Coronavirus 229E-Related Pneumonia in Immunocompromised Patients

Pène, Frédéric; Merlat, A; Vabret, Astrid; Rozenberg, Flore; Buzyn, Agnès; Dreyfus, F.; Cariou, Alain; Freymuth, F.; Lebon, Pierre

doi:10.1086/377612

Cited by 272 publications

(232 citation statements)

References 25 publications

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“…Mortality rates following SARSCoV infection approached <1% under 24 years of age, 6% for ages 15-44, 15% for ages 45-64 and >50% over 65, and survivors developed lung and cardiac complications (Han et al, 2003). The disease caused by this pathogenic human coronavirus is in stark contrast to that seen with other strains (229E and OC43), which produce only mild common cold symptoms, although more serious disease has been reported in infants and individuals with underlying comorbidities (Pene et al, 2003). SARS-CoV has been isolated from humans, civet cats, raccoon dogs, swine and bats, suggesting that several animal species may function as natural reservoirs for future outbreaks (Guan et al, 2003).…”

Section: Introductionmentioning

confidence: 92%

SARS-CoV replication and pathogenesis in an in vitro model of the human conducting airway epithelium

et al. 2008

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SARS coronavirus (SARS-CoV) emerged in 2002 as an important cause of severe lower respiratory tract infection in humans and in vitro models of the lung are needed to elucidate cellular targets and the consequences of viral infection. The severe and sudden onset of symptoms, resulting in an atypical pneumonia with dry cough and persistent high fever in cases of severe acute respiratory virus brought to light the importance of coronaviruses as potentially lethal human pathogens and the identification of several zoonotic reservoirs has made the reemergence of new strains and future epidemics all the more possible. In this chapter, we describe the pathology of SARS-CoV infection in humans and explore the use of two models of the human conducting airway to develop a better understanding of the replication and pathogenesis of SARS-CoV in relevant in vitro systems. The first culture model is a human bronchial epithelial cell line Calu3 that can be inoculated by viruses either as a nonpolarized monolayer of cells or polarized cells with tight junctions and microvilli. The second model system, derived from primary cells isolated from human airway epithelium and grown on Transwells, form a pseudostratified mucociliary epithelium that recapitulates the morphological and physiological features of the human conducting airway in vivo. Experimental results using these lung epithelial cell models demonstrate that in contrast to the pathology reported in late stage cases SARSCoV replicates to high titers in epithelial cells of the conducting airway. The SARS-CoV receptor, human angiotensin 1 converting enzyme 2 (hACE2), was detected exclusively on the apical surface of cells in polarized Calu3 cells and human airway epithelial cultures (HAE), indicating that hACE2 was accessible by SARS-CoV after airway lumenal delivery. Furthermore, in HAE, hACE2 was exclusively localized to ciliated airway epithelial cells. In support of the hACE2 localization data, the most productive route of inoculation and progeny virion egress in both polarized Calu3 and ciliated cells of HAE was the apical surface suggesting mechanisms to release large quantities of virus into the lumen of the human lung. Preincubation of the apical surface of cultures with antisera directed against hACE2 reduced viral titers by 2 logs while antisera against DC-SIGN/DC-SIGNR did not reduce viral replication levels suggesting that hACE2 is the primary receptor for entry of SARS-CoV into the ciliated cells of HAE cultures. To assess infectivity in ciliated airway cultures derived from susceptible animal species we generated a recombinant SARS-CoV by deletion of open reading frame 7a/7b (ORF 7a/b) and insertion of the green fluorescent protein (GFP) resulting in SARS-CoV GFP. SARS-CoV GFP replicated to similar titers as wild type viruses in Vero E6, MA104, and CaCo2 cells. In addition, SARS-CoV replication in airway epithelial cultures generated Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service ...

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Section: Introductionmentioning

confidence: 92%

SARS-CoV replication and pathogenesis in an in vitro model of the human conducting airway epithelium

et al. 2008

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“…In addition, the present study provides evidence that HCoV-NL63 may have been associated with an outbreak of ARI in a personal-care home. All hospitalizations occurred in the 0-5-year-old and 150-year-old age groups, which suggests that, like the other HCoVs and RSV, HCoV-NL63 may cause more-severe ARI in frail patients, such as infants and the elderly, than in other patients [4,6,[11][12][13].…”

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confidence: 94%

Human Coronavirus NL63 Infection in Canada

et al. 2005

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The isolation of human coronavirus NL63 (HCoV-NL63) in The Netherlands raised questions about its contribution to respiratory illness. In this study, a total of 525 respiratory specimens, collected in Canada primarily during the winter months of 2001-2002, were tested for HCoV-NL63; 19 tested positive for HCoV-NL63, demonstrating virus activity during January-March 2002. Patients with HCoV-NL63 were 1 month-100 years old (median age, 37 years). The main clinical presentations were fever (15/19), sore throat (5/19), and cough (9/19), and 4 patients were hospitalized. These results provide evidence for the worldwide distribution of HCoV-NL63.

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“…However, it is now known that HCoVs can cause severe disease in immunocompromised individuals [9]. The study of HCoVs has been hampered by the difficulty in propagating these viruses in vitro and the lack of specific diagnostic tests with which to identify potentially novel viruses.…”

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confidence: 99%