Viral Load In Patients Research Articles

Co-relation of SARS-CoV-2 related 30-d mortality with HRCT score and RT-PCR Ct value-based viral load in patients with solid malignancy.

BACKGROUNDCoronavirus disease 2019 (COVID-19) patients with malignancy are published worldwide but are lacking in data from India.AIMTo characterize COVID-19 related mortality outcomes within 30 d of diagnosis with HRCT score and RT-PCR Ct value-based viral load in various solid malignancies.METHODSPatients included in this study were with an active or previous malignancy and with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the institute database. We collected data on demographic details, baseline clinical conditions, medications, cancer diagnosis, treatment and the COVID-19 disease course. The primary endpoint was the association between the mortality outcome and the potential prognostic variables, specially, HRCT score, RT-PCR Ct value-based viral load, etc. using logistic regression analyses treatment received in 30 d.RESULTSOut of 131 patients, 123 met inclusion criteria for our analysis. The median age was 57 years (interquartile range = 19-82) while 7 (5.7%) were aged 75 years or older. The most prevalent malignancies were of GUT origin 49 (39.8%), hepatopancreatobiliary (HPB) 40 (32.5%). 109 (88.6%) patients were on active anticancer treatment, 115 (93.5%) had active (measurable) cancer. At analysis on May 20, 2021, 26 (21.1%) patients had died. In logistic regression analysis, independent factors associated with an increased 30-d mortality were in patients with the symptomatic presentation. Chemotherapy in the last 4 wk, number of comorbidities (≥ 2 vs none: 3.43, 1.08-8.56). The univariate analysis showed that the risk of death was significantly associated with the HRCT score: for moderate (8-15) [odds ratio (OR): 3.44; 95% confidence interval (CI): 1.3-9.12; P = 0.0132], severe (> 15) (OR: 7.44; 95%CI: 1.58-35.1; P = 0.0112).CONCLUSIONTo the best of our knowledge, this is the first study from India reporting the association of HRCT score and RT-PCR Ct value-based 30-d mortality outcomes in SARS-CoV-2 infected cancer patients.

Evaluation of viral load in patients with Ebola virus disease in Liberia: a retrospective observational study

SummaryBackgroundViral load in patients with Ebola virus disease affects case fatality rate and is an important parameter used for diagnostic cutoffs, stratification in randomised controlled trials, and epidemiological studies. However, viral load in Ebola virus disease is currently estimated using numerous different assays and protocols that were not developed or validated for this purpose. Here, our aim was to conduct a laboratory-based re-evaluation of the viral loads of a large cohort of Liberian patients with Ebola virus disease and analyse these data in the broader context of the west Africa epidemic.MethodsIn this retrospective observational study, whole blood samples from patients at the Eternal Love Winning Africa Ebola treatment unit (Monrovia, Liberia) were re-extracted with an optimised protocol and analysed by droplet digital PCR (ddPCR) using a novel semi-strand specific assay to measure viral load. To allow for more direct comparisons, the ddPCR viral loads were also back-calculated to cycle threshold (Ct) values. The new viral load data were then compared with the Ct values from the original diagnostic quantitative RT-PCR (qRT-PCR) testing to identify differing trends and discrepancies.FindingsBetween Aug 28 and Dec 18, 2014, 727 whole blood samples from 528 individuals were collected. 463 (64%) were first-draw samples and 409 (56%) were from patients positive for Ebola virus (EBOV), species Zaire ebolavirus. Of the 307 first-draw EBOV-positive samples, 127 (41%) were from survivors and 180 (59%) were from non-survivors; 155 (50%) were women, 145 (47%) were men, and seven (2%) were not recorded, and the mean age was 29·3 (SD 15·0) years for women and 31·8 (SD 14·8) years for men. Survivors had significantly lower mean viral loads at presentation than non-survivors in both the reanalysed dataset (5·61 [95% CI 5·34–5·87] vs 7·19 [6·99–7·38] log10 EBOV RNA copies per mL; p<0·0001) and diagnostic dataset (Ct value 28·72 [27·97–29·47] vs 26·26 [25·72–26·81]; p<0·0001). However, the prognostic capacity of viral load increased with the reanalysed dataset (odds ratio [OR] of death 8·06 [95% CI 4·81–13·53], p<0·0001 for viral loads above 6·71 log10 EBOV RNA copies per mL vs OR of death 2·02 [1·27–3·20], p=0·0028 for Ct values below 27·37). Diagnostic qRT-PCR significantly (p<0·0001) underestimated viral load in both survivors and non-survivors (difference in diagnostic Ct value minus laboratory Ct value of 1·79 [95% CI 1·16–2·43] for survivors and 5·15 [4·43–5·87] for non-survivors). Six samples that were reported negative by diagnostic testing were found to be positive upon reanalysis and had high viral loads.InterpretationInaccurate viral load estimation from diagnostic Ct values is probably multifactorial; however, unaddressed PCR inhibition from tissue damage in patients with fulminant Ebola virus disease could largely account for the discrepancies observed in our study. Testing protocols for Ebola virus disease require further standardisation and validation to produce accurate viral load estimates, minimise false negatives, and allow for reliable epidemiological investigation.

