Impact of Circulating Anti-Spike Protein Antibody Levels on Multi-Organ Long COVID Symptoms

Patients with long COVID syndrome present with various symptoms affecting multiple organs. Vaccination before or after SARS-CoV-2 infection appears to reduce the incidence of long COVID or at least limit symptom deterioration. However, the impact of vaccination on the severity and extent of multi-organ long COVID symptoms and the relationship between the circulating anti-spike protein antibody levels and the severity and extent of multi-organ symptoms are unclear. This prospective cohort study included 198 patients with previous PCR-verified SARS-CoV-2 infection who met the criteria for long COVID syndrome. Patients were divided into vaccinated (n = 138, 69.7%) or unvaccinated (n = 60, 30.3%) groups. Anti-spike protein antibody levels were determined at initial clinical presentation and compared between the groups. Long COVID symptoms were quantified on the basis of the number of affected organs: Class I (mild) with symptoms in three organs, Class II (moderate) with symptoms in four to five organs, and Class III (severe) with symptoms in six or more organ systems. Associations between time to infection and vaccination with anti-spike protein antibody levels were assessed. The anti-spike protein antibody levels were 1925 ± 938 vs. 481 ± 768 BAU/mL (p < 0.001) in the vaccinated vs. unvaccinated patients. The circulating anti-spike antibody cutoff of 665.5 BAU/mL allowed us to differentiate the vaccinated from the unvaccinated patients. Vaccinated patients had fewer class II and class III multi-organ symptoms (Class II 39.9% vs. 45.0%; Class III 10.1% vs. 23.3%, p-value 0.014). Anti-spike antibody level correlated negatively with multi-organ symptom classes (p = 0.016; 95% CI -1.229 to -0.126). Anti-spike antibody levels in unvaccinated patients declined markedly with time, in contrast to the persistence of high anti-spike antibody levels in the vaccinated patients. Multi-organ symptoms were lower in vaccinated long-COVID patients, especially in those with higher anti-spike antibody levels (≥665.5 BAU/mL). Classifying the symptoms on the basis of the number of affected organs enables a more objective symptom quantification.