Emergence of SARS-CoV-2 Omicron Variant JN.1 in Tamil Nadu, India - Clinical Characteristics and Novel Mutations.

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.

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.

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.

Clinical characteristics and novel mutations of omicron subvariant XBB in Tamil Nadu, India - a cohort study.

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).

Plasma CXCL8 and MCP-1 as surrogate plasma biomarkers of latent tuberculosis infection among household contacts-A cross-sectional study.

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.

Depolarized Mitochondrial Membrane Potential and Elevated Calcium in Platelets of Sickle Cell Disease.

Hemolysis, a crucial feature of Sickle cell disease (SCD), is a key player for cellular activation leading to various complications including thrombosis. In response to hemolysis, platelets get activated and release components that are necessary for further platelet activation and aggregation. Thus, it is believed that platelets contribute to the development of thrombotic complications. Platelets in SCD are expected to be affected due to common cause of hemolysis. To measure the surface markers of platelets including P-Selectin, Phosphatidyl Serine and integrin αIIbß3 in SCD patients and healthy controls in order to understand the status of the platelets in SCD. To measure the surface markers of activated platelets using flow cytometry. Since mitochondria and calcium play an important role in cellular functions, the mitochondrial membrane potential and calcium content of platelets in SCD were also evaluated using flow cytometry. In the present study, we have observed significant increase of calcium level in SCD platelets. Further, the loss of mitochondrial membrane potential in SCD platelets was found to be significantly higher when compared to platelets of healthy controls. Though the surface markers of activated platelets in SCD remain unchanged, increased level of calcium and mitochondrial membrane potential loss suggest that the platelets in SCD are more prone to become activated. In order to understand the status of the platelets in SCD, apart from the surface markers, it is also important to assess the calcium levels and mitochondrial membrane potential of platelets.

Plasma CXCL8 and MCP-1 as biomarkers of latent tuberculosis infection.

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.

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.

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.

TFPI and FXIII negatively and S100A8/A9 and Cystatin C positively correlate with D-dimer in COVID-19.

D-dimer is an established biomarker of thromboembolism and severity in COVID-19. We and others have recently reported the dysregulation of tissue factor pathway inhibitor (TFPI), FXIII, fibrinolytic pathway, inflammatory markers, and tissue injury markers, particularly in severe COVID-19. However, association of these markers with thromboembolism in COVID-19 remains elusive. The correlation analyses between these markers in patients with moderate (non-ICU) and severe COVID-19 (ICU) were performed to delineate the potential pathomechanisms and impact of thromboembolism. We observe a negative correlation of plasma TFPI (r2 = 0.148, P = 0.035), FXIII (r2 = 0.242, P = 0.006), and plasminogen (r2 = 0.27, P = 0.003) with D-dimer, a biomarker of thromboembolism, levels in these patients. Further analysis revealed a strong positive correlation between fibrinolytic markers tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) (r2 = 0.584, P < 0.0001). Interestingly, a significant positive correlation of PAI-1, but not tPA, was observed with platelets and endothelial cells dysfunction markers P-selectin (r2 = 0.184, P = 0.01) and soluble CD40 ligand (sCD40 L) (r2 = 0.163, P = 0.02). Moreover, calprotectin (S100A8/A9) and cystatin C (CST3), previously linked with thromboembolism, exhibited positive correlations with each other (r2 = 0.339, P = 0.0007) and with the level of D-dimer independently in COVID-19. Finally, the tissue injury marker myoglobin demonstrated a strong positive correlation with D-dimer (r2 = 0.408, P = 0.0001). Taken together, inverse correlations of TFPI and FXIII with D-dimer suggest the TF pathway activation and aberrant fibrin polymerization in COVID-19 patients. The elevated level of PAI-1 is potentially contributed by activated platelets and endothelial cells. S100A8/A9 may also play roles in impaired fibrinolysis and thromboembolism, in part, through regulating the CST3. These findings strengthen the understanding of thromboembolism and tissue injury and may help in better management of thromboembolic complications in COVID-19 patients.

SARS-CoV-2 infection- induced growth factors play differential roles in COVID-19 pathogenesis.

