ABSTRACT
Neutrophilic granulocytes (NG) are the main drivers of pathological inflammation in COVID-19. Objective. To specify the mechanisms of immunopathogenesis of COVID-19 based on a comparative immunological study of the number and phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets with an assessment of their effector functions against changing profile of NG-associated cytokines IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma. Patients and methods. In patients with moderate-to-severe and severe COVID-19, we determined IL-1beta, TNFalpha, IL-6, IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma (ELISA), the phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets, NF-kappaB-NG (CYTOMICS FC500), phagocytically active NG (%), neutrophil extracellular traps (NETs), NG in apoptosis, and the activity of NADPH oxidase. Results. In COVID-19 against the background of IFNalpha and IFNgamma production blockade and high levels of NG-associated IL-8, IL-18, IL-17A, VEGF-A, a reduction in the number of mature and functionally active CD16brightSD62LbrightCD11bbrightCD63-NG subsets was revealed, as well as an increase in the number of CD16dimSD62LdimSD11bbrightCD63-NG subsets with an immunosuppressive phenotype and CD16brightSD62LbrightSD11bbrightCD63bright-NG subsets with high cytotoxic activity and ability to form NETs, a decrease in the percentage of phagocytically active NG and an increase in the activity of NADPH oxidase, NETs, and NG in apoptosis. Conclusion. IFNalpha deficiency provokes a hyperergic response of NG-associated cytokines, which leads to the formation of uncontrolled immune inflammation involving NG subsets with an immunosuppressive and cytotoxic phenotype, exacerbating the course of COVID-19. The use of recombinant IFNalpha-2b with antioxidants (Viferon) in the early stages of the disease can help to restore immune homeostasis, normalize the level of NG-associated cytokines, reduce NERTs, and achieve good clinical efficacy.Copyright © 2022, Dynasty Publishing House. All rights reserved.
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Objective:To determine the therapeutic effect of Gegentang granules on a disease-syndrome mouse model combining human coronavirus 229EhCoV-229Epneumonia with Hanshi Yidu Xifei syndrome in vivo. Method(s): Mice were randomly divided into normal group,infection group,cold-dampness group,model group,chloroquine phosphate group0.18 g.kg-1,interferon-alpha2bIFN-alpha2bgroup1.83x106 U.kg-1, Gegentang granules high-dose and low-dose groups6.6,3.3 g.kg-1with 10 mice in each group. Cold-dampness environment and hCoV-229E infection were used for modeling,and the general status and lung index of mice in each group were observed. The viral load in lung tissue was detected by real-time fluorescent quantitative polymerase chain reactionReal-time PCR,the pathological changes in lung tissue were evaluated by hematoxylin-eosinHEstaining,the levels of serum gastrointestinal hormones and inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assayELISA,and the percentage of peripheral blood lymphocytes was detected by flow cytometry. Result(s):Comparing with model group,Gegentang granules could significantly alleviate the physical signs of Hanshi Yidu Xifei syndrome,including listlessness,weakness of limbs,sticky stool,etc. Comparing with model group,Gegentang granules high-dose group significantly reduced lung index,histopathological score of interstitial lung and bronchus,and the level of serum motilinP< 0.05,P<0.01,two doses of Gegentang granules could significantly increase the level of serum gastrinP< 0.05,P<0.01,the percentage of CD4+ ,CD8+ T lymphocytes in peripheral bloodP<0.05,P<0.01,and the level of tumor necrosis factor-alphaTNF-alphain lung tissue was significantly decreasedP<0.01,and the level of interleukin-6IL-6showed decreasing tendency. Conclusion(s): Gegentang granules has therapeutic effect on model mice. It can improve the appearance and behavior characterization,regulate the level of gastrointestinal hormones,decrease lung index and histopathological score,and possibly play an immunomodulatory role by inhibiting the expression of inflammatory cytokines in lung tissue and restoring the percentage of peripheral blood lymphocytes.Copyright © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.
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Objective: To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon alpha-2b (rIFNalpha-2b) and the combination of lopinavir/ritonavir plus rIFNalpha-2b for patients with COVID-19 in Zhejiang province. Method(s): A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNalpha-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data. Result(s): The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2+/-4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0+/-5.0) d] (t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] (H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively (Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8+/-3.9), (13.5+/-5.1) and (11.2+/-4.3) d, respectively(Z=6.722, P<0.05). Conclusion(s): The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNalpha-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy;and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.Copyright © 2020 by the Chinese Medical Association.
