key: cord-0051709-itj6v1jl
authors: Syambani Ulhaq, Z.; Vita Soraya, G.; Arkham Fauziah, F.
title: Recurrent positive SARS-CoV-2 RNA tests in recovered and discharged patients()
date: 2020-10-17
journal: Rev Clin Esp (Barc)
DOI: 10.1016/j.rceng.2020.06.005
sha: f695df4ce184fac4c3fe1ea4db0cc72e26080f68
doc_id: 51709
cord_uid: itj6v1jl

nan

The ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic remains a global concern that requires a comprehensive approach to reduce rapid transmission, starting from case detection, inpatient care, as well as post-hospital management. Guidelines recommend [Supp. Ref. 1, 2] two consecutive negative polymerase chain reaction (PCR) tests from respiratory specimens at a 24 h interval as hospital discharge criteria. However, concerns have risen over recent reports of increasing re-detectable positive (RP) SARS-CoV-2 RNA tests observed among recovered and discharged patients 1-2 .

These reports raise questions about whether recovered patients are at risk of relapse/reinfection, and whether they are capable of infecting others. However, no clear evidence is currently available on this matter. Aiming to summarize the current evidence, a meta-analysis was performed to estimate the prevalence of RP SARS-CoV-2 RNA tests among recovered patients, in addition to the days of RNA-positive conversion since last negative/discharge. A comprehensive literature search was conducted through an electronic database dated up to May 2020, with search terms such as "recovered/discharged patients", "coronavirus 2019/COVID-19", "SARS-CoV-2", "positive PCR" used in combination without language restriction. The inclusion criteria were:

1. Observational studies or case reports that described some RP SARS-CoV-2 RNA tests among recovered/discharged patients.

Fourteen studies were included in this meta-analysis (Table 1 Table 1) (Table 1 Table 1) .

A plausible explanation for the RP cases is prolonged viral RNA shedding, shown to be detectable in nasopharyngeal swab/stool specimens up to one month after symptom onset [Supp. Ref. 8, 9] . Additionally, as demonstrated by Hu et al., viral fragments were mainly detected in the stool of recovered patients, emphasizing that these fragments are unlikely to be a source of infection [Supp. Ref. 10] . However, it is important to note that the current evidence has shown RNA-positive conversion in patients that have previously presented with two consecutive negative PCR tests. This fact implies the strong possibility of relapse or reinfection. And although one animal study has demonstrated a failure of reinfection after SARS-CoV-2 re-challenge in a primate model [Supp. Ref. 11] , more studies are required to confirm this result.

In the absence of reinfection, another plausible explanation of the RP occurrence is the high false-negative rate of SARS-CoV-2 RT-PCR [Supp. Ref. 12] . False negativity can be due to low viral loads under the detection threshold, poor specimen quality, inappropriate sampling and handling techniques, and other technical issues [Supp. Ref. 12, 13] . In addition to careful assessment of these issues, other options such as alternative molecular detection techniques and sampling of both upper and lower respiratory tracts may be considered to optimize test sensitivity.

Hence, these results emphasize the importance of accurate diagnostics and appropriate post-hospitalization management during the pandemic, since the infectious capacity of RP cases remain unknown. Based on the evidence on time to conversion, 2 -3 weeks home quarantine post-discharge is strongly suggested, alongside personal protective measures (rigorous hand hygiene, cough etiquette, and face masks) to reduce the risk of virus transmission. Intensive monitoring and surveillance should also continue post-discharge, through phone consultation or home visits.

The authors declare that they have no conflict of interest. 

General Office of National Health Commission, General Office of National Administration of Traditional Chinese Medicine. Diagnostic and treatment protocol for novel coronavirus pneumonia (Trial version 5, revised form)

Discharge criteria for confirmed COVID-19 cases -When is it safe to discharge COVID-19 cases from the hospital or end home isolation? 2020

Viral RNA in Feces of Three Children during Recovery Period of COVID-19

False-negative of RT-PCR and prolonged nucleic acid conversion in COVID-19: Rather than recurrence

Follow-up testing of viral nucleic acid in discharged patients with moderate type of

Positive SARS-Cov-2 test in a woman with COVID-19 at 22 days after hospital discharge: A case report

Failed detection of the full-length genome of SARS-CoV-2 by ultra-deep sequencing from the recovered and discharged patients retested viral PCR positive. medRxiv

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features

Failed detection of the full-length genome of SARS-CoV-2 by ultra-deep sequencing from the recovered and discharged patients retested viral PCR positive

Reinfection could not occur in SARS-CoV-2 infected rhesus macaques

Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19

Difficulties in False Negative Diagnosis of Coronavirus Disease

J o u r n a l P r e -p r o o f