SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper respiratory symptoms, suggesting potential to constrain viral pathology to the ...nasopharynx. Which cells SARS-CoV-2 primarily targets and how infection influences the respiratory epithelium remains incompletely understood. We performed scRNA-seq on nasopharyngeal swabs from 58 healthy and COVID-19 participants. During COVID-19, we observe expansion of secretory, loss of ciliated, and epithelial cell repopulation via deuterosomal cell expansion. In mild and moderate COVID-19, epithelial cells express anti-viral/interferon-responsive genes, while cells in severe COVID-19 have muted anti-viral responses despite equivalent viral loads. SARS-CoV-2 RNA+ host-target cells are highly heterogenous, including developing ciliated, interferon-responsive ciliated, AZGP1high goblet, and KRT13+ “hillock”-like cells, and we identify genes associated with susceptibility, resistance, or infection response. Our study defines protective and detrimental responses to SARS-CoV-2, the direct viral targets of infection, and suggests that failed nasal epithelial anti-viral immunity may underlie and precede severe COVID-19.
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•scRNA-seq on nasopharyngeal swabs of 58 COVID-19 and healthy participants•SARS-CoV-2 induces ciliated cell loss with secretory and deuterosomal expansion•Early, muted anti-viral responses in nasal epithelia in severe COVID-19•Host-virus co-detection maps cell tropism and intrinsic responses to SARS-CoV-2
A study of nasopharyngeal swabs from healthy and COVID-19-infected individuals shows how infection leads to compositional changes in the respiratory epithelium, with early dampened antiviral responses in the nasal epithelia likely underlying and preceding severe disease.
Proton pump inhibitor (PPI) use was recently reported to be associated with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and worse clinical outcomes. The ...underlying mechanism(s) for this association are unclear.
We performed a prospective study of hospitalized coronavirus disease 2019 (COVID-19) patients and COVID-negative controls to understand how PPI use may affect angiotensin-converting enzyme 2 (ACE2) expression and stool SARS-CoV-2 RNA. Analysis of a retrospective cohort of hospitalized patients with COVID-19 from March 15, 2020 to August 15, 2020 in 6 hospitals was performed to evaluate the association of PPI use and mortality. Covariates with clinical relevance to COVID-19 outcomes were included to determine predictors of in-hospital mortality.
Control PPI users had higher salivary ACE2 mRNA levels than nonusers, 2.39 ± 1.15 vs 1.22 ± 0.92 (P = 0.02), respectively. Salivary ACE2 levels and stool SARS-CoV-2 RNA detection rates were comparable between users and nonusers of PPI. In 694 hospitalized patients with COVID-19 (age = 58 years, 46% men, and 65% black), mortality rate in PPI users and nonusers was 30% (68/227) vs 12.1% (53/439), respectively. Predictors of mortality by logistic regression were PPI use (adjusted odds ratio aOR = 2.72, P < 0.001), age (aOR = 1.66 per decade, P < 0.001), race (aOR = 3.03, P = 0.002), cancer (aOR = 2.22, P = 0.008), and diabetes (aOR = 1.95, P = 0.003). The PPI-associated mortality risk was higher in black patients (aOR = 4.16, 95% confidence interval: 2.28-7.59) than others (aOR = 1.62, 95% confidence interval: 0.82-3.19, P = 0.04 for interaction).
COVID-negative PPI users had higher salivary ACE2 expression. PPI use was associated with increased mortality risk in patients with COVID-19, particularly African Americans.
Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the frequency of fungal colonization ...in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing data set characterizing the upper respiratory microenvironment during COVID-19 and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our previous study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection of
species-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals. Using matched single-cell transcriptomic profiles of these individuals' respiratory mucosa, we identify epithelial immune signatures suggestive of IL17 stimulation and anti-fungal immunity. Further, we observe a significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggest that IL17 stimulation-in part driven by
colonization-and blunted interferon signaling represent a common feature of severe COVID-19 infection.
