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The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient - a case study
Chiara Sepulcri Jr.; Chiara Dentone Sr.; Malgorzata Mikulska Sr.; Bianca Bruzzone Sr.; Alessia Lai Sr.; Daniela Fenoglio Sr.; Federica Bozzano Sr.; Annalisa Bergna Jr.; Alessia Parodi Sr.; Tiziana Altosole Jr.; Emanuele Delfino Sr.; Giulia Bartalucci Sr.; Andrea Orsi Sr.; Antonio Di Biagio Sr.; Gianguglielmo Zehender Sr.; Filippo Ballerini Sr.; Stefano Bonora Sr.; Raffaele De Palma Sr.; Guido Silvestri Sr.; Andrea De Maria Sr.; Matteo Bassetti Sr..
Affiliation
  • Chiara Sepulcri Jr.; Infectious Diseases Unit, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
  • Chiara Dentone Sr.; Infectious Diseases Unit, Ospedale Policlinico San Martino, IRCCS for Oncology and Neurosciences, Genoa, Italy
  • Malgorzata Mikulska Sr.; Infectious Diseases Unit, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
  • Bianca Bruzzone Sr.; Hygiene Unit, Ospedale Policlinico San Martino, IRCCS for Oncology and Neurosciences Genoa, Italy
  • Alessia Lai Sr.; Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan Italy
  • Daniela Fenoglio Sr.; Center of Excellence for Biomedical Research, Cytofluorimetry Unit, University of Genoa ; Department of Internal Medicine (DiMI), University of Genoa, Genoa, It
  • Federica Bozzano Sr.; Infectious Diseases Unit, Ospedale Policlinico San Martino, IRCCS for Oncology and Neurosciences, Genoa, Italy
  • Annalisa Bergna Jr.; Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan Italy
  • Alessia Parodi Sr.; Biotherapy Unit, Ospedale Policlinico San Martino, IRCCS for Oncology and Neurosciences, Genoa, Italy
  • Tiziana Altosole Jr.; Center of Excellence for Biomedical Research, Cytofluorimetry Unit, University of Genoa
  • Emanuele Delfino Sr.; Infectious Diseases Unit, Ospedale Policlinico San Martino, IRCCS for Oncology and Neurosciences, Genoa, Italy
  • Giulia Bartalucci Sr.; Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
  • Andrea Orsi Sr.; Hygiene Unit, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
  • Antonio Di Biagio Sr.; Infectious Diseases Unit, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
  • Gianguglielmo Zehender Sr.; Hygiene Unit, Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan Italy
  • Filippo Ballerini Sr.; Hematology Unit, Ospedale Policlinico San Martino, IRCCS for Oncology and Neurosciences Genoa, Italy
  • Stefano Bonora Sr.; Infectious Diseases Unit, Ospedale Amedeo di Savoia, University of Turin, Turin, Italy
  • Raffaele De Palma Sr.; Immunology Unit, Ospedale Policlinico San Martino, IRCCS for Oncology and Neurosciences, Genoa, Italy
  • Guido Silvestri Sr.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, USA; Division of Microbiology and Immunology Yerkes National Prim
  • Andrea De Maria Sr.; Infectious Diseases Unit, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
  • Matteo Bassetti Sr.; Infectious Diseases Unit, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
Preprint in English | medRxiv | ID: ppmedrxiv-21249554
ABSTRACT
BackgroundImmunocompromised patients show prolonged shedding of SARS-CoV-2 in nasopharyngeal swabs. We report a case of a prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of COVID-19 in a lymphoma patient. MethodsNasopharyngeal swabs and blood samples were tested for SARS-CoV-2 by Real time-PCR (RT-PCR). On five positive nasopharyngeal swabs, we performed viral culture and next generation sequencing. We analysed the patients adaptive and innate immunity to characterize T and NK cell subsets. FindingsSARS-CoV-2 RT-PCR on nasopharyngeal swabs samples remained positive with cycle threshold mean values of 22 {+/-} 1{middle dot}3 for over 8 months. All five performed viral cultures were positive and genomic analysis confirmed a persistent infection with the same strain. Viremia resulted positive in three out of four COVID-19 clinical relapses and cleared each time after remdesivir treatment. T and NK cells dynamic was different in aviremic and viremic samples and no SARS-CoV-2 specific antibodies were detected throughout the disease course. InterpretationIn our patient, SARS-CoV-2 persisted with proven infectivity for over eight months. Viremia was associated with COVID-19 relapses and remdesivir treatment was effective in viremia clearance and symptoms remission, although it was unable to clear the virus from the upper respiratory airways. During the viremic phase, we observed a low frequency of terminal effector CD8+ T lymphocytes in peripheral blood that are probably recruited in inflammatory tissue for viral eradication. In addition we found a high level of NK cells repertoire perturbation with a relevant involvement during SARS-CoV-2 viremia. FundingNone.
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Full text: Available Collection: Preprints Database: medRxiv Type of study: Case report / Prognostic study Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: medRxiv Type of study: Case report / Prognostic study Language: English Year: 2021 Document type: Preprint
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