Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

doi:10.1016/j.jinf.2020.06.073

Observational Study

. 2020 Nov;81(5):816-846.

doi: 10.1016/j.jinf.2020.06.073. Epub 2020 Jun 30.

Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

Marie Gousseff¹, Pauline Penot², Laure Gallay³, Dominique Batisse⁴, Nicolas Benech⁵, Kevin Bouiller⁶, Rocco Collarino⁷, Anne Conrad⁸, Dorsaf Slama⁹, Cédric Joseph¹⁰, Adrien Lemaignen¹¹, François-Xavier Lescure¹², Bruno Levy¹³, Matthieu Mahevas¹⁴, Bruno Pozzetto¹⁵, Nicolas Vignier¹⁶, Benjamin Wyplosz¹⁷, Dominique Salmon¹⁸, Francois Goehringer¹⁹, Elisabeth Botelho-Nevers²⁰; in behalf of the COCOREC study group

Affiliations

¹ Service de Medecine interne, Maladies Infectieuses, hematologie, Centre Hospitalier Bretagne Atlantique, 20, boulevard Maurice Guillaudot, 56000 Vannes, France. Electronic address: marie.gousseff@ch-bretagne-atlantique.fr.
² Hôpital intercommunal André Grégoire, groupement hospitalier Grand Paris Nord Est, 56, boulevard de la Boissière, 93100 Montreuil, France. Electronic address: pauline.penot@ght-gpne.fr.
³ Service Médecine Interne, Pr Hot, INMG CNRS UMR5310 INSERM U1217, Place d'arsonvaal, 69003 Lyon, France. Electronic address: laure.gallay@chu-lyon.fr.
⁴ Department of Infectious Diseases and Immunology, Cochin-Hôtel-Dieu Hospital, Publique -Hôpitaux de Paris (APHP), University of Paris. 1, place parvis Notre Dame, 75014 Paris, France.
⁵ Service des Maladies Infectieuses et Tropicales, Hôpital de La Croix-Rousse, Hospices Civils de Lyon, 103, Grande Rue de La Croix-Rousse, 69004 Lyon, France. Electronic address: nicolas.benech@chu-lyon.fr.
⁶ Department of infectious disease, University Hospital of Besançon, F-25000 Besançon, France; UMR-CNRS 6249 Chrono-environnement, Université Bourgogne Franche-Comté, 25000 Besançon, France. Electronic address: kbouiller@chu-besancon.fr.
⁷ Service des Maladies infectieuses et tropicales, Assistance publique- hôpitaux de Paris, Centre hospitalier universitaire Bicêtre, 78 rue du général Leclerc, 94270 Le Kremlin-Bicêtre, France. Electronic address: rocco.collarino@aphp.fr.
⁸ Service des Maladies Infectieuses et Tropicales, Hôpital de La Croix-Rousse, Hospices Civils de Lyon, 103, Grande Rue de La Croix-Rousse, 69004 Lyon, France. Electronic address: anne.conrad@chu-lyon.fr.
⁹ Department of Infectious Diseases and Immunology, Cochin-Hôtel-Dieu Hospital, Assistance, Publique -Hôpitaux de Paris (APHP), University of Paris. 1, place parvis Notre Dame, 75014 Paris, France.