In this paper, we present an analysis suggesting that symptomatic and asymptomatic fungal coinfections can impact patient disease progression during COVID-19 hospitalization. By looking into the presence of other pathogens and their effect on the host immune response during COVID-19 hospitalizations, we aim to offer insight into an underestimated scenario, furthering our current knowledge of determinants of severity that could be considered for future diagnostic and intervention strategies.
Introduction
There is a paucity of noninvasive respiratory monitors for patients outside of critical care settings. The Linshom respiratory monitoring device is a novel temperature‐based respiratory ...monitor that measures the respiratory rate as accurately as capnography.
Objectives
Determine whether the amplitude of the Linshom temperature profile was an accurate, surrogate and qualitative metric of the tidal volume (VT) that tracks VT in healthy volunteers.
Methods
Forty volunteers breathed room air spontaneously through a tight‐fitting continuous positive airway pressure mask with a Linshom device mounted in the mask. VT was measured contemporaneously using a standalone Maquet Servo‐i ICU ventilator. The amplitudes of the Linshom temperature profiles were paired with the contemporaneous VT measurements using least squares linear regression analysis and the coefficient of variation (R2) was determined.
Results
Forty volunteers completed the study. The data from 30 of the volunteers were analysed and are presented; data from 10 volunteers were not included due to protocol violations and/or technical issues unrelated to Linshom. The fluctuations in the amplitude of the Linshom temperature profiles mapped closely with the measured VT using least squares linear regression analyses yielding a mean R2 (95% CI) value of 0.87 (0.84‐0.90).
Conclusion
These results support the notion that the Linshom temperature profile is an accurate and reliable surrogate that tracks changes in VT in healthy volunteers. Further studies are warranted in patients in clinical settings to establish the effectiveness of this monitor.
Flexible bronchoscopy is a common and safe outpatient procedure, with complications arising in less than 1% of cases. The case presented herein details the occurrence of pneumomediastinum, ...pneumopericardium, pneumoperitoneum, interstitial lung emphysema and subcutaneous emphysema during flexible bronchoscopy. Although these complications have been reported individually in various circumstances, they have not been reported concomitantly in this setting. Recovery was rapid and complete, requiring only supplemental oxygen and monitoring. After a literature and chart review, the authors postulate that the complications were not a direct result of bronchoscopy but rather the simple act of placing an oxygen delivery cannula in a patient with possible prior trauma to the site.
About long-term oxygen therapy Abraham, 3rd, George E; Dwyer, Terry M; Bhagat, Rajesh
Journal of the Mississippi State Medical Association
55, Številka:
9
Journal Article
Mucosa-associated lymphoid tissue (MALT) lymphoma is a diagnostic challenge when arising from bronchiolar submucosal tissue. The case herein describes a man with a lung mass and a remote history of ...gastric MALT lymphoma. After undergoing a bronchoscopic examination and tissue sampling, he was diagnosed with pulmonary recurrence of gastric MALT lymphoma. The diagnosis of MALT lymphoma in the lung can be challenging. Radiographic findings are typically nonspecific, and tissue biopsy by surgical means is often required. The diagnosis of bronchus-associated lymphoid tissue lymphoma has been previously demonstrated bronchoscopically when a needle aspiration is performed. This case supports the position that bronchoscopy with needle aspiration, and flow cytometry should be performed in all patients in whom pulmonary MALT lymphoma is suspected.
The most common cardiovascular manifestation of Systemic Lupus Erythematosus is pericardial disease. Tamponade in SLE is rarely described. The patient discussed in this case report presented with ...symptoms of heart failure. Physical exam, laboratory testing, echocardiography, and right heart catheterization revealed multiple morbid conditions including tamponade. The diagnoses satisfied four criteria for the classification of SLE. This case emphasizes the importance of a thorough physical exam in guiding diagnostic and therapeutic measures.
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