scholarly journals Multiorgan tropism of SARS-CoV-2 lineage B.1.1.7

2021 ◽  
Author(s):  
Benjamin Ondruschka ◽  
Fabian Heinrich ◽  
Maja Lindenmeyer ◽  
Carolin Edler ◽  
Dustin Möbius ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Respiratory System ◽  
Tissue Analysis ◽  
Post Mortem ◽  
Multiple Organs ◽  
Autopsy Data ◽  
Autopsy Tissue ◽  
The Given ◽  
Organ Tropism

AbstractDue to the development of novel functionalities, distinct SARS-CoV-2 variants such as B.1.1.7 fuel the current pandemic. B.1.1.7 is not only more transmissible, but may also cause an increased mortality compared to previous SARS-CoV-2 variants. Human tissue analysis of the SARS-CoV-2 lineage B.1.1.7 is urgently needed, and we here present autopsy data from 7 consecutive SARS-CoV-2 B.1.1.7 cases. The initial RT-qPCR analyses from nasopharyngeal swabs taken post mortem included typing assays for B.1.1.7. We quantitated SARS-CoV-2 B.1.1.7 viral load in autopsy tissue of multiple organs. Highest levels of SARS-CoV-2 B.1.1.7 copies normalized to ß-globin were detected in the respiratory system (lung and pharynx), followed by the liver and heart. Importantly, SARS-CoV-2 lineage B.1.1.7 was found in 100% of cases in the lungs and in 85.7% in pharynx tissue. Detection also in the kidney and brain highlighting a pronounced organ tropism. Comparison of the given results to a former cohort of SARS-CoV-2 deaths during the first wave in spring 2020 showed resembling organ tropism. Our results indicate that also SARS-CoV-2 B.1.1.7 has a relevant organ tropism beyond the respiratory tract. We speculate that B.1.1.7 spike protein’s affinity to human ACE2 facilitates transmission, organ tropism, and ultimately morbidity and mortality. Further studies and larger cohorts are obligatory to proof this link.

scholarly journals Persistence of SARS-CoV-2 Viral RNA in Nasopharyngeal Swabs after Death: An Observational Study

2021 ◽  
Vol 9 (4) ◽  
pp. 800
Author(s):  
Francesca Servadei ◽  
Silvestro Mauriello ◽  
Manuel Scimeca ◽  
Bartolo Caggiano ◽  
Marco Ciotti ◽  
...  
Keyword(s):  
Viral Load ◽  
Observational Study ◽  
Real Time ◽  
Real Time Pcr ◽  
Pcr Detection ◽  
Viral Rna ◽  
Clinical Documentation ◽  
Post Mortem ◽  
Medical Assistance ◽  
Time Points

The aim of this study was to investigate the persistence of SARS-CoV-2 in post-mortem swabs of subjects who died from SARS-CoV-2 infection. The presence of the virus was evaluated post-mortem from airways of 27 SARS-CoV-2 positive patients at three different time points (T1 2 h; T2 12 h; T3 24 h) by real-time PCR. Detection of antibodies to SARS-CoV-2 was performed by Maglumi 2019-nCoV IgM/IgG chemiluminescence assay. SARS-CoV-2 viral RNA was still detectable in 70.3% of cases within 2 h after death and in 66,6% of cases up to 24 h after death. Our data showed an increase of the viral load in 78,6% of positive individuals 24 h post-mortem (T3) in comparison to that evaluated 2 h after death (T1). Noteworthy, we detected a positive T3 post-mortem swab (24 h after death) from 4 subjects who were negative at T1 (2 h after death). The results of our study may have an important value in the management of deceased subjects not only with a suspected or confirmed diagnosis of SARS-CoV-2, but also for unspecified causes and in the absence of clinical documentation or medical assistance.

scholarly journals Rapid Diagnosis of SARS-CoV-2 Pneumonia on Lower Respiratory Tract Specimens

2021 ◽  
Author(s):  
Vanessa De Pace ◽  
Patrizia Caligiuri ◽  
Valentina Ricucci ◽  
Nicola Nigro ◽  
Barbara Galano ◽  
...  
Keyword(s):  
Intensive Care ◽  
Viral Load ◽  
Respiratory Tract ◽  
Intensive Care Units ◽  
Lower Respiratory Tract ◽  
Clinical Decision Making ◽  
High Viral Load ◽  
Rt Pcr ◽  
Predictive Values ◽  
Rapid Pcr

