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Background: COVID-19 resulted in loss of human lives owing to respiratory failure caused by dysregulated immune system. Though many treatments are evaluated, the most appropriate is yet to be established. Objective: To determine the safety and efficacy of Siddha add-on therapy in COVID -19 in terms of accelerated recovery, reduced hospital stay & mortality and follow up assessment of post discharge status until 90 days as compared to the Standard Care management. Methods: In a randomized, controlled, single-center, open-label trial conducted on 200 hospitalized COVID-19 patients, they were allocated equally to be treated with add-on Siddha regimen with Standard care or only Standard care. Standard care was in accordance to the Government norms. Recovery was defined as amelioration of symptoms, viral clearance and attaining SpO2 > 94% in room air indicating the derived score of zero on WHO clinical progression scale. The primary and secondary end points were accelerated recovery (≤ 7 days) and mortality comparison between the groups respectively. Also, disease duration, length of hospital stays and laboratory parameters were assessed for safety and efficacy. Patients were followed through for 90 days after admission. Results: In this study the accelerated recovery was 59.0% and 27.0% in treatment and control groups (ITT analyses) (p < 0.001) respectively and Odds for it were four times higher in the treatment group (OR: 3.9; 95% CI: 1.9, 8.0). The estimated median time for recovery in the treatment group was 7 days (95% CI: 6.0, 8.0; p=0.003) and 10 days (95% CI: 8.7, 11.3) in control. Hazard ratio for death in control was 2.3 times that of treatment group. No adverse reactions or alarming laboratory values were observed in response to intervention. In Severe COVID treatment group (n=80), mortality was 15.0% and 39.5% in control (n=81). The COVID stage progression was 65% less in test group. Mortality during treatment and 90 days follow up in Severe COVID patients were 12 (15%) and 35 (43.2%) in treatment and control groups respectively. Conclusion: The selected Siddha regimen when co-administered with Standard of Care have demonstrated that they can synergistically act to improve oxygenation status of patients, enhance the recovery rate from COVID-19 and reduce the mortality better when compared to administration of only Standard of Care. Clinical Trial Registry of India: CTRI/2020/06/025768 Registered on: 09/06/2020.

Background: Children with tuberculous meningitis (TBM) present with diagnostic challenges as they often have atypical clinical features., Objective: To describe the baseline characteristic features of children diagnosed with central nervous system (CNS) TB (TBM and tuberculoma)., Design: Retrospective descriptive study., Methods: Children less than 12 years presenting with neurological signs and symptoms were assessed for a therapeutic TBM trial eligibility. The results of their clinical, laboratory, neuroimaging, cerebrospinal fluid evaluations were analysed for TBM diagnosis., Results: Of 600 children evaluated, 61(10%) had CNS tuberculosis; TBM 47, tuberculoma 14. 20(33%) had definite TBM. Mean age of children with TBM was 5 ± 3.4 years. Of 47, 13(28%), 21(45%) and 13(28%) had grade I, II, and III disease respectively. Abnormalities suggestive of TBM in MRI and computed tomography brain were observed in 76% (26/34) and 77% (24/31) respectively. Abnormal cerebrospinal fluid white blood cell count, protein and glucose were observed in 56% (24/43), 49% (22/45), 47% (21/45) respectively. Among 41 patients with TBM followed up until discharge, five died., Conclusion: Younger children with TBM have severe forms. Confirmatory results may not be available in all. A holistic approach to care including addressing complications of hydrocephalus and strokes is needed., (© The Author(s), 2024.)

Background: It has been reported that differential diagnosis of bacterial or viral pneumonia and tuberculosis (TB) in infants and young children is complex. This could be due to the difficulty in microbiological confirmation in this age group. In this study, we aimed to assess the utility of a real-time multiplex PCR for diagnosis of respiratory pathogens in children with pulmonary TB., Methods: A total of 185 respiratory samples [bronchoalveolar lavage (15), gastric aspirates (98), induced sputum (21), and sputum (51)] from children aged 3-12 years, attending tertiary care hospitals, Chennai, India, were included in the study. The samples were processed by N acetyl L cysteine (NALC) NAOH treatment and subjected to microbiological investigations for Mycobacterium tuberculosis (MTB) diagnosis that involved smear microscopy, Xpert® MTB/RIF testing, and liquid culture. In addition, DNA extraction from the processed sputum was carried out and was subjected to a multiplex real-time PCR comprising a panel of bacterial and fungal pathogens., Results: Out of the 185 samples tested, a total of 20 samples were positive for MTB by either one or more identification methods (smear, culture, and GeneXpert). Out of these 20 MTB-positive samples, 15 were positive for one or more bacterial or fungal pathogens, with different cycle threshold values. Among patients with negative MTB test results ( n  = 165), 145 (87%) tested positive for one or more than one bacterial or fungal pathogens., Conclusion: The results suggest that tuberculosis could coexist with other respiratory pathogens causing pneumonia. However, a large-scale prospective study from different geographical settings that uses such simultaneous detection methods for diagnosis of childhood tuberculosis and pneumonia will help in assessing the utility of these tests in rapid diagnosis of respiratory infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Rajendran, Thomas, Balaji, Selladurai, Jayachandran, Malayappan, Bhaskar, Palanisamy, Ramamoorthy, Hasini and Hissar.)

