The effect of antidepressants on the severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis

{ 'indexed': {'date-parts': [[2022, 10, 6]], 'date-time': '2022-10-06T18:18:00Z', 'timestamp': 1665080280106}, 'reference-count': 79, 'publisher': 'Public Library of Science (PLoS)', 'issue': '10', 'license': [ { 'start': { 'date-parts': [[2022, 10, 6]], 'date-time': '2022-10-06T00:00:00Z', 'timestamp': 1665014400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['www.plosone.org'], 'crossmark-restriction': False}, 'abstract': '<jats:sec id="sec001">\n' '<jats:title>Introduction</jats:title>\n' '<jats:p>Clinical Depression and the subsequent low immunity is a comorbidity that can act as ' 'a risk factor for the severity of COVID-19 cases. Antidepressants such as Selective serotonin ' 'reuptake inhibitor and Serotonin-norepinephrine reuptake inhibitors are associated with ' 'immune-modulatory effects, which dismiss inflammatory responses and reduce lung tissue ' 'damage. The current systematic review and meta-analysis aims to evaluate the effect of ' 'antidepressant drugs on the prognosis and severity of COVID-19 in hospitalized ' 'patients.</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec002">\n' '<jats:title>Methods</jats:title>\n' '<jats:p>A systematic search was carried out in PubMed/Medline, EMBASE, and Scopus up to June ' '14, 2022. The following keywords were used: "COVID-19", "SARS-CoV-2", "2019-nCoV", "SSRI", ' '"SNRI", “TCA”, “MAOI”, and “Antidepressant”. A fixed or random-effect model assessed the ' 'pooled risk ratio (RR) with 95% CI. We considered P &lt; 0.05 as statistically significant ' 'for publication bias. Data were analyzed by Comprehensive Meta-Analysis software, Version 2.0 ' '(Biostat, Englewood, NJ).</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec003">\n' '<jats:title>Results</jats:title>\n' '<jats:p>Fourteen studies were included in our systematic review. Five of them were ' 'experimental with 2350, and nine of them were observational with 290,950 participants. Eight ' 'out of fourteen articles revealed the effect of antidepressants on reducing the severity of ' 'COVID-19. Selective serotonin reuptake inhibitors drugs, including Fluvoxamine, Escitalopram, ' 'Fluoxetine, and Paroxetine, and among the Serotonin-norepinephrine inhibitors medications ' 'Venlafaxine, are reasonably associated with reduced risk of intubation or death. Five studies ' 'showed no significant effect, and only one high risk of bias article showed the negative ' 'effect of antidepressants on the prognosis of Covid-19. The meta-analysis of clinical trials ' 'showed that fluvoxamine could significantly decrease the severity outcomes of COVID-19 (RR: ' '0.763; 95% CI: 0.602–0.966, I2: 0.0)</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec004">\n' '<jats:title>Findings</jats:title>\n' '<jats:p>Most evidence supports that the use of antidepressant medications, mainly ' 'Fluvoxamine, may decrease the severity and improve the outcome in hospitalized patients with ' 'SARS-CoV-2. Some studies showed contradictory findings regarding the effects of ' 'antidepressants on the severity of COVID-19. Further clinical trials should be conducted to ' 'clarify the effects of antidepressants on the severity of COVID-19.