The after-effects of COVID-19 on academia and scientific community: Researchers perspective

The commotion pandemic has caused has affected almost every aspect of the academic community. Distancing and issues related to the risk of spread have caused researchers to stop most of their most non-COVID clinical trials and experiments, causing a reduction in recruitment of research associates and a lag in data entry into clinical trial databases. Fresh graduates and research scholars who have not yet begun their doctoral research or postdoctoral fellowship are among the most who will endure the consequences. Few valuable crowdfunding options have surfaced to help fund effective scientific research that may otherwise not receive financial support. The institutes affected by the COVID-19 pandemic can seek extra financial aid to cover expenditures that arise from projects being delayed or derailed. The research community should raise awareness of the challenges faced by universities and researchers worldwide and clearly explain the need for action to prevent or limit any further unfavorable consequences.

Immunological alterations in tuberculosis associated immune reconstitution inflammatory syndrome in HIV infected patients

The tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) frequently complicates the course of HIV/AIDS and HIV-TB treatment and its immunological mechanisms are poorly understood. Here, we investigated T-cells frequencies, their secreted chemokines and cytokines. In this prospective case-control study, HIV/AIDS and HIV-TB patients during treatment with highly active antiretroviral treatment (HAART) and anti-TB treatment were followed for TB-IRIS development. Age, gender and BMI-matched patients without IRIS constituted as “Controls” (non-IRIS). Activation and proliferation were assessed in CD4 and CD8 cell compartments. CCR4, CCR6 and T-reg cells were also analysed in PBMCs. Cytokines (IL-2, IL-4, IL-10, IFN-γ and TGF-β1) and chemokines (IP-10, MCP-1, MIG and RANTES) were measured in culture supernatants. Of 560 enrolled HIV/AIDS patients, TB-IRIS developed in 50 (8.9%) patients (25-paradoxical and 25-unmasking) at a median interval of 35-days (IQR, 24-78). After ART therapy, CD8+ T-cell proportion decreased in both paradoxical and unmasking-TB-IRIS as compared to non-IRIS. Simultaneously, activation of CD4+ T-cells was observed in unmasking TB-IRIS only. Similarly, CD161+ T-cells, Th17-cells and inflammatory cytokines like IFN-γ, IP-10 and MIG elevated in both TB-IRIS subgroups as compared to non-IRIS.In conclusion, during HAART treatment the dominance of pro-inflammatory cells and cytokines in TB-IRIS patients favours the development of IRIS event. On the other hand, in non-IRIS patients relative increase of anti-inflammatory cells and cytokines prevents the development of IRIS event.

Ophthalmic manifestations of acute and chronic leukemias presenting to a tertiary care center in India.

Context: Screening for ocular manifestations of leukemia, although not a routine practice, is important as they may antedate systemic disease or form an isolated focus of its relapse. Aims: This study evaluates the spectrum of ocular manifestations in acute and chronic leukemias presenting to a tertiary care center in India. Settings and Design: Subjects of leukemia presenting to a tertiary care center in India. Subjects and Methods: A prospective, cross‑sectional study looking at the spectrum of ocular manifestations in all inpatients of acute or chronic leukemia. Statistical Analysis Used: The collected data were analyzed using the Statistical Package for Social Sciences for Windows software, version 16 (SPSS Inc., Chicago, Illinois, USA). Results: The study subjects (n = 96) comprised 61 males and 35 females whose age ranged from 18 months to 91 years (mean = 39.73, ±22.1). There were 79 adults and 17 children, 53 new and 43 existing patients, 68 acute and 28 chronic, 61 myeloid and 35 lymphoid patients. Ocular lesions were found in 42 patients (43.8%). The ocular manifestations of leukemia were significantly (P = 0.01467) more frequent in acute 35/68 (51.9%) than chronic 7/28 (25%) leukemias. Primary or direct leukemic infiltration was seen in 8 (8.3%) subjects while secondary or indirect involvement due to anemia, thrombocytopenia, hyperviscosity, total body irradiation, and immunosuppression were seen in 42 (43.8%) subjects. Ocular changes were present in 37/79 (46.8%) adults and 5/17 (29.4%) children (P = 0.09460). Twenty‑eight males (28/61) 45.9% and 14/35 (40%) females had ocular manifestations (P = 0.2874). The ocular manifestations were significantly (P = 0.01158) more frequent in myeloid leukemias 32/61 (52.9%) than lymphoid leukemias 10/35 (28.6%). Conclusions: Leukemic ophthalmic lesions were found in 42/96 (43.8%) patients. Ocular involvement is more often seen in adults, acute and myeloid leukemias. All the primary leukemic manifestations were seen in males. A periodic ophthalmic examination should be mandatory for all leukemic patients, as ocular changes are often picked up in asymptomatic patients.

