The Fatal Clinical Outcome of Severe COVID-19 in Hospitalized Patients: Findings from a Prospective Cohort Study in Dhaka, Bangladesh.

Background and Objectives: The morbidity and mortality associated with COVID-19 have burdened worldwide healthcare systems beyond their capacities, forcing them to promptly investigate the virus characteristics and its associated outcomes. This clinical analysis aimed to explore the key factors related to the fatal outcome of severe COVID-19 cases. Materials and Methods: Thirty-five adult severe COVID-19 patients were enrolled from two COVID-19 hospitals in Dhaka, Bangladesh. Clinical manifestation, comorbid conditions, medications, SARS-CoV-2 RT-PCR related cycle threshold (CT) value, hematology, biochemical parameters with SARS-CoV-2 specific IgG and IgM responses at enrollment were compared between the survivors and deceased participants. Results: Total 27 patients survived and 8 patients died within 3 months of disease onset. Deceased patients suffered longer from shortness of breath than the survived (p = 0.049). Among the severe cases, 62% of the deceased patients had multiple comorbid condition compared to 48% of those who survived. Interestingly, the anti-viral was initiated earlier among the deceased patients [median day of 1 (IQR: 0, 1.5) versus 6.5 (IQR: 6.25, 6.75)]. Most of the survivors (55%) received a combination of anticoagulant (p = 0.034). Liver enzymes, creatinine kinase, and procalcitonin were higher among the deceased patients during enrollment. The median CT value among the deceased was significantly lower than the survivors (p = 0.025). A significant difference for initial IgG (p = 0.013) and IgM (p = 0.030) responses was found between the survivor and the deceased groups. Conclusions: The factors including older age, male gender, early onset of respiratory distress, multiple comorbidities, low CT value, and poor antibody response may contribute to the fatal outcome in severe COVID-19 patients. Early initiation of anti-viral and a combination of anticoagulant treatment may prevent or lower the fatality among severe COVID-19 cases.

Extracellular vesicles released from ganglioside GD2-expressing melanoma cells enhance the malignant properties of GD2-negative melanomas.

Exosomes (small extracellular vesicles: EVs) have attracted increasing attention from basic scientists and clinicians since they play important roles in cell-to-cell communication in various biological processes. Various features of EVs have been elucidated regarding their contents, generation and secretion mechanisms, and functions in inflammation, regeneration, and cancers. These vesicles are reported to contain proteins, RNAs, microRNAs, DNAs, and lipids. Although the roles of individual components have been rigorously studied, the presence and roles of glycans in EVs have rarely been reported. In particular, glycosphingolipids in EVs have not been investigated to date. In this study, the expression and function of a representative cancer-associated ganglioside, GD2, in malignant melanomas was investigated. Generally, cancer-associated gangliosides have been shown to enhance malignant properties and signals in cancers. Notably, EVs derived from GD2-expressing melanomas enhanced the malignant phenotypes of GD2-negative melanomas, such as cell growth, invasion, and cell adhesion, in a dose-dependent manner. The EVs also induced increased phosphorylation of signaling molecules such as EGF receptor and focal adhesion kinase. These results suggest that EVs released from cancer-associated ganglioside-expressing cells exert many functions that have been reported as a function of these gangliosides and regulate microenvironments, including total aggravation of heterogeneous cancer tissues, leading to more malignant and advanced cancer types.

Longevity of memory B cells and antibodies, as well as the polarization of effector memory helper T cells, are associated with disease severity in patients with COVID-19 in Bangladesh.

The longevity of immune responses induced by different degrees of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides information important to understanding protection against coronavirus disease 2019 (COVID-19). Here, we report the persistence of SARS-CoV-2 spike receptor-binding domain (RBD) specific antibodies and memory B cells recognizing this antigen in sequential samples from patients in Bangladesh with asymptomatic, mild, moderate and severe COVID-19 out to six months following infection. Since the development of long-lived memory B cells, as well as antibody production, is likely to be dependent on T helper (Th) cells, we also investigated the phenotypic changes of Th cells in COVID-19 patients over time following infection. Our results show that patients with moderate to severe COVID-19 mounted significant levels of IgG antibodies out to six months following infection, while patients with asymptomatic or mild disease had significant levels of IgG antibodies out to 3 months following infection, but these then fell more rapidly at 6 months than in patients with higher disease severity. Patients from all severity groups developed circulating memory B cells (MBCs) specific to SARS-CoV-2 spike RBD by 3 months following infection, and these persisted until the last timepoint measured at 6 months. A T helper cell response with an effector memory phenotype was observed following infection in all symptomatic patients, while patients with asymptomatic infection had no significant increases in effector Th1, Th2 and Th17 effector memory cell responses. Our results suggest that the strength and magnitude of antibody and memory B cells induced following SARS-CoV-2 infection depend on the severity of the disease. Polarization of the Th cell response, with an increase in Th effector memory cells, occurs in symptomatic patients by day 7 following infection, with increases seen in Th1, Th2, Th17 and follicular helper T cell subsets.

Correlation of antigen-specific immune response with disease severity among COVID-19 patients in Bangladesh.

