Numerical Study of Titanium Dioxide and MXene Nanomaterial-Based Surface Plasmon Resonance Biosensor for Virus SARS-CoV-2 Detection.

A novel surface plasmon resonance-based biosensor for SARS-CoV-2 virus is proposed in this article. The biosensor is a Kretschmann configuration-based structure that consists of CaF2 prism as base, at which silver (Ag), TiO2, and MXene nanolayers are used to enhance the performance. Theoretically, the performance parameters have been investigated by means of Fresnel equations and transfer matrix method (TMM). The TiO2 nanolayer not only prevents oxidation of Ag layer but also enhances the evanescent field in its vicinity. The sensor provides an ultrahigh angular sensitivity of 346°/RIU for the detection of SARS-CoV-2 virus. Some other performance parameters, including FWHM (full width at half maxima), detection accuracy (DA), limit of detection (LOD), and quality factor (QF) have also been calculated for proposed SPR biosensor with their optimized values 2.907°, 0.3439 deg-1, 1.445 × 10-5, and 118.99 RIU-1, respectively. The obtained results designate that the proposed surface plasmon resonance (SPR) based biosensor has notably enhanced angular sensitivity as compared to previous results reported in the literatures till date. This work may facilitate a significant biological sample sensing device for fast and accurate diagnosis at early stage of SARS-CoV-2 virus.

"Mitochondrial pathogenic mutations and metabolic alterations associated with COVID-19 disease severity".

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused global pandemic and drastically affected the humankind. Mitochondrial mutations have been found to be associated with several respiratory diseases. Missense mutation and pathogenic mitochondrial variants might unveil the potential involvement of the mitochondrial genome in coronavirus disease 2019 (COVID-19) pathogenesis. The present study aims to elucidate the role of mitochondrial DNA (mtDNA) mutations, mitochondrial haplogroup, and energy metabolism in disease severity. The study was performed on 58 subjects comprising COVID-19-positive (n = 42) and negative (n = 16) individuals. COVID-19-positive subjects were further categorized into severe deceased (SD), severe recovered (SR), moderate (Mo), and mild (Mi) patients, while COVID-19-negative subjects were healthy control (HC) for the study. High throughput next-generation sequencing was done to investigate mtDNA mutations and haplogroups. The computational approach was applied to study the effect of mtDNA mutations on protein secondary structure. Real time polymerase chain reaction was used for mtDNA copy number determination and mitochondrial function parameters were also analyzed. We found 15 mtDNA mutations in MT-ND5, MT-ND4, MT-ND2, and MT-COI genes uniquely associated with COVID-19 severity affecting the secondary structure of proteins in COVID-19-positive subjects. Haplogroup analysis suggests that mtDNA haplogroups M3d1a and W3a1b might be potentially associated with COVID-19 pathophysiology. The mitochondrial function parameters were significantly altered in severe patients (SD and SR; p < 0.05). No significant relationship was found between mtDNA mutations and oxidative stress markers (p > 0.05). The study highlights the importance of mitochondrial reprogramming in COVID-19 patients and may provide a feasible approach toward finding a path for therapeutic interventions to COVID-19 disease.

Evaluation of altered miRNA expression pattern to predict COVID-19 severity.

Outbreak of COVID-19 pandemic in December 2019 affected millions of people globally. After substantial research, several biomarkers for COVID-19 have been validated however no specific and reliable biomarker for the prognosis of patients with COVID-19 infection exists. Present study was designed to identify specific biomarkers to predict COVID-19 severity and tool for formulating treatment. A small cohort of subjects (n = 43) were enrolled and categorized in four study groups; Dead (n = 16), Severe (n = 10) and Moderate (n = 7) patients and healthy controls (n = 10). Small RNA sequencing was done on Illumina platform after isolation of microRNA from peripheral blood. Differential expression (DE) of miRNA (patients groups compared to control) revealed 118 down-regulated and 103 up-regulated known miRNAs with fold change (FC) expression ≥2 folds and p ≤ 0.05. DE miRNAs were then subjected to functional enrichment and network analysis. Bioinformatic analysis resulted in 31 miRNAs (24 Down-regulated; 7 up-regulated) significantly associated with COVID-19 having AUC>0.8 obtained from ROC curve. Seventeen out of 31 DE miRNAs have been linked to COVID-19 in previous studies. Three miRNAs, hsa-miR-147b-5p and hsa-miR-107 (down-regulated) and hsa-miR-1299 (up-regulated) showed significant unique DE in Dead patients. Another set of 4 miRNAs, hsa-miR-224-5p (down-regulated) and hsa-miR-4659b-3p, hsa-miR-495-3p and hsa-miR-335-3p were differentially up-regulated uniquely in Severe patients. Members of three miRNA families, hsa-miR-20, hsa-miR-32 and hsa-miR-548 were significantly down-regulated in all patients group in comparison to healthy controls. Thus a distinct miRNA expression profile was observed in Dead, Severe and Moderate COVID-19 patients. Present study suggests a panel of miRNAs which identified in COVID-19 patients and could be utilized as potential diagnostic biomarkers for predicting COVID-19 severity.

