To contain COVID-19 and re-open the economy, the U.S. should be performing 500,000 tests per day. We are nowhere near that number. Widespread implementation of CRISPR-based testing would address deficits in the current testing landscape. The most common method of testing for COVID-19—reverse transcription-polymerase chain reaction (RT-PCR)—costs $100 per test, takes four-six hours to run, involves long wait times for results, and requires bulky laboratory instruments. An innovative method has been developed that may revolutionize the current state of COVID-19 testing. Researchers at UC San Francisco have recently developed a rapid, inexpensive, and easy-to-implement CRISPR-Cas12-based test for COVID-19. In contrast to RT-PCR, CRISPR-based testing would cost less than $5 per test, takes 30-40 minutes to run, and can be done with commonly accessible laboratory materials. CRISPR technology is most commonly used as a gene-editing tool with the ability to detect specific genes. Now, CRISPR is being developed as a diagnostic tool to detect COVID-19. After collecting nasal swab samples, CRISPR can be used to specifically target unique genes of the virus that causes COVID-19. The CRISPR-Cas12 protein acts like a pair of scissors and cuts the viral DNA, generating a fluorescent signal that can be qualitatively visualized to determine COVID-19 infection. Beyond the laboratory, the future development of a portable CRISPR-based test could enable testing to be done at home. However, transitioning to point-of-care testing would lead to bioethical issues concerning test sensitivity, result interpretation, and privacy. CRISPR-based testing is slightly less sensitive than conventional RT-PCR testing. In the clinical study, about 5 percent of COVID-19 positive patients received a false negative result. On a larger scale, this might induce feelings of uncertainty or false security for individuals testing themselves at home. Such feelings would be amplified by the lack of a medical professional’s presence to interpret the results. Furthermore, in collecting at-home test results, how would public health departments and governmental institutions maintain patient privacy? To mitigate bioethical issues stemming from CRISPR-based testing at home, we propose the development of a companion diagnostic app. After registering the serial number on the test package, the app would “read” and confirm the qualitative CRISPR-based test results through a standardized image processing protocol. With options and visual aids presented in different languages, the app would be easily accessible to users with language barriers or a lack of medical literacy. To address current deficits in wait times for test results and interpretation, the app would confirm results and promptly connect users with licensed medical professionals for remote clinical counseling. Such counseling would contextualize the results and lessen the negative ramifications of ~5 percent false-negative test results. For example, if a user with symptoms or known COVID-19 exposure were to test negative, a clinical counselor through the app might recommend that the user repeat the test or undergo RT-PCR testing. Individuals testing positive would be provided with a personalized, regulated, and step-by-step process to follow, based on symptom severity. There would be clear terms and conditions agreement discussing the user’s privacy and protection for HIPAA-compliant remote clinical counseling. In order for users to receive test results, the app would require validation of identity by submitting government-issued photo identification. By requiring an electronic signature, this authentication process would promote the individual’s autonomy. To protect user privacy, anonymous CRISPR-based test results would be recorded in an encrypted central database only accessible by the government and public health entities. Users could opt-in to share their anonymous positive results with contact tracing initiatives to prevent further spread of COVID-19. Furthermore, users could opt-in to transmit their test results to their own primary care physician, pharmacy, or hospital for further clinical support. The CRISPR-based COVID-19 test and companion diagnostic app would further change the existing landscape of testing by facilitating repeat testing. For example, healthcare workers, who are at higher risk for exposure to the virus, could find comfort in testing at home to continuously ensure that they and their family members are not infected. For such individuals testing frequently, the app would store their medical history and previous results, allowing for seamless follow-ups and further counseling. In the future, researchers hope to develop CRISPR-based tests with improved sensitivity that can be processed at home. Despite being less accurate than conventional testing, the ongoing need for widespread testing justifies the implementation of CRISPR-based biotechnology in grappling with the COVID-19 pandemic. By dramatically increasing testing, within an ethical framework, we can begin safely reopening the country and rebuilding our economy and society. Ilaria Simeone and Raisa Alam are undergraduate premedical students. John D. Loike is a bioethicist. Source
