AUTHOR=Capoluongo Ettore , Nardelli Carmela , Esposito Maria Valeria , Buonomo Antonio Riccardo , Gelzo Monica , Pinchera Biagio , Zappulo Emanuela , Viceconte Giulio , Portella Giuseppe , Setaro Mario , Gentile Ivan , Castaldo Giuseppe TITLE=Case Report: Discovery a Novel SARS-CoV-2 Variant in a Six-Months Long-Term Swab Positive Female Suffering From Non-Hodgkin Lymphoma JOURNAL=Frontiers in Oncology VOLUME=Volume 11 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.705948 DOI=10.3389/fonc.2021.705948 ISSN=2234-943X ABSTRACT=Background: We report the case of a woman with non-Hodgkin lymphoma who remained positive on the molecular assay for SARS-CoV-2 for six months: she has never experienced a severe form of COVID-19 although in absence of seroconversion. Methods: The whole SARS-CoV-2 genome analysis was performed by the CleanPlex SARS-CoV-2 Research and Surveillance NGS Panel (PARAGON GENOMICS, Hayward, USA). Results: we found twenty-two mutations in SARS-CoV-2 genome and a novel deleterious ORF3a frameshift c.766_769del corresponding to a unique and novel lineage. The region affected by this frameshift variant is reported as being important in determining SARS-CoV-2 immunogenicity. Patient’s immunophenotype showed the absence of B lymphocytes and significantly reduced T-cell count. Only after the treatment with hyperimmune plasma she finally became negative on the swab. Conclusions: Our findings could be helpful in the management of patients with immunodeficiency, particularly when novel variants, potentially altering the virus immune-response, are present.