Abstract:Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with r… Show more
“…In conclusion, lower ACE2 levels in CF upper respiratory cells might be one of the factors explaining the apparently lower incidence of SARS-CoV-2 infection in CF patients compared with the general population [ 3 , 4 ]. In apparent contrast, a recent study reported a remarkable upregulation of ACE2 (and TMPRSS2) expression in biopsies from CF lungs with respect to controls [ 11 ].…”
Section: Discussionmentioning
confidence: 99%
“…Patients with a clinical diagnosis of CF attending the Regional (Lazio) CF Reference Center of the University Hospital Policlinico Umberto I were enrolled during the 2019/2020 winter season. Real-time (RT) PCR reactions targeting the RNA-dependent RNA polymerase (RdRp) and the envelope (E) genes of SARS-CoV-2 were developed in-house following published protocols [ 4 , 16 ]. Cells were collected from oropharyngeal swabs taken for routine diagnostic testing.…”
Section: Methodsmentioning
confidence: 99%
“…Despite the fact that the CF condition could represent a risk of worse outcomes than the general population, an apparently low spread of SARS-CoV-2 has been reported in CF patients [ 1 , 2 , 3 ] as well as a wide range of clinical symptoms from completely asymptomatic to acute respiratory distress [ 2 , 3 ]. In this scenario, we previously found no case of SARS-CoV-2 infection in CF patients who attended clinic visits at the Regional (Lazio) CF Reference Center in Italy either with respiratory disease that required medical attention or in stable conditions, both before and after the Italian government restrictions for the first COVID-19 wave [ 4 ].…”
The expression rate of SARS-CoV-2 entry genes, angiotensin-converting enzyme 2 (ACE2), the main viral receptor and the proteases, furin and transmembrane serine protease 2 (TMPRSS2) in cystic fibrosis (CF) individuals is poorly known. Hence, we examined their levels in upper respiratory samples of CF patients (n = 46) and healthy controls (n = 45). Moreover, we sought to understand the interplay of type I interferon (IFN-I) with ACE2, furin and TMPRSS2 by evaluating their gene expression with respect to ISG15, a well-known marker of IFN activation, in upper respiratory samples and after ex vivo IFNβ exposure. Lower ACE2 levels and trends toward the reduction of furin and TMPRSS2 were found in CF patients compared with the healthy controls; decreased ACE2 amounts were also detected in CF individuals with pancreatic insufficiency and in those receiving inhaled antibiotics. Moreover, there was a strong positive correlation between ISG15 and ACE2 levels. However, after ex vivo IFNβ stimulation of nasopharyngeal cells, the truncated isoform (dACE2), recently demonstrated as the IFN stimulated one with respect to the full-length isoform (flACE2), slightly augmented in cells from CF patients whereas in those from healthy donors, dACE2 levels showed variable levels of upregulation. An altered expression of SARS-COV-2 entry genes and a poor responsiveness of dACE2 to IFN-I stimulation might be crucial in the diffusion of SARS-CoV-2 infection in CF.
