Discharge mechanism in focus after false Covid-19 negatives

Scientists have called for urgently revisiting the discharge protocol for Covid-19 patients after recent international studies showed people can test positive for the virus even after two consecutive negative results.

The research comes at a time when South Korean authorities reported 91 patients who were previously cleared of the coronavirus had tested positive again, with experts saying the scare of reinfection was yet unproven, and that a more plausible reason was the unreliability of two RT-PCR (Reverse transcriptase polymerase chain reaction) tests to conclusively prove a patient cured.

"RT-PCR testing is most useful when it is positive," said Dr Priya Sampathkumar, an infectious diseases specialist at Mayo Clinic in Minnesota, US. "It is less useful in ruling out Covid-19. A negative test often does not mean the person does not have the disease, and test results need to be considered in the context of patient characteristics and exposure."

Their hospital discharge protocol was four-pronged: Normal body temperature for more than three consecutive days, significant reduction of respiratory symptoms, improvement in chest CT, and two consecutively negative results of RT-PCR testing separated by a 24-hour interval. This is the common global standard, for patient discharge. But within an average of roughly 5-9 days from their discharge, 25 patients returned positive tests.

The first study, by Chinese medical experts in the Clinical Infectious Diseases journal, found that 14.5% of 172 patients discharged from the Shenzhen Third People's Hospital between Jan 23 and Feb 21 tested positive again, Hindustan Times reported.

"According to our study, it is probably that two negative RT-PCR tests 24 hours apart may not be sufficient for viral clearance evaluation. Repeated viral RT-PCR testing separated by prolonged duration like 48 hours is essential…we suggested that some immunological parameters such as D-dimer and absolute lymphocyte count, and even antibody test should be combined with RT-PCR negative test," the study added.

A second study, by doctors at the Tongji hospital in Wuhan, found that 15 out of 70 patients between Jan 21 and Feb 12 with confirmed Sars-CoV-2 infection tested positive after two consecutive negative results.

But the doctors cautioned that this was likely not a case of recurrence, but one of false negative test and prolonged viral clearance period, which can throw the RT-PCR test off. "Traces of virus detected by RT-PCR were not necessarily correlated with the ability of transmission. However, longer observation period should be considered for certain group of COVID-19 patients," the doctors concluded.

But why is the RT-PCR test, which relies on identifying the virus's genetic material, unreliable when it comes to discharge? A third study, by Chinese doctors in the Journal of Medical Virology, offers some clues.

In this study, of 610 hospitalised patients from Wuhan between February 2 and 17, the scientists reported a "potentially high false negative rate" of the RT-PCR tests. The doctors conducted six tests on the patients, and found that in a number of cases, tests of a particular patient, turned from negative to positive and again negative – indicating the high fluctuating nature of the tests. Eighteen patients tested positive after two consecutive negative tests. Only after five rounds of tests did all patients consistently test negative.

"To reduce the number of new cases, strict adherence to discharge criteria is needed. In addition, it is recommended that patients should be isolated for several days after discharge to reduce the risk of transmission," the study concluded.