Sex-Specific Inflammatory Profiles Affect Neuropsychiatric Issues in COVID-19 Survivors
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 interpla...
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MDPI AG
2025-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/15/4/600 |
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| author | Mariagrazia Palladini Mario Gennaro Mazza Beatrice Bravi Margherita Bessi Maria Cristina Lorenzi Sara Spadini Rebecca De Lorenzo Patrizia Rovere-Querini Roberto Furlan Francesco Benedetti |
| author_facet | Mariagrazia Palladini Mario Gennaro Mazza Beatrice Bravi Margherita Bessi Maria Cristina Lorenzi Sara Spadini Rebecca De Lorenzo Patrizia Rovere-Querini Roberto Furlan Francesco Benedetti |
| author_sort | Mariagrazia Palladini |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e4e902e080a8437d8a59c4b9758a3875 |
| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-e4e902e080a8437d8a59c4b9758a38752025-08-20T02:17:14ZengMDPI AGBiomolecules2218-273X2025-04-0115460010.3390/biom15040600Sex-Specific Inflammatory Profiles Affect Neuropsychiatric Issues in COVID-19 SurvivorsMariagrazia Palladini0Mario Gennaro Mazza1Beatrice Bravi2Margherita Bessi3Maria Cristina Lorenzi4Sara Spadini5Rebecca De Lorenzo6Patrizia Rovere-Querini7Roberto Furlan8Francesco Benedetti9Vita-Salute San Raffaele University, 20132 Milano, ItalyPsychiatry and Clinical Psychobiology Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milano, ItalyPsychiatry and Clinical Psychobiology Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milano, ItalyPsychiatry and Clinical Psychobiology Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milano, ItalyPsychiatry and Clinical Psychobiology Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milano, ItalyPsychiatry and Clinical Psychobiology Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milano, ItalyVita-Salute San Raffaele University, 20132 Milano, ItalyVita-Salute San Raffaele University, 20132 Milano, ItalyVita-Salute San Raffaele University, 20132 Milano, ItalyVita-Salute San Raffaele University, 20132 Milano, ItalyPost-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.https://www.mdpi.com/2218-273X/15/4/600COVID-19inflammationdepressioncognition |
| spellingShingle | Mariagrazia Palladini Mario Gennaro Mazza Beatrice Bravi Margherita Bessi Maria Cristina Lorenzi Sara Spadini Rebecca De Lorenzo Patrizia Rovere-Querini Roberto Furlan Francesco Benedetti Sex-Specific Inflammatory Profiles Affect Neuropsychiatric Issues in COVID-19 Survivors Biomolecules COVID-19 inflammation depression cognition |
| title | Sex-Specific Inflammatory Profiles Affect Neuropsychiatric Issues in COVID-19 Survivors |
| title_full | Sex-Specific Inflammatory Profiles Affect Neuropsychiatric Issues in COVID-19 Survivors |
| title_fullStr | Sex-Specific Inflammatory Profiles Affect Neuropsychiatric Issues in COVID-19 Survivors |
| title_full_unstemmed | Sex-Specific Inflammatory Profiles Affect Neuropsychiatric Issues in COVID-19 Survivors |
| title_short | Sex-Specific Inflammatory Profiles Affect Neuropsychiatric Issues in COVID-19 Survivors |
| title_sort | sex specific inflammatory profiles affect neuropsychiatric issues in covid 19 survivors |
| topic | COVID-19 inflammation depression cognition |
| url | https://www.mdpi.com/2218-273X/15/4/600 |
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