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2.
AIDS Patient Care STDS ; 37(2): 66-83, 2023 02.
Article in English | MEDLINE | ID: covidwho-20240507

ABSTRACT

To broaden access to HIV viral load monitoring (VLM), the use of blood samples from dried blood spots (DBS) or point-of-care (POC) devices, could be of great help in settings where plasma is not easily accessible. The variety of assays available makes the choice complex. This systematic review and meta-analysis aims to estimate the sensitivity and specificity of DBS and POC devices to identify patients in virological failure using World Health Organization (WHO) recommendations (viral load ≥1000 copies/mL), compared with plasma, for the assays currently available. Four databases were searched for articles, and two reviewers independently identified articles reporting sensitivity and specificity of DBS and/or POC to identify patients in virological failure. We excluded articles that used other thresholds as well as articles with a total number of participants below 50 to avoid reporting bias. Heterogeneity and factors associated with assays' performances were assessed by I2 statistics and metaregression. The protocol of this review follows the PRISMA guidelines. Out of 941 articles, 47 were included: 32 DBS evaluations and 16 POC evaluations. Overall, when using DBS, the Abbott RT HIV-1, Roche CAP-CTM, NucliSENS BioMerieux and Aptima assays presented sensitivity and specificity exceeding 85%, but reported results were highly heterogeneous. Factors associated with better performances were high volume of blood and the use of the same assay for DBS and plasma VLM. Regarding the POC devices, SAMBA I, SAMBA II, and GeneXpert devices presented high sensitivity and specificity exceeding 90%, with less heterogeneity. DBS is suitable VLM, but performances can vary greatly depending on the protocols, and should be performed in trained centers. POC is suitable for VLM with less risk of heterogeneity but is more intensive in costs and logistics.


Subject(s)
HIV Infections , HIV Seropositivity , Humans , Point-of-Care Systems , Sensitivity and Specificity , Viral Load , RNA, Viral
3.
J Infect Chemother ; 29(7): 678-682, 2023 Jul.
Article in English | MEDLINE | ID: covidwho-20237106

ABSTRACT

BACKGROUND: Parainfluenza virus type 3 (PIV-3) is one of the common pathogens for respiratory infections in children. Whether viral load of PIV-3 is associated with severity of respiratory diseases in children is not yet known. Our aim was to determine significance of PIV-3 viral load among infected children. METHODS: We conducted a single-center, retrospective study at Tokyo Metropolitan. Children's Medical Center, Japan, from June to August 2021. Hospitalized children were screened with a posterior nasal swab for multiplex PCR, and viral load was subsequently measured from remained samples by real-time PCR. Demographic data were collected from digital charts. PIV-3 positive patients were categorized into mild group with no oxygen demand, moderate group with low-flow oxygen demand and severe group with high-flow nasal cannula oxygen or non-invasive positive pressure ventilation or mechanical ventilation. Viral loads were compared among mild, moderate and severe groups. RESULTS: 151 patients were positive for PIV-3. We found no statistically significant association among PIV-3 viral load and severity of respiratory diseases (p = 0.35), and no statistically significant association between severity of illness and co-detection of other viruses. In each severity group, relatively high viral load per posterior nasal swab was observed at the time of testing. CONCLUSION: Among PIV-3 patients, we could not find statistically significant between viral load and their severity, therefore we could not conclude that viral load is a good surrogate marker for clinical severity of PIV-3.


Subject(s)
Respiratory Tract Infections , Virus Diseases , Child , Humans , Infant , Parainfluenza Virus 3, Human/genetics , Viral Load , Retrospective Studies , Respiratory Tract Infections/diagnosis , Multiplex Polymerase Chain Reaction
4.
Pathog Glob Health ; 117(5): 476-484, 2023 07.
Article in English | MEDLINE | ID: covidwho-20236771