SARS-CoV-2突变背景下的病毒入侵机制研究进展与干预策略

<p indent="0mm">Since coronavirus disease 2019 (COVID-19) was reported in late 2019, its causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been spreading worldwide for more than two years, and the trend continues unabated. SARS-CoV-2 is a single positive-stranded RNA virus from the same β-coronavirus family as SARS-CoV, which caused a severe acute respiratory syndrome (SARS) epidemic in 2003. Entry into the cell is mediated by the binding of the spike glycoprotein on the envelope to angiotensin converting enzyme 2 (ACE2) on the host cell, possibly with the help of co-receptors, adhesion factors, or alternative receptors. During the process of virus assembly, release, cell adhesion, and entry into the host cell, the SARS-CoV-2 spike protein must undergo a series of structural changes, including cleavage and conformational changes, to achieve membrane fusion function. After binding to cell surface receptors, SARS-CoV-2 has two invasion pathways: (i) The direct fusion pathway at the cell membrane interface, and (ii) the clathrin-mediated endocytosis pathway. In both cases, the SARS-CoV-2 spike protein must be cleaved by furin-like proteins at the S1/S2 site. Host proteases, mainly TMPRSS-2 or cathepsin, are involved in cleavage at the S2′ site, corresponding to pathway (i) or (ii). The entire entry process ends when the viral genome enters the cytosol. During the replication cycle of SARS-CoV-2, genomic RNA can be mutated. Accumulation of mutations, particularly in the spike protein, may result in new variants that differ in infectivity, transmissibility, virulence, and/or immune escape capability. These changes can alter the prevailing lineage in circulation, trigger a new wave of public health events, and threaten scientific research, clinical prevention, and treatment. The World Health Organization (WHO) has identified five mutant strains as variants of concern (VOCs) by assessing their public health significance worldwide: Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529). The Omicron variant is currently in circulation. The entry-related characteristics of VOCs may indicate global epidemiological trends and shed light on future pandemic dynamics. The entry mechanism of SARS-CoV-2, the first and crucial step in the establishment of a viral infection, has been extensively studied over the past two years. As the molecular mechanisms involved in entry are gradually being elucidated, interventions in key events may prevent viral entry and provide information for drug development and clinical treatment. Because the cellular entry mechanism of coronaviruses is relatively conserved, the first step in interrupting viral infection—blocking the entry process—is a promising target for the development of new preventive and therapeutic drugs against COVID-19 and even pan-coronavirus inhibitors, including small molecules, peptides, and monoclonal antibodies. Researchers have identified potential drug targets involved in the SARS-CoV-2 entry process, such as spike proteins, ACE2, and host proteases. Inhibition of the viral entry process is expected to reduce viral load in patients, thereby alleviating symptoms and improving prognosis. Recently, computer-aided drug design has emerged as a powerful and productive tool for drug discovery, in addition to experimental methods in the wet lab. In future anti-SARS-CoV-2 drug discovery, the flexible combination and optimized design of drug discovery strategies to improve the efficiency of drug development will be the trend. In this review, we outline the mechanism of SARS-CoV-2 entry into cells, describe the entry properties of VOCs currently defined by the WHO, and present the progress in the discovery of SARS-CoV-2 entry inhibitors.

Distribution of HCV genotypes and HCV RNA viral load in hepatitis infected patients of Kolar region, Karnataka, India.

