| 1. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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Clinical characteristics and novel mutations of omicron subvariant XBB in Tamil Nadu, India - a cohort study
- 2023
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Ingår i: The Lancet Regional Health - Southeast Asia. - : ELSEVIER. - 2772-3682. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background Despite the continued vaccination efforts, there had been a surge in breakthrough infections, and the emergence of the B.1.1.529 omicron variant of SARS-CoV-2 in India. There is a paucity of information globally on the role of newer XBB variants in community transmission. Here, we investigated the mutational patterns among hospitalised patients infected with the XBB omicron sub-variant, and checked if there was any association between the rise in the number of COVID-19 cases and the observed novel mutations in Tamil Nadu, India. Methods Nasopharyngeal and oropharyngeal swabs, collected from symptomatic and asymptomatic COVID-19 patients were subjected to real-time PCR followed by Next Generation Sequencing (NGS) to rule out the ambiguity of mutations in viruses isolated from the patients (n = 98). Using the phylogenetic association, the mutational patterns were used to corroborate clinico-demographic characteristics and disease severity among the patients. Findings Overall, we identified 43 mutations in the S gene across 98 sequences, of which two were novel mutations (A27S and T747I) that have not been reported previously with XBB sub-variants in the available literature. Additionally, the XBB sequences from our cohort had more mutations than omicron B.1.1.529. The phylogenetic analysis comprising six major branches clearly showed convergent evolution of XBB. Our data suggests that age, and underlying conditions (e.g., diabetes, hypertension, and cardiovascular disease) or secondary complications confers increased susceptibility to infection rather than vaccination status or prior exposure. Many vaccinated individuals showed evidence of a breakthrough infection, with XBB.3 being the predominant variant identified in the study population. Interpretation Our study indicates that the XBB variant is highly evasive from available vaccines and may be more transmissible, and potentially could emerge as the 'next' predominant variant, which likely could overwhelm the existing variants of SARS-CoV-2 omicron variants.Funding National Health Mission (India), SIDA SARC, VINNMER (Sweden), ORIP/NIH (USA).Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 2. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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Evolution of the Omicron B.1.1.529 Sars-Cov-2 and its Variants in Tamil Nadu, India – a State-Wide Prospective Longitudinal Genomic Surveillance
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The emergence of the omicron SARS-CoV-2 variant beholding many mutations, especially in the spike (S) protein severely threatens global health. With an aim to understand the mutational pattern of the variant and its genetic interrelationship in the Indian population, here we prospectively followed the viral evolution and transmission between December 2021 and March 2023 in Tamil Nadu.Methods: A total of 11526 nasopharyngeal and oropharyngeal swabs (6431 males, 5095 females including 603 children) collected from across the 38 districts of Tamil Nadu were subjected to WGS. Of the 10663 samples (92.5%) positive for omicron variants, 1688 were sequenced at the State Public Health Laboratory. We longitudinally studied the evolutionary dynamics of the different omicron variants, starting from the first detected case (B.1.1.529) to the recently reported recombinant XBB variants by sequencing the S gene and by performing phylo-geographic and molecular modeling analyses.Findings: Administration of a booster dose was associated with reduced risk of hospitalization and death. BA.1 sub-variants and BA.2.75 were associated with increased risk of severe disease, whereas BA.1 and BA.2 were associated with increased risk of death. High quality WGS data from 150 samples revealed six major omicron clusters and several other sub-clusters. Seven variants in the same BA lineages with different divergences in the S protein were noticed. Of the 5009 mutations detected, the highest was seen in the receptor-binding domain (RBD) followed by the N-terminal domain (NTD) in varying proportions among the different omicron lineages. Importantly, the mutations were observed in the sub-domain (SD1/2) furin cleavage site, fusion peptide (FP), and the heptapeptide repeat sequence (HR1) regions. Notably, unique mutations Y473I, P479F, C480F, V483T, E484C, G485T, P491G, L492K, S494M, Y495C, and G496Q were detected in BA.2.43 whereas A475Q and T478S occurred in the RBD domain of the BA.2.43 variant. The XBB variant showed 41 different mutations between the HR1 and HR2 domains of the S2 subunit. Molecular modeling using BA.2 lineage as a template for seven divergent proteins showed that BA.2.12.1, BA.4 and BA.5 exhibited strong binding affinity towards ACE2.Interpretation: The high frequency of mutations in the RBD highlights the wider distribution of vaccine escape-variants that would impact the structural and functional attributes of the omicron variant in the population. Further, our work provides key insights on the evolutionary pattern leading to the identification of seven divergent variants of omicron in Tamil Nadu, India.
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| 3. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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Factors Associated With the Decay of Anti-SARS-CoV-2 S1 IgG Antibodies Among Recipients of an Adenoviral Vector-Based AZD1222 and a Whole-Virion Inactivated BBV152 Vaccine
- 2022
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe magnitude of protection conferred following recovery from COVID-19 or by vaccine administration, and the duration of protective immunity developed, remains ambiguous. MethodsWe investigated the factors associated with anti-SARS-CoV-2 S1 IgG decay in 519 individuals who recovered from COVID-19 illness or received COVID-19 vaccination with two commercial vaccines, viz., an adenoviral vector-based (AZD1222) and a whole-virion-based inactivated (BBV152) vaccine in Chennai, India from March to December 2021. Blood samples collected during regular follow-up post-infection/-vaccination were examined for anti-SARS-CoV-2 S1 IgG by a commercial automated chemiluminescent immunoassay (CLIA). ResultsAge and underlying comorbidities were the two variables that were independently associated with the development of a breakthrough infection. Individuals who were >60 years of age with underlying comorbid conditions (viz., hypertension, diabetes mellitus and cardiovascular disease) had a ~15 times and ~10 times greater odds for developing a breakthrough infection and hospitalization, respectively. The time elapsed since the first booster dose was associated with attrition in anti-SARS-CoV-2 IgG, where each month passed was associated with an ebb in the anti-SARS-CoV-2 IgG antibody levels by a coefficient of -6 units. ConclusionsOur findings advocate that the elderly with underlying comorbidities be administered with appropriate number of booster doses with AZD1222 and BBV152 against COVID-19.
