Artificial Intelligence-Assisted Loop Mediated Isothermal Amplification (ai-LAMP) for Rapid and Reliable Detection of SARS-CoV-2

Abstract

<jats:p>Until vaccines and effective therapeutics become available, the practical way to transit safely out of the current lockdown may include the implementation of an effective testing, tracing and tracking system. However, this requires a reliable and clinically validated diagnostic platform for the sensitive and specific identification of SARS-CoV-2. Here, we report on the development of a de novo, high-resolution and comparative genomics guided reverse-transcribed loop-mediated isothermal amplification (LAMP) assay. To further enhance the assay performance and to remove any subjectivity associated with operator interpretation of result, we engineered a novel hand-held smart diagnostic device. The robust diagnostic device was further furnished with automated image acquisition and processing algorithms, and the collated data was processed through artificial intelligence (AI) pipelines to further reduce the assay run time and the subjectivity of the colorimetric LAMP detection. This advanced AI algorithm-implemented LAMP (ai-LAMP) assay, targeting the RNA-dependent RNA polymerase gene, showed high analytical sensitivity and specificity for SARS-CoV-2. A total of ~200 coronavirus disease (CoVID-19)-suspected patient samples were tested using the platform and it was shown to be reliable, highly specific and significantly more sensitive than the current gold standard qRT-PCR. The system could provide an efficient and cost-effective platform to detect SARS-CoV-2 in resource-limited laboratories.</jats:p>

Nucleic acid amplification tests on respiratory samples for the diagnosis of coronavirus infections: a systematic review and meta-analysis

“…Tests targeting more than one gene had better sensitivity than tests targeting a single gene ( Supplementary Figure 4 ). Three studies showed a specificity >90% 41 , 47 , 51 and no covariate explained the heterogeneity. Preprint publication (13 studies) was not associated with significantly different results than peer-reviewed, published, studies (16 studies).…”

“…Three studies showed a specificity >90% 41,47,51 and no covariate explained the heterogeneity. Preprint publication (13 studies) was not associated with significantly different results than peer-reviewed, published, studies (16 studies).…”

“… 43 Altogether the 51 studies analyzed 18,923 persons, of them 10,181 persons (22 studies) before COVID-19 and 8,742 persons for SARS-CoV-2 (29 studies). 7 , 9 , 13 , 14 , 17 , 18 , 19 , 22 , 23 , 25 , 26 , 27 , 34 , 35 , 36 , 38 , 39 , 41 , 43 , 45 , 46 , 47 , 50 , 51 , 53 , 54 , 55 , 56 The studies evaluated mostly patients with non-specific ILI or suspected COVID-19, the latter including both upper ARTI and pneumonia. Five studies included only children <2 years 16 , 21 , 31 , 32 , 48 , 25 studies included a mixed age range and 21 did not address patients' age.…”

“…All the differences in sensitivity did not affect the typically excellent specificity shown in these studies (pooled specificity 98.1%, 95% 95.9-99.2%). Two of the three studies with <90% specificity concluded that the new tests (Droplet Digital PCR 51 and Artificial Intelligence-Assisted Loop Mediated Isothermal Amplification 47 ) were more sensitive than the reference standard commercial PCR, resulting in the low negative agreement rate.…”