Decisions and disease progression prediction, understanding the distribution of the hepatitis C virus (HCV) genotype and its association with viral load is significant for treatment. Therefore, it is of interest to document the distribution pattern of HCV genotypes and their association with viral load among HCV infected patients in Kolar, Karnataka. Seventy-four HCV-positive patients and not on antiviral therapy were enrolled from R.L. Jalappa hospital in Kolar, Karnataka. Blood samples were taken and demographics were recorded. HCV RNA was isolated after plasma was separated. qPCR was performed to measure the viral load, and RT-PCR was performed to determine the genotype. Genotype 3 was the prevalent (n=11, 40.7%) followed by genotype 4 (n=8, 29.6%), 2 (n=6, 22.2%), 1 (n= 13.7%), and mix (n=1, 13.7%). The median viral load of genotype 3 was a 2,87,835 IU/mL (IQR 10, 780-3, 71, 66) , genotype 2 was 81,030 IU/mL (IQR 66,495-95,565), genotype 4 was 43, 410 IU/mL (IQR 38, 355-48, 465) belongs to viral load less than 8,00,000 IU/mL. The median viral load genotype 3 was a 1, 05, 19, 500 IU/mL (IQR 49, 37, 250-2, 36, 71, 500), genotype 2 was 2,55,99,000 IU/mL (IQR 2,00,10,000-32,725,500), genotype 4 was 1,67,40,000 IU/mL (IQR 1,45,50,000-17,493,000) belonging to viral load more than 8,00,000 IU/mL category. A correlation between genotype and viral load was observed (p =1.5x10-12), of which genotype 3 showed a high viral load. Thus, HCV genotypes 1 2, 3, 4, and mixed genotype was observed in the patients studied. HCV genotype was associated with viral load in patient plasma. This data finds use in the treatment and prevention of hepatitis C in Kolar, Karnataka.

Reliable quantification of Cytomegalovirus DNAemia in Letermovir treated patients

Polymerase chain reaction (PCR) based methods are a fast and sensitive approach to detect and monitor viral load in Cytomegalovirus (CMV) patients. Letermovir (LMV) acts at a late stage during the CMV replication cycle and does not inhibit CMV DNA replication per se. Therefore, quantitative nucleic acid amplification testing might lead to the overestimation of viral load in patients treated with LMV and underestimate treatment success. To study this discrepancy, we treated infected cells with LMV or Ganciclovir (GCV) and compared viral progeny DNA levels. Prior to nucleic acid extraction and qPCR measurements we pretreated cell lysates and cell culture supernatants from infected cells with DNase I. This step assumes the degradation of DNA which is not protected from a viral capsid. LMV treatment did not reduce genomic copies (GC) in samples from whole cell lysates compared to samples treated with GCV. DNase treatment prior to DNA extraction, decreased GC in the LMV treated group to comparable levels as seen in the GCV group. In cell culture supernatants, LMV or GCV treatment led to an equivalent reduction of CMV GC. In this case, DNase treatment exerted a negligible effect on both groups. We conclude that the accumulation of concatemeric DNA within cells seems to be a confounding variable when monitoring LMV efficacy via qPCR. However, qPCR shows to be a reliable method to evaluate antiviral efficacy of LMV in cell free specimens. These results have strong clinical implications for the monitoring of CMV therapy during LMV treatment.

Association of viral load with age, gender, disease severity, and death in severe acute respiratory syndrome coronavirus 2 variants.

In this study, the relationship between viral load, demographic characteristics, and disease information in 1007 (48.5%) patients with Delta variant (B.1.617.2), and 1070 (51.5%) patients with Alpha variant (B1.1.7) were investigated. We found that there was a significant difference in viral load between patients who died from the Alpha variant and those who were discharged (p < 0.05). Nevertheless, no significant difference was observed in patients with the Delta variant. The viral load in patients who died from the Alpha variant was significantly higher than those who were discharged (p < 0.05). The viral load was found to be higher in females in patients with the Delta variant, whereas it was very close in males and females in patients with the Alpha variant (p > 0.05). No significant difference was detected between the cycle threshold values (Ct) and disease severity. In terms of the mean Ct values, statistical differences were observed in patients with Delta and Alpha variants. The Alpha variant was found to have a higher viral load than the Delta variant. Furthermore, the Delta variant was found to be higher in the 40-year-old and under-age group than the Alpha variant, whereas the Alpha variant was higher in the groups over 40 years old. Althoughthe rate of moderate and severe patients in the Alpha variant was found to be higher, the rate of mild survivors was found to be higher in the Delta variant. In conclusion, the increase in vaccination before the appearance of the Delta variant in our region may have influenced the viral load and clinical status of the patients.

Advances in the epidemiology, clinical features, diagnosis, clinical management and prevention of coronavirus disease 2019.

