Anomalous COVID-19 tests hinder researchers

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Science  15 Jan 2021:
Vol. 371, Issue 6526, pp. 244-245
DOI: 10.1126/science.abf8873

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Some positive COVID-19 test results reflect researchers' exposure to non-infectious nucleic acids rather than a true infection.


Universities conduct a large proportion of the community surveillance testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1). At the same time, they have shifted focus to SARS-CoV-2 research to address critical needs during this pandemic. There are now multiple reports of asymptomatic researchers who worked with or near non-infectious SARS-CoV-2 nucleic acids and subsequently tested positive during SARS-CoV-2 surveillance screening (2, 3). Such positive test results and the resulting isolation and quarantine are deleterious to the health of researchers, their research programs, and their close contacts. Universities and labs should take steps to identify and prevent misleading test results among their researchers.

Because health departments cannot distinguish positive test results reflecting exposure to non-infectious nucleic acids from those revealing true active SARS-CoV-2 infections, affected U.S. researchers are removed from the testing pool for 90 days, a period during which true infections could be missed (4). Additional false positives could result when monitoring of wastewater for viral outbreaks detects DNA products that are washed down the drain as non-biohazardous waste (5). As polymerase chain reaction tests, other DNA amplification tests (6, 7), and the recently approved at-home nucleic acid tests (8) become more widespread, these cases will likely become more frequent among researchers.

To mitigate harm from misleading results, we recommend the implementation of extra safety controls (2) in addition to standard practices for handling nucleic acids (9). Genetic loci should be chosen with care to not interfere with any available tests. Incorporation of deoxyuridine triphosphate, codon optimization, and DNA watermarks can prevent detection of a laboratory-generated nucleic acid and differentiate it from circulating pathogens (10, 11). DNA products should be treated with bleach or other DNA-damaging agents before disposal. The best policies and practices for preventing laboratory contamination should take place before initiating research: Once a space is contaminated with DNA, it is extremely difficult to decontaminate (2). These policies should accommodate the specific needs of the research and the institutions and not place undue burden on the essential work of studying these pathogens.

For individuals who are asymptomatic, have no history of SARS-CoV-2 exposure, and are affected by anomalous surveillance test results, we propose verification with orthogonal follow-up testing. At an institutional level, administrators, environmental health and safety personnel, and departments of public health should collaborate to determine who is at risk for anomalous tests and coordinate immediate follow-up testing. Alternate providers using orthogonal tests should be established before surveillance testing and/or research initiation.

Community-wide COVID-19 surveillance testing directly improves human health (12). Given the extensive development in testing infrastructure amassed during this short period, viral testing will likely extend to other pathogens, endemic or emergent. Sensible policies governing the stewardship of nucleic acids will help protect this vital asset.

References and Notes

Competing Interests

L.R.R.-M., A.J.M., G.T.F., R.F., O.D., D.T.-O., G.M.C., and J.M.T. are co-inventors of MAP-Dx, a COVID diagnostic platform. J.J.C. is a co-founder and director of Sherlock Biosciences. G.M.C.'s tech transfer, advisory roles, and funding sources can be found at http://v.ht/PHNc.

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