Performance characteristics and operational feasibility assessment of a CRISPR based tata MD CHECK diagnostic test for SARS-CoV-2 (COVID-19)

BACKGROUND: Tata MD CHECK SARS-CoV-2 kit 1.0, a CRISPR based reverse transcription PCR (TMC-CRISPR) test was approved by Indian Council of Medical Research (ICMR) for COVID-19 diagnosis in India. To determine the potential for rapid roll-out of this test, we conducted performance characteristic and an operational feasibility assessment (OFA) at a tertiary care setting. INTERVENTION: The study was conducted at an ICMR approved COVID-19 RT-PCR laboratory of King Edward Memorial (KEM) hospital, Mumbai, India. The TMC-CRISPR test was evaluated against the gold-standard RT-PCR test using the same RNA sample extracted from fresh and frozen clinical specimens collected from COVID-19 suspects for routine diagnosis. TMC-CRISPR results were determined manually and using the Tata MD CHECK application. An independent agency conducted interviews of relevant laboratory staff and supervisors for OFA. RESULTS: Overall, 2,332 (fresh: 2,121, frozen: 211) clinical specimens were analysed of which, 140 (6%) were detected positive for COVID-19 by TMC-CRISPR compared to 261 (11%) by RT-PCR. Overall sensitivity and specificity of CRISPR was 44% (95% CI: 38.1%-50.1%) and 99% (95% CI: 98.2%-99.1%) respectively when compared to RT-PCR. Discordance between TMC-CRISPR and RT-PCR results increased with increasing Ct values and corresponding decreasing viral load (range: <20% to >85%). In the OFA, all participants indicated no additional requirements of training to set up RT PCR. However, extra post-PCR steps such as setting up the CRISPR reaction and handling of detection strips were time consuming and required special training. No significant difference was observed between manual and mobile app-based readings. However, issues such as erroneous results, difficulty in interpretation of faint bands, internet connectivity, data safety and security were highlighted as challenges with the app-based readings. CONCLUSION: The evaluated version-Tata MD CHECK SARS-CoV-2 kit 1.0 of TMC-CRISPR test cannot be considered as an alternative to the RT-PCR. There is a definite scope for improvement in this assay.