Some patients who have recovered from COVID-19, with a negative molecular swab, at varying intervals of time, may again test positive on the swab, even without any symptoms suggestive of re-infection. The observation, resultingfrom the collaboration between physicians, researchers and professors of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Università Cattolica, campus of Rome, Maurizio Sanguinetti and Paola Cattani (Department of Laboratory and Infectivological Sciences), Brunella Posteraro (Department of Medical and Surgical Sciences) and Francesco Landi (Department of Aging, Neurological, Orthopaedic and Head-Neck Sciences) has recently been published as a research letterin JAMA Internal Medicine.

«At the moment it is not known whether these patients are contagious and therefore need to be quarantined again, since molecular testing is not the equivalent of a viral culture and, therefore, it is not possible to determine whether the sample taken from the patients’ nose and pharynx contains a vital and, consequently, transmissible virus», said Professor Maurizio Sanguinetti, Professor of Microbiology at Università Cattolica and Director of the Department of Laboratory and Infectivological Sciences at the Policlinico Universitario A. Gemelli IRCCS.

The detection of the so-called viral replicative RNA is proposed by the authors as an indicator of the presence of vital and potentially transmissible viruses, but further studies will be needed to establish whether these patients can actually transmit the virus.

The study was carried out on 176 recovered COVID-19 patients  who were admitted to the post-acute outpatient service of the A. Gemelli IRCCS University Hospital, coordinated by Professor Francesco Landi, from April to June The recovery was previously evaluated on the basis of the following criteria: absence of fever for 3 consecutive days, improvement in other symptoms, 2 negative molecular swabs for SARS CoV-2 RNA 24 hours apart. During the follow-up (approximately 50 days after the diagnosis of COVID-19), the nasal-oropharyngeal samples of these patients were tested for the presence of both total (genomic) and replicative (subgenomic) viral RNA.

«The presence of replicative RNAs in the samples was used as an indicator of ongoing viral replication. In patients who tested positive for total RNA, the samples obtained at the time of the diagnosis of COVID-19 (which had been stored at -112 F°) were again analysed for the presence of replicative RNA. All patients were also serologically tested for virus-specific IgG/IgA. Of the 176 recovered patients, 32 (nearly 1 in 5) were positive for total SARS CoV-2 RNA, albeit at varying levels. Only one of these, however, also tested positive for SARS CoV-2 replicative RNA. Samples obtained from patients at the time of the disease were reanalysed and, as expected, all tested positive for SARS CoV-2 replicative RNA», said Professor Sanguinetti.

All patients retesting positive (with one exception) and all the other patients testingnegative on the control swab had a positive serologic test at follow-up. The only patient who tested positive for both total and replicative RNA became positive 16 days after recovery (and 39 days after the initial diagnosis of COVID-19) was an elderly patient with hypertension, diabetes and cardiovascular disease, who had a symptomatology compatible with COVID-19 at follow-up.“All these data make us suspect that this is a re-infection or recurrence of infection for this patient while for the remaining 31 patients (all asymptomatic) who tested positive only for total RNA, it is more likely to be a removal of fragments of viral RNA, following resolution of the infection”said Professor Sanguinetti.

«This study confirms the usefulness of performing an accurate follow-up of recovered COVID-19 patients and reinforces the concept that reinfections in recovered COVID-19 patients are rare ‒ concluded Sanguinetti ‒although testing positive to the ‘conventional’ molecular test (which detects total SARS CoV-2 RNA). Therefore, research into SARS CoV-2 replicating RNA could help resolve the dilemma about the real infectivity of recovered COVID-19 patients who return positive for SARS CoV-2 RNA».