Gene variants in pro-coagulant and anti-coagulant genes could be prognostic genetic markers of COVID-19 susceptibility.

Background: Present study aimed to identify DNA polymorphisms (variants) which can modulate the risk of COVID-19 infection progression to severe condition. TaqMan based SNP genotyping assay was performed for 11 single nucleotide polymorphisms (SNPs) in pro-coagulant and anti-coagulant genes. Methodology: A total of 33 COVID-19 patients, including dead, severe and moderately infected individuals were compared to 35 healthy controls. Both alleles in the SNP were labelled with two different fluorescent dyes (FAM and VIC) during assay formulation. DNA of study subjects were mixed with SNP assay and TaqMan master mix on 96 well PCR plate according to manufacturer's protocol and RT-PCR was performed. Allelic discrimination assay gave clear results for presence of specific allele in each sample. Three SNPs were located in the pro-coagulant genes, another three involved in blood clot dissolution while rest five were in the genes encoding natural anti-coagulants. COVID-19 infected patients were further sub-divided into three groups, deceased (n = 16), severe (n = 10) and moderately infected (n = 7). Results: SNP genotyping showed significant differences between COVID-19 patients and controls in two SNPs, rs6133 in Selectin-P (SELP) and rs5361 in Selectin-E (SELE) gene. Also, rs2020921 and rs8176592, in clot dissolution genes, tissue Plasminogen activator (tPA) and tissue factor pathway inhibitor (TFPI) respectively showed significant genotypic and allelic difference in patients of COVID-19 compared to healthy controls. Further three SNPs rs2227589, rs757583846, and rs121918476 in natural anti-coagulant genes anti-thrombin III (ATIII), protein C (PROC), and protein S (PROS) respectively showed statistically significant difference between the study groups. Conclusion: Our findings indicate that gene variants, those involved in coagulation and anti-coagulation may play a major role in determining individual susceptibility to COVID-19.

Implications of COVID-19 on Thrombotic Profile of Severely Affected Patients.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a novel viral disease that spread as a global pandemic in 2020 by infecting millions of people across the world. Its clinical prognosis is dependent on various coagulatory parameters since thrombotic events are frequently associated with infection severity. METHODS: A total of 383 COVID-19 patients enrolled in Rajiv Gandhi Super Specialty Hospital, Delhi, India, were included in the present retrospective study. Patients were divided into three categories, severe (n = 141), moderate (n = 138), and mild (n = 104) based on infection severity. Various thrombotic parameters and anticoagulant levels were measured in 70 patients and further analyzed. RESULTS: Coagulopathy is seen in COVID-19 patients (n = 70) with a significant increase in fibrinogen, D-dimer levels, and prothrombin time in patients with severe and moderate disease compared to patients with a mild infection. Approximately, 70% of patients with severe and moderate disease demonstrated fibrinogen levels higher than the standard reference range. 60.41% of patients with severe disease showed significantly higher D-dimer levels. Thrombotic parameters were notably elevated in the nonsurvivors group compared to COVID-19 survivors. Nearly, 91% of patients with severe infection had anticoagulant protein S levels below the reference range. CONCLUSION: COVID-19 infection severely impacts the blood coagulation cascade, which might lead to the manifestation of severe symptoms and increased mortality in patients.

Potential association of COVID-19 and ABO blood group: An Indian study.

Coronavirus disease 2019 (COVID-19) transmits from person to person mainly through respiratory droplets and coughing. Infection severity ranges from asymptomatic and mild infection to those with moderate and severe symptoms which may lead to multiple organ failure and mortality. Infection severity largely depends on individual's immune response, age and co-morbidities. Present study categorized COVID-19 infected patients based on their infection severity and linked COVID-19 severity with age, gender and ABO blood group types. Clinical details of 383 COVID-19 patients were collected from Rajiv Gandhi Super Specialty hospital (RGSSH), India; divided into three groups; mild, moderate and severe patients, based on their symptoms. Present analysis revealed that age plays major role in infection severity, as the symptoms are more severe in patients above 45 years. Infection rate was higher in males compared to females. Most patients with A(+ve) and B(+ve) blood group were severely affected compared to those of blood group type O(+ve) and AB(+ve). O(+ve) blood group was least represented in severe patients. Present findings could be helpful in generating awareness amongst the population regarding susceptibility towards the COVID-19 infection. This supportive information would help clinicians and health workers to propose new strategies and tactical solution against COVID-19 infection.

