correspondence Research priorities for COVID-19 sensor technology

To the Editor — The COVID-19 pandemic This priority-setting project involved 83 access to treatment, preserve finite resources has spurred efforts to develop sensor patients with COVID-19, family members, (in terms of staffing, facilities for quarantine technology to manage the disease1–3. Most the general public, scientists, engineers, and personal protective equipment) and of these projects have been driven by health professionals (including specialist to provide prognostic to medical researchers, scientists and engineers clinicians from multiple disciplines, inform patient care. Second, ‘Minimizing without explicit involvement and input such as infectious diseases, diagnostic societal disruption’ was emphasized to from patients and the broader community. pathology, cardiology or cardiovascular enable a return to normal life and to reduce Here, we define sensor technology broadly diseases, respiratory medicine, geriatrics, stigma and isolation. Third, ‘Protecting to include physical, cellular and molecular emergency medicine, critical care medicine, the community’ supported the need for platforms that produce to identify gastroenterology, hematology, pediatrics, sensor technology that could trigger contact specific events associated with SARS-CoV-2 infection prevention and control, and tracing, establish safe environments, and/or its interaction with the host. The digital health), policy makers, industry safeguard the vulnerable, gauge individual main applications of sensor technology representatives and funders. susceptibility to COVID-19, and manage the in COVID-19 have been to detect fever We conducted an online survey to risk among healthcare workers. And finally, using infrared sensing devices and the prioritize research statements in which ‘Preparedness for the next phase of the presence of viral RNA using polymerase respondents (n = 43) rated their importance pandemic’ required sensor technology to be chain reaction (PCR) tests1. However, a using a 9-point Likert scale (7–9 indicating relevant and responsive to the development substantial proportion of individuals with ‘critical importance’). The mean score, of immunity and vaccines, and to help COVID-19 never develop fever1. PCR tests median and proportion of participants who maintain the suppression phase over the have been developed to detect SARS-CoV-2 rated the statement to be critically important long term. A detailed description with in nasopharyngeal samples, but to date they are provided in Supplementary Table 1. supporting quotations for each theme is have been expensive, resource-intensive, Research statements that had a mean and provided in Supplementary Table 3. cumbersome and relatively slow. Moreover, median of ≥7 were discussed at a consensus For each of the top research priority positive PCR tests do not imply a person is workshop, conducted using Zoom statements, the specific suggestions for still infectious and thus have not provided videoconferencing on 20 August 2020, with sensor technology (including compounds information about transmissibility or the following goals: to achieve agreement and devices) and its application are virulence1,4,5, hampering the development of on the research priorities, generate ideas summarized in Table 1. The suggestions more effective action plans in the societal, for sensor technologies and discuss of ensuring feasibility, usability and economic and public health dimensions6. facilitators and barriers to implementation. acceptability of sensor technology and Given the urgent need to better control To encourage diverse discussions, the 65 applications to address COVID-19 are the pandemic and its impact on the attendees were preassigned to six virtual outlined in Supplementary Table 4. These community, resources should be allocated breakout groups, with each group including have been identified as essential attributes in a strategic and targeted manner that patients who had been diagnosed previously for an ideal sensor for pandemics in general, takes into account community perspectives, with COVID-19 and/or family members, including accuracy, a fast response time, through an explicit consensus-based process health professionals, scientists or engineers, multiplexing capabilities, multiple sensing with equitable involvement of patients, and policymakers or funders. Each breakout modes (sensor fusion and the use of artificial the public, researchers and clinicians. group was managed by a facilitator and intelligence to detect signatures that reveal Co-production in research specifically cofacilitator who moderated the discussion infection), disposability, long shelf life, ease involving consumers or end-users is now using the workshop question guide of use, cost-effectiveness, manufacturability, widely advocated to improve the relevance, (Supplementary Table 2). All discussions and autonomy2. Particular emphasis was use and