Viral Load Levels Research Articles

Hepatitis C virus core antigen: A diagnostic and treatmentmonitoring marker of hepatitis C virus in Indian population.

The diagnosis and treatment monitoring of hepatitis C is quite challenging. The screening test, i.e. antibody assay, is unable to detect acute cases, while the gold standard hepatitis C virus (HCV) reverse transcriptase polymerase chain reaction (RTPCR) assay is not feasible in resource-limited countries such as India due to high cost and infrastructure requirement. European Association for the Study of the Liver and World Health Organization have approved a new marker, i.e. HCV core antigen (HCVcAg) assay, as an alternative to molecular assay. In this study, we have evaluated HCVcAg assay for diagnosis and treatment monitoring follow-up in Indian population infected with hepatitis C. Blood specimen of 90 clinically suspected cases of acute hepatitis C were tested simultaneously for anti-HCV antibody assay via ELISA (enzyme-linked immunoassay), HCVcAg assay by chemiluminescence immune assay (CLIA) and HCV RTPCR VL (viral load) assay. Thirty-four HCV RTPCR positive patients were further enrolled in treatment monitoring group whose blood samples were tested at thebeginning of treatment, twoweeks, fourweeks and 12weeks via HCV core Ag assay and HCV RTPCR Viral Load assay. Considering HCV RTPCR as gold standard, diagnostic performance of HCV core Ag assay and anti-HCV antibody assay was evaluated. The sensitivity and specificity of HCV core Ag assay were higher than that of anti-HCV Antibody assay, i.e. 88.3% and 100% vs. 23.3% and 83.3%, respectively. The overall diagnostic accuracy of HCV core Ag assay was 92.20%. Among treatment follow-up group, HCV core Ag levels correlated well with HCV viral load levels, at the beginning of treatment (baseline) till 12weeks showing highly significant Spearman rank correlation coefficient of > 0.9 with HCV viral load levels. HCV core Ag assay is a cost-effective, practically feasible substitute of HCV RTPCR viral load assay for diagnosis as well as long duration treatment monitoring of hepatitis C infection in resource-limited settings.

The importance of monitoring viral activity and viral load of SARS-CoV-2

The COVID-19 pandemic has made it possible to study many aspects of the laboratory diagnosis of this infection, including the assessment of the viral load and viral activity of SARS-CoV-2. The review presents data on modern views on the virological characteristics of the SARS-CoV-2 virus, however, many aspects of this problem remain debatable. The issues of the relationship between the level of viral load and the clinical profile of patients are proposed for discussion, and the possibility of using the obtained data in practical healthcare is discussed. The control of viral load in patients with COVID-19 has not only a certain clinical significance, but is also undoubtedly important in the epidemiological aspect. Monitoring of a number of SARS-CoV-2 parameters. will allow to solve practical problems in the context of the ongoing pandemic.

Abstract 787: SARS-COV-2 P.1 strain infection in lung, breast and colon tumoral patient-derived organoids

Abstract Coronavirus 2019 disease (COVID-19), caused by the newly identified strain of the coronavirus family capable of inducing acute respiratory syndrome, rapidly escalated into a pandemic, triggering a public health emergency. Throughout this period, it became evident that increased attention should be addressed towards at-risk groups, particularly individuals with chronic illnesses, including cancer. World widely, lung, breast, and colon cancer stand as the most prevalent types of cancer exhibiting high mortality rates in both men and women. Epidemiological data demonstrate that cancer patients, particularly those with lung, breast, and colon cancer, face elevated risk and severity when infected by SARS-CoV-2, resulting in even higher mortality rates. However, there is a knowledge gap concerning the interaction between COVID-19 and cancer patients, and thus, the current proposal evaluated SARS-CoV-2 infection in biopsy cells extracted from lung, breast, and colon cancer patients, cultivated as a patient-derived organoid (PDOs). Additionally, we also evaluated SARS-CoV-2 infection in a 3D model of spheroids in LC319, CALU-3, A549, H460, MRC-5, MDA-MB-231, MCF-10A and CACO-2 cell lines. Both PDOs and spheroids were infected with the SARS-Cov-2 P.1 strain with a multiplicity of infection (MOI) of 0.01 for 24 hours. We observed that PDOs and tumoral and non-tumoral spheroids were equally permissive to SARS-CoV-2 infection showing similar viral load levels. However, we observed a cytopathic effect after SARS-CoV-2 P.1 strain infection only in tumoral cells in comparison to non-tumoral cells from the same tissue. Furthermore, we explored the cytopathic effects caused by SARS-CoV-2 infection in PDOs and in tumoral and non-tumoral spheroids by scanning electron microscopy (SEM). Interestingly, we observed morphological alterations on the surface of SARS-CoV-2 P.1 strain -tumoral infected cells, with the occurrence of surface projections after 1 hour infection. Finally, we performed an exome sequencing analysis of PDOs and tumoral and non-tumoral cells which preliminarily indicated an intriguing and informative crosstalk between cancer-related genes and SARS-CoV-2 infection pathways. Here we have identified missense and nonsense mutations in genes involved in PI3K pathway, immune function, and cell cycle regulation. In summary, our study showed that SARS-CoV-2 P.1 strain can infect and directly induce cytopathic effects in lung, breast, and colon tumors. Citation Format: Tayanne F. Sassaro, Anael Viana, Mariano Zalis, Carlos Gil Moreira Ferreira, Jorge Canedo, Danielle Ferreira, Aline S. Moreira, Elen Mello, Fabiana Rondão, Beatriz I. Ferreira, Otacilio C. Moreira, Daniel A. Moreira, Bruno Souza, Mariana C. Waghabi, Tatiana M. Tilli. SARS-COV-2 P.1 strain infection in lung, breast and colon tumoral patient-derived organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 787.