ABSTRACT

The cycle threshold (Ct) in quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) is inversely correlated to the amount of viral nucleic acid or viral load and can be regarded as an indicator of infectivity. We examined the association of socio-demographic and clinical characteristics of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) polymerase chain reaction (PCR) positive cases with PCR cycle threshold (Ct) values at the time of diagnosis. SARS-CoV-2 cases reported between 12 October 2020 and 24 January 2021 in Regensburg were analyzed employing bivariate and multivariable methods. We included 3,029 SARS-CoV-2 cases (31% asymptomatic at diagnosis) and analyzed the association of case characteristics with Ct values in 2,606 cases. Among symptomatic patients, cough (38.0%), rhinitis (32.4%), headache (32.0), and fever/chills (29.9%) were the most frequent complaints. Ct values ≤20 were more frequent in symptomatic cases (20.9% vs. 11.3%), whereas Ct values >30 were more common in asymptomatic cases (32.6% vs. 18.0%). Ct values >20 and ≤30 were most common in symptomatic and asymptomatic cases (48.0% vs 40.7%). We observed lower median Ct values of E and N gene in symptomatic cases. In a random forest model, the total number of symptoms, respiratory symptoms, and age were most strongly associated with low Ct values. In conclusion, certain symptoms and age were associated with lower Ct values. Ct values can be used as a pragmatic approach in estimating infectivity at the first notification of a case and, thus, in guiding containment measures.


Subject(s)
COVID-19 , Humans , SARS-CoV-2/genetics , Cross-Sectional Studies , Real-Time Polymerase Chain Reaction , Viral Load , COVID-19 Testing
5.
J Med Virol ; 95(5): e28773, 2023 05.
Article in English | MEDLINE | ID: covidwho-20234567

ABSTRACT

This review will provide an overview of the notion that Kaposi sarcoma (KS) is a disease that manifests under diverse and divergent circumstances. We begin with a historical introduction of KS and KS-associated herpesvirus (KSHV), highlight the diversity of clinical presentations of KS, summarize what we know about the cell of origin for this tumor, explore KSHV viral load as a potential biomarker for acute KSHV infections and KS-associated complications, and discuss immune modulators that impact KSHV infection, KSHV persistence, and KS disease.


Subject(s)
Herpesvirus 8, Human , Sarcoma, Kaposi , Humans , Viral Load
6.
BMC Res Notes ; 16(1): 90, 2023 May 25.
Article in English | MEDLINE | ID: covidwho-20235604

ABSTRACT

BACKGROUND: Adherence to antiretroviral therapy and COVID-19 preventive behaviours among people living with HIV during the pandemic has received little attention in the literature. To address this gap in knowledge, the present study assessed the associations between viral load, adherence to antiretroviral therapy and the use of COVID-19 prevention strategies during the first wave of the COVID-19 pandemic. This was a secondary analysis of data generated through an online survey recruiting participants from 152 countries. Complete data from 680 respondents living with HIV were extracted for this analysis. RESULTS: The findings suggest that detectable viral load was associated with lower odds of wearing facemasks (AOR: 0.44; 95% CI:0.28-0.69; p < 0.01) and washing hands as often as recommended (AOR: 0.64; 95% CI: 0.42-0.97; p = 0.03). Also, adherence to the use of antiretroviral drugs was associated with lower odds of working remotely (AOR: 0.60; 95% CI: 0.38-0.94; p = 0.02). We found a complex relationship between HIV positive status biological parameters and adherence to COVID-19 preventive measures that may be partly explained by risk-taking behaviours. Further studies are needed to understand the reasons for the study findings.


Subject(s)
COVID-19 , HIV Infections , Humans , Pandemics/prevention & control , COVID-19/epidemiology , Viral Load , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/prevention & control , Anti-Retroviral Agents/therapeutic use
7.
Front Public Health ; 11: 1167104, 2023.
Article in English | MEDLINE | ID: covidwho-20235542

