Post-COVID Trajectory of Pentraxin 3 Plasma Levels Over 6 Months and Their Association with the Risk of Developing Post-Acute Depression and Anxiety.

Publisher: Adis, Springer International Country of Publication: New Zealand NLM ID: 9431220 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1179-1934 (Electronic) Linking ISSN: 11727047 NLM ISO Abbreviation: CNS Drugs Subsets: MEDLINE

Publication: Auckland : Adis, Springer International
Original Publication: Mairangi Bay, Auckland, N.Z. ; Philadelphia : Adis International, c1994-

Anxiety*/blood ; Anxiety*/diagnosis ; Biomarkers*/blood ; C-Reactive Protein*/metabolism ; C-Reactive Protein*/analysis ; COVID-19*/blood ; COVID-19*/complications ; Post-Acute COVID-19 Syndrome*/blood ; Post-Acute COVID-19 Syndrome*/diagnosis ; Serum Amyloid P-Component*/analysis ; Serum Amyloid P-Component*/metabolism; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Depression/blood ; Follow-Up Studies ; Longitudinal Studies

Background and Objectives: Clinical manifestations of coronavirus disease 2019 (COVID-19) often persist after acute disease resolution. Underlying molecular mechanisms are unclear. The objective of this original article was to longitudinally measure plasma levels of markers of the innate immune response to investigate whether they associate with and predict post-COVID symptomatology.
Methods: Adult patients with previous severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first pandemic wave who underwent the 6-month multidisciplinary follow-up were included. Plasma levels of pentraxin 3 (PTX3), the complement components C3a and C5a, and chitinase-3 like-protein-1 (CHI3L1) were measured at hospital admission during acute disease (baseline) and at 1 and 6 months after hospital discharge. Associations with post-COVID-19 sequelae at 6 months were investigated using descriptive statistic and multiple regression models.
Results: Ninety-four COVID-19 patients were included. Baseline PTX3, C5a, C3a, and CHI3L1 did not predict post-COVID-19 sequelae. The extent of the reduction of PTX3 over time (delta PTX3) was associated with lower depressive and anxiety symptoms at 6 months (both p < 0.05). When entering sex, age, need for intensive care unit or non-invasive ventilation during hospital stay, psychiatric history, and baseline PTX3 as nuisance covariates into a generalized linear model (GLM), the difference between baseline and 6-month PTX3 levels (delta PTX3) significantly predicted depression (χ ² = 4.66, p = 0.031) and anxiety (χ ² = 4.68, p = 0.031) at 6 months. No differences in PTX3 levels or PTX3 delta were found in patients with or without persistent or new-onset other COVID-19 symptoms or signs at 6 months. Plasma levels of C3a, C5a, and CHI3L1 did not correlate with PTX3 levels at either time point and failed to associate with residual or de novo respiratory or systemic clinical manifestations of the disease at 6 months.
Conclusions: A lower reduction of plasma PTX3 after acute COVID-19 associates with the presence of depression and anxiety, suggesting an involvement of inflammation in post-COVID-19 psychopathology and a potential role of PTX3 as a biomarker.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Carfì A, Bernabei R, Landi F. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324(6):603–5. https://doi.org/10.1001/jama.2020.12603 . (PMID: 10.1001/jama.2020.12603326441297349096)
Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601–15. https://doi.org/10.1038/s41591-021-01283-z . (PMID: 10.1038/s41591-021-01283-z337539378893149)
Huang S, Zhou Z, Yang D, Zhao W, Zeng M, Xie X, et al. Persistent white matter changes in recovered COVID-19 patients at the 1-year follow-up. Brain. 2022;145(5):1830–8. (PMID: 10.1093/brain/awab43534918020)
Venkatesan P. NICE guideline on long COVID. Lancet Respir Med. 2021;9(2):129. https://doi.org/10.1016/S2213-2600(21)00031-X . (PMID: 10.1016/S2213-2600(21)00031-X334531627832375)
Nasserie T, Hittle M, Goodman SN. Assessment of the frequency and variety of persistent symptoms among patients With COVID-19: a systematic review. JAMA Netw Open. 2021;4(5): e2111417. https://doi.org/10.1001/jamanetworkopen.2021.11417 . (PMID: 10.1001/jamanetworkopen.2021.11417340377318155823)
Poletti S, Mazza MG, Calesella F, Vai B, Lorenzi C, Manfredi E, et al. Circulating inflammatory markers impact cognitive functions in bipolar depression. J Psychiatr Res. 2021;140:110–6. https://doi.org/10.1016/j.jpsychires.2021.05.071 .