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare manifestation of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection that can result in increased morbidity and mortality. Mounting evidence describes sex disparities in the clinical outcomes of coronavirus disease 2019 (COVID-19). However, there is a lack of information on sex-specific differences in immune responses in MIS-C. This study is an observational and cross-sectional study and we wanted to examine immune parameters such as cytokines, chemokines, acute phase proteins (APPs), growth factors, microbial translocation markers (MTMs), complement components and matrix metalloproteinases (MMPs) in MIS-C children, based on sex. Male children were associated with heightened levels of pro-inflammatory cytokines-IFNγ, IL-2, TNFα, IL-1α, IL-1β, IL-6, IL-12, G-CSF and GM-CSF, chemokines-CCL2, CCL11, CXCL1, CXCL8 and CXCL10, acute phase proteins-α-2M, CRP, growth factors VEGF and TGFα, microbial translocation markers- iFABP, LBP, EndoCAb, complement components-C1q, MBL and C3 and matrix metalloproteinases MMP-8 and MMP-9 compared to female children with MIS-C. These results indicate that the heightened immune response in males is a characteristic feature of MIS-C. These findings might explain the differential disease pathogenesis in males compared to females with MIS-C and facilitate a deeper understanding of this disease., (© 2024. The Author(s).)

Background: Multisystem inflammatory syndrome (MIS) in children is considered to be a post-infectious complication of COVID-19. T-cell responses in children with this condition have not been well-studied., Methods: We aimed to study the immune responses in children with MIS in comparison to children with acute COVID-19 and children with other infections. Whole blood was stimulated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific antigens and flow cytometry was performed to examine CD4 + and CD8 + T-cell responses., Results: Children with MIS had higher frequencies of CD4 + and CD8 + T cells expressing cytokines at baseline and upon SARS-CoV-2 antigen-specific stimulation in comparison to children with COVID-19 and/or other infections. Children with COVID-19 also exhibited higher frequencies of CD4 + and CD8 + T cells expressing cytokines at baseline and upon SARS-CoV-2 antigen-specific stimulation in comparison to children with other infections. At 6-9 months following treatment and recovery, this enhanced response against SARS-CoV-2 antigens was down modulated in children with MIS., Conclusion: Our study, therefore, provides evidence of enhanced activation of CD4 + and CD8 + T-cell responses in children with MIS and reversal following recovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Pavan Kumar, Abbas, Renji, Venkataraman, Nancy, Varadarjan, Selladurai, Sangaralingam, Selvam, Thimmaiah, Natarajan, Ramasamy, Hissar, Ranganathan, Nutman and Babu.)

Introduction: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases., Methods: To elucidate the role of MMPs in pathogenesis of pediatric COVID-19, we examined their plasma levels in MIS-C and acute COVID-19 children and compared them to convalescent COVID-19 and children with other common tropical diseases (with overlapping clinical manifestations)., Results: Children with MIS-C had elevated levels of MMPs ( P < 0.005 statistically significant) in comparison to acute COVID-19, other tropical diseases (Dengue fever, typhoid fever, and scrub typhus fever) and convalescent COVID-19 children. PCA and ROC analysis (sensitivity 84-100% and specificity 80-100%) showed that MMP-8, 12, 13 could help distinguish MIS-C from acute COVID-19 and other tropical diseases with high sensitivity and specificity. Among MIS-C children, elevated levels of MMPs were seen in children requiring intensive care unit admission as compared to children not needing intensive care. Similar findings were noted when children with severe/moderate COVID-19 were compared to children with mild COVID-19. Finally, MMP levels exhibited significant correlation with laboratory parameters, including lymphocyte counts, CRP, D-dimer, Ferritin and Sodium levels., Discussion: Our findings suggest that MMPs play a pivotal role in the pathogenesis of MIS-C and COVID-19 in children and may help distinguish MIS-C from other conditions with overlapping clinical presentation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pavan Kumar, Venkataraman, Varadarjan, Nancy, Rajamanickam, Selladurai, Sankaralingam, Thiruvengadam, Selvam, Thimmaiah, Natarajan, Ramaswamy, Putlibai, Sadasivam, Sundaram, Hissar, Ranganathan, Nutman and Babu.)

The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8+ T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4+ and CD8+ T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6-9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242., Competing Interests: The authors have declared that no competing interests exist.