Leveraging novel technologies for COVID-19 for a better AMR response

SPEAKER: In this section, we will discuss the various new innovations stimulated by the COVID-19 pandemic. How lessons from COVID can be applied for better AMR test, and the power of connectivity and data dashboards. COVID provided an unprecedented response from industry with more than 1,000 new tests. Point of care molecular technologies provide results between 5 and 15 minutes, and more sensitive rapid antigen tests can be used for scaling up community-based testing. There are more home or self tests now available and diagnostics are being used as public health tools in non-health care settings. Low and middle income countries have expanded capacity to perform molecular testing, and data connectivity has become an essential component of diagnostics to ensure reporting to surveillance programmes.

COVID has converged diagnostics with digital and telecommunication technologies for real time tracking of the pandemic. This is what we need for AMR, for resistance testing, and data connectivity, to make that data available to clinicians for early alert of outbreaks and AMR stewardship programmes. We will soon see opportunities to use rapid tests at primary health care settings combined with artificial intelligence and machine learning for improved differential diagnosis for common clinical syndromes, such as urinary tract and respiratory infections.

This table provides the characteristics of different types of tests and their use cases. There are currently more than 350 molecular tests being marketed today, either as test kits or reagent packages, to detect the SARS-CoV-2 RNA. These would optimally be used within seven days of onset of symptoms in order to confirm infection. There are more than 110 antigen tests that detect the viral proteins, and could be used as early as day 0 up through day 10, and also can be used to confirm infections. And with more than 390 serology tests that detect host antibodies, these are ideally used between days 7 and 40 in order to inform exposure and provide data for surveillance programmes.

Understanding the types of tests available and how and when they should be used allows for the right test for the right patient at the right time and in the right setting.

In settings where molecular tests are not available or time to result is delayed, WHO has recommended the use of rapid antigen tests for anyone with COVID-19 symptoms to confirm clinical diagnosis. These rapid antigen tests should have a minimal performance of 80% sensitivity and 97% specificity, compared to a molecular test, such as PCR, approved for emergency use by WHO, or other stringent regulatory authorities, such as the US FDA. This table lists the instrument-based rapid antigen tests that have been granted emergency use authorization by the US FDA. All tests performed above the WHO recommendations and provide results on average between 15 and 30 minutes. The column in the middle informs us that the clinical samples used were from symptomatic or asymptomatic patients.

The COVID-19 pandemic has also shown us enhanced testing capacity and surveillance. In both health care settings, such as hospitals, elderly care homes, clinics, and doctor’s offices, and nursing stations, as well as non-health care settings, such as pharmacies, schools, workplaces, and mass gatherings. As COVID testing has expanded beyond traditional health settings, such as the lab and hospital, the need for increased digital solutions for surveillance is also increased. We need to be able to gather data from all of these settings for both clinical and public health action.

Rapid and easily accessible diagnostics have become powerful public health tools, particularly for low and middle income countries, when placed at either high risk or convenient access points. In the top portion of this figure, we show various settings for symptomatic patients are tested using lab-based molecular tests to diagnose infection, such as health facilities. But we also show how rapid tests could be used to quickly screen health care workers, care home workers, and first responders. Rapid screening tests could also be used in community settings and at entry points at mass gatherings and border crossings. Community screening is often done online. A person can pay for a molecular or rapid antigen test online.

The company sends a specimen collection kit to the buyer’s address. The buyer collects the specimen by either following the instructions that come with the collection kit or access video instructions online. The specimen is then mailed back to the company for testing and the results are sent back to the buyers by mail. In this slide, we briefly touch on the ability for patients to test themselves, either at home or at pharmacies. We are all familiar with the most common self-test, the pregnancy dipstick test, and how it is accurate, cheap, and easy to use. Another example is the HIV self-test.

Made available over the counter in 2012, it allows for increased uptake of testing, especially for those not reached by traditional services or stigmatised. And most recently, the COVID-19 rapid antigen home self-test is flying off the shelves at pharmacies as it allows anyone to self-test and receive immediate results. The question then would be, could a self-test able to distinguish between bacterial and viral infection made available at pharmacies pave a new way to combat overuse of antibiotics?

One of the most recent potential innovations for AMR is based on sequencing and the ability to monitor the spread of antimicrobial resistance, and CRISPR technology to target and destroy antibiotic resistant bacteria. In 1977, Sanger discovered a method to sequence DNA. Since then, we have used sequencing to monitor the spread of antimicrobial resistance and develop better diagnostic tools. Then in 2020, two pioneers again revolutionised the field of gene sequencing and editing. Scientists can now use CRISPR technology, which is Clustered Regulatory Interspaced Short Palindromic Repeats, for sequencing and to develop even better diagnostic tools.

But also are looking to the future with CRISPR/Cas and how it could help revolutionise the treatment of infections with its ability to easily alter DNA sequences and modify gene function. CRISPR/Cas could be used to target drug resistant bacterial infections by selectively killing AMR bacteria.

Most new technologies have data capability. We live in a world of data. We collect data either directly from instruments that can store data locally or report to centralised hubs. We can also use electronic readers to read and report results from, for example, lateral flow assays, or even use phone apps to help us visually read results and report these. With COVID, tests are being reported as QR codes, so you can simply show the code at points of entry, and the person will see your results and when the test was taken.

But given all of the potential of new technologies and the data coming from various sources, now is the time to consider how to turn this into real time intelligence to improve programmes, public health monitoring, outbreak response, and patient management, particularly for AMR.

Home testing is increasing, and a concern is how to ensure quality testing and data capture and reporting. This table shows us again tests that meet FDA and WHO sensitivity and specificity criteria, and those that can be used at home, and even provide an app to help with testing. And again, these can be used with both symptomatic and asymptomatic individuals. This is a good time now to mention how to visualise all of this data being generated. COVID really brought dashboards front and centre as a public health tool.

All of us are used to visiting the Johns Hopkins website to see case counts and deaths by region and country, the geographic distribution of COVID-19 worldwide, including hotspots, and of trends of COVID-19 cases, deaths, and vaccinations. One can envision how a similar dashboard could be used to monitor progress against AMR and where hotspots are.