Benedetti F, Poletti S, Vai B, Mazza MG, Lorenzi C, Brioschi S, et al. Higher baseline interleukin-1beta and TNF-alpha hamper antidepressant response in major depressive disorder. Eur Neuropsychopharmacol. 2021;42:35–44. https://doi.org/10.1016/j.euroneuro.2020.11.009 .
Mazza MG, Palladini M, Villa G, De Lorenzo R, Rovere Querini P, Benedetti F. Prevalence, trajectory over time, and risk factor of post-COVID-19 fatigue. J Psychiatr Res. 2022;155:112–9. https://doi.org/10.1016/j.jpsychires.2022.08.008 .
Manning K, Zvolensky MJ, Garey L, Long LJ, Gallagher MW. The explanatory role of fatigue severity in the relation between COVID-19 perceived stress and depression, anxiety, and panic severity. Cogn Behav Therapy. 2021:1-11. https://doi.org/10.1080/16506073.2021.1874503 .
Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun. 2020;87:34-9. https://doi.org/10.1016/j.bbi.2020.04.027 .
Passavanti M, Argentieri A, Barbieri DM, Lou B, Wijayaratna K, Foroutan Mirhosseini AS, et al. The psychological impact of COVID-19 and restrictive measures in the world. J Affect Disord. 2021;15(283):36–51. https://doi.org/10.1016/j.jad.2021.01.020 . (PMID: 10.1016/j.jad.2021.01.020)
Kumar R, Aktay-Cetin O, Craddock V, Morales-Cano D, Kosanovic D, Cogolludo A, et al. Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: Multilayered cross-talks in the setting of coinfections and comorbidities. PLoS Pathog. 2023;19(1): e1011063. https://doi.org/10.1371/journal.ppat.1011063 . (PMID: 10.1371/journal.ppat.1011063366340489836319)
Maamar M, Artime A, Pariente E, Fierro P, Ruiz Y, Gutierrez S, et al. Post-COVID-19 syndrome, low-grade inflammation and inflammatory markers: a cross-sectional study. Curr Med Res Opin. 2022;38(6):901-9. https://doi.org/10.1080/03007995.2022.2042991 .
Saini G, Aneja R. Cancer as a prospective sequela of long COVID-19. BioEssays. 2021;43(6): e2000331. https://doi.org/10.1002/bies.202000331 . (PMID: 10.1002/bies.20200033133914346)
Mazza MG, Palladini M, Poletti S, Benedetti F. Post-COVID-19 depressive symptoms: epidemiology, pathophysiology, and pharmacological treatment. CNS Drugs. 2022;36(7):681–702. https://doi.org/10.1007/s40263-022-00931-3 . (PMID: 10.1007/s40263-022-00931-3357275349210800)
Porte R, Davoudian S, Asgari F, Parente R, Mantovani A, Garlanda C, et al. The long pentraxin PTX3 as a humoral innate immunity functional player and biomarker of infections and sepsis. Front Immunol. 2019;10:794. https://doi.org/10.3389/fimmu.2019.00794 .
Mantovani A, Garlanda C. Humoral innate immunity and acute-phase proteins. N Engl J Med. 2023;388(5):439–52. https://doi.org/10.1056/NEJMra2206346 . (PMID: 10.1056/NEJMra2206346367243309912245)
Hansen CB, Sandholdt H, Moller MEE, Perez-Alos L, Pedersen L, Bastrup Israelsen S, et al. Prediction of respiratory failure and mortality in COVID-19 patients using long pentraxin PTX3. J Innate Immun. 2022;14(5):493–501. https://doi.org/10.1159/000521612 . (PMID: 10.1159/000521612350665009059012)
Lapadula G, Leone R, Bernasconi DP, Biondi A, Rossi E, D'Angio M, et al. Long pentraxin 3 (PTX3) levels predict death, intubation and thrombotic events among hospitalized patients with COVID-19. Front Immunol. 2022;13:933960; https://doi.org/10.3389/fimmu.2022.933960 .