The current article reviews the latest information on the epidemiology, clinical features, diagnostics, clinical management and prevention of coronavirus disease 2019 (COVID-19). Atypical pneumonia due to severe acute respiratory syndrome coronavirus-2 emerged in December 2019 in a market in Wuhan, China and rapidly evolved into a pandemic in March 2020. Viral loads of patients with COVID-19 peak in the first week of illness around day 2-4 and hence there is very high-transmission potential causing community outbreaks. Asymptomatic and presymptomatic transmission is a hallmark of COVID-19. Several variants of concern (VOC) have emerged over the last 2 years and Omicron is the predominant variant in many countries. PCR is the standard diagnostic test while rapid antigen test is a useful supplementary test. Serology tests provide indirect evidence of infection 1 -2 weeks after the onset of symptoms. Molnupiravir and nirmatrelvir are oral antiviral agents that may reduce the risk of hospitalization and deaths if administered early to high-risk subjects. Remdesivir, baricitinib, anti-IL-6 tocilizumab and dexamethasone are frequently used for treatment of patients with respiratory failure. COVID-19 pandemic progresses relentlessly with substantial morbidity and mortality especially in unvaccinated subjects. Mass COVID-19 vaccinations are the most important measure for control of the COVID-19 pandemic.

Increase in Viral Load in Patients With SARS-CoV-2 Delta Variant Infection in the Republic of Korea.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly, causing in COVID-19 being declared a global pandemic by the World Health Organization. The key variants include alpha, beta, gamma, and delta; these exhibit high viral transmission, pathogenicity, and immune evasion mechanisms. The delta variant, first confirmed in India, was detected in the majority of COVID-19 patients at the recent wave in the Republic of Korea. Here, the features of the delta variant were compared to the earlier waves, with focus on increased transmissibility. The viral load, from the initial days of infection to 14 days later, was compared based on epidemiological data collected at the time of confirmed diagnosis. The increased viral load observed in the delta variant-led infections influences the scale of the wave, owing to the increased rate of transmission. Infections caused by the delta variant increases the risk of hospitalization within 14 days after symptom onset, and the high viral load correlates with COVID-19 associated morbidity and mortality. Therefore, the future studies should compare the trend of disease severity caused by the high viral load of delta variant with previous waves and analyze the vaccine effects in light of the delta variant of fourth wave.

Assessment of High-Titer Convalescent Plasma as an Adjunctive Therapy in the Reduction of Mortality Rate and Viral Load in Patients with Severe COVID-19: A Meta-Analysis

PurposeCOVID-19 has emerged as the "first pandemic of the 21st Century" and continues to pose challenges to global health. Currently, the most common symptomatic management of COVID-19 patients involves isolation and oxygen therapy. However, present protocols are still deemed insufficient; hence, other treatment options are being considered and tested. This includes convalescent plasma therapy (CPT), which involves a strategy of passive immunization.With this, the primary objective of this systematic review/meta-analysis is to collate, systematically compare, and synthesize available clinical trials involving convalescent plasma (CP), more specifically, high-titer CP, as adjunctive therapy in the treatment of patients with severe COVID-19.Methods & MaterialsThis was accomplished by comparing the effect of high-titer CP with standard treatment alone, in terms of mortality rate and viral clearance, by reviewing selected studies based on an inclusion-exclusion criteria and synthesizing selected studies through qualitative analysis and meta-analysis.ResultsA total of five studies were included, which consist of: three randomized clinical trials (RCTs); one retrospective trial; and one single arm trial. Four studies were subjected to meta-analysis for mortality rate. For instance, it was determined that the overall incidence mortality rate of patients who received high-titer CP is 11.59% of the experimental group, while the incidence mortality rate of patients who only received standard care is 20.25% of the control group (Risk Ratio (RR), 0.71; 95% confidence interval (CI),0.46-1.09; P-value = 0.46). Moreover, three of the included trials were subjected to qualitative analysis, all of which depicted undetectable viral levels in some patients as early as 3 days, while others exhibited a steady decline.ConclusionTreatment of COVID-19 with the use of high-titer convalescent plasma as an adjunctive therapy, compared with standard care or treatment, was not significantly associated with reduction of all-cause mortality. High-Titer CPT also shows potential in increasing COVID-19 viral clearance, which indicates an antiviral effect; however, controlled clinical trials with comparator or placebo groups are needed to further support these findings.

Activation of the NLRP3 inflammasome and elevation of interleukin-1\u03b2 secretion in infection by sever fever with thrombocytopenia syndrome virus