Coronavirus disease 2019 (COVID-19) is a protean disease causing different degrees of clinical severity including fatality. In addition to humoral immunity, antigen-specific T cells may play a critical role in defining the protective immune response against SARS-CoV-2, the virus that causes this disease. As a part of a longitudinal cohort study in Bangladesh to investigate B and T cell-specific immune responses, we sought to evaluate the activation-induced marker (AIM) and the status of different immune cell subsets during a COVID-19 infection. We analyzed a total of 115 participants, which included participants with asymptomatic, mild, moderate, and severe clinical symptoms. We observed decreased mucosal-associated invariant T (MAIT) cell frequency on the initial days of the COVID-19 infection in symptomatic patients compared to asymptomatic patients. However, natural killer (NK) cells were found to be elevated in symptomatic patients just after the onset of the disease compared to both asymptomatic patients and healthy individuals. Moreover, we found a significant increase of AIM+ (both OX40+CD137+ and OX40+CD40L+) CD4+ T cells in moderate and severe COVID-19 patients in response to SARS-CoV-2 peptides (especially spike peptides) compared to pre-pandemic controls who are unexposed to SARS-CoV-2. Notably, we did not observe any significant difference in the CD8+ AIMs (CD137+CD69+), which indicates the exhaustion of CD8+ T cells during a COVID-19 infection. These findings suggest that patients who recovered from moderate and severe COVID-19 were able to mount a strong CD4+ T-cell response against shared viral determinants that ultimately induced T cells to mount further immune responses to SARS-CoV-2.

Disease characteristics and serological responses in patients with differing severity of COVID-19 infection: A longitudinal cohort study in Dhaka, Bangladesh.

BACKGROUND: COVID-19 caused by SARS-CoV-2 ranges from asymptomatic to severe disease and can cause fatal and devastating outcome in many cases. In this study, we have compared the clinical, biochemical and immunological parameters across the different disease spectrum of COVID-19 in Bangladeshi patients. METHODOLOGY/PRINCIPAL FINDINGS: This longitudinal study was conducted in two COVID-19 hospitals and also around the community in Dhaka city in Bangladesh between November 2020 to March 2021. A total of 100 patients with COVID-19 infection were enrolled and classified into asymptomatic, mild, moderate and severe cases (n = 25/group). In addition, thirty age and sex matched healthy participants were enrolled and 21 were analyzed as controls based on exclusion criteria. After enrollment (study day1), follow-up visits were conducted on day 7, 14 and 28 for the cases. Older age, male gender and co-morbid conditions were the risk factors for severe COVID-19 disease. Those with moderate and severe cases of infection had low lymphocyte counts, high neutrophil counts along with a higher neutrophil-lymphocyte ratio (NLR) at enrollment; this decreased to normal range within 42 days after the onset of symptom. At enrollment, D-dimer, CRP and ferritin levels were elevated among moderate and severe cases. The mild, moderate, and severe cases were seropositive for IgG antibody by day 14 after enrollment. Moderate and severe cases showed significantly higher IgM and IgG levels of antibodies to SARS-CoV-2 compared to mild and asymptomatic cases. CONCLUSION/SIGNIFICANCE: We report on the clinical, biochemical, and hematological parameters associated with the different severity of COVID-19 infection. We also show different profile of antibody response against SARS-CoV-2 in relation to disease severity, especially in those with moderate and severe disease manifestations compared to the mild and asymptomatic infection.

A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness.

Ivermectin, a US Food and Drug Administration-approved anti-parasitic agent, was found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. A randomized, double-blind, placebo-controlled trial was conducted to determine the rapidity of viral clearance and safety of ivermectin among adult SARS-CoV-2 patients. The trial included 72 hospitalized patients in Dhaka, Bangladesh, who were assigned to one of three groups: oral ivermectin alone (12 mg once daily for 5 days), oral ivermectin in combination with doxycycline (12 mg ivermectin single dose and 200 mg doxycycline on day 1, followed by 100 mg every 12 h for the next 4 days), and a placebo control group. Clinical symptoms of fever, cough, and sore throat were comparable among the three groups. Virological clearance was earlier in the 5-day ivermectin treatment arm when compared to the placebo group (9.7 days vs 12.7 days; p = 0.02), but this was not the case for the ivermectin + doxycycline arm (11.5 days; p = 0.27). There were no severe adverse drug events recorded in the study. A 5-day course of ivermectin was found to be safe and effective in treating adult patients with mild COVID-19. Larger trials will be needed to confirm these preliminary findings.

Undiagnosed Isolated Systolic and Diastolic Hypertension Subtypes and Their Correlates in Bangladesh: A Nationwide Survey.