impact of the findings7,8. It requires were transcribed. We identified reasons for placed on the need for samples to be easy partnership and collaboration between the priorities, ideas for sensor technologies and safe to collect and the need for sensor researchers and the broader community from (compounds, devices, general application), devices to be non-invasive and their use the outset, beginning with priority-setting8. and the implementation of each (feasibility, regulated appropriately to ensure data There have been few research priority-setting usability, acceptability). privacy. The legal, ethical and privacy partnerships in COVID-19, with very few Of the 18 research statements, 8 had concerns surrounding the use of digital involving patients and the public, and none a mean and median score of 7 or more technology in COVID-19 are highly with a focus on sensor technology. Below, (Table 1). The top three priorities were the relevant given the need for public trust and we describe the development and outcome following: develop a point-of-care screening engagement to ensure widespread uptake1. of a process through which we identified the test for COVID-19; detect how contagious Patients in particular emphasized the shared priorities of patients, the community, a person with COVID-19 is; and identify profound impacts of COVID-19 on mental health professionals, scientists, engineers the level of immunity a person has to health as a consequence of self-isolation and and policy makers for research in sensor COVID-19. The reasons for priorities were quarantine. Specifically, patients gave high technology to address COVID-19, the summarized in four themes. First, ‘Enabling priority to the detection of immunity and reasons for their priorities, and ideas for more efficient clinical decision-making’ wanted assurance that they were no longer implementation. was driven by the need to prevent delays in contagious because families and friends were

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Table 1 | Suggestions and ideas for sensor technology to address COVID-19 Statement Ideas for compounds, devices and general application Develop a point-of-care (instant) • Target a different type of sample or organ (other than , nasal or throat swab, or temperature), for example, screening test for COVID-19 urine (non-aerosol-generating procedure) • Detect other compounds or chemicals that the body generates due to infection and that may be used as a signature of disease • Detect viral components • Use microfluidic technology: capture particles on a microfluidic ; they go to the optic sensor and the optic sensor functions as a screener • Develop wearable non-intrusive devices for healthcare workers that capture temperature and other clinical parameters, with data captured in a central service for , and use artificial intelligence to analyze the data • Create a device used in the toilet to measure microbiome, with data connected to a phone or other device; sample viral loads in sewage • Support rapid transmission of data packets • F or individual screening, offer conventional methods such as a strip and a reader, with results transmitted to a central location • Develop a dipstick test using saliva • Analyze physiological or responses (similarly to browsers that assess whether people are robots) with artificial intelligence learning • Use a microphone to detect characteristics of breathing • Provide a device to monitor hypoxia • Develop a device to monitor the ability to smell, olfactory type of sensing • Provide a device to monitor heart rate • Use sensors to detect inflammation in the mucosal tract • Develop a mask with breath analysis to infection Detect how infectious a person with • Develop face masks with sensors (for example, one that changes color if a person is contagious) a virus is • Use sensors to measure breathing, cough, inflammation • Develop a tongue swab to determine viral load on site • Develop cell cultures with cell types that are very susceptible infection by the virus, and expose them to infected people to measure transmissibility • Measure the aerosol and droplet release that come from talking, sneezing, coughing, perspiration; quantify the particle release from a person and their interaction with other people nearby • Use processing to detect particle exchange Identify the level of immunity a • Develop a saliva test that uses spike protein as a capture medium for immunoglobulin person has to COVID-19, or its • Develop a microneedle patch-based device that may be inserted under the skin in the arm (similar to ones used change over time for monitoring in patients with diabetes) for ongoing monitoring • Identify signals of immunity from, for example, sweat, breath Develop tests to assess people’s • Measure serological responses, T cell responses immunity against the virus Identify who needs a COVID-19 test • Use surveillance technology such as infrared sensors or camera networks and wearables