European archives of psychiatry and clinical neuroscienceMay 8, 2023

Physical and mental symptoms, inflammation, and treatment response in first-time versus repeated depression after COVID-19

Updated Feb 20, 2026

Abstract

At least 30% of patients post-COVID-19 experience depressive symptoms.

Psychiatric symptoms, including new and recurring depressive episodes, have been reported in post-COVID-19 patients.
Among 116 evaluated patients, 38.8% had first-onset major depressive episodes (MDE) and 61.2% had recurrent MDE.
Treatment with antidepressants led to significant reductions in depression and anxiety symptoms, as well as improvements in physical and cognitive symptoms.
Inflammatory levels decreased significantly during treatment in both first-onset and recurrent MDE groups.
Recurrent MDE was associated with a more severe course of symptoms and persistently higher inflammation compared to first-onset episodes.
A continued inflammatory status may hinder treatment effectiveness for physical and cognitive symptoms in recurrent depression.

Simplified

Psychiatric symptoms have been frequently reported in patients affected by COVID-19, both as new occurring and recurrences of pre-existing diseases. Depressive symptoms are estimated to affect at least 30% of patients following infection, with specific physical and cognitive features and relevant immune-inflammatory alterations. This study aimed to retrospectively characterize post-COVID-19 first-onset and recurrent major depressive episodes (MDE) and to evaluate the effects of antidepressants on physical and cognitive correlates of depression, in addition to mood, anxiety, and underlying inflammatory status. We evaluated 116 patients (44.8% males, 51.1 ± 17 years) with post-COVID-19 first-onset (38.8%) and recurrent (61.2%) MDE at baseline and after one- and three-month treatment with antidepressants (31% SSRIs, 25.9% SNRIs, 43.1% others). We assessed sociodemographic and clinical features and psychopathological dimensions through: Hamilton Depression and Anxiety Rating Scales; Short Form-36 Health Survey Questionnaire; Perceived Deficits Questionnaire-Depression 5-items. The systemic immune-inflammatory index was calculated to measure inflammation levels. Alongside the reduction of depression and anxiety (p < 0.001), physical and cognitive symptoms improved (p < 0.001) and inflammatory levels decreased (p < 0.001) throughout treatment in both groups. Post-COVID-19 recurrent MDE showed a significantly more severe course of physical and cognitive symptoms and persistently higher levels of inflammation than first-onset episodes. Antidepressants proved to be effective in both post-COVID-19 first-onset and recurrent MDE. However, a sustained inflammatory status might blunt treatment response in patients with recurrent depression in terms of physical correlates and cognition. Therefore, personalized approaches, possibly involving combinations with anti-inflammatory compounds, could promote better outcomes in this clinical population.

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