Stressing out-carp edema virus induces stress and modulates immune response in common carp.

Carp edema virus (CEV) is a fish poxvirus that primarily infects the gills of common carp. CEV causes koi sleepy disease (KSD), which is highly contagious and can result in mortality of up to 100%. In the present study, we analyzed the stress and immune responses during KSD in two strains of common carp with different resistance to CEV: susceptible koi and resistant Amur sazan. Experiments were performed at two temperatures: 12°C and 18°C. In the case of koi carp, we also analyzed the effect of supplementation of 0.6% NaCl into tank water, which prevents mortality of the CEV-infected fish (salt rescue model). We found that CEV-infected koi kept at 18°C had the highest viral load, which correlated with the most severe histopathological changes in the gills. CEV infection resulted in the activation of stress response reflected by the upregulated expression of genes involved in stress response in the stress axis organs and increased levels of cortisol and glucose in the blood plasma. These changes were the most pronounced in CEV-infected koi kept at 18°C. At both temperatures, the activation of antiviral immune response was observed in koi kept under freshwater and NaCl conditions upon CEV infection. Interestingly, a clear downregulation of the expression of adaptive immune genes was observed in CEV-infected koi kept under freshwater at 18°C. CEV induces a stress response and modulates adaptive immune response in koi, and this is correlated with the level of viral load and disease development.

Clinical and immunologic features of co-infection in COVID-19 patients, along with potential traditional Chinese medicine treatments.

With the increasing number of people worldwide infected with SARS-CoV-2, the likelihood of co-infection and/or comorbidities is rising. The impact of these co-infections on the patient's immune system remains unclear. This study aims to investigate the immunological characteristics of secondary infections in hospitalized COVID-19 patients, and preliminarily predict potential therapeutic effects of traditional Chinese medicine and their derivatives for the treatment of co-infections. In this retrospective cohort study, we included 131 hospitalized patients with laboratory-confirmed COVID-19, of whom there were 64 mild and 67 severe cases. We analyzed clinical characteristics and immunologic data, including circulating immune cell numbers, levels of inflammatory factors and viral load, comparing COVID-19 patients with and without co-infection. Among 131 hospitalized COVID-19 patients, 41 (31.3%) were co-infection positive, with 33 (80.5%) having severe disease and 14 (34.1%) of them resulting in fatalities. Co-infected patients exhibited significantly higher severity and mortality rates compared to non-co-infected counterparts. Co-infected patients had significantly lower absolute counts of lymphocytes, total T lymphocytes, CD4+ T cells, CD8+ T cells and B lymphocytes, while levels of hs-CRP, PCT and IL-6 were significantly elevated compared to non-co-infected patients. Additionally, the viral load of co-infected patients was significantly higher than non-co-infected patients. Co-infection emerges as a dangerous factor for COVID-19 patients, elevating the risk of severe pneumonia and mortality. Co-infection suppresses the host's immune response by reducing the number of lymphocytes and increasing inflammation, thereby diminishing the antiviral and anti-infective effects of the immune system, which promotes the severity of the disease. Therefore, it is crucial to implement infection prevention measures to minimize the spread of co-infections among COVID-19 hospitalized patients. Additionally, changes in these biomarkers provide a theoretical basis for the effective treatment of co-infections with traditional Chinese medicine.

