Serum Level of Anti-Nucleocapsid, but Not Anti-Spike Antibody, Is Associated with Improvement of Long COVID Symptoms.

BACKGROUND: Long COVID is a condition characterized by long-term sequelae persisting after the typical convalescence period of COVID-19. Previous reports have suggested the role of an unsatisfactory immune response and impaired viral clearance in the pathogenesis of long COVID syndrome. We focused on potential associations between post-vaccination changes of antibody titers and the severity of long COVID symptoms and factors influencing the state of remission observed in patients with long COVID after vaccination. METHODS: The severity of long COVID symptoms and serum anti-SARS-CoV-2 spike (S-Ig) and nucleocapsid (NC-Ig) levels were assessed in 107 post-COVID subjects at two time points: at baseline, and 17-24 weeks later. Besides, vaccination status was also assessed. Symptoms were evaluated based on the Chalder fatigue scale (CFQ-11) and visual analogue scale (VAS). RESULTS: Serum level of S-Ig and NC-Ig at baseline were significantly higher in the patients with non-severe fatigue than those with severe fatigue, and this difference remained significant at follow-up in the case of NC-Ig. NC-Ig level above median was as an independent predictor for complete remission at follow-up. The difference in NC-Ig levels in subgroup analyses (severe fatigue vs. non-severe fatigue; complete remission vs. incomplete remission or progression) was found to be significant only in patients who received vaccination. CONCLUSIONS: The immune response against the SARS-CoV-2 nucleocapsid may play a more important role than the spike in the course of long-term COVID syndrome.

Severe Fatigue and Memory Impairment Are Associated with Lower Serum Level of Anti-SARS-CoV-2 Antibodies in Patients with Post-COVID Symptoms.

BACKGROUND: Post-COVID manifestation is defined as persistent symptoms or long-term complications beyond 4 weeks from disease onset. Fatigue and memory impairment are common post-COVID symptoms. We aimed to explore associations between the timeline and severity of post-COVID fatigue and anti-SARS-CoV-2 antibodies. METHODS: Fatigue and memory impairment were assessed in a total of 101 post-COVID subjects using the Chalder fatigue scale (CFQ-11) and a visual analogue scale. Using the bimodal scoring system generated from CFQ-11, a score ≥4 was defined as severe fatigue. Serum anti-SARS-CoV-2 spike (anti-S-Ig) and nucleocapsid (anti-NC-Ig) antibodies were examined at two time points: 4-12 weeks after onset of symptoms, and beyond 12 weeks. RESULTS: The serum level of anti-S-Ig was significantly higher in patients with non-severe fatigue compared to those with severe fatigue at 4-12 weeks (p = 0.006) and beyond 12 weeks (p = 0.016). The serum level of anti-NC-Ig remained high in patients with non-severe fatigue at both time points. In contrast, anti-NC-Ig decreased significantly in severe fatigue cases regardless of the elapsed time (4-12 weeks: p = 0.024; beyond 12 weeks: p = 0.005). The incidence of memory impairment was significantly correlated with lower anti-S-Ig levels (-0.359, p < 0.001). CONCLUSION: The systemic immune response reflected by antibodies to SARS-CoV-2 is strongly correlated with the severity of post-COVID fatigue.