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.
ABSTRACT
Secretory immunoglobulin A, as a marker of the immune response in the mucous membrane, is an available indicator for detecting changes in the local immunity of mucous patients who have undergone COVID-19. Objective. To evaluate the dynamics of changes in the level of sIgA in saliva samples and the effectiveness of the use of interferon alpha-2b in individuals after a coronavirus infection. Patients and methods. Patients aged 18 to 60 years after COVID-19 infection (group 1 on therapy, n = 65;group 2 without therapy, n = 65) and conditionally healthy individuals (control group, n = 15) were monitored. The material is saliva samples, where the sIgA level was determined initially and after a month. The drug - interferon alpha-2b, in the form of a gel for topical use (Viferon, dosage 36,000 IU/g) was administered intranasally 2 times a day, for 1 month. Results. In all groups of patients who underwent COVID-19, the level of saliva sIgA was lower compared to the conditional norm of healthy individuals (6,45 +/- 1,81 mg/ml). A month after the administration of interferon alpha-2b the best effect was observed in patients in the time interval of 1-3 months from the infection, where sIgA was noted a statistically significant increase from 1,84 +/- 0,28 to 5,78 +/- 1,96 mg/ml. In the groups of patients with later terms, a moderate increase in sIgA was determined (3-6 months: 2,83 +/- 0,71 to 3,33 +/- 1,78 mg/ml;6-9 months: 3,53 +/- 0,45 to 4,76 +/- 2,3 mg/ml) and the absence of infectious diseases during rehabilitation period. In the group without therapy, in all temporal aspects, a persistent decrease in sIgA indicators below normal values was revealed, and the frequency of incidence of respiratory viral infections was noted in 9,2% of cases. Conclusions. During the rehabilitation period, the greatest changes in sIgA in saliva were observed in patients in the first 3 months after the COVID infection. The administration of interferon alpha-2b to patients in the post-COVID period is accompanied by the normalization of sIgA and prevents the development of respiratory infections. In similar groups, after COVID-19 without therapy, the indicator tends to decrease, and this category of people is at a higher risk of developing other infectious pathologies.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 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
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.
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.
ABSTRACT
Background: COVID-19 has been a devastating disease and a major public health concern mainly to susceptible populations. Methods: We accessed two groups of pregnant women at the time of delivery: SARS-CoV2 active infection and convalescents. To investigate the factors contributing to COVID19 severity we have assessed several immunological parameters including cytokines/chemokine levels in the maternal and cord blood plasma. We have evaluated 33 cytokines. Our findings were validated in vitro in HTBE (Human tracheobronchial epithelial) cells infected with live SARS-COV2 (wild type). Results: Our cohort was enriched in high-risk subjects, including African American and obese women. Only 6% had severe or critical disease, contrasting with the 20-25% reported in some pregnant cohorts. TGFb2 levels were significantly associated with asymptomatic/mild disease in both active and convalescent cohorts, and inversely correlated with IP10, IL6 and IL8, known to be part of the cytokine storm post-infection. Pre-treatment of HTBE with TGFb2 for 48 hours led to a significant decay in viral loads at 72h post-infection. This control was associated with significantly higher IL-6 (IFNb2) levels prior to infection, and significantly higher expression of anti-viral genes at 72h pi (MX1, IFNA1, IFNA2, IFNL1, STAT1). Additionally, TGFb2 pre-treatment suppressed the expression of the cytokines IP-10, IL1b and IL8. Conclusion: Altogether this data suggested that TGFB2 plays a protective role in SARS-COV2 infection in this high-risk population by improving epithelial cells intrinsic antiviral function and by modulating the expression of the cytokines associated to the heightened inflammation in severe cases.
ABSTRACT
Background: Interferons play a pivotal role as a first line of the innate immune host response to viral infections, including COVID-19. Accumulating data suggests dysregulated interferon (IFN) responses in COVID-19. However, the clinical relevance of circulating levels of interferon to COVID-19 disease severity remains unclear Methods: In plasma from individuals with PCR confirmed SARS-CoV-2 infection recruited to the All Ireland Infectious Diseases Cohort, collected within 10 days from onset of symptoms, we measured levels of type I (IFN-α2a and IFN-β), type II (IFN-γ), and type III (IFN-a;1) interferons by electro-chemiluminescence immunoassays. Subsequent maximum COVID-19 disease severity was classified according to World Health Organization guidance (Critical, Severe, Moderate and Mild). We used Kruskal-Wallis tests to explore differences in IFN levels between COVID-19 severity groups, and logistic regression to determine associations, adjusting for demographics (age, sex at birth, ethnicity), comorbidities (obesity, hypertension, respiratory disease, heart disease) and medical management (antibiotics, immunosuppressants, anticoagulants, invasive ventilation) Results: Out of the 335 subjects with early infection and available samples, 319 had data on disease severity, 33 (10.3%) Critical, 37 (11.6%) Severe, 76 (23.8%) Moderate and 173 (54.2%) Mild. The population was predominantly Caucasian (79.3%), with a median [IQR] age of 64 [53,77] and male (52.7%). There was a significant difference between the 4 groups for the levels of Type I IFN-α2a (p=0.0028) and Type 3 IFN-a;1 (p=0.0001), both being higher in the critical group. In adjusted analyses, higher levels of Type I IFN-α2a but not Type 3 IFN-a;1 remained significantly associated with the development of Critical COVID-19 (Odds Ratio: 5.911/95% CI: 0.608, 52.388/p=0.029). (Fig 1) Conclusion: Increased circulating Type I IFN-α2a, but not other IFN classes, measured in the early stages of SARS-CoV-2 infection was associated with higher odds of Critical COVID-19 infection. These data point to specific differences in host responses that may lead to more targeted interventions to prevent development of severe COVID-19 infection.