</jats:p>\n' '</jats:sec>', 'DOI': '10.1371/journal.pone.0267423', 'type': 'journal-article', 'created': {'date-parts': [[2022, 10, 6]], 'date-time': '2022-10-06T17:31:21Z', 'timestamp': 1665077481000}, 'page': 'e0267423', 'update-policy': 'http://dx.doi.org/10.1371/journal.pone.corrections_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'The effect of antidepressants on the severity of COVID-19 in hospitalized patients: A systematic ' 'review and meta-analysis', 'prefix': '10.1371', 'volume': '17', 'author': [ { 'ORCID': 'http://orcid.org/0000-0003-0929-2495', 'authenticated-orcid': True, 'given': 'Hosein', 'family': 'Nakhaee', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-7454-7944', 'authenticated-orcid': True, 'given': 'Moein', 'family': 'Zangiabadian', 'sequence': 'additional', 'affiliation': []}, {'given': 'Reza', 'family': 'Bayati', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mohammad', 'family': 'Rahmanian', 'sequence': 'additional', 'affiliation': []}, {'given': 'Amir', 'family': 'Ghaffari Jolfayi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sakineh', 'family': 'Rakhshanderou', 'sequence': 'additional', 'affiliation': []}], 'member': '340', 'published-online': {'date-parts': [[2022, 10, 6]]}, 'reference': [ { 'key': 'pone.0267423.ref001', 'author': 'Organization, W.H.', 'year': '2022', 'journal-title': 'WHO Coronavirus (COVID-19) Dashboard'}, { 'issue': '10223', 'key': 'pone.0267423.ref002', 'doi-asserted-by': 'crossref', 'first-page': '497', 'DOI': '10.1016/S0140-6736(20)30183-5', 'article-title': 'Clinical features of patients infected with 2019 novel coronavirus in ' 'Wuhan, China', 'volume': '395', 'author': 'C. Huang', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': 'pone.0267423.ref003', 'doi-asserted-by': 'crossref', 'first-page': '100', 'DOI': '10.1016/j.bbi.2020.04.069', 'article-title': 'Do psychiatric patients experience more psychiatric symptoms during ' 'COVID-19 pandemic and lockdown? A case-control study with service and ' 'research implications for immunopsychiatry', 'volume': '87', 'author': 'F. Hao', 'year': '2020', 'journal-title': 'Brain Behav Immun'}, { 'issue': '1', 'key': 'pone.0267423.ref004', 'doi-asserted-by': 'crossref', 'first-page': '112', 'DOI': '10.4103/psychiatry.IndianJPsychiatry_850_20', 'article-title': 'Susceptibility of clinically depressed patients to COVID-19: Is there a ' 'link?', 'volume': '63', 'author': 'A. Das', 'year': '2021', 'journal-title': 'Indian J Psychiatry'}, { 'issue': '1', 'key': 'pone.0267423.ref005', 'doi-asserted-by': 'crossref', 'first-page': '131', 'DOI': '10.1093/ije/dyv333', 'article-title': 'Depression and the risk of severe infections: prospective analyses on a ' 'nationwide representative sample', 'volume': '45', 'author': 'N.W. Andersson', 'year': '2016', 'journal-title': 'Int J Epidemiol'}, { 'issue': '3', 'key': 'pone.0267423.ref006', 'doi-asserted-by': 'crossref', 'first-page': '472', 'DOI': '10.1037/0033-2909.113.3.472', 'article-title': 'Depression and immunity: a meta-analytic review', 'volume': '113', 'author': 'T.B. Herbert', 'year': '1993', 'journal-title': 'Psychol Bull'}, { 'issue': '1', 'key': 'pone.0267423.ref007', 'doi-asserted-by': 'crossref', 'first-page': 'e6', 'DOI': '10.1192/bjo.2021.1053', 'article-title': 'Analysis of the impact of antidepressants and other medications on ' 'COVID-19 infection risk in a chronic psychiatric in-patient cohort', 'volume': '8', 'author': 'C.L. Clelland', 'year': '2021', 'journal-title': 'BJPsych Open'}, { 'issue': '9', 'key': 'pone.0267423.ref008', 'doi-asserted-by': 'crossref', 'first-page': '5199', 'DOI': '10.1038/s41380-021-01021-4', 'article-title': 'Association between antidepressant use and reduced risk of intubation ' 'or death in hospitalized patients with COVID-19: results from an ' 'observational study', 'volume': '26', 'author': 'N. Hoertel', 'year': '2021', 'journal-title': 'Mol Psychiatry'}, { 'issue': '6', 'key': 'pone.0267423.ref009', 'doi-asserted-by': 'crossref', 'first-page': '526', 'DOI': '10.1111/acps.13304', 'article-title': 'Mental disorders, psychopharmacological treatments, and mortality in ' '2150 COVID-19 Spanish inpatients', 'volume': '143', 'author': 'C. Diez-Quevedo', 'year': '2021', 'journal-title': 'Acta Psychiatr Scand'}, { 'issue': '1', 'key': 'pone.0267423.ref010', 'doi-asserted-by': 