The Janus face of proliferating plasmablasts in dengue and COVID-19 infections.

Introduction: B cells play an integral role in the immune response to both dengue fever and COVID-19. Prior scRNAseq analyses of peripheral plasmablasts in COVID-19 have revealed a heterogeneous population with distinct cell subsets associated with proliferation; prior studies in patients with dengue fever have likewise shown the presence of proliferative pre-plasmablasts in the circulation. These findings may have implications for disease severity. In this study, we sought to gain a mechanistic understanding of the intracellular processes in naive and memory B cells that are associated with and may lead to an expanded proliferative plasmablast population in the circulation. Methods: We analyzed age-controlled (pediatric and adult), peripheral blood mononuclear cell scRNAseq datasets from patients infected with either dengue (primary or secondary) or COVID-19 (non-severe or severe) from previously published studies. Our preliminary analysis showed that pediatric patients with dengue and adults with COVID-19 had an expanded proliferative plasmablast (p-PB) population. By contrast, neither the adults with dengue nor the children with COVID-19 in our dataset had p-PBs. We used this distinctive preliminary signature to guide our analyses design and expanded our analyses to naive and memory B cells. Results: In age/disease conditions with and without p-PBs, we found differences in cell sensing and activation, including via the B cell receptor and downstream signal transduction. Likewise, inflammation was mediated differently: relative to groups without p-PBs, those with p-PBs had increased expression of interferon response and S100 genes (particularly severe COVID-19). Furthermore, several transcription factors at the nexus of activation, inflammation, and cell fate decisions were expressed differently in groups with and without p-PBs. Discussion: We used dengue and COVID-19 infections in adult and pediatric patients (focusing on naive B, memory B, and plasmablast cells) as a model to better understand the mechanisms that may give rise to p-PB populations in the circulation. Our results indicate that a more pro-inflammatory state in naive and memory B cells correlated with - and could influence the generation of- proliferating plasmablasts. Further exploration of these mechanisms will have implications for immune memory, vaccine development, and post-viral autoimmune syndromes.

HER 2/neu Overexpression in Oral Squamous Cell Carcinoma and Its Clinico-Pathological Association at a Tertiary Care Center in Eastern India.

Human epidermal growth factor receptor 2/neu (HER2/neu) is known to serve as a prognostic and predictive biomarker in several cancers such as breast, gastric and ovarian cancers. In head and neck squamous cell carcinoma, HER2/neu expression is seen but in a fluctuated manner. Hence, its role as a prognostic factor in oral squamous cell carcinoma (OSCC) needs evaluation. To determine the HER 2/neu overexpression in OSCC patients and its association with clinical and pathological parameters. 74 patients of OSCC treated between 2016 and 2018 were included in the study. Immunohistochemistry was done on tissue samples from these patients and HER2/neu expression was measured. Both biopsy and resected specimens were considered for the study. Out of 74 patients, 47.3% (35) were operated and 52.7% (39) were not operated due to loss to follow-up. No significant association was found (p = 0.636, OR = 0.68, CI = 0.14-3.34) between lymphovascular invasion (LVI) and HER2/neu expression. Similar results were seen for perineural invasion (PNI) (p = 0.490, OR = 0.53, CI = 0.88-3.24), depth of invasion (p = 0.21), grade of tumor (p = 0.214), clinical-stage (p = 0.511) and pathological stage (p = 0.091). No significant association existed between HER2/neu expression and LVI, PNI, clinical-stage, the grade of tumor and the pathological stage of oral squamous cell carcinoma.

Hypercalcemia of Malignancy: Time to Pull the Brakes.

Hypercalcemia of malignancy (HOM) is usually seen in advanced stage and carries a poor prognosis. Survival outcomes are dismal and most of the patients are unable to receive subsequent definite anti-cancer therapy. There is lack of any retrospective or prospective data regarding hypercalcemia of malignancy in Indian population. We aim to describe survival outcomes in hypercalcemia associated with solid organ malignancies. Forty-five patients diagnosed with HOM associated with solid organ malignancies were included in the study. Patients were followed up till death. Clinical features and survival outcomes were noted. Squamous cell carcinoma of head and neck region and lung comprised most of the cases associated with HOM. Most of the patients presented with poor performance status. Median overall survival (OS) was 20 days (2-78 days). Median OS was 35 days (9-58 days) in those who received definite anti-cancer therapy. Four-week mortality rate was estimated as 59.5%, while this increased to 75.7% within 6 weeks from the diagnosis of hypercalcemia. Survival outcomes are poor after the diagnosis of hypercalcemia in cancer patients. Best supportive care including hospice care should be strongly considered at this point of time instead of definite systemic anti-cancer therapy.

Immune Response in Severe and Non-Severe Coronavirus Disease 2019 (COVID-19) Infection: A Mechanistic Landscape.

The mechanisms underlying the immune remodeling and severity response in coronavirus disease 2019 (COVID-19) are yet to be fully elucidated. Our comprehensive integrative analyses of single-cell RNA sequencing (scRNAseq) data from four published studies, in patients with mild/moderate and severe infections, indicate a robust expansion and mobilization of the innate immune response and highlight mechanisms by which low-density neutrophils and megakaryocytes play a crucial role in the cross talk between lymphoid and myeloid lineages. We also document a marked reduction of several lymphoid cell types, particularly natural killer cells, mucosal-associated invariant T (MAIT) cells, and gamma-delta T (γδT) cells, and a robust expansion and extensive heterogeneity within plasmablasts, especially in severe COVID-19 patients. We confirm the changes in cellular abundances for certain immune cell types within a new patient cohort. While the cellular heterogeneity in COVID-19 extends across cells in both lineages, we consistently observe certain subsets respond more potently to interferon type I (IFN-I) and display increased cellular abundances across the spectrum of severity, as compared with healthy subjects. However, we identify these expanded subsets to have a more muted response to IFN-I within severe disease compared to non-severe disease. Our analyses further highlight an increased aggregation potential of the myeloid subsets, particularly monocytes, in COVID-19. Finally, we provide detailed mechanistic insights into the interaction between lymphoid and myeloid lineages, which contributes to the multisystemic phenotype of COVID-19, distinguishing severe from non-severe responses.

Evaluation of Iron Status in Patients of Solid Organ Malignancies: Study from a Cancer Research Centre.

Anemia associated with cancer is a major public health issue. The gravity of this problem is likely to be higher in India due to already existing malnutrition in the general population. Iron deficiency anemia (IDA) as a subset has not been evaluated in Indian population of cancer patients. This study was undertaken to evaluate iron status among newly diagnosed advanced-stage cancer patients with anemia at a cancer research institute in India. Sixty-four patients of anemia were identified who fulfilled the inclusion criteria. Iron status was noted. Absolute iron deficiency (AID) was identified in 8 (12.5%) patients. Functional iron deficiency (FID) was seen in 48 (75%) patients. Probable functional iron deficiency (PFID) was seen in 2 (3.1%) patients while no iron deficiency (NID) was seen in 6 (9.3%) patients. FID is seen in majority of advanced-stage solid organ cancer patients in India. Large sample studies are required to better define the exact prevalence of iron deficiency, chemotherapy-induced anemia, and anemia in cancer subtypes.