SARS-CoV-2 and dengue virus co-infection: Epidemiology, pathogenesis, diagnosis, treatment, and management.

SARS-CoV-2 and dengue virus co-infection cases have been on the rise in dengue-endemic regions as coronavirus disease 2019 (COVID-19) spreads over the world, posing a threat of a co-epidemic. The risk of comorbidity in co-infection cases is greater than that of a single viral infection, which is a cause of concern. Although the pathophysiologies of the two infections are different, the viruses have comparable effects within the body, resulting in identical clinical symptoms in the case of co-infection, which adds to the complexity. Overlapping symptoms and laboratory features make proper differentiation of the infections important. However, specific biomarkers provide precise results that can be utilised to diagnose and treat a co-infection, whether it is simply COVID-19, dengue, or a co-infection. Though their treatment is distinguished, it becomes more complicated in circumstances of co-infection. As a result, regardless of whatever infection the first symptom points to, confirmation diagnosis of both COVID-19 and dengue should be mandatory, particularly in dengue-endemic regions, to prevent health deterioration in individuals treated for a single infection. There is still a scarcity of concise literature on the epidemiology, pathophysiology, diagnosis, therapy, and management of SARS-CoV-2 and dengue virus co-infection. The epidemiology of SARS-CoV-2 and dengue virus co-infection, the mechanism of pathogenesis, and the potential impact on patients are summarised in this review. The possible diagnosis with biomarkers, treatment, and management of the SARS-CoV-2 and dengue viruses are also discussed. This review will shed light on the appropriate diagnosis, treatment, and management of the patients suffering from SARS-CoV-2 and dengue virus co-infection.

COVID-19 and the brain: understanding the pathogenesis and consequences of neurological damage.

SARS-CoV-2 has been known remarkably since December 2019 as a strain of pathogenic coronavirus. Starting from the earlier stages of the COVID-19 pandemic until now, we have witnessed many cases of neurological damage caused by SARS-CoV-2. There are many studies and research conducted on COVID-19-positive-patients that have found brain-related abnormalities with clear neurological symptoms, ranging from simple headaches to life-threatening strokes. For treating neurological damage, knowing the actual pathway or mechanism of causing brain damage via SARS-CoV-2 is very important. For this reason, we have tried to explain the possible pathways of brain damage due to SARS-CoV-2 with mechanisms and illustrations. The SARS-CoV-2 virus enters the human body by binding to specific ACE2 receptors in the targeted cells, which are present in the glial cells and CNS neurons of the human brain. It is found that direct and indirect infections with SARS-CoV-2 in the brain result in endothelial cell death, which alters the BBB tight junctions. These probable alterations can be the reason for the excessive transmission and pathogenicity of SARS-CoV-2 in the human brain. In this precise review, we have tried to demonstrate the neurological symptoms in the case of COVID-19-positive-patients and the possible mechanisms of neurological damage, along with the treatment options for brain-related abnormalities. Knowing the transmission mechanism of SARS-CoV-2 in the human brain can assist us in generating novel treatments associated with neuroinflammation in other brain diseases.

Choice of assemblers has a critical impact on de novo assembly of SARS-CoV-2 genome and characterizing variants.

BACKGROUND: Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic following its initial emergence in China. SARS-CoV-2 has a positive-sense single-stranded RNA virus genome of around 30Kb. Using next-generation sequencing technologies, a large number of SARS-CoV-2 genomes are being sequenced at an unprecedented rate and being deposited in public repositories. For the de novo assembly of the SARS-CoV-2 genomes, a myriad of assemblers is being used, although their impact on the assembly quality has not been characterized for this virus. In this study, we aim to understand the variabilities on assembly qualities due to the choice of the assemblers. RESULTS: We performed 6648 de novo assemblies of 416 SARS-CoV-2 samples using eight different assemblers with different k-mer lengths. We used Illumina paired-end sequencing reads and compared the assembly quality of those assemblers. We showed that the choice of assembler plays a significant role in reconstructing the SARS-CoV-2 genome. Two metagenomic assemblers, e.g. MEGAHIT and metaSPAdes, performed better compared with others in most of the assembly quality metrics including, recovery of a larger fraction of the genome, constructing larger contigs and higher N50, NA50 values, etc. We showed that at least 09% (259/2873) of the variants present in the assemblies between MEGAHIT and metaSPAdes are unique to one of the assembly methods. CONCLUSION: Our analyses indicate the critical role of assembly methods for assembling SARS-CoV-2 genome using short reads and their impact on variant characterization. This study could help guide future studies to determine the best-suited assembler for the de novo assembly of virus genomes.