'crossref', 'first-page': '37', 'DOI': '10.1186/s41232-020-00146-3', 'article-title': 'How COVID-19 induces cytokine storm with high mortality', 'volume': '40', 'author': 'S. Hojyo', 'year': '2020', 'journal-title': 'Inflammation and Regeneration'}, { 'issue': '5', 'key': 'pone.0267423.ref011', 'first-page': '4195', 'article-title': 'Peripheral Alterations in Cytokine and Chemokine Levels After ' 'Antidepressant Drug Treatment for Major Depressive Disorder: Systematic ' 'Review and Meta-Analysis', 'volume': '55', 'author': 'C.A. Köhler', 'year': '2018', 'journal-title': 'Mol Neurobiol'}, { 'issue': '7', 'key': 'pone.0267423.ref012', 'doi-asserted-by': 'crossref', 'first-page': '934', 'DOI': '10.1038/nm.3214', 'article-title': 'Acid sphingomyelinase-ceramide system mediates effects of ' 'antidepressant drugs', 'volume': '19', 'author': 'E. Gulbins', 'year': '2013', 'journal-title': 'Nat Med'}, { 'issue': '4', 'key': 'pone.0267423.ref013', 'doi-asserted-by': 'crossref', 'first-page': '264', 'DOI': '10.7326/0003-4819-151-4-200908180-00135', 'article-title': 'Preferred reporting items for systematic reviews and meta-analyses: the ' 'PRISMA statement', 'volume': '151', 'author': 'D. Moher', 'year': '2009', 'journal-title': 'Annals of internal medicine'}, { 'key': 'pone.0267423.ref014', 'author': 'Institute JB', 'year': '2021', 'journal-title': 'Critical Appraisal Tools, J.B.I.U.o.A., South Australia'}, { 'issue': '11', 'key': 'pone.0267423.ref015', 'doi-asserted-by': 'crossref', 'first-page': '1539', 'DOI': '10.1002/sim.1186', 'article-title': 'Quantifying heterogeneity in a meta‐analysis', 'volume': '21', 'author': 'J.P. Higgins', 'year': '2002', 'journal-title': 'Statistics in medicine'}, { 'key': 'pone.0267423.ref016', 'doi-asserted-by': 'crossref', 'first-page': '1088', 'DOI': '10.2307/2533446', 'article-title': 'Operating characteristics of a rank correlation test for publication ' 'bias', 'author': 'C.B. Begg', 'year': '1994', 'journal-title': 'Biometrics'}, { 'key': 'pone.0267423.ref017', 'first-page': '991', 'article-title': 'Is it possible that antidepressants protect against COVID-19?', 'author': 'E.S. Bora', 'year': '2021', 'journal-title': 'Annals of Clinical and Analytical Medicine'}, { 'key': 'pone.0267423.ref018', 'article-title': 'Can SSRI/SNRI antidepressants decrease the’cytokine storm’in the course ' 'of COVID-19 pneumonia?', 'author': 'L. Fei', 'year': '2021', 'journal-title': 'Panminerva medica'}, { 'issue': '11', 'key': 'pone.0267423.ref019', 'doi-asserted-by': 'crossref', 'first-page': 'e2133090', 'DOI': '10.1001/jamanetworkopen.2021.33090', 'article-title': 'Mortality risk among patients with COVID-19 prescribed selective ' 'serotonin reuptake inhibitor antidepressants', 'volume': '4', 'author': 'T. Oskotsky', 'year': '2021', 'journal-title': 'JAMA network open'}, { 'issue': '1', 'key': 'pone.0267423.ref020', 'first-page': '70', 'article-title': 'Ongoing Use of SSRIs Does Not Alter Outcome in Hospitalized COVID-19 ' 'Patients', 'volume': '11', 'author': 'S.H. Rauchman', 'year': '2022', 'journal-title': 'A Retrospective Analysis. Journal of Clinical Medicine'}, { 'key': 'pone.0267423.ref021', 'volume-title': 'Open Forum Infectious Diseases', 'author': 'D. Seftel', 'year': '2021'}, { 'key': 'pone.0267423.ref022', 'doi-asserted-by': 'crossref', 'first-page': 'e68165', 'DOI': '10.7554/eLife.68165', 'article-title': 'Identification of drugs associated with reduced severity of COVID-19–a ' 'case-control study in a large population', 'author': 'A. Israel', 'year': '2021', 'journal-title': 'Elife'}, { 'issue': '1', 'key': 'pone.0267423.ref023', 'first-page': '1', 'article-title': 'Relation of severe COVID-19 to polypharmacy and prescribing of ' 'psychotropic drugs: the REACT-SCOT case-control study', 'volume': '19', 'author': 