Influence of clinical features in acute COVID-19 infection on the course of post-COVID syndrome

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The work is completed on the topic of State assignments FBIS Federal Scientific Research Institute of Viral Infections “VIROM” Federal Service for Supervision of Consumer Rights Protection and Human Consumption “Study of the mechanisms of chronic viral infection formation in patients with post-COVID syndrome and impaired immune system functions. Development of pathogenetic approaches to effective prevention and immunocorrection of identified disorders in patients with “post-COVID syndrome”. State Registration No. 124031800093-5.

Introduction

The COVID-19 coronavirus pandemic caused by the SARS-CoV-2 virus has led to mass morbidity and high mortality on the planet. According to a survey of those who have recovered from acute COVID-19, for a long time (from six months to 2-3 years), patients experience significant asthenia, decreased performance, an increase in the incidence of acute respiratory viral infections per year, an increase in the frequency and severity of relapses of diseases of various organs and systems: skin, allergic, cardiovascular, endocrine, chronic injection and others. The examination of patients was carried out at least six months after recovery from acute COVID-19. Such persistent post-infectious consequences are known as post-COVID syndrome [11]. When assessing post-COVID syndrome, it is necessary to reveal the main clinical manifestations of multiorgan pathology characteristic of post-COVID patients according to the literature [6]. For example, out of 410 participants in a Swiss study, 7-9 months after diagnosis with COVID-19, 39.0% of patients reported long-term fatigue (20.7%), loss of taste or smell (16.8%), shortness of breath (11.7%), and headache (10.0%), including among young, previously healthy individuals [10]. In China, 1,733 patients were examined 6 months after acute COVID-19; prolonged tachycardia was recorded in 9% and chest pain in 5% of patients [3]. During autopsy of 39 people who died from COVID-19, the SARS-CoV-2 virus was detected in the heart in 62.5% of cases [6, 7]. The inflammatory response it induced often leads to the death of cardiomyocytes and fibro-fatty replacement of desmosomal proteins important for intercellular adhesion [17]. In patients recovered from COVID-19, the cardiac metabolic demand may be persistently increased, which has been observed in the long term [20]. This may be due to decreased cardiac reserve, corticosteroid use, and dysregulation of the renin-angiotensin-aldosterone system. Fibrosis, myocardial scarring, and cardiomyopathy that occur after a viral infection often lead to cardiac arrhythmia via the re-entry mechanism [1, 6, 18]. COVID-19 can also exacerbate cardiac arrhythmia due to increased catecholamine influence as a result of the cytokines interleukin-6, interleukin-1, and TNFα, which can prolong the ventricular action potential by modulating the expression of cardiomyocyte ion channels [8]. Autonomic dysfunction with adrenergic influences predominating after viral diseases, including COVID-19, leads to postural orthostatic tachycardia syndrome and non-physiological sinus tachycardia [12]. Diabetic ketoacidosis was observed in patients who did not previously have diabetes mellitus, weeks or months after the disappearance of COVID-19 symptoms [18]. Unfortunately, there is still insufficient information on how long after COVID-19 the severity of pre-existing diabetes mellitus worsens or a hereditary predisposition to diabetic ketoacidosis manifests itself, and this issue is addressed to the international CoviDiab registry [15]. Ruggeri R.M. et al. (2021) write about subacute thyroiditis with clinical manifestations of thyrotoxicosis weeks after the disappearance of respiratory symptoms [16]. Endocrine manifestations of post-COVID syndrome may be due to direct damage by the virus, immunological and inflammatory damage, and iatrogenic complications. Expression of ACE2 and transmembrane serine protease in pancreatic β-cells has been reported, but researchers believed that the primary insulin deficiency in COVID-19 is likely mediated by inflammation or response to infectious stress along with peripheral insulin resistance [2]. Autopsy studies of COVID-19 patients confirmed the possibility of SARS-CoV-2 infection and replication in human pancreatic β cells, leading to their death or transdifferentiation, decreased insulin production and release [9, 19]. Thus, according to the conducted theoretical research, there are indications in the literature of various clinical pathological manifestations of post-COVID syndrome, however, there is no systematization of these studies, there is insufficient data on the pathogenesis of the formation of clinical manifestations of post-COVID syndrome, there is no data on the relationship between the course of post-COVID syndrome and the severity of acute coronavirus infection in the anamnesis. All this served as the basis for this study.

