The universal proteinase inhibitor α₂-macroglobulin (α₂-MG) exhibiting antiviral and immunomodulatory activities, is considered as an important participant in the infectious process. The activity of α₂-MG in the new coronavirus infection and post-covid syndrome (long COVID) has not been studied yet. We examined 85 patients diagnosed with community-acquired bilateral polysegmental pneumonia developed under conditions of a new coronavirus infection SARS-CoV-2. For assessment of the post-COVID period, 60 patients were examined 5.0±3.6 months after the coronavirus infection. Among these patients, 40 people had complications, manifested in the form of neurological, cardiological, gastroenterological, dermatological, bronchopulmonary symptoms. The control group included 30 conditionally healthy individuals with a negative PCR result for SARS-CoV-2 RNA and lack of antibodies to the SARS-CoV-2 virus. The α₂-MG activity in serum samples of patients with coronavirus infection dramatically decreased, up to 2.5% of the physiological level. This was accompanied by an increase in the activity of the α₁-proteinase inhibitor, elastase- and trypsin-like proteinases by 2.0-, 4.4- and 2.6-fold respectively as compared with these parameters in conditionally healthy individuals of the control. In the post-COVID period, despite the trend towards normalization of the activity of inhibitors, the activity of elastase-like and especially trypsin-like proteinases in serum remained elevated. In overweight individuals, the increase in the activity of trypsin-like proteinases was most pronounced and correlated with an increase in the antibody titer to the SARS-CoV-2 virus. In the post-COVID period, the α₂-MG activity not only normalized, but also exceeded the control level, especially in patients with dermatological and neurological symptoms. In patients with neurological symptoms or with dermatological symptoms, the α₂-MG activity was 1.3 times and 2.1 times higher than in asymptomatic persons. Low α₂-MG activity in the post-COVID period persisted in overweight individuals. The results obtained can be used to monitor the course of the post-COVID period and identify risk groups for complications.
Keywords: alpha-2-macroglobulin, alpha-1-proteinase inhibitor, trypsin-like proteases, elastase-like proteases, post-COVID period
Akbasheva O.E., Mitrofanova D.K., Spirina L.V., Samoilova Yu.G., Matveeva M.V., Podchinenova D.V., Oleynik O.A. (2023) Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period. Biomeditsinskaya Khimiya, 69(4), 240-247.
Akbasheva O.E. et al. Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period // Biomeditsinskaya Khimiya. - 2023. - V. 69. -N 4. - P. 240-247.
Akbasheva O.E. et al., "Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period." Biomeditsinskaya Khimiya 69.4 (2023): 240-247.
Akbasheva, O. E., Mitrofanova, D. K., Spirina, L. V., Samoilova, Yu. G., Matveeva, M. V., Podchinenova, D. V., Oleynik, O. A. (2023). Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period. Biomeditsinskaya Khimiya, 69(4), 240-247.
Zorina V.N., Trofimenko N.A., Arkhipova S.V., Zorina R.M., Zorin N.A. (2005) Alpha-2-macroglobulin complexes with IgG class antibodies, plasmin and their relationship with other humoral immunity factors in the development of rheumatoid arthritis. Medical Immunology, 7(5-6), 557-562. CrossRef Scholar google search
Luan B., Huynh T., Cheng X., Lan G., Wang H.R. (2020) Targeting proteases for treating COVID-19. J. Proteome Res., 19(11), 4316-4326. CrossRef Scholar google search
Majchrzak M., Poręba M. (2022) The roles of cellular protease interactions in viral infections and programmed cell death: A lesson learned from the SARS-CoV-2 outbreak and COVID-19 pandemic. Pharmacological Reports, 74(6), 1149-1165. CrossRef Scholar google search
Sinha S., Tam B., Wang S.M. (2021) RBD double mutations of SARS-CoV-2 strains increase transmissibility through enhanced interaction between RBD and ACE2 receptor. Viruses, 14(1), 1. CrossRef Scholar google search