Abstract Background: The ongoing pandemic of SARS-CoV-2 requires the availability of accurate and rapid diagnostic tests, especially in some clinical settings like emergency and intensive care units. The objective of this study was to evaluate the diagnostic performances of rapid PCR kit Vivalytic SARS-CoV-2 in lower respiratory tract (LRT) specimens.Methods: A consecutive sample of LRT specimens (bronchoalveolar lavage and bronchoaspirates) was collected from Intensive Care Units of San Martino Hospital (Genoa, Italy) between November 2020 and January 2021. All samples were tested in RT-PCR by using Allplex™ SARS-CoV-2 assay (Seegene Inc., South Korea). Based on RT-PCR results, specimens were categorized into negative, positive with high viral load [cycle threshold (Ct) ≤30] and positive with low viral load (Ct of 31–35). A quota 1:1:1 sampling was used to achieve a sample size of 75. Then, all specimens were tested in the rapid PCR assay Vivalytic SARS-CoV-2 (Bosch Healthcare Solutions GmbH, Germany). The diagnostic performance of the rapid PCR against RT-PCR was assessed through calculation of accuracy, Cohen’s κ, sensitivity, specificity and expected positive (PPV) and negative (NPV) predictive values.Results: The overall diagnostic accuracy of the Vivalytic SARS-CoV-2 was 97.3% (95% CI: 90.9–99.3%) with an excellent Cohen’s κ of 0.94 (95% CI: 0.72–1). The sensitivity and specificity were 96% (95% CI: 86.5–98.9%) and 100% (95% CI: 86.7–100%), respectively. Samples with high viral loads had a sensitivity of 100% (Table 1). The distributions of E gene Ct values were similar (Wilcoxon’s test: P=0.070) with medians of 35 (IQR: 25–36) and 35 (IQR: 25–35), respectively (Figure 1). NPV and PPV was 92.6% and 100%, respectively.Conclusions: This study shows Vivalytic SARS-CoV-2 can be used following the sample liquefaction on LRT specimens. It’s a feasible and highly accurate molecular procedure especially in high viral load samples. This assay allows having a result in about 40 min and therefore may accelerate the clinical decision making in urgent/emergency situations.

scholarly journals Experimental Evaluation of Dry Powder Inhalers During In- and Exhalation Using a Model of the Human Respiratory System (xPULM™)

2021 ◽  
Author(s):  
Richard Pasteka ◽  
Joao Pedro Santos da Costa ◽  
Mathias Forjan
Keyword(s):  
Respiratory Tract ◽  
Respiratory System ◽  
Particle Number ◽  
Particle Diameter ◽  
Upper Airway ◽  
System Model ◽  
Dry Powder Inhalers ◽  
Dry Powder ◽  
Pharmaceutical Aerosols ◽  
Airway Model

Dry powder inhalers are used by a large number of patients worldwide to treat respiratory diseases. The objective of this work is to experimentally investigate changes in aerosol particle diameter and particle number concentration of pharmaceutical aerosols generated by five dry powder inhalers under realistic inhalation and exhalation conditions. The active respiratory system model (xPULM™) was used as a model of the human respiratory system and to simulate a patient undergoing inhalation therapy. A mechanical upper airway model was developed, manufactured and introduced as a part of the xPULM™ to represent the human upper respiratory tract with high fidelity. Integration of optical aerosol spectrometry technique into the setup allowed for evaluation of pharmaceutical aerosols. The results show that the upper airway model increases the resistance of the overall system and act as a filter for bigger particles (>3 µm). Furthermore, there is a significant difference (p < 0.05) in mean particle diameter between inhaled and exhaled particles with the majority of the particles depositing in the lung. The minimum deposition is reached for particle size of 0.5 µm. The mean particle number concentrations exhaled are 2.94% (BreezHaler®), 2.66% (Diskus®), 10.24% (Ellipta®) 2.13% (HandiHaler®) and 6.22% (Turbohaler®). In conclusion, the xPULM™ active respiratory system model is a viable option for studying interactions of pharmaceutical aerosols and the respiratory tract in terms of applicable deposition mechanisms. The model can support the reduction of animal experimentation in aerosol research and provide an alternative to experiments with human subjects.