Objective of the study: to assess the impact of the severity of acute COVID-19 on the course of post-COVID syndrome.

Research objectives:

1. To analyze the severity of clinical manifestations of the symptom complex of cardiovascular damage in post-COVID patients depending on the degree of lung damage in the acute period of COVID-19.
2. To analyze the severity of clinical manifestations of endocrine system pathology, including newly diagnosed, in post-COVID patients depending on the degree of lung damage in the acute period of COVID-19. Since no statistically significant differences by gender and age were found, all patients were divided into groups by the degree of lung damage in the acute period of COVID-19 according to clinical guidelines for the diagnosis and treatment of a new coronavirus infection:

Materials and methods

A total of 131 patients who had recovered from SARS-CoV-2 infection were examined. Of these, 48 were men aged 20 to 76 years (mean age 55.3 years) and 83 were women aged 21 to 79 years (mean age 53.4 years). The inclusion criteria in the study groups were: confirmed diagnosis of SARS-CoV-2 infection by polymerase chain reaction (PCR), the presence of IgA, IgM to the SARS-CoV-2 virus in the acute and post-acute periods of infection and IgG to the SARS-CoV-2 virus during the recovery period, computed tomography data of the lungs on the presence or absence of changes of the “ground glass” type. This study was conducted at least 6-12 months after the infection caused by SARS-CoV-2. All patients were preliminarily examined by a general practitioner and an immunologist-allergist in order to identify concomitant diseases, as well as by doctors of other specialties before COVID-19 to establish concomitant diagnoses. The groups were randomized by gender, age, concomitant diseases according to the χ² criterion. All studies were approved by the Independent Local Ethics Committee at the State Autonomous Healthcare Institution of the Republic of Chelyabinsk “City Clinical Hospital No. 1” of Chelyabinsk (protocol No. 8 dated 04/11/2022), on the basis of which these studies were conducted, and by the Independent Local Ethics Committee at the Federal Research Institute of Virology and Infection “Virom” of Rospotrebnadzor of Yekaterinburg, protocol No. 1 dated 03/22/2024, on the basis of which these studies were conducted.

Clinical research methods:

• Identification of persons with post-COVID syndrome after examination by doctors: therapist, allergist-immunologist.
• Filling out the immunological examination card.
• Physical, laboratory and instrumental examinations for diagnosis.

Statistical research methods

Based on the study results, a database was created in Excel (MS Office 2007). Data processing and analysis were performed using R 3.1.1 12 (RFoundation for Statistical Computing, Vienna, Austria) and Microsoft Excel version 14.0. Student’s t-tests were used for parametric data; differences were considered significant at p < 0.05.

Equipment

The following equipment was used: computers with software packages required for mathematical and statistical analysis of the results.

Results and discussion

No statistically significant differences by gender and age were found, all patients were divided into groups by the degree of lung damage in the acute period of COVID-19, which is the determining criterion for assessing the severity of acute COVID-19 according to clinical guidelines for the diagnosis and treatment of a new coronavirus infection [13, 14]:

Group 1 – CT0 (without lung damage of the “ground glass” type according to CT data)

Group 2 – CT1-2 (less than 50% lung damage of the “ground glass” type according to CT data)

Group 3 – CT3-4 (more than 50% lung damage of the “ground glass” type according to CT data)

According to the questionnaire, the percentage of patients who had complaints of aggravation of symptoms of comorbid pathology already existing before the pandemic (increased relapses, worsening of the severity of the course), or of newly diagnosed somatic diseases was determined after COVID-19. This study presents data on cardiovascular and endocrine pathology.

According to these data, presented in Table 1, reliable differences were obtained between groups CT0 and CT1-2, as well as CT0 and CT3-4: the frequency of exacerbations of cardiovascular diseases in the post-COVID period is significantly higher in groups with lung damage in the acute period of COVID-19 compared to the group of patients without lung damage. These data indicate that cardiovascular damage is directly related to the severity of COVID-19, viral load and was detected most often (68%) in post-COVID patients who had a severe coronavirus infection.

