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Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial.
Li, C, Luo, F, Liu, C, Xiong, N, Xu, Z, Zhang, W, Yang, M, Wang, Y, Liu, D, Yu, C, et al
Annals of medicine. 2021;(1):391-401
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Abstract
BACKGROUND There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir-ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19. METHOD In this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion. RESULTS A total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81, p = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days (p = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days (p = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups. CONCLUSIONS AND RELEVANCE rSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.Key messagesThere are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus.In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir-ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.
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[Viferon suppositories in the treatment of influenza in adults].
Gatich, RZ, Kolobukhina, LV, Vasil'ev, AN, Isaeva, EI, Burtseva, EI, Orlova, TG, Voronina, FV, Kol'tsov, VD, Malinovskaia, VV
Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic]. 2008;(3-4):13-7
Abstract
One hundred and one patients at the age of 18 to 60 years suffering from influenza were observed during increased ratio of the sickness due to the influenza virus types A (H1N1 and H3N2) and B. The diagnosis of influenza was confirmed by the laboratory tests. Viferon was used in the treatment of 35 patients. The randomized double blind placebo-controlled study revealed high therapeutic efficacy ofviferon and its immunomodulating effect on the T-cells, the neutrophil phagocytic activity and the decrease of the levels of the circulating immune complexes. Viferon and arbidol decreased the fever periods and the toxicosis symptoms vs. the placebo. The therapeutic efficacies of viferon and arbidol were on the whole comparable, whereas the clinical findings and the results of the immunological tests were evident of the viferon higher therapeutic and immunomodulating efficacy. No side effects of the drugs were recorded. The tolerability was excellent. Viferon can be recommended for the treatment of influenza in adults.
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[Effect of spleen-invigorating prescription on dendritic cell function in patients with chronic hepatitis B of TCM Pi-deficiency syndrome type].
Gao, YQ, Zheng, YJ, Wang, LT
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine. 2007;(4):300-2
Abstract
OBJECTIVE To observe the effect of Spleen-invigorating Prescription (SIP) on dendritic cell function in patients with chronic hepatitis B. METHODS A total of 60 patients with chronic HBV of Pi-deficiency syndrome type were enrolled and randomized to 2 groups, 30 in each group. Patients in the control group were given intramuscular injection with human interferon alpha 1b, 3 times a week, while those in the treated group were given orally with SIP twice a day, the therapy lasted for 6 months. Dendritic cells (DCs) were isolated from peripheral blood and cultured, then the expression of surface markers, HLA-DR, CD86, CD80, CD40, CD14 and CD11c were detected before and after treatment by flow cytometry, and the function of DCs was also evaluated by mixed lymphocyte reaction (MLR) determination once before treatment and once after treatment. RESULTS The expressions of DCs' surface CD86, CD80, CD40 and CD11c in the treated group were higher (P < 0.05, P < 0.01) and the changes of stimulating index, IFN-gamma and IL-12 were superior in the treated group to those in the control group (P < 0.05). CONCLUSIONS SIP can significantly improve DC's function, so, one of mechanisms of SIP in improving clinical efficacy may be the regulation of immune function.
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Fate and function of hepatitis-C-virus-specific T-cells during peginterferon-alpha2b therapy for acute hepatitis C.
Wiegand, J, Cornberg, M, Aslan, N, Schlaphoff, V, Sarrazin, C, Kubitschke, A, Buggisch, P, Ciner, A, Jaeckel, E, Manns, MP, et al
Antiviral therapy. 2007;(3):303-16
Abstract
BACKGROUND Strong hepatitis C virus (HCV)-specific T-cell responses are associated with spontaneous clearance of acute hepatitis C. However, recent studies described a decline in HCV-specific CD8+ T-cells during interferon treatment, suggesting that the success of acute HCV therapy might be independent of adaptive immunity. METHODS T-cell responses of eight human leukocyte antigen (HLA)-A2-positive, acutely infected patients treated with peginterferon-alpha2b were studied by ELISPOT and proliferation assays and flow cytometry analysis using HCV-specific tetramers. RESULTS HCV-specific T-cells predominately declined during therapy. However, diverse patterns of CD4+ and CD8+ T-cell kinetics were observed. In patients with sustained virological response chemokine receptor 3 (CXCR-3) expression of HCV-specific CD8+ T-cells was upregulated, indicating homing to the liver. Low levels of T-cells remained detectable throughout treatment and follow up. In contrast, T-cells of a relapse patient did not upregulate CXCR-3 but displayed a higher staining for annexin-V, followed by a complete loss of peripheral virus-specific CD8+ T-cells by week 12. CONCLUSIONS Kinetics of HCV-specific T-cell responses are heterogeneous in interferon-treated patients with acute hepatitis C. The decline of T-cells might be a consequence of both apoptosis and homing. The balance between cell death and regulation of chemokine receptors might lead to different long-term outcomes.
