Role of Transforming Growth Factor-β in Pathogenesis of Pulmonary Fibrosis in COVID-19, Post-COVID Syndrome, Oncological and Chronic Inflammatory Lung Diseases

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Abstract

INTRODUCTION: Persistent post-COVID syndrome is the persistent physical, medical and cognitive sequelae of coronavirus disease 2019 (COVID-19), including persistent immunosuppression, pulmonary, cardiac and vascular fibrosis which lead to increased mortality and impair the quality of life of patients.

АIM: To analyze the completed foreign and domestic studies on the pathophysiology of transforming growth factor-β (TGF-β) in conditions of COVID-19, post-COVID syndrome, oncological and chronic inflammatory lung diseases.

Mast cells are among the main producers of inflammatory cytokines in COVID-19, their stimulation leads to the release of many proinflammatory cytokines, such as interleukin 1β, tumor necrosis factor α, interleukin 6, and also TGF-β. The basis of the pathogenesis of post-COVID syndrome is the overexpression of TGF-β leading to a prolonged state of immunosuppression and fibrosis. TGF-β acts as a tumor suppressor inhibiting proliferation and inducing apoptosis in the early stages of oncogenesis; plays an important role in most cellular biological processes leading to remodeling of the airway structures; is involved in epithelial changes, in subepithelial fibrosis, remodeling of smooth muscle of airways and in microvascular changes; induces resistance to glucocorticosteroids; stimulates the production of blood coagulation factor XII, thereby leading to development of potentially fatal complications, such as pulmonary embolism and ischemic stroke.

CONCLUSION: In this literature review, a structured analysis of a multicomponent role of TGF-β in the pathogenesis of post-COVID syndrome, pulmonary fibrosis in COVID-19, tumors of respiratory system, chronic obstructive pulmonary disease, bronchial asthma, is given. A possible use of TGF-β as a biomarker of severe and moderate degree of COVID-19 is substantiated.

About the authors

Andrey V. Budnevsky

N. N. Burdenko Voronezh State Medical University

Email: budnev@list.ru
ORCID iD: 0000-0002-1171-2746
SPIN-code: 7381-0612

MD, Dr. Sci. (Med.), Professor

Russian Federation, Voronezh

Sergey N. Avdeev

I. M. Sechenov First Moscow State Medical University (Sechenov University)

Email: serg_avdeev@list.ru
ORCID iD: 0000-0002-5999-2150
SPIN-code: 1645-5524

MD, Dr. Sci. (Med.), Professor

Russian Federation, Moscow

Evgeny S. Ovsyannikov

N. N. Burdenko Voronezh State Medical University

Email: ovses@yandex.ru
ORCID iD: 0000-0002-8545-6255
SPIN-code: 7999-0433

MD, Dr. Sci. (Med.), Associate Professor

Russian Federation, Voronezh

Viktoria V. Shishkina

N. N. Burdenko Voronezh State Medical University

Email: 4128069@gmail.ru
ORCID iD: 0000-0001-9185-4578
SPIN-code: 9339-7794

MD, Cand. Sci. (Med.)

Russian Federation, Voronezh

Nadezhda G. Alekseeva

N. N. Burdenko Voronezh State Medical University

Author for correspondence.
Email: nadya.alekseva@mail.ru
ORCID iD: 0000-0002-3357-9384
SPIN-code: 2284-2725
Russian Federation, Voronezh

Inna M. Perveeva

N. N. Burdenko Voronezh State Medical University; Voronezh Regional Clinical Hospital No. 1

Email: perveeva.inna@yandex.ru
ORCID iD: 0000-0002-5712-9302
SPIN-code: 5995-6533

MD, Cand. Sci. (Med.)

Russian Federation, Voronezh; Voronezh

Avag G. Kitoyan

N. N. Burdenko Voronezh State Medical University

Email: kitoyan9812@gmail.com
ORCID iD: 0009-0003-7869-5519
SPIN-code: 6865-4727
Russian Federation, Voronezh

Lyubov N. Antakova

N. N. Burdenko Voronezh State Medical University

Email: tsvn@bk.ru
ORCID iD: 0000-0001-5212-1005
SPIN-code: 3936-3381

Cand. Sci. (Biology)

Russian Federation, Voronezh

Anastasia S. Yurchenko

N. N. Burdenko Voronezh State Medical University

Email: yurch.01@mail.ru
ORCID iD: 0000-0002-0880-5562
SPIN-code: 3045-5502
Russian Federation, Voronezh

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2. Fig. 1. Role of TGF-β in the pathogenesis of lung fibrosis in COVID-19 and post-COVID syndrome (authors’ scheme, modified by [27]).

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