Chandelier
Senior Member (Voting Rights)
Early HHV-6 IgG and IgA responses during acute SARS-CoV-2 infection in relation to long COVID: a multicohort observational study
However, herpesvirus-directed antibody responses during acute SARS-CoV-2 infection and their relationship to subsequent long COVID remain poorly understood.
Antibody responses were profiled in longitudinal samples from acute SARS-CoV-2 infection and in early post-infection samples from participants in the NIH RECOVER observational cohort.
IgG, IgA, and IgM responses were analysed using peptide-, virus-, and factor-level approaches.
In RECOVER participants, subsequent long COVID was associated with herpesvirus- and isotype-specific enrichment of high responders, most prominently HHV-6 IgA and HHV-1/HHV-2 IgG.
Unsupervised factorisation identified distinct HHV-6 IgG- and IgA-dominant antibody programs with differing clinical and demographic associations.
HHV-6 IgG responses were associated with lower symptom burden and relative enrichment among participants without long COVID, whereas HHV-6 IgA responses were associated with greater symptom burden.
HHV-6 IgG responses also declined with increasing age, with the association more readily detected among females.
Web | DOI | eBioMedicine | Open Access
Choudhury, Ananya; Burry, Michael J.; Kwon, Woo Joo; Yin, Xihui; Rallistan, Alysa; Presti, Sonia; Ndakwah, Gabrielle S.; Cheng, Emily Q.; Kalaycioglu, Muge; Harris, Marlayna; Frankovich, Jennifer; Karlson, Elizabeth W.; Bollyky, Jenna; Utz, Paul J.; Prestwood, Tyler R.
Summary
Background
Long COVID is a heterogeneous condition associated with both early immune responses to SARS-CoV-2 and antibody responses to herpesviruses.However, herpesvirus-directed antibody responses during acute SARS-CoV-2 infection and their relationship to subsequent long COVID remain poorly understood.
Methods
We developed a multiplex bead-based serologic assay using recurrent, public peptide epitopes spanning all eight human herpesviruses.Antibody responses were profiled in longitudinal samples from acute SARS-CoV-2 infection and in early post-infection samples from participants in the NIH RECOVER observational cohort.
IgG, IgA, and IgM responses were analysed using peptide-, virus-, and factor-level approaches.
Findings
During acute SARS-CoV-2 infection, a subset of individuals exhibited increased herpesvirus-directed IgA responses, particularly against beta-herpesviruses, without corresponding increases in IgG or IgM.In RECOVER participants, subsequent long COVID was associated with herpesvirus- and isotype-specific enrichment of high responders, most prominently HHV-6 IgA and HHV-1/HHV-2 IgG.
Unsupervised factorisation identified distinct HHV-6 IgG- and IgA-dominant antibody programs with differing clinical and demographic associations.
HHV-6 IgG responses were associated with lower symptom burden and relative enrichment among participants without long COVID, whereas HHV-6 IgA responses were associated with greater symptom burden.
HHV-6 IgG responses also declined with increasing age, with the association more readily detected among females.
Interpretation
Early herpesvirus-directed antibody responses following SARS-CoV-2 infection exhibit distinct virus- and isotype-specific patterns associated with long COVID. These findings suggest that heterogeneity in long COVID may be linked to differential herpesvirus-directed humoural immune responses that emerge early after infection.Web | DOI | eBioMedicine | Open Access