Immunological Density Shapes Recovery Trajectories in Long COVID

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Authors: Jing Wang, Tong Zhang, Xing Niu, Jie Shen, Yiming Luo, Qiaomin Xie, Amar Sra, Zorina S. Galis, Jeremy C. Weiss
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Abstract

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 $\geq 12$), 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 ($r=0.0521$, $P=1.26\times10^{-59}$), whereas cumulative vaccination showed an inverse association with severity ($r=-0.0434$, $P=5.95\times10^{-42}$). 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.

Fields of Study & Subjects

Long-Term Effects of COVID-19 SARS-CoV-2 and COVID-19 Research COVID-19 Clinical Research Studies

Publication details

Journal / source
arXiv (Cornell University)
Publication date
9 January 2026
Document type
Preprint