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Vol. 220. Núm. 8.
Páginas 524-526 (Noviembre 2020)
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Vol. 220. Núm. 8.
Páginas 524-526 (Noviembre 2020)
Correspondence
DOI: 10.1016/j.rceng.2020.06.005
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Recurrent positive SARS-CoV-2 RNA tests in recovered and discharged patients
Test ARN para SARS-CoV-2 positivos recurrentes en pacientes recuperados y dados de alta hospitalaria
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...
Z.S. Ulhaqa,
Autor para correspondencia
, G.V. Sorayab, F.A. Fauziahc
a Department of Biochemistry, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim Islamic State University of Malang, Batu, Indonesia
b Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
c Scaling Up Nutrition Secretariat, Ministry of National Development Planning, Indonesia
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Table 1. Characteristic of the included studies.
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Dear Director:

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 24h 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.

  • 2

    Studies that recorded a time of RNA-positive conversion since last negative/discharge.

Fourteen studies were included in this meta-analysis (Table 1)1–10 [Sup. Ref. 3–6]. The pooled prevalence of the RP SARS-CoV-2 RNA test among recovered patients was 32.9% (93/450 subjects, 95% CI 20.7–45.1%, Fig. 1)1,4,5,9,10 [Sup. Ref. 4,5], which was higher than previously reported [Supp. Ref. 7]. The shortest time to RNA-positive conversion since last negative/discharge was 1 day while the longest was 24 days (Table 1).

Table 1.

Characteristic of the included studies.

Study, Year  Country  Study type  No. of RP  Sample  Days of RNA-positive conversion since last negative  Days of RNA-positive conversion since discharge  Symptoms 
An et al., 2020  China  Observational  262  38  Nasopharyngeal swab/stool  –  ∼ 14  Asymptomatic 
Chen et al., 2020  China  Case report  Oropharyngeal swab  –  Asymptomatic 
Lan et al., 2020  China  Case report  Throat swab  –  5 – 13  Asymptomatic 
Ling et al., 2020  China  Observational  66  11  Oropharyngeal swab  ∼ 10 – 15  –  Asymptomatic 
Li et al., 2020  China  Observational  Respiratory swab  –  5 – 7 
Lo et al., 2020  Macau  Observational  10  Throat swab/stool  1 – 5  – 
Luo et al., 2020  China  Case report  Throat swab  24  22  Asymptomatic 
Qu et al., 2020  China  Case report  Sputum  Asymptomatic 
Xiao et al., 2020  China  Observational  70  15  Throat swab/Deep nasal cavity  –  – 
Xing et al., 2020 [a]  China  Case report (Pediatric)  Throat swab/stool  6 – 18  Asymptomatic 
Xing et al., 2020 [b]  China  Case report  Throat swab  2 – 6  1 – 5  Asymptomatic 
Xu et al., 2020  China  Observational (Pediatric)  10  Throat swab/stool  1 – 15  6 – 13  Non-specific and mild symptoms 
Yuan et al., 2020  China  Observational  25  14  Cloacal/nasal/oropharyngeal swab  7.32±3.859 [mean±SD]  5.32±4.13 [mean±SD]  Asymptomatic 
Zhang et al., 2020  China  Case report (Pediatric)  Stool  –  10 – 13 

RP, re-detectable positive; SD, standard deviation.

Figure 1.

Forest plot of the seven studies estimating the pooled prevalence of re-detectable positive SARS-CoV-2 RNA test among recovered patients.

(0,12MB).

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.

Conflicts of interest

The authors declare that they have no conflict of interest.

Appendix A
Supplementary data

The following is Supplementary data to this article:

References
[1]
J. An, X. Liao, T. Xiao, S. Qian, J. Yuan, H. Ye, et al.
Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test.
[2]
D. Chen, W. Xu, Z. Lei, Z. Huang, J. Liu, Z. Gao, et al.
Recurrence of positive SARS-CoV-2 RNA in COVID-19: A case report.
Int J Infect Dis, 93 (2020), pp. 297-299
[3]
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Positive RT-PCR test results in patients recovered from COVID-19.
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Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients.
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[7]
Y. Xing[a], W. Ni, Q. Wu, W. Li, G. Li, J. Tong, et al.
Prolonged presence of SARS-CoV-2 in feces of pediatric patients during the convalescent phase.
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Y. Xing[b], P. Mo, Y. Xiao, O. Zhao, Y. Zhang, F. Wang.
Post-discharge surveillance and positive virus detection in two medical staff recovered from coronavirus disease 2019 (COVID-19), China, January to February 2020.
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Y. Xu, X. Li, B. Zhu, Y. Xu, X. Li, B. Zhu, et al.
Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding.
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Please cite this article as: Ulhaq Z.S., Soraya G.V., Fauziah F.A. Test ARN para SARS-CoV-2 positivos recurrentes en pacientes recuperados y dados de alta hospitalaria. Rev Clin Esp. 2020;220:524–526.

Copyright © 2020. Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)
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