Immunological Density Shapes Recovery Trajectories in Long COVID

Post-acute sequelae of SARS-CoV-2 infection (Long COVID) frequently persists for months, yet drivers of clinical remission remain incompletely defined. Here we analyzed 97,564 longitudinal PASC assessments from 13,511 participants with linked vaccination histories to disentangle passive temporal progression from vaccine-associated change. Using a clinically validated threshold (PASC ≥ 12), trajectories separated into three phenotypes: Protected (persistently sub-threshold), Refractory (persistently symptomatic), and Responders (transitioning from symptomatic to recovered). Across the full cohort, symptom severity increased modestly with elapsed time (r=0.0521, P=1.26×10-59), whereas cumulative vaccination showed an inverse association with severity (r=-0.0434, P=5.95×10-42). In summary, baseline Long COVID severity appears clinically deterministic. In the absence of intervention, symptoms typically persist without spontaneous resolution. Recovery is primarily associated with repeated immunization.