ABSTRACT

Introduction: Virtual and low-touch behavioral interventions are needed for African American/Black and Latino persons living with HIV (PLWH) with barriers to HIV viral suppression, particularly during COVID-19. Guided by the multiphase optimization strategy, we explored three components for PLWH without viral suppression, grounded in motivational interviewing and behavioral economics: (1) motivational interviewing counseling, (2) 21-weeks of automated text messages and quiz questions about HIV management, and (3) financial rewards for viral suppression (lottery prize vs. fixed compensation). Methods: This pilot optimization trial used sequential explanatory mixed methods to explore the components' feasibility, acceptability, and preliminary evidence of effects using an efficient factorial design. The primary outcome was viral suppression. Participants engaged in baseline and two structured follow-up assessments over an 8-month period, and provided laboratory reports to document HIV viral load. A subset engaged in qualitative interviews. We carried out descriptive quantitative analyses. Then, qualitative data were analyzed using directed content analysis. Data integration used the joint display method. Results: Participants (N = 80) were 49 years old, on average (SD = 9), and 75% were assigned male sex at birth. Most (79%) were African American/Black, and the remainder were Latino. Participants were diagnosed with HIV 20 years previously on average (SD = 9). Overall, components were feasible (>80% attended) and acceptability was satisfactory. A total of 39% (26/66) who provided laboratory reports at follow-up evidenced viral suppression. Findings suggested no components were entirely unsuccessful. The lottery prize compared to fixed compensation was the most promising component level. In qualitative analyses, all components were seen as beneficial to individual wellbeing. The lottery prize appeared more interesting and engaging than fixed compensation. However, structural barriers including financial hardship interfered with abilities to reach viral suppression. The integrated analyses yielded areas of convergence and discrepancy and qualitative findings added depth and context to the quantitative results. Conclusions: The virtual and/or low-touch behavioral intervention components tested are acceptable and feasible and show enough potential to warrant refinement and testing in future research, particularly the lottery prize. Results must be interpreted in the context of the COVID-19 pandemic. Trial registration: NCT04518241 (https://clinicaltrials.gov/ct2/show/NCT04518241).


Subject(s)
COVID-19 , HIV Infections , Motivational Interviewing , Humans , Male , Middle Aged , Black or African American , Economics, Behavioral , Hispanic or Latino , HIV Infections/epidemiology , Pandemics , Viral Load , Adult , Female
8.
Viruses ; 15(5)2023 05 08.
Article in English | MEDLINE | ID: covidwho-20235357

ABSTRACT

BACKGROUND: Since limited data are available, we aimed to compare the efficacy and durability of dolutegravir and darunavir in advanced naïve patients. METHODS: Retrospective multicenter study including AIDS- or late-presenting (def. CD4 ≤ 200/µL) HIV-infected patients starting dolutegravir or ritonavir/cobicistat-boosted darunavir+2NRTIs. Patients were followed from the date of first-line therapy initiation (baseline, BL) to the discontinuation of darunavir or dolutegravir, or for a maximum of 36 months of follow-up. RESULTS: Overall 308 patients (79.2% males, median age 43 years, 40.3% AIDS-presenters, median CD4 66 cells/µL) were enrolled; 181 (58.8%) and 127 (41.2%) were treated with dolutegravir and darunavir, respectively. Incidence of treatment discontinuation (TD), virological failure (VF, defined as a single HIV-RNA > 1000 cp/mL or two consecutive HIV-RNA > 50 cp/mL after 6 months of therapy or after virological suppression had been achieved), treatment failure (the first of TD or VF), and optimal immunological recovery (defined as CD4 ≥ 500/µL + CD4 ≥ 30% + CD4/CD8 ≥ 1) were 21.9, 5.2, 25.6 and 1.4 per 100 person-years of follow-up, respectively, without significant differences between dolutegravir and darunavir (p > 0.05 for all outcomes). However, a higher estimated probability of TD for central nervous system (CNS) toxicity (at 36 months: 11.7% vs. 0%, p = 0.002) was observed for dolutegravir, whereas darunavir showed a higher probability of TD for simplification (at 36 months: 21.3% vs. 5.7%, p = 0.046). CONCLUSIONS: Dolutegravir and darunavir showed similar efficacy in AIDS- and late-presenting patients. A higher risk of TD due to CNS toxicity was observed with dolutegravir, and a higher probability of treatment simplification with darunavir.