¹⁰ Service des Maladies Infectieuses et Tropicales, CHU Amiens-Picardie, Place Victor Pauchet 80054 Amiens, France. Electronic address: joseph.cedric@chu-amiens.fr.
¹¹ Service de Médecine Interne et Maladies Infectieuses, CHRU de Tours, Hôpital Bretonneau, Université de Tours, 2, Boulevard Tonnellé, 37000 Tours, France. Electronic address: adrien.lemaignen@univ-tours.fr.
¹² AP-HP, Infectious and Tropical Diseases Department, Bichat-Claude Bernard University, Hospital, Paris, France; University of Paris, French Institute for Health and Medical Research (INSERM), IAME, U1137, Team DesCID, Paris, France. 46 rue Henri Huchard, 75018 Paris, France. Electronic address: xavier.lescure@aphp.fr.
¹³ Service de Médecine Intensive et Reanimation Brabois, CHRU Nancy, Pôle Cardio-Médico-Chirurgical, Vandoeuvre-les-Nancy, INSERM U1116, Faculté de Médecine, Vandoeuvre-les-Nancy, and Université de Lorraine, France.
¹⁴ Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris Est Créteil, Créteil, France. IMRB - U955 - INSERM Equipe n°2 "Transfusion et maladies du globule rouge" EFS Île-de-France, Hôpital Henri-Mondor, AP-HP, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil, France. Electronic address: matthieu.mahevas@aphp.fr.
¹⁵ GIMAP (EA 3064), University of Saint-Etienne, University of Lyon, Faculty of Medicine of Saint-Etienne, 42023 cedex 02 Saint-Etienne, France. Electronic address: bruno.pozzetto@chu-st-etienne.fr.
¹⁶ Groupe hospitalier Sud Ile de France & INSERM, Institut Pierre Louis d'Épidémiologie et de, Santé Publique (IPLESP), Sorbonne Université, Paris, France, 270 avenue Marc Jacquet, 77 000 Melun, France.
¹⁷ Service des Maladies infectieuses et tropicales, Assistance publique- hôpitaux de Paris, Centre hospitalier universitaire Bicêtre, 78 rue du général Leclerc, 94270 Le Kremlin-Bicêtre, France. Electronic address: Benjamin.wyplosz@aphp.fr.
¹⁸ Department of Infectious Diseases and Immunology, Cochin-Hôtel-Dieu Hospital, Assistance, Publique -Hôpitaux de Paris (APHP), University of Paris. 1, place parvis Notre Dame, 75014 Paris, France. Electronic address: Dominique.salmon@aphp.fr.
¹⁹ Service de Maladies Infectieuses et Tropicales, Centre Régional Universitaire de Nancy, Hôpitaux de Brabois, Rue du Morvan, 54511 Vandoeuvre Lés Nancy, France. Electronic address: f.goehringer@chru-nancy.fr.
²⁰ Infectious Diseases Department, University Hospital of Saint-Etienne, 42055 cedex 02 Saint-Etienne, GIMAP (EA 3064), France; University of Saint-Etienne, University of Lyon, Faculty of Medicine of Saint-Etienne, 42023 cedex 02 Saint-Etienne, France. Electronic address: elisabeth.botelho-nevers@chu-st-etienne.fr.