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| 4. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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Genomic surveillance of omicron B.1.1.529 SARS‐CoV‐2 and its variants between December 2021 and March 2023 in Tamil Nadu, India—A state‐wide prospective longitudinal study
- 2024
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Ingår i: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 96:2
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Tidskriftsartikel (refereegranskat)abstract
- A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution.
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| 5. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and Omicron BA.1.1.529 but not with Omicron BA.1.1 and BA.2 variants
- 2022
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Ingår i: Frontiers In Public Health. - : Frontiers Media SA. - 2296-2565. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The rapid spread of SARS-CoV-2 variants in the global population is indicative of the development of selective advantages in emerging virus strains. Here, we performed a case-control investigation of the clinical and demographic characteristics, clinical history, and virological markers to predict disease progression in hospitalized adults for COVID-19 between December 2021 and January 2022 in Chennai, India. COVID-19 diagnosis was made by a commercial TaqPath COVID-19 RT-PCR, and WGS was performed with the Ion Torrent Next Generation Sequencing System. High-quality (<5% of N) complete sequences of 73 Omicron B.1.1.529 variants were randomly selected for phylogenetic analysis. SARS-CoV-2 viral load, number of comorbidities, and severe disease presentation were independently associated with a shorter time-to-death. Strikingly, this was observed among individuals infected with Omicron BA.2 but not among those with the BA.1.1.529, BA.1.1, or the Delta B.1.617.2 variants. Phylogenetic analysis revealed severe cases predominantly clustering under the BA.2 lineage. Sequence analyses showed 30 mutation sites in BA.1.1.529 and 33 in BA.1.1. The mutations unique to BA.2 were T19I, L24S, P25del, P26del, A27S, V213G, T376A, D405N and R408S. Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and the Omicron BA.1.1.529 variant but not with Omicron BA.1.1 or BA.2 suggests that the newer strains are largely immune escape variants. The number of vaccine doses received was independently associated with increased odds of developing asymptomatic disease or recovery. We propose that the novel mutations reported herein could likely bear a significant impact on the clinical characteristics, disease progression, and epidemiological aspects of COVID-19. Surging rates of mutations and the emergence of eclectic variants of SARS-CoV-2 appear to impact disease dynamics.
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| 6. |
- Selvavinayagam, Sivaprakasam T, et al.
(författare)
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Plasma CXCL8 and MCP-1 as biomarkers of latent tuberculosis infection
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundEarly detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy.Methods We investigated whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. We also measured the plasma cytokines using a commercial Bio-Plex Pro Human Cytokine 17-plex assay.ResultsIncreased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold.ConclusionsWe postulated that CXCL8 and MCP-1 could be the surrogate biomarkers of LTBI, especially in resource-limited settings.
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| 7. |
- Selvavinayagam, Sivaprakasam T, et al.
(författare)
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Plasma CXCL8 and MCP-1 as surrogate plasma biomarkers of latent tuberculosis infection among household contacts-A cross-sectional study
- 2023
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Ingår i: PLOS Global Public Health. - : Public Library of Science (PLoS). - 2767-3375. ; 3:11
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Tidskriftsartikel (refereegranskat)abstract
- Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy. The study investigates whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. The plasma cytokines were measured using a commercial Bio-Plex Pro Human Cytokine 17-plex assay. Increased plasma CXCL8 and decreased MCP-1, TNF-a, and IFN-? were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold. Our study suggests that CXCL-8 and MCP-1 could serve as the surrogate biomarkers of LTBI, particularly in resource-limited settings. Further laboratory investigations are warranted before extrapolating CXCL8 and MCP-1 for their usefulness as surrogate biomarkers of LTBI in resource-limited settings.
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| 8. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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Platelet-Large Cell Ratio and Erythrocyte Sedimentation Rate are Surrogate Predictors of Latent Tuberculosis Infection
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Aims: Prompt detection and treatment of latent tuberculosis infection (LTBI) holds the key to global TB elimination. The lack of an established test for predicting LTBI poses a substantial challenge in disease management. Here, we identified the biochemical and hematological markers of LTBI, and correlated their usefulness to discriminate LTBI from healthy controls. Main Methods: We conducted a cross-sectional investigation and correlated the various biochemical and hematological markers for detecting LTBI among household contacts (HHCs) of TB infection. Our study included 90 individuals – 30 healthy controls, 30 interferon-gamma release assay (IGRA) positive HHCs, and 30 IGRA-negative HHCs. Biomarkers were measured using designated auto analyzers. Key Findings: ESR, MPV, D-dimer, P-LCR, and PDW were significantly higher among LTBI subjects. ESR, PDW, and P-LCR were markedly associated with LTBI. Multivariate analysis showed that either ESR or P-LCR greater than their respective predetermined cut-off values showed higher odds of developing LTBI. Our study demonstrated that ESR and P-LCR are good surrogate markers for diagnosing LTBI. Also, significantly low ferritin in females and MCHC in males belonging to the HHC/IGRA-ve were observed. Significance: The ESR and P-LCR could aid in predicting LTBI among HHCs. Further, the low serum ferritin is associated with TB resisters.
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