ABSTRACT
Several drugs have been explored for the antiviral action against COVID-19 disease but none of them has been approved barring few such as Remdesivir which got emergency use authorization from USFDA. Interferon are attractive agents due to their broad anti-viral and immunological properties. Interferon alpha-2b has been recently investigated for this purpose. This study presents a systematic review of all the clinical studies involving Interferon alpha-2b to determine its efficacy and safety. A systematic review of literature was done using relevant terms for 'COVID-19" and "Interferon alpha". The studies evaluating the effect of Interferon alpha were identified and included in the study for qualitative analysis. All four clinical studies have shown that Interferon alpha 2b has efficacy as antiviral agent as shown by different clinical and laboratory parameters. It has also found to be safe and free of any major side effects. Interferon alpha 2b is an effective antiviral agent with potential to be use in COVID-19. This drug has already been given restricted use authorization in India.
ABSTRACT
Introduction: The Covid-19 pandemic is a global threat to public health, mainly affecting vulnerable groups, such as the elderly, chronically ill patients, or patients with substance use disorders (SUD) [1]. Prolonged use results in neurobiological changes in the cerebral area, activating the "reward system," leading to development of drug-seeking behaviors and upregulating proinflammatory cytokines, as well as growth factors [2,3]. The immune system's response inducing Covid-19 virus even to moderate symptoms by adapting the immunomodulation, seems to lead to an inflammatory process, especially in patients with pre-existing production of inflammatory agents, such as patients with SUD [4]. Objective: The investigation of biopsychosocial responses of the Covid-19 pandemic in patients under medication-assisted treatment (MAT) with methadone and buprenorphine and their correlation to biological factors. Material and Methods: 64 patients with Covid-19 were included in the study sample, 26 (40.6%) under methadone administration and 38 (59.4%) under buprenorphine ones. The Control group consisted of patients with SUD that had not been infected by the virus and Covid-19 patients without previous history of substance use. Blood samples were obtained in both groups to determine C-reactive protein (CRP), cortisol, IFNa1, IFNa2, IFNγ, IL-1a, IL-1β, IL-5, IL-6, IL-8, IL-10, IL-18, MCP-1, TNF-a, but in patients with Covid-19, blood samples were obtained at the first, seventh and sixteenth day after infection. The sample with SUD had completed a structured questionnaire (Medication-Assisted Treatment Questionnaire Covid-19 – MATQ/Covid-19) about Covid-19 effect in terms of medications’ administration (methadone and buprenorphine) and psychosocial life. Statistical significance was ascertained by t-tests, ANOVA and Pearson's x2 test as appropriate. Results: Reduced management of medications at take-home doses (p<0.05) and physical dysfunctions (p<0.05) were observed in both groups with SUD. Regarding the patients under methadone treatment, social isolation (p<0.05) and the need for psychosocial support from the therapeutic programs (p<0.001) were found increased. According to the results, the values of cortisol, IL-1a, IL-1b, IL-8 and MCP-1 were significantly elevated (p<0.05) in the study sample compared to the control group. Furthermore, biological factors on the 7th and 16th day after Covid-19 infection (cortisol, IL-1b, IL-8, TNF-a, MCP-1, IL-6) in methadone administration were significantly increased (p<0.05) while greater values of CRP (p<0.05) on the first and seventh day were observed in the buprenorphine group. In respect of the findings, the IL-8 and MCP-1 were significantly increased in the methadone group compared to the buprenorphine group. Moreover, increased values of IL-8 and MCP-1 positively were correlated with the need for psychosocial support, drug-seeking behavior and relapse. Conclusions: In conclusion, the Covid-19 virus negatively influences the immune system in patients under substitution treatment. Although methadone and buprenorphine are key substances as MAT, they seem able to exacerbate the dysregulated cellular functions due to the Covid-19 virus and, thus, lead progressively in drug-seeking behaviors and relapsing disorders. No conflict of interest
ABSTRACT
Objective. To evaluate pregnancy and childbirth outcomes after the combined use of VIFERON® (interferon α-2b with antioxidants) rectal suppositories (3,000,000 IU) and VIFERON® gel for external and local use (36,000 IU/g) in the treatment of new coronavirus infection (COVID-19) in pregnant women against the background of standard complex therapy. Patients and methods. A total of 140 pregnant women diagnosed with COVID-19 were examined and divided into two groups: group 1 consisted of 70 patients who received VIFERON® and standard complex therapy;group 2 – 70 patients who received only standard therapy. Results. Patients from group 1 had a significantly decreased incidence of preterm birth, perinatal loss, and severe birth asphyxia. Most of these pregnant women gave birth at 38-40 weeks of gestation, and no antenatal fetal death was recorded. Conclusion. Inclusion of VIFERON® (rectal suppositories and gel for external and local use) in the complex treatment of COVID-19 in pregnant women contributed to more prompt relief of symptoms and improved pregnancy and childbirth outcomes.
