ABSTRACT
Background: It has been more than a year and a half since the WHO announced a pandemic of a new coronavirus infection caused by SARS-CoV-2. The virus belongs to the respiratory group, but it it can damage various organs and tissues of the body. COVID-19 infection is characterized by pathological activation of immunity, violated synthesis of pro-infammatory, immunoregulatory, anti-infammatory cytokines, such as interleukins-1 and-6, tumor necrosis factor α and others. These features contribute to the development of rheumatic diseases and syndromes in people who have had COVID-19. Cellular and humoral immune responses are also of primary importance in the pathogenesis of infammatory myopathies. Objectives: Description of a case of severe dermatomyositis after COVID-19. Methods: The 34-year-old female patient complained of pain and weakness in the proximal muscles of the upper and lower extremities, difficulty swallowing solid and liquid food, rash on the face, neck, chest and arms. In August 2020 she had a mild case of COVID-19. A month later, faky erythematous papules like Gottron's sign appeared on the extensor surfaces of the metacarpophalangeal joints and proximal interphalangeal joints of the hands. Six months later, sore throats, hoarseness of voice, belching of air, choking on solid food and episodes of subfebrility joined. Refux esophagitis, duodenitis was detected by fbrogastroduodenoscopy. After 9 months, there were muscle pains and muscle weakness, erythema on the face, neck and chest, the patient lost 11 kg. She was hospitalized in the rheumatology department with suspected dermatomyositis. Results: On objective examination: proximal myopathy, erythematous rashes on the face, neck, chest, Gottron's erythema on the hands. In the analyses: clinical analysis of blood and urine without pathology, ANA 1:1280, creatinkinase 5370 IU/l, with an increase in dynamics up to 9260 IU/l, CRP 0.03 mg/dl, LDH 1023 IU/l, rheumatoid factor and anti-ds DNA were negative. Nasal regurgitation was detected during radiography of the pharynx with contrast. Instrumental examination revealed no signs of a tumor process. Fibrogastroduodenoscopy-superfcial refux-esophagitis, duodenitis, Chest CT-interstitial pneumonitis, abdominal ultrasound without pathology, ECG-sinus rhythm, normal EOS position, accelerated A-V conduction, echocardiography-minor separation of pericardial leaves (up to 5 mm), colonoscopy-dolichosigma. The patient was diagnosed with idiopathic dermatomyositis of high activity. Because of progressive myopathy and increasing dysphagia, pulse therapy with methylpredniso-lone500 mg for 3 days and rituximab 1000 mg was performed. She also received metipred 48 mg per day orally, methotrexate 15 mg per week subcutaneously and folic acid 5 mg per week. Against the background of therapy, positive dynamics was noted: swallowing normalized, the severity of myopathy decreased, after 10 days CKdecreased to 2049 IU/l. After 6 months during the control examination: there are no skin rashes, muscle strength is restored, CK 300 IU/l. The dose of methylprednisolone is reduced to 10 mg per day, the patient continues injections of methotrexate 15 mg per week. Conclusion: COVID-19 may be a trigger for the development of infammatory myopathy. In this clinical case there are features of the course and therapy of infammatory myopathies in patients after coronavirus infection.
ABSTRACT
Background: Patients with non-Hodgkin's lymphomas (NHL) develop abnormalities in the structural and functional organization of the immune system leading to immune deficiency. Chemotherapy (CT) in patients after SARS-CoV infection is associated with a more severe disease course affecting the treatment results. The cytokine-producing activity (CPA) of blood cells is poorly studied, while it determines the effectiveness of antitumor and anti-infective functions of the immune system. The purpose of this study was to evaluate CPA of peripheral blood mononuclear cells in patients receiving treatment for NHL after COVID-19. Methods: The study included 8 patients with large B-cell NHL with PCR-confirmed COVID-19 infection in past medical history. All patients received from 3 to 4 chemotherapy cycles. K2EDTA blood samples obtained before and after 3-4 CT cycles were divided into 2 parts after dilution with a sterile nutrient medium solution: part 1, to assess spontaneous CPA;part 2, with addition of a sterile mitogen (phytohemagglutinin 4 μg, concanavalin A 4 μg, and lipopolysaccharide 2 μg) to assess stimulated CPA. The samples were incubated for 24 hours at 370C, and the levels of IL-1β, IL-6, IL-8, IL-10, IL-18, IL-4, IL-2, TNF- α, INF-γ, INF-α were determined in the obtained plasma. The stimulation coefficient (SC) was calculated as the ratio of stimulated CPA to spontaneous CPA. Results: 3-4 CT cycles in patients after COVID-19 was accompanied by an elevation of spontaneous CPA of the blood cells IL-6, INF-γ, TNF-α, IL-8, compared to the initial levels, by 678%, 127%, 64% and 57%, respectively. The ability of cells to spontaneous production of IL-10 and INF-α decreased by 30% and 100%. The mitogen-induced CPA of mononuclear cells in relation to IL-10, IL-6, IL-2, IL-1β and INF-α increased by 300%, 130%, 92%, 52% and 52%, respectively. Stimulated CPA in relation to INF-γ decreased by 21% compared to initial levels. As a result of the revealed CPA changes, SC in NHL patients after COVID-19 receiving CT increased, compared to the initial levels, by 465%, 92% and 48% respectively for IL-10, IL-2, IL-1β, as well as the appearing ability to INF-α production. SC for IL-6, INF-γ, TNF-α, and IL-8 decreased by 70%, 66%, 33% and 27% respectively. Conclusions: Certain features of spontaneous and mitogen-activated CPA of blood mononuclear cells were revealed in NHL patients after COVID-19, indicating a change in the functional activity of immune cells which could affect the development of the disease and the effectiveness of the therapy. The data obtained require additional studies and can be used to assess the condition of patients, as well as to predict the therapy efficacy.
