Impact of fluvoxamine on outpatient treatment of COVID-19 in Honduras in a prospective observational real-world study
Estela Pineda, Jarmanjeet Singh, Miguel Vargas Pineda, Jose Garay Umanzor, Fernando Baires, Luis G Benitez, Cesar Burgos, Anupamjeet Kaur Sekhon, Nicole Crisp, Anita S Lewis, Jana Radwanski, Marco Bermudez, Karen Sanchez Barjun, Oscar Diaz, Elsa Palou, Rossany E Escalante, Carlos Isai Hernandez, Mark L Stevens, Deke Eberhard, Manuel Sierra, Tito Alvarado, Omar Videa, Miguel Sierra-Hoffman, Fernando Valerio-Pascua
Frontiers in Pharmacology, doi:10.3389/fphar.2022.1054644
Background: The COVID-19 pandemic has impacted millions of lives globally. While COVID-19 did not discriminate against developed or developing nations, it has been a significant challenge for third world countries like Honduras to have widespread availability of advanced therapies. The concept of early treatment was almost unheard of when early outpatient treatments utilizing repurposed drugs in Latin American countries began showing promising results. One such drug is fluvoxamine, which has shown tremendous potential in two major studies. As a direct result, fluvoxamine was added to the standard of care in a major medical center outpatient COVID-19 clinic.
Ethics statement The studies involving human participants were reviewed and approved by Institutional Review Board (IRB) of the Hospital Centro Médico Sanpedrano and the Ethics committee of investigation of infectious and zoonotic disease masters of the Universidad Nacional Autónoma de Honduras. The patients/ participants provided their written informed consent to participate in this study.
Author contributions All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
Akbari, Tabrizi, Lankarani, Aria, Vakili et al., The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (Covid-19): A systematic review and meta-analysis, Life Sci,
doi:10.1016/j.lfs.2020.118167Almqvist, Skudder, Kuenzig, Schwartz, Effect of cyproheptadine on endotoxin-induced pulmonary platelet trapping, Am. Surg
Alsabhan, Alshammari, New use of the SSRI fluvoxamine in the treatment of Covid-19 symptoms, COVID-19 pandemic, mental Health and neuroscience -new scenarios for understanding and treatment
Bhuta, Khokher, Kesireddy, Iftikhar, Beran et al., Fluvoxamine in nonhospitalized patients with acute COVID-19 infection and the lack of efficacy in reducing rates of hospitalization, mechanical ventilation, and mortality in placebo-controlled trials: A systematic review and meta-analysis, Am. J. Ther,
doi:10.1097/mjt.0000000000001496Bortolotti, Gentili, Rizzo, Rotola, Rizzo, SARS-COV-2 spike 1 protein controls Natural Killer cell activation via the HLA-E/NKG2A pathway, Cells,
doi:10.3390/cells9091975Brimson, Prasanth, Malar, Brimson, Thitilertdecha, None
Calusic, Marcec, Luksa, Jurkovic, Kovac et al., Safety and efficacy of fluvoxamine in COVID-19 ICU patients: An open label, prospective cohort trial with matched controls, Br. J. Clin. Pharmacol,
doi:10.1111/bcp.15126Cheema, Jafar, Elrashedy, Shahid, Awan et al., Efficacy and safety of fluvoxamine for the treatment of COVID-19 patients: A systematic review and meta-analysis, J. Infect,
doi:10.1016/j.jinf.2022.10.012Chen, Subbarao, The immunobiology of sars, Annu. Rev
Dalton, Johansen, Mellemkjaer, Sørensen, Nørgård, None
Dawson, Christensen, Rickaby, Linehan, Johnston, Lung damage and pulmonary uptake of serotonin in intact dogs, J. Appl. Physiol,
