Seasonal Coronavirus-Induced Immunological Imprinting and Previous Herpesvirus Infections in Patients With Long COVID

Long COVID (LC) is a post-acute infection syndrome affecting 5%–10% of individuals infected by SARS-CoV-2. Here, we aimed to study SARS-CoV-2 humoral immunity, immunological imprinting by endemic coronaviruses, and previous herpesvirus infections in LC. We included 47 LC patients and 41 controls who fully recovered from COVID-19. We assessed IgG, IgA, and IgM antibody levels against SARS-CoV-2, seasonal coronaviruses, and herpesviruses using ELISAs and Microblot-Array panels. Additionally, we performed PCR to detect viral RNA/DNA and evaluated anti-nuclear autoantibodies linked to systemic autoimmune conditions. LC patients showed significantly reduced levels of SARS-CoV-2 anti-spike IgG and IgA but increased levels of endemic coronaviruses OC43 and HKU1 anti-spike IgG, suggesting immunological imprinting potentially driven by these coronaviruses. Furthermore, LC patients had higher levels of SARS-CoV-2 anti-spike IgM compared to anti-Spike IgG, possibly indicating impaired class switching. Interestingly, cytomegalovirus (CMV) p65 IgG levels were lower in LC patients and negatively correlated with fatigue severity. This study highlights immunological imprinting by seasonal coronaviruses and impaired antibody class switching as potential causes of SARS-CoV-2 immune escape and persistence in LC patients. Furthermore, our findings suggest an inverse association between CMV p65 IgG and fatigue severity in LC.