Lyudmila P. Sizyakina, Dr. Sci. (Med.), Professor, head of the Department of Clinical Immunology and Allergology
Rostov-on-Don
Vita Ya. Zakurskaya, Assistant of the Department of Clinical Immunology and Allergology
Rostov-on-Don
Nadezhda A. Skripkina, Infectious Disease Specialist at the monoinfective Hospital №1
Rostov-on-Don
Elena A. Antonova, Head of the Laboratory Research Quality Department
Rostov-on-Don
Dmitry V. Sizyakin, Dr. Sci. (Med.), Professor, Professor of the Department of urology, Rostov State Medical University; head of the Semashko City Hospital №1
Rostov-on-Don
Objective: To study the features of the immune status in patients with a moderate-to-severe course of COVID-19, depending the levels of blood lactate dehydrogenase.
Materials and Methods: A total of 24 patients with a moderate-to-severe form of COVID-19 were examined. The control group consisted of 21 healthy volunteers. Methods: clinical, paraclinical (computed tomography of the lungs; complete blood count, blood biochemistry; immunological studies), statistical.
Results: Changes in complete blood count and blood biochemistry in patients with moderate-to-severe COVID-19 consist in granulocytosis, lymphopenia, monocytopenia, and an increase in the level of C-reactive protein, lactate dehydrogenase, with a simultaneous decrease in the total protein content. In patients with high levels of lactate dehydrogenase, a redistribution of lymphocyte populations towards B-cells was revealed with a decrease in the total number of T-cells. At the same time, there was a decrease in the production of IgM and IgG and a simultaneous increase in the synthesis of IgA.
Conclusions: The increase in blood LDH in COVID-19 patients is associated with a decrease in the content of T-cells due to severe lymphopenia, and a simultaneous increase in the content of B-cells without adequate enhancement of their antibody production function.
Цель: изучение особенностей иммунного статуса у пациентов со среднетяжёлым вариантом течения COVID-19 в зависимости от разных уровней лактатдегидрогеназы крови.
Материалы и методы: обследованы 24 пациента со среднетяжёлой формой инфекции СOVID-19. Группа сравнения — 21 здоровый доброволец. Методы — клинический, параклинический (компьютерная томография лёгких; оценка общего анализа крови, биохимических показателей; иммунологические исследования), статистический.
Результаты: изменения в общеклиническом и биохимическом анализах крови у больных среднетяжёлыми формами COVID-19 проявляются гранулоцитозом, лимфопенией, моноцитопенией и повышением уровня С-реактивного белка, лактатдегидрогеназы с одновременным снижением содержания общего белка. У пациентов с высоким уровнем лактатдегидрогеназы выявлено перераспределение популяций лимфоцитов в сторону В-лимфоцитов при снижении общего числа Т-клеток. При этом отмечено снижение антителопродукции иммуноглобулинов класса M и G и одновременное усиление синтеза IgA.
Выводы: рост содержания ЛДГ в крови у больных COVID-19 ассоциирован со снижением содержания Т-лимфоцитов, обусловленным выраженной лимфопенией и одновременным ростом содержания В-лимфоцитов без адекватного усиления их функции антителопродукции.
The new coronavirus SARS-CoV-2, designated COVID-19 by the World Health Organization (WHO) on February 11, 2020, is one of the highly pathogenic β-coronaviruses affecting humans [
The study aims to analyze an immune status in patients with moderate COVID-19 course depending on different LDH levels.
The study included 24 patients with a moderate COVID-19 infection who were hospitalized in the monoinfectious hospital of the N.A. Semashko Central City Hospital with the diagnosis "New coronavirus infection COVID-19 (confirmed), moderate". The mean age of the subjects was 65 years [ 51.5, 68.5]. The distribution within the group by gender was 10 men and 14 women. Practically healthy subjects of comparable age (21 people) were taken as a comparison group. All patients signed voluntary informed consent to participate in the study. The clinical trial was retrospective and conducted under the World Medical Association Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects as amended (2000), WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects (2013), Rules for Clinical Practice in the Russian Federation, approved by Order of the Russian Ministry of Health No. 266 from 19-Jun-2003. The patient's medical history was analyzed, identifying the patient's main complaints and the nature of the disease course. The pulmonary tissue damage was assessed by computed tomography (CT). On admission, blood was sampled for a full blood count (FBC), including estimation of RBC count, hemoglobin, hematocrit, thrombocrit, and total WBC count with WBC differential. Among the chemistry values, we determined C-reactive protein (CRP), ALT, AST, albumin, urea, creatinine, glucose, LDH, total protein, amylase, and bilirubin. The expression of species markers on the surface of the lymphocytes was determined by flow cytofluorimetry. The number of CD3+, CD4+, and CD8+ differentiation clusters for T cells, CD19+ for B cells, and CD16+ for natural killer cells was assessed. According to the Mancini method, the serum immunoglobulins of A, M, G classes were detected by radial immunodiffusion in a gel. Statistical analysis was performed using the STATISTICA 10 program (StatSoft Inc., USA). Descriptive statistics for the continuous character were presented as median and interquartile range (25th and 75th percentiles) central tendency, represented in the text as Me [LQ; UQ]. The medians in the groups were compared using Wilkinson's U-criterion. Differences were considered statistically significant at the p < 0.05 level.