ABSTRACT
Background: Patients with immunosuppression, including those with hematologic cancers, are at greater risk of developing SARS-CoV infection. The virus is capable of infecting monocytes, macrophages and dendritic cells in order to promote the secretion of cytokines, and IL-6 can contribute to the excessive activation of the effects of the acquired immune system (usually lymphocytes) and innate immunity (neutrophils, monocytes, NK cells, etc.). Aims: The purpose of the study was an assessment of the immune status of patients with hematological cancers after multi-course chemotherapy, therapy with anti-CD20+ antibodies and PCR-confirmed COVID19. Methods: The study included12 adult patients with lymphoproliferative diseases with a history of PCR-confirmed COVID-19. All patients underwent 4 to 6 chemotherapy cycles. The BD FACSCanto II flow cytometer with Becton Dickinson reagents were used to assess the immune status of patients. The research group consisted of patients with non-Hodgkin's large B-cell lymphomas. The blood plasma taken into a vacuum system with K2EDTA as an anticoagulant was used. The relative and absolute numbers of the main populations of T- and B-lymphocytes, the immunoregulatory index, and subpopulations of T-lymphocytes were assessed. Results: Most patients showed a decrease in the relative number of lymphocytes, on average by 73%. The absolute and relative numbers of monocytes in half of the cases exceeded the norm or were similar to it. The immunoregulatory index in most cases (N=7) was decreased on average by 42%, compared to the norm. The absolute number of T-lymphocytes (CD3+) in 6 patients decreased on average by 42%±0.6. The population of T-helpers (CD3+CD4+) in 5 patients was reduced by an average of 44%±0.8. The number of double-positive (CD3+CD4+CD8+) T-lymphocytes in most cases (N=10) was reduced by 80%±0.8. At the same time, the number of double-negative (CD3+CD4-CD8-) T-lymphocytes increased by177% in 7 patients. All patients showed a decrease in the B-cell immunity component. The relative number of B-lymphocytes (CD19+) was decreased on average by 78%, absolute number by 61%. The increase in all types of memory cells, both helper-inducer and cytotoxic populations, was registered. Summary/Conclusion: Conclusions. Elevated numbers of various memory cells, together with a decrease in T-lymphocytes, could indicate the activation of the cellular adaptive immunity. A decrease in B-lymphocytes could indicate a decrease in the activity of the humoral component of adaptive immunity. The latter could also be a result of multi-course chemotherapy with anti-CD20+ monoclonal antibodies.
ABSTRACT
Background: The development of lymphomas is accompanied by disorders in the structural and functional organization of the immune system leading to immune deficiency. Such patients are at greater risk of severe SARS-CoV infection. Our purpose was to assess the parameters of cellular immunity in patients with lymphomas with a history of multi-course chemotherapy, therapy with anti-CD20+ antibodies and PCRconfirmed COVID19. Methods: The study included 12 adult patients with lymphoproliferative diseases (non-Hodgkin's large B-cell lymphomas (NHL) -7, Hodgkin's lymphomas (HL) -5) with a history of PCRconfirmed COVID-19. All patients underwent 4 to 6 chemotherapy cycles. The relative numbers of the main populations of leukocytes, T-and Blymphocytes, as well as subpopulations of Tlymphocytes, were assessed in the whole blood collected in K2EDTA anticoagulant using the BD FACSCanto II flow cytometer with a panel of antibodies according to the manufacturer's instructions (Becton Dickinson, USA). Results: Patients with HL showed a number of changes in the parameters of cellular immunity. The content of total lymphocytes and monocytes was reduced in comparison with patients with NHL by 34% and 56%, respectively: 14.3 (11;17) vs. 21.7 (15.2;32), and 6.0 (4.8;7.1) vs. 13.5 (12.9;13.7), respectively. An increase in granulocytes by 30% was revealed in patients with HL. No differences were found in the content of both general and main populations (CD3+, CD3+CD4+, CD3+CD8+, central and effector memory cells). However, the content of naive CD3+CD4+ and CD3+CD8+ lymphocytes in patients with HL increased by 43% and 62%, respectively. While the number of CD3+CD4-CD8-lymphocytes was 47% lower, the number of CD3+CD4+CD8+, on the contrary, exceeded the values in patients with NHL by 4.6 times. Patients with HL also showed a tendency towards a decrease in the number of NK and NKT-lymphocytes. Conclusions: The increased levels of naive lymphocytes and both populations of memory cells and a sharp increase in double-negative T-lymphocytes and B-lymphocytes in patients with HL could indicate certain characteristics of the disease course affected by COVID-19. The data require additional research and can be used to assess the condition of patients and to predict the therapy efficacy.