Factors associated with HIV viral load control in the early postpartum period – a Canadian prospective cohort study

ABSTRACT Despite success in managing HIV during pregnancy, challenges remain around sustained adherence with antiretroviral therapy (ART), and the suboptimal viral load (VL) suppression during the postpartum period. The objective of this study was to compare VL levels at delivery and during the postpartum period and assess factors associated with lack of viral suppression during the postpartum period in Canada. We combined data from two Canadian prospective cohorts, which included 286 HIV-positive women (352 pregnancies) who delivered between 2012 and 2020. Delivery VL, postpartum VL, and potential factors associated with an undetectable VL (<50 copies/mL), 2–18 weeks after delivery were assessed. To account for the correlation between multiple pregnancies from the same woman, generalized estimating equations were used to assess bivariate associations. Ninety-nine per cent of pregnant women were on ART during pregnancy compared to 93% during the postpartum period. Of those with available VL results (n = 214 pregnancies), 94% of women achieved an undetectable VL at delivery compared to 87% during the postpartum period. The postpartum period is a challenging time for ART use and VL control. Qualitative studies are needed to better understand these challenges and guide us in designing adequate interventions.

Routine evaluation of HBV-specific T cell reactivity in chronic hepatitis B using a broad-spectrum T-cell epitope peptide library and ELISpot assay

BackgroundThe clinical routine test of HBV-specific T cell reactivity is still limited due to the high polymorphisms of human leukocyte antigens (HLA) in patient cohort and the lack of universal detection kit, thus the clinical implication remains disputed.MethodsA broad-spectrum peptide library, which consists of 103 functionally validated CD8+ T-cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins and fits to the HLA polymorphisms of Chinese and Northeast Asian populations, was grouped into eight peptide pools and was used to establish an ELISpot assay for enumerating the reactive HBV-specific T cells in PBMCs. Totally 294 HBV-infected patients including 203 ones with chronic hepatitis B (CHB), 13 ones in acute resolved stage (R), 52 ones with liver cirrhosis (LC) and 26 ones with hepatocellular carcinoma (HCC) were detected, and 33 CHB patients were longitudinally monitored for 3 times with an interval of 3–5 months.ResultsThe numbers of reactive HBV-specific T cells were significantly correlated with ALT level, HBsAg level, and disease stage (R, CHB, LC and HCC), and R patients displayed the strongest HBV-specific T cell reactivity while CHB patients showed the weakest one. For 203 CHB patients, the numbers of reactive HBV-specific T cells presented a significantly declined trend when the serum viral DNA load, HBsAg, HBeAg or ALT level gradually increased, but only a very low negative correlation coefficient was defined (r = − 0.21, − 0.21, − 0.27, − 0.079, respectively). Different Nucleotide Analogs (NUCs) did not bring difference on HBV-specific T cell reactivity in the same duration of treatment. NUCs/pegIFN-α combination led to much more reactive HBV-specific T cells than NUCs monotherapy. The dynamic numbers of reactive HBV-specific T cells were obviously increasing in most CHB patients undergoing routine treatment, and the longitudinal trend possess a high predictive power for the hepatitis progression 6 or 12 months later.ConclusionThe presented method could be developed into an efficient reference method for the clinical evaluation of cellular immunity. The CHB patients presenting low reactivity of HBV-specific T cells have a worse prognosis for hepatitis progression and should be treated using pegIFN-α to improve host T-cell immunity.