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging phlebovirus that causes a hemorrhagic fever known as the severe fever with thrombocytopenia syndrome (SFTS). Inflammasomes are a molecular platform that are assembled to process pro-caspase 1 and subsequently promote secretion of interleukin (IL)-1β/IL-18 for proinflammatory responses induced upon infection. We hypothesize that inflammasome activation and pyroptosis induced in SFTS results in elevated levels of IL-1β/IL-18 responsible for high fever and hemorrhage in the host, characteristic of SFTS. Here we report that IL-1β secretion was elevated in SFTS patients and infected mice and IL-1β levels appeared to be reversibly associated to disease severity and viral load in patients’ blood. Increased caspase-1 activation, IL-1β/IL-18 secretion, cell death, and processing of gasdermin D were detected, indicating that pyroptosis was induced in SFTSV-infected human peripheral blood monocytes (PBMCs). To characterize the mechanism of pyroptosis induction, we knocked down several NOD-like receptors (NLRs) with respective shRNAs in PBMCs and showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome was critical for processing pro-caspase-1 and pro-IL-1β. Our data with specific inhibitors for NLRP3 and caspase-1 further showed that activation of the NLRP3 inflammasome was key to caspase-1 activation and IL-1β secretion which may be inhibitory to viral replication in PBMCs infected with SFTSV. The findings in this study suggest that the activation of the NLPR3 inflammasome and pyroptosis, leading to IL-1β/IL-18 secretion during the SFTSV infection, could play important roles in viral pathogenesis and host protection. Pyroptosis as part of innate immunity might be essential in proinflammatory responses and pathogenicty in humans infected with this novel phlebovirus.

A possible dose-response equation: Viral load after plasma infusion in COVID-19 patients and anti-SARS-CoV-2 antibody titers in convalescent plasma.

Clinical trials of convalescent plasma therapy for coronavirus disease 2019 (COVID-19) are extensive, but the relationship between antibody titers, infused volume of plasma and virus clearance in patients remains unknown. This study proposed a possible estimating equation for clinical use of high antibody titer convalescent plasma. A total of 38 patients were recruited in the Guanggu District Maternal and Child Health Hospital of Hubei Province from March 1 to 30, 2020. COVID-19 convalescent plasma was collected and high-titer (≥1:640) anti-S-RBD units used. The SARS-CoV-2 nucleic acid viral load was measured 24 h before and 72 h after convalescent plasma infusion. Convalescent plasma therapy was associated with reduced viral load in patients with moderate and severe severity. The viral negative rate at 72 h was 65.8%. The disappearance of viral nucleic acid in study patients was positively correlated with infuscate antibody titer and volume (r=0.3375, p=0.04). A possible estimation equation was as follows: Log10 (Reduction in viral load)=0.18 + 0.001 × (Log2 S-RBD antibody titer × Plasma infusion volume) (r=0.424, p=0.009). In a single case, the viral nucleic acid persisted 14 days after the fourth plasma infusion. This study proposes a potential dose-response equation that adds a convenient way to estimate the dose of convalescent plasma product. It is beneficial to facilitate the rational allocation of plasma with high antibody titers and provide an individualised use strategy for convalescent plasma therapy.

Effect of 0.5% povidone-iodine on the nasopharyngeal and oropharyngeal viral loads in patients with COVID-19: A double-blind placebo-controlled randomized clinical trial.

The povidone-iodine (PvP-I) nasal antiseptic has been shown to completely inactivate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro at variable concentrations. This study was performed to investigate the effect of 0.5% PvP-I nasal drops and oral gargles on the nasopharyngeal and oropharyngeal viral loads in SARS-CoV-2-positive patients. This was a double-blind, placebo-controlled, randomized clinical trial among patients aged ≥18 years with reverse-transcriptase polymerase chain reaction confirmed in the mild to moderate category of SARS-CoV-2 infection. A total of 32 patients were randomly assigned to receive either freshly prepared 0.5% PvP-I solution or distilled water in the form of supervised self-administered 4-5 nasal drops, followed by 20 ml for gargling for at least 30 seconds. The main outcome measure was the mean change in viral titer and Ct values in the nasopharyngeal and oropharyngeal samples at baseline, 5 minutes, and 3 hours post intervention. The mean change in viral titers across the time duration for the test group when compared with the control group was not statistically significant (P = 0.109). However, the mean change in Ct value was found to be borderline statistically significant (P = 0.042). Noticeable differences were noted among the mean viral titers and Ct values in the intervention group when plotted against the time of testing as compared to the control group. PvP-I solution at 0.5% dilution was well tolerated, and no evident side effects were reported. This study shows that 0.5% PvP-I has an effect on reducing nasopharyngeal and oropharyngeal viral loads in COVID-19 patients. This can be of substantial aid for the primary care physicians, especially for the practitioners in remote and resource poor areas.

Serum levels of IL-12, IL-18, and IL-21 are indicators of viral load in patients chronically infected with HBV.

