| Title: |
Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity |
| Authors: |
Brunet-Ratnasingham, E.; Morin, S.; Randolph, H.; Labrecque, M.; Bélair, J.; Lima-Barbosa, R.; Pagliuzza, A.; Marchitto, L.; Hultström, M.; Niessl, J.; Cloutier, R.; Sreng Flores, A.; Brassard, N.; Benlarbi, M.; Prévost, J.; Ding, S.; Anand, S.; Sannier, G.; Marks, A.; Wågsäter, D.; Bareke, E.; Zeberg, H.; Lipcsey, M.; Frithiof, R.; Larsson, A.; Zhou, S.; Nakanishi, T.; Morrison, D.; Vezina, D.; Bourassa, C.; Gendron-Lepage, G.; Medjahed, H.; Point, F.; Richard, J.; Larochelle, C.; Prat, A.; Cunningham, J.; Arbour, N.; Durand, M.; Richards, J.; Moon, K.; Chomont, N.; Finzi, A.; Tétreault, M.; Barreiro, L.; Wolf, G.; Kaufmann, D. |
| Source: |
Nature Communications |
| Publication Year: |
2024 |
| Collection: |
Max Planck Society: MPG.PuRe |
| Description: |
Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the “Interferon paradox” previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity. © The Author(s) 2024. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Availability: |
http://hdl.handle.net/21.11116/0000-000F-58BB-C; http://hdl.handle.net/21.11116/0000-000F-58BD-A |
| Rights: |
info:eu-repo/semantics/openAccess ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.21431FB1 |
| Database: |
BASE |