Brazilian initial experience with lung transplantation due to irreversible lung fibrosis post-COVID-19 in a national reference center: a cohort study.

BACKGROUND: Lung transplantation (LTx) has been discussed as an option for treating irreversible lung fibrosis post-coronavirus disease 2019 (COVID-19), in selected cases. OBJECTIVES: To report on the initial experience and management of end-stage lung disease due to COVID-19 at a national center reference in Brazil. DESIGN AND SETTING: Cohort study conducted at a national reference center for lung transplantation. METHODS: Medical charts were reviewed regarding patients' demographics and pre-COVID-19 characteristics, post-LTx due to COVID-19. RESULTS: Between March 2020 and September 2021, there were 33 cases of LTx. During this period, we evaluated 11 cases of severe COVID-19-related acute respiratory distress syndrome (ARDS) that were potentially candidates for LTx. Among these, LTx was only indicated for three patients (9.1%). All of these patients were on venovenous extracorporeal membrane oxygenation (ECMO), and the procedure that they underwent was central venoarterial ECMO. All three patients were still alive after the first 30 postoperative days. However, patient #1 and patient #2 subsequently died due to fungal sepsis on the 47th and 52nd postoperative days, respectively. Patient #3 was discharged on the 30th postoperative day. CONCLUSIONS: LTx is feasible among these complex patients. Survival over the first 30 days was 100%, and this favors surgical feasibility. Nonetheless, these were critically ill patients.

Nanoplasmonic amplification in microfluidics enables minute-scale colorimetric quantification of nucleic acid biomarkers (preprint)

Nucleic acid amplification is the gold standard molecular diagnostic test, but it is not easily deployable due to required lengthy protocols and specialized equipment. The point of care testing to date is limited by versatility and rapidity in reading the amplification signal. We propose a new molecular test by integrating nanoplasmonically boosted nucleic acid amplification and microfluidic sample collection/preparation to achieve fully automated minute-scale (sample-to-answer time of 13 minutes) colorimetric detection of multiple nucleic acid biomarkers at single nucleotide resolution (QolorEX). Here, one-step isothermal amplification of RNA/DNA with loop-mediated amplification (RT-LAMP) and rolling circle amplification (RCA) can be boosted three-folds via plasmonic color enhancement generated on the surface of plasmonic nanostructures confined in the microfluidics. This offers a label/probe-free colorimetric approach deployable for the detection of a variety of targets by simple tuning of amplification reagents with a quantitative response as a function of the pathogen load. We demonstrated the versatility of the QolorEX through the detection of respiratory viruses such as SARS-CoV-2, and Influenza A H1N1, as well as antimicrobial-resistant bacteria such as Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA). We also demonstrated discrimination between SARS-CoV-2 variants by incorporating RCA to detect viral RNA alternatives at the level of single nucleotide polymorphism. We illustrated the diagnostic capability of QolorEX in clinical setting by testing 33 saliva samples from COVID-19 patients and achieved quantitative detection of viral RNA in saliva with a detection limit of 5 RNA copies/μl and 95% accuracy on par with qPCR. The simplicity, sensitivity, and robustness of QolorEX’s technology might eventually help with real-time monitoring of pathogenic infections and assist in clinical decision-making.

SARS-CoV-2 impairs interferon production via NSP2-induced repression of mRNA translation (preprint)

Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a novel mechanism by which the SARS-CoV-2 virus co-opts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-{beta}. We reveal that the SARS-CoV-2 encoded Non-Structural Protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein. This interaction enhances the binding of GIGYF2 to the mRNA cap-binding protein 4EHP, thereby repressing the translation of the Ifnb1 mRNA. Depletion of GIGYF2 or 4EHP significantly enhances IFN-{beta} production, leading to reduced viral infection. Our findings reveal a new target for rescuing the antiviral innate immune response to SARS-CoV-2 and other RNA viruses.