doi:10.1152/jappl.1985.58.6.1761Duerschmied, Suidan, Demers, Herr, Carbo et al., Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice, Blood,
doi:10.1182/blood-2012-06-437392Facente, Reiersen, Lenze, Boulware, Klausner et al., Changes in histamine and serotonin secretion from rat peritoneal mast cells caused by antidepressants, Inflamm. Res,
doi:10.1007/bf02265168Fung, Huang, Liu, Coronavirus-induced ER stress response and its involvement in regulation of coronavirus-host interactions, Virus Res,
doi:10.1016/j.virusres.2014.09.016Halperin, Reber, Hayashi, Su, Sigma-1 receptor chaperones at the ERmitochondrion interface regulate ca2+ signaling and cell survival, Dialogues Clin. Neurosci,
doi:10.1016/j.cell.2007.08.036Iqubal, Hoda, Najmi, Haque, Macrophage activation and cytokine release syndrome in COVID-19: Current updates and analysis of repurposed and investigational anti-cytokine drugs, Drug Res,
doi:10.1055/a-1291-7692Jalali, Rezaie, Rola, Kyle-Sidell, Covid-19 pathophysiology: Are platelets and serotonin hiding in plain sight?, SSRN J,
doi:10.2139/ssrn.3800402Lenze, Mattar, Zorumski, Stevens, Schweiger et al., Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: A randomized clinical trial, JAMA,
doi:10.1001/jama.2020.22760Liu, Li, Liu, Liang, Wang et al., Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-COV-2 infected patients, EBioMedicine,
doi:10.1016/j.ebiom.2020.102763Liu, Tan, Chen, Zhu, Wan et al., Dynamic changes in lymphocyte subsets and parallel cytokine levels in patients with severe and critical COVID-19, BMC Infect. Dis,
doi:10.1186/s12879-021-05792-7Maclean, Herve, Eddahibi, Adnot, 5-hydroxytryptamine and the pulmonary circulation: Receptors, transporters and relevance to pulmonary arterial hypertension, Br. J. Pharmacol,
doi:10.1038/sj.bjp.0703570Marik, Iglesias, Varon, Kory, A scoping review of the pathophysiology of Covid-19, Int. J. Immunopathol. Pharmacol,
doi:10.1177/20587384211048026Martins-Gonçalves, Campos, Palhinha, Azevedo-Quintanilha, Mendes et al., Persisting platelet activation and hyperactivity in COVID-19 survivors, Circ. Res,
doi:10.1161/circresaha.122.321659Mazzoni, Salvati, Maggi, Capone, Vanni et al., Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent, J. Clin. Invest,
doi:10.1172/jci138554Mcgonagle, Ramanan, Bridgewood, Immune cartography of macrophage activation syndrome in the COVID-19 ERA, Nat. Rev. Rheumatol,
doi:10.1038/s41584-020-00571-1Mcgonagle, Sharif, O'regan, Bridgewood, The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease, Autoimmun. Rev,
doi:10.1016/j.autrev.2020.102537Meikle, Creeden, Mccullumsmith, Worth, SSRIs: Applications in inflammatory lung disease and implications for Covid-19, Neuropsychopharmacol. Rep,
doi:10.1002/npr2.12194Merad, Martin, Pathological inflammation in patients with COVID-19: A key role for monocytes and macrophages, Nat. Rev. Immunol,
doi:10.1038/s41577-020-0331-4Motta Junior, Miggiolaro, Nagashima, De Paula, Baena et al., Mast cells in alveolar septa of COVID-19 patients: A pathogenic pathway that may link interstitial edema to immunothrombosis, Front. Immunol,
doi:10.3389/fimmu.2020.574862Nochaiwong, Ruengorn, Awiphan, Chai-Adisaksopha, Tantraworasin et al., Use of serotonin reuptake inhibitor antidepressants and the risk of bleeding complications in patients on anticoagulant or antiplatelet agents: A systematic review and meta-analysis, Ann. Med,