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A 23-year-old male patient received moxifloxacin, recombinant human interferon alpha-2b for injection, and lopinavir and ritonavir for 7 days for novel coronavirus pneumonia. There was no abnor-malityof serum potassium. Moxifloxacin was stopped, Qingfei Paidu decoction() was given, and then the patient's serum potassium began to rise. On day 10 after taking the decoction, laboratory tests showed serum potassium 5.7 mmol/L and the patient was diagnosed with hyperkalemia. Insulin injection 4 U diluted to 5% glucose injection 250 ml was given once by IV infusion, and then the serum potassium decreased to 5.0 mmol/L 6 hours later and 4.6 mmol/L 2 days later. After 5 days, the serum potassium rose again and finally to 5.4 mmol/L on day 17 after taking the decoction. Insulin was given once that day and 2 days later once daily according to the previous method. Then the serum potassium decreased and did not rise again. The patient recovered from novel coronavirus pneumonia and was discharged on day 28 after hospitalization.Copyright © 2020 by the Chinese Medical Association.
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Two female patients (patient 1, 22-year-old;patient 2, 50-year-old) received IV infusion of ribavirin injection (4 g in the first dose and the next day 1.2 g thrice daily), oral 2 lopinavir and ritonavir tablets twice daily, and aerosol inhalation of recombinant human interferon alpha2b for injection for novel coronavirus pneumonia. There was no obvious abnormality in blood routine and liver function before treatment. Laboratory tests showed red blood cell count (RBC) 2.89x1012/L, hemoglobin (Hb) 75 g/L, alanine aminotransferase (ALT) 22.8 U/L, aspartate aminotransferase (AST) 33.9 U/L, total bilirubin (TBil) 71.2 mumol/L, and indirect bilirubin (IBil) 63.5 mumol/L in patient 1 on the 2nd day of treatment, and RBC 3.46x1012/L, Hb 95 g/L, ALT 17.7 U/L, AST 21.3 U/L, TBil 86.1 mumol/L, and IBil 67.1 mumol/L in patient 2 on the 3rd day of treatment. The direct antiglobulin test was positive, indirect antiglobulin test was negative, and antinuclear antibody test was negative in both patients. They were diagnosed as having acute hemolytic anemia. Con-sidering the relationship to ribavirin, ribavirin was given in reduced dose and then finally discontinued in patient 1, and was discontinued directly in patient 2. On the basis of continued use of the other 2 drugs, both of them were treated with ursodeoxycholic acid. The Hb and bilirubin level of the 2 patients gradually returned to normal.Copyright © 2020 by the Chinese Medical Association.
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The clinical efficacy of recombinant IFN-alpha2b in therapy for COVID-19 in children is the basis for studying the parameters of the cytokine production activity of immune system cells and will allow to optimize antiviral therapy regimens. Objective. To study the effect of recombinant IFN-alpha2b on serum IFN-alpha and IFN-gamma concentrations and their synthesis by immune system cells in children with COVID-19. Materials and methods. Peripheral blood samples from 100 patients aged 1 to 17 years (1-7 years - 50 people, 8-17 years - 50 people) with a moderate course of COVID-19 were examined. Patients in the study group received recombinant IFN-alpha2b as part of complex therapy. Patients in the comparison group received antiviral therapy with Arbidol. Multiplex analysis was used to determine serum IFN-alpha and IFN-gamma concentrations and the level of their synthesis by immune system cells. The enzyme-linked immunosorbent assay (ELISA) was used to determine serum concentrations of antibodies to IFN-alpha. Results. Combination therapy with recombinant IFN-alpha2b in children of both age groups led to an increase in serum IFN-alpha concentrations compared to baseline values prior to treatment, in children in the control group and patients with COVID-19 after treatment with Arbidol. There were no significant changes in serum IFN-alpha and IFN-gamma concentrations and their synthesis in intact and PHA-stimulated cells in children of both age groups during treatment with Arbidol. Serum concentrations of antibodies to IFN-alpha during treatment with recombinant IFN-alpha2b did not depend on the age of children and remained within the reference range. Conclusion. A significant increase in serum IFN-alpha concentrations and restoration of its synthesis level induced by PHA to reference values indicate that the use of recombinant interferon medications with their antiviral and immunomodulatory effects should become an integral part of COVID-19 therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.
