Palladini Mariagrazia, Mazza Mario Gennaro, Bravi Beatrice, Bessi Margherita, Lorenzi Maria Cristina, Spadini Sara, De Lorenzo Rebecca, Rovere-Querini Patrizia, Furlan Roberto, Benedetti Francesco
Vita-Salute San Raffaele University, 20132 Milano, Italy.
Psychiatry and Clinical Psychobiology Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milano, Italy.
Biomolecules. 2025 Apr 18;15(4):600. doi: 10.3390/biom15040600.
Post-COVID syndrome has unveiled intricate connections between inflammation, depressive psychopathology, and cognitive impairment. This study investigates these relationships in 101 COVID-19 survivors, focusing on sex-specific variations. Utilizing path modelling techniques, we analyzed the interplay of a one-month 48-biomarker inflammatory panel, with three-months of depressive symptoms and cognitive performance. The findings indicate that cognitive impairment is influenced by both inflammation and depression in the overall cohort. However, prominent sex-specific differences emerged. In females, a lingering imbalance between pro- and anti-inflammatory responses-likely reflecting the long-lasting immune alterations triggered by COVID-19-significantly affects cognitive functioning and shows a marginal, though not statistically significant, association with depressive symptoms. This suggests that a mixed inflammatory profile may contribute to these outcomes. Conversely, in males, inflammation was inversely associated with depression severity, with protective effects from regulatory mediators (IL-2, IL-4, IL-6, IL-15, LIF, TNF-α, β-NGF) against depression. In males, cognitive impairment appeared to be driven mainly by depressive symptoms, with minimal influence from inflammatory markers. These results highlight distinct sex-specific pathways in immune and inflammatory responses post-COVID-19, potentially shaped by endocrine mechanisms. The findings suggest that persistent inflammation may foster long-term neuropsychiatric sequelae, possibly through its effects on the brain, and underscore the need for sex-tailored therapeutic strategies to address the lasting impact of COVID-19.
新冠后综合征揭示了炎症、抑郁性精神病理学和认知障碍之间的复杂联系。本研究对101名新冠病毒感染者康复者进行调查，重点关注性别差异。利用路径建模技术，我们分析了为期一个月的48种生物标志物炎症指标与三个月的抑郁症状和认知表现之间的相互作用。研究结果表明，在整个队列中，认知障碍受到炎症和抑郁的影响。然而，明显的性别差异出现了。在女性中，促炎和抗炎反应之间持续存在的失衡——可能反映了新冠病毒引发的长期免疫改变——显著影响认知功能，并与抑郁症状存在微弱但无统计学意义的关联。这表明混合性炎症特征可能导致这些结果。相反，在男性中，炎症与抑郁严重程度呈负相关，调节介质（白细胞介素-2、白细胞介素-4、白细胞介素-6、白细胞介素-15、白血病抑制因子、肿瘤坏死因子-α、β-神经生长因子）对抑郁有保护作用。在男性中，认知障碍似乎主要由抑郁症状驱动，炎症标志物的影响最小。这些结果突出了新冠病毒感染康复后免疫和炎症反应中明显的性别特异性途径，可能由内分泌机制塑造。研究结果表明，持续的炎症可能通过对大脑的影响促进长期神经精神后遗症，并强调需要针对性别的治疗策略来应对新冠病毒的持久影响。
