Divergent adaptive immune responses define two types of long COVID

• DOI: 10.3389/fimmu.2023.1221961
• Publication Date: 2023-07-20T22:31:05Z
• Authors: Jérôme Kervevan; Isabelle Staropoli; Dorsaf Slama; Raphaël Jeger-Madiot; Françoise Donnadieu; Delphine Planas; Marie-Pierre Pietri; Wiem Loghmari-Bou...; Motolete Alaba Tanah; Rémy Robinot; Faroudy Boufassa; Michael White; Dominique Salmon-...; Lisa A. Chakrabarti
• Keywords: 2019-20 coronavirus outbreak

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