ABSTRACT
The post-COVID-19 recovery period is characterized by persistence of some symptoms, with immunological alterations being of great importance. Development of preventive measures to normalize mucosal immunity after a coronavirus infection determines the relevance of the current study. The aim was to study dynamics of clinical symptoms and level of secretory immunoglobulin A in individuals after a novel coronavirus infection as well as evaluate effectiveness of using IFNalpha-2b. Materials and methods. A study was conducted with patients aged 18 to 60 years old (n = 130), surveyed 1 to 9 months after post-infection, as well as in apparently healthy individuals lacking COVID-19 (n = 15). Previous novel coronavirus infection and post-COVID manifestations were verified based on medical documentation, complaints, anamnesis data, physical examination and questionnaires. The concentration of salivatory and nasopharyngeal mucosal sIgA was measured dynamically prior to and after administration of local therapy with IFNalpha-2b (gel applied intranasally twice a day for 30 days). Results. The acute period of COVID-19 was characterized by fever, anosmia, severe asthenia (fatigue and weakness), muscle and joint pain. Among the post-COVID manifestations at early period (1-3 months), pain in the joints and muscles (75.0%) as well as elevated body temperature (21.2%) were reliably detected, whereas in the long period (6-9 months) there were revealed dominance with the same frequency of shortness of breath, muscle and joint pain (75.8%, respectively). Based on examination data in healthy subjects, there was determined an arbitrary normal range of secretory IgA in saliva - 6.45+/-1.81 mg/ml and nasal swabs - 13.43+/-3.24 mg/ml. In the group of patients 1-3 months post-infection, therapy with IFNalpha-2b one month later resulted in significantly increased level of secretory IgA in saliva (from 1.84+/-0.28 to 5.78+/-1.96 mg/ml) and in nasal swabs (from 28.61+/-3.0 to 39.83+/-3.85 mg/ml) by more than 3- and 1.5-fold, respectively. In the group of patients without therapy was featured with stably sustained decline in sIgA level up to 9 months after COVID-19. In particular, the level of saliva sIgA ranged from 2.36+/-0.56 down to 2.16+/-0.66 mg/ml, and in nasal smears - from 15.66+/-1.32 to 10.23+/-1.07 mg/ml that differed insignificantly compared to baseline level. The rate of respiratory diseases prevailed in this group (27.6% of cases), which fully lacked in the group of topically administered IFNalpha-2b. Conclusion. In the post-COVID period, multiple organ disorders persist and reduced sIgA level is registered. Intranasally applied IFNalpha-2b made possible to normalize sIgA level and prevent accumulation of respiratory infectious pathologies.Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.
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Background: Currently, the present world is facing a new deadly challenge from a pandemic disease called COVID-19, which is caused by a coronavirus named SARS-CoV-2. To date, no drug or vaccine can treat COVID-19 completely, but some drugs have been used primarily, and they are in different stages of clinical trials. This review article discussed and compared those drugs which are running ahead in COVID-19 treatments. Method(s): We have explored PUBMED, SCOPUS, WEB OF SCIENCE, as well as press releases of WHO, NIH and FDA for articles related to COVID-19 and reviewed them. Result(s): Drugs like favipiravir, remdesivir, lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin, corticosteroids and interferons have been found effective to some extent, and partially approved by FDA and WHO to treat COVID-19 at different levels. However, some of these drugs have been disapproved later, although clinical trials are going on. In parallel, plasma therapy has been found fruitful to some extent too, and a number of vaccine trials are going on. Conclusion(s): This review article discussed the epidemiologic and mechanistic characteristics of SARS-CoV-2, and how drugs could act on this virus with the comparative discussion on progress and drawbacks of major drugs used till date, which might be beneficial for choosing therapies against COVID-19 in different countries.Copyright © 2022 Bentham Science Publishers.
