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  1. Rothan HA, Bidokhti MRM, Byrareddy SN
    J Autoimmun, 2018 05;89:11-20.
    PMID: 29352633 DOI: 10.1016/j.jaut.2018.01.002
    Dissemination of vector-borne viruses, such as Zika virus (ZIKV), in tropical and sub-tropical regions has a complicated impact on the immunopathogenesis of other endemic viruses such as dengue virus (DENV), chikungunya virus (CHIKV) and human immunodeficiency virus (HIV). The consequences of the possible co-infections with these viruses have specifically shown significant impact on the treatment and vaccination strategies. ZIKV is a mosquito-borne flavivirus from African and Asian lineages that causes neurological complications in infected humans. Many of DENV and CHIKV endemic regions have been experiencing outbreaks of ZIKV infection. Intriguingly, the mosquitoes, Aedes Aegypti and Aedes Albopictus, can simultaneously transmit all the combinations of ZIKV, DENV, and CHIKV to the humans. The co-circulation of these viruses leads to a complicated immune response due to the pre-existence or co-existence of ZIKV infection with DENV and CHIKV infections. The non-vector transmission of ZIKV, especially, via sexual intercourse and placenta represents an additional burden that may hander the treatment strategies of other sexually transmitted diseases such as HIV. Collectively, ZIKV co-circulation and co-infection with other viruses have inevitable impact on the host immune response, diagnosis techniques, and vaccine development strategies for the control of these co-infections.
  2. Selvavinayagam ST, Sankar S, Yong YK, Murugesan A, Suvaithenamudhan S, Hemashree K, et al.
    Sci Rep, 2024 Jul 30;14(1):17476.
    PMID: 39080396 DOI: 10.1038/s41598-024-68678-z
    In December 2023, we observed a notable shift in the COVID-19 landscape, when JN.1 omicron emerged as the predominant SARS-CoV-2 variant with a 95% incidence. We characterized the clinical profile, and genetic changes in JN.1, an emerging SARS-CoV-2 variant of interest. Whole genome sequencing was performed on SARS-CoV-2 positive clinical specimens, followed by sequence analysis. Mutations within the spike protein sequences were analysed and compared with the previously reported lineages and sub-lineages, to identify the potential impact of the unique mutations on protein structure and possible alterations in the functionality. Several unique and dynamic mutations were identified herein. Molecular docking analysis showed changes in the binding affinity, and key interacting residues of wild-type and mutated structures with key host cell receptors of SARS-CoV-2 entry viz., ACE2, CD147, CD209L and AXL. Our data provides key insights on the emergence of newer variants and highlights the necessity for robust and sustained global genomic surveillance of SARS-CoV-2.
  3. Selvavinayagam ST, Aswathy B, Yong YK, Frederick A, Murali L, Kalaivani V, et al.
    PLOS Glob Public Health, 2023;3(11):e0002327.
    PMID: 37992019 DOI: 10.1371/journal.pgph.0002327
    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-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. 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.
  4. Selvavinayagam ST, Karishma SJ, Hemashree K, Yong YK, Suvaithenamudhan S, Rajeshkumar M, et al.
    PMID: 38076717 DOI: 10.1016/j.lansea.2023.100272
    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), SIDASARC, VINNMER (Sweden), ORIP/NIH (USA).

  5. Selvavinayagam ST, Suvaithenamudhan S, Yong YK, Hemashree K, Rajeshkumar M, Kumaresan A, et al.
    J Med Virol, 2024 Feb;96(2):e29456.
    PMID: 38329187 DOI: 10.1002/jmv.29456
    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.
  6. Selvavinayagam ST, Sankar S, Yong YK, Anshad AR, Chandramathi S, Somasundaram A, et al.
    PLOS Glob Public Health, 2024;4(11):e0003608.
    PMID: 39570962 DOI: 10.1371/journal.pgph.0003608
    The decline in dengue incidence and/or prevalence during the COVID-19 pandemic (2020-22) appears to be attributed to reduced treatment-seeking rates, under-reporting, misdiagnosis, disrupted health services and reduced exposure to mosquito vectors due to prevailing lockdowns. There is limited scientific data on dengue virus (DENV) disease during the COVID-19 pandemic. Here, we conducted a community-based, cross-sectional, cluster-randomized survey to assess anti-DENV and anti-SARS-CoV-2 seroprevalence, and also estimated the spatial distribution of DENV-positive aedine mosquito vectors during the COVID-19 pandemic across all the 38 districts of Tamil Nadu, India. Using real-time PCR, the prevalence of DENV in mosquito pools during 2021 was analyzed and compared with the previous and following years of vector surveillance, and correlated with anti-DENV IgM and IgG levels in the population. Results implicate that both anti-DENV IgM and IgG seroprevalence and DENV positivity in mosquito pools were reduced across all the districts. A total of 13464 mosquito pools and 5577 human serum samples from 186 clusters were collected. Of these, 3.76% of the mosquito pools were positive for DENV. In the human sera, 4.12% were positive for anti-DENV IgM and 6.4% for anti-DENV IgG. While the anti-SARS-CoV-2 levels significantly correlated with overall DENV seropositivity, COVID-19 vaccination status significantly correlated with anti-DENV IgM levels. The study indicates a profound impact of anti-SARS-CoV-2 levels on DENV-positive mosquito pools and seropositivity. Continuous monitoring of anti-DENV antibody levels, especially with the evolving variants of SARS-CoV-2 and the surge in COVID-19 cases will shed light on the distribution, transmission and therapeutic attributes of DENV infection.
  7. Selvavinayagam ST, Aswathy B, Yong YK, Frederick A, Murali L, Kalaivani V, et al.
    medRxiv, 2023 Aug 09.
    PMID: 37609153 DOI: 10.1101/2023.08.07.23293767
    BACKGROUND: Early 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.

    RESULTS: Increased 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.

    CONCLUSIONS: We postulated that CXCL8 and MCP-1 could be the surrogate biomarkers of LTBI, especially in resource-limited settings.

  8. Selvavinayagam ST, Sankar S, Yong YK, Murugesan A, Suvaithenamudhan S, Hemashree K, et al.
    medRxiv, 2024 Apr 19.
    PMID: 38699322 DOI: 10.1101/2024.04.16.24305882
    In December 2023, we observed a notable shift in the COVID-19 landscape, when the JN.1 emerged as a predominant SARS-CoV-2 variant with a 95% incidence. We characterized the clinical profile, and genetic changes in JN.1, an emerging SARS-CoV-2 variant of interest. Whole genome sequencing was performed on SARS-CoV-2 positive samples, followed by sequence analysis. Mutations within the spike protein sequences were analyzed and compared with the previous lineages and sublineages of SARS-CoV-2, to identify the potential impact of these unique mutations on protein structure and possible functionality. Several unique and dynamic mutations were identified herein. Our data provides key insights into the emergence of newer variants of SARS-CoV-2 in our region and highlights the need for robust and sustained genomic surveillance of SARS-CoV-2.
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