Assessment of nitric oxide (NO) potential to mitigate COVID-19 severity.

Novel coronavirus disease by SARS-CoV-2 virus (also known as COVID-19) has emerged as major health concern worldwide. While, there is no specific drugs for treating this infection till date, SARS-CoV-2 had spread to most countries around the globe. Nitric oxide (NO) gas serves as an important signaling molecule having vasodilatory effects as well as anti-microbial properties. Previous studies from the 2004 SARS-CoV infection demonstrated that NO may also help to reduce respiratory tract infection by inactivating viruses and inhibiting their replication cycle and is an effective supportive measure for treating infection in patients with pulmonary complications. NO gas inhalation is being suggested as potential therapy for managing severe acute respiratory distress syndrome in COVID-19 patients. In view of COVID-19 pandemic, several clinical trials are underway to examine the effects of NO inhalation on infected patients. Previously published reports on beneficial effects of endogenous NO and NO inhalation therapy were thoroughly searched to assess the potential of NO therapy for treating COVID-19 patients. Present report summarized the therapeutic importance of NO to reverse pulmonary hypertension, restore normal endothelial activity and produce anti-thrombotic effects. In addition to this, NO also reduces viral infection by inhibiting its replication and entry into the host cell. In absence of vaccine and effective treatment strategies, we suggest that NO inhalation therapy and NO releasing foods/compounds could be considered as an alternative measure to combat COVID-19 infection.

COVID-19 infection and thrombosis.

BACKGROUND: Recent reports on outbreak of SARS-CoV-2 coronavirus (COVID-19) have shown its association with abnormal blood clots. The viral infection initiates inflammatory responses leading to endothelial damage and coagulation cascade dysfnction. Spread of COVID-19 has been associated with disseminated intravascular coagulation (DIC) and subsequent coagulopathy. Initially coagulopathy in COVID-19 patients result in significant elevation of D-dimer, fibrin/fibrinogen degradation products (FDP), and abnormalities in coagulatory parameters, which resulting in formation of thrombus and eventually death. METHODOLOGY: Present report intends to summarize the information of the research reports available so far on the complications of formation of unusal blood clots (thrombosis) during COVID-19 infection and its therapeutic strategies. Extensive web search was done for various reports associating COVID-19 infection with increased coagulopathy and abnormal coagulatory parameters such as PT, PTT, and platelet counts; along with increased D-dimer and fibrinogen levels. RESULTS AND CONCLUSION: Findings of these research reports were summarized to recommend cautions for clinicians while treating COVID-19 patient. Screening of coagulatory parameters upon admission and during entire course of treatment is recommended, especially those who are at increased risk of thrombosis. Also, anticoagulant treatment can be used as thromboprophylaxis measure. Dose and duration of anticoagulation treatment requirement may vary and thus regular monitoring is needed.

SARS-CoV-2 infection: physiological and environmental gift factors at high altitude.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a global pandemic. This viral disease primarily causes lung pneumonia and has a wide range of clinical manifestations. The severity of infection ranges from those who are asymptomatic or with mild symptoms which do not require hospital admission, to those who require ventilator support and eventually die, depending on immunity, age and other comorbidities existing with the patients. The present report is an attempt to study the effect of physiological and environmental factors existing at high altitudes (HA) with spread of SARS-CoV-2 infection. Analysis of existing data revealed that HA natives do possess certain physiological advantages such as (1) improved hypoxic ventilatory response, (2) higher concentration of oxygen carrying molecules, haemoglobin, (3) increased production of Vitamin D, due to intense solar radiation, (4) lower rates of comorbidities such as lung infections, obesity etc. and (5) most importantly reduced production of angiotensin converting enzyme 2, a carrier molecule for SARS-CoV-2 virus entry into the host cell; all of which can collectively account for improved tolerance to SARS-CoV-2 infection in HA natives. In addition, environmental factors at HA such as (6) dry and chilly winds, (7) low air density and (8) intense UV radiations may further inhibit viral growth and spread into the atmosphere. We thus conclude that, high altitude natives may posses physiological and environmental advantage over low landers in terms of reduced severity of SARS-CoV-2 infection and its limited spread. Graphic abstract: Gift factors associated with COVID-19 spread at high altitude.