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      Artificial intelligence vs COVID-19: limitations, constraints and pitfalls

      research-article
      Ai & Society
      Springer London
      COVID-19, Data science, AI, Surveillance, Public health

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          Abstract

          This paper provides an early evaluation of Artificial Intelligence (AI) against COVID-19. The main areas where AI can contribute to the fight against COVID-19 are discussed. It is concluded that AI has not yet been impactful against COVID-19. Its use is hampered by a lack of data, and by too much data. Overcoming these constraints will require a careful balance between data privacy and public health, and rigorous human-AI interaction. It is unlikely that these will be addressed in time to be of much help during the present pandemic. In the meantime, extensive gathering of diagnostic data on who is infectious will be essential to save lives, train AI, and limit economic damages.

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          Most cited references10

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          An interactive web-based dashboard to track COVID-19 in real time

          In December, 2019, a local outbreak of pneumonia of initially unknown cause was detected in Wuhan (Hubei, China), and was quickly determined to be caused by a novel coronavirus, 1 namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak has since spread to every province of mainland China as well as 27 other countries and regions, with more than 70 000 confirmed cases as of Feb 17, 2020. 2 In response to this ongoing public health emergency, we developed an online interactive dashboard, hosted by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University, Baltimore, MD, USA, to visualise and track reported cases of coronavirus disease 2019 (COVID-19) in real time. The dashboard, first shared publicly on Jan 22, illustrates the location and number of confirmed COVID-19 cases, deaths, and recoveries for all affected countries. It was developed to provide researchers, public health authorities, and the general public with a user-friendly tool to track the outbreak as it unfolds. All data collected and displayed are made freely available, initially through Google Sheets and now through a GitHub repository, along with the feature layers of the dashboard, which are now included in the Esri Living Atlas. The dashboard reports cases at the province level in China; at the city level in the USA, Australia, and Canada; and at the country level otherwise. During Jan 22–31, all data collection and processing were done manually, and updates were typically done twice a day, morning and night (US Eastern Time). As the outbreak evolved, the manual reporting process became unsustainable; therefore, on Feb 1, we adopted a semi-automated living data stream strategy. Our primary data source is DXY, an online platform run by members of the Chinese medical community, which aggregates local media and government reports to provide cumulative totals of COVID-19 cases in near real time at the province level in China and at the country level otherwise. Every 15 min, the cumulative case counts are updated from DXY for all provinces in China and for other affected countries and regions. For countries and regions outside mainland China (including Hong Kong, Macau, and Taiwan), we found DXY cumulative case counts to frequently lag behind other sources; we therefore manually update these case numbers throughout the day when new cases are identified. To identify new cases, we monitor various Twitter feeds, online news services, and direct communication sent through the dashboard. Before manually updating the dashboard, we confirm the case numbers with regional and local health departments, including the respective centres for disease control and prevention (CDC) of China, Taiwan, and Europe, the Hong Kong Department of Health, the Macau Government, and WHO, as well as city-level and state-level health authorities. For city-level case reports in the USA, Australia, and Canada, which we began reporting on Feb 1, we rely on the US CDC, the government of Canada, the Australian Government Department of Health, and various state or territory health authorities. All manual updates (for countries and regions outside mainland China) are coordinated by a team at Johns Hopkins University. The case data reported on the dashboard aligns with the daily Chinese CDC 3 and WHO situation reports 2 for within and outside of mainland China, respectively (figure ). Furthermore, the dashboard is particularly effective at capturing the timing of the first reported case of COVID-19 in new countries or regions (appendix). With the exception of Australia, Hong Kong, and Italy, the CSSE at Johns Hopkins University has reported newly infected countries ahead of WHO, with Hong Kong and Italy reported within hours of the corresponding WHO situation report. Figure Comparison of COVID-19 case reporting from different sources Daily cumulative case numbers (starting Jan 22, 2020) reported by the Johns Hopkins University Center for Systems Science and Engineering (CSSE), WHO situation reports, and the Chinese Center for Disease Control and Prevention (Chinese CDC) for within (A) and outside (B) mainland China. Given the popularity and impact of the dashboard to date, we plan to continue hosting and managing the tool throughout the entirety of the COVID-19 outbreak and to build out its capabilities to establish a standing tool to monitor and report on future outbreaks. We believe our efforts are crucial to help inform modelling efforts and control measures during the earliest stages of the outbreak.
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            COVID-19: combining antiviral and anti-inflammatory treatments

            Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are characterised by an overexuberant inflammatory response and, for SARS, viral load is not correlated with the worsening of symptoms.1, 2 In our previous Correspondence to The Lancet, 3 we described how BenevolentAI's proprietary artificial intelligence (AI)-derived knowledge graph, 4 queried by a suite of algorithms, enabled identification of a target and a potential therapeutic against SARS coronavirus 2 (SARS-CoV-2; the causative organism in COVID-19). We identified a group of approved drugs that could inhibit clathrin-mediated endocytosis and thereby inhibit viral infection of cells (appendix). The drug targets are members of the numb-associated kinase (NAK) family—including AAK1 and GAK—the inhibition of which has been shown to reduce viral infection in vitro.5, 6 Baricitinib was identified as a NAK inhibitor, with a particularly high affinity for AAK1, a pivotal regulator of clathrin-mediated endocytosis. We suggested that this drug could be of use in countering SARS-CoV-2 infections, subject to appropriate clinical testing. To take this work further in a short timescale, a necessity when dealing with a new human pathogen, we re-examined the affinity and selectivity of all the approved drugs in our knowledge graph to identify those with both antiviral and anti-inflammatory properties. Such drugs are predicted to be of particular importance in the treatment of severe cases of COVID-19, when the host inflammatory response becomes a major cause of lung damage and subsequent mortality. Comparison of the properties of the three best candidates are shown in the table . Baricitinib, fedratinib, and ruxolitinib are potent and selective JAK inhibitors approved for indications such as rheumatoid arthritis and myelofibrosis. All three are powerful anti-inflammatories that, as JAK–STAT signalling inhibitors, are likely to be effective against the consequences of the elevated levels of cytokines (including interferon-γ) typically observed in people with COVID-19· 2 Although the three candidates have similar JAK inhibitor potencies, a high affinity for AAK1 suggests baricitinib is the best of the group, especially given its once-daily oral dosing and acceptable side-effect profile. 7 The most significant side-effect seen over 4214 patient-years in the clinical trial programmes used for European Medicines Agency registration was a small increase in upper respiratory tract infections (similar to that observed with methotrexate), but the incidence of serious infections (eg, herpes zoster) over 52 weeks' dosing was small (3·2 per 100 patient-years), and similar to placebo. 7 Use of this agent in patients with COVID-19 over 7–14 days, for example, suggests side-effects would be trivial. Table Properties of three antiviral and anti-inflammatory candidate drugs Baricitinib Ruxolitinib Fedratinib Daily dose, mg 2–10 25 400 Affinity and efficacy: Kd or IC50, nM* AAK1† Cell free 17 100 32 Cell 34 700 960 GAK† Cell free 136 120 1 Cell 272 840 30 BIKE† Cell free 40 210 32 Cell 80 1470 960 JAK1 Cell free 6 3 20 Cell 12 20 600 JAK2 Cell free 6 3 3 Cell 11 21 100 JAK3 Cell free >400 2 79 Cell >800 14 2370 TYK2 Cell free 53 1 20 Cell 106 7 600 Pharmacokinetics Plasma protein binding 50% 97% 95% Cmax (unbound), nM 103‡ 117 170 Safety: tolerated dose ≤10 mg/day ≤20 mg twice daily ≤400 mg/day See regulatory approval documents for further information on these drugs. Kd=dissociation constant. IC50=half-maximal inhibitory concentration. Cmax=maximum serum concentration. * All values are IC50 except the cell free values for AAK1, GAK, and BIKE; “cell free” values indicate inhibitory activity against purified protein in biochemical assay; “cell” values indicate enzyme-inhibitory activity inside a cell. † In the absence of direct measurements of drug inhibition in cells, the predicted cell affinity and efficacy values are derived from the ratio of each compound for their primary target; for example, for baricitinib, IC50 AAK1[cell] = (IC50AK1[cell] / IC50AK1[cell free]) × IC50AAK1[cell free]. ‡ At a 10 mg dose. Other AI-algorithm-predicted NAK inhibitors include a combination of the oncology drugs sunitinib and erlotinib, shown to reduce the infectivity of a wide range of viruses, including hepatitis C virus, dengue virus, Ebola virus, and respiratory syncytial virus.5, 6 However, sunitinib and erlotinib would be difficult for patients to tolerate at the doses required to inhibit AAK1 and GAK. By contrast, at therapeutic doses used for the treatment of patients with rheumatoid arthritis, the free plasma concentrations of baricitinib are predicted to be sufficient to inhibit AAK1, and potentially GAK, in cell-based assays. The predicted inhibition of clathrin-mediated endocytosis by baricitinib is unlikely to be observed with other anti-arthritic drugs or JAK inhibitors. Our analysis of the closely related JAK inhibitors ruxolitinib and fedratinib (table) illustrates that the predicted unbound plasma exposure required to inhibit the enzymes needed for clathrin-mediated endocytosis greatly exceeds the currently tolerated exposures used therapeutically. These drugs are, therefore, unlikely to reduce viral infectivity at tolerated doses, although they might reduce the host inflammatory response through JAK inhibition. Intriguingly, another JAK inhibitor, tofacitinib, shows no detectable inhibition of AAK1. The high affinity of baricitinib for NAKs, its anti-inflammatory properties, and its ability to ameliorate associated chronic inflammation in interferonopathies, 8 together with its advantageous pharmacokinetic properties, appear to make it a special case among the approved drugs. In addition, the potential for combination therapy with baracitinib is high because of its low plasma protein binding and minimal interaction with CYP enzymes and drug transporters. Furthermore, there is the potential for combining baricitinib with the direct-acting antivirals (lopinavir or ritonavir and remdesivir) currently being used in the COVID-19 outbreak, since it has a minimal interaction with the relevant CYP drug-metabolising enzymes. Combinations of baricitinib with these direct-acting antivirals could reduce viral infectivity, viral replication, and the aberrant host inflammatory response. This work demonstrates that the use of an AI-driven knowledge graph can facilitate rapid drug development.
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              Planning chemical syntheses with deep neural networks and symbolic AI