Stravalaci M, Pagani I, Paraboschi EM, Pedotti M, Doni A, Scavello F, et al. Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules. Nat Immunol. 2022;23(2):275–86. https://doi.org/10.1038/s41590-021-01114-w . (PMID: 10.1038/s41590-021-01114-w35102342)
Brunetta E, Folci M, Bottazzi B, De Santis M, Gritti G, Protti A, et al. Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19. Nat Immunol. 2021;22(1):19–24. https://doi.org/10.1038/s41590-020-00832-x . (PMID: 10.1038/s41590-020-00832-x33208929)
Phetsouphanh C, Darley DR, Wilson DB, Howe A, Munier CML, Patel SK, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol. 2022;23(2):210–6. https://doi.org/10.1038/s41590-021-01113-x . (PMID: 10.1038/s41590-021-01113-x35027728)
De Lorenzo R, Conte C, Lanzani C, Benedetti F, Roveri L, Mazza MG, et al. Residual clinical damage after COVID-19: a retrospective and prospective observational cohort study. PLoS One. 2020;15(10): e0239570. https://doi.org/10.1371/journal.pone.0239570 . (PMID: 10.1371/journal.pone.0239570330529207556454)
Farina N, Ramirez GA, De Lorenzo R, Di Filippo L, Conte C, Ciceri F, et al. COVID-19: Pharmacology and kinetics of viral clearance. Pharmacol Res. 2020;161:105114; https://doi.org/10.1016/j.phrs.2020.105114 .
Rovere Querini P, De Lorenzo R, Conte C, Brioni E, Lanzani C, Yacoub MR, et al. Post-COVID-19 follow-up clinic: depicting chronicity of a new disease. Acta Biomed. 2020;91(9-S):22-8. https://doi.org/10.23750/abm.v91i9-S.10146 .
Rovere-Querini P, Tresoldi C, Conte C, Ruggeri A, Ghezzi S, R DEL, et al. Biobanking for COVID-19 research. Panminerva Med. 2022;64(2):244-52. https://doi.org/10.23736/S0031-0808.20.04168-3.
De Lorenzo R, Magnaghi C, Cinel E, Vitali G, Martinenghi S, Mazza MG, et al. A Nomogram-based model to predict respiratory dysfunction at 6 months in non-critical COVID-19 survivors. Front Med (Lausanne). 2022;9:781410. https://doi.org/10.3389/fmed.2022.781410 .
R Del, Cinel E, Cilla M, Compagnone N, Ferrante M, Falbo E, et al. Physical and psychological sequelae at three months after acute illness in COVID-19 survivors. Panminerva Med. 2021. https://doi.org/10.23736/S0031-0808.21.04399-8 .
First MB. Diagnostic and statistical manual of mental disorders, 5th edition, and clinical utility. J Nerv Ment Dis. 2013;201(9):727-9. https://doi.org/10.1097/NMD.0b013e3182a2168a .
Zung WW. A self-rating depression scale. Arch Gen Psychiatry. 1965;12(1):63–70. https://doi.org/10.1001/archpsyc.1965.01720310065008 . (PMID: 10.1001/archpsyc.1965.0172031006500814221692)
Beck AT, Steer RA. Internal consistencies of the original and revised Beck Depression Inventory. J Clin Psychol. 1984;40(6):1365–7. https://doi.org/10.1002/1097-4679(198411)40:6%3c1365::aid-jclp2270400615%3e3.0.co;2-d . (PMID: 10.1002/1097-4679(198411)40:6<1365::aid-jclp2270400615>3.0.co;2-d6511949)
Creamer M, Bell R, Failla S. Psychometric properties of the impact of event scale—revised. Behav Res Ther. 2003;41(12):1489–96. https://doi.org/10.1016/j.brat.2003.07.010 . (PMID: 10.1016/j.brat.2003.07.01014705607)
Vigneau F, Cormier S. The factor structure of the State-Trait Anxiety Inventory: an alternative view. J Pers Assess. 2008;90(3):280–5. https://doi.org/10.1080/00223890701885027 . (PMID: 10.1080/0022389070188502718444124)
Lore NI, De Lorenzo R, Rancoita PMV, Cugnata F, Agresti A, Benedetti F, et al. CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study. Mol Med. 2021;27(1):129. https://doi.org/10.1186/s10020-021-00390-4 . (PMID: 10.1186/s10020-021-00390-4346632078521494)
McCullagh P, Nelder JA. Generalized linear models. 2nd ed. New York: Chapman & Hall; 1989. (PMID: 10.1007/978-1-4899-3242-6)
Agresti A. An introduction to categorical data analysis. New York: Wiley; 1996.