doi:10.1080/07853890.2021.2017474Olsen, Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: A population-based cohort study, Arch. Intern. Med,
doi:10.1001/archinte.163.1.59Ontai, Zeng, Choi, Sierra Hoffman, Valerio Pascua et al., Early multidrug treatment of SARS-COV-2 (COVID-19) and decreased case fatality rates in Honduras, Epidemiol. Int. J,
doi:10.23880/eij-16000217Pineda, None
Reis, Dos, Moreira-Silva, Silva, Thabane et al., Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with Covid-19: The together randomised, platform clinical trial, Lancet. Glob. Health,
doi:10.1016/s2214-109x(21)00448-4Retamozo, Brito-Zerón, Sisó-Almirall, Flores-Chávez, Soto-Cárdenas et al., Haemophagocytic syndrome and Covid-19, Clin. Rheumatol,
doi:10.1007/s10067-020-05569-4Samuel, Seifert, Risk of bleeding in patients on full-dose enoxaparin with venous thromboembolism and selective serotonin reuptake inhibitors, Ann. Pharmacother,
doi:10.1177/1060028016677309Scala, Pacelli, Fighting the host reaction to SARS-COV-2 in critically ill patients: The possible contribution of off-label drugs, Front. Immunol,
doi:10.3389/fimmu.2020.01201Sciacchitano, Giovagnoli, Amodeo, Santino, Simmaco et al., AIDS and Covid-19 are two diseases separated by a common lymphocytopenia,
doi:10.21203/rs.3.rs-43462/v1Seftel, Boulware, Prospective cohort of fluvoxamine for early treatment of coronavirus disease 19,
doi:10.1093/ofid/ofab050Skurikhin, Andreeva, Khmelevskaya, Ermolaeva, Pershina et al., Effect of antiserotonin drug on the development of lung fibrosis and blood system reactions after intratracheal administration of Bleomycin, Bull. Exp. Biol. Med,
doi:10.1007/s10517-012-1567-1Tencomnao, Drugs that offer the potential to reduce hospitalization and mortality from SARS-COV-2 infection: The possible role of the sigma-1 receptor and autophagy, Expert Opin. Ther. Targets,
doi:10.1080/14728222.2021.1952987Valerio Pascua, Baires, Diaz, Sierra, Palou et al., Repurposing drugs for Covid-19 by a developing country, Epidemiol. Int. J
Valerio Pascua, Diaz, Medina, Contreras, Mistroff et al., A multi-mechanism approach reduces length of stay in the ICU for severe COVID-19 patients, PLOS ONE,
doi:10.1371/journal.pone.0245025Wang, Hu, Hu, Zhu, Liu et al., Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China, JAMA,
doi:10.1001/jama.2020.1585Zaid, Guessous, Puhm, Elhamdani, Chentoufi et al., Platelet reactivity to thrombin differs between patients with COVID-19 and those with Ards unrelated to COVID-19, Blood Adv,
doi:10.1182/bloodadvances.2020003513{ 'indexed': {'date-parts': [[2023, 3, 21]], 'date-time': '2023-03-21T14:30:49Z', 'timestamp': 1679409049267},
'reference-count': 48,
'publisher': 'Frontiers Media SA',
'license': [ { 'start': { 'date-parts': [[2022, 11, 30]],
'date-time': '2022-11-30T00:00:00Z',
'timestamp': 1669766400000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by/4.0/'}],
'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True},
'abstract': '<jats:p><jats:bold>Background:</jats:bold> The COVID-19 pandemic has impacted millions of '
'lives globally. While COVID-19 did not discriminate against developed or developing nations, '
'it has been a significant challenge for third world countries like Honduras to have '
'widespread availability of advanced therapies. The concept of early treatment was almost '