'P.M. McKeigue', 'year': '2021', 'journal-title': 'BMC medicine'}, { 'issue': '11–12', 'key': 'pone.0267423.ref024', 'doi-asserted-by': 'crossref', 'first-page': '389', 'DOI': '10.18071/isz.74.0389', 'article-title': 'Fluoxetine use is associated with improved survival of patients with ' 'COVID–19 pneumonia: A retrospective case-control study', 'volume': '74', 'author': 'Z.K. Németh', 'year': '2021', 'journal-title': 'Ideggyogy Sz'}, { 'key': 'pone.0267423.ref025', 'article-title': 'Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open ' 'label, prospective cohort trial with matched controls', 'author': 'M. Calusic', 'year': '2021', 'journal-title': 'British journal of clinical pharmacology'}, { 'issue': '22', 'key': 'pone.0267423.ref026', 'doi-asserted-by': 'crossref', 'first-page': '2292', 'DOI': '10.1001/jama.2020.22760', 'article-title': 'Fluvoxamine vs placebo and clinical deterioration in outpatients with ' 'symptomatic COVID-19: a randomized clinical trial', 'volume': '324', 'author': 'E.J. Lenze', 'year': '2020', 'journal-title': 'Jama'}, { 'issue': '1', 'key': 'pone.0267423.ref027', 'doi-asserted-by': 'crossref', 'first-page': 'e42', 'DOI': '10.1016/S2214-109X(21)00448-4', 'article-title': 'Effect of early treatment with fluvoxamine on risk of emergency care ' 'and hospitalisation among patients with COVID-19: the TOGETHER ' 'randomised, platform clinical trial', 'volume': '10', 'author': 'G. Reis', 'year': '2022', 'journal-title': 'The Lancet Global Health'}, { 'key': 'pone.0267423.ref028', 'author': 'E. Lenze', 'year': '2021', 'journal-title': 'Fluvoxamine for early treatment of COVID-19: a fully-remote, randomized ' 'placebo controlled trial. ClinicalTrials. gov'}, { 'issue': '1', 'key': 'pone.0267423.ref029', 'doi-asserted-by': 'crossref', 'first-page': '102', 'DOI': '10.3947/ic.2021.0142', 'article-title': 'Fluvoxamine Treatment of Patients with Symptomatic COVID-19 in a ' 'Community Treatment Center: A Preliminary Result of Randomized ' 'Controlled Trial', 'volume': '54', 'author': 'H. Seo', 'year': '2022', 'journal-title': 'Infection & chemotherapy'}, { 'issue': '3', 'key': 'pone.0267423.ref030', 'doi-asserted-by': 'crossref', 'first-page': 'e333', 'DOI': '10.1016/S2214-109X(21)00588-X', 'article-title': 'Fluvoxamine for the treatment of COVID-19—Author’s reply', 'volume': '10', 'author': 'G. Reis', 'year': '2022', 'journal-title': 'Lancet Glob Health'}, { 'issue': '3', 'key': 'pone.0267423.ref031', 'doi-asserted-by': 'crossref', 'first-page': '143', 'DOI': '10.1007/s00005-019-00543-8', 'article-title': 'The Influence of Antidepressants on the Immune System', 'volume': '67', 'author': 'P. Szałach Ł', 'year': '2019', 'journal-title': 'Arch Immunol Ther Exp (Warsz)'}, { 'issue': '7', 'key': 'pone.0267423.ref032', 'doi-asserted-by': 'crossref', 'first-page': '1564', 'DOI': '10.1111/all.14364', 'article-title': 'Immune response to SARS-CoV-2 and mechanisms of immunopathological ' 'changes in COVID-19', 'volume': '75', 'author': 'A.K. Azkur', 'year': '2020', 'journal-title': 'Allergy'}, { 'key': 'pone.0267423.ref033', 'doi-asserted-by': 'crossref', 'first-page': '1844', 'DOI': '10.3389/fpsyg.2020.01844', 'article-title': 'Influence of Stress and Depression on the Immune System in Patients ' 'Evaluated in an Anti-aging Unit', 'volume': '11', 'author': 'B. Cañas-González', 'year': '2020', 'journal-title': 'Front Psychol'}, { 'issue': '4', 'key': 'pone.0267423.ref034', 'first-page': '201', 'article-title': 'Modulation of microglial function by the antidepressant drug ' 'venlafaxine', 'volume': '7', 'author': 'M. Dubovický', 'year': '2014', 'journal-title': 'Interdiscip Toxicol'}, { 'issue': '4', 'key': 'pone.0267423.ref035', 'doi-asserted-by': 'crossref', 'first-page': '853', 'DOI': '10.1016/j.pbb.2012.12.003', 'article-title': 'Effects