The Deltacron conundrum: Its origin and potential health risks.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), since its outbreak in December 2019, has been capable of continuing the pandemic by mutating itself into different variants. Mass vaccinations, antibiotic treatment therapy, herd immunity, and preventive measures have reduced the disease's severity from the emerging variants. However, the virus is undergoing recombination among the current two variants: Delta and Omicron, resulting in a new variant, informally known as "Deltacron," which was controversial as it might be a product of lab contamination between Omicron and Delta samples. However, the proclamation was proved wrong, and the experts are putting more effort into better understanding the variant's epidemiological characteristics to control potential outbreaks. This review has discussed the potential mutations in the novel variant and prospective risk factors and therapeutic options in the context of this new variant. This study could be used as a guide for implementing appropriate controls in a sudden outbreak of this new variant.

Omicron variant of SARS-CoV-2: Genomics, transmissibility, and responses to current COVID-19 vaccines.

Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide as an Omicron variant. This variant is a heavily mutated virus and designated as a variant of concern by the World Health Organization (WHO). WHO cautioned that the Omicron variant of SARS-CoV-2 held a very high risk of infection, reigniting anxieties about the economy's recovery from the 2-year pandemic. The extensively mutated Omicron variant is likely to spread internationally, posing a high risk of infection surges with serious repercussions in some areas. According to preliminary data, the Omicron variant of SARS-CoV-2 has a higher risk of reinfection. On the other hand, whether the current COVID-19 vaccines could effectively resist the new strain is still under investigation. However, there is very limited information on the current situation of the Omicron variant, such as genomics, transmissibility, efficacy of vaccines, treatment, and management. This review focused on the genomics, transmission, and effectiveness of vaccines against the Omicron variant, which will be helpful for further investigation of a new variant of SARS-CoV-2.

Corticosteroids for COVID-19: worth it or not?

Pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced COVID-19 implied the presence of excessive proinflammatory cytokines and chemokines in patients causing significant morbidity and mortality. To diminish systemic hyper inflammation, a few physicians and researchers have utilized corticosteroids. Corticosteroid implementation has increased after the publication of interim guidelines regarding corticosteroid use in COVID-19 patients by WHO, despite the remaining controversies regarding long-term side effects and disease progression capability of corticosteroids. In different studies, the implementation of corticosteroids on COVID-19 patients revealed controversial results, which require further intensive research. This review will present the current outcomes and possibilities of using corticosteroids to treat COVID-19 patients.

COVID-19-associated-mucormycosis: possible role of free iron uptake and immunosuppression.

COVID-19-associated-mucormycosis, commonly referred to as the "Black Fungus," is a rare secondary fungal infection in COVID-19 patients prompted by a group of mucor molds. Association of this rare fungal infection with SARS-CoV-2 infection has been declared as an endemic in India, with minor cases in several other countries around the globe. Although the fungal infection is not contagious like the viral infection, the causative fungal agent is omnipresent. Infection displays an overall mortality rate of around 50%, with many other secondary side effects posing a potential threat in exacerbating COVID-19 mortality rates. In this review, we have accessed the role of free iron availability in COVID-19 patients that might correlate to the pathogenesis of the causative fungal agent. Besides, we have analyzed the negative consequences of using immunosuppressive drugs in encouraging this opportunistic fungal infection.