Genomic architecture of HIV-1 infection: Current status & challenges.

Studies on host genomics have revealed the existence of identifiable HIV-1 specific protective factors among infected individuals who remain naturally resistant viraemia controllers with little or no evidence of virus replication. These factors are broadly grouped into those that are immune associated (MHC, chemokines, cytokines, CTLs and others), linked to viral entry (chemokine co-receptors and ligands), act as post-entry restriction elements (TRIM5a, APOBEC3) and those associated with viral replication (cytokines and others). These features have been identified through multiple experimental approaches ranging from candidate gene approaches, genome wide association studies (GWAS), expression analysis in conjunction with functional assays in humans to primate based models. Several studies have highlighted the individual and population level gross differences both in the viral clade sequences as well as host determined genetic associations. This review collates current information on studies involving major histocompatibility complex (MHC) as well as non MHC genes in the context of HIV-1 infection and AIDS involving varied ethnic groups. Special focus of the review is on the genetic studies carried out on the Indian population. Further challenges with regard to therapeutic interventions based on current knowledge have been discussed along with discussion on documented cases of stem cell therapy and very early highly active antiretroviral therapy (HAART) interventions.

Evident stabilization of the clinical profile in HIV/AIDS as evaluated in an open label clinical trial using a polyherbal formulation.

Background & objectives: The complementary and alternative medicines (CAM) have not been systematically evaluated for the management of HIV/AIDS patients. In a prospective, single-site, open-label, non-randomized, controlled, pilot trial, we evaluated a polyherbal formulation (PHF) for its safety and efficacy in treating subjects with HIV-AIDS. Methods: A total of 32 and 31 subjects were enrolled under the PHF and highly active antiretroviral treatment (HAART) arms, respectively, and followed up for a period of 24 months. Plasma viral RNA, CD4 cell count and blood chemistry were monitored at 3-month intervals. Following mid-term safety evaluation, 12 subjects from the PHF arm were shifted to HAART and were followed separately as PHF-to-HAART arm, for the rest of the period. Results: The HAART arm was characterized by significant improvements in CD4 cell count (154.4 cells/μl/year, P<0.001) and reduction in plasma viral load within 3 to 6 months (-0.431+ 0.004 log10 IU/month, P<0.001). In contrast, the PHF arm showed a profile of CD4 cell loss at remarkably slower kinetics (14.3 cells/μl/year, P=0.021) and insignificant reduction in the viral load. The PHF and HAART arms did not differ significantly in the occurrence of AIDS-related illnesses over the study period of 24 months. In the PHF-to-HAART arm, the rates of CD4 count and reduction in viral load were significant and comparable to that of the HAART group. In the PHF arm, at 1 month, a significant increase in CD4 cell count and a concomitant decrease in viral load were seen. Interpretation & conclusions: The PHF appears to have provided protection by delaying the kinetics of CD4 cell reduction. Given the several study limitations, drawing assertive inferences from the data is challenging. Future studies with a stringent study design are warranted to confirm these findings.

Genetic correlates influencing immunopathogenesis of HIV infection.