Karampoor S., Hesamizadeh K., Maleki F., Farahmand M., Zahednasab H., Mirzaei R., Banoun, H., Zamani F., Hajibaba M., Tabibzadeh A., Bouzari B., Bastani M.N., Laali A., Keyvani H. (2021) Apossible pathogenic correlation between neutrophil elastase (NE) enzyme and inflammation in the pathogenesis of coronavirus disease 2019 (COVID-19). Int. Immunopharmacol., 100, 108137. CrossRef Scholar google search
Kim Y., Jang G., Lee D., Kim N., Seon J.W., Kim Y.H., Lee C. (2022) Trypsin enhances SARS-CoV-2 infection by facilitating viral entry. Arch. Virology, 167(2), 441-458. CrossRef Scholar google search
Dubrovin S.M., Muromtseva A.V., Novikova L.I. (2000) α2-macroglobulin: The current state of the issue. Clinical Laboratory Diagnostics, 6, 3-7. Scholar google search
Kostinov M.P., Zorin N.A., Kazharova S.V., Zorina V.N. (2020) Comparative effect of the influence of immunomodulators on the concentrations of hydrolase and lactoferrin inhibitors in community-acquired pneumonia in adults. Medical Immunology, 22(4), 791-798. CrossRef Scholar google search
Zorin N.A., Zorina V.N., Zorina R.M. (2006) The role of macroglobulin family proteins in the regulation of inflammatory reactions. Biomeditsinskaya Khimiya, 52(3), 229-238. Scholar google search
Lagrange J., Lecompte T., Knopp T., Lacolley P., Regnault V. (2022) Alpha-2-macroglobulin in hemostasis and thrombosis: An underestimated old double-edged sword. J. Thromb. Haemost., 20(4), 806-815. CrossRef Scholar google search
Chen C., Haupert S.R., Zimmermann L., Shi X., Fritsche L.G., Mukherjee B. (2022) Global prevalence of post-coronavirus disease 2019 (COVID-19) condition or long COVID: A meta-analysis and systematic review. J. Infect. Dis., 226(9), 1593-1607. CrossRef Scholar google search
Nartikova V.F., Paskhina T.S. (1989) Unified method for determining the activity of alpha 1-proteinase inhibitor, alpha 2-macroglobulin in human serum. Problems of Medical Chemistry, 25(4), 494-499. Scholar google search
Ogloblina O.G., Platonova L.V., Paskhina T.S. (1984) Measuring the activity of trypsin- and elastase-like proteinases of polymorphonuclear leukocytes and the level of their acid-stable inhibitors in human bronchial secretions: Methodical Recommendations. Izd-vo MGU, Moscow, 14 p. Scholar google search
Wang J., Li Q., Yin Y., Zhang Y., Cao Y., Lin X., Huang L., Hoffmann D., Lu M., Qiu Y. (2020) Excessive neutrophils and neutrophil extracellular traps in COVID-19. Front. Immunol., 11, 2063. CrossRef Scholar google search
Vianello A., Braccioni F. (2020) Geographical overlap between alpha-1 antitrypsin deficiency and COVID-19 infection in Italy: Casual or causal? Archivos de Bronconeumologia, 56(9), 609-610. CrossRef Scholar google search
Varma V.R., Varma S., An Y., Hohman T.J., Seddighi S., Casanova R., Beri A., Dammer E.B., Seyfried N.T., Pletnikova O., Moghekar A., Wilson M.R., Lah J.J., O'Brien R.J., Levey A.I., Troncoso J.C., Albert M.S., Thambisetty M. (2017) Alpha-2 macroglobulin in Alzheimer's disease: A marker of neuronal injury through the RCAN1 pathway. Molecular Psychiatry, 22(1), 13-23. CrossRef Scholar google search
Mocchegiani E., Malavolta M. (2007) Zinc dyshomeostasis, ageing and neurodegeneration: implications of A2M and inflammatory gene polymorphisms. J. Alzheimer's Dis., 12(1), 101-109. CrossRef Scholar google search
Rugsarash W., Tungtrongchitr R., Petmitr S., Phonrat B., Pongpaew P., Harnroongroj T., Tungtrongchitr A. (2006) The genetic association between alpha-2-macroglobulin (A2M) gene deletion polymorphism and low serum A2M concentration in overweight/obese Thais. Nutritional Neuroscience, 9(1-2), 93-98. CrossRef Scholar google search
Rehman Khan A., Awan F.R. (2016) Leptin resistance: A possible interface between obesity and pulmonary-related disorders. Int. J. Endocrinol. Metab., 14(1), e32586. CrossRef Scholar google search
Pavlova Z.Sh., Golodnikov I.I. (2020) Obesity = inflammation. Pathogenesis. How does this threaten men? Medical Herald of the South of Russia, 11(4), 6-23. CrossRef Scholar google search