On average, patients were admitted to the department on the 5th-6th day from the onset of the disease and remained in the department for 18.4±5.5 days. When evaluating the FBC results in patients with moderate COVID-19, changes were characterized by significant lymphopenia 10.75% [ 8; 18.6], as well as granulocytosis 86.85% [ 75; 90] and monocytopenia 1.7% [ 1.3; 2.6]. Significant changes in the patient blood chemistry value were expressed by increasing CRP, LDH with a simultaneous decrease of total protein (Table 1). In addition, there was an increase in blood transaminases and glucose.
When comparing the indices in the cellular arm of adaptive immunity, the relative indices are within the normal range, but when recalculated into absolute values, were significantly lower than similar indices in healthy donors. Such changes are explained by significant lymphopenia accompanying COVID-19 infection. A higher serum IgA level manifested significant differences in the humoral arm in COVID-19 patients (Table 2).
Although all patients were admitted to the department with the same disease severity, their laboratory values differed significantly according to the formulated diagnosis, as did their total time in the hospital. First of all, the difference between the blood LDH levels, which in some patients were significantly higher than the norm, while others remained within the reference values, was noteworthy. Given the proven role of LDH as a predictor of severe COVID-19 course, the study subjects were divided into two groups – those with high LDH (799 U/dL [ 624; 898], 14 subjects) and those with normal LDH (247 U/dL [ 117; 392], 10 subjects).
Analysis of the COVID-19 clinical course in patients with high LDH revealed that their hospitalization time was, on average, four days longer. In the FBC, significant changes change has involved greater lymphopenia and severe granulocytosis in patients in the high LDH group. We should note monocytopenia, equally characteristic of patients in both groups, which may indicate marked dysregulatory processes in the system of innate immunity (Table 3).
When assessing the blood chemistry values, significant differences between the two groups were in the CRP content (6-fold higher in the group with high LDH levels). In addition, significant hypoproteinemia was noted in the same group (Table 4).
The results were interesting when comparing the immune status indices. Thus, it was found that moderate COVID-19 in patients with normal LDH are determined by the preservation of the maturation and differentiation of the cellular arm and are characterized by a higher CD3+, CD4+, and CD8+ T-lymphocytes in relative and in absolute values, which is explained by higher lymphocyte levels in the blood. The results obtained in the humoral arm of the adaptive immune response are quite interesting. Thus, the relative B-lymphocyte level was twice as high in the high LDH group. Furthermore, in absolute values, its level was significantly higher than in patients in the second group. These changes are exciting when considering the more significant lymphopenia observed in these patients. In addition, there were multidirectional changes in the serum immunoglobulin, such as a higher IgA and a lower LDH in the high LDH group (Table 5).
As ongoing efforts to develop and introduce the SARS-CoV-2 vaccine move forward, there is an urgent need to characterize the immune responses to COVID-19 infection, especially adaptive immunity. The development of pathogenetic approaches to the therapy of new coronavirus infection is also impossible without understanding the interaction mechanisms between the virus and immune cells. Discovery of the fundamental mechanism of pathogenesis and assessing the nature of the relationship between biochemical changes and dysregulatory processes in the immune system will allow successful treatment and predict the likely outcome already in the early stages of the disease. As a result of this study, the identified biochemical shifts, such as an increase in LDH, CRP, and a simultaneous decrease in total protein levels in COVID-19 patients, are in complete agreement with previously published works [
The LDH increase in the blood of COVID-19 patients is associated with changes in the immune system, manifested by a significant decrease in relative and absolute T-lymphocytes count due to significant lymphopenia. And it is characterized by a simultaneous increase in B-lymphocytes without an adequate enhancement of their antibody production function. These changes appear to be due to the effect of SARS-CoV-2 on immunoregulatory mechanisms, which requires further study.
The authors declare that there are no conflicts of interest present.