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

Anne-Gaëlle Goubet; Agathe Dubuisson; Arthur Geraud; François-Xavier Danlos; Safae Terrisse; Carolina Alves Costa Silva; Damien Drubay; Lea Touri; Marion Picard; Marine Mazzenga; Aymeric Silvin; Garett Dunsmore; Yacine Haddad; Eugenie Pizzato; Pierre Ly; Caroline Flament; Cléa Melenotte; Eric Solary; Michaela Fontenay; Gabriel Garcia; Corinne Balleyguier; Nathalie Lassau; Markus Maeurer; Claudia Grajeda-Iglesias; Nitharsshini Nirmalathasan; Fanny Aprahamian; Sylvère Durand; Oliver Kepp; Gladys Ferrere; Cassandra Thelemaque; Imran Lahmar; Jean-Eudes Fahrner; Lydia Meziani; Abdelhakim Ahmed-Belkacem; Nadia Saïdani; Bernard La Scola; Didier Raoult; Stéphanie Gentile; Sébastien Cortaredona; Giuseppe Ippolito; Benjamin Lelouvier; Alain Roulet; Fabrice Andre; Fabrice Barlesi; Jean-Charles Soria; Caroline Pradon; Emmanuelle Gallois; Fanny Pommeret; Emeline Colomba; Florent Ginhoux; Suzanne Kazandjian; Arielle Elkrief; Bertrand Routy; Makoto Miyara; Guy Gorochov; Eric Deutsch; Laurence Albiges; Annabelle Stoclin; Bertrand Gachot; Anne Florin; Mansouria Merad; Florian Scotte; Souad Assaad; Guido Kroemer; Jean-Yves Blay; Aurélien Marabelle; Frank Griscelli; Laurence Zitvogel; Lisa Derosa

doi:10.1038/s41418-021-00817-9

Journal articles

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}

1 UMR 1015 - Immunologie des tumeurs et immunothérapie

2 Université Paris-Saclay

3 IGR - Institut Gustave Roussy

4 Oncostat team [Villejuif]

IGR - Institut Gustave Roussy

5 Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall

6 IC UM3 (UMR 8104 / U1016) - Institut Cochin

7 BIOMAPS - Unité BioMaps

8 Champalimaud Centre for the Unknown [Lisbon]

9 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers

10 RaMo-IT - Radiothérapie Moléculaire et Innovation Thérapeutique

11 U955 Inserm - UPEC - IMRB - "Transfusion et Maladies du Globule Rouge" [Créteil]

IMRB - Institut Mondor de Recherche Biomédicale

12 CHIC - Centre Hospitalier Intercommunal de Cornouaille

13 MEPHI - Microbes évolution phylogénie et infections

14 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection

15 CEReSS - Centre d'études et de recherche sur les services de santé et la qualité de vie

16 VITROME - Vecteurs - Infections tropicales et méditerranéennes

17 National Institute for Infectious Diseases "Lazzaro Spallanzani"

18 Vaiomer

19 U981 - Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse

20 CRCM - Centre de Recherche en Cancérologie de Marseille

21 SIgN - Singapore Immunology Network

22 E-institute of Shanghai University Immunology Division

23 Duke-NUS Medical School [Singapore]

24 MUHC - McGill University Health Center [Montreal]

25 CR CHUM - Centre de Recherche du Centre Hospitalier de l’Université de Montréal

26 CIMI - Centre d'Immunologie et de Maladies Infectieuses

27 Centre Léon Bérard [Lyon]

28 UCBL - Université Claude Bernard Lyon 1

29 UNICANCER

30 UP - Université de Paris

31 Karolinska Institutet [Stockholm]

32 HEGP - Hôpital Européen Georges Pompidou [APHP]

33 CAMS - Chinese Academy of Medical Sciences [Suzhou, Chine]

34 Modèles de Cellules Souches Malignes et Thérapeutiques

35 National Infrastructure INGESTEM, Université Paris Sud

36 Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France

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.

Keywords : Medical research Prognostic markers

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Microbiology and Parasitology / Bacteriology

Life Sciences [q-bio] / Human health and pathology / Infectious diseases

Complete list of metadata

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Submitted on : Thursday, September 23, 2021 - 1:05:52 PM
Last modification on : Tuesday, October 19, 2021 - 10:59:17 PM

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

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

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