'unheard of when early outpatient treatments utilizing repurposed drugs in Latin American '
'countries began showing promising results. One such drug is fluvoxamine, which has shown '
'tremendous potential in two major studies. As a direct result, fluvoxamine was added to the '
'standard of care in a major medical center outpatient COVID-19 '
'clinic.</jats:p><jats:p><jats:bold>Methods:</jats:bold> This is a prospective observational '
'study performed at the Hospital Centro Médico Sampedrano (CEMESA) in San Pedro Sula, Cortes, '
'Honduras in the COVID-19 outpatient clinic. All patients were at least 15\xa0years of age who '
'had presented with mild or moderate signs and symptoms of COVID-19, and who also had a '
'documented positive SARS-CoV-2 antigen or Reverse Transcription Polymerase Chain Reaction '
'(RT-PCR) were included in the study. These patients then were all prescribed fluvoxamine. The '
'cohort of patients who decided to take fluvoxamine were compared for primary endpoints of '
'mortality and hospitalization risk to the cohort who did not take fluvoxamine. Patients were '
'then monitored for 30\xa0days with the first follow up at 7\xa0days and the second follow up '
'at 10–14\xa0days of symptom onset. Categorical variables were compared by Pearson Chi-square '
'test. The Relative risk was calculated using regression models. Continuous variables were '
'compared by t-test and Wilcoxon rank-sum '
'tests.</jats:p><jats:p><jats:bold>Results:</jats:bold> Out of total 657 COVID-19 cases, 594 '
'patients took fluvoxamine and 63 did not take fluvoxamine. A total of five patients (0.76 '
'percent) died, with only one death occurring in the fluvoxamine group. Patients who received '
'fluvoxamine had a significantly lower relative risk of mortality (RR 0.06, '
'<jats:italic>p</jats:italic> 0.011, 95% CI 0.007–0.516). There was a lower relative risk of '
'hospitalization in the patients who in the fluvoxamine group. (−10 vs. 30 hospitalizations, '
'RR 0.49, <jats:italic>p</jats:italic> = 0.035, 95% CI 0.26–0.95). There was 73 percent '
'reduction in relative risk of requiring oxygen in the fluvoxamine group (RR 0.27, '
'<jats:italic>p</jats:italic> &lt; 0.001, 95% CI 0.14–0.54 Mean lymphocytes count on the '
'first follow-up visit was significantly higher in the fluvoxamine group (1.72 vs. 1.38, Δ '
'0.33, <jats:italic>p</jats:italic> 0.007, CI '
'0.09–0.58).</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> The results of our study '
'suggest that fluvoxamine lowers the relative risk of death, hospitalization, and oxygen '
'requirement in COVID 19 patients.</jats:p>',
'DOI': '10.3389/fphar.2022.1054644',
'type': 'journal-article',
'created': { 'date-parts': [[2022, 11, 30]],
'date-time': '2022-11-30T06:16:23Z',
'timestamp': 1669788983000},
'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy',
'source': 'Crossref',
'is-referenced-by-count': 1,
'title': 'Impact of fluvoxamine on outpatient treatment of COVID-19 in Honduras in a prospective '
'observational real-world study',
'prefix': '10.3389',
'volume': '13',
'author': [ {'given': 'Estela', 'family': 'Pineda', 'sequence': 'first', 'affiliation': []},
{'given': 'Jarmanjeet', 'family': 'Singh', 'sequence': 'additional', 'affiliation': []},
{'given': 'Miguel Vargas', 'family': 'Pineda', 'sequence': 'additional', 'affiliation': []},