Phylogenetic position and genetic features of HIV-1 in CNS

Background. Due to the wide coverage with antiretroviral therapy, the life expectancy of HIV infected people has significantly increased. Against the background of a decrease in mortality from HIV infection, HIV-associated neurocognitive disorders, which develop even during effective treatment, are of high importance. The overall prevalence of this pathology among HIV-infected people reaches 42.6%.&#x0D; The objective of the study was to research the genetic features and phylogenetic position of HIV-1 persisting in the central nervous system.&#x0D; Materials and methods. The clinical study group consisted of 38 patients with severe neurocognitive disorders against the background of HIV infection in stage 4B. The viral load of HIV-1 in blood plasma and cerebrospinal fluid (CSF) was measured using the "AmpliSens HIV Monitor-FRT" reagents kit. Sanger sequencing was performed using the AmpliSens HIV-Resist-Seq assay kit on an Applied Biosystems 3500 analyzer. Phylogenetic analysis of the pol gene fragments of HIV-1 strains (the site encoding the viral protease and part of the reverse transcriptase) was carried out using maximum likelihood method with the GTR+G nucleotide substitution model. Comparisons of the tertiary structure of viral proteins were performed according to three-dimensional models of the protease and p51 and p66 reverse transcriptase subunits obtained by homologous reconstruction using the SWISS-MODEL tools.&#x0D; Results. The viral load in the sample of patients with severe CNS lesions in blood plasma was 6.27 times higher than in CSF and amounted to 4.67 and 3.87 lg copies/ml respectively by median (p = 0,004).&#x0D; Phylogenetic analysis with the use of all available HIV-1 genomes from GenBank, which differed from the studied ones by less than 5% showed close genetic relations of viruses circulating in Chelyabinsk region, apart from strains circulating in Russian Federation, with viruses circulating in neighboring countries, in most abundance — from Ukraine and Kyrgyzstan, slightly less — from Belarus, Tajikistan, Kazakhstan and Armenia and also with strains from certain foreign countries: Poland and Germany. Phylogenetic analysis of 38 HIV-1 genomes revealed significant genetic distances between HIV isolates from blood plasma and CSF in 5 patients, 4 of whom were PWID, which may indicate an event of superinfection.&#x0D; The amount of independent amino acid substitutions in protease in isolates from blood plasma ranged from 1 to 3, in isolates from CSF — from 1 to 2. An amount of such substitutions in a fragment of reverse transcriptase in isolates from blood plasma ranged from 1 to 6, while in isolates from CSF, it ranged from 1 to 7. HIV isolates from blood plasma and CSF from 5 patients had differences in the tertiary structure of HIV-1 reverse transcriptase p51 subunit in amino acid positions 16–20 and 210–235. Isolates from 3 other patients differed in the tertiary structure only in amino acid positons 210–235. Isolates from 3 patients differed in the structure of HIV-1 RT p66 subunit in a non-nucleoside reverse transcriptase inhibitor binding pocket (NNRTI) region. Fixed differences in the tertiary structure of p51 subunit required at minimum only 1 amino acid substitution to emerge. Alterations in the tertiary structure of p66 subunit required at least 3 amino acid substitutions.&#x0D; Conclusion. Microevolution of HIV-1 proceeds in parallel within the same patient, in different compartments, which is reflected in the accumulation of amino acid substitutions different from another compartment in the conserved pol gene. There is a weak correlation between the viral load level in plasma and in CSF. The genetic heterogeneity of HIV strains from patients of the Chelyabinsk region indicates a high frequency of reintroduction of HIV infection in the region from other countries. Differences in the tertiary structure of HIV-1 reverse transcriptase between blood plasma and CSF isolates are regularly fixed in certain domens, which also confirms the presence of parallel HIV microevolution during virus persistence in tissues separated by the blood-brain barrier which allows a better understanding of the fixation trends of individual amino acid substitutions during HIV-induced damage to central nervous system.

Prolonged coagulation times in severe fever with thrombocytopenia syndrome virus infection, the indicators of heparin-like effect and increased haemorrhagic risk.

Prolonged coagulation times, such as activated partial thromboplastin time (APTT) and thrombin time (TT), are common in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV) and have been confirmed to be related to patient's poor outcome by previous studies. To find out the reason for prolonged coagulation time in patients with SFTSV infection, and whether it predicts haemorrhagic risk or not. Seventy-eight consecutive patients with confirmed SFTSV infection were enrolled in this prospective, single-centre, observational study. Several global and specific coagulation parameters of these patients on admission were detected, and the haemorrhagic events during hospitalization and their outcomes were recorded. Most of the enrolled patients had prolonged APTT (82.1%) and TT (80.8%), normal prothrombin time (83.3%) and intrinsic coagulation factors above haemostatic levels (97.4%). The heparin-like effect was confirmed by a protamine neutralization test and anti-Xa activity detection in most patients. Interestingly, the APTT and TT results were significantly positively correlated with the levels of endothelial markers and viral load, respectively. The APTT was independently associated with the haemorrhage of patients. The prolonged APTT and TT of SFTS patients may mainly be attributed to endogenous heparinoids and are associated with increased haemorrhagic risk.

