Major Depressive Disorder in Long COVID and Exposure to Pro‐Inflammatory Cytokines During Infection by SARS‐CoV‐2

Objective Major Depressive Disorder (MDD) is common in long COVID syndrome; however, the neurobiological mechanisms are unclear. An immune activation response has been associated with COVID‐19 severity as well as in MDD. We hypothesize that high levels of pro‐inflammatory cytokines during SARS‐CoV‐2...

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Main Authors: Hernan F. Guillen‐Burgos, Juan F. Gálvez‐Flórez, Sergio Moreno‐López, Sabrina Wong, Angela T. H. Kwan, Mariana Ramirez‐Posada, Juan‐Manuel Anaya, Roger S. McIntyre
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Psychiatric Research and Clinical Practice
Online Access:https://doi.org/10.1176/appi.prcp.20240112
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author Hernan F. Guillen‐Burgos
Juan F. Gálvez‐Flórez
Sergio Moreno‐López
Sabrina Wong
Angela T. H. Kwan
Mariana Ramirez‐Posada
Juan‐Manuel Anaya
Roger S. McIntyre
author_facet Hernan F. Guillen‐Burgos
Juan F. Gálvez‐Flórez
Sergio Moreno‐López
Sabrina Wong
Angela T. H. Kwan
Mariana Ramirez‐Posada
Juan‐Manuel Anaya
Roger S. McIntyre
author_sort Hernan F. Guillen‐Burgos
collection DOAJ
description Objective Major Depressive Disorder (MDD) is common in long COVID syndrome; however, the neurobiological mechanisms are unclear. An immune activation response has been associated with COVID‐19 severity as well as in MDD. We hypothesize that high levels of pro‐inflammatory cytokines during SARS‐CoV‐2 infection may be associated with new‐onset MDD and severe outcomes such as treatment‐resistant depression (TRD) and risk of suicide ideation and behavior (SI/SB). Methods A case‐control nested to a cohort study was carried out on a total of 678 COVID‐19 survivors (MDD = 184 vs. non‐MDD = 494). A pro‐inflammatory panel of serum levels of cytokines (IL‐1β, IL‐4, IL‐6, IL‐8, IL‐13, IL‐17α, TNF‐α) was evaluated during COVID‐19 hospitalization and severe outcomes such as TRD and SI/SB were assessed in individuals with new onset of MDD after hospital discharge compared to non‐MDD COVID‐19 survivors. Results High levels of pro‐inflammatory cytokines during SARS‐CoV‐2 infection were identified in MDD participants compared to non‐MDD subgroups during long COVID. These differences were sustained also for TRD and SI/SB severity outcomes. There is a mild association of high levels of pro‐inflammatory cytokines and MDD, TRD, and SI/SB. Conclusion High levels of pro‐inflammatory cytokines during severe or critical COVID‐19 exposure may explain long COVID associated MDD and thus severe outcomes such as TRD and SI/SB. Relevance to clinical practice Identifying elevated pro‐inflammatory cytokines during COVID‐19 as a risk factor for MDD and severe outcomes underscores the need for early screening and targeted treatments in long COVID. Monitoring cytokine levels may help clinicians predict and manage TRD and SI/SB in this population, improving long‐term psychiatric outcomes.