This study explored the correlation between interleukins (IL)-12, IL-18, and IL-21 and the viral load in patients with chronic hepatitis B virus (HBV). A total of 142 patients were consecutively enrolled. All were hepatitis B surface antigen (HBsAg)-positive for >6 months and did not receive drug therapy. An ELISA kit was used to test the IL-12, IL-18, IL-21, and acetylcholinesterase (AchE) levels in serum samples from chronic HBV patients and healthy control groups. The amounts of IL-12 and IL-18 were highest in the 5-6log10 (high viral load) group, while IL-21 was highest in the 3-4log10 (low viral load) group. Also, the IL-21 amount was decreased in the HBsAg+/HBeAg/HBcAb+ group, and IL-12, IL-18, and IL-21 were decreased in the normal alanine aminotransferase (ALT) group compared to the abnormal ALT group. These data suggested that IL-12, IL-18, and IL-21 serum levels were positively correlated with disease progression and could reflect disease severity for different HBV-DNA loads. Detection of IL-12, IL-18, and IL-21 levels was found to be helpful for evaluating the degree of liver cell damage and predicting the progression of hepatitis.

The Evaluation of Surrogate Laboratory Parameters for Predicting the Trend of Viral Loads in Patients with Severe Fever with Thrombocytopenia Syndrome: Cross-Correlation Analysis of Time Series

BackgroundThere is a correlation between the severe fever with thrombocytopenia syndrome (SFTS) viral load and disease severity; however, measurement of viral load is difficult in general laboratory and it takes time to obtain a viral load value. Here, the laboratory parameters for predicting the dynamic changes in SFTS viral load were identified. In addition, we tried to evaluate a specific time point for the early determination of clinical deterioration using dynamic change of laboratory parameters.Materials and MethodsThis observational study included SFTS patients in Korea (2013 - 2020). Cross-correlation analysis at lagged values was used to determine the temporal correlation between the SFTS viral loads and time-series variables. Fifty-eight SFTS patients were included in the non-severe group (NSG) and 11 in the severe group (SG).ResultsIn the cross-sectional analyses, 10 parameters -white blood cell, absolute neutrophil cell, lymphocyte, platelet, activated partial thromboplastin time (aPTT), C-reactive protein, aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK)- were assessed within 30 days from the onset of symptoms; they exhibited three different correlation patterns: (1) positive, (2) positive with a time lag, and (3) negative. A prediction score system was developed for predicting SFTS fatality based on age and six laboratory variables -platelet, aPTT, AST, ALT, LDH, and CPK- in 5 days after the onset of symptoms; this scoring system had 87.5% sensitivity and 86.0% specificity (95% confidence interval: 0.831 - 1.00, P <0.001).ConclusionThree types of correlation patterns between the dynamic changes in SFTS viral load and laboratory parameters were identified. The dynamic changes in the viral load could be predicted using the dynamic changes in these variables, which can be particularly helpful in clinical settings where viral load tests cannot be performed. Also, the proposed scoring system could provide timely treatment to critical patients by rapidly assessing their clinical course.

Factors Associated with Virological Suppression of HIV Viral Load in Patients on Antiretroviral Therapy in Conakry, Guinea

Viral load testing is a key indicator for assessing ART success and diagnosing drug resistance in people living with HIV/AIDS on antiretroviral therapy. This study aimed to assess virological suppression among people living with HIV / AIDS on antiretroviral therapy in Guinea. This was a three years descriptive cross-sectional that involved adult HIV-positive patients treated in different sites in Conakry. The study population consisted of patients living with HIV/AIDS, followed up at Conakry ART care and treatment sites, samples collected from the study population were sent to the National Institute of Public Health for viral load testing between January 2018 and June 2021. The viral load was quantified by the Generic Biocentric technique and the detection threshold set at 350 copies/ml. Factors associated with virological suppression were analysed by univariate or multivariate logistic regression. Statistical analysis were performed by R software version R4.0.3. A total of 9815 samples were collected and viral load data analyzed at the national public health laboratory. The sample was dominated by women (72%), with an average age of 29. Of these, 6,706 (68%) of people on ART had viral load suppression. The univaried analysis showed that women were (22%) more likely to have VL suppression (p-value < 0.001) moreover, the chance for all HIV-positive people on treatment to achieve viral load suppression was related to the length of treatment. The results of this study show viral load suppression greater than 68%. The length of antiretroviral therapy, female gender, and advancing age of PLHIV were associated with VL suppression. Targeted awareness raising actions must be undertaken with patients who have an important risk.