COVID-19-Associated Candidiasis: Possible Patho-Mechanism, Predisposing Factors, and Prevention Strategies.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is threatening public health. A large number of affected people need to be hospitalized. Immunocompromised patients and ICU-admitted patients are predisposed to further bacterial and fungal infections, making patient outcomes more critical. Among them, COVID-19-associated candidiasis is becoming more widely recognized as a part of severe COVID-19 sequelae. While the molecular pathophysiology is not fully understood, some factors, including a compromised immune system, iron and zinc deficiencies, and nosocomial and iatrogenic transmissions, predispose COVID-19 patients to candidiasis. In this review, we discuss the existing knowledge of the virulence characteristics of Candida spp. and summarize the key concepts in the possible molecular pathogenesis. We analyze the predisposing factors that make COVID-19 patients more susceptible to candidiasis and the preventive measures which will provide valuable insights to guide the effective prevention of candidiasis in COVID-19 patients.

Analysis of plant-derived phytochemicals as anti-cancer agents targeting cyclin dependent kinase-2, human topoisomerase IIa and vascular endothelial growth factor receptor-2.

Cancer is caused by a variety of pathways, involving numerous types of enzymes. Among them three enzymes i.e. Cyclin-dependent kinase-2 (CDK-2), Human topoisomerase IIα, and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) are three of the most common enzymes that are involved in the cancer development. Although many chemical drugs are already available in the market for cancer treatment, plant sources are known to contain a wide variety of agents that are proved to possess potential anticancer activity. In this experiment, total thirty phytochemicals were analyzed against the mentioned three enzymes using different tools of bioinformatics and in silico biology like molecular docking study, drug likeness property experiment, ADME/T test, PASS prediction, and P450 site of metabolism prediction as well as DFT calculation to determine the three best ligands among them that have the capability to inhibit the mentioned enzymes. From the experiment, Epigallocatechin gallate was found to be the best ligand to inhibit CDK-2, Daidzein showed the best inhibitory activities towards the Human topoisomerase IIα, and Quercetin was predicted to be the best agent against VEGFR-2. They were also predicted to be quite safe and effective agents to treat cancer. However, more in vivo and in vitro analyses are required to finally confirm their safety and efficacy in this regard.

SARS-CoV-2: a new dimension to our understanding of coronaviruses.

Coronaviruses have marked their significant emergence since the twenty-first century with the outbreaks of three out of the seven existing human coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. These viruses have not only acquired large-scale transmission during their specified outbreak period, but cases of MERS-CoV still remain active, although there is only limited transmission. While, on the other hand, SARS-CoV-2 continues to remain a rising threat to global public health. The recent novel coronavirus, SARS-CoV-2, responsible for the ongoing coronavirus disease 2019 (COVID-19), emerged during December 2019 in Wuhan, China, and has repeatedly raised questions about its characteristic variability. Despite belonging to the same family, SARS-CoV-2 has proven to be quite difficult to control and contain in terms of transmissibility, leading to around 19.8 million reported cases and more than 730,000 deaths of individuals worldwide. Here, we discuss how SARS-CoV-2 differs from its two other related human coronaviruses in terms of genome composition, site of infection, and transmissibility, among several other notable aspects-all indicating to the possibility that it is these variations in addition to other unknowns that are contributing to this virus' differing deadly pattern.

Silent hypoxia in COVID-19: pathomechanism and possible management strategy.

The novel coronavirus disease 2019 (COVID-19) has become a severe health issue, especially to the patients who develop silent hypoxia condition after SARS-CoV-2 infection. Due to the lack of dyspnoea and extremely low oxygen saturation level, these patients are at exceptionally higher risk. Although the prevalence of silent hypoxia in COVID-19 patients has been evident in several cases, the underlying pathomechanism behind this condition is still unclear. Silent hypoxia in SARS-CoV-2 infected patients can be diagnosed with the help of a pulse oximeter, blood gas levels, and a 6-min walking test. While the clinicians and researchers figure out the exact reason for this phenomenon, the patients must be under strict day-to-day monitoring. In this article, we aim to provide comprehensive insights into the underlying symptoms, mechanism, and possible factors behind the occurrence of silent hypoxia among COVID-19 patients.

