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Authors: Nicolas de Lamballerie et al.

Link to paper: https://www.biorxiv.org/content/10.1101/2020.05.19.103630v1

Journal/ Pre-Print: BioRxiv

Tags: Immunology/Immunity, Cell Biology, Inflammation

Research Highlights

1. mRNA-sequencing of in vitro models of reconstituted human airway epithelium shows the upregulation of genes involved in inflammation, antiviral response, and cell death upon SARS-CoV-2 infection and the downregulation of cilium-related genes.

2. SARS-CoV-2-infected human airway epithelium models with Aspergillus superinfection was shown to further downregulate the expression of cilium-related genes and upregulate IL-10 signalling genes.

Summary

In this study, the authors explored the biological impact of invasive pulmonary aspergillosis superinfections in the context of SARS-CoV-2. They used a reconstituted human airway epithelial model and compared the resulting transcriptional response to the virus and to the virus with Aspergillosis niger superinfection. In the bronchial epithelium model, superinfection co-occurred with higher viral production. mRNA-sequencing showed upregulation of genes involved in inflammation, antiviral response, and cell death upon in vitro SARS-CoV-2 infection, and downregulation of cilium-related genes. These responses were further enhanced by Aspergillus superinfection, more so in the bronchial epithelium than in the nasal epithelium.

Impact for SARS-CoV2/COVID19 research efforts

· Understand the immune response to SARS-CoV-2/COVID19

· Clinical symptoms and pathogenesis of SARS-CoV-2/COVID19

Study Type

· In vitro study

Strengths and limitations of the paper

Novelty: To this day, data on superinfections/coinfections in COVID-19 pneumonia has been sparse and limited. Their findings suggest that Aspergillus superinfection increases viral production in vitro which warrants further investigation into the mechanism.

Standing in the field: A number of patients in intensive care across the world have been diagnosed with secondary infections including invasive pulmonary Aspergillus (Alanio et al., 2020), making these experiments relevant to clinical findings.

Appropriate statistics: Satisfactory

Viral model used: BetaCoV/France/IDF0571/2020 SARS-CoV-2

Translatability: Not close to bedside. This study provides some insight into the potential immune and inflammatory response in COVID-19 patients with an Aspergillus superinfection, but no hypothesis is made on its clinical management.

Main limitations:

· A reconstituted human airway epithelium model was used in this study, but no details were provided on the cultures it was derived from.

· They do not mention how many biological replicates were used for RNA isolation.

· GSEA plots only show p-values instead of fold change, making it difficult to judge relative size of the responses.

· They did not offer any explanation on the potential mechanism behind the observed differences between nasal and bronchial epithelium.

· The axes labels of Figure 2A and 2B are difficult to read.