The impact of COVID-19 epidemic phase and changes in mean viral loads: implications for SARS-CoV-2 testing strategies

The sensitivity of SARS-CoV-2 diagnostic tests is inherently linked to viral load. We explored whether average viral loads changed at a population level in Queensland, Australia during the early phase of the pandemic. RT-PCR threshold cycle (CT) values, a crude marker for viral load, were compared for samples collected in February/March-2020 to those collected in April/May-2020, noting that the major public health interventions began in late-March 2020. Positive detections peaked mid-March, which coincided with the highest detection numbers and lowest CT values. However, this changed from April where the later CT samples (CT > 30) predominated. Overall, in February/March 29% (267/922) of samples had CT values >30 cycles compared to 88% (559/636) in April/May. Our study shows that SARS-CoV-2 viral loads in patients may vary at a population level over time. This needs considering when assessing suitability of diagnostic methods, particularly when methods in question are known to have reduced sensitivity.

Successful Treatment with ALVR105 for Disseminated Adenovirus Infection in an Infant after Allogeneic Hematopoietic Cell Transplantation: A Case Report

Background: Adenovirus (AdV) disease is one of the most difficult-to-manage complications in infants and children who have received allogeneic hematopoietic cell transplantation (HCT). Cidofovir has been used off-label as preemptive anti-adenoviral therapy. It is the current standard of care treatment, but data supporting its therapeutic value are lacking, and its use is limited by severe renal toxicity.Case: A 10-month-old male with infantile osteopetrosis underwent a single-unit umbilical cord blood transplant (TNC = 21.78 × 10 7/kg, CD34 = 10.5 × 10 5/kg) after myeloablative conditioning (busulfan, cyclophosphamide, and anti-thymocyte globulin). Cyclosporine and mycophenolate mofetil (MMF) were used for graft versus host disease (GVHD) prophylaxis. A positive test for adenovirus from a respiratory viral panel pre-transplant delayed conditioning for six weeks until the patient had two negative tests, one week apart. His post-transplant course was complicated by severe veno-occlusive disease starting on day +3, with secondary respiratory and renal failure. The patient was started on continuous renal replacement therapy along with intravenous defibrotide and high-dose steroids. Neutrophil engraftment did not occur until day +38. Post-engraftment, the patient developed a skin rash diagnosed as GVHD by biopsy, which was treated with corticosteroids at 2 mg/kg/day. As part of viral infection surveillance, the patient received a weekly blood PCR test for adenovirus; on day +25 it was noted he had reactivated adenovirus. He had been demonstrating overall clinical improvement, including declining hepatic transaminases and bilirubin, and reduced respiratory support requirements until day +39, when he developed fever with an increased need for respiratory support and rising transaminases. The respiratory viral panel showed that the patient was positive for adenovirus. Further workup also showed adenovirus PCR positive in stool and increase in quantitative adenoviremia, all consistent with disseminated adenoviral infection. The use of cidofovir was contraindicated in this patient due to renal toxicity.ALVR105 (Viralym-M), an allogeneic, off-the-shelf, multivirus-specific T-cell therapy (VST) that can target AdV, BKV, CMV, EBV, HHV-6, and JCV, was provided by AlloVir on a compassionate-use basis. A cell line that was HLA matched to the patient at 2 out of 8 HLA-A, HLA-B, HLA-DR, and HLA-DQ alleles was identified. After emergency IND approval, institutional review board approval, and family consent, one ALVR105 dose of 0.7 × 10 7 cells was infused on day +48. The dosage was calculated based on the patient's age, weight (8.5 kg), body surface area (0.35 m 2), and the dosing regimen used in a previous phase 2 trial. The patient developed fever and low blood pressure around 30 hours post-infusion, requiring an increase in his existing inotropic support and stress dose hydrocortisone. This was likely associated with underlying post-transplant complications, but a possible association with ALVR105 infusion could not be ruled out.The patient's viral load decreased substantially in the following weeks (Table 1). Concurrently, his liver enzymes, pulmonary secretions, and respiratory support requirements all improved. His respiratory secretions became negative for adenovirus PCR at day +28 post-infusion of ALVR105.At the time of writing, the patient was day +100 post-transplant (day +56 post-infusion of ALVR105), and his veno-occlusive disease had improved. Supplemental oxygen was no longer required, but volume-assured pressure was still in use, likely due to hepatosplenomegaly. The patient had detectable adenovirus viremia but below the threshold of quantitative measurement (<190 copies/ ml). The patient remains well-engrafted with evidence of persistent ALVR105 (Viralym-M) as illustrated in Table-2, but the % of Allovir cells are below our lab's 5% validation threshold. The patient's GVHD has resolved. MMF dosing was stopped on day + 31 from transplant, and the patient is receiving only cyclosporine and physiologic doses of hydrocortisone.Conclusion: In this infant with post allogeneic HCT disseminated adenovirus infection, ALVR105 appeared to be safe and was temporally associated with marked clinical improvement, suggesting VSTs may be of value in very young patients with adenovirus infection. This represents the first use of ALVR105 in an infant (< 1-year-old) patient. [Display omitted] DisclosuresMoon: Allovir: Current Employment, Current equity holder in publicly-traded company. OffLabel Disclosure:Virus specific cell therapy, used against adenovirus infection in post-transplant setting.