of antidepressants on alternations in serum cytokines and ' 'depressive-like behavior in mice after lipopolysaccharide ' 'administration', 'volume': '103', 'author': 'Y. Ohgi', 'year': '2013', 'journal-title': 'Pharmacol Biochem Behav'}, { 'key': 'pone.0267423.ref036', 'article-title': 'Mechanisms of action of fluvoxamine for COVID-19: a historical review', 'author': 'Y. Hashimoto', 'year': '2022', 'journal-title': 'Molecular Psychiatry'}, { 'key': 'pone.0267423.ref037', 'doi-asserted-by': 'crossref', 'first-page': '163', 'DOI': '10.1016/j.jocn.2021.03.010', 'article-title': 'Drug repurposing of selective serotonin reuptake inhibitors: Could ' 'these drugs help fight COVID-19 and save lives?', 'volume': '88', 'author': 'Y. Pashaei', 'year': '2021', 'journal-title': 'J Clin Neurosci'}, { 'issue': '5', 'key': 'pone.0267423.ref038', 'doi-asserted-by': 'crossref', 'first-page': '2253', 'DOI': '10.4049/jimmunol.169.5.2253', 'article-title': 'Shaping gene expression in activated and resting primary macrophages by ' 'IL-10', 'volume': '169', 'author': 'R. Lang', 'year': '2002', 'journal-title': 'J Immunol'}, { 'issue': '26', 'key': 'pone.0267423.ref039', 'doi-asserted-by': 'crossref', 'first-page': '2557', 'DOI': '10.1016/0024-3205(91)90612-F', 'article-title': 'Serotonin inhibition of tumor necrosis factor-alpha synthesis by human ' 'monocytes', 'volume': '48', 'author': 'E. Arzt', 'year': '1991', 'journal-title': 'Life Sci'}, { 'issue': '1', 'key': 'pone.0267423.ref040', 'doi-asserted-by': 'crossref', 'first-page': '89', 'DOI': '10.1016/S0893-133X(99)00150-5', 'article-title': 'Effects of serotonin and serotonergic agonists and antagonists on the ' 'production of interferon-gamma and interleukin-10', 'volume': '23', 'author': 'M. Kubera', 'year': '2000', 'journal-title': 'Neuropsychopharmacology'}, { 'key': 'pone.0267423.ref041', 'doi-asserted-by': 'crossref', 'first-page': '365', 'DOI': '10.1007/978-3-662-45805-1_15', 'article-title': 'Serotonin transporter and serotonin receptors', 'volume': '218', 'author': 'S. Adnot', 'year': '2013', 'journal-title': 'Handb Exp Pharmacol'}, { 'issue': '2', 'key': 'pone.0267423.ref042', 'doi-asserted-by': 'crossref', 'first-page': '340', 'DOI': '10.1111/j.1365-2249.2007.03492.x', 'article-title': 'Serotonin modulates the cytokine network in the lung: involvement of ' 'prostaglandin E2', 'volume': '150', 'author': 'G. Ménard', 'year': '2007', 'journal-title': 'Clin Exp Immunol'}, { 'issue': '4', 'key': 'pone.0267423.ref043', 'doi-asserted-by': 'crossref', 'first-page': '356', 'DOI': '10.1055/s-0037-1617140', 'article-title': 'The role of serotonin in haemostasis', 'volume': '29', 'author': 'D. Duerschmied', 'year': '2009', 'journal-title': 'Hamostaseologie'}, { 'issue': '22', 'key': 'pone.0267423.ref044', 'doi-asserted-by': 'crossref', 'first-page': '3508', 'DOI': '10.1182/blood.V114.22.3508.3508', 'article-title': 'Effect of SSRI Use On Platelet Function Testing and Bleeding Symptoms', 'volume': '114', 'author': 'N. Rastogi-Chawla', 'year': '2009', 'journal-title': 'Blood'}, { 'issue': '3', 'key': 'pone.0267423.ref045', 'doi-asserted-by': 'crossref', 'first-page': '168', 'DOI': '10.1016/j.trsl.2007.10.004', 'article-title': 'Selective serotonin reuptake inhibitors: measurement of effect on ' 'platelet function', 'volume': '151', 'author': 'D.J. McCloskey', 'year': '2008', 'journal-title': 'Transl Res'}, { 'issue': '7807', 'key': 'pone.0267423.ref046', 'doi-asserted-by': 'crossref', 'first-page': '215', 'DOI': '10.1038/s41586-020-2180-5', 'article-title': 'Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ' 'ACE2 receptor', 'volume': '581', 'author': 'J. Lan', 'year': '2020', 'journal-title': 'Nature'}, { 'issue': '4', 'key': 'pone.0267423.ref047', 'doi-asserted-by': 'crossref', 'first-page': '894', 