Subject(s)
Acquired Immunodeficiency Syndrome , Anti-HIV Agents , HIV Infections , Male , Humans , Adult , Female , Darunavir/therapeutic use , HIV Infections/drug therapy , Acquired Immunodeficiency Syndrome/drug therapy , Heterocyclic Compounds, 3-Ring/adverse effects , RNA , Anti-HIV Agents/adverse effects , Viral Load
9.
J Infect Public Health ; 16(8): 1209-1219, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-2327617

ABSTRACT

BACKGROUND: This prospective follow-up study aimed to determine the temporal changes in respiratory outcomes over 6 months period in patients with and without cancer hospitalized for severe COVID-19 and to determine the associated risk factors based on admission viral load. METHODS: All adult patients hospitalized with a confirmed diagnosis of severe SARS-CoV-2 infection were investigated using rRT-PCR on nasopharyngeal swab specimens. Patients were divided into three arbitrary groups according to their cycle threshold (CT) values obtained at admission as high (CT<25.0), medium (CT between 25.0 and 30.0), and low (CT>30.0) viral load. Patients had pulmonary function tests, chest high-resolution computed tomography (HRCT), and a 6-minute walking time distance measured at each follow-up visit. RESULTS: This follow-up study had a total of 112 participants, of which 75 were cancer-free and 37 had active cancer. Overall, 29.5% had a low viral load, compared to 48.2% who had a high viral load, and 22.3% had a medium viral load. For patients who did not have cancer, the mean age was 57.3 (SD 15.4) and for those who had cancer, it was 62.3 (SD 18.4). Most patients had overall better temporal changes in pulmonary function and tolerance, as well as exercise capacity, even though severe and chronic respiratory abnormalities persisted in a fraction of the patients. In patients without cancer who had a high viral load, we have seen a substantial reduction in diffusion capacity of the lungs for carbon monoxide (DLCO) predicted value with a median of 65 (IQR 63-70) while in patients with cancer, it was 60 (IQR 56-67) at 2 months. At 4 and 6 months, the predicted DLCO values for patients without cancer were 65 (IQR 61-70), whereas the predicted DLCO values for patients with active cancer were 62 (IQR 60-67) and 67 (59-73). Importantly, radiological abnormalities persisted in 22 (29%) non-cancer patients and 16 (43%) cancer patients. Multivariate regression analysis showed an increased odds ratio of impaired HRCT associated with a high viral load of 3.04 (95% CI:1.68-6.14; p < 0.001) for patients without cancer and 5.07 (95% CI: 4.04-10.8; p < 0.0001) for patients with cancer. The CT pneumonia score at hospitalization was 2.25 (95% CI:1.76-3.08; p = 0.041) and 2.85 (95% CI:1.89-5.14; p = 0.031) for non-cancer and cancer patients respectively. CONCLUSIONS: The evidence of persistent pulmonary abnormalities and radiographic changes was found in both patient groups who had high viral load at hospital admission and suggesting that SARS-CoV-2 viral load might serve as a useful indicator to predict the development of respiratory complications in patients with COVID-19.


Subject(s)
COVID-19 , Neoplasms , Adult , Humans , Middle Aged , SARS-CoV-2 , Follow-Up Studies , Prospective Studies , Viral Load , Hospitalization , Neoplasms/complications
10.
Niger J Clin Pract ; 26(4): 391-396, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2321395