scholarly journals New prospects for local etiotropic treatment of acute respiratory viral infections

2019 ◽  
pp. 105-108
Author(s):  
A. A. Krivopalov ◽  
V. A. Shatalov ◽  
S. V. Shervashidze
Keyword(s):  
Respiratory Tract ◽  
Respiratory System ◽  
Safety Profile ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Upper Respiratory Tract ◽  
Positive Experience ◽  
High Efficacy ◽  
Upper Respiratory ◽  
Respiratory Viral Infections

According to WHO, the respiratory system diseases are currently inside the ten most common pathologies. The modern strategy for treating influenza and ARVI gives priority to the antiviral and immunostimulating agents, but the symptomatic drugs, which include preparations based on silver and its compounds, also play an important role. The large positive experience in using silver preparations supported by numerous clinical studies shows their high efficacy and satisfactory safety profile in the treatment of infectious and inflammatory diseases of the nose and upper respiratory tract in children and adults.

scholarly journals An outbreak of SARS-CoV-2 with high mortality in mink (Neovison vison) on multiple Utah farms

2021 ◽  
Author(s):  
Chrissy Eckstrand ◽  
Tom Baldwin ◽  
Mia Kim Torchetti ◽  
Mary Lea Killian ◽  
Kerry A Rood ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Clinical Signs ◽  
Viral Transmission ◽  
Viral Rna ◽  
Upper Respiratory Tract ◽  
Tracheobronchial Lymph Node ◽  
Multiple Organs ◽  
Upper Respiratory ◽  
Polymerase Chain

The breadth of animal hosts that are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may serve as reservoirs for continued viral transmission are not known entirely. In August 2020, an outbreak of SARS-CoV-2 occurred in multiple mink farms in Utah and was associated with high mink mortality and rapid viral transmission between animals. The outbreak's epidemiology, pathology, molecular characterization, and tissue distribution of virus within infected mink is provided. Infection of mink was likely by reverse zoonosis. Once established, infection spread rapidly between independently housed animals and farms, and caused severe respiratory disease and death. Clinical signs were most notably sudden death, anorexia, and increased respiratory effort. Gross pathology examination revealed severe pulmonary congestion and edema. Microscopically there was pulmonary edema with moderate vasculitis, perivasculitis, and fibrinous interstitial pneumonia. Reverse transcriptase polymerase chain reaction (RT-PCR) of tissues collected at necropsy demonstrated the presence of SARS-CoV-2 viral RNA in multiple organs including nasal turbinates, lung, tracheobronchial lymph node, epithelial surfaces, and others. Whole genome sequencing from multiple mink was consistent with published SARS-CoV-2 genomes with few polymorphisms. The Utah mink SARS-CoV-2 strain fell into Clade GH, which is unique among mink and other animal strains sequenced to date and did not share other spike RBD mutations Y453F and F486L found in mink. Localization of viral RNA by in situ hybridization revealed a more localized infection, particularly of the upper respiratory tract. Mink in the outbreak reported herein had high levels of virus in the upper respiratory tract associated with mink-to-mink transmission in a confined housing environment and were particularly susceptible to disease and death due to SARS-CoV-2 infection.

scholarly journals A Phase 2b, Randomized, Double-blind, Placebo-Controlled Multicenter Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of Presatovir in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus Infection of the Lower Respiratory Tract

2019 ◽  
Vol 71 (11) ◽  
pp. 2787-2795 ◽  
Author(s):  
Francisco M Marty ◽  
Roy F Chemaly ◽  
Kathleen M Mullane ◽  
Dong-Gun Lee ◽  
Hans H Hirsch ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Weighted Average ◽  
Supplemental Oxygen ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Average Change ◽  
Time Weighted Average ◽  
Syncytial Virus