AIMS: Biologically active molecules cytokines and growth factors (GFs) are critical regulators of tissue injury/repair and emerge as key players in COVID-19 pathophysiology. However, specific disease stage of GFs dysregulation and, whether these GFs have associations with thromboembolism and tissue injury/repair in COVID-19 remain vague. MAIN METHODS: GF profiling in hospitalized moderate (non-ICU) and critically ill (ICU) COVID-19 patients was performed through legendPlex assay. KEY FINDINGS: Investigation revealed profound elevation of VEGF, PDGFs, EGF, TGF-α, FGF-basic, and erythropoietin (EPO) in moderate cases and decline or trend of decline with disease advancement. We found strong positive correlations of plasma VEGF, PDGFs, and EPO with endothelial dysfunction markers P-selectin and sCD40L. Interestingly, the HGF and G-CSF were upregulated at the moderate stage and remained elevated at the severe stage of COVID-19. Moreover, strong negative correlations of PDGFs (r2 = 0.238, P = 0.006), EPO (r2 = 0.18, P = 0.01) and EGF (r2 = 0.172, P = 0.02) and positive correlation of angiopoietin-2 (r2 = 0.267, P = 0.003) with D-dimer, a marker of thromboembolism, was observed. Further, plasma PDGFs (r2 = 0.199, P = 0.01), EPO (r2 = 0.115, P = 0.02), and EGF (r2 = 0.108, P = 0.07) exhibited negative correlations with tissue injury marker, myoglobin. SIGNIFICANCE: Taken together, unlike cytokines, most of the assessed GFs were upregulated at the moderate stage of COVID-19. The induction of GFs likely occurs due to endothelial dysfunction and may counter the adverse effects of cytokine storms which is reflected by inverse correlations of PDGFs, EPO, and EGF with thromboembolism and tissue injury markers. The findings suggest that the assessed GFs play differential roles in the pathogenesis of COVID-19.

Lipocalin-2, S100A8/A9, and cystatin C: Potential predictive biomarkers of cardiovascular complications in COVID-19.

Severe coronavirus (SARS-COV-2) infection often leads to systemic inflammation accompanied by cardiovascular complications including venous thromboembolism (VTE). However, it is largely undefined if inflammatory markers such as lipocalin-2 (LNC2), calprotectin (S100A8/A9), and cystatin C (CST3), previously linked with VTE, play roles in cardiovascular complications and advancement of COVID-19 severity. To investigate the same, hospitalized moderate and severe (presented pneumonia and required intensive care) COVID-19 patients were recruited. The levels of plasma LNC2, S100A8/A9, CST3, myoglobin, and cardiac Troponin I (cTnI) were assessed through enzyme-linked immunosorbent assay (ELISA). The investigation revealed a significantly upregulated level of plasma LNC2 at the moderate stage of SARS-CoV-2 infection. In contrast, the levels of S100A8/A9 and CST3 in moderate patients were comparable to healthy controls; however, a profound induction was observed only in severe COVID-19 patients. The tissue injury marker myoglobin was unchanged in moderate patients; however, a significantly elevated level was observed in the critically ill COVID-19 patients. In contrast, cTnI level was unchanged both in moderate and severe patients. Analysis revealed a positive correlation between the levels of S100A8/A9 and CST3 with myoglobin in COVID-19. In silico analysis predicted interactions of S100A8/A9 with toll-like receptor 4 (TLR-4), MyD88 LY96, and LCN2 with several other inflammatory mediators including MMP2, MMP9, TIMP1, and interleukins (IL-6, IL-17A, and IL-10). In summary, early induction of LCN2 likely plays a role in advancing the COVID-19 severity. A positive correlation of S100A8/A9 and CST3 with myoglobin suggests that these proteins may serve as predictive biomarkers for thromboembolism and tissue injury in COVID-19.

SARS-CoV-2 infection induces soluble platelet activation markers and PAI-1 in the early moderate stage of COVID-19.

INTRODUCTION: Coagulation dysfunction and thromboembolism emerge as strong comorbidity factors in severe COVID-19. However, it is unclear when particularly platelet activation markers and coagulation factors dysregulated during the pathogenesis of COVID-19. Here, we sought to assess the levels of coagulation and platelet activation markers at moderate and severe stages of COVID-19 to understand the pathogenesis. METHODS: To understand this, hospitalized COVID-19 patients with (severe cases that required intensive care) or without pneumonia (moderate cases) were recruited. Phenotypic and molecular characterizations were performed employing basic coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT), D-Dimer, and tissue factor pathway inhibitor (TFPI). The flow cytometry-based multiplex assays were performed to assess FXI, anti-thrombin, prothrombin, fibrinogen, FXIII, P-selectin, sCD40L, plasminogen, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and D-Dimer. RESULTS: The investigations revealed induction of plasma P-selectin and CD40 ligand (sCD40L) in moderate COVID-19 cases, which were significantly abolished with the progression of COVID-19 severity. Moreover, a profound reduction in plasma tissue factor pathway inhibitor (TFPI) and FXIII were identified particularly in the severe COVID-19. Further analysis revealed fibrinogen induction in both moderate and severe patients. Interestingly, an elevated PAI-1 more prominently in moderate, and tPA particularly in severe COVID-19 cases were observed. Particularly, the levels of fibrinogen and tPA directly correlated with the severity of the disease. CONCLUSIONS: In summary, induction of soluble P-selectin, sCD40L, fibrinogen, and PAI-1 suggests the activation of platelets and coagulation system at the moderate stage before COVID-19 patients require intensive care. These findings would help in designing better thromboprophylaxis to limit the COVID-19 severity.