ABSTRACT

Background and Aim: This study evaluates the salivary viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in hospitalized patients and outpatients before and after gargling with 1% hydrogen peroxide and 0.25% povidone-iodine in comparison with normal saline. Patients and Methods: This clinical trial was conducted on 120 participants with laboratory-confirmed coronavirus disease 2019 (COVID-19) in two groups: outpatients (n = 60) and hospitalized patients (n = 60). In each group, the patients were randomly divided into three subgroups of 20 based on their given mouthwash for gargling (hydrogen peroxide, povidone-iodine, or normal saline). Two saliva samples were taken from each patient: the first one before gargling and the second one 10 minutes after gargling 10 ml of the respected mouthwashes for 30 seconds. The TaqMan real-time polymerase chain reaction (PCR) amplification of SARS-CoV-2 was used to measure the viral load. Results: Saliva samples from 46% of patients were positive for coronavirus before gargling the mouthwashes. The percentage of patients with an initial positive saliva sample was significantly higher in the outpatient group (83.3%) than in the hospitalized group (5.4%) (P = 0.01). According to the findings, gargling any mouthwash similar to saline did not reduce the viral load (P > 0.05). Conclusion: The saliva of COVID-19 patients in the initial stage of the disease was more likely to contain SARS-CoV-2 than the saliva of the hospitalized patients. Gargling hydrogen peroxide or povidone-iodine did not reduce the salivary SARS-CoV-2 viral load.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Povidone-Iodine , Hydrogen Peroxide , Mouthwashes , Viral Load , Saline Solution , Pilot Projects
12.
J Med Case Rep ; 17(1): 215, 2023 May 16.
Article in English | MEDLINE | ID: covidwho-2317946

ABSTRACT

INTRODUCTION: Cytomegalovirus establishes life-long latency after primary infection in childhood. Cytomegalovirus reactivation has been well reported in immune-compromised patients; however, in the last few years it has been observed that cytomegalovirus reactivation also occurs in critically ill patients without exogenous immunosuppression, which increases length of intensive care unit stay and mortality rate. CASE REPORT: A 63-year-old Indian male, without any known comorbidity, developed severe coronavirus disease 2019 and was admitted to the intensive care unit. He received remdesivir, tocilizumab, steroids, anticoagulants, and empiric antibiotics over the next 3 weeks. However, his clinical condition did not improve much, and during the 9th week of illness his condition started deteriorating and routine bacterial cultures, fungal cultures, and cytomegalovirus real-time polymerase chain reaction on blood were negative. His clinical condition worsened rapidly, which led to the need for invasive mechanical ventilation. Tracheal aspirate bacterial and fungal culture showed no growth, but cytomegalovirus real-time polymerase chain reaction showed 21,86,000 copies/mL in tracheal aspirates. After 4 weeks of ganciclovir treatment, the patient improved clinically and was discharged. Currently he is doing well and able to do his routine activity without the need of oxygen. CONCLUSION: Timely management with ganciclovir is associated with favorable outcome in cytomegalovirus infection. Thus, it can be suggested that treatment should be initiated with ganciclovir if a patient with coronavirus disease 2019 has high cytomegalovirus load in tracheal aspirates, along with unexplained and prolonged clinical and/or radiological features.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Male , Middle Aged , Cytomegalovirus , Viral Load , Ganciclovir/therapeutic use , Antiviral Agents/therapeutic use
13.
J R Soc Interface ; 20(202): 20220827, 2023 05.
Article in English | MEDLINE | ID: covidwho-2315220

ABSTRACT

Early estimates of the transmission properties of a newly emerged pathogen are critical to an effective public health response, and are often based on limited outbreak data. Here, we use simulations to investigate how correlations between the viral load of cases in transmission chains can affect estimates of these fundamental transmission properties. Our computational model simulates a disease transmission mechanism in which the viral load of the infector at the time of transmission influences the infectiousness of the infectee. These correlations in transmission pairs produce a population-level convergence process during which the distributions of initial viral loads in each subsequent generation converge to a steady state. We find that outbreaks arising from index cases with low initial viral loads give rise to early estimates of transmission properties that could be misleading. These findings demonstrate the potential for transmission mechanisms to affect estimates of the transmission properties of newly emerged viruses in ways that could be operationally significant to a public health response.