to pick up infected in individuals who are asymptomatic people (who may not exhibit traditional symptoms) by temperature, heat mapping, changes in heart rate, (do not have symptoms) blood pressure, sounds or other observables • Monitor sewage systems Develop a non-invasive, quick, cheap, • Develop breath analysis devices that can detect viral particles and effective diagnostic test that • Use blood samples (similarly to a glucose monitor) people can do themselves • Use respiratory secretions for a home test • Develop a urine-based test (similar to a pregnancy test) Develop a detector for airborne virus • Use detectors in ventilation systems to detect viruses in crowded or high-risk places (for example, nursing homes, supermarkets) • Connect detectors to an alert system (one that does not cause panic) • Use animals such as trained dogs to detect COVID-19 • Detect the virus using a physical process, for example, an integrated device that works with light as the virus absorbs and scatters light • Develop a device for the room or environment (rather than for people) Identify who needs a COVID-19 test in • Develop a device to sense variability in heart rate, skin temperature; that is, change in people who have a chronic condition and with symptoms similar to COVID-19 (for example, persistent cough) avoiding them for an indefinite period of Developing sensor technology for the of vaccines and uncertainty regarding time (for some, over six months), given the detection of protective immunity is also long-term immunity and reinfection3,9,10. fear and stigma attached to COVID-19. important, given the imminent distribution Detection of immunity can further

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David Martinez-Martin 6,8, Alistair McEwan6,8, Rex Wang6, Alice Motion 6,9, Alvaro Casas Bedoya6,10, Jun Huang6,8, Enabling efficient clinical Minimizing societal disruption Lamiae Azizi6,11, Benjamin J. Eggleton 6,10 decision-making and consequences and The COVID-19 Sensor Research • Prevent delays in access to treatment • Allow a return to normal life Priority-Setting Investigators* • Preserve resources • Reduce stigma and isolation • Provide prognostic information 1Sydney School of Public Health, Te University of Sydney, Sydney, NSW, Australia. 2Marie Bashir Detect infection Detect infectivity Assess immunity Institute for Infectious Disease and Biosecurity, Te University of Sydney and Westmead Institute for Medical Research, Sydney, NSW, Australia. 3Sydney Medical School, Te University of Sydney, 4 Protecting the community Preparing for the next phase of the pandemic Sydney, NSW, Australia. Westmead Living Lab, • Trigger contact tracing • Develop immunity and vaccines Te University of Sydney, Sydney, NSW, Australia. 5 • Establish safe environments • Maintain suppression Charles Perkins Centre, Te University of Sydney, • Safeguard the vulnerable Sydney, NSW, Australia. 6Te University of Sydney • Gauge individual susceptibility Nano Institute (Sydney Nano), Te University of • Manage risks among healthcare Implementation Sydney, Sydney, NSW, Australia. 7School of Medical workers • Feasibility and acceptability Sciences, Te University of Sydney, Sydney, NSW, Australia. 8School of Biomedical Engineering, Te University of Sydney, Sydney, NSW, Australia. 9School Fig. 1 | A roadmap for research priorities for COVID-19 sensor technology. of , Te University of Sydney, Sydney, NSW, Australia. 10School of , University of Sydney, Sydney, NSW, Australia. 11School of Mathematics and Statistics, Te University of Sydney, Sydney, NSW, inform strategies to minimize societal and pandemic. Nevertheless, collectively, such Australia. *A list of authors and their afliations economic disruption. Of note, physiological studies can help to formulate an equitable appears at the end of the paper. monitoring was perceived to be lower in and coordinated international response to ✉e-mail: [email protected] priority compared with rapid diagnosis future pandemics and other global threats, and assessment of immunity, despite the including antimicrobial resistance, and Published online: 18 January 2021 possibility of its detecting early changes in mitigate the threat of such crises on people’s https://doi.org/10.1038/s41587-021-00816-8 clinical status that require rapid intervention lives and the world’s economy (Fig. 1). References or admission to hospital (that is, its potential Advances in nanotechnology and 1. Budd, J. et al. Nat. Med. 26, 1183–1192 (2020). as a screening tool). the have stimulated 2. Bhalla, N., Pan, Y., Yang, Z. & Payam, A. F. ACS Nano 14, The research priorities were motivated the proliferation and ubiquity of sensor 7783–7807 (2020). 2 3. Kof, W. C. & Williams, M. A. N. Engl. J. Med. 383, by personal and altruistic concerns. These technology . Traditionally, advances in 804–805 (2020). included anxiety and concern about the sensor research have been the province of 4. Udugama, B. et al. ACS Nano 14, 3822–3835 (2020). need for urgency in diagnosis vis-à-vis experts in smart technology and have not 5. Nagura-Ikeda, M. et al. J. Clin. Microbiol. 