Abstract Background Presatovir significantly reduced nasal viral load, signs, and symptoms of respiratory syncytial virus (RSV) infection in a human challenge study. We evaluated presatovir in hematopoietic-cell transplant (HCT) recipients with RSV lower respiratory tract infection (LRTI). Methods Patients with confirmed RSV in upper and lower respiratory tract and new chest X-ray abnormalities were randomized (1:1), stratified by supplemental oxygen and ribavirin use, to receive oral presatovir 200 mg or placebo every 4 days for 5 doses. The primary endpoint was time-weighted average change in nasal RSV viral load through day 9. Secondary endpoints included supplemental oxygen-free days, incident respiratory failure requiring mechanical ventilation, and all-cause mortality. Results From January 31, 2015, to March 20, 2017, 60 patients from 17 centers were randomized (31 presatovir, 29 placebo); 59 received study treatment (50 allogeneic, 9 autologous HCT). In the efficacy population (29 presatovir, 28 placebo), presatovir treatment did not significantly reduce time-weighted average change in viral load (−1.12 vs −1.09 log10 copies/mL; treatment difference −0.02 log10 copies/mL, 95% confidence interval: −.62, .57; P = .94), median supplemental oxygen-free days (26 vs 28 days, P = .84), incident respiratory failure (10.3 vs 10.7%, P = .98), or all-cause mortality (0 vs 7.1%, P = .19) versus placebo. Adverse events were similar between arms (presatovir 80%, placebo 79%). Resistance-associated substitutions in RSV fusion protein emerged in 6/29 presatovir-treated patients. Conclusions Presatovir treatment was well tolerated in HCT patients with RSV LRTI but did not improve virologic or clinical outcomes versus placebo. Clinical Trials Registration www.clinicaltrials.gov, NCT02254421; EudraCT, #2014-002475-29

Comparison of Estimates of Systemic Pu From Urinary Excretion With Estimates From Post-mortem Tissue Analysis

1987 ◽  
Vol 53 (5) ◽  
pp. 487-493 ◽  
Author(s):  
Ronald L. Kathren ◽  
Kenneth R. Heid ◽  
Margery J. Swint
Keyword(s):  
Urinary Excretion ◽  
Tissue Analysis ◽  
Post Mortem

scholarly journals Convalescent Plasma Treatment Reduced Mortality in Patients With Severe Pandemic Influenza A (H1N1) 2009 Virus Infection

2011 ◽  
Vol 52 (4) ◽  
pp. 447-456 ◽  
Author(s):  
Ivan FN Hung ◽  
Kelvin KW To ◽  
Cheuk-Kwong Lee ◽  
Kar-Lung Lee ◽  
Kenny Chan ◽  
...  
Keyword(s):  
Intensive Care ◽  
Viral Load ◽  
Treatment Group ◽  
Respiratory Tract ◽  
Plasma Treatment ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Control Group ◽  
Severity Scores ◽  
Influenza A H1n1

Background. Experience from treating patients with Spanish influenza and influenza A(H5N1) suggested that convalescent plasma therapy might be beneficial. However, its efficacy in patients with severe pandemic influenza A(H1N1) 2009 virus (H1N1 2009) infection remained unknown. Methods. During the period from 1 September 2009 through 30 June 2010, we conducted a prospective cohort study by recruiting patients aged ≥18 years with severe H1N1 2009 infection requiring intensive care. Patients were offered treatment with convalescent plasma with a neutralizing antibody titer of ≥1:160, harvested by apheresis from patients recovering from H1N1 2009 infection. Clinical outcome was compared with that of patients who declined plasma treatment as the untreated controls. Results. Ninety-three patients with severe H1N1 2009 infection requiring intensive care were recruited. Twenty patients (21.5%) received plasma treatment. The treatment and control groups were matched by age, sex, and disease severity scores. Mortality in the treatment group was significantly lower than in the nontreatment group (20.0% vs 54.8%; P =  .01). Multivariate analysis showed that plasma treatment reduced mortality (odds ratio [OR], .20; 95% confidence interval [CI], .06-.69; P =  .011), whereas complication of acute renal failure was independently associated with death (OR, 3.79; 95% CI, 1.15-12.4; P =  .028). Subgroup analysis of 44 patients with serial respiratory tract viral load and cytokine level demonstrated that plasma treatment was associated with significantly lower day 3, 5, and 7 viral load, compared with the control group (P <  .05). The corresponding temporal levels of interleukin 6, interleukin 10, and tumor necrosis factor α (P <  .05) were also lower in the treatment group. Conclusions. Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.

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