'DOI': '10.1016/j.cell.2020.03.045', 'article-title': 'Structural and functional basis of SARS-CoV-2 entry by using human ACE2', 'volume': '181', 'author': 'Q. Wang', 'year': '2020', 'journal-title': 'Cell'}, { 'key': 'pone.0267423.ref048', 'doi-asserted-by': 'crossref', 'first-page': '122', 'DOI': '10.1016/j.jbior.2016.10.002', 'article-title': 'Ceramidases, roles in sphingolipid metabolism and in health and disease', 'volume': '63', 'author': 'N. Coant', 'year': '2017', 'journal-title': 'Advances in biological regulation'}, { 'issue': '3', 'key': 'pone.0267423.ref049', 'doi-asserted-by': 'crossref', 'first-page': '285', 'DOI': '10.1002/1097-4652(200009)184:3<285::AID-JCP2>3.0.CO;2-3', 'article-title': 'Compartmentalization of ceramide signaling: physical foundations and ' 'biological effects', 'volume': '184', 'author': 'R.N. Kolesnick', 'year': '2000', 'journal-title': 'Journal of cellular physiology'}, { 'issue': '45', 'key': 'pone.0267423.ref050', 'doi-asserted-by': 'crossref', 'first-page': '7070', 'DOI': '10.1038/sj.onc.1207146', 'article-title': 'Raft ceramide in molecular medicine', 'volume': '22', 'author': 'E. Gulbins', 'year': '2003', 'journal-title': 'Oncogene'}, { 'issue': '1', 'key': 'pone.0267423.ref051', 'doi-asserted-by': 'crossref', 'first-page': '20866', 'DOI': '10.1038/s41598-021-00286-7', 'article-title': 'Inferring a causal relationship between ceramide levels and COVID-19 ' 'respiratory distress', 'volume': '11', 'author': 'M.M. Khodadoust', 'year': '2021', 'journal-title': 'Scientific Reports'}, { 'issue': '19', 'key': 'pone.0267423.ref052', 'doi-asserted-by': 'crossref', 'first-page': '10198', 'DOI': '10.3390/ijms221910198', 'article-title': 'Severity of COVID-19 Patients Predicted by Serum Sphingolipids ' 'Signature', 'volume': '22', 'author': 'E. Torretta', 'year': '2021', 'journal-title': 'International Journal of Molecular Sciences'}, { 'key': 'pone.0267423.ref053', 'first-page': '2022.01.19.22269391', 'article-title': 'COVID-19 and its clinical severity are associated with alterations of ' 'plasma sphingolipids and enzyme activities of sphingomyelinase and ' 'ceramidase', 'author': 'C. Mühle', 'year': '2022', 'journal-title': 'medRxiv'}, { 'issue': '12', 'key': 'pone.0267423.ref054', 'doi-asserted-by': 'crossref', 'first-page': '7098', 'DOI': '10.1038/s41380-021-01254-3', 'article-title': 'Repurposing antidepressants inhibiting the sphingomyelinase ' 'acid/ceramide system against COVID-19: current evidence and potential ' 'mechanisms', 'volume': '26', 'author': 'N. Hoertel', 'year': '2021', 'journal-title': 'Mol Psychiatry'}, { 'key': 'pone.0267423.ref055', 'doi-asserted-by': 'crossref', 'first-page': '100701', 'DOI': '10.1016/j.jbc.2021.100701', 'article-title': 'Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 ' 'entry into epithelial cells', 'volume': '296', 'author': 'A. Carpinteiro', 'year': '2021', 'journal-title': 'J Biol Chem'}, { 'issue': '11', 'key': 'pone.0267423.ref056', 'doi-asserted-by': 'crossref', 'first-page': '6377', 'DOI': '10.1128/JVI.03557-12', 'article-title': 'Sigma-1 receptor regulates early steps of viral RNA replication at the ' 'onset of hepatitis C virus infection', 'volume': '87', 'author': 'M. Friesland', 'year': '2013', 'journal-title': 'J Virol'}, { 'key': 'pone.0267423.ref057', 'doi-asserted-by': 'crossref', 'first-page': '100', 'DOI': '10.1016/j.virusres.2015.03.013', 'article-title': 'Cellular stress responses in hepatitis C virus infection: Mastering a ' 'two-edged sword', 'volume': '209', 'author': 'C. Vasallo', 'year': '2015', 'journal-title': 'Virus Res'}, { 'issue': '8', 'key': 'pone.0267423.ref058', 'doi-asserted-by': 'crossref', 'first-page': 'e23852', 'DOI': '10.1371/journal.pone.0023852', 'article-title': 'Identification of novel functional inhibitors of acid sphingomyelinase', 