Dobson AJ. An introduction to generalized linear models. New York: Chapman & Hall; 1990. (PMID: 10.1007/978-1-4899-7252-1)
Magrini E, Mantovani A, Garlanda C. The dual complexity of PTX3 in health and disease: a balancing act? Trends Mol Med. 2016;22(6):497–510. https://doi.org/10.1016/j.molmed.2016.04.007 . (PMID: 10.1016/j.molmed.2016.04.007271797435414840)
Staubli SM, Schafer J, Rosenthal R, Zeindler J, Oertli D, Nebiker CA. The role of CRP and Pentraxin 3 in the prediction of systemic inflammatory response syndrome and death in acute pancreatitis. Sci Rep. 2019;9(1):18340. https://doi.org/10.1038/s41598-019-54910-8 . (PMID: 10.1038/s41598-019-54910-8317980026893028)
Carvelli J, Demaria O, Vely F, Batista L, Chouaki Benmansour N, Fares J, et al. Association of COVID-19 inflammation with activation of the C5a–C5aR1 axis. Nature. 2020;588(7836):146–50. https://doi.org/10.1038/s41586-020-2600-6 . (PMID: 10.1038/s41586-020-2600-6327268007116884)
Rajkovic I, Denes A, Allan SM, Pinteaux E. Emerging roles of the acute phase protein pentraxin-3 during central nervous system disorders. J Neuroimmunol. 2016;15(292):27–33. https://doi.org/10.1016/j.jneuroim.2015.12.007 . (PMID: 10.1016/j.jneuroim.2015.12.007)
Bourgeois MA, Denslow ND, Seino KS, Barber DS, Long MT. Gene expression analysis in the thalamus and cerebrum of horses experimentally infected with West Nile virus. PLoS One. 2011;6(10): e24371. https://doi.org/10.1371/journal.pone.0024371 . (PMID: 10.1371/journal.pone.0024371219913023186766)
Zhang Y, Hu H, Liu C, Wu J, Zhou S, Zhao T. Serum pentraxin 3 as a biomarker for prognosis of acute minor stroke due to large artery atherosclerosis. Brain Behav. 2021;11(1): e01956. https://doi.org/10.1002/brb3.1956 . (PMID: 10.1002/brb3.195633210471)
Lee HW, Choi J, Suk K. Increases of pentraxin 3 plasma levels in patients with Parkinson’s disease. Mov Disord. 2011;26(13):2364–70. https://doi.org/10.1002/mds.23871 . (PMID: 10.1002/mds.2387121953577)
Ryu WS, Kim CK, Kim BJ, Kim C, Lee SH, Yoon BW. Pentraxin 3: a novel and independent prognostic marker in ischemic stroke. Atherosclerosis. 2012;220(2):581–6. https://doi.org/10.1016/j.atherosclerosis.2011.11.036 . (PMID: 10.1016/j.atherosclerosis.2011.11.03622178425)
Sezer S, Ucar F, Ulusoy EK, Erdogan S, Bilen S, Zungun C, et al. Serum amyloid A, fetuin-A, and pentraxin-3 levels in patients with ischemic stroke: novel prognostic biomarkers? Turk J Med Sci. 2014;44(1):16–23. https://doi.org/10.3906/sag-1211-90 . (PMID: 10.3906/sag-1211-9025558553)
Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19. J Infect. 2020;80(6):607–13. https://doi.org/10.1016/j.jinf.2020.03.037 . (PMID: 10.1016/j.jinf.2020.03.037322831527194613)
Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: an overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 2020;53:25–32. https://doi.org/10.1016/j.cytogfr.2020.05.003 . (PMID: 10.1016/j.cytogfr.2020.05.003324467787211650)
Cheng Y, Desse S, Martinez A, Worthen RJ, Jope RS, Beurel E. TNFalpha disrupts blood brain barrier integrity to maintain prolonged depressive-like behavior in mice. Brain Behav Immun. 2018;69:556–67. https://doi.org/10.1016/j.bbi.2018.02.003 . (PMID: 10.1016/j.bbi.2018.02.003294522185963697)
Dantzer R. Neuroimmune Interactions: from the brain to the immune system and vice versa. Physiol Rev. 2018;98(1):477–504. https://doi.org/10.1152/physrev.00039.2016 . (PMID: 10.1152/physrev.00039.201629351513)
Najjar S, Pearlman DM, Alper K, Najjar A, Devinsky O. Neuroinflammation and psychiatric illness. J Neuroinflamm. 2013;10:43; https://doi.org/10.1186/1742-2094-10-43.
Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16(1):22–34. https://doi.org/10.1038/nri.2015.5 . (PMID: 10.1038/nri.2015.5267116765542678)
Benedetti F, Aggio V, Pratesi ML, Greco G, Furlan R. Neuroinflammation in bipolar depression. Front Psychiatry. 2020;11:71. https://doi.org/10.3389/fpsyt.2020.00071.
Polentarutti N, Bottazzi B, Di Santo E, Blasi E, Agnello D, Ghezzi P, et al. Inducible expression of the long pentraxin PTX3 in the central nervous system. J Neuroimmunol. 2000;106(1–2):87–94. https://doi.org/10.1016/s0165-5728(00)00214-9 . (PMID: 10.1016/s0165-5728(00)00214-910814786)
Goldsmith DR, Rapaport MH, Miller BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry. 2016;21(12):1696–709. https://doi.org/10.1038/mp.2016.3 . (PMID: 10.1038/mp.2016.3269032676056174)
Wang AK, Miller BJ. Meta-analysis of cerebrospinal fluid cytokine and tryptophan catabolite alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder, and depression. Schizophr Bull. 2018;44(1):75–83. https://doi.org/10.1093/schbul/sbx035 . (PMID: 10.1093/schbul/sbx03528338954)
Zhang Y, Wang J, Ye Y, Zou Y, Chen W, Wang Z, et al. Peripheral cytokine levels across psychiatric disorders: a systematic review and network meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2023;125:110740. https://doi.org/10.1016/j.pnpbp.2023.110740 .
Benedetti F, Dallaspezia S, Melloni EMT, Lorenzi C, Zanardi R, Barbini B, et al. Effective antidepressant chronotherapeutics (sleep deprivation and light therapy) normalize the IL-1beta:IL-1ra ratio in bipolar depression. Front Physiol. 2021;12:740686. https://doi.org/10.3389/fphys.2021.740686 . (PMID: 10.3389/fphys.2021.740686345394548440979)
Benedetti F, Poletti S, Hoogenboezem TA, Mazza E, Ambree O, de Wit H, et al. Inflammatory cytokines influence measures of white matter integrity in Bipolar Disorder. J Affect Disord. 2016;15(202):1–9. https://doi.org/10.1016/j.jad.2016.05.047 . (PMID: 10.1016/j.jad.2016.05.047)
Maes M, Song C, Yirmiya R. Targeting IL-1 in depression. Expert Opin Ther Targets. 2012;16(11):1097–112. https://doi.org/10.1517/14728222.2012.718331 . (PMID: 10.1517/14728222.2012.71833122925041)
Mazza MG, De Lorenzo R, Conte C, Poletti S, Vai B, Bollettini I, et al. Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors. Brain Behav Immun. 2020;89:594–600. https://doi.org/10.1016/j.bbi.2020.07.037 . (PMID: 10.1016/j.bbi.2020.07.037327382877390748)
Mazza MG, Palladini M, De Lorenzo R, Magnaghi C, Poletti S, Furlan R, et al. Persistent psychopathology and neurocognitive impairment in COVID-19 survivors: effect of inflammatory biomarkers at three-month follow-up. Brain Behav Immun. 2021;94:138–47. https://doi.org/10.1016/j.bbi.2021.02.021 . (PMID: 10.1016/j.bbi.2021.02.021336392397903920)
Mazza MG, Palladini M, De Lorenzo R, Bravi B, Poletti S, Furlan R, et al. 1-year mental health outcomes in a cohort of COVID-19 survivors. J Psychiatr Res. 2021;22(145):118–24. https://doi.org/10.1016/j.jpsychires.2021.11.031 . (PMID: 10.1016/j.jpsychires.2021.11.031)
Poletti S, Paolini M, Mazza MG, Palladini M, Furlan R, Querini PR, et al. Lower levels of glutathione in the anterior cingulate cortex associate with depressive symptoms and white matter hyperintensities in COVID-19 survivors: Glutathione in COVID-19. Eur Neuropsychopharm. 2022.