Association of VEGF and p53 Polymorphisms and Spiral Artery Remodeling in Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis.

Many studies have reported the association of VEGF-1154G/A, VEGF 936C/T, and p53 Arg72Pro polymorphisms with recurrent pregnancy loss (RPL), but the outcomes are inconsistent. We have used a meta-analysis to associate these polymorphisms with RPL, having the spiral artery remodeling as a major risk factor. The studies were identified from three different reputed databases, namely ScienceDirect, PubMed/Medline, and Scopus. The eligible studies of VEGF-1154G/A, VEGF 936C/T, and p53Arg72Pro polymorphisms associated with the RPL were selected for the analysis. They were segregated into three different ethnic groups as Asians, Caucasians, and mixed population. For the analysis, the overall prevalence, odds ratio, risk ratio, relative risk ratio, and p-values were calculated. A total of 3,241 RPL cases and 3,205 healthy controls from 21 different case-control studies were analyzed. RPL was highly prevalent in the mixed population with VEGF-1154G/A and p53 Arg72Pro polymorphisms (70.04 and 66.46%, respectively) and in the Asian population with VEGF 936C/T polymorphism (53.58%). The homozygous recessive genotypes of VEGF and p53 exhibited significant association between the respective polymorphisms and RPL along with the increased risk of outcome. The current analysis conclusively reports the geographic distribution of the different genetic polymorphisms which shows high association with the progression of RPL. Understanding the spectrum of polymorphisms on different populations with the spiral artery remodeling as a risk factor encloses the importance of the vasculature during the pregnancy.

Role of SARS-CoV-2 -induced cytokines and growth factors in coagulopathy and thromboembolism.

Severe COVID-19 patients frequently present thrombotic complications which commonly lead to multiorgan failure and increase the risk of death. Severe SARS-CoV-2 infection induces the cytokine storm and is often associated with coagulation dysfunction. D-dimer, a hallmark of venous thromboembolism (VTE), is observed at a higher level in the majority of hospitalized COVID-19 patients. The precise molecular mechanism of the disproportionate effect of SARS-CoV-2 infection on the coagulation system is largely undefined. SARS-CoV-2 -induced endotheliopathy and, induction of cytokines and growth factors (GFs) most likely play important roles in platelet activation, coagulopathy, and VTE. Generally, viral infections lead to systemic inflammation and induction of numerous cytokines and GFs and many of them are reported to be associated with increased VTE. Most importantly, platelets play key thromboinflammatory roles linking coagulation to immune mediators in a variety of infections including response to viral infection. Since the pathomechanism of coagulopathy and VTE in COVID-19 is largely undefined, herein we highlight the association of dysregulated inflammatory cytokines and GFs with thrombotic complications and coagulopathy in COVID-19.

The COVID-19 Pandemic and the Need for an Integrated and Equitable Approach: An International Expert Consensus Paper.

BACKGROUND: One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis. MANAGEMENT: Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic. CURRENT ISSUES: The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments. PERSPECTIVES: There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) Prevention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA). CONCLUSION: The "PDA strategy" integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide.

The ISTH bleeding assessment tool as predictor of bleeding events in inherited platelet disorders: Communication from the ISTH SSC Subcommittee on Platelet Physiology.

BACKGROUND: The ISTH Bleeding Assessment Tool (ISTH-BAT) has been validated for clinical screening of suspected von Willebrand disease (VWD) and for bleeding prediction. Recently it has been validated for subjects with inherited platelet disorders (IPD) (BAT-VAL study). OBJECTIVES: To determine whether the ISTH-BAT bleeding score (BS) predicts subsequent bleeding events requiring treatment in IPD patients. METHODS: Patients with IPD, type 1 VWD (VWD-1) and age- and sex-matched healthy controls enrolled in the BAT-VAL study were prospectively followed-up for 2 years and bleeding episodes requiring treatment were recorded. RESULTS: Of the 1098 subjects initially enrolled, 955 were followed-up and 124 suffered hemorrhages during follow-up, 60% of whom had inherited platelet function disorders (IPFD). Total number of events was significantly higher in IPFD (n = 235) than VWD-1 (n = 52) or inherited thrombocytopenia (IT; n = 20). Events requiring transfusions were 66% in IPFD, 5.7% in VWD-1, and 3% in IT. Baseline BS was significantly higher in IPFD patients with a bleeding event at follow-up than in those without (p < .01) and the percentage of subjects suffering a bleeding event increased proportionally to baseline BS quartile. A significant association between the BS and the chance of suffering severe bleeding was found in the overall, IPFD, and VWD-1 populations. Similar results were obtained for the pediatric population. CONCLUSIONS: Inherited platelet function disorder patients with high BS at enrollment are more likely to suffer from bleeding events requiring treatment at follow-up. Moreover, the higher the baseline BS quartile the greater the incidence of subsequent events, suggesting that independently from diagnosis a high BS is associated with a greater risk of subsequent hemorrhage.

