tetano
Editor, Senior Moderator
J Infect Dis
. 2025 Oct 11:jiaf514.
doi: 10.1093/infdis/jiaf514. Online ahead of print. Autoantibodies against type I interferons are a prominent feature in SARS-CoV-2 fatal disease and hospitalization
Rebeca Linhares Abreu Netto[SUP] 1 2 [/SUP], Catherine Chen[SUP] 3 [/SUP], Victor Irungu Mwangi[SUP] 1 2 [/SUP], Carlos Eduardo Padron de Morais[SUP] 1 2 [/SUP], Mariana Simão Xavier[SUP] 1 [/SUP], Luiz Gustavo Gardinassi[SUP] 4 [/SUP], Emily Marie Eriksson[SUP] 3 5 [/SUP], Nicholas Kiernan-Walker[SUP] 3 5 [/SUP], Eamon Conway[SUP] 3 5 [/SUP], Ivo Mueller[SUP] 3 5 [/SUP], Marcus Vinícius Guimarães Lacerda[SUP] 1 6 [/SUP], Wuelton Marcelo Monteiro[SUP] 1 2 [/SUP], Fernando Fonseca Almeida-Val[SUP] 1 2 [/SUP], Gisely Cardoso de Melo[SUP] 1 2 [/SUP]
Affiliations
Background: Autoantibodies have been implicated as key players in COVID-19 pathogenesis, with evidence of impacting disease severity and poor outcomes.
Methods: We analyzed autoantibody profiles in 435 PCR-confirmed COVID-19 patients in Manaus, Brazil, comparing hospitalized (263) and non-hospitalized (172) individuals, and 37 healthy controls. Twenty autoantibodies and SARS-CoV-2-specific IgA/IgG antibodies were measured using multiplex Luminex® assays from plasma samples collected on days 1, 7, 14, and 28.
Results: Hospitalized patients had significantly higher levels of autoantibodies targeting ACE2, MPO, IFNΩ, IFNα1 and IFNα2 at baseline, with 127 hospitalized patients positive for IFNα1, 161 for IFNα2 and 68 for IFNΩ. Longitudinal analysis revealed progressively increasing levels of anti-ACE2, B2G1, C1q, IFNα1, IFNα2, PADI4, PF4 and PR3 autoantibodies in hospitalized patients, however the neutralizing capacity of IFNs were not investigated. Survival analysis showed that elevated type I IFN autoantibodies correlated with reduced survival (p=0.023). Stronger correlations between autoantibodies and SARS-CoV-2 IgA/IgG were found in severe cases.
Conclusions: In this cohort, autoantibodies were linked to COVID-19 severity and mortality, indicating their potential as biomarkers for patient risk stratification and therapeutic targets. Further research is needed to explore their impact in long-term immune dysregulation and post-acute sequelae in COVID-19 survivors.
Keywords: Autoantibodies; Autoimmunity; Biomarkers; Immune dysregulation; Mortality; SARS-CoV-2; Severity.
. 2025 Oct 11:jiaf514.
doi: 10.1093/infdis/jiaf514. Online ahead of print. Autoantibodies against type I interferons are a prominent feature in SARS-CoV-2 fatal disease and hospitalization
Rebeca Linhares Abreu Netto[SUP] 1 2 [/SUP], Catherine Chen[SUP] 3 [/SUP], Victor Irungu Mwangi[SUP] 1 2 [/SUP], Carlos Eduardo Padron de Morais[SUP] 1 2 [/SUP], Mariana Simão Xavier[SUP] 1 [/SUP], Luiz Gustavo Gardinassi[SUP] 4 [/SUP], Emily Marie Eriksson[SUP] 3 5 [/SUP], Nicholas Kiernan-Walker[SUP] 3 5 [/SUP], Eamon Conway[SUP] 3 5 [/SUP], Ivo Mueller[SUP] 3 5 [/SUP], Marcus Vinícius Guimarães Lacerda[SUP] 1 6 [/SUP], Wuelton Marcelo Monteiro[SUP] 1 2 [/SUP], Fernando Fonseca Almeida-Val[SUP] 1 2 [/SUP], Gisely Cardoso de Melo[SUP] 1 2 [/SUP]
Affiliations
- PMID: 41074539
- DOI: 10.1093/infdis/jiaf514
Background: Autoantibodies have been implicated as key players in COVID-19 pathogenesis, with evidence of impacting disease severity and poor outcomes.
Methods: We analyzed autoantibody profiles in 435 PCR-confirmed COVID-19 patients in Manaus, Brazil, comparing hospitalized (263) and non-hospitalized (172) individuals, and 37 healthy controls. Twenty autoantibodies and SARS-CoV-2-specific IgA/IgG antibodies were measured using multiplex Luminex® assays from plasma samples collected on days 1, 7, 14, and 28.
Results: Hospitalized patients had significantly higher levels of autoantibodies targeting ACE2, MPO, IFNΩ, IFNα1 and IFNα2 at baseline, with 127 hospitalized patients positive for IFNα1, 161 for IFNα2 and 68 for IFNΩ. Longitudinal analysis revealed progressively increasing levels of anti-ACE2, B2G1, C1q, IFNα1, IFNα2, PADI4, PF4 and PR3 autoantibodies in hospitalized patients, however the neutralizing capacity of IFNs were not investigated. Survival analysis showed that elevated type I IFN autoantibodies correlated with reduced survival (p=0.023). Stronger correlations between autoantibodies and SARS-CoV-2 IgA/IgG were found in severe cases.
Conclusions: In this cohort, autoantibodies were linked to COVID-19 severity and mortality, indicating their potential as biomarkers for patient risk stratification and therapeutic targets. Further research is needed to explore their impact in long-term immune dysregulation and post-acute sequelae in COVID-19 survivors.
Keywords: Autoantibodies; Autoimmunity; Biomarkers; Immune dysregulation; Mortality; SARS-CoV-2; Severity.