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Cell Rep Med . Systemic and mucosal immune signatures of protection against SARS-CoV-2 transmission in humans

tetano

Editor, Senior Moderator
Cell Rep Med


. 2025 Dec 16;6(12):102505.
doi: 10.1016/j.xcrm.2025.102505. Systemic and mucosal immune signatures of protection against SARS-CoV-2 transmission in humans

Amaya Rojo-Fernandez[SUP] 1 [/SUP], Sadaf Aslam[SUP] 1 [/SUP], Fahmida Alam[SUP] 2 [/SUP], Alba Escalera[SUP] 2 [/SUP], Vicente Villamandos[SUP] 3 [/SUP], Beatriz Catón[SUP] 3 [/SUP], Gregoria Megías[SUP] 3 [/SUP], Angel Gonzalez[SUP] 4 [/SUP], Luis Buzón-Martín[SUP] 3 [/SUP], Juan Ayllon[SUP] 5 [/SUP], Adolfo García-Sastre[SUP] 6 [/SUP], Teresa Aydillo[SUP] 7 [/SUP]



Affiliations
Abstract

Binding and neutralizing antibodies against the spike (S) protein of SARS-CoV-2 have been associated with a reduced risk of symptomatic infection. However, precise immune protection thresholds remain unclear. We aim to define systemic and mucosal antibody correlates of protection against SARS-CoV-2 infection. Our household COVID-19 cohort (the CIDS) consists of 52 families (52 index cases and 139 exposed contacts). Immunoglobulin subtyping against S of SARS-CoV-2 and HCoV-OC43 in the serum and upper respiratory tract is quantified to assess the protection provided by virus-specific pre-existing immunity. Logistic regression analyses indicate that multiple antibody isotypes are associated with reduced infection risk. Specifically, multivariable models show that systemic anti-SARS-CoV-2 S1 IgG and anti-OC43 S2 IgM independently correlate with protection. Besides, local mucosal anti-SARS-CoV-2 S IgG and HCoV-OC43 S IgA antibodies add protective potential. However, an integrated analysis reveals that systemic antibodies against SARS-CoV-2 remain the best predictor against virus infection.

Keywords: COVID-19; SARS-CoV-2; antibodies; correlates of protection; cross-reactivity; household study; nasal antibodies; seasonal coronaviruses; transmission.

 
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