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Interferons (IFN) have antiviral activity against many viruses, including SARS-CoV-2. A combination of IFN-a2b and the antioxidant taurine is widely used in the Russian Federation, and its antiviral activity has not been studied before. The aim of this study was to determine the antiviral activity of interferon drugs, in combination with taurine and without it. The study included cytotoxicity and antiviral activity assays of IFN-a2b preparations, when stored according to the instructions at 2-8degreeC, and after 1 month storage at the temperature of 20-26degreeC in a pre-opened state. The combination of IFN alpha-2b with taurine has a higher antiviral activity compared to IFN alpha-2b mono-preparation by more than 25% at a <<low>> and 85% at a <<high>> multiplicity of infection. Selectivity index for combinations of IFN-a2b (50,000 IU/dose) + taurine (1 mg/ml) and IFN-a2b (10,000 IU/ml) + taurine (0.8 mg/ml) was more than 600 units, whereas for the IFN-a2b (10,000 IU/ml) it was 200 units. Antiviral activity does not change after one month at room temperature. The combination of interferon with taurine at high concentrations was less toxic than interferon. The results obtained demonstrate practicability of interferon alpha-2b and taurine combination use for treatment and prevention of COVID-19.Copyright © Team of Authors, 2022.
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Objective: To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon alpha-2b (rIFNalpha-2b) and the combination of lopinavir/ritonavir plus rIFNalpha-2b for patients with COVID-19 in Zhejiang province. Method(s): A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNalpha-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data. Result(s): The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2+/-4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0+/-5.0) d] (t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] (H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively (Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8+/-3.9), (13.5+/-5.1) and (11.2+/-4.3) d, respectively(Z=6.722, P<0.05). Conclusion(s): The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNalpha-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy;and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.Copyright © 2020 by the Chinese Medical Association.
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Introduction. The tactics of managing and treating patients with chronic recurrent bacterial prostatitis (CRBP) in some cases is a difficult-to-treat condition for a practicing urologist. This circumstance occurs because the disease has several predisposing factors, a complex and multifaceted pathogenesis, and certain difficulties in diagnosis and treatment. Objective. To study the effectiveness of recombinant interferon alpha-2b medications in post-COVID-19 patients with chronic recurrent prostatitis against the background of antibiotic multi-drug resistance of microorganisms verified in prostate secretion. Materials and methods. The treatment of 52 post-COVID-19 patients with CRBP was analyzed, divided into three therapy-dependent groups. Group 1 patients (n = 18) received antibiotic therapy (ABT): Levofloxacin 500 mg q.d. PO for 28 days. Group 2 patients (n = 18) underwent combined therapy: ABT supplemented with recombinant interferon alpha-2b with an antioxidant complex of vitamins E and C ("Viferon" rectal suppositories) 3.000.000 IU b.i.d. PR q12h for 28 days. Group 3 patients (n = 16) received monotherapy with recombinant interferon alpha-2b with an antioxidant complex of vitamins E and C ("Viferon"rectal suppositories) 3.000.000 IU b.i.d. PR q12h for 28 days. The follow-up period was 6 months with monitoring of clinical and laboratory parameters assessed before treatment, after 1, 3 and 6 months from the start of therapy. Results. Based on the monitoring of the clinical picture and laboratory parameters, after 1 follow-up month, there was a significant decrease in the symptoms of the disease in all study groups. However, after 3 and 6 follow-up months, this trend was observed only in patients of groups 2 and 3 receiving recombinant interferon alfa-2b with an antioxidant complex (vitamins E and C). Conclusions. Strengthening the standard CRBP-therapy with recombinant interferon alpha-2b with an antioxidant complex of vitamins E and C makes it possible to normalize both clinical and laboratory parameters in most patients.Copyright © Rostovskii Gosudarstvennyi Meditsinskii Universitet. All rights reserved.