Evaluation of the ELITechGroup solution for plasma HIV-1 RNA quantification

In the last few years, many manufacturers have developed new kits for plasma HIV-1 RNA quantification. Recently, a solution consisting of the ELITe InGenius® instrument and the HIV1 ELITe MGB®kit has been commercialized worldwide. Our aim was to compare its clinical performance with the Aptima® HIV-1 Quant Dx kit by Hologic, on a panel of HIV-1 group M circulating variants, representative of viral load levels found during the pre- and post-treatment follow-up of patients. The linearity was evaluated on the AcroMetrix® HIV-1 Panel. Clinical specificity was evaluated on 100 plasma samples negative for HIV; and clinical sensitivity and sequential follow-up were evaluated on 166 HIV-1 positive plasma samples from 126 patients. The linearity data showed a difference obtained for each point of less than 0.2 Log cp/mL. No amplification was found for the 100 HIV negative clinical specimens. The overall agreement between the two kits was 83.7 %; the differences corresponded to a slightly higher detection for the Aptima kit (with more samples detected below the lower limit of quantification). A Bland & Altman analysis of the quantifiable samples showed a mean difference of −0.05 Log and Spearman's coefficient was 0.975. Only six samples presented discrepancies (above 0.5 Log), but these differences were overall similar between the two kits. Our study has shown that the HIV1 ELITe MGB® Kit can be successfully used for the monitoring of patients infected with various epidemic HIV-1 strains, and for the precise quantification of the viral load.

Cordycepin Inhibits Enterovirus A71 Replication and Protects Host Cell from Virus-Induced Cytotoxicity through Adenosine Action Pathway.

Enterovirus A71 (EV-A71) infection typically causes mild illnesses, such as hand-foot-and-mouth disease (HFMD), but occasionally leads to severe or fatal neurological complications in infants and young children. Currently, there is no specific antiviral treatment available for EV-A71 infection. Thus, the development of an effective anti-EV-A71 drug is required urgently. Cordycepin, a major bioactive compound found in Cordyceps fungus, has been reported to possess antiviral activity. However, its specific activity against EV-A71 is unknown. In this study, the potency and role of cordycepin treatment on EV-A71 infection were investigated. Results demonstrated that cordycepin treatment significantly reduced the viral load and viral ribonucleic acid (RNA) level in EV-A71-infected Vero cells. In addition, EV-A71-mediated cytotoxicity was significantly inhibited in the presence of cordycepin in a dose-dependent manner. The protective effect can also be extended to Caco-2 intestinal cells, as evidenced by the higher median tissue culture infectious dose (TCID50) values in the cordycepin-treated groups. Furthermore, cordycepin inhibited EV-A71 replication by acting on the adenosine pathway at the post-infection stage. Taken together, our findings reveal that cordycepin could be a potential antiviral candidate for the treatment of EV-A71 infection.

Efficacy and Safety of Nirmatrelvir/Ritonavir in Severe Hospitalized Patients with COVID-19 and in Patients at High Risk for Progression to Critical Illness: A Real-World Study.

Background: Nirmatrelvir/Ritonavir is an orally administered anti-SARS-Cov-2 drug used in mild-to-moderate COVID-19 patients. Our retrospective cohort study aims to evaluate the efficacy and safety of Nirmatrelvir/Ritonavir in severe hospitalized patients with Omicron infection, as well as in patients at high risk for progression to critical illness in real-world settings. Methods: A total of 350 patients received Nirmatrelvir/Ritonavir while 350 matched controls did not. Patients with confirmed COVID-19 were administered Nirmatrelvir 300 mg and Ritonavir 100 mg orally twice a day for 5 days, with the medication initiated on the first day after admission. The primary endpoint of the study was a composite outcome of hospitalization or death from any cause within 28 days. Secondary endpoints included the occurrence of adverse events and the evaluation of serum levels of IL-6 and viral load. Results: We documented the mortality risk from any cause within 28 days, viral load, serum IL-6 levels, and adverse events. Nirmatrelvir/Ritonavir reduced the 28-day risk of all-cause mortality by 86% (P = .011, hazard ratio (HR) = 0.14, 95% confidence interval (CI) = 0.03, 0.64). At baseline, the serum level of IL-6 was significantly higher in the antiviral treatment group compared to the control group (P < .001), but no significant difference (P = .990) was found between the two groups at discharge. In CKD patients undergoing hemodialysis, no significant worsening of renal function was observed in the Nirmatrelvir/Ritonavir treatment group compared to the control group. Conclusion: Nirmatrelvir/Ritonavir may reduce the 28-day risk of all-cause mortality in critically ill patients with COVID-19 and in patients at high risk for critical disease progression.