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spelling doaj-art-d22c9ebab738431c95d8899cc5b8a2a62025-08-20T03:21:43ZengWileyPsychiatric Research and Clinical Practice2575-56092025-06-017213914910.1176/appi.prcp.20240112Major Depressive Disorder in Long COVID and Exposure to Pro‐Inflammatory Cytokines During Infection by SARS‐CoV‐2Hernan F. Guillen‐Burgos0Juan F. Gálvez‐Flórez1Sergio Moreno‐López2Sabrina Wong3Angela T. H. Kwan4Mariana Ramirez‐Posada5Juan‐Manuel Anaya6Roger S. McIntyre7Centro de Investigaciones en Ciencias de la Vida Universidad Simón Bolívar Center for Clinical and Translational Research Barranquilla ColombiaCentro de Investigaciones en Ciencias de la Vida Universidad Simón Bolívar Center for Clinical and Translational Research Barranquilla ColombiaFaculty of Medicine Universidad de Los Andes Bogotá ColombiaMood Disorders Psychopharmacology Unit University Health Network Toronto ON CanadaMood Disorders Psychopharmacology Unit University Health Network Toronto ON CanadaCentro de Investigaciones en Ciencias de la Vida Universidad Simón Bolívar Center for Clinical and Translational Research Barranquilla ColombiaCoosalud IPS Research and Innovation Center, and Universidad de la Costa Barranquilla ColombiaDepartment of Psychiatry and Pharmacology University of Toronto Toronto ON CanadaObjective Major Depressive Disorder (MDD) is common in long COVID syndrome; however, the neurobiological mechanisms are unclear. An immune activation response has been associated with COVID‐19 severity as well as in MDD. We hypothesize that high levels of pro‐inflammatory cytokines during SARS‐CoV‐2 infection may be associated with new‐onset MDD and severe outcomes such as treatment‐resistant depression (TRD) and risk of suicide ideation and behavior (SI/SB). Methods A case‐control nested to a cohort study was carried out on a total of 678 COVID‐19 survivors (MDD = 184 vs. non‐MDD = 494). A pro‐inflammatory panel of serum levels of cytokines (IL‐1β, IL‐4, IL‐6, IL‐8, IL‐13, IL‐17α, TNF‐α) was evaluated during COVID‐19 hospitalization and severe outcomes such as TRD and SI/SB were assessed in individuals with new onset of MDD after hospital discharge compared to non‐MDD COVID‐19 survivors. Results High levels of pro‐inflammatory cytokines during SARS‐CoV‐2 infection were identified in MDD participants compared to non‐MDD subgroups during long COVID. These differences were sustained also for TRD and SI/SB severity outcomes. There is a mild association of high levels of pro‐inflammatory cytokines and MDD, TRD, and SI/SB. Conclusion High levels of pro‐inflammatory cytokines during severe or critical COVID‐19 exposure may explain long COVID associated MDD and thus severe outcomes such as TRD and SI/SB. Relevance to clinical practice Identifying elevated pro‐inflammatory cytokines during COVID‐19 as a risk factor for MDD and severe outcomes underscores the need for early screening and targeted treatments in long COVID. Monitoring cytokine levels may help clinicians predict and manage TRD and SI/SB in this population, improving long‐term psychiatric outcomes.https://doi.org/10.1176/appi.prcp.20240112
spellingShingle Hernan F. Guillen‐Burgos
Juan F. Gálvez‐Flórez
Sergio Moreno‐López
Sabrina Wong
Angela T. H. Kwan
Mariana Ramirez‐Posada
Juan‐Manuel Anaya
Roger S. McIntyre
Major Depressive Disorder in Long COVID and Exposure to Pro‐Inflammatory Cytokines During Infection by SARS‐CoV‐2
Psychiatric Research and Clinical Practice
title Major Depressive Disorder in Long COVID and Exposure to Pro‐Inflammatory Cytokines During Infection by SARS‐CoV‐2
title_full Major Depressive Disorder in Long COVID and Exposure to Pro‐Inflammatory Cytokines During Infection by SARS‐CoV‐2
title_fullStr Major Depressive Disorder in Long COVID and Exposure to Pro‐Inflammatory Cytokines During Infection by SARS‐CoV‐2
title_full_unstemmed Major Depressive Disorder in Long COVID and Exposure to Pro‐Inflammatory Cytokines During Infection by SARS‐CoV‐2
title_short Major Depressive Disorder in Long COVID and Exposure to Pro‐Inflammatory Cytokines During Infection by SARS‐CoV‐2
title_sort major depressive disorder in long covid and exposure to pro inflammatory cytokines during infection by sars cov 2
url https://doi.org/10.1176/appi.prcp.20240112
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