'volume': '6', 'author': 'J. Kornhuber', 'year': '2011', 'journal-title': 'PLoS One'}, { 'issue': '8', 'key': 'pone.0267423.ref059', 'doi-asserted-by': 'crossref', 'first-page': '100142', 'DOI': '10.1016/j.xcrm.2020.100142', 'article-title': 'Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of ' 'SARS-CoV-2 by Epithelial Cells', 'volume': '1', 'author': 'A. Carpinteiro', 'year': '2020', 'journal-title': 'Cell Rep Med'}, { 'issue': '1', 'key': 'pone.0267423.ref060', 'doi-asserted-by': 'crossref', 'first-page': '2245', 'DOI': '10.1080/22221751.2020.1829082', 'article-title': 'Targeting the endolysosomal host-SARS-CoV-2 interface by clinically ' 'licensed functional inhibitors of acid sphingomyelinase (FIASMA) ' 'including the antidepressant fluoxetine', 'volume': '9', 'author': 'S. Schloer', 'year': '2020', 'journal-title': 'Emerg Microbes Infect'}, { 'issue': '11', 'key': 'pone.0267423.ref061', 'doi-asserted-by': 'crossref', 'first-page': 'e2136510', 'DOI': '10.1001/jamanetworkopen.2021.36510', 'article-title': 'Do the Selective Serotonin Reuptake Inhibitor Antidepressants ' 'Fluoxetine and Fluvoxamine Reduce Mortality Among Patients With ' 'COVID-19?', 'volume': '4', 'author': 'N. Hoertel', 'year': '2021', 'journal-title': 'JAMA Network Open'}, { 'issue': '7816', 'key': 'pone.0267423.ref062', 'doi-asserted-by': 'crossref', 'first-page': '459', 'DOI': '10.1038/s41586-020-2286-9', 'article-title': 'A SARS-CoV-2 protein interaction map reveals targets for drug ' 'repurposing', 'volume': '583', 'author': 'D.E. Gordon', 'year': '2020', 'journal-title': 'Nature'}, { 'issue': '3', 'key': 'pone.0267423.ref063', 'doi-asserted-by': 'crossref', 'first-page': '221', 'DOI': '10.1007/s40261-021-01001-0', 'article-title': 'Observational Study of Chlorpromazine in Hospitalized Patients with ' 'COVID-19', 'volume': '41', 'author': 'N. Hoertel', 'year': '2021', 'journal-title': 'Clin Drug Investig'}, { 'issue': '1', 'key': 'pone.0267423.ref064', 'doi-asserted-by': 'crossref', 'first-page': '84', 'DOI': '10.1002/jnr.490310112', 'article-title': 'Calmodulin antagonists chlorpromazine and W-7 inhibit exogenous ' 'cholesterol esterification and sphingomyelinase activity in human skin ' 'fibroblast cultures. Similarities between drug-induced and Niemann-Pick ' 'type C lipidoses', 'volume': '31', 'author': 'M. Masson', 'year': '1992', 'journal-title': 'J Neurosci Res'}, { 'issue': '477', 'key': 'pone.0267423.ref065', 'article-title': 'Fluoxetine pharmacokinetics and tissue distribution quantitatively ' 'supports a therapeutic role in COVID-19 at a minimum dose of 20 mg per ' 'day [version 2; peer review: 1 approved, 1 approved with reservations]', 'volume': '10', 'author': 'A. Eugene', 'year': '2022', 'journal-title': 'F1000Research'}, { 'issue': '20', 'key': 'pone.0267423.ref066', 'doi-asserted-by': 'crossref', 'first-page': '2073', 'DOI': '10.2174/0929867033456783', 'article-title': 'Understanding the molecular mechanism of sigma-1 receptors: towards a ' 'hypothesis that sigma-1 receptors are intracellular amplifiers for ' 'signal transduction', 'volume': '10', 'author': 'T.P. Su', 'year': '2003', 'journal-title': 'Curr Med Chem'}, { 'issue': '8', 'key': 'pone.0267423.ref067', 'doi-asserted-by': 'crossref', 'first-page': '4885', 'DOI': '10.1128/AAC.03036-14', 'article-title': 'Repurposing of clinically developed drugs for treatment of Middle East ' 'respiratory syndrome coronavirus infection', 'volume': '58', 'author': 'J. Dyall', 'year': '2014', 'journal-title': 'Antimicrob Agents Chemother'}, { 'key': 'pone.0267423.ref068', 'doi-asserted-by': 'crossref', 'first-page': '582310', 'DOI': '10.3389/fphar.2020.582310', 'article-title': 'Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?', 'volume': '11', 'author': 'J.M. Vela', 'year': '2020', 'journal-title': 