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Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis

Anne-Gaëlle Goubet 1, 2, 3 Agathe Dubuisson 1, 3 Arthur Geraud 3 François-Xavier Danlos 3, 1 Safae Terrisse 3, 1 Carolina Alves Costa Silva 3, 1 Damien Drubay 3, 2, 4 Lea Touri 3 Marion Picard 3, 1, 5 Marine Mazzenga 3, 1 Aymeric Silvin 3, 1 Garett Dunsmore 3, 1 Yacine Haddad 3, 1 Eugenie Pizzato 3, 1 Pierre Ly 3, 1 Caroline Flament 3, 1 Cléa Melenotte 3, 1 Eric Solary 2, 3 Michaela Fontenay 6 Gabriel Garcia 3 Corinne Balleyguier 3 Nathalie Lassau 2, 3, 7 Markus Maeurer 8 Claudia Grajeda-Iglesias 3, 1, 9 Nitharsshini Nirmalathasan 3, 9 Fanny Aprahamian 3, 9 Sylvère Durand 3, 9 Oliver Kepp 3, 9 Gladys Ferrere 3, 1 Cassandra Thelemaque 3, 1 Imran Lahmar 3, 1 Jean-Eudes Fahrner 3, 1 Lydia Meziani 3, 10 Abdelhakim Ahmed-Belkacem 11 Nadia Saïdani 12 Bernard La Scola 13, 14 Didier Raoult 13, 14 Stéphanie Gentile 15 Sébastien Cortaredona 16, 14 Giuseppe Ippolito 17 Benjamin Lelouvier 18 Alain Roulet 18 Fabrice Andre 2, 3, 19 Fabrice Barlesi 3, 20 Jean-Charles Soria 2, 3 Caroline Pradon 3 Emmanuelle Gallois 3 Fanny Pommeret 3 Emeline Colomba 3 Florent Ginhoux 21, 22, 23 Suzanne Kazandjian 24 Arielle Elkrief 24, 25 Bertrand Routy 25 Makoto Miyara 26 Guy Gorochov 26 Eric Deutsch 2, 3, 10 Laurence Albiges 2, 3 Annabelle Stoclin 3 Bertrand Gachot 3 Anne Florin 3 Mansouria Merad 3 Florian Scotte 3 Souad Assaad 27, 28, 29 Guido Kroemer 3, 9, 30, 31, 32, 33 Jean-Yves Blay 27, 28, 29 Aurélien Marabelle 3, 1 Frank Griscelli 3, 34, 35, 30 Laurence Zitvogel 2, 3, 1 Lisa Derosa 36, 3, 1
4 Oncostat team [Villejuif]
IGR - Institut Gustave Roussy
Abstract : Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus–host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B + FasL + , Eomes high TCF-1 high , PD-1 + CD8 + Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.
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Submitted on : Thursday, September 23, 2021 - 1:05:52 PM
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Anne-Gaëlle Goubet, Agathe Dubuisson, Arthur Geraud, François-Xavier Danlos, Safae Terrisse, et al.. Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis. Cell Death and Differentiation, Nature Publishing Group, 2021, ⟨10.1038/s41418-021-00817-9⟩. ⟨hal-03333920⟩

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