58, e01438–20 (2020). 6. Tom, M. R. & Mina, M. J. Clin. Infect. Dis. 71, 2252–2254 (2020). impact of diagnostic delays on the severity systematically and explicitly included the 7. Anonymous. Nature 562, 7 (2018). and spread of COVID-19, a uniform perspectives of the ultimate end users or 8. Hickey, G., Richards, T. & Sheehy, J. Nature 562, 29–31 (2018). preference for convenient sample types beneficiaries. Although consideration is 9. Chaturvedi, R., Naidu, R., Sheth, S. & Chakravarthy, K. Disaster Med. Public Health Prep. https://doi.org/10.1017/dmp.2020.216 for testing, and the personal and public given to the end user in the design of sensor (2020). health need to be confident in the validity technology, the process is usually linear 10. Goussef, M. et al. J. Infect. 81, 816–846 (2020). of markers of protective immunity and the and between only two stakeholder groups. Acknowledgements duration of such immunity in response to The inclusion of diverse stakeholder groups The project is funded by Sydney Nano. A.T. is supported either natural infection or vaccination. provides a more complete perspective to by the University of Sydney Robinson Fellowship and a The high priority that patients gave to support uptake. Coproduction brings in the National Health and Medical Research Council Investigator measuring infectivity and immunity to human context and attention to the areas of Grant (1197324). The funding organizations had no address stigma, fears and rejection they greatest importance, which are underpinned role in the design and conduct of the study; collection, management, analysis and interpretation of the data; or encountered from community members by social, ethical and human dimensions preparation, review or approval of the manuscript. We when told of their COVID-19 diagnosis beyond just technical considerations. We acknowledge, with permission, all the attendees who would not have been considered without believe this process provides a roadmap for participated in the research priority-setting workshop: inclusion of this stakeholder group in the the allocation of resources to purposefully Sarah Al-Horani, Tomas Andersen, Rodney Aggett, Lamiae prioritization process. advance sensor technology, which will Azizi, Andrew Baillie, Andrew Black, Celine Boehm, Philip Britton, Anthony Brown, Mitchell Burger, Corinne Further work is required to identify strengthen the whole of society’s response Caillaud, Alvaro Casas Bedoya, Steve Chadban, Elaine the extent to which these priorities can be to the COVID-19 pandemic and enhance Chan, Nanda Sakaleshpura Chandrashekar, Gael Clerc, generalized globally or in specific settings, preparedness for future pandemics. ❐ Wojciech Chrzanowski, Ben Eggleton, Simon Fleming, such as in low-resource settings or countries, Gregory Fox, Luke Gordon, Nicholas Haskins, Anita where access to healthcare is limited. Ho-Baillie, Martin Howell, Jun Huang, Nicholas Hunt, Owen Hutchings, Jonathan Iredell, Garry Jennings, Craig Allison Tong 1 ✉ , Tania C. Sorrell2,3, Furthermore, immediate research priorities Jin, Omid Kavehei, Paris Kilham, Leonard Kritharides, 4 5,6,7 may differ in countries, locations or Andrew J. Black , Corinne Caillaud , Ben Kwan, Sergio Leon-Saval, Eugena Li, Steven Maguire, cultures experiencing different stages of the Wojciech Chrzanowski5,6, Eugena Li6, David Martinez-Martin, Annie McCluskey, Alistair

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McEwan, Nicholas McKay, Julian Morgans, Alice Motion, Benjamin Eggleton13, Simon Fleming13, 12University of Technology, Ultimo, NSW, Australia. Stefano Palomba, Alan Pettigrew, Svetlana Postnova, Gregory Fox13, Nicky Gilroy20, Luke Gordon13, 13Te University of Sydney, Camperdown, NSW, Cathy Quinlan, James Rabeau, Katie Richmond, Damien Nicholas Haskins23, Anita Ho-Baillie13, 14 15 Rothstein, Nicole Scholes-Robertson, Tim Shaw, Vitali Australia. Sydney, NSW, Australia. Te 13 13 13 Sintchenko, Thomas Snelling, Tania Sorrell, Allison Tong, Martin Howell , Ian Hickie , Jun Huang , University of Sydney, Sydney Local Health District, Alessandro Tuniz, Pegah Varamini, Audrey Wang, Kailing Nicholas Hunt13, Owen Hutchings24, Camperdown, NSW, Australia. 16Te University Wang, Rex Wang, Alexander Witherden, Benjamin Wright, Jonathan Iredell25, Garry Jennings26, Craig Jin13, of Sydney, Te Children’s Hospital at Westmead, Wilson Yeung and Hans Zoellner. We acknowledge and Kristina Kairaitis13, Omid Kavehei13, Westmead, NSW, Australia. 17Health Consumers pay respect to the Gadigal people of the Eora Nation, the 27 14 18 traditional owners of the land on which we research, teach Peter Kennedy , Paris Kilham , NSW, Sydney, NSW, Australia. Sydney Local 13 28 and collaborate at The University of Sydney. Leonard Kritharides , Ben Kwan , Health District, Sydney, NSW, Australia. 