 

Table 1. Severity of clinical manifestations of a symptom complex of damage to the cardiovascular system in kidney-shaped patients, depending on the degree of lung damage in the acute period of COVID-19

Diseases with increased recurrence or first identified after clinical recovery from acute COVID-19 infection / degree of lung damage according to CT	Total number of examined patients (n = 131)		Group 1 CT0 (n = 38)		Group 2 CT1-2 (n = 68)		Group 3 CT3-4 (n = 25)
	abs	%	abs	%	abs	%	abs	%
Diseases of the cardiovascular system (hypertension, coronary heart disease, acute myocardial infarction, acute cerebrovascular accident)	49	37.4	5	13.2	27	39.7 p1-2 < 0.05	17	68.0 p1-3 < 0.05 p2-3 < 0.05

Note. The significance of differences between groups p₁-p₂, p₁-p₃, p₂-p₃. Differences of p < 0.05 (Student’s criterion) were considered significant.

 

According to the data presented in Table 2, the frequency of glucose metabolism disorders, including those newly identified, increased significantly in the post-COVID period in patients with lung damage during the acute period of infection, while no significant differences were found in thyroid diseases, with the exception of autoimmune thyroiditis.

 

Table 2. Severity of clinical manifestations of endocrine system pathology, including those newly identified, in postmenopausal patients, depending on the degree of lung damage in the acute period of COVID-19

Diseases with increased recurrence or first identified after clinical recovery from acute COVID-19 infection / degree of lung damage according to CT	Total number of examined patients (n = 131)		Group 1 CT0 (n = 38)		Group 2 CT1-2 (n = 68)		Group 3 CT3-4 (n = 25)
	abs	%	abs	%	abs	%	abs	%
Glucose metabolism disorder	47	35.9	2	5.3	30	44.1 p1-2 < 0.05	15	60.0 p1-3 < 0.05
Diseases of the thyroid gland, with the exception of autoimmune thyroiditis	35	26.7	7	18.4	19	27.9	9	36.0

Note. As for Table 1.

 

Perhaps these disorders are also associated, on the one hand, with the use of corticosteroid therapy during the acute period of coronavirus infection, and on the other hand, with disruption of the regulatory mechanisms of the endocrine and immune systems under the influence of the SARS-CoV-2 virus, which once again confirms our assumptions about the formation of multiple organ pathology in post-COVID patients.

According to ICD-10 and ICD-11 [4, 5], the above-mentioned somatic diseases have, among other things, pathogenetically significant mechanisms of immune system disorders, as does COVID-19, the severe forms of which are also based on damage to the immune system. In this regard, the immune status of patients included in this clinical study was assessed.

Thus, the clinical picture of post-COVID syndrome is characterized by a pronounced diversity of the formation of multiple organ pathology, both newly identified and manifested in the exacerbation of chronic diseases.

Conclusions

1. According to the data obtained, reliable differences were obtained between groups CT0 and CT1-2, as well as CT0 and CT3-4: the frequency of exacerbations of cardiovascular diseases in the post-COVID period is significantly higher in groups with lung damage in the acute period of COVID-19 compared to the group of patients without lung damage. These data indicate that cardiovascular disorders are directly related to the severity of COVID-19, viral load, and were detected most frequently (68%) in post-COVID patients who had a severe coronavirus infection.
2. According to the data obtained, the frequency of glucose metabolism disorders, including those detected for the first time, significantly increased in the post-COVID period in patients with lung damage in the acute period of infection, while no significant differences were found in thyroid diseases, with the exception of AIT. Perhaps these disorders are also associated, on the one hand, with the use of corticosteroid therapy in the acute period of coronavirus infection, and on the other hand, with disruption of the regulatory mechanisms of the endocrine and immune systems under the influence of the SARS-CoV-2 virus, which once again confirms our assumptions about the formation of multiple organ pathology in post-COVID patients.

About the authors

Maria A. Dobrynina

Federal Research Institute of Viral Infections “Virom”

Author for correspondence.
Email: mzurochka@mail.ru

PhD (Medicine), Senior Researcher, Laboratory of Transmissible Viral Diseases

Russian Federation, Ekaterinburg

Vladimir A. Zurochka

Federal Research Institute of Viral Infections “Virom”

Email: v_zurochka@mail.ru

PhD, MD (Medicine), Senior Researcher, Laboratory of Immunobiotechnology

Russian Federation, Ekaterinburg

A. V. Zurochka

Federal Research Institute of Viral Infections “Virom”

Email: av_zurochka@mail.ru

PhD, MD (Medicine), Professor, Honored Scientist of the Russian Federation, Leading Researcher, Laboratory of Transmissive Viral Infections

Russian Federation, Ekaterinburg

References

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