Precise control of digital dental unit to reduce aerosol and splatter production: new challenges for future epidemics

BackgroundDuring dental procedures, critical parameters, such as cooling condition, speed of the rotary dental turbine (handpiece), and distance and angle from pollution sources, were evaluated for transmission risk of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), simulated by spiking in a plasmid encoding a modified viral spike protein, HexaPro (S6P), in droplets and aerosols.MethodsTo simulate routine operation in dental clinics, dental procedures were conducted on a dental manikin within a digital dental unit, incorporating different dental handpiece speeds and cooling conditions. The tooth model was immersed in Coomassie brilliant blue dye and was pre-coated with 100 μL water spiked-in with S6P-encoding plasmid. Furthermore, the manikin was surrounded by filter papers and Petri dishes positioned at different distances and angles. Subsequently, the filter papers and Petri dishes were collected to evaluate the aerosol splash points and the viral load of S6P-encoding plasmid in aerosols and splatters generated during the dental procedure.ResultsAerosol splashing generated a localized pollution area extended up to 60 cm, with heightened contamination risks concentrated within a 30 cm radius. Significant differences in aerosol splash points and viral load by different turbine handpiece speeds under any cooling condition (P < 0.05) were detected. The highest level of aerosol splash points and viral load were observed when the handpiece speed was set at 40,000 rpm. Conversely, the lowest level of aerosol splash point and viral load were found at a handpiece speed of 10,000 rpm. Moreover, the aerosol splash points with higher viral load were more prominent in the positions of the operator and assistant compared to other positions. Additionally, the position of the operator exhibited the highest viral load among all positions.ConclusionsTo minimize the spread of aerosol and virus in clinics, dentists are supposed to adopt the minimal viable speed of a dental handpiece with limited cooling water during dental procedures. In addition, comprehensive personal protective equipment is necessary for both dental providers and dental assistants.

Prior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters.

Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza A (H1N1pdm09) interactions in Syrian hamsters. H1N1 given 48 h prior to SARS-CoV-2 profoundly mitigated weight loss and lung pathology compared to SARS-CoV-2 infection alone. This was accompanied by the normalization of granulocyte dynamics and accelerated antigen-presenting populations in bronchoalveolar lavage and blood. Using nasal transcriptomics, we identified a rapid upregulation of innate and antiviral pathways induced by H1N1 by the time of SARS-CoV-2 inoculation in 48 h dual-infected animals. The animals that were infected with both viruses also showed a notable and temporary downregulation of mitochondrial and viral replication pathways. Quantitative RT-PCR confirmed a decrease in the SARS-CoV-2 viral load and lower cytokine levels in the lungs of animals infected with both viruses throughout the course of the disease. Our data confirm that H1N1 infection induces rapid and transient gene expression that is associated with the mitigation of SARS-CoV-2 pulmonary disease. These protective responses are likely to begin in the upper respiratory tract shortly after infection. On a population level, interaction between these two viruses may influence their relative seasonal infection rates.

Net-Shaped DNA Nanostructure-Based Lateral Flow Assays for Rapid and Sensitive SARS-CoV-2 Detection.

Lateral flow assay (LFA)-based rapid antigen tests are experiencing extensive global uptake as an expeditious and highly effective modality for the screening of viral infections during the COVID-19 pandemic. While these devices have played a significant role in alleviating the burden on the public healthcare system, their specificity and sensitivity fall short compared with molecular tests. In this study, we endeavor to address both limitations through the utilization of DNA nanotechnology in LFA format, wherein we substitute the target-specific antibody with designer DNA nanostructure-based molecular probes for recognizing the SARS-CoV-2 virus via multivalent, pattern-matching interactions. We meticulously designed a Net-shaped DNA nanostructure and strategically arranged trimeric clusters of aptamers that specifically recognize the spike proteins of SARS-CoV-2. This approach has proven instrumental in bolstering virus-binding affinity on the LFAs. Our findings indicate high LFA sensitivity, enabling the detection of viral loads ranging from 103 to 108 viral copies/mL. This notable sensitivity is maintained across various SARS-CoV-2 viral strains, obviating the need for intricate sample preparation protocols. The significance of this heightened sensitivity lies in the crucial role played by the designer DNA nanostructure, which facilitates the detection of extremely low levels of viral loads. This not only enhances the overall reliability of self-testing but also reduces the likelihood of false-negative results, especially in cases of low viral load within patient samples.

