Variations in infection control practices suggest a need for guidelines in primary ciliary dyskinesia patient care (preprint)

Primary ciliary dyskinesis (PCD) is an autosomal recessive disorder associated with impaired mucociliary clearance caused by defects in ciliary structure and function. The major clinical feature of PCD is recurring or persistent respiratory tract infection. Respiratory tract colonization with drug-resistant organisms impact the frequency of infections and lung function decline. Protective gear has been employed by caregivers in an attempt to control respiratory tract bacterial spread between patients with cystic fibrosis but use in PCD is not known. We conducted a web-based survey to investigate infection control and prevention practices of PCD centers in North America. The response rate was 87.0%. Prior to the COVID-19 pandemic, glove, gown and mask use was variable, and only 3.7% of centers used masks during encounters with PCD outpatients. After COVID-19 mandates are lifted, 48.1% of centers plan to continue to use masks during outpatient care, while the practice regarding use of gloves and gowns was not influenced by the current pandemic. There is no uniform practice for infection control in PCD care indicating the need for practice guidelines. Mitigation of respiratory virus transmission learned during the COVID-19 pandemic may impact future infection control approaches used for patients with PCD and other lung diseases.

Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell (preprint)

Established in vitro models for SARS-CoV-2 infection are limited and include cell lines of non-human origin and those engineered to overexpress ACE2, the cognate host cell receptor. We identified human H522 lung adenocarcinoma cells as naturally permissive to SARS-CoV-2 infection despite complete absence of ACE2. Infection of H522 cells required the SARS-CoV-2 spike protein, though in contrast to ACE2-dependent models, spike alone was not sufficient for H522 infection. Temporally resolved transcriptomic and proteomic profiling revealed alterations in cell cycle and the antiviral host cell response, including MDA5-dependent activation of type-I interferon signaling. Focused chemical screens point to important roles for clathrin-mediated endocytosis and endosomal cathepsins in SARS-CoV-2 infection of H522 cells. These findings imply the utilization of an alternative SARS-CoV-2 host cell receptor which may impact tropism of SARS-CoV-2 and consequently human disease pathogenesis.

The translational landscape of SARS-CoV-2 and infected cells (preprint)

SARS-CoV-2, a betacoronavirus with a positive-sense RNA genome, has caused the ongoing COVID-19 pandemic. Although a large number of transcriptional profiling studies have been conducted in SARS-CoV-2 infected cells, little is known regarding the translational landscape of host and viral proteins. Here, using ribosome profiling in SARS-CoV-2-infected cells, we identify structural elements that regulate viral gene expression, alternative translation initiation events, as well as host responses regulated by mRNA translation. We found that the ribosome density was low within the SARS-CoV-2 frameshifting element but high immediately downstream, which suggests the utilization of a highly efficient ribosomal frameshifting strategy. In SARS-CoV-2-infected cells, although many chemokine, cytokine and interferon stimulated genes were upregulated at the mRNA level, they were not translated efficiently, suggesting a translational block that disarms host innate host responses. Together, these data reveal the key role of mRNA translation in SARS-CoV-2 replication and highlight unique mechanisms for therapeutic development.

Identification, Isolation, Propagation And Inactivation Of SARS-CoV2 Isolated From Egypt (preprint)

Severe Acute Respiratory Syndrome Coronavirus 2 causes the novel pandemic Pneumonia disease. It is a positive single strand ssRNA virus that infect human. COVID-19 appeared in Egypt in Feb 2020. The samples were taken from patients with COVID-19 symptoms at military hospital in Egypt and transported to the main chemical laboratories under all the biosafety measures according to WHO guidelines. All samples were tested with RT-PCR. Positive samples were cultured using VeroE6 cell lines. The propagated virus was isolated and inactivated. The isolated virus was sequenced using next generation sequencing and submitted into gene bank. This study provides an isolation, propagation and inactivation methodology which is valuable for production of inactivated vaccines against SARS-CoV2 in Egypt.