Influence on attitudes and lifestyle due to lockdown amidst COVID-19 pandemic: a perception-based analysis among Bangladeshi residents.

BACKGROUND: Countrywide lockdown or stay-at-home order has been implemented to slow down the transmission of emergent coronavirus. However, the influence on attitudes and lifestyle due to lockdown amidst the coronavirus disease 2019 (COVID-19) pandemic has been poorly understood. The present study aimed to investigate the influence on attitudes and lifestyle due to lockdown amidst the COVID-19 pandemic among Bangladeshi residents. METHODS: A cross-sectional survey carried out involving 1635 community dwellers across eight divisions in Bangladesh conducted from April 15, 2020 to May 10, 2020. A structured questionnaire incorporating socio-demographic, attitudes towards lockdown and adverse lifestyle amidst lockdown measures was employed to collect data using the Google Forms. Multiple regression analyses were executed to determine the associated factors of positive attitudes towards lockdown and adverse lifestyle. RESULTS: The mean scores of attitudes towards lockdown were 67.9 (SD = 8.4) out of 85 with an overall correct rate (positive attitudes) of 79.9%; whereas the mean scores of adverse lifestyle amidst lockdown were 16.1 (SD = 4.8) out of 34 with an overall rate of 47.4%. The factors associated with more positive attitudes towards lockdown included being female, divorced, higher educated, and students. Conversely, being male, having no formal education, and rural residence were associated factors of adverse lifestyle amidst the COVID-19 pandemic. CONCLUSIONS: The findings reflect how the COVID-19 lockdown has preciously impacted the attitudes, and lifestyle of Bangladeshi citizens, which will contribute to promoting appropriate measures during a subsequent zonal or complete lockdown.

Curcumin analogs as the inhibitors of TLR4 pathway in inflammation and their drug like potentialities: a computer-based study.

Toll-like receptor 4 (TLR4) pathway is one of the major pathways that mediate the inflammation in human body. There are different anti-inflammatory drugs available in the market which specifically act on different signaling proteins of TLR4 pathway but they do have few side effects and other limitations for intended use in human body. In this study, Curcumin and its different analogs have been analyzed as the inhibitors of signaling proteins, i.e. Cycloxygenase-2 (COX-2), inhibitor of kappaß kinase (IKK) and TANK binding kinase-1 (TBK-1) of TLR4 pathway using different computational tools. Initially, three compounds were selected for respective target based on free binding energy among which different compounds were reported to have better binding affinity than commercially available drug (control). Upon continuous computational exploration with induced fit docking (IFD), 6-Gingerol, Yakuchinone A and Yakuchinone B were identified as the best inhibitors of COX-2, IKK, and TBK-1 respectively. Then their drug-like potentialities were analyzed in different experiments where they were also predicted to perform well. Hopefully, this study will uphold the efforts of researchers to identify anti-inflammatory drugs from natural sources.

Insights into the Transmission, Host Range, Genomics, Vaccination, and Current Epidemiology of the Monkeypox Virus.

This review delves into the historical context, current epidemiological landscape, genomics, and pathobiology of monkeypox virus (MPXV). Furthermore, it elucidates the present vaccination status and strategies to curb the spread of monkeypox. Monkeypox, caused by the Orthopoxvirus known as MPXV, is a zoonotic ailment. MPXV can be transmitted from person to person through respiratory droplets during prolonged face-to-face interactions. While many cases of monkeypox are self-limiting, vulnerable groups such as young children, pregnant women, and immunocompromised individuals may experience severe manifestations. Diagnosis predominantly relies on clinical presentations, complemented by laboratory techniques like RT-PCR. Although treatment is often not required, severe cases necessitate antiviral medications like tecovirimat, cidofovir, and brincidofovir. Vaccination, particularly using the smallpox vaccine, has proven instrumental in outbreak control, exhibiting an efficacy of at least 85% against mpox as evidenced by data from Africa. Mitigating transmission requires measures like wearing surgical masks, adequately covering skin lesions, and avoiding handling wild animals.

