RESUMEN
BACKGROUND: Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in many regions of Asia. Cytokines, including pro-inflammatory and anti-inflammatory are key regulators playing a detrimental role in the host response to JE infection, pathogenesis and disease outcome. Evidently, the host's cytokine response is genetically determined, representing the complexity of interindividual differences regarding immune response to viral infection. The current study assesses the association of single nucleotide polymorphisms of classical interleukin IL-1ß and IL-10 with JEV susceptibility and disease severity in north Indian population. METHODS: We performed a case-control study using 85 JE patients and 85 healthy controls. Polymorphisms in the IL-1ß (-511 C/T) and IL-10 (-1082 A/G) genes were genotyped using PCR-RFLP. All continuous variables were expressed as mean ± standard deviation, and categorical variables were expressed in percentage. RESULTS: The mRNA level of IL-1ß and IL-10 were found significantly increased in JE patients. In severe JE patients, IL-1ß mRNA level was significantly higher with heterozygous (C/T) and homozygous (C/C) genotype compared to wild (T/T) genotype and mRNA level of IL-10 was higher in heterozygous genotype (A/G) compared to wild genotype (A/A). The C/T and C/C genotypes of IL-1ß were significantly associated with higher risk of JE infection (p < 0.05, OR = 7.25 and 4.40) whereas, the A/G genotype of IL-10 was associated with a reduced risk of JEV infection (p < 0.05, OR = 0.30). The C allele of IL-1ß was associated with fever and neck stiffness (p < 0.05) and CT genotype was associated with disease severity and worse outcomes in JE patients. Along with this, IL-10 polymorphism was found associated with fever, and AG genotype was found to be associated with worse disease outcomes such as neurological sequelae (p < 0.05). CONCLUSION: Mutant allele and genotype at IL-1ß (-511 C/T) and IL-10 (-1082 A/G) gene polymorphism show increased expression of IL-1ß and IL-10 in JE patients which contribute to disease severity as well as adverse outcomes of disease. Overall this is the first report from northern India, which shows the association of IL-1ß and IL-10 polymorphisms with JEV infection.
Asunto(s)
Citocinas/genética , Encefalitis Japonesa/genética , Predisposición Genética a la Enfermedad/genética , Inflamación/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Alelos , Estudios de Casos y Controles , Virus de la Encefalitis Japonesa (Especie)/patogenicidad , Femenino , Frecuencia de los Genes/genética , Genotipo , Heterocigoto , Homocigoto , Humanos , India , Interleucina-10/genética , Interleucina-1beta/genética , Masculino , Adulto JovenRESUMEN
ObjectivesTo compare the co-administration of an Ayurvedic drug AYUSH 64 as an adjunct to standard of care (SOC) and SOC for efficacy and safety in the management of COVID-19. DesignMulticentre, parallel efficacy, randomized, controlled, open label, assessor blind, exploratory trial with a convenience sample. Patients followed to complete 12 weeks of study duration. SettingCOVID-19 dedicated non-intensive care wards at 1 government hospital, 1 medical college teaching hospital and 1 medical university teaching hospital Participants140 consenting, eligible, hospitalized adult patients suffering from mild and moderate symptomatic COVID-19 and confirmed by a diagnostic (SARS-CoV-2) RT-PCR assay on nasal and throat swab were randomized to SOC or SOC plus AYUSH 64. To be withdrawn if disease becomes severe. InterventionsTwo tablets of AYUSH 64, 500 mg each, twice daily after meals, and continued till study completion. SOC (symptomatic and supportive) as per national guidelines of India for mild and moderate disease. Main outcome measuresTime period to clinical recovery (CR) from randomization baseline and proportion with CR within 28 days time frame; CR defined in the protocol Results140 patients randomized (70 in each arm); 138 patients with CR qualified for analysis. Both groups were matched at baseline. The mean time to CR from randomization was significantly superior in AYUSH 64 group (95% CI -3.03 to 0.59 days); a higher proportion (69.7%) in the first week (p=0.046, Chi-square). No significant differences observed for COVID-19 related blood assays (such as D-Dimer). AYUSH 64 arm showed significant (p<0.05) superior persistent improvement in general health, quality of life, fatigue, anxiety, stress, sleep and other psychosocial metrics. 1 patient on SOC required critical care. 48 adverse events (AE) reported in each group. Barring three SAE (in SOC), AE were mild and none were drug related. 22 participants (8 on AYUSH) were withdrawn. No deaths were reported. ConclusionsAYUSH 64 hastened recovery, reduced hospitalization and improved overall health in mild and moderate COVID-19 when co-administered with SOC under medical supervision. It was safe and well tolerated. Further studies are warranted. Trial registrationThe Clinical Trials Registry India Number CTRI/2020/06/025557 FundingCCRAS, Ministry of AYUSH, Government of India
RESUMEN
ObjectivesConvalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. DesignOpen-label, parallel-arm, phase II, multicentre, randomized controlled trial. SettingThirty-nine public and private hospitals across India. ParticipantsHospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 [≤] 93% on room air). InterventionParticipants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome MeasureComposite of progression to severe disease (PaO2/FiO2< 100) or all-cause mortality at 28 days post-enrolment. ResultsBetween 22nd April to 14th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. InterpretationCP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19. Trial registrationThe trial was registered with Clinical Trial Registry of India (CTRI); CTRI/2020/04/024775.
