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Colorized scanning electron micrograph of an apoptotic cell (red) infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Credit: National Institute of Allergy and Infectious Diseases, NIH.

Testing for severe acute respiratory coronavirus 2 (SARS-CoV-2) in human tears can help spot infections that go undetected with current nose-pharyngeal molecular swabs, according to a study in JAMA Ophthalmology. "Double checking the result of nasopharyngeal molecular tests with a second eyes swab could reduce the rate of false-negative results," says Claudio Azzolini, professor in Ophthalmology at Università dell’Insubria in Varese, who lead the study. He and his co-authors suspect that infected tears could be another transmission route for COVID-19, a hypothesis that has been much debated, but not fully proven.

Between April and May 2020, the researchers collected tears’ samples from both eyes of 108 patients, 91 of which had been diagnosed with COVID-19 and hospitalized at three Intensive Care Units (ICUs) in Northern Lombardy, the epicentre of the first European outbreak. The other 17 were healthy volunteers enrolled as the control group.

Overall, the virus was detected on the ocular surface in 52 out of 91 patients. The trial's core results1 refer to a subgroup of 41 COVID-19 patients whom the researchers managed to screen with both nasopharyngeal and conjunctival swabs less than 48 hours apart. This way, there were no significant changes in the viral load from one test to the others, a factor that could otherwise bias the results. Out of those 41 patients, 17 were found negative for the nasopharyngeal swab despite their COVID-19 diagnosis. However, when researchers screened both eyes with a second swab, 10 of them turned out positive.

“This suggests that an extra molecular test on the eyes of those who were found negative to the nasopharyngeal swab can reverse the initial result,” Azzolini adds. As for the 24 patients with a positive nasal swab, 15 of them (63%) also got a positive result for the eye test. In the control group, all tests were negative.

The authors believe the most likely explanation for the virus to show up in the eyes is that SARS-CoV-2 could ride on atmospheric particulate matter and remain in the atmosphere for hours or days, especially in a non-windy and polluted area, like the Lombardy’s Po Valley. Once infected by particulates, tears would reach the throat, potentially infecting both the upper and lower respiratory systems.

The possible role of tears in the transmission of the coronavirus is still debated, as is the actual efficiency of ocular swabs. But Azzolini thinks some previous studies may have been biased by varying skill levels among the personnel performing swabs across the conjunctiva, as well as by the diagnostic experience of the labs.

“In our study, we had the same ophthalmologist perform the eyes swabs with a dedicated procedure in all patients and volunteers, in order to avoid any distortion due to differently skilled hands, rather than to the test itself,” he says.