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Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period
O E Akbasheva1, D K Mitrofanova1, L V Spirina2
1Siberian State Medical University, Tomsk, Russia.
Abstract:
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.
Insights
Alpha-2-macroglobulin (α₂-MG) levels dropped significantly during SARS-CoV-2 infection, with elevated proteinase activity. Post-COVID, α₂-MG normalized, but high proteinase activity persisted, especially in overweight individuals.
Area of Science:
- Biochemistry
- Immunology
- Virology
Background:
- Alpha-2-macroglobulin (α₂-MG) is a key proteinase inhibitor with antiviral and immunomodulatory roles.
- Its role in SARS-CoV-2 infection and long COVID remains unexplored.
- Understanding α₂-MG dynamics is crucial for managing post-viral syndromes.
Purpose of the Study:
- To investigate the activity of α₂-MG and other proteinases in patients with SARS-CoV-2 infection and long COVID.
- To identify potential biomarkers for monitoring disease progression and complications.
- To explore correlations between α₂-MG levels, symptoms, and patient characteristics.
Main Methods:
- Serum samples were analyzed from 85 patients with COVID-19 pneumonia, 60 in the post-COVID period (including those with complications), and 30 healthy controls.
- Activity of α₂-MG, α₁-proteinase inhibitor, elastase-like, and trypsin-like proteinases was measured.
- Patients were assessed for symptoms like neurological, cardiological, and dermatological issues, and categorized by weight.
Main Results:
- COVID-19 patients showed a dramatic decrease in α₂-MG activity (2.5% of normal) with increased activity of other proteinases.
- In the post-COVID period, α₂-MG levels trended towards normalization, but elastase- and trypsin-like proteinases remained elevated.
- Overweight individuals exhibited higher trypsin-like proteinase activity, correlating with SARS-CoV-2 antibody titers.
- α₂-MG levels exceeded control levels in post-COVID patients with dermatological and neurological symptoms.
Conclusions:
- α₂-MG activity is significantly altered during SARS-CoV-2 infection and in the post-COVID period.
- Elevated proteinase activity post-COVID, particularly in overweight individuals, suggests ongoing inflammation.
- α₂-MG levels may serve as a biomarker for monitoring long COVID, identifying complications, and stratifying risk groups.
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