Subject(s)
Disease Outbreaks , SARS-CoV-2 , Viral Load , Basic Reproduction Number
15.
Br Dent J ; 234(8): 593-600, 2023 04.
Article in English | MEDLINE | ID: covidwho-2294893

ABSTRACT

Introduction The purpose of this study was to test the short-term efficacy of four commercial mouthwashes versus water in reducing SARS-CoV-2 viral load in the oral cavity over clinically relevant time points.Methods In total, 32 subjects that were proven SARS-CoV-2-positive via polymerase chain reaction (PCR)-based diagnostic test were recruited and randomised into five parallel arms. Cycle threshold (Ct) values were compared in saliva samples between the groups, as well as within the groups at baseline (pre-rinse), zero hours, one hour and two hours post-rinse, using SARS-CoV-2 reverse transcription-PCR analysis.Results We observed a significant increase in Ct values in saliva samples collected immediately after rinsing with all the four mouthwashes - 0.12% chlorhexidine gluconate, 1.5% hydrogen peroxide, 1% povidone iodine, or Listerine - compared to water. A sustained increase in Ct values for up to two hours was only observed in the Listerine and chlorohexidine gluconate groups. We were not able to sufficiently power this clinical trial, so the results remain notional but encouraging and supportive of findings in other emerging mouthwash studies on COVID-19, warranting additional investigations.Conclusions Our evidence suggests that in a clinical setting, prophylactic rinses with Listerine or chlorhexidine gluconate can potentially reduce SARS-CoV-2 viral load in the oral cavity for up to two hours. While limited in statistical power due to the difficulty in obtaining this data, we advocate for pre-procedural mouthwashing, like handwashing, as an economical and safe additional precaution to help mitigate the transmission of SARS-CoV-2 from a potentially infected patient to providers.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Mouthwashes/therapeutic use , COVID-19/prevention & control , Viral Load
16.
Sci Rep ; 13(1): 6156, 2023 04 15.
Article in English | MEDLINE | ID: covidwho-2300589

ABSTRACT

The inability to predict the evolution of the COVID-19 epidemic hampered abilities to respond to the crisis effectively. The cycle threshold (Ct) from the standard SARS-CoV-2 quantitative reverse transcription-PCR (RT-qPCR) clinical assay is inversely proportional to the amount of SARS-CoV-2 RNA in the sample. We were interested to see if population Ct values could predict future increases in COVID-19 cases as well as subgroups that would be more likely to be affected. This information would have been extremely helpful early in the COVID-19 epidemic. We therefore conducted a retrospective analysis of demographic data and Ct values from 2,076,887 nasopharyngeal swab RT-qPCR tests that were performed at a single diagnostic laboratory in the Czech Republic from April 2020 to April 2022 and from 221,671 tests that were performed as a part of a mandatory school surveillance testing program from March 2021 to March 2022. We found that Ct values could be helpful predictive tools in the real-time management of viral epidemics. First, early measurement of Ct values would have indicated the low viral load in children, equivalent viral load in males and females, and higher viral load in older individuals. Second, rising or falling median Ct values and differences in Ct distribution indicated changes in the transmission in the population. Third, monitoring Ct values and positivity rates would have provided early evidence as to whether prevention measures are effective. Health system authorities should thus consider collecting weekly median Ct values of positively tested samples from major diagnostic laboratories for regional epidemic surveillance.


Subject(s)
COVID-19 , SARS-CoV-2 , Male , Child , Female , Humans , Aged , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/diagnosis , RNA, Viral/genetics , RNA, Viral/analysis , Czech Republic/epidemiology , Retrospective Studies , Viral Load
17.
J Hosp Infect ; 136: 110-117, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2298590

ABSTRACT

BACKGROUND: Healthcare workers treating SARS-CoV-2 patients are at risk of infection by respiratory exposure to patient-emitted, virus-laden aerosols. Source control devices such as ventilated patient isolation hoods have been shown to limit the dissemination of non-infectious airborne particles in laboratory tests, but data on their performance in mitigating the airborne transmission risk of infectious viruses are lacking. AIM: We used an infectious airborne virus to quantify the ability of a ventilated hood to reduce infectious virus exposure in indoor environments. METHODS: We nebulized 109 plaque forming units (pfu) of bacteriophage PhiX174 virus into a ∼30-m3 room when the hood was active or inactive. The airborne concentration of infectious virus was measured by BioSpot-VIVAS and settle plates using plaque assay quantification on the bacterial host Escherichia coli C. The airborne particle number concentration (PNC) was also monitored continuously using an optical particle sizer. FINDINGS: The median airborne viral concentration in the room reached 1.41 × 105 pfu/m3 with the hood inactive. When active, the hood reduced infectious virus concentration in air samples by 374-fold. The deposition of infectious virus on the surface of settle plates was reduced by 87-fold. This was associated with a 109-fold reduction in total airborne particle number escape rate. CONCLUSION: A personal ventilation hood significantly reduced airborne particle escape, considerably lowering infectious virus contamination in an indoor environment. Our findings support the further development of source control devices to mitigate nosocomial infection risk among healthcare workers exposed to airborne viruses in clinical settings.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/prevention & control , Viral Load , Respiration, Artificial , Respiratory Aerosols and Droplets
18.
Sci Rep ; 13(1): 6839, 2023 04 26.
Article in English | MEDLINE | ID: covidwho-2298000