              To plan the syntheses of small organic molecules, chemists use retrosynthesis, a problem-solving technique in which target molecules are recursively transformed into increasingly simpler precursors. Computer-aided retrosynthesis would be a valuable tool but at present it is slow and provides results of unsatisfactory quality. Here we use Monte Carlo tree search and symbolic artificial intelligence (AI) to discover retrosynthetic routes. We combined Monte Carlo tree search with an expansion policy network that guides the search, and a filter network to pre-select the most promising retrosynthetic steps. These deep neural networks were trained on essentially all reactions ever published in organic chemistry. Our system solves for almost twice as many molecules, thirty times faster than the traditional computer-aided search method, which is based on extracted rules and hand-designed heuristics. In a double-blind AB test, chemists on average considered our computer-generated routes to be equivalent to reported literature routes.
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                Author and article information

                Contributors
                naude@time.rwth-aachen.de
                Journal
                AI Soc
                AI Soc
                Ai & Society
                Springer London (London )
                0951-5666
                1435-5655
                28 April 2020
                28 April 2020
                : 1-5
                Affiliations
                GRID grid.1957.a, ISNI 0000 0001 0728 696X, Technology, Innovation, Entrepreneurship and Marketing, , RWTH Aachen University, ; Kackertstrasse 7, 52072 Aachen, Germany
                Article
                978
                10.1007/s00146-020-00978-0
                7186767
                32346223
                8a22eb19-9d44-4171-a060-116120d8116d
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 1 April 2020
                : 3 April 2020
                Categories
                Curmudgeon Corner

                covid-19,data science,ai,surveillance,public health
                covid-19, data science, ai, surveillance, public health

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