“…In conclusion, lower ACE2 levels in CF upper respiratory cells might be one of the factors explaining the apparently lower incidence of SARS-CoV-2 infection in CF patients compared with the general population [ 3 , 4 ]. In apparent contrast, a recent study reported a remarkable upregulation of ACE2 (and TMPRSS2) expression in biopsies from CF lungs with respect to controls [ 11 ].…”
Section: Discussionmentioning
confidence: 99%
“…Patients with a clinical diagnosis of CF attending the Regional (Lazio) CF Reference Center of the University Hospital Policlinico Umberto I were enrolled during the 2019/2020 winter season. Real-time (RT) PCR reactions targeting the RNA-dependent RNA polymerase (RdRp) and the envelope (E) genes of SARS-CoV-2 were developed in-house following published protocols [ 4 , 16 ]. Cells were collected from oropharyngeal swabs taken for routine diagnostic testing.…”
Section: Methodsmentioning
confidence: 99%
“…Despite the fact that the CF condition could represent a risk of worse outcomes than the general population, an apparently low spread of SARS-CoV-2 has been reported in CF patients [ 1 , 2 , 3 ] as well as a wide range of clinical symptoms from completely asymptomatic to acute respiratory distress [ 2 , 3 ]. In this scenario, we previously found no case of SARS-CoV-2 infection in CF patients who attended clinic visits at the Regional (Lazio) CF Reference Center in Italy either with respiratory disease that required medical attention or in stable conditions, both before and after the Italian government restrictions for the first COVID-19 wave [ 4 ].…”
The expression rate of SARS-CoV-2 entry genes, angiotensin-converting enzyme 2 (ACE2), the main viral receptor and the proteases, furin and transmembrane serine protease 2 (TMPRSS2) in cystic fibrosis (CF) individuals is poorly known. Hence, we examined their levels in upper respiratory samples of CF patients (n = 46) and healthy controls (n = 45). Moreover, we sought to understand the interplay of type I interferon (IFN-I) with ACE2, furin and TMPRSS2 by evaluating their gene expression with respect to ISG15, a well-known marker of IFN activation, in upper respiratory samples and after ex vivo IFNβ exposure. Lower ACE2 levels and trends toward the reduction of furin and TMPRSS2 were found in CF patients compared with the healthy controls; decreased ACE2 amounts were also detected in CF individuals with pancreatic insufficiency and in those receiving inhaled antibiotics. Moreover, there was a strong positive correlation between ISG15 and ACE2 levels. However, after ex vivo IFNβ stimulation of nasopharyngeal cells, the truncated isoform (dACE2), recently demonstrated as the IFN stimulated one with respect to the full-length isoform (flACE2), slightly augmented in cells from CF patients whereas in those from healthy donors, dACE2 levels showed variable levels of upregulation. An altered expression of SARS-COV-2 entry genes and a poor responsiveness of dACE2 to IFN-I stimulation might be crucial in the diffusion of SARS-CoV-2 infection in CF.
“…A lower seroprevalence was noted in individuals with CF (2.7%) versus the general population (4.9%), suggesting a lower infection rate [14] . An overview study conducted in Italy concluded that the infection rate was indeed lower in the CF population than that of the general population [15] , [16] .…”
Section: Epidemiology Of Sars-cov-2 In Cystic Fibrosismentioning
confidence: 99%
“…Secondly, ENaC is significantly increased in CF, promoting inflammation and affecting airway surface liquid homeostasis. Figure 1 Role of ACE and ACE2 in SARS-CoV-2 Lung Infection [15] …”
Section: Role Of Angiotensin Converting Enzyme 2 (Ace2) and Furin In Sars-cov-2 Infectionmentioning
The novel SARS-CoV-2 coronavirus (COVID-19) has become a global health crisis since its initial outbreak in Wuhan, China in December 2019. On January 30, 2020, the WHO recognized the COVID-19 outbreak as a Public Health Emergency, and on March 11, 2020, it was declared a pandemic. Although all age groups have been affected, patients with cystic fibrosis (CF) and patients with diabetes have been categorized as highly vulnerable to SARS-CoV-2 infection. Thus far, studies have found that the incidence of SARS-CoV-2 in the CF population is lower than the general population. We review the underlying protective mechanisms which may reduce inflammation and lung damage in CF patients, thus decreasing their risk of severe COVID-19. While the effect of SARS-CoV-2 in those with
diabetes
related to CF is unknown, other forms of diabetes have been associated with more severe disease. To further understand the potential impact of SARS-CoV-2 in cystic fibrosis-related diabetes, we provide a comprehensive overview of the potential factors contributing to COVID-19 severity in other forms of diabetes, including direct viral effect on the pancreas and indirect effects related to hyperglycemia and immune dysregulation.
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