tetano
Editor, Senior Moderator
Nat Commun
. 2024 May 16;15(1):4177.
doi: 10.1038/s41467-024-48556-y. Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
Elsa Brunet-Ratnasingham[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Sacha Morin[SUP] #[/SUP][SUP] 4 5 [/SUP], Haley E Randolph[SUP] #[/SUP][SUP] 6 [/SUP], Marjorie Labrecque[SUP] 1 7 [/SUP], Justin Bélair[SUP] 8 9 [/SUP], Raphaël Lima-Barbosa[SUP] 8 9 [/SUP], Amélie Pagliuzza[SUP] 1 [/SUP], Lorie Marchitto[SUP] 1 2 [/SUP], Michael Hultström[SUP] 10 11 12 13 [/SUP], Julia Niessl[SUP] 1 2 14 [/SUP], Rose Cloutier[SUP] 1 [/SUP], Alina M Sreng Flores[SUP] 1 [/SUP], Nathalie Brassard[SUP] 1 [/SUP], Mehdi Benlarbi[SUP] 1 2 [/SUP], Jérémie Prévost[SUP] 1 2 [/SUP], Shilei Ding[SUP] 1 [/SUP], Sai Priya Anand[SUP] 1 2 [/SUP], Gérémy Sannier[SUP] 1 2 [/SUP], Amanda Marks[SUP] 15 [/SUP], Dick Wågsäter[SUP] 16 [/SUP], Eric Bareke[SUP] 1 [/SUP], Hugo Zeberg[SUP] 17 18 [/SUP], Miklos Lipcsey[SUP] 19 20 [/SUP], Robert Frithiof[SUP] 19 [/SUP], Anders Larsson[SUP] 21 [/SUP], Sirui Zhou[SUP] 22 23 [/SUP], Tomoko Nakanishi[SUP] 22 23 24 25 [/SUP], David Morrison[SUP] 22 [/SUP], Dani Vezina[SUP] 1 2 [/SUP], Catherine Bourassa[SUP] 1 [/SUP], Gabrielle Gendron-Lepage[SUP] 1 [/SUP], Halima Medjahed[SUP] 1 [/SUP], Floriane Point[SUP] 1 [/SUP], Jonathan Richard[SUP] 1 [/SUP], Catherine Larochelle[SUP] 1 26 [/SUP], Alexandre Prat[SUP] 1 26 [/SUP], Janet L Cunningham[SUP] 27 [/SUP], Nathalie Arbour[SUP] 1 26 [/SUP], Madeleine Durand[SUP] 1 28 [/SUP], J Brent Richards[SUP] 29 22 23 30 [/SUP], Kevin Moon[SUP] 31 [/SUP], Nicolas Chomont[SUP] 1 2 [/SUP], Andrés Finzi[SUP] 1 2 32 [/SUP], Martine Tétreault[SUP] 1 26 [/SUP], Luis Barreiro[SUP] 6 33 34 [/SUP], Guy Wolf[SUP] 35 36 37 [/SUP], Daniel E Kaufmann[SUP] 38 39 40 [/SUP]
Affiliations
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[SUP]+[/SUP] 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.
. 2024 May 16;15(1):4177.
doi: 10.1038/s41467-024-48556-y. Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
Elsa Brunet-Ratnasingham[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Sacha Morin[SUP] #[/SUP][SUP] 4 5 [/SUP], Haley E Randolph[SUP] #[/SUP][SUP] 6 [/SUP], Marjorie Labrecque[SUP] 1 7 [/SUP], Justin Bélair[SUP] 8 9 [/SUP], Raphaël Lima-Barbosa[SUP] 8 9 [/SUP], Amélie Pagliuzza[SUP] 1 [/SUP], Lorie Marchitto[SUP] 1 2 [/SUP], Michael Hultström[SUP] 10 11 12 13 [/SUP], Julia Niessl[SUP] 1 2 14 [/SUP], Rose Cloutier[SUP] 1 [/SUP], Alina M Sreng Flores[SUP] 1 [/SUP], Nathalie Brassard[SUP] 1 [/SUP], Mehdi Benlarbi[SUP] 1 2 [/SUP], Jérémie Prévost[SUP] 1 2 [/SUP], Shilei Ding[SUP] 1 [/SUP], Sai Priya Anand[SUP] 1 2 [/SUP], Gérémy Sannier[SUP] 1 2 [/SUP], Amanda Marks[SUP] 15 [/SUP], Dick Wågsäter[SUP] 16 [/SUP], Eric Bareke[SUP] 1 [/SUP], Hugo Zeberg[SUP] 17 18 [/SUP], Miklos Lipcsey[SUP] 19 20 [/SUP], Robert Frithiof[SUP] 19 [/SUP], Anders Larsson[SUP] 21 [/SUP], Sirui Zhou[SUP] 22 23 [/SUP], Tomoko Nakanishi[SUP] 22 23 24 25 [/SUP], David Morrison[SUP] 22 [/SUP], Dani Vezina[SUP] 1 2 [/SUP], Catherine Bourassa[SUP] 1 [/SUP], Gabrielle Gendron-Lepage[SUP] 1 [/SUP], Halima Medjahed[SUP] 1 [/SUP], Floriane Point[SUP] 1 [/SUP], Jonathan Richard[SUP] 1 [/SUP], Catherine Larochelle[SUP] 1 26 [/SUP], Alexandre Prat[SUP] 1 26 [/SUP], Janet L Cunningham[SUP] 27 [/SUP], Nathalie Arbour[SUP] 1 26 [/SUP], Madeleine Durand[SUP] 1 28 [/SUP], J Brent Richards[SUP] 29 22 23 30 [/SUP], Kevin Moon[SUP] 31 [/SUP], Nicolas Chomont[SUP] 1 2 [/SUP], Andrés Finzi[SUP] 1 2 32 [/SUP], Martine Tétreault[SUP] 1 26 [/SUP], Luis Barreiro[SUP] 6 33 34 [/SUP], Guy Wolf[SUP] 35 36 37 [/SUP], Daniel E Kaufmann[SUP] 38 39 40 [/SUP]
Affiliations
- PMID: 38755196
- DOI: 10.1038/s41467-024-48556-y
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[SUP]+[/SUP] 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.