Divergent Long-Term Recovery After Long COVID in Tobacco Use Disorder and Healthy Controls: A Longitudinal Study

Although tobacco use disorder (TUD) and long COVID (LC) have been associated to neuropsychiatric disturbances, it remains unclear how tobacco dependence affects the recovery of clinical, cognitive, and biological processes over time.

This study compared individuals with tobacco use disorder and healthy controls using longitudinal assessments from pre-infection baseline through two post-COVID follow-ups over 12 months. Comprehensive assessments covered clinical, neuropsychiatric, and cognitive functioning, tobacco dependence and exposure, and peripheral biomarkers reflecting neuroendocrine regulation, inflammation, neuroplasticity-related processes, and nicotine metabolism relevant to post-COVID recovery.

Both groups exhibited marked clinical, cognitive, and biological alterations following LC; however, recovery trajectories diverged over time. Healthy controls showed clear improvement by 12 months, whereas individuals with TUD showed persistent impairment across clinical and cognitive functioning. Cognitive performance recovered in controls but remained reduced in the TUD group. Biological trajectories paralleled clinical recovery patterns. Dimensional analyses identified two latent components reflecting neuropsychiatric and inflammatory-neurobiological processes. Within the TUD group, two recovery-related phenotypes emerged: a persistently impaired subgroup and an adaptive subgroup showing partial recovery.

Tobacco use disorder is associated with impaired and incomplete clinical and biological recovery following long COVID, beyond smoking exposure alone. These findings emphasize the need for post-COVID care models that integrate tobacco dependence with recovery-related clinical and biological processes, supporting sustained recovery and cessation outcomes.