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

  • Gidari, Anna1
  • Nofri, Marco1
  • Saccarelli, Luca1
  • Bastianelli, Sabrina1
  • Sabbatini, Samuele1
  • Bozza, Silvia1
  • Camilloni, Barbara1
  • Fusco-Moffa, Igino2
  • Monari, Claudia1
  • De Robertis, Edoardo1
  • Mencacci, Antonella1
  • Francisci, Daniela1
  • 1 University of Perugia,
  • 2 Department of Prevention, Local Health Unit Umbria 1, Travel Medicine Unit, Perugia, Italy
Published Article
European Journal of Clinical Microbiology & Infectious Diseases
Publication Date
Oct 10, 2020
DOI: 10.1007/s10096-020-04057-6
PMID: 33037944
PMCID: PMC7547550
PubMed Central


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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