Haapasalo K, Meri S. Regulation of the complement system by pentraxins. Front Immunol. 2019;10:1750. https://doi.org/10.3389/fimmu.2019.01750 . (PMID: 10.3389/fimmu.2019.01750314280916688104)
Shelton RC, Liang S, Liang P, Chakrabarti A, Manier DH, Sulser F. Differential expression of pentraxin 3 in fibroblasts from patients with major depression. Neuropsychopharmacology. 2004;29(1):126–32. https://doi.org/10.1038/sj.npp.1300307 . (PMID: 10.1038/sj.npp.130030714603263)
Dickerson F, Katsafanas E, Schweinfurth LA, Savage CL, Stallings C, Origoni A, et al. Immune alterations in acute bipolar depression. Acta Psychiatr Scand. 2015;132(3):204–10. https://doi.org/10.1111/acps.12451 . (PMID: 10.1111/acps.1245126061032)
Drexhage RC, Hoogenboezem TH, Versnel MA, Berghout A, Nolen WA, Drexhage HA. The activation of monocyte and T cell networks in patients with bipolar disorder. Brain Behav Immun. 2011;25(6):1206–13. https://doi.org/10.1016/j.bbi.2011.03.013 . (PMID: 10.1016/j.bbi.2011.03.01321443944)
Dickerson F, Stallings C, Origoni A, Katsafanas E, Schweinfurth LA, Savage CL, et al. Pentraxin 3 is reduced in bipolar disorder. Bipolar Disord. 2015;17(4):409–14. https://doi.org/10.1111/bdi.12281 . (PMID: 10.1111/bdi.1228125425421)
Miller LM, Jenny NS, Rawlings AM, Arnold AM, Fitzpatrick AL, Lopez OL, et al. Sex differences in the association between pentraxin 3 and cognitive decline: the cardiovascular health study. J Gerontol A Biol Sci Med Sci. 2020;75(8):1523–9. https://doi.org/10.1093/gerona/glz217 . (PMID: 10.1093/gerona/glz21731808814)
Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21(3):133–46. https://doi.org/10.1038/s41579-022-00846-2 . (PMID: 10.1038/s41579-022-00846-2366396089839201)
Castanares-Zapatero D, Chalon P, Kohn L, Dauvrin M, Detollenaere J, Maertens de Noordhout C, et al. Pathophysiology and mechanism of long COVID: a comprehensive review. Ann Med. 2022;54(1):1473-87; https://doi.org/10.1080/07853890.2022.2076901 .
Benedetti F, Zanardi R, Mazza MG. Antidepressant psychopharmacology: is inflammation a future target? Int Clin Psychopharmacol. 2022;37(3):79–81. https://doi.org/10.1097/YIC.0000000000000403 . (PMID: 10.1097/YIC.000000000000040335357329)
Kohler CA, Freitas TH, Stubbs B, Maes M, Solmi M, Veronese N, et al. Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis. Mol Neurobiol. 2018;55(5):4195–206. https://doi.org/10.1007/s12035-017-0632-1 . (PMID: 10.1007/s12035-017-0632-128612257)
Hashimoto Y, Suzuki T, Hashimoto K. Mechanisms of action of fluvoxamine for COVID-19: a historical review. Mol Psychiatry. 2022;27(4):1898–907. https://doi.org/10.1038/s41380-021-01432-3 . (PMID: 10.1038/s41380-021-01432-3349971968739627)
Mazza MG, Palladini M, Villa G, Agnoletto E, Harrington Y, Vai B, et al. Prevalence of depression in SARS-CoV-2 infected patients: An umbrella review of meta-analyses. Gen Hosp Psychiatry. 2023;80:17–25. https://doi.org/10.1016/j.genhosppsych.2022.12.002 . (PMID: 10.1016/j.genhosppsych.2022.12.00236535239)

GR-2021-12374872-1 Ministero della Salute; COVID-2020-12371640 Ministero della Salute; COVID-2020-12371617 Ministero della Salute; PE00000007 NextGeneration EU-MUR PNRR

0 (Biomarkers)
9007-41-4 (C-Reactive Protein)
148591-49-5 (PTX3 protein)
0 (Serum Amyloid P-Component)

Date Created: 20240424 Date Completed: 20240516 Latest Revision: 20240814

20240814

10.1007/s40263-024-01081-4

38658499