Distribution and Clinical Significance of Hepatitis B virus A1762T/G1764A Double Mutation in Chronic Hepatitis B Patients: A Cross-Sectional Study.

Chronic hepatitis B (CHB) is well-known as a major risk for liver cirrhosis and hepatocellular carcinoma (HCC). The A1762T/G1764A double mutation in the hepatitis B virus genome affects the production of HBe antigen and is established as a predictive marker for progression to HCC. Thus, this study aimed to investigate the prevalence and clinical significance of the mutation in Thai CHB patients. A cross-sectional study was conducted in 78 Thai CHB patients who were assessed for hepatitis B profiles, HBsAg, HBeAg and anti-HBeAg, transaminitis, liver fibrosis defined by FIB-4 (FIB-4) score and AST to platelet ratio index (APRI), alpha-fetoprotein (AFP) and active hepatitis B status. HBV A1762T/G1764A mutation was examined by SYBR Green I Real-time PCR. Chi-square and Mann-Whiney U tests were performed to determine the association between the mutation and variables. The prevalence of patients infected with the A1762T/G1764A mutation was 44.9%. The mutation was associated with HBeAg status (p=0.027) and HBsAg levels (p=0.008), transaminitis (p=0.011), and active hepatitis B (p=0.037), but not liver fibrosis markers, FIB-4 score and APRI, and AFP. Binary logistic regression identified the mutation as a predictive factor of active hepatitis B (OR 3.5, 95%CI, 1.1-11.3, p=0.037). Patients infected with the mutant exhibited significantly higher levels of HBsAg (p=0.011) and HBV viral load (p=0.047), but lower levels of HBeAg (p=0.12) than those infected with the wild-type HBV. The data indicate the high prevalence of the A1762T/G1764A mutation and its significant association with the severity of Thai CHB patients and the HBV mutation is proposed as a predictive marker of active hepatitis B status in CHB patients.

Genetic and Epigenetic Determinants of COVID-19 Susceptibility: A Systematic Review.

The molecular mechanisms regulating coronavirus pathogenesis are complex, including virus-host interactions associated with replication and innate immune control. However, some genetic and epigenetic conditions associated with comorbidities increase the risk of hospitalization and can prove fatal in infected patients. This systematic review will provide insight into host genetic and epigenetic factors that interfere with COVID-19 expression in light of available evidence. This study conducted a systematic review to examine the genetic and epigenetic susceptibility to COVID-19 using a comprehensive approach. Through systematic searches and applying relevant keywords across prominent online databases, including Scopus, PubMed, Web of Science, and Science Direct, we compiled all pertinent papers and reports published in English between December 2019 and June 2023. The findings reveal that the host's HLA genotype plays a substantial role in determining how viral protein antigens are showcased and the subsequent immune system reaction to these antigens. Within females, genes responsible for immune system regulation are found on the X chromosome, resulting in reduced viral load and inflammation levels when contrasted with males. Possessing blood group A may contribute to an increased susceptibility to contracting COVID-19 as well as a heightened risk of mortality associated with the disease. The capacity of SARS-CoV-2 involves inhibiting the antiviral interferon (IFN) reactions, resulting in uncontrolled viral multiplication. There is a notable absence of research into the gender-related predisposition to infection, necessitating a thorough examination. According to the available literature, a significant portion of individuals affected by the ailment or displaying severe ramifications already had suppressed immune systems, categorizing them as a group with elevated risk.

Epidemiology of hepatitis C infection among pregnant women and parturients in Nizhny Novgorod