{'given': 'Jose Garay', 'family': 'Umanzor', 'sequence': 'additional', 'affiliation': []},
{'given': 'Fernando', 'family': 'Baires', 'sequence': 'additional', 'affiliation': []},
{'given': 'Luis G.', 'family': 'Benitez', 'sequence': 'additional', 'affiliation': []},
{'given': 'Cesar', 'family': 'Burgos', 'sequence': 'additional', 'affiliation': []},
{'given': 'Anupamjeet Kaur', 'family': 'Sekhon', 'sequence': 'additional', 'affiliation': []},
{'given': 'Nicole', 'family': 'Crisp', 'sequence': 'additional', 'affiliation': []},
{'given': 'Anita S.', 'family': 'Lewis', 'sequence': 'additional', 'affiliation': []},
{'given': 'Jana', 'family': 'Radwanski', 'sequence': 'additional', 'affiliation': []},
{'given': 'Marco', 'family': 'Bermudez', 'sequence': 'additional', 'affiliation': []},
{'given': 'Karen Sanchez', 'family': 'Barjun', 'sequence': 'additional', 'affiliation': []},
{'given': 'Oscar', 'family': 'Diaz', 'sequence': 'additional', 'affiliation': []},
{'given': 'Elsa', 'family': 'Palou', 'sequence': 'additional', 'affiliation': []},
{'given': 'Rossany E.', 'family': 'Escalante', 'sequence': 'additional', 'affiliation': []},
{'given': 'Carlos Isai', 'family': 'Hernandez', 'sequence': 'additional', 'affiliation': []},
{'given': 'Mark L.', 'family': 'Stevens', 'sequence': 'additional', 'affiliation': []},
{'given': 'Deke', 'family': 'Eberhard', 'sequence': 'additional', 'affiliation': []},
{'given': 'Manuel', 'family': 'Sierra', 'sequence': 'additional', 'affiliation': []},
{'given': 'Tito', 'family': 'Alvarado', 'sequence': 'additional', 'affiliation': []},
{'given': 'Omar', 'family': 'Videa', 'sequence': 'additional', 'affiliation': []},
{'given': 'Miguel', 'family': 'Sierra-Hoffman', 'sequence': 'additional', 'affiliation': []},
{'given': 'Fernando', 'family': 'Valerio-Pascua', 'sequence': 'additional', 'affiliation': []}],
'member': '1965',
'published-online': {'date-parts': [[2022, 11, 30]]},
'reference': [ { 'key': 'B1',
'doi-asserted-by': 'publisher',
'first-page': '365',
'DOI': '10.1007/978-3-642-38664-0_15',
'article-title': 'Serotonin transporter and serotonin receptors',
'volume': '218',
'author': 'Adnot',
'year': '2013',
'journal-title': 'Handb. Exp. Pharmacol.'},
{ 'key': 'B2',
'doi-asserted-by': 'publisher',
'first-page': '118167',
'DOI': '10.1016/j.lfs.2020.118167',
'article-title': 'The role of cytokine profile and lymphocyte subsets in the severity of '
'coronavirus disease 2019 (Covid-19): A systematic review and '
'meta-analysis',
'volume': '258',
'author': 'Akbari',
'year': '2020',
'journal-title': 'Life Sci.'},
{ 'key': 'B3',
'first-page': '503',
'article-title': 'Effect of cyproheptadine on endotoxin-induced pulmonary platelet '
'trapping',
'volume': '50',
'author': 'Almqvist',
'year': '1984',
'journal-title': 'Am. Surg.'},
{ 'key': 'B4',
'doi-asserted-by': 'crossref',
'article-title': 'New use of the SSRI fluvoxamine in the treatment of Covid-19 symptoms',
'volume-title': 'COVID-19 pandemic, mental Health and neuroscience - new scenarios for '
'understanding and treatment [working title]',
'author': 'Alsabhan',
'year': '2022',
'DOI': '10.5772/intechopen.105023'},
{ 'key': 'B5',
'doi-asserted-by': 'publisher',
'first-page': 'e298',
'DOI': '10.1097/mjt.0000000000001496',
'article-title': 'Fluvoxamine in nonhospitalized patients with acute COVID-19 infection '
'and the lack of efficacy in reducing rates of hospitalization, '
