Divergent adaptive immune responses define two types of long COVID

Frontiers in Immunology

Immunology

Dorsaf Slama¹  Wiem Loghmari-Bouchneb¹  Motolete Alaba Tanah¹  Marie-Pierre Pietri¹  Dominique Salmon-Ceron¹  Faroudy Boufassa²  Michael White³  Françoise Donnadieu³  Lisa A. Chakrabarti⁴  Raphaël Jeger-Madiot⁴  Rémy Robinot⁴  Isabelle Staropoli⁴  Delphine Planas⁴  Jérôme Kervevan⁴ 

[1] Department of Infectious Diseases and Immunology, Hôtel Dieu Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris Cité, Paris, France;INSERM U1018, Center for Research in Epidemiology and Population Health (CESP), Le Kremlin-Bicêtre, France;Infectious Disease Analytics and Epidemiology G5 Unit, Institut Pasteur, Université de Paris Cité, Paris, France;Virus and Immunity Unit, Institut Pasteur, Université de Paris Cité, CNRS UMR3569, Paris, France;

关键词: long COVID;    T cell;    humoral immune response;    seronegative and seropositive;    common cold coronavirus;    SARS-CoV-2;   

DOI  :  10.3389/fimmu.2023.1221961

 received in 2023-05-13, accepted in 2023-07-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThe role of adaptive immune responses in long COVID remains poorly understood, with contrasting hypotheses suggesting either an insufficient antiviral response or an excessive immune response associated with inflammatory damage. To address this issue, we set to characterize humoral and CD4+ T cell responses in long COVID patients prior to SARS-CoV-2 vaccination.MethodsLong COVID patients who were seropositive (LC+, n=28) or seronegative (LC-, n=23) by spike ELISA assay were recruited based on (i) an initial SARS-CoV-2 infection documented by PCR or the conjunction of three major signs of COVID-19 and (ii) the persistence or resurgence of at least 3 symptoms for over 3 months. They were compared to COVID patients with resolved symptoms (RE, n=29) and uninfected control individuals (HD, n=29).ResultsThe spectrum of persistent symptoms proved similar in both long COVID groups, with a trend for a higher number of symptoms in the seronegative group (median=6 vs 4.5; P=0.01). The use a highly sensitive S-flow assay enabled the detection of low levels of SARS-CoV-2 spike-specific IgG in 22.7% of ELISA-seronegative long COVID (LC-) patients. In contrast, spike-specific IgG levels were uniformly high in the LC+ and RE groups. Multiplexed antibody analyses to 30 different viral antigens showed that LC- patients had defective antibody responses to all SARS-CoV-2 proteins tested but had in most cases preserved responses to other viruses. A sensitive primary T cell line assay revealed low but detectable SARS-CoV-2-specific CD4 responses in 39.1% of LC- patients, while response frequencies were high in the LC+ and RE groups. Correlation analyses showed overall strong associations between humoral and cellular responses, with exceptions in the LC- group.ConclusionsThese findings provide evidence for two major types of antiviral immune responses in long COVID. Seropositive patients showed coordinated cellular and humoral responses at least as high as those of recovered patients. In contrast, ELISA-seronegative long COVID patients showed overall low antiviral responses, with detectable specific CD4+ T cells and/or antibodies in close to half of patients (52.2%). These divergent findings in patients sharing a comparable spectrum of persistent symptoms raise the possibility of multiple etiologies in long COVID.

【 授权许可】

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Copyright © 2023 Kervevan, Staropoli, Slama, Jeger-Madiot, Donnadieu, Planas, Pietri, Loghmari-Bouchneb, Alaba Tanah, Robinot, Boufassa, White, Salmon-Ceron and Chakrabarti