Relationship between gut microbiome diversity and hepatitis B viral load in patients with chronic hepatitis B

BackgroundHepatitis B virus (HBV) infection is associated with a reduced risk of developing dyslipidemia and non-alcoholic fatty liver diseases. Given that the gut microbiota plays a significant role in cholesterol metabolism, we compared the differences in gut microbial diversity and composition between HBV-infected and uninfected subjects.ResultsA prospective case–control study was designed comprising healthy controls (group A) and HBV-infected individuals (group B) in a 1:1 ratio (57 participants each; total = 114). The patients in group B were divided into two subgroups according to their HBV DNA loads: B1 < 2000 IU/mL (N = 40) and B2 ≥ 2000 IU/mL (N = 17). In a pairwise comparison of HBV-infected individuals and controls, higher alpha diversity was noted in group B, and the difference was significant only in patients in group B1. Alloprevotella and Eubacterium coprostanoligenes were predominant in group B1 compared to the control, whereas the abundance of Bacteroides fragilis and Prevotella 2 was lower.ConclusionsThe gut microbiome in HBV-infected individuals with a low viral load is highly diverse and is dominated by specific taxa involved in fatty acid and lipid metabolism. To our knowledge, this is the first demonstration of a correlation between the presence of certain bacterial taxa and chronic HBV infection depending on the load of HBV DNA.

Viral Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 in Patients with Coronavirus Disease 2019.

ABSTRACTTo determine the relationship between viral kinetics and severity of disease in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we investigated the viral kinetics and compared the viral loads of patients with coronavirus disease 2019 (COVID-19; the disease caused by SARS-CoV-2), stratified by symptoms and severity. We determined the viral kinetics of 100 patients diagnosed with COVID-19 at Chosun University Hospital between February 2020 and May 2021 and analyzed the differences between asymptomatic, symptomatic, and nonsurvivor patients and between patients who died and those who survived. Clinical samples, comprising respiratory specimens (sputum samples and nasopharynx and oropharynx swab samples), were obtained at different time points of hospitalization, at 1, 3 to 5, 7, 10, 14, and 30 days. SARS-CoV-2 was detected using real-time reverse transcription-PCR (RT-PCR). All three groups, asymptomatic, symptomatic, and deceased patients, had higher numbers of viral copies at symptom onset, and the asymptomatic group had lower numbers of viral copies than the symptomatic or nonsurvivor group. Viral RNA release was detected until 30 days after symptom onset. The virus cleared up earlier in asymptomatic patients than in symptomatic and nonsurvivor patients, and it cleared up earlier in mildly affected patients than in severely affected patients. The cycle threshold values tended to be significantly lower in the group receiving steroids than in the nonsteroid group, even in the low-risk group with a pneumonia severity index of less than 90. The viral loads in patients with COVID-19 were significantly different according to disease severity and steroid use.IMPORTANCE In our study, we analyzed the viral kinetics of COVID-19 patients. Our study reveals differences in viral shedding according to the severity of disease in COVID-19 patients. Viral shedding had a longer duration in severely affected patients, and the cyclic threshold values were lower in the group receiving steroids. This study is expected to be helpful in analyzing the trend of the disease course according to steroid use and severity of SARS-CoV-2 disease.

Oral Microbiome Alterations and SARS-CoV-2 Saliva Viral Load in Patients with COVID-19.

ABSTRACTBacterial-viral interactions in saliva have been associated with morbidity and mortality for respiratory viruses such as influenza and SARS-CoV. However, such transkingdom relationships during SARS-CoV-2 infection are currently unknown. Here, we aimed to elucidate the relationship between saliva microbiota and SARS-CoV-2 in a cohort of newly hospitalized COVID-19 patients and controls. We used 16S rRNA sequencing to compare microbiome diversity and taxonomic composition between COVID-19 patients (n = 53) and controls (n = 59) and based on saliva SARS-CoV-2 viral load as measured using reverse transcription PCR (RT-PCR). The saliva microbiome did not differ markedly between COVID-19 patients and controls. However, we identified significant differential abundance of numerous taxa based on saliva SARS-CoV-2 viral load, including multiple species within Streptococcus and Prevotella.IMPORTANCE Alterations to the saliva microbiome based on SARS-CoV-2 viral load indicate potential biologically relevant bacterial-viral relationships which may affect clinical outcomes in COVID-19 disease.