'Front Pharmacol'}, { 'issue': '3', 'key': 'pone.0267423.ref069', 'doi-asserted-by': 'crossref', 'first-page': '596', 'DOI': '10.1016/j.cell.2007.08.036', 'article-title': 'Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate ' 'Ca(2+) signaling and cell survival', 'volume': '131', 'author': 'T. Hayashi', 'year': '2007', 'journal-title': 'Cell'}, { 'issue': '5', 'key': 'pone.0267423.ref070', 'doi-asserted-by': 'crossref', 'first-page': '557', 'DOI': '10.1517/14728222.2011.560837', 'article-title': 'Targeting ligand-operated chaperone sigma-1 receptors in the treatment ' 'of neuropsychiatric disorders', 'volume': '15', 'author': 'T. Hayashi', 'year': '2011', 'journal-title': 'Expert Opin Ther Targets'}, { 'issue': '478', 'key': 'pone.0267423.ref071', 'doi-asserted-by': 'crossref', 'DOI': '10.1126/scitranslmed.aau5266', 'article-title': 'Modulation of the sigma-1 receptor-IRE1 pathway is beneficial in ' 'preclinical models of inflammation and sepsis', 'volume': '11', 'author': 'D.A. Rosen', 'year': '2019', 'journal-title': 'Sci Transl Med'}, { 'issue': '4', 'key': 'pone.0267423.ref072', 'first-page': '3376', 'article-title': 'Effect of TLR4/MyD88 signaling pathway on sepsis-associated acute ' 'respiratory distress syndrome in rats, via regulation of macrophage ' 'activation and inflammatory response', 'volume': '15', 'author': 'S. Zhou', 'year': '2018', 'journal-title': 'Experimental and therapeutic medicine'}, { 'issue': '1', 'key': 'pone.0267423.ref073', 'doi-asserted-by': 'crossref', 'first-page': '93', 'DOI': '10.1002/iub.2537', 'article-title': 'Endoplasmic reticulum stress and NF-kB activation in SARS-CoV-2 ' 'infected cells and their response to antiviral therapy', 'volume': '74', 'author': 'D. Bartolini', 'year': '2022', 'journal-title': 'IUBMB Life'}, { 'issue': '1', 'key': 'pone.0267423.ref074', 'doi-asserted-by': 'crossref', 'first-page': '1748', 'DOI': '10.1080/22221751.2020.1799723', 'article-title': 'Dysregulation in Akt/mTOR/HIF-1 signaling identified by ' 'proteo-transcriptomics of SARS-CoV-2 infected cells', 'volume': '9', 'author': 'S. Appelberg', 'year': '2020', 'journal-title': 'Emerg Microbes Infect'}, { 'key': 'pone.0267423.ref075', 'doi-asserted-by': 'crossref', 'first-page': '752563', 'DOI': '10.1155/2012/752563', 'article-title': 'Roles of PI3K/AKT/GSK3/mTOR Pathway in Cell Signaling of Mental ' 'Illnesses', 'volume': '2012', 'author': 'Y. Kitagishi', 'year': '2012', 'journal-title': 'Depression Research and Treatment'}, { 'key': 'pone.0267423.ref076', 'doi-asserted-by': 'crossref', 'first-page': '117583', 'DOI': '10.1016/j.lfs.2020.117583', 'article-title': 'COVID-19: Melatonin as a potential adjuvant treatment', 'volume': '250', 'author': 'R. Zhang', 'year': '2020', 'journal-title': 'Life Sci'}, { 'issue': '10', 'key': 'pone.0267423.ref077', 'doi-asserted-by': 'crossref', 'first-page': '1231', 'DOI': '10.1002/phar.1992', 'article-title': 'Effect of Abrupt Discontinuation of Antidepressants in Critically Ill ' 'Hospitalized Adults', 'volume': '37', 'author': 'T.B. Bainum', 'year': '2017', 'journal-title': 'Pharmacotherapy'}, { 'issue': '6', 'key': 'pone.0267423.ref078', 'doi-asserted-by': 'crossref', 'first-page': 'e607', 'DOI': '10.1097/CCM.0000000000002308', 'article-title': 'Using Selective Serotonin Reuptake Inhibitors and ' 'Serotonin-Norepinephrine Reuptake Inhibitors in Critical Care: A ' 'Systematic Review of the Evidence for Benefit or Harm', 'volume': '45', 'author': 'J.M. Kelly', 'year': '2017', 'journal-title': 'Crit Care Med'}, { 'issue': '1', 'key': 'pone.0267423.ref079', 'doi-asserted-by': 'crossref', 'first-page': '47', 'DOI': '10.31887/DCNS.2007.9.1/dhalperin', 'article-title': 'Influence of antidepressants on hemostasis', 'volume': '9', 'author': 'D. 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