Persistent positivity and fluctuations of SARS-CoV-2 RNA in clinically-recovered COVID-19 patients

Cento, Valeria; Colagrossi, Luna; Nava, Alice; Lamberti, Anna; Senatore, Sabrina; Travi, Giovanna; Rossotti, Roberto; Vecchi, Marta; Casati, Ornella; Matarazzo, E.; Bielli, Alessandra; Casalicchio, G.; Antonello, Maria; Renica, Silvia; Costabile, Valentino; Scaglione, Francesco; Fumagalli, Roberto; Ughi, Nicola; Epis, Oscar Massimiliano; Puoti, Massimo; Vismara, Chiara; Faccini, Marino; Fanti, Diana; Alteri, Claudia; Perno, Carlo Federico

doi:10.1016/j.jinf.2020.06.024

Cited by 66 publications

(58 citation statements)

References 6 publications

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“…Cento et al retrospectively analyzed data of 2521 recovered COVID-19. Negative-to-positive RT-PCR fluctuations occurred in 264/2521 patients, while none of them has ever shown a recurring of COVID-19 symptoms, regardless of RT-PCR results [82].…”

Section: Discussionmentioning

confidence: 92%

Is recurrence possible in coronavirus disease 2019 (COVID-19)? Case series and systematic review of literature

Gidari

Nofri

Saccarelli

et al. 2020

Eur J Clin Microbiol Infect Dis

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Can a patient diagnosed with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) be infected again? This question is still unsolved. We tried to analyze local and literature cases with a positive respiratory swab after recovery. We collected data from symptomatic patients diagnosed with SARS-CoV-2 infection in the Italian Umbria Region that, after recovery, were again positive for SARS-CoV-2 in respiratory tract specimens. Samples were also assessed for infectivity in vitro. A systematic review of similar cases reported in the literature was performed. The study population was composed of 9 patients during a 4-month study period. Among the new positive samples, six were inoculated in Vero-E6 cells and showed no growth and negative molecular test in culture supernatants. All patients were positive for IgG against SARS-CoV-2 nucleoprotein and/or S protein. Conducting a review of the literature, 1350 similar cases have been found. The presumptive reactivation occurred in 34.5 days on average (standard deviation, SD, 18.7 days) after COVID-19 onset, when the 5.6% of patients presented fever and the 27.6% symptoms. The outcome was favorable in 96.7% of patients, while the 1.1% of them were still hospitalized at the time of data collection and the 2.1% died. Several hypotheses have been formulated to explain new positive respiratory samples after confirmed negativity. According to this study, the phenomenon seems to be due to the prolonged detection of SARS-CoV-2 RNA traces in respiratory samples of recovered patients. The failure of the virus to replicate in vitro suggests its inability to replicate in vivo.

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Section: Discussionmentioning

confidence: 92%

Is recurrence possible in coronavirus disease 2019 (COVID-19)? Case series and systematic review of literature

Gidari

Nofri

Saccarelli

et al. 2020

Eur J Clin Microbiol Infect Dis

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“…A plausible explanation for the negative detection is that the samples were collected during a down phase of viral replication, whereas detection during the rising phase may cause recurrent positivity. It has been argued that these observations of prolonged viral RNA positivity may only represent "dead viruses" in recurrently positive patients, since most previous reports only described the prevalence of RNA positivity 4,5 . Our data clearly showed that infectious viruses could also be isolated from sputum.…”

Section: Discussionmentioning

confidence: 97%

“…Typically, patients with COVID-19 recover from infection within two weeks, particularly those with mild cases 2,3 . However, several reports have shown the prolonged presence of viral nucleotides (nts) in the upper or lower respiratory tract, lung tissues, or intestinal tract (fecal matter) in recovered patients [4][5][6][7] . Likewise, an estimated range of 10-20% recurrent positivity for viral nt was also reported 7 .…”

Section: Introductionmentioning

confidence: 99%

“…Isolating infectious viruses from recurrent or persistent carriers has not been successful, raising the possibility that viral RNA positivity in such carriers only represents "dead viruses." Similarly, most documented prolonged carriers or recurrently positive patients appear to be asymptomatic or have mild cases, and their transmission risk is largely unclear 4,6 . However, a large amount of viral particles was found in a ready-for-Panel V1.0 (MGI, BGI-Shenzhen, China), following the manufacturer's instructions.…”

Section: Introductionmentioning

confidence: 99%

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Prolonged shedding of severe acute respiratory syndrome coronavirus 2 in patients with COVID-19

Zheng

Shen

et al. 2020

Emerging Microbes & Infections

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“…Exactly how these inactivation methods are applied in SRLs will relate directly to the sample type and the level of risk posed. Samples infected with cultured virus should be treated with significant caution, followed by SARS‐CoV‐2 positive human tissues known to generate propagative virus, and then those tissues not known to carry propagative virus (34, 61–70). Standard precautions apply to all human samples, with a biological safety assessment utilized to help guide the application of additional control measures relative to the local context (1) (Supporting Information Table S1).…”

Section: Resultsmentioning

confidence: 99%

Biosafety during a pandemic: shared resource laboratories rise to the challenge

Aspland

Douagi²,

Filby

et al. 2021

Cytometry Pt A

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Biosafety has always been an important aspect of daily work in any research institution, particularly for cytometry Shared Resources Laboratories (SRLs). SRLs are common-use spaces that facilitate the sharing of knowledge, expertise, and ideas. This sharing inescapably involves contact and interaction of all those within this working environment on a daily basis. The current pandemic caused by SARS-CoV-2 has prompted the re-evaluation of many policies governing the operations of SRLs. Here we identify and review the unique challenges SRLs face in maintaining biosafety standards, highlighting the potential risks associated with not only cytometry instrumentation and samples, but also the people working with them. We propose possible solutions to safety issues raised by the COVID-19 pandemic and provide tools for facilities to adapt to evolving guidelines and future challenges.

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Persistent positivity and fluctuations of SARS-CoV-2 RNA in clinically-recovered COVID-19 patients

Cited by 66 publications

References 6 publications

Is recurrence possible in coronavirus disease 2019 (COVID-19)? Case series and systematic review of literature

Is recurrence possible in coronavirus disease 2019 (COVID-19)? Case series and systematic review of literature

Prolonged shedding of severe acute respiratory syndrome coronavirus 2 in patients with COVID-19

Biosafety during a pandemic: shared resource laboratories rise to the challenge

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