Authors: Professor Abiola Senok (Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE), Dr Carolina Coelho (University of Exeter, UK), Dr Stefano Rusconi (University of Milan, Italy) and Abigail Sawyer (Future Science Group, UK).
2020 was a crucial year for the field of infectious disease. Therefore, for our 2020 panelist picks, members of the Expert Panel have selected papers that they believe have afforded crucial contributions during the COVID-19 pandemic and beyond. Discover more below.
Detecting SARS-CoV-2 through saliva
The global impact of the ongoing COVID-19 pandemic has been unprecedented impacting all spheres of life. Repeated testing for rapid identification of infected persons with prompt implementation of isolation and contact tracing protocols remain crucial for containing the spread of SARS-CoV-2. Nasopharyngeal swab (NPS) is the gold standard respiratory specimen for SARS-CoV-2 reverse-transcriptase PCR (RT-PCR) tests for COVID-19 screening. However, the risk to healthcare workers which necessitates the use of personal protective equipment when collecting specimens as well as the use of special swabs with transport media, puts a strain on overstretched healthcare systems. Indeed, shortages of PPE and swab collection devices hampered testing in many countries. Furthermore, patients’ discomfort during collection of nasopharyngeal swab specimens limits the acceptability for repeated testing. Hence, the call for the identification of an alternative non-invasive specimen for COVID-19 screening.
This paper by Vogels et al describes SalivaDirect which is “a saliva-based, nucleic-acid-extraction-free, dualplex qRT-PCR method for SARS-CoV-2 detection”. I selected this paper as it builds upon a previous report by this team as well as publications by other researchers, including my group in the United Arab Emirates, which have all documented good diagnostic accuracy indices for saliva SARS-CoV RT-PCR -2, highlighting saliva as an alternative diagnostic specimen for COVID-19 screening [2-5]. In this report, the authors describe a simple and flexible platform that can enhance SARS-CoV-2 capacity testing using saliva as the diagnostic specimen. With SalivaDirect, the use of saliva samples collected without preservatives, the replacement of the nucleic acid extraction step with a simple enzymatic and heating step as well as testing with a dualplex qRT-PCR assay are described. The robustness of SalivaDirect was demonstrated through tests carried out on samples from inpatients, healthcare workers and healthy individuals which showed very good diagnostic accuracy indices. To mitigate against supply chain issues, the platform was validated using reagents and instruments from multiple providers. This simplified testing approach which is not dependent on commercialized kits was also shown to have a lower cost per sample.
SalivaDirect, has already received Emergency Use Authorization from the US Food and Drug Administration. This diagnostic approach can easily be adapted to suit the needs and budgets of different SARS-CoV-2 surveillance health systems. The SalivaDirect protocol is an open-source platform designed to be freely accessible and not commercialized. Indeed, as mentioned by the authors it is “not only a unique assay but also a unique way to approach testing during a pandemic”.
Fungal kinases and transcription factors regulating brain infection in Cryptococcus neoformans
Cryptococcus species complex are fungal pathogens responsible for up to 15% of AIDS-related deaths worldwide. In this highlighted article, the group of Yong-Sun Bahn combines high-throughput approaches, fungal genetics and mouse models to determine which kinases and transcription factors are required for survival in the mouse host. This elegant study compared different routes of infection to identify which fungal genes are required in each host compartment. The authors identified at least three novel transcription factors which are critically important for cryptococcal capacity to survive in the mammalian host. Additionally, this study begins to elucidate which factors are required for each different host environment, i.e., how different host tissues impose and require distinct fungal responses. This will improve understanding of tissue-specific virulence strategies and may help to devise better therapies for this lethal disease.
Yeasts collectively extend the limits of habitable temperatures by secreting glutathione
Using the model organisms Saccharomyces cerevisiae, this article studies cellular death in response to heat stress. These important findings demonstrate that cell density and intercellular cooperation can mitigate heat-induced damage and cell death, a mechanism mediated by extracellular glutathione.
Furthermore, this study provides a simple and wonderfully clear illustration of how a deterministic system can sometimes show randomness. I’ve bookmarked this study as a journal club pick and precious teaching tool, because of its clear illustration of randomness in the laboratory setting.
Mechanism elucidation in COVID-19
Stefano’s picks for 2020 focus on mechanism elucidation in different aspects of research surrounding COVID-19 and have been crucial in understanding the SARS-CoV-2 virus.
The first paper explores the multiple mechanisms through which human antibodies protect against SARS-CoV-2 infection. The second highlights the genetic mechanisms at play in those who are critically ill with COVID-19, identifying potential targets for repurposed medications.
 Vogels CBF, Watkins AE, Harden CA et al. SalivaDirect: A Simplified and Flexible Platform to Enhance SARS-CoV-2 Testing Capacity. medRxiv doi:10.1101/2020.08.03.20167791 (2020).
 Pasomsub E, Watcharananan SP, Boonyawat K et al. Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease-2019 (COVID-19): a cross-sectional study. Clin. Microbiol. Infect. doi:10.1016/j.cmi.2020.05.001 (2020).
 Senok A, Alsuwaidi H, Atrah Y et al. Saliva as an Alternative Specimen for Molecular COVID-19 Testing in Community Settings and Population-Based Screening. Infect. Drug Resist. doi:10.2147/IDR.S275152 (2020).
 Williams E, Bond K, Zhang B, Putland M, Williamson DA. Saliva as a non-invasive specimen for detection of SARS-CoV-2. J. Clin. Microbiol. doi:10.1128/JCM.00776-20 (2020).
 Wyllie AL, Fournier J, Casanovas-Massana A et al. Saliva is more sensitive for SARS-CoV-2 detection in COVID-19 patients than nasopharyngeal swabs. N. Engl. J. Med. doi:10.1056/NEJMc2016359 (2020).
Lee K-T, Hong J, Lee D-G et al. Fungal kinases and transcription factors regulating brain infection in Cryptococcus neoformans. Nat. Commun. doi:10.1038/s41467-020-15329-2 (2020).
Laman Trip DS, Youk H. Yeasts collectively extend the limits of habitable temperatures by secreting glutathione. Nat. Microbiol. doi:10.1038/s41564-020-0704-2 (2020).
Tortorici MA, Beltramello M, Lempp FA et al. Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms. Science doi:10.1126/science.abe3354 (2020).
Pairo-Castineira E, Clohisey S, Klaric L et al. Genetic mechanisms of critical illness in Covid-19. Nature doi:10.1038/s41586-020-03065-y (2020).