PMID: 32619697
PMCID: PMC7326402
DOI: 10.1016/j.jinf.2020.06.073

Observational Study

Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

Marie Gousseff et al. J Infect. 2020 Nov.

. 2020 Nov;81(5):816-846.

doi: 10.1016/j.jinf.2020.06.073. Epub 2020 Jun 30.

Authors

Affiliations

¹ Service de Medecine interne, Maladies Infectieuses, hematologie, Centre Hospitalier Bretagne Atlantique, 20, boulevard Maurice Guillaudot, 56000 Vannes, France. Electronic address: marie.gousseff@ch-bretagne-atlantique.fr.
² Hôpital intercommunal André Grégoire, groupement hospitalier Grand Paris Nord Est, 56, boulevard de la Boissière, 93100 Montreuil, France. Electronic address: pauline.penot@ght-gpne.fr.
³ Service Médecine Interne, Pr Hot, INMG CNRS UMR5310 INSERM U1217, Place d'arsonvaal, 69003 Lyon, France. Electronic address: laure.gallay@chu-lyon.fr.
⁴ Department of Infectious Diseases and Immunology, Cochin-Hôtel-Dieu Hospital, Publique -Hôpitaux de Paris (APHP), University of Paris. 1, place parvis Notre Dame, 75014 Paris, France.
⁵ Service des Maladies Infectieuses et Tropicales, Hôpital de La Croix-Rousse, Hospices Civils de Lyon, 103, Grande Rue de La Croix-Rousse, 69004 Lyon, France. Electronic address: nicolas.benech@chu-lyon.fr.
⁶ Department of infectious disease, University Hospital of Besançon, F-25000 Besançon, France; UMR-CNRS 6249 Chrono-environnement, Université Bourgogne Franche-Comté, 25000 Besançon, France. Electronic address: kbouiller@chu-besancon.fr.
⁷ Service des Maladies infectieuses et tropicales, Assistance publique- hôpitaux de Paris, Centre hospitalier universitaire Bicêtre, 78 rue du général Leclerc, 94270 Le Kremlin-Bicêtre, France. Electronic address: rocco.collarino@aphp.fr.
⁸ Service des Maladies Infectieuses et Tropicales, Hôpital de La Croix-Rousse, Hospices Civils de Lyon, 103, Grande Rue de La Croix-Rousse, 69004 Lyon, France. Electronic address: anne.conrad@chu-lyon.fr.
⁹ Department of Infectious Diseases and Immunology, Cochin-Hôtel-Dieu Hospital, Assistance, Publique -Hôpitaux de Paris (APHP), University of Paris. 1, place parvis Notre Dame, 75014 Paris, France.
¹⁰ Service des Maladies Infectieuses et Tropicales, CHU Amiens-Picardie, Place Victor Pauchet 80054 Amiens, France. Electronic address: joseph.cedric@chu-amiens.fr.
¹¹ Service de Médecine Interne et Maladies Infectieuses, CHRU de Tours, Hôpital Bretonneau, Université de Tours, 2, Boulevard Tonnellé, 37000 Tours, France. Electronic address: adrien.lemaignen@univ-tours.fr.
¹² AP-HP, Infectious and Tropical Diseases Department, Bichat-Claude Bernard University, Hospital, Paris, France; University of Paris, French Institute for Health and Medical Research (INSERM), IAME, U1137, Team DesCID, Paris, France. 46 rue Henri Huchard, 75018 Paris, France. Electronic address: xavier.lescure@aphp.fr.
¹³ Service de Médecine Intensive et Reanimation Brabois, CHRU Nancy, Pôle Cardio-Médico-Chirurgical, Vandoeuvre-les-Nancy, INSERM U1116, Faculté de Médecine, Vandoeuvre-les-Nancy, and Université de Lorraine, France.
¹⁴ Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris Est Créteil, Créteil, France. IMRB - U955 - INSERM Equipe n°2 "Transfusion et maladies du globule rouge" EFS Île-de-France, Hôpital Henri-Mondor, AP-HP, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil, France. Electronic address: matthieu.mahevas@aphp.fr.
¹⁵ GIMAP (EA 3064), University of Saint-Etienne, University of Lyon, Faculty of Medicine of Saint-Etienne, 42023 cedex 02 Saint-Etienne, France. Electronic address: bruno.pozzetto@chu-st-etienne.fr.
¹⁶ Groupe hospitalier Sud Ile de France & INSERM, Institut Pierre Louis d'Épidémiologie et de, Santé Publique (IPLESP), Sorbonne Université, Paris, France, 270 avenue Marc Jacquet, 77 000 Melun, France.
¹⁷ Service des Maladies infectieuses et tropicales, Assistance publique- hôpitaux de Paris, Centre hospitalier universitaire Bicêtre, 78 rue du général Leclerc, 94270 Le Kremlin-Bicêtre, France. Electronic address: Benjamin.wyplosz@aphp.fr.
¹⁸ Department of Infectious Diseases and Immunology, Cochin-Hôtel-Dieu Hospital, Assistance, Publique -Hôpitaux de Paris (APHP), University of Paris. 1, place parvis Notre Dame, 75014 Paris, France. Electronic address: Dominique.salmon@aphp.fr.
¹⁹ Service de Maladies Infectieuses et Tropicales, Centre Régional Universitaire de Nancy, Hôpitaux de Brabois, Rue du Morvan, 54511 Vandoeuvre Lés Nancy, France. Electronic address: f.goehringer@chru-nancy.fr.
²⁰ Infectious Diseases Department, University Hospital of Saint-Etienne, 42055 cedex 02 Saint-Etienne, GIMAP (EA 3064), France; University of Saint-Etienne, University of Lyon, Faculty of Medicine of Saint-Etienne, 42023 cedex 02 Saint-Etienne, France. Electronic address: elisabeth.botelho-nevers@chu-st-etienne.fr.

