Peripheral lymphocyte subset alteration in patients with COVID-19 having differential clinical manifestations

Background & objectives: The COVID-19 disease profile in Indian patients has been found to be different from the Western world. Changes in lymphocyte compartment have been correlated with disease course, illness severity and clinical outcome. This study was aimed to assess the peripheral lymphocyte phenotype and subset distribution in patients with COVID-19 disease from India with differential clinical manifestations. Methods: Percentages of peripheral lymphocyte subsets were measured by flow cytometry in hospitalized asymptomatic (n=53), mild symptomatic (n=36), moderate and severe (n=30) patients with SARS-CoV-2 infection, recovered individuals (n=40) and uninfected controls (n=56) from Pune, Maharashtra, India. Results: Percentages of CD4+Th cells were significantly high in asymptomatic, mild symptomatic, moderate and severe patients and recovered individuals compared to controls. Percentages of Th memory (CD3+CD4+CD45RO+), Tc memory (CD3+CD8+CD45RO+) and B memory (CD19+CD27+) cells were significantly higher in the recovered group compared to both asymptomatic, mild symptomatic patient and uninfected control groups. NK cell (CD56+CD3-) percentages were comparable among moderate +severe patient and uninfected control groups. Interpretation & conclusions: The observed lower CD4+Th cells in moderate+severe group requiring oxygen support compared to asymptomatic+mild symptomatic group not requiring oxygen support could be indicative of poor prognosis. Higher Th memory, Tc memory and B memory cells in the recovered group compared to mild symptomatic patient groups might be markers of recovery from mild infection; however, it remains to be established if the persistence of any of these cells could be considered as a correlate of protection.

Envelope specific T cell responses & cytokine profiles in chikungunya patients hospitalized with different clinical presentations.

Background & objectives: Since the 2006 massive outbreaks, chikungunya (CHIK) is a major public health concern in India. The aim of this study was to assess envelope specific immune responses in patients with chikungunya infection. Methods: This study included 46 hospitalized patients with chikungunya virus infection (encephalitis, n=22, other systemic involvement, OSI, n=12, classical, n=12) and six controls from Ahmedabad city, Gujarat, India. T cell responses and the levels of Th1, pro/ anti-inflammatory cytokines against the CHIK virus envelope antigens were assessed by lymphocyte proliferation assay and by cytometric bead array in flow cytometry, respectively. Results: Lymphoproliferative response was uniform among the patients. Comparisons of cytokines revealed significantly higher levels of interleukin (IL)-4 and IL-5 in encephalitis, OSI and classical patients versus controls. The levels of tumour necrosis factor (TNF)-α were higher in classical patients categories compared to the controls. Interferon (IFN)-γ levels were lower in encephalitis patients versus control. Interpretation & conclusions: Our findings showed recognition of T cell epitopes on the envelope region of chikungunya virus by all patient categories. Lower level of IFN-γ may be associated with the severity of disease in these patients.

Association of HLA alleles with hepatitis C infection in Maharashtra, western India.

Background & objectives: Host genetic diversity is believed to contribute to the spectrum of clinical outcomes in hepatitis C virus (HCV) infection. The present study aimed at finding out the frequencies of HLA class I and class II alleles of HCV infected individuals from western India. Methods: Forty three clinically characterized anti-HCV positive patients from Maharashtra were studied for HLA A, B, C, DRB1 and DQB1 alleles by PCR- sequence specific primer (SSP) typing method and compared with 67 and 113 ethnically matched, anti-HCV negative healthy controls from western India. Results: Our analysis revealed an association of HLA alleles HLA A*03 (OR= 16.69, EF, 0.44, P=7.9E-12), A*32 (OR= 1474, EF 0.21, P=1.8E-9), HLA B*15 (OR=14.11, EF 0.39, P=2.18E-10), B*55 (OR= 12.09, EF 0.07, P=0.005), Cw*16 (OR= 7.45, EF 0.12, P=0.001), Cw*18 (OR= 402, EF 0.05, P=0.003), DRB1*03 (OR= 4.01, EF 0.08, P=0.01) and DQB1*03 (OR= 3.02, EF 0.22, P=0.001), with HCV infection. HLA II locus haplotype DRB1*11-DQB1*03 (HF=17.64, OR=5.16, P=0.0001) was significantly increased among HCV infected individuals. Interpretation & conclusions: Our data suggest that among the western Indian population, certain HLA alleles or associated haplotype influence HCV infection as a host genetic factor.