ABSTRACT
The post-COVID-19 recovery period is characterized by persistence of some symptoms, with immunological alterations being of great importance. Development of preventive measures to normalize mucosal immunity after a coronavirus infection determines the relevance of the current study. The aim was to study dynamics of clinical symptoms and level of secretory immunoglobulin A in individuals after a novel coronavirus infection as well as evaluate effectiveness of using IFNα-2b. Materials and methods. A study was conducted with patients aged 18 to 60 years old (n = 130), surveyed 1 to 9 months after post-infection, as well as in apparently healthy individuals lacking COVID-19 (n = 15). Previous novel coronavirus infection and post-COVID manifestations were verified based on medical documentation, complaints, anamnesis data, physical examination and questionnaires. The concentration of salivatory and nasopharyngeal mucosal sIgA was measured dynamically prior to and after administration of local therapy with IFNα-2b (gel applied intranasally twice a day for 30 days). Results. The acute period of COVID-19 was characterized by fever, anosmia, severe asthenia (fatigue and weakness), muscle and joint pain. Among the post-COVID manifestations at early period (1–3 months), pain in the joints and muscles (75.0%) as well as elevated body temperature (21.2%) were reliably detected, whereas in the long period (6–9 months) there were revealed dominance with the same frequency of shortness of breath, muscle and joint pain (75.8%, respectively). Based on examination data in healthy subjects, there was determined an arbitrary normal range of secretory IgA in saliva — 6.45±1.81 mg/ml and nasal swabs — 13.43±3.24 mg/ml. In the group of patients 1–3 months post-infection, therapy with IFNα-2b one month later resulted in significantly increased level of secretory IgA in saliva (from 1.84±0.28 to 5.78±1.96 mg/ml) and in nasal swabs (from 28.61±3.0 to 39.83±3.85 mg/ml) by more than 3- and 1.5-fold, respectively. In the group of patients without therapy was featured with stably sustained decline in sIgA level up to 9 months after COVID-19. In particular, the level of saliva sIgA ranged from 2.36±0.56 down to 2.16±0.66 mg/ml, and in nasal smears — from 15.66±1.32 to 10.23±1.07 mg/ml that differed insignificantly compared to baseline level. The rate of respiratory diseases prevailed in this group (27.6% of cases), which fully lacked in the group of topically administered IFNα-2b. Conclusion. In the post-COVID period, multiple organ disorders persist and reduced sIgA level is registered. Intranasally applied IFNα-2b made possible to normalize sIgA level and prevent accumulation of respiratory infectious pathologies.
ABSTRACT
Interferons (IFN) have antiviral activity against many viruses, including SARS-CoV-2. A combination of IFN-a2b and the antioxidant taurine is widely used in the Russian Federation, and its antiviral activity has not been studied before. The aim of this study was to determine the antiviral activity of interferon drugs, in combination with taurine and without it. The study included cytotoxicity and antiviral activity assays of IFN-a2b preparations, when stored according to the instructions at 2-8°C, and after 1 month storage at the temperature of 20-26°C in a pre-opened state. The combination of IFN alpha-2b with taurine has a higher antiviral activity compared to IFN alpha-2b mono-preparation by more than 25% at a «low» and 85% at a «high» multiplicity of infection. Selectivity index for combinations of IFN-a2b (50,000 IU/dose) + taurine (1 mg/ml) and IFN-a2b (10,000 IU/ml) + taurine (0.8 mg/ml) was more than 600 units, whereas for the IFN-a2b (10,000 IU/ml) it was 200 units. Antiviral activity does not change after one month at room temperature. The combination of interferon with taurine at high concentrations was less toxic than interferon. The results obtained demonstrate practicability of interferon alpha-2b and taurine combination use for treatment and prevention of COVID-19.
ABSTRACT
Introduction. The tactics of managing and treating patients with chronic recurrent bacterial prostatitis (CRBP) in some cases is a difficult-to-treat condition for a practicing urologist. This circumstance occurs because the disease has several predisposing factors, a complex and multifaceted pathogenesis, and certain difficulties in diagnosis and treatment. Objective. To study the effectiveness of recombinant interferon α-2b medications in post-COVID-19 patients with chronic recurrent prostatitis against the background of antibiotic multi-drug resistance of microorganisms verified in prostate secretion. Materials and methods. The treatment of 52 post-COVID-19 patients with CRBP was analyzed, divided into three therapy-dependent groups. Group 1 patients (n = 18) received antibiotic therapy (ABT): Levofloxacin 500 mg q.d. PO for 28 days. Group 2 patients (n = 18) underwent combined therapy: ABT supplemented with recombinant interferon α-2b with an antioxidant complex of vitamins E and C ("Viferon®” rectal suppositories) 3.000.000 IU b.i.d. PR q12h for 28 days. Group 3 patients (n = 16) received monotherapy with recombinant interferon α-2b with an antioxidant complex of vitamins E and C ("Viferon®”rectal suppositories) 3.000.000 IU b.i.d. PR q12h for 28 days. The follow-up period was 6 months with monitoring of clinical and laboratory parameters assessed before treatment, after 1, 3 and 6 months from the start of therapy. Results. Based on the monitoring of the clinical picture and laboratory parameters, after 1 follow-up month, there was a significant decrease in the symptoms of the disease in all study groups. However, after 3 and 6 follow-up months, this trend was observed only in patients of groups 2 and 3 receiving recombinant interferon alfa-2b with an antioxidant complex (vitamins E and C). Conclusions. Strengthening the standard CRBP-therapy with recombinant interferon α-2b with an antioxidant complex of vitamins E and C makes it possible to normalize both clinical and laboratory parameters in most patients.
