Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis - Aix-Marseille Université Access content directly
Journal Articles Cell Death and Differentiation Year : 2021

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 (4, 2) , Arthur Geraud (2) , François-Xavier Danlos (2, 3) , Safae Terrisse (2, 3) , Carolina Alves Costa Silva (2, 3) , Damien Drubay (2, 1, 5, 6) , Lea Touri (2) , Marion Picard (2, 4, 7, 3) , Marine Mazzenga (2, 3) , Aymeric Silvin (2, 3) , Garett Dunsmore (2, 3) , Yacine Haddad (2, 3) , Eugenie Pizzato (2, 3) , Pierre Ly (2, 3) , Caroline Flament (2, 3) , Cléa Melenotte (2, 3) , Eric Solary (1, 2, 8) , Michaela Fontenay (9) , Gabriel Garcia (2, 10) , Corinne Balleyguier (2, 10) , Nathalie Lassau (1, 2, 11) , Markus Maeurer (12) , Claudia Grajeda-Iglesias (2, 13, 3) , Nitharsshini Nirmalathasan (2, 13) , Fanny Aprahamian (2, 13) , Sylvère Durand (2, 13) , Oliver Kepp (2, 13) , Gladys Ferrere (2, 3) , Cassandra Thelemaque (2, 3) , Imran Lahmar (2, 3) , Jean-Eudes Fahrner (2, 3) , Lydia Meziani (2, 14) , Abdelhakim Ahmed-Belkacem (15) , Nadia Saïdani (16) , Bernard La Scola (17, 18) , Didier Raoult (17, 18) , Stéphanie Gentile (19) , Sébastien Cortaredona (20, 18) , Giuseppe Ippolito (21) , Benjamin Lelouvier (22) , Alain Roulet (22) , Fabrice Andre (1, 2, 23) , Fabrice Barlesi (2, 24) , Jean-Charles Soria (1, 2) , Caroline Pradon (2, 25) , Emmanuelle Gallois (2, 25) , Fanny Pommeret (2) , Emeline Colomba (2) , Florent Ginhoux (26, 27, 28) , Suzanne Kazandjian (29) , Arielle Elkrief (29, 30) , Bertrand Routy (30) , Makoto Miyara (31) , Guy Gorochov (31) , Eric Deutsch (1, 2, 14) , Laurence Albiges (1, 2) , Annabelle Stoclin (2) , Bertrand Gachot (2) , Anne Florin (2) , Mansouria Merad (2) , Florian Scotte (2) , Souad Assaad (32, 33, 34) , Guido Kroemer (2, 13, 35, 36, 37, 38) , Jean-Yves Blay (32, 33, 34) , Aurélien Marabelle (2, 3) , Frank Griscelli (2, 39, 40, 35) , Laurence Zitvogel (1, 2, 3) , Lisa Derosa (2, 2, 3)
1 Université Paris-Saclay
2 IGR - Institut Gustave Roussy
3 ITIC - Immunologie anti-tumorale et immunothérapie des cancers
4 UMR 1015 - Immunologie des tumeurs et immunothérapie
5 U1018 (Équipe 2) - Oncostat
6 CESP - Centre de recherche en épidémiologie et santé des populations
7 Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall
8 CSHMyelo - U1287 Inserm - Cellules souches hématopoïétiques et développement des hémopathies myéloïdes
9 IC UM3 (UMR 8104 / U1016) - Institut Cochin
10 Département d'imagerie médicale [Gustave Roussy]
11 BIOMAPS - LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay
12 Champalimaud Centre for the Unknown [Lisbon]
13 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
14 RaMo-IT - Radiothérapie Moléculaire et Innovation Thérapeutique
15 U955 Inserm - UPEC - IMRB - "Transfusion et Maladies du Globule Rouge" [Créteil]
16 CHIC - Centre Hospitalier Intercommunal de Cornouaille
17 MEPHI - Microbes évolution phylogénie et infections
18 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
19 CEReSS - Centre d'études et de recherche sur les services de santé et la qualité de vie
20 VITROME - Vecteurs - Infections tropicales et méditerranéennes
21 National Institute for Infectious Diseases "Lazzaro Spallanzani"
22 Vaiomer
23 PMNCO - Prédicteurs moléculaires et nouvelles cibles en oncologie
24 CRCM - Centre de Recherche en Cancérologie de Marseille
25 Département de biologie et pathologie médicales [Gustave Roussy]
26 SIgN - Singapore Immunology Network
27 E-institute of Shanghai University Immunology Division
28 Duke-NUS Medical School [Singapore]
29 MUHC - McGill University Health Center [Montreal]
30 CR CHUM - Centre de Recherche du Centre Hospitalier de l’Université de Montréal
31 CIMI - Centre d'Immunologie et des Maladies Infectieuses
32 Centre Léon Bérard [Lyon]
33 UCBL - Université Claude Bernard Lyon 1
34 UNICANCER
35 UPCité - Université Paris Cité
36 Karolinska Institutet [Stockholm]
37 HEGP - Hôpital Européen Georges Pompidou [APHP]
38 China Academy of Chinese Medical Sciences
39 Modèles de Cellules Souches Malignes et Thérapeutiques
40 National Infrastructure INGESTEM, Université Paris Sud
Michaela Fontenay
Benjamin Lelouvier
  • Function : Author
Alain Roulet
  • Function : Author

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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hal-03333920 , version 1 (23-09-2021)

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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, 2021, ⟨10.1038/s41418-021-00817-9⟩. ⟨hal-03333920⟩
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