'mechanical ventilation, and mortality in placebo-controlled trials: A '
'systematic review and meta-analysis',
'volume': '29',
'author': 'Bhuta',
'year': '2022',
'journal-title': 'Am. J. Ther.'},
{ 'key': 'B6',
'doi-asserted-by': 'publisher',
'first-page': '1975',
'DOI': '10.3390/cells9091975',
'article-title': 'SARS-COV-2 spike 1 protein controls Natural Killer cell activation via '
'the HLA-E/NKG2A pathway',
'volume': '9',
'author': 'Bortolotti',
'year': '2020',
'journal-title': 'Cells'},
{ 'key': 'B7',
'doi-asserted-by': 'publisher',
'first-page': '435',
'DOI': '10.1080/14728222.2021.1952987',
'article-title': 'Drugs that offer the potential to reduce hospitalization and mortality '
'from SARS-COV-2 infection: The possible role of the sigma-1 receptor '
'and autophagy',
'volume': '25',
'author': 'Brimson',
'year': '2021',
'journal-title': 'Expert Opin. Ther. Targets'},
{ 'key': 'B8',
'doi-asserted-by': 'publisher',
'first-page': '2065',
'DOI': '10.1111/bcp.15126',
'article-title': 'Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open '
'label, prospective cohort trial with matched controls',
'volume': '88',
'author': 'Calusic',
'year': '2021',
'journal-title': 'Br. J. Clin. Pharmacol.'},
{ 'key': 'B9',
'doi-asserted-by': 'publisher',
'article-title': 'Efficacy and safety of fluvoxamine for the treatment of COVID-19 '
'patients: A systematic review and meta-analysis',
'author': 'Cheema',
'year': '2022',
'journal-title': 'J. Infect.',
'DOI': '10.1016/j.jinf.2022.10.012'},
{ 'key': 'B10',
'doi-asserted-by': 'publisher',
'first-page': '443',
'DOI': '10.1146/annurev.immunol.25.022106.141706',
'article-title': 'The immunobiology of sars',
'volume': '25',
'author': 'Chen',
'year': '2007',
'journal-title': 'Annu. Rev. Immunol.'},
{ 'key': 'B11',
'doi-asserted-by': 'publisher',
'first-page': '1334',
'DOI': '10.1182/blood-2012-02-413047',
'article-title': 'Platelets can enhance vascular permeability',
'volume': '120',
'author': 'Cloutier',
'year': '2012',
'journal-title': 'Blood'},
{ 'key': 'B12',
'doi-asserted-by': 'publisher',
'first-page': '59',
'DOI': '10.1001/archinte.163.1.59',
'article-title': 'Use of selective serotonin reuptake inhibitors and risk of upper '
'gastrointestinal tract bleeding: A population-based cohort study',
'volume': '163',
'author': 'Dalton',
'year': '2003',
'journal-title': 'Arch. Intern. Med.'},
{ 'key': 'B13',
'doi-asserted-by': 'publisher',
'first-page': '1761',
'DOI': '10.1152/jappl.1985.58.6.1761',
'article-title': 'Lung damage and pulmonary uptake of serotonin in intact dogs',
'volume': '58',
'author': 'Dawson',
'year': '1985',
'journal-title': 'J. Appl. Physiol.'},
{ 'key': 'B14',
'doi-asserted-by': 'publisher',
'first-page': '1008',
'DOI': '10.1182/blood-2012-06-437392',
'article-title': 'Platelet serotonin promotes the recruitment of neutrophils to sites of '
'acute inflammation in mice',
'volume': '121',
'author': 'Duerschmied',
'year': '2013',
'journal-title': 'Blood'},
{ 'key': 'B15',
'doi-asserted-by': 'publisher',
'first-page': '2081',
'DOI': '10.1007/s40265-021-01636-5',
'article-title': 'Fluvoxamine for the early treatment of SARS-COV-2 infection: A review '
'of current evidence',
'volume': '81',
'author': 'Facente',
'year': '2021',
'journal-title': 'Drugs'},
{ 'key': 'B16',
'doi-asserted-by': 'publisher',
'first-page': '141',
'DOI': '10.1007/bf02265168',
'article-title': 'Changes in histamine and serotonin secretion from rat peritoneal mast '