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Despite the measures taken and the molecular advances for the development of new agents for the control of SARS-CoV-2 infection, there is still insufficient development of an effective treatment. The objective of the review was to de-scribe the clinical studies and reported articles on drugs used as possible therapeutic agents for COVID-19 and the main conclusions on their reuse. A non-systematic review through PubMed, ScienceDirect, and clinical trials at ClinicalTrials. gov on original articles and case report in English and Span-ish that will report information on COVID-19 treatment and its main conclusions. Articles that were not relevant or that did not mention updated information to that reported in other articles were excluded. A total of 99 bibliographic references were included. COVID-19 appears as a multisystemic disease with variable clinical symptoms. Since no specific treatment is yet known, multiple drugs have been proposed that attack the different pathways of SARS-CoV-2. For severe disease in patients who require hospitalization and oxygen support, the use of remdesivir, dexamethasone, or tocilizumab is recommended if there are patient conditions that apply to use them. The use of ivermectin, colchicine, lopinavir/ritonavir, hydroxy-chloroquine, and chloroquine have not reported benefits that surpass adverse effects.
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The post-COVID-19 recovery period is characterized by persistence of some symptoms, with immunological alterations being of great importance. Development of preventive measures to normalize mucosal immunity after a coronavirus infection determines the relevance of the current study. The aim was to study dynamics of clinical symptoms and level of secretory immunoglobulin A in individuals after a novel coronavirus infection as well as evaluate effectiveness of using IFNalpha-2b. Materials and methods. A study was conducted with patients aged 18 to 60 years old (n = 130), surveyed 1 to 9 months after post-infection, as well as in apparently healthy individuals lacking COVID-19 (n = 15). Previous novel coronavirus infection and post-COVID manifestations were verified based on medical documentation, complaints, anamnesis data, physical examination and questionnaires. The concentration of salivatory and nasopharyngeal mucosal sIgA was measured dynamically prior to and after administration of local therapy with IFNalpha-2b (gel applied intranasally twice a day for 30 days). Results. The acute period of COVID-19 was characterized by fever, anosmia, severe asthenia (fatigue and weakness), muscle and joint pain. Among the post-COVID manifestations at early period (1-3 months), pain in the joints and muscles (75.0%) as well as elevated body temperature (21.2%) were reliably detected, whereas in the long period (6-9 months) there were revealed dominance with the same frequency of shortness of breath, muscle and joint pain (75.8%, respectively). Based on examination data in healthy subjects, there was determined an arbitrary normal range of secretory IgA in saliva - 6.45+/-1.81 mg/ml and nasal swabs - 13.43+/-3.24 mg/ml. In the group of patients 1-3 months post-infection, therapy with IFNalpha-2b one month later resulted in significantly increased level of secretory IgA in saliva (from 1.84+/-0.28 to 5.78+/-1.96 mg/ml) and in nasal swabs (from 28.61+/-3.0 to 39.83+/-3.85 mg/ml) by more than 3- and 1.5-fold, respectively. In the group of patients without therapy was featured with stably sustained decline in sIgA level up to 9 months after COVID-19. In particular, the level of saliva sIgA ranged from 2.36+/-0.56 down to 2.16+/-0.66 mg/ml, and in nasal smears - from 15.66+/-1.32 to 10.23+/-1.07 mg/ml that differed insignificantly compared to baseline level. The rate of respiratory diseases prevailed in this group (27.6% of cases), which fully lacked in the group of topically administered IFNalpha-2b. Conclusion. In the post-COVID period, multiple organ disorders persist and reduced sIgA level is registered. Intranasally applied IFNalpha-2b made possible to normalize sIgA level and prevent accumulation of respiratory infectious pathologies. Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.
