ABSTRACT
Background: People with cystic fibrosis (PwCF) have chronic, pronounced respiratory damage and have been considered among those at highest risk for serious harm from SARS-CoV-2. Numerous clinical studies have reported that individuals with CF in North America and Europe, although highly susceptible to COVID-19, do not have mortality levels that exceed those of the general population. Method(s): To understand features that might influence lethality of COVID- 19 in PwCF, we tested potential relationships between CFTR and viral pathogenesis. As one approach to evaluate impact of CF transmembrane conductance regulator (CFTR) on COVID-19 severity, independent sets of blood samples fromvirally infected individualswere genotyped. Bloodwas obtained from 424 U.S. patients hospitalized with severe COVID-19 and a much larger European cohort of 7147 healthy individuals and 2587 individuals with severe COVID-19. Deoxyribonucleic acid in both studies was probed for the F508del variant. In other experiments, we investigated the possibility that lack of CFTR might alter viral binding and propagation. We used human bronchial epithelial cell (HBEC) monolayers from individuals without functional CFTR for this purpose. Finally, we examined effects of CF airway secretions and features such as viscosity, pH, and protease/anti-protease imbalance during SARS-CoV-2 infection. Result(s): We found no evidence of a relationship between deficient CFTR function (based on carrier status for the severe F508del defect) and clinical outcomes from COVID-19. In addition, viral propagation studies using airway epithelial monolayers (a model that reproduces many aspects of in vivo tissue biology) were not influenced by homozygous absence of CFTR. We show that levels of angiotensin converting enzyme-2 receptor messenger ribonucleic acid (mRNA) appear normal in CF primary epithelium, whereas transmembrane serine protease 2 mRNA is variable but lower ( p < 0.001) in a manner that correlates with viral infectivity (R2 = 0.76). Dependence of viral proliferation on features of CF mucosal fluid-including pH (viral replication optimum at pH 7-7.5), viscosity (diminished propagation in highly viscous apical media), and protease/ anti-protease imbalancewere identified as likely contributors to efficiency of SARS-CoV-2 replication and pathogenesis. Conclusion(s): These findings using patient data, CF and non-CF primary airway epithelia, and CF airway secretions fail to demonstrate a causal relationship between loss of CFTR and susceptibility to severe COVID-19. Notwithstanding the caveat that addition of virus in small buffer volumes disrupts airway surface liquid depth and composition, our findings also argue against a role for CFTR during acute infection of airway cells in vitro. On the other hand, chronic disruption of periciliary liquid, diminished pH, altered protease/anti-protease homeostasis, and increased fluid viscosity (sequelae that occur in CF lungs) were implicated as contributors to impaired SARS-CoV-2 propagation. Such studies provide a basis for future work to test relationships between CFTR and severity of COVID-19. Copyright © 2022, European Cystic Fibrosis Society. All rights reserved
ABSTRACT
The objective of the article was to evaluate the stability of SARS-CoV-2 and SARS-CoV-1 in aerosols and on various surfaces and estimated their decay rates using a Bayesian regression model. Results showed that the stability of SARS-CoV-2 was similar to that of SARS-CoV-1 under the experimental circumstances tested. This indicates that differences in the epidemiologic characteristics of these viruses probably arise from other factors, including high viral loads in the upper respiratory tract and the potential for persons infected with SARS-CoV-2 to shed and transmit the virus while asymptomatic. The results indicate that aerosol and fomite transmission of SARS-CoV-2 is plausible, since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days (depending on the inoculum shed). These findings echo those with SARS-CoV-1, in which these forms of transmission were associated with nosocomial spread and super-spreading events, and they provide information for pandemic mitigation efforts.
ABSTRACT
PURPOSE: Our aim was to study the association between abnormal findings on chest and brain imaging in patients with coronavirus disease 2019 (COVID-19) and neurologic symptoms. MATERIALS AND METHODS: In this retrospective, international multicenter study, we reviewed the electronic medical records and imaging of hospitalized patients with COVID-19 from March 3, 2020, to June 25, 2020. Our inclusion criteria were patients diagnosed with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and available chest CT and brain imaging. The 5 lobes of the lungs were individually scored on a scale of 0-5 (0 corresponded to no involvement and 5 corresponded to >75% involvement). A CT lung severity score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). RESULTS: A total of 135 patients met the inclusion criteria with 132 brain CT, 36 brain MR imaging, 7 MRA of the head and neck, and 135 chest CT studies. Compared with 86 (64%) patients without acute abnormal findings on neuroimaging, 49 (36%) patients with these findings had a significantly higher mean CT lung severity score (9.9 versus 5.8, P < .001). These patients were more likely to present with ischemic stroke (40 [82%] versus 11 [13%], P < .0001) and were more likely to have either ground-glass opacities or consolidation (46 [94%] versus 73 [84%], P = .01) in the lungs. A threshold of the CT lung severity score of >8 was found to be 74% sensitive and 65% specific for acute abnormal findings on neuroimaging. The neuroimaging hallmarks of these patients were acute ischemic infarct (28%), intracranial hemorrhage (10%) including microhemorrhages (19%), and leukoencephalopathy with and/or without restricted diffusion (11%). The predominant CT chest findings were peripheral ground-glass opacities with or without consolidation. CONCLUSIONS: The CT lung disease severity score may be predictive of acute abnormalities on neuroimaging in patients with COVID-19 with neurologic manifestations. This can be used as a predictive tool in patient management to improve clinical outcome.