Comprehensive analysis of antigenic variations and genomic properties of hepatitis B virus in clinical samples in the mid-north east region of Bangladesh.

This investigation delineates an exhaustive analysis of the clinical, immunological, and genomic landscapes of hepatitis B virus (HBV) infection across a cohort of 22 verified patients. The demographic analysis unveiled a pronounced male bias (77.27%), with patient ages spanning 20 to 85 years and durations of illness ranging from 10 days to 4 years. Predominant clinical manifestations included fever, fatigue, anorexia, abdominal discomfort, and arthralgia, alongside observed co-morbidities such as chronic renal disorders and hepatocellular carcinoma. Antigenic profiling of the HBV envelope proteins elucidated significant heterogeneity among the infected subjects, particularly highlighted by discordances in the detection capabilities of small and large HBsAg assays, suggesting antigenic diversity. Quantitative assessment of viral loads unveiled a broad spectrum, accompanied by atypical HBeAg reactivity patterns, challenging the reliability of existing serological markers. Correlative studies between viral burden and antigenicity of the envelope proteins unearthed phenomena indicative of diagnostic evasion. Notably, samples demonstrating robust viral replication were paradoxically undetectable by the large HBsAg ELISA kit, advocating for more sophisticated diagnostic methodologies. Genotypic examination of three HBV isolates classified them as genotype D (D2), with phylogenetic alignment to strains from various global origins. Mutational profiling identified pivotal mutations within the basic core promoter and preS2/S1 regions, associated with an augmented risk of hepatocellular carcinoma. Further, mutations discerned in the small HBsAg and RT/overlap regions were recognized as contributors to vaccine and/or diagnostic escape mechanisms. In summation, this scholarly discourse elucidates the intricate interplay of clinical presentations, antigenic diversity, and genomic attributes in HBV infection, accentuating the imperative for ongoing investigative endeavors to refine diagnostic and therapeutic modalities.

COVID-19 in Bangladesh: Wave-centric assessments and mitigation measures for future pandemics.

The ongoing pandemic COVID-19 caused by Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) has wreaked havoc globally by affecting millions of lives. Although different countries found the implementation of emergency measures useful to combat the viral pandemic, many countries are still experiencing the resurgence of COVID-19 cases with new variants even after following strict containment guidelines. Country-specific lessons learned from the ongoing COVID-19 pandemic can be utilized in commencing a successful battle against the potential future outbreaks. In this article, we analyzed the overall scenario of the COVID-19 pandemic in Bangladesh from Alpha to Omicron variant and discussed the demographic, political, economic, social, and environmental influences on the mitigation strategies employed by the country to combat the pandemic. We also tried to explore the preparedness and precautionary measures taken by the responsible authorities, the choice of strategies implemented, and the effectiveness of the response initiated by the government and relevant agencies. Finally, we discussed the possible strategies that might help Bangladesh to combat future COVID-19 waves and other possible pandemics based on the experiences gathered from the ongoing COVID-19 pandemic.

Corrigendum: Insights into the coinfections of human immunodeficiency virus-hepatitis B virus, human immunodeficiency virus-hepatitis C virus, and hepatitis B virus-hepatitis C virus: prevalence, risk factors, pathogenesis, diagnosis, and treatment.

[This corrects the article DOI: 10.3389/fmicb.2021.780887.].

A computational approach to design a polyvalent vaccine against human respiratory syncytial virus.