ABSTRACT

With the changing epidemiology of COVID-19 and its impact on our daily lives, there is still an unmet need of COVID-19 therapies treating early infections to prevent progression. The current study was a randomized, parallel, double-blind, placebo-controlled trial. Ninety SARS-CoV-2 positive patients were randomized into 3 groups receiving placebo, 0.02% or 0.1% azelastine nasal spray for 11 days, during which viral loads were assessed by quantitative PCR. Investigators assessed patients' status throughout the trial including safety follow-ups (days 16 and 60). Symptoms were documented in patient diaries. Initial viral loads were log10 6.85 ± 1.31 (mean ± SD) copies/mL (ORF 1a/b gene). After treatment, virus load was reduced in all groups (p < 0.0001) but was greater in the 0.1% group compared to placebo (p = 0.007). In a subset of patients (initial Ct < 25) viral load was strongly reduced on day 4 in the 0.1% group compared to placebo (p = 0.005). Negative PCR results appeared earlier and more frequently in the azelastine treated groups: being 18.52% and 21.43% in the 0.1% and 0.02% groups, respectively, compared to 0% for placebo on day 8. Comparable numbers of adverse events occurred in all treatment groups with no safety concerns. The shown effects of azelastine nasal spray may thus be suggestive of azelastine's potential as an antiviral treatment.Trial registration: The study was registered in the German Clinical Trial Register (DRKS-ID: DRKS00024520; Date of Registration in DRKS: 12/02/2021). EudraCT number: 2020-005544-34.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Nasal Sprays , Viral Load , Double-Blind Method , Treatment Outcome
20.
J Theor Biol ; 565: 111470, 2023 05 21.
Article in English | MEDLINE | ID: covidwho-2276002

ABSTRACT

The SARS-CoV-2 coronavirus continues to evolve with scores of mutations of the spike, membrane, envelope, and nucleocapsid structural proteins that impact pathogenesis. Infection data from nasal swabs, nasal PCR assays, upper respiratory samples, ex vivo cell cultures and nasal epithelial organoids reveal extreme variabilities in SARS-CoV-2 RNA titers within and between the variants. Some variabilities are naturally prone to clinical testing protocols and experimental controls. Here we focus on nasal viral load sensitivity arising from the timing of sample collection relative to onset of infection and from heterogeneity in the kinetics of cellular infection, uptake, replication, and shedding of viral RNA copies. The sources of between-variant variability are likely due to SARS-CoV-2 structural protein mutations, whereas within-variant population variability is likely due to heterogeneity in cellular response to that particular variant. With the physiologically faithful, agent-based mechanistic model of inhaled exposure and infection from (Chen et al., 2022), we perform statistical sensitivity analyses of the progression of nasal viral titers in the first 0-48 h post infection, focusing on three kinetic mechanisms. Model simulations reveal shorter latency times of infected cells (including cellular uptake, viral RNA replication, until the onset of viral RNA shedding) exponentially accelerate nasal viral load. Further, the rate of infectious RNA copies shed per day has a proportional influence on nasal viral load. Finally, there is a very weak, negative correlation of viral load with the probability of infection per virus-cell encounter, the model proxy for spike-receptor binding affinity.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , RNA, Viral/genetics , Viral Load , COVID-19 Testing
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