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Risk factors for hepatic decompensation in patients with HIV/HCV coinfection and liver cirrhosis during interferon-based therapy.
Mauss, S, Valenti, W, DePamphilis, J, Duff, F, Cupelli, L, Passe, S, Solsky, J, Torriani, FJ, Dieterich, D, Larrey, D
AIDS (London, England). 2004;(13):F21-5
Abstract
OBJECTIVE Hepatic decompensation was reported from two recent trials (APRICOT and RIBAVIC) assessing interferon (IFN)-based treatment of hepatitis C virus (HCV) in HIV/HCV-coinfected patients. This paper identifies risk factors associated with hepatic decompensation in APRICOT. METHODS APRICOT is a randomized, partially-blinded, controlled trial comparing treatment with peg-IFN alpha-2a 180 microg once weekly plus ribavirin/placebo 400 mg twice daily with IFN alpha-2a 3 million units three times weekly plus ribavirin 400 mg twice daily for 48 weeks in a total of 859 patients. Multiple logistic regression analysis was performed comparing the baseline characteristics of those cirrhotic patients who experienced decompensation with those of the other cirrhotic patients enrolled. RESULTS Fourteen patients, all cirrhotic, experienced hepatic decompensation during the study. The incidence in the cirrhotic subgroup of the study was 10.4% (14/134). Six of the 14 patients died as a result of hepatic decompensation. The risk factors associated with hepatic decompensation were increased bilirubin, decreased haemoglobin, increased alkaline phosphatase or decreased platelets, and treatment with didanosine. Markers of viral replication, histological activity, cellular immune status or HCV-therapy, treatment with ribavirin and pegylated versus non-pegylated IFN were not associated with hepatic decompensation. CONCLUSIONS The results from APRICOT indicate that the overall risk of hepatic decompensation in HIV/HCV-coinfected patients without cirrhosis receiving IFN-based treatment is low. In contrast, patients with markers of advanced cirrhosis, despite the absence of a history of hepatic decompensation, should be monitored closely during IFN-based therapy, because they are at risk of hepatic decompensation. Treatment with antiretrovirals such as didanosine may increase the risk further.
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Unexpected cytokines in serum of malignant melanoma patients during sequential biochemotherapy.
Grimm, EA, Smid, CM, Lee, JJ, Tseng, CH, Eton, O, Buzaid, AC
Clinical cancer research : an official journal of the American Association for Cancer Research. 2000;(10):3895-903
Abstract
Biochemotherapy, which combines traditional chemotherapy with immune modulating biologicals, produces an unexpectedly high response rate (>50%) in advanced melanoma patients. We hypothesize that immunological mechanism(s) are responsible for the increased response rate, and particularly that macrophage activation is involved in tumor reduction. Patients were randomized to receive chemotherapy, composed of cisplatin, vinblastine, and dacarbazine (CVD), or biochemotherapy, which is CVD followed by interleukin (IL)-2 and IFN-alpha2b (CVD-BIO). Laboratory analysis was performed on sera from 41 patients from each arm. Measurements of macrophage activation (neopterin), nitric oxide production (nitrite), and tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, IL-1beta, IFN-gamma, IL-6, IL-10, and soluble IL-2 receptor (sIL-2R) were performed. Six of the nine biological responses (nitrite, neopterin, IFN-gamma, IL-6, soluble IL-2R, and IL-10) significantly (P < 0.0002) increased in the CVD-BIO patients but not in the CVD patients. The increased IL-6 (P = 0.04) and IL-10 (P = 0.05) correlated with patient response, but only when the minor responders were included in the analysis. Evidence of macrophage activation was found in CVD-BIO patients and not in those receiving CVD alone. In addition, an unusual cytokine elaboration composed of IL-6, IFN-gamma, IL-10, nitrite, neopterin, and sIL-2R, but not the expected TNF-alpha and IL-1, was detected. A trend of higher increase in IL-6 and IL-10 in patients having clinical response was found, suggesting an incomplete Th2 pattern of cytokine elaboration. These data show that macrophage activation does not appear to be critical in the response to CVD-BIO, but that IL-10 and IL-6 induced by the BIO component of the CVD-BIO were associated with tumor regression, and that their biology should be pursued further in the analysis of mechanism(s) of response.