ABSTRACT
Introduction: A working hypothesis is that juvenile dermatomyositis (JDM) is a type 1 interferon driven inflammatory response, triggered by one or more environmental stimuli, such as infection. Objectives: We aimed to test the hypothesis that SARS-CoV-2 infection could promote JDM onset or relapse. Methods: We studied SARS-CoV-2 infection history in all JDM patients seen in our center for disease onset (n=6) or relapse (n=4) since the start of the pandemic. IgG and IgM directed against whole spike protein, spike Receptor Binding Domain (RBD), spike S2 subunit, nucleocapsid protein (NP) and Membrane glycoprotein (ME) were measure in the plasma by multiplex bead-based assay at diagnosis. IFNα2 level in the plasma was measure by digital ELISA. Results: Out of the 10 patients we identified concomitant infection by SARS-CoV-2 with disease onset in one patient, and concomitant infection by SARS-CoV-2 with disease relapse after 8 years out of treatment in one other. IFNa2 dosages in the plasma of these two patients revealed abnormally elevated concentrations (73476 fg/ml and 4612fg/ml respectively, median active JDM: 491fg/ml). Conclusion: Our results strongly suggest that SARS-CoV-2 infection could trigger the development of JDM, possibly through induction of IFNα.
ABSTRACT
Background: Both myocardial infarction (MI) and COVID-19 are characterized by cytokine storm in blood. Purpose: The objective of this study was to compare the concentration of 39 cytokines, chemokines, and growth factors in blood sera of patients with MI, COVID-19 (COV), and healthy donors. Methods: Patients' blood was collected within 1-2 days after hospitalization in the cardiovascular or COVID intensive care units. All COV patients were in a severe condition;all had increased C reactive protein, 86 and 95% had increased ferritin and D-dimers levels accordingly, 8-10 times decreased lymphocyte numbers. The analysis of the humoral factors in blood serum of MI (n=22), COV (n=23) and donors (n=27) was performed using a 39-plex cytometric analysis. Results: Among all factors analyzed TGFa, IL-1b, 2, 3, 5, 9, 13, 17A were almost not detectable both in patient and donor sera. The concentrations of the other 31 humoral factors in normal sera differed significantly from 0 to 22000 pg/mL. We divided them into house-keeping factors HKF ranged from 1000 to 22000 pg/mL;sentinel innate immunity factors SIF (30-200 pg/mL), and acute phase factors APF (0-30 pg/mL). HKF were detected in all samples. Among SIF and APF IL-1a, G-CSF, IFNa2, IL-7, MIP-1a, IL- 12, and IFNg were detected in 56-80% donor blood while IL-1RA, MCP-3, IL-2, 6, 10, 12, 15, FLT-3F, GM-CSF, TNF-b - only in 10-55%. At the same time all MI patients were 100% positive in all these factors showing extensive activation of blood secretome. Among low incidence APF cytokines in COV patients, percentage of IL-1RA, MCP-3, IFNa2, IL-6, 10, 15, FLT-3L negative sera decreased 3-5 times;and all sera were positive for MIP-1a and IL-12. At the same time TNF-a level decreased significantly from 0 in control to 85% of negative sera in COV patients. Summarized results are shown as the ratios of factor concentrations in MI or COV sera to normal control (Fig). Blood secretome of MI changed more significantly than of COV patients. The major factors (shown in red) in MI were IL-6, IL-12, IFNg, FLT-3L, GM-CSF, and IL-15, which increased 12, 9, 6, 6, 6, and 5 times accordingly. In COV sera IL-6, IL-10, IP-10, and MCP-3 increased by 28, 12, 10, and 9 times accordingly. Less expressed however significant increases are marked with asterisks. Conclusions: Acute MI is characterized by severe disturbances in blood secretome with an increased level of 25 out of 39 factors studied. Contrary to it, in COV patients the levels of IL-6, 10, IP-10, and MCP-3 were more enhanced while only 15 out of 31 exceeded normal levels.