Variability to HIV infection, its progression as well as responsiveness to antiretroviral therapy (ART) is observed among individuals including viraemia controllers or exposed uninfected, rapid versus slow progressors and ART responders compared to non responders. This differential responsiveness/ vulnerability to HIV-1 is governed by multiple host genetic factors that include HLA, cytokines, chemokines, their receptors and others. This review highlights the influence of these genetic factors on HIV/AIDS outcome; however, in India, the information in this area is very limited and most of these genetic studies have been conducted in Caucasian and South African populations. Considering, the population specific differences in the frequencies of protective or susceptibility favouring alleles and their influence on the disease outcome, it is of utmost importance to strengthen ongoing efforts towards defining largely unknown genetic propensity in Indian population, particularly by recruitment of large cohorts of well categorized exposed uninfected individuals, rapid, long term non progressors and elite viraemic controllers. Multi-parametric analysis of these potentially interactive immunogenetic variables in these cohorts may help to define potential targets for diagnostics and therapy in a population specific manner.

Biomarkers of susceptibility to type 1 diabetes with special reference to the Indian population.

Type 1 diabetes (T1D) is a polygenic autoimmune disease. Susceptibility to T1D is strongly linked to a major genetic locus that is the major histocompatibility complex (MHC) and several other minor loci including insulin, CTLA4 that contribute to diabetes risk in an epistatic way. MHC harbours genes whose primary function is to govern immune responsiveness. Being the most polymorphic genomic region known in humans, MHC serves as a very exciting minigenome model for studying susceptibility to T1D. We have observed enormous diversity in HLA class I and class II genes in the north Indian population and identified several 'novel alleles' and 'unique haplotypes'. For example, multiple DR3+ve autoimmunity favouring haplotypes have been identified, some of which are unique to the Asian north Indian T1D patients. Our molecular studies have revealed that (i) the classical Caucasian autoimmunity favouring AH8.1 (HLA-A1 B8 DR3) is rare in the Indian population and has been replaced by a variant AH8.1v that differs from the Caucasian AH8.1 at several gene loci, (ii) AH8.2 (HLA-A26 B8 DR3) is the most common DR3 positive haplotype in this population and resembles the Indian AH8.1v rather than Caucasian AH8.1, and (iii) there are additional HLA-DR3 haplotypes HLA-A24 B8 DR3 (AH8.3), A3 B8 DR3 (AH8.4) and A31 B8 DR 3 (AH 8.5) that occur in the Indian population. The studies have led to a hypothesis that AH8.1 and AH8.1v might have co-evolved from a common ancestor but preferential divergence of AH8.2 over AH8.1 leading to survival advantage might have been driven by vigorous pathogenic challenges encountered by the Indian population. These studies have important implications in our understanding of disease pathogenesis, identification of high risk individuals, disease diagnosis, disease management and immunological therapeutic approaches.

Distribution of C282Y and H63D mutations in the HFE gene in healthy Asian Indians and patients with thalassaemia major.

BACKGROUND: Mutations in the HFE gene have been shown to be strongly associated with hereditary haemochromatosis, an autosomal recessive disease of iron overloading. The majority of patients with hereditary haemochromatosis possess a homozygous mutation C282Y that disrupts the binding of the HFE gene with beta2 microglobulin and prevents its surface expression. Another HFE mutation H63D is known to increase the relative risk of developing hereditary haemochromatosis. This disease is rare in India although secondary haemochromatosis is commonly seen among children suffering from thalassaemia major. The status of HFE mutations has not been explored among Indians, particularly in patients with thalassaemia major. It is also possible that in India clinical haemochromatosis could be masked by iron deficiency. METHODS: We examined a cohort of 59 unrelated, healthy individuals from north India, 57 from south India and 75 thalassaemia major patients from north India for HFE mutations (C282Y and H63D) in cis/trans by the polymerase chain reaction sequence-specific primer method. RESULTS: The C282Y and H63D mutations in the HFE gene were rare among Indians. Although the HFE mutations were increased among patients of thalassaemia their effect on iron burden or disease pathogenesis remains unclear. CONCLUSIONS: Hereditary haemochromatosis is rarely observed among Indians and so are the C282Y and H63D mutations in the HFE gene. Long-term follow up studies would be required to determine whether the relatively higher frequency of these mutations among patients of thalassaemia has any influence on iron accumulation.