Human Respiratory Syncytial Virus (RSV) is one of the leading causes of lower respiratory tract infections (LRTI), responsible for infecting people from all age groups-a majority of which comprises infants and children. Primarily, severe RSV infections are accountable for multitudes of deaths worldwide, predominantly of children, every year. Despite several efforts to develop a vaccine against RSV as a potential countermeasure, there has been no approved or licensed vaccine available yet, to control the RSV infection effectively. Therefore, through the utilization of immunoinformatics tools, a computational approach was taken in this study, to design a multi-epitope polyvalent vaccine against two major antigenic subtypes of RSV, RSV-A and RSV-B. Potential predictions of the T-cell and B-cell epitopes were followed by extensive tests of antigenicity, allergenicity, toxicity, conservancy, homology to human proteome, transmembrane topology, and cytokine-inducing ability. The peptide vaccine was modeled, refined, and validated. Molecular docking analysis with specific Toll-like receptors (TLRs) revealed excellent interactions with suitable global binding energies. Additionally, molecular dynamics (MD) simulation ensured the stability of the docking interactions between the vaccine and TLRs. Mechanistic approaches to imitate and predict the potential immune response generated by the administration of vaccines were determined through immune simulations. Subsequent mass production of the vaccine peptide was evaluated; however, there remains a necessity for further in vitro and in vivo experiments to validate its efficacy against RSV infections.

Computational designing of a novel subunit vaccine for human cytomegalovirus by employing the immunoinformatics framework.

Human cytomegalovirus (HCMV) is a widespread virus that can cause serious and irreversible neurological damage in newborns and even death in children who do not have the access to much-needed medications. While some vaccines and drugs are found to be effective against HCMV, their extended use has given rise to dose-limiting toxicities and the development of drug-resistant mutants among patients. Despite half a century's worth of research, the lack of a licensed HCMV vaccine heightens the need to develop newer antiviral therapies and vaccine candidates with improved effectiveness and reduced side effects. In this study, the immunoinformatics approach was utilized to design a potential polyvalent epitope-based vaccine effective against the four virulent strains of HCMV. The vaccine was constructed using seven CD8+ cytotoxic T lymphocytes epitopes, nine CD4+ helper T lymphocyte epitopes, and twelve linear B-cell lymphocyte epitopes that were predicted to be antigenic, non-allergenic, non-toxic, fully conserved, and non-human homologous. Subsequently, molecular docking study, protein-protein interaction analysis, molecular dynamics simulation (including the root mean square fluctuation (RMSF) and root mean square deviation (RMSD)), and immune simulation study rendered promising results assuring the vaccine to be stable, safe, and effective. Finally, in silico cloning was conducted to develop an efficient mass production strategy of the vaccine. However, further in vitro and in vivo research studies on the proposed vaccine are required to confirm its safety and efficacy.Communicated by Ramaswamy H. Sarma.

Circulating tumor DNA in cancer diagnosis, monitoring, and prognosis.

BACKGROUND: Circulating tumor DNA (ctDNA) has become one of the crucial components for cancer detection with the increase of precision medicine practice. ctDNA has great potential as a blood-based biomarker for the detection and treatment of cancer in its early stages. The purpose of this article was to discuss ctDNA and how it can be utilized to detect cancer. The benefits and drawbacks of this cancer detection technology, as well as the field's future possibilities in various cancer management scenarios, are discussed. MAIN TEXT: ctDNA has clinical applications in disease diagnosis and monitoring. It can be used to identify mutations of interest and genetic heterogeneity. Another use of ctDNA is to monitor the effects of therapy by detecting mutation-driven resistance. Different technologies are being used for the detection of ctDNA. Next-generation sequencing, digital PCR, real-time PCR, and mass spectrometry are used. Using dPCR makes it possible to partition and analyze individual target sequences from a complex mixture. Mass-spectrometry technology enables accurate detection and quantification of ctDNA mutations at low frequency. Surface-enhanced Raman spectroscopy (SERS) and UltraSEEK are two systems based on this technology. There is no unified standard for detecting ctDNA as it exists in a low concentration in blood. As there is no defined approach, false positives occur in several methods due to inadequate sensitivities. Techniques used in ctDNA are costly and there is a limitation in clinical settings. SHORT CONCLUSION: A detailed investigation is urgently needed to increase the test's accuracy and sensitivity. To find a standard marker for all forms of cancer DNA, more study is needed. Low concentrations of ctDNA in a sample require improved technology to provide the precision that low concentrations of ctDNA in a sample afford.