OBJECTIVES: This study was performed to identify the distribution of undiagnosed isolated hypertension subtypes and their correlates amongst adults aged 35 years and older in Bangladesh using data from the Bangladesh Demography and Health Survey 2011. METHODS: Out of a total of 17,964 selected households, 7,880 were included in the final analysis for this study. Systolic and diastolic blood pressure (BP) were measured 3× at 10-minute intervals. Hypertension subtypes were defined for individuals not under antihypertensive treatment as systolic-diastolic hypertension (SDH): systolic BP (SBP) ≥ 140 mm Hg and diastolic BP (DBP) ≥ 90 mm Hg; isolated diastolic hypertension (IDH): SBP < 140 mm Hg and DBP ≥ 90 mm Hg, and isolated systolic hypertension (ISH): SBP ≥140 mm Hg and DBP < 90 mm Hg. RESULTS: The predominant hypertension subtypes were SDH and IDH [5.2%; 95% confidence interval (CI): 4.7-5.1] followed by ISH (3.8%; 95% CI: 3.4-4.2). Multiple logistic regression showed that age and gender were significant predictors of ISH. SDH was associated with females [odds ratio (OR): 1.8; 95% CI: 1.3-2.6], the older age group (OR-7.4; 95% CI: 4.3-12.7), and overweight or obese individuals (OR: 1.6; 95% CI: 1.1-2.4). Non-manual work (OR: 1.5; 95% CI: 1.0-2.0]) and being overweight or obese (OR: 1.9; 95% CI: 1.4-2.8) were factors associated with IDH. CONCLUSION: ISH, IDH and SDH represent salient subtypes of hypertension in Bangladesh. To identify preventive intervention for averting adverse cardiovascular events, further research is needed.

The relationship between serum uric acid and lipid profile in Bangladeshi adults.

BACKGROUND: Although the link between elevated uric acid and metabolic syndrome has been reported in some studies; the relationship of serum uric acid (SUA) with lipid profile has not well studied or little is known so far. This study was conducted to assess the relationship between SUA and lipid profile among the general adults in Bangladesh. METHODS: In total, 280 blood samples were collected from general adult participants (male, n = 150 and female, n = 130) and analyzed for serum lipid profile (TC, TG, HDL and LDL) and SUA levels. The study subjects were divided by quartiles based on SUA levels (Q1: ≤225 µmol/L, Q2: 226-285 µmol/L, Q3: 286-340 µmol/L and Q4: > 340 µmol/L). Linear regression modeling was used to evaluate the relationship between SUA and lipid levels. RESULTS: The prevalence of hyperuricemia was 9.2% in males and 10.4% in females. The mean level of SUA was significantly higher in male (317 ± 90 µmol/L) than in the female (255 ± 65 µmol/L) subjects (p < 0.001). An increasing trend for elevated lipid profile was observed in both gender with increasing levels of SUA in the quartiles (p < 0.05). In regression analysis, a significant positive correlation was found between SUA and TG, TC and LDL (p < 0.01) while an inverse correlation was observed between SUA and HDL (p < 0.01). After adjusting for potential confounders, lipid profile was linearly associated with SUA levels (p < 0.01 for trend). CONCLUSIONS: Present study showed a significant positive relationship for SUA with TG, TC and LDL levels, and an inverse relationship for SUA with HDL. Early prevention of hyperuricemia and dyslipidemia may be helpful to reduce the incidence of associated cardiovascular diseases.

Regional variation in chronic kidney disease and associated factors in hypertensive individuals in rural South Asia: findings from control of blood pressure and risk attenuation-Bangladesh, Pakistan and Sri Lanka.

BACKGROUND: We aimed to determine the prevalence of chronic kidney disease (CKD) and its cross-country variation among hypertensive individuals in rural Bangladesh, Pakistan and Sri Lanka. We also explored the factors associated with CKD in these populations. METHOD: We studied baseline data from the Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan and Sri Lanka (COBRA-BPS) trial, an ongoing cluster randomized controlled trial on 2643 hypertensive adults ≥40 years of age from 30 randomly selected rural clusters, 10 in each of the three countries. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or a urine albumin:creatinine ratio (UACR) ≥30 mg/g. Determinants for CKD were assessed using logistic regression analysis. RESULTS: The overall prevalence of CKD was 38.1% (95% confidence interval 36.2-40.1%): 21.5% with eGFR <60 mL/min/1.73 m2 and 24.4% with UACR ≥30 mg/g. CKD prevalence varied across the three countries (58.3% in Sri Lanka, 36.4% Bangladesh and 16.9% Pakistan; P <0.001). The factors independently associated with higher odds of CKD were older age, being unmarried, higher 24-h urinary sodium excretion, presence of diabetes, elevated systolic blood pressure, diuretic use and living in Bangladesh or Sri Lanka (versus Pakistan). CONCLUSIONS: The prevalence of CKD is alarmingly high in community-dwelling hypertensive adults, with significant cross-country variation in South Asia. Our findings underscore the urgency for further research into the etiology of CKD and address associated factors in targeted public health strategies with hypertension care outreach services in rural South Asia. CLINICALTRIALS.GOV: NCT02657746.

Electrocatalytic nitrate hydrogenation over an H+ -conducting solid polymer electrolyte membrane-modified cathode assembly.

Selective electrocatalytic hydrogenation of NO3- to N2 in water has successfully been achieved at room temperature using a membrane-electrode assembly (MEA) consisting of an H+ -conducting solid polymer electrolyte (Nafion-117) and a surface-modified Pt cathode.