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Early on in the pandemic, while PCR was getting most of the attention, reverse transcription loop-mediated isothermal amplification (RT-LAMP), an isothermal nucleic acid amplification technique that allows for RNA amplification, was also quietly being discussed, and it has since gained more attention. In July 2020, the University of Oxford was in the process of getting a rapid, affordable, clinically-validated RT-LAMP test approved for the European market. Oxford also notes that "[a]n advantage of using LAMP technology is that it uses different reagents to most laboratory-based PCR tests." Thi et al. have tested a two-color RT-LAMP assay with an N gene primer set and diagnostic validation using LAMP-sequencing, concluding that the pairing of the two "could offer scalable testing that would be difficult to achieve with conventional qRT-PCR based tests." And California-based Color Genomics set up their own proprietary RT-LAMP system in the summer of 2020, capable of handling up to 10,000 tests per day.

In most cases, LAMP-based testing is much simpler than PCR, lacking the requirement of specialized instruments. Despite LAMP generally being thought of as less sensitive than PCR, the explosion of research into RT-LAMP methods for testing for the presence of SARS-CoV-2 continues to indicate that "under optimized conditions," RT-LAMP methods may actually be able to rival the sensitivity and specificity of many RT-PCR COVID-19 tests. Esbin et al. add:

These methods allow for faster amplification, less specialized equipment, and easy readout. LAMP methods also benefit from the ability to multiplex targets in a single reaction and can be combined with other isothermal methods, like [recombinase polymerase amplification] in the RAMP technique, to increase test accuracy even more. These techniques may be particularly useful for rapid, point-of-care diagnoses or for remote clinical testing without the need for laboratory equipment.

CRISPR methods are also being used in conjunction with RT-LAMP. RT-LAMP creates complementary double-stranded DNA (cDNA) from specimen RNA and then copies (amplifies) it. Then CRISPR methods are used to detect a predefined coronavirus sequence (from a cleaved molecular marker) in the resulting amplified specimen. Though as of September 2021 approved assays using CRISPR-based detection of SARS-CoV-2 are limited to a handful of companies, the technology has some promise as an alternative testing method. CRISPR has the additional advantage of being readily coupled with lateral flow assay technology to be deployed in the point-of-care (POC) setting, though it's worth noting the currently EUAed RT-LAMP-based CRISPR kits are only approved for high-complexity CLIA labs. (The current molecular diagnostic test kits running CRISPR technology are Sherlock BioSciences' Sherlock CRISPR SARS-CoV-2 Kit and Mammoth Biosciences' SARS-CoV-2 DETECTR Reagent Kit, both high-complexity.)