Enhanced In Vitro Wound Healing Using PVA/B-PEI Nanofiber Mats: A Promising Wound Therapeutic Agent against ESKAPE and Opportunistic Pathogens.

Opportunistic skin pathogens and their resistance to pre-existing therapeutics are a challenge to normal physiological wound healing processes. Consistent development of antimicrobial agents is required to overcome the complications raised by antimicrobial resistance. An effective alternative proposed in recent research includes the use of antimicrobial nanoparticles or nanobiopolymers. Unfortunately, metallic nanoparticles that have been proven as antimicrobial agents also possess a certain level of toxicity. In this work, we demonstrate the use of a cationic polymer, branched polyethyleneimine (B-PEI), that has been electrospun to obtain a scaffold/fiber (B-PEI NF) mat resulting in a large surface area-to-volume ratio. SEM analysis revealed that the average diameter of the obtained fibers is 240 nm. The formation of nanoscaffold modulates the controlled release of the polymer from the matrix resulting in long-term effects. The antimicrobial and antibiofilm activity of the B-PEI nanofiber (B-PEI NF) was evaluated against ESKAPE pathogens (Pseudomonas aeruginosa and Staphylococcus aureus) and also against Candida albicans. Dose-dependent inhibition was observed for microbial growth and biofilm for all three test organisms, the minimum inhibitory concentration required for inhibiting P. aeruginosa, S. aureus, and C. albicans is 33.125, 26.5, and 19.875 µM, respectively, in 2 mL of bacterial/fungal broth. Crystal violet and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed significant reduction in biomass and cell viability of sessile cells, respectively, within the biofilm after treatment using B-PEI NFs. A B-PEI NF matrix promotes cell migration and wound healing processes by mimicking the extracellular matrix. In vitro wound healing studies showed a fivefold increase in cell migration and wound healing by B-PEI NFs (97% wound coverage in 17 h) when compared to B-PEI (15% wound coverage in 17 h). The in vitro wound healing assays confirmed the biocompatibility and better wound healing activity of B-PEI NF mats.

Increase of Plasma TNF-α Is Associated with Decreased Levels of Blood Platelets in Clinical Dengue Infection.

Dengue virus (DENV) infection has become an increasingly common concern in tropical and subtropical regions. It has protean manifestations ranging from febrile phase to severe life-threatening illness. In this study, we estimated Th1 and Th2 cytokines and correlated the levels with dengue severity along with certain hematological and biochemical parameters. We also studied the seroprevalence of dengue between October and December 2017 at the Government Theni Medical College, India. Individuals with dengue fever (DF) were positive for either IgM or IgG, or both. The biochemical and hematological parameters along with plasma tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), granulocyte monocyte-colony stimulating factor (GM-CSF), interleukin (IL)-13, IL-12p70, IL-10, IL-5, IL-4, and IL-2 cytokines were estimated. The prevalence of DF was 42.9% during the study period. IL-2, TNF-α, IL-4, and IL-10 levels were significantly elevated (p < 0.005) in patients with secondary DENV infection, whereas the level of IL-13 remained unaltered during both primary and secondary infections. No statistically significant difference was noticed with IL-12p70, IL-5, IFN-γ, and GM-CSF between the healthy controls and the primary and secondary DENV-infected groups. Increase of 1 unit of TNF-α was associated with a decrease of 160 units of blood platelets. Together, the study suggests that TNF-α could play a key role in the pathogenesis of dengue, and despite the decrease in platelet levels, it remains to be seen whether any other inflammatory cells regulate the levels of TNF-α in DENV infection.

Platelet activation markers in evaluation of thrombotic risk factors in various clinical settings.

Platelets play a major role in primary hemostasis and thrombus formation. After vascular injury, platelets adhere to injured site and rapidly change their shape that switches the resting platelets to active state. Activated platelets aggregate and secrete biologically active intermediate substances that further potentiate platelet activation through autocrine as well as paracrine mechanisms. The activated platelet expresses certain proteins that are not seen on the resting platelets, thus these proteins serve as markers of platelet activation. Other subsequent events of platelet activation include release of microvesicles and formation of complexes with other circulating cells, like monocytes and neutrophils. Platelet activation markers are useful tools in evaluating risk factors of thrombosis in a variety of clinical conditions. Increased platelet activation has been associated with various pathological conditions such as acute coronary syndrome, stroke, peripheral vascular disease and other inflammatory diseases. The advancement in technologies helps in determining the status of platelet activation in such clinical conditions. This article focuses on the sources, mechanism and diagnosis of platelet activation and their clinical implications.