Hepatitis C is an urgent global health problem. The high prevalence of infection among the population leads to the involvement of women of reproductive age in the epidemic process. In order to study the prevalence of specific markers of hepatitis C virus in pregnant women and to assess the risk of intrauterine infection of the fetus, an epidemiologic analysis was conducted using information collections of statistical and analytical materials of Rospotrebnadzor, blood serum samples of pregnant and postpartum women (n = 28394) at admission to obstetric institutions for the period 2018–2022 were examined. According to statistical reporting, the average annual prevalence of anti-HCV prevalence in pregnant women was 1.7% (95% CI: 1.5–1.9%). Women aged 40–49 years were found to be most actively involved in the epidemic process (4.3% [95% CI: 3.3–5.6%]). Among anti-HCV-positive samples, HCV RNA was detected in 47.0% (95% CI: 41.7–52.9%) of cases, the prevalence of current infection confirmed by HCV RNA detection in pregnant women was 0.9% (95% CI: 0.8–1.0%). The pattern of HCV genotypes in pregnant women was as follows: subtype 1b was detected in 34.9% (95% CI: 25.6–45.7%) of cases, subtype 3a in 42.2% (95% DI: 32.1–52.9%), minor subtype 1a was 9.6% (95% CI: 5.0–17.9%) and genotype 2 was 7.0% (95% CI: 3.4–14.9%). Samples containing two genotypes simultaneously (1a/1b, 1b/3a) were 3.6% (95% CI: 1.2–10.1%) and non-genotyped samples were 2.4% (95% CI: 0.7–4.1%). The results of the assessment of the significance of risk factors for perinatal transmission of hepatitis C virus show a high degree of influence on vertical transmission of HCV RNA in the presence of active infection in the mother (RR = 6.4; [95% CI: 0.9–44.6%]: p &lt; 0.05), no statistical significance of HCV genotypic affiliation (p &gt; 0.05) and maternal viral load level (R = 0.00009; p &gt; 0.05). The obtained data argue the necessity of screening examinations for molecular genetic markers of hepatitis C virus in women planning pregnancy in order to conduct antiviral therapy and, as a consequence, to reduce the risk of perinatal infection of children.

Chikusetsusaponin IVa Protects against H9N2 Avian Influenza Virus Infection by Inhibiting Inflammation and TLR4/NF-κB Signaling Pathways in vitro and in vivo

Background The prevalence of Hemagglutinin 9 Neuraminidase 2 (H9N2) avian influenza virus (AIV) in poultry in Asia has raised serious concerns about its zoonotic transmission and the potential for a pandemic, underscoring the need for effective therapeutics. Chikusetsusaponin IVa (CHS), a bioactive triterpenoid saponin from Radix saposhnikoviae, has exhibited anti-inflammatory activity in preclinical studies. We hypothesized that CHS could mitigate immunopathology during tumor necrosis factor (TNF)-infection by suppressing excessive inflammation. Objectives CHS is a natural saponin with anti-inflammatory activity. This research aimed to explore the in vitro and in vivo protective effects and mechanisms of CHS against H9N2 AIV infection. Materials and Methods We employed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis for the prediction of the underlying mechanisms, followed by a network analysis approach. In animal experiments, the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathways and associated proteins were assessed using immunohistochemistry and western blot analysis. Results In A549 cells, CHS treatment reduced H9N2 AIV-induced apoptosis in a dose-dependent manner. CHS was found to have a suppressive effect on the mRNA expression of various inflammatory cytokines (including TNF-α, interleukin (IL)-6, IL-1β, and IL-8) as well as mediators such as inducible nitric oxide synthase (iNOS) and prostaglandin-endoperoxide synthase 2 (PTGS2). It can be seen that CHS does have anti-inflammatory effects. Bioinformatics analysis indicated that CHS might exhibit anti-inflammatory effects by modulating cytokine–cytokine receptor interaction and the NF-κB signaling pathways. Building upon this, it was found that CHS blocked the activation of TLR4 and NF-κB signaling pathways in A549 cells infected with H9N2 AIV. In vivo, CHS prolonged the survival time and increased the survival rate of H9N2 AIV-infected mice. CHS was found to have a protective effect on the lungs of infected mice, resulting in reduced damage and lower levels of viral load and inflammation. CHS inhibited the production of proinflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-8) and inhibited the activation of TLR4 and NF-κB signaling pathways in the pulmonary tissues of mice that were infected. Conclusion CHS exerts protective effects against H9N2 AIV infection in vitro and in vivo. The anti-inflammatory mechanisms may involve the inhibition of cytokine production and the blockade of TLR4 and NF-κB signaling pathways.

Temporal cytokine storm dynamics in dengue infection predicts severity

The immunopathogenesis of dengue severity is convoluted. The primary objective of the research was to examine the dynamics of cytokine storm and its correlation with disease development in individuals affected by DENV infection. Additionally, the study aimed to discover potential biomarkers that could indicate severe dengue infection and determine the most suitable timeframe for predicting the severity of these biomarkers during the acute stage of dengue infections. We conducted a temporal analysis of the daily viral load and cytokine levels in 60 hospitalized dengue patients until discharge. Our findings reveal a distinct cytokine profile (elevated IL-8, IL-10, IL-6, GM-CSF, MCP-1, IL-13, and IL-4 and decreased IL-12, MIP-1β) on the third day after symptom onset is predictive of severe dengue in secondary dengue infection. The imbalanced cytokine signature may inform clinical decision-making in treating severe dengue infections.