PMID: 32619697
PMCID: PMC7326402
DOI: 10.1016/j.jinf.2020.06.073

Abstract

For the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences.

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Conflict of interest statement

Declaration of Competing Interest None of the authors has any conflict of interest to declare regarding this subject. This work had no financial support.

Comment in

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AlFehaidi A, Ahmad SA, Hamed E. AlFehaidi A, et al. J Infect. 2021 Mar;82(3):414-451. doi: 10.1016/j.jinf.2020.10.019. Epub 2020 Oct 25. J Infect. 2021. PMID: 33115660 Free PMC article. No abstract available.
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Hamed E, Sedeeq S, Alnuaimi AS, Syed M, ElHamid MA, Alemrayat B, Mukhtar A, AlFehaidi A, A/Qotba H. Hamed E, et al. J Infect. 2021 Apr;82(4):84-123. doi: 10.1016/j.jinf.2020.10.029. Epub 2020 Nov 2. J Infect. 2021. PMID: 33144191 Free PMC article. No abstract available.
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Buskermolen M, Te Paske K, van Beek J, Kortbeek T, Götz H, Fanoy E, Feenstra S, Richardus JH, Vollaard A. Buskermolen M, et al. J Infect. 2021 Aug;83(2):e6-e8. doi: 10.1016/j.jinf.2021.06.015. Epub 2021 Jun 18. J Infect. 2021. PMID: 34147529 Free PMC article. No abstract available.

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References

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[1] Kiyuka P.K., Agoti C.N., Munywoki P.K., Njeru R., Bett A., Otieno J.R. Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya. J Infect Dis. 2018;217(11):1728–1739. 05. - PMC - PubMed

[2] Kiyuka P.K., Agoti C.N., Munywoki P.K., Njeru R., Bett A., Otieno J.R. Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya. J Infect Dis. 2018;217(11):1728–1739. 05. - PMC - PubMed

[3] Tang F., Quan Y., Xin Z.-.T., Wrammert J., Ma M.-.J., Lv H. Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study. J Immunol Baltim Md 1950. 2011;186(12):7264–7268. Jun 15. - PubMed

[4] Tang F., Quan Y., Xin Z.-.T., Wrammert J., Ma M.-.J., Lv H. Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study. J Immunol Baltim Md 1950. 2011;186(12):7264–7268. Jun 15. - PubMed

[5] Ye G., Pan Z., Pan Y., Deng Q., Chen L., Li J. Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation. J Infect. 2020;80(5):e14–e17. - PMC - PubMed

[6] Ye G., Pan Z., Pan Y., Deng Q., Chen L., Li J. Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation. J Infect. 2020;80(5):e14–e17. - PMC - PubMed

[7] Ravioli S., Ochsner H., Lindner G. Reactivation of COVID-19 pneumonia: a report of two cases. J Infect. 2020 doi: 10.1016/j.jinf.2020.05.008. [published online ahead of print, 2020 May 7] - DOI - PMC - PubMed

[8] Ravioli S., Ochsner H., Lindner G. Reactivation of COVID-19 pneumonia: a report of two cases. J Infect. 2020 doi: 10.1016/j.jinf.2020.05.008. [published online ahead of print, 2020 May 7] - DOI - PMC - PubMed

[9] Loconsole D., Passerini F., Palmieri V.O., Centrone F., Sallustio A., Pugliese S. Recurrence of COVID-19 after recovery: a case report from Italy. Infection. 2020:1–3. doi: 10.1007/s15010-020-01444-1. [published online ahead of print, 2020 May 16] - DOI - PMC - PubMed

[10] Loconsole D., Passerini F., Palmieri V.O., Centrone F., Sallustio A., Pugliese S. Recurrence of COVID-19 after recovery: a case report from Italy. Infection. 2020:1–3. doi: 10.1007/s15010-020-01444-1. [published online ahead of print, 2020 May 16] - DOI - PMC - PubMed

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Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

Affiliations

Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

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