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Objective: to study the clinical and epidemiological features of the course of a new coronavirus infection in children of different ages undergoing outpatient treatment. The study participants were 812 children with COVID-19 aged from 1 month to 17 years, who were on outpatient treatment in the children's polyclinic of the city of Kirov from July to December 2021. The average age of patients with COVID-19 was 5.9 +/- 1.1 years. Among the sick young children there were 28%, adolescents - 16%. In 76% of cases, contact with patients with a new coronavirus infection was detected, mainly in the family, as well as in educational institutions. In 70% of cases, an early request for medical help was registered - in the first three days of illness. In most cases (89%), a mild severity of the disease was established with the development of subfebrile fever and pharyngitis. Rhinitis phenomena were recorded in 20% of cases. 7% of children complained of a dry cough. Lung tissue lesion (RG1) was detected in 5% of patients, gastrointestinal tract - 5%. In adolescents, the phenomena of rhinitis, pharyngitis, dry cough were less common than in other age groups. Recombinant interferon alpha-2b and umifenovir were used for etiotropic therapy. All children recovered within 7-10 days from the onset of the disease. Copyright © 2022 GEOTAR Media. All rights reserved.
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Objective. To clarify the features of the defect in the function of NK cells, T lymphocytes, the interferon system in patients with moderate and severe COVID-19. Patients and methods. Tests of the peripheral blood of 50 COVID-19 patients aged 61(57–71) and having the moderate and severe disease were performed. The following parameters were measured: the quantity of CD3+CD19–, CD3+CD4+, CD3+CD8+ T lymphocytes, NK – (CD3–CD16+CD56+), and TNK – CD3+CD16+CD56+ with expression density considered membrane receptors (MFI) (FC 500 Beckman Coulter, USA), the levels of IFN-α, IFN-γ, IL-6, TNF-α cytokines (IFA). Results. Combined immunodeficiency associated with quantitative and functional defects in NK, T lymphocytes and their subsets was revealed in moderate and severe COVID-19. An imbalance of cytokines has been established: blockade of the production of IFN-α and IFN-γ against the background of a significant increase in IL-6 and TNF-α, which negatively affects both the number and functionality of the participants in the immune response and is associated with a severe course and poor prognosis of COVID-19. Conclusion. The data obtained demonstrate the need to develop new strategies and tactics for the treatment of COVID-19, including replacement systemic therapy with recombinant IFN-α2b in combination with antioxidants (Viferon®) in adequate therapeutic doses, aimed at restoring the normal functioning of T lymphocytes, NK and the interferon system.
ABSTRACT
Objective. To assess the effectiveness of different preventive measures for novel coronavirus infection in pregnant women. Patients and Methods. This study included 125 pregnant women hospitalized with moderate to severe laboratory-confirmed SARS-CoV-2 infection between September and November 2021 (the fourth pandemic wave), and 175 pregnant women who were not infected with COVID-19 during the same period. All women in these two groups were comparable for gestational age (II–III trimesters, 24–39 weeks), age (20–40 years), social status, parity, body mass index, and had no known COVID-19 risk factors. Results. Our findings revealed that vaccination 3-5 months before pregnancy (OR = 4.12;95% CI 1.28–13.27;χ2 = 0.022), inconsistent use and/or non-timely replacement of face masks (OR = 5.71;95% CI 2.83–11.51) were associated with the increased risk of COVID-19 in the second and third trimesters of gestation. It was showed that systematic (once in the morning at 24–48-hour intervals) intranasal administration of recombinant interferon alpha-2b (IFN-α;Grippferon) as compared with a single application after exposure to COVID-19 reduced the disease incidence rate and there was no evident risk of illness (OR = 0.08;95% CI 0.05–0.14;19.2% vs 74,3%, p < 0.001). This can be explained by the fact that women were mostly infected in unpredictable conditions (e.g., 29.2% of pregnant women were infected from family members, 23.9% had unknown source of exposure). The use of umifenovir, not currently authorised for the medication-assisted prevention of COVID-19 in pregnant women, and rectal administration of IFN-α suppositories did not reduce the disease incidence rate. Rectal use of IFN-α suppositories by pregnant women off-label increased the incidence (32.0 vs 15.4%, p = 0.001) and risk of developing novel coronavirus infection (OR = 2.58;95% CI 1.48–4.50). Conclusion. There is a need to improve awareness among pregnant women about the mandatory and timely vaccination against COVID-19 during pregnancy and the importance of strict adherence to wearing face masks. Increased efforts should be made to monitor and inform pregnant women about the use of only authorised medication-assisted preventive measures of SARS-CoV-2 infection, such as intranasal administration of recombinant IFN α-2b (Grippferon). During the epidemic rise in COVID-19 cases, the systematic intranasal administration of recombinant interferon-based medication Grippferon (once in the morning at 24–48-hour intervals) is recommended for pregnant women.