RESUMEN
BACKGROUND: Japanese encephalitis virus (JEV) is a neurotropic mosquito-borne Flavivirus, mainly prevalent in Asia. It is the most important causative agent of acute viral encephalitis in humans. Recently, micro RNAs are discovered as a key regulator of inflammatory and immune responses in various diseases including neurological and viral infections. Thus, this study was proposed to check whether changes in cellular miRNA expression due to JE virus infection, can be detected in circulation which would be helpful in diagnosis and treatment. METHODS: miRNAs (miR-29b and miR-146a) were analyzed in the serum of JEV infected patients using quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: miR-146a was found significantly decreased (pâ¯=â¯0.0008) in JEV infected patients as compared to healthy controls whereas miR-29b was significantly increased (pâ¯=â¯0.001) in JEV patients recovered with neurological sequelae when compared to those recovered without sequelae. CONCLUSION: In conclusion, miRNA can be measured in serum. Studying microRNAs will provide novel information and help us to identify the components that can serve as biomarkers and can lead to new discovery in controlling disease recovery.
Asunto(s)
Virus de la Encefalitis Japonesa (Especie)/aislamiento & purificación , Encefalitis Japonesa/sangre , Encefalitis Japonesa/diagnóstico , MicroARNs/sangre , Recuperación de la Función/fisiología , Adolescente , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Encefalitis Japonesa/genética , Femenino , Expresión Génica , Humanos , Masculino , MicroARNs/biosíntesis , MicroARNs/genética , Adulto JovenRESUMEN
BACKGROUND: Japanese encephalitis virus (JEV) is most important cause of viral encephalitis worldwide. The pathogenesis of this is probably attributed to the host genetic makeup. Intercellular adhesion molecule-1 (ICAM-1) and monocytes chemoattractant protein-1 (MCP-1) play a vital role in host defense mechanism against flavivirus causing encephalitis. We assessed the possible genetic association between ICAM-1 (K469E) and MCP-1-2518 Aâ¯>â¯G polymorphisms and Japanese Encephalitis in North Indian population. METHODS: We studied ICAM-1(K469E) and MCP-1-2518 Aâ¯>â¯G polymorphisms with the help of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Expression of ICAM-1 and MCP-1 were determined at mRNA and protein levels in JE patients and healthy controls by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). RESULTS: Homozygous (E/E) genotype of ICAM-1 was associated with clinical severity (pâ¯=â¯0.015) and outcome (pâ¯=â¯0.04) of JE, whereas, heterozygous (A/G) genotype of MCP-1-2518 Aâ¯>â¯G was associated with outcome in JE patients (pâ¯=â¯0.01). Among severe cases of JE, a higher level of ICAM-1 was observed in patients with E allele (E/Kâ¯+â¯E/E) of ICAM-1 (K469E) than non-E allele (K/K). The level of MCP-1 was found significantly increased in JE patients with homozygous (G/G) genotype when compared to wild (A/A) genotype of MCP-1-2518 Aâ¯>â¯G (pâ¯=â¯0.03). CONCLUSION: ICAM-1 (K469E) and MCP-1-2518 Aâ¯>â¯G polymorphisms lead to increased level of ICAM-1 and MCP-1 in Japanese Encephalitis which may be associated with severity as well as an adverse outcome of the disease. ICAM-1 (K469E) polymorphism may affect host susceptibility to Japanese encephalitis in North Indian population.