19Te Sergio Leon-Saval13, Eugena Li13, University of Sydney, Royal Prince Alfred Hospital, Competing interests Richard Lindley13, Deena Lynch29, Camperdown, NSW, Australia. 20Westmead Hospital, The authors declare no competing interests. Steven Maguire13, David Martinez-Martin13, Westmead, NSW, Australia. 21eHealth NSW, Annie McCluskey13, Alistair McEwan13, Sydney, NSW, Australia. 22Bepatient, Sydney, NSW, Additional information Nicholas McKay13, Geofrey Mifsud30, Australia. 23NSW Smart Sensing Network, Sydney, Supplementary information The online version contains Julian Morgans31, Alice Motion13, NSW, Australia. 24Royal Prince Alfred Hospital, supplementary material available at https://doi.org/ Stefano Palomba13, Alan Pettigrew13, Camperdown, NSW, Australia. 25Te University 10.1038/s41587-021-00816-8. Svetlana Postnova13, Joseph Prinable32, of Sydney, NSW Health Pathology, Westmead Cathy Quinlan33, James Rabeau13, The COVID-19 Sensor Research Institute for Medical Research, Westmead, NSW, Mark Rees13, Katie Richmond13, 26 Priority-Setting Investigators Australia. Sydney Health Partners, Camperdown, Damien Rothstein14, Richard Savoie34, NSW, Australia. 27eHealth NSW, Chatswood, NSW, Sarah Al-Horani12, Tomas Andersen13, Nicole Scholes-Robertson13, Ian Seppelt13, Australia. 28Sutherland Hospital, Caringbah, NSW, Rodney Aggett14, Lamiae Azizi13, Tim Shaw13, Vitali Sintchenko13, Australia. 29Jonze Society, Brisbane, QLD, Australia. Andrew Baillie15, Alexandra Barratt13, Thomas Snelling16, Tania Sorrell13, 30Te University of Sydney, Westmead Hospital, Andrew Black13, Celine Boehm13, Philip Britton16, Armando Teixeira-Pinto13, Allison Tong16, Westmead, NSW, Australia. 31Vice, Melbourne, Anthony Brown17, Mitchell Burger18, Euan Tovey13, Alessandro Tuniz13, VIC, Australia. 32Te University of Sydney, ACRF Corinne Caillaud13, Alvaro Casas Bedoya13, Pegah Varamini13, Kavita Varshney20, Image X Institute, Camperdown, NSW, Australia. Steve Chadban19, Elaine Chan20, Audrey P. Wang13, Kailing Wang13, Rex Wang13, 33Royal Children’s Hospital, Parkville, Victoria, Nanda Sakaleshpura Chandrashekar21, Steven Wise13, Alexander Witherden35, Australia. 34Adionatech, Sydney, NSW, Australia. Clara Chow13, Gael Clerc22, Benjamin Wright36, Wilson Yeung21 and 35Camperdown, NSW, Australia. 36Nanosonics Ltd, Wojciech Chrzanowski13, Chris Douglas14, Hans Zoellner13 Sydney, NSW, Australia.

Will Ethiopia be a springboard or a stonewall for GM crops in Africa?

To the Editor — As a systems agronomist research on GM maize and enset (Ensete As debates intensified following the with substantial experience in the ventricosum), a food plant whose cultivation USDA report, rather than Ethiopia’s Consortium of International Agricultural is endemic to Ethiopia. As a result, Bt-cotton decision per se, one explanation is that Research centers (CGIAR) and national has been under widespread production and the controversy is driven by paranoia research institutions in sub-Saharan the country has lately issued a five-year that the United States is using Ethiopia Africa, I have followed with interest the permit to conduct confined field trails on as biotech strategic entry point to expand recent controversy around plantings drought-tolerant and pest-resistant GM its GMO portfolio in Africa. Anti-biotech of transgenic crops in Ethiopia. Until maize3. GM maize trails were successfully activists often amplify these kinds of 2015, the country took a vocal stand conducted in 2019 by the Ethiopian Institute strong rhetorical statements8, which against genetically modified (GM) crops, of Agricultural Research4. have a potential to entrench throughout underlined by its strict proclamation In a recent report4, the US Department the continent. As regulatory systems on biosafety in 2009 (Proclamation No. of (USDA) recognized in most African countries are grappling 655/2009)1. The regulation was so inflexible Ethiopia’s commitment to implementing with the GMO dilemma, Ethiopia’s that a special permission was required to the amended protocol. Although debates final regulatory stance on biotech products transit any “modified organisms” through about gene-modified organisms (GMOs) will have broader implications. Given Ethiopian customs. Six years later, the in Ethiopia started immediately after the Ethiopia’s diplomatic muscle in the country loosened its restrictions in an first prohibitive proclamation in 2009, they region, this forms a turning point for amended proclamation (Proclamation No. were low-key and mostly pro-GMO (Fig. 1). the fate of biotech products all over the 896/2015)2. The latter proclamation allows Severe criticisms against GMOs exploded continent and beyond. Because Ethiopia ‘the commercial cultivation of genetically following USDA’s accolades for Ethiopia’s is Africa’s diplomatic epicenter, its modified (GM) cotton and confined field relaxation of rules5–7. endorsement or dismissal of GMOs may

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