathic pulmonary fibrosis and systemic sclerosis. They have a different mechanism of action and the ability to slow down the progression of fibrosis in the early stages of the process. So far, there is experience in the use of one of these medications in the initial stage of acute respiratory distress syndrome - with the aim of preventing the development of post-covid pulmonary fibrosis.

It should be noted that both preparations can show hepatotoxicity, and one of them, although rare, can cause bleeding and arterial thrombotic incidents, taking into account that in severely ill patients with covid, in most cases Anticoagulant therapy is also administered. If patients show progression of fibrosis and develop respiratory failure, the application of long-term home oxygen therapy and respiratory rehabilitation is strongly recommended. In a long-term aspect, the possibility of reaching a lung transplant comes into consideration.

Considering that at this stage there is no evidence of successful treatment of post-covid-pulmonary fibrosis and that the main risk factor is the severity of the pulmonary pathological process, an important element is the possibility to prevent the severe course of the disease. For now, vaccination is a proven preventive measure. It is a fact that more than 90% of the patients who died from covid in intensive care units were not vaccinated.

For example, a study in Israel showed that 93% of patients with a severe form of covid were not vaccinated with a booster dose, and only 7% of them received one. It is important to assess the state of the fibrotic process through periodic clinical, imaging and functional follow-up. Whether it is regressing, stabilizing, or progressing, and making appropriate therapeutic decisions.

The introduction of affordable and harmless oral antiviral preparations approved by the European Medicines Agency (EMA) into outpatient practice is pending. They will be administered in the initial stage of patients at risk of severe disease. For example, the drug Paxlovid (which was the first oral antiviral drug) is believed to reduce hospitalizations by 89%. In this way, the development of post-covid - pulmonary fibrosis will also be prevented.

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