'cells caused by antidepressants',
'volume': '45',
'author': 'Ferjan',
'year': '1996',
'journal-title': 'Inflamm. Res.'},
{ 'key': 'B17',
'doi-asserted-by': 'publisher',
'first-page': '110',
'DOI': '10.1016/j.virusres.2014.09.016',
'article-title': 'Coronavirus-induced ER stress response and its involvement in '
'regulation of coronavirus–host interactions',
'volume': '194',
'author': 'Fung',
'year': '2014',
'journal-title': 'Virus Res.'},
{ 'key': 'B18',
'doi-asserted-by': 'publisher',
'first-page': '47',
'DOI': '10.31887/dcns.2007.9.1/dhalperin',
'article-title': 'Influence of antidepressants on hemostasis',
'volume': '9',
'author': 'Halperin',
'year': '2007',
'journal-title': 'Dialogues Clin. Neurosci.'},
{ 'key': 'B19',
'doi-asserted-by': 'publisher',
'first-page': '596',
'DOI': '10.1016/j.cell.2007.08.036',
'article-title': 'Sigma-1 receptor chaperones at the ER- mitochondrion interface regulate '
'ca2+ signaling and cell survival',
'volume': '131',
'author': 'Hayashi',
'year': '2007',
'journal-title': 'Cell'},
{ 'key': 'B20',
'doi-asserted-by': 'publisher',
'first-page': '173',
'DOI': '10.1055/a-1291-7692',
'article-title': 'Macrophage activation and cytokine release syndrome in COVID-19: '
'Current updates and analysis of repurposed and investigational '
'anti-cytokine drugs',
'volume': '71',
'author': 'Iqubal',
'year': '2021',
'journal-title': 'Drug Res.'},
{ 'key': 'B21',
'doi-asserted-by': 'publisher',
'article-title': 'Covid-19 pathophysiology: Are platelets and serotonin hiding in plain '
'sight?',
'author': 'Jalali',
'year': '2021',
'journal-title': 'SSRN J.',
'DOI': '10.2139/ssrn.3800402'},
{ 'key': 'B22',
'doi-asserted-by': 'publisher',
'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': 'Lenze',
'year': '2020',
'journal-title': 'JAMA'},
{ 'key': 'B23',
'doi-asserted-by': 'publisher',
'first-page': '102763',
'DOI': '10.1016/j.ebiom.2020.102763',
'article-title': 'Longitudinal characteristics of lymphocyte responses and cytokine '
'profiles in the peripheral blood of SARS-COV-2 infected patients',
'volume': '55',
'author': 'Liu',
'year': '2020',
'journal-title': 'EBioMedicine'},
{ 'key': 'B24',
'doi-asserted-by': 'publisher',
'first-page': '79',
'DOI': '10.1186/s12879-021-05792-7',
'article-title': 'Dynamic changes in lymphocyte subsets and parallel cytokine levels in '
'patients with severe and critical COVID-19',
'volume': '21',
'author': 'Liu',
'year': '2021',
'journal-title': 'BMC Infect. Dis.'},
{ 'key': 'B25',
'doi-asserted-by': 'publisher',
'first-page': '161',
'DOI': '10.1038/sj.bjp.0703570',
'article-title': '5-hydroxytryptamine and the pulmonary circulation: Receptors, '
'transporters and relevance to pulmonary arterial hypertension',
'volume': '131',
'author': 'MacLean',
'year': '2000',
'journal-title': 'Br. J. Pharmacol.'},
{ 'key': 'B26',
'doi-asserted-by': 'publisher',
'first-page': '20587384211048026',
'DOI': '10.1177/20587384211048026',
'article-title': 'A scoping review of the pathophysiology of Covid-19',
'volume': '35',
'author': 'Marik',
'year': '2021',
'journal-title': 'Int. J. Immunopathol. Pharmacol.'},
{ 'key': 'B27',
'doi-asserted-by': 'publisher',
'first-page': '944',
'DOI': '10.1161/circresaha.122.321659',
'article-title': 'Persisting platelet activation and hyperactivity in COVID-19 survivors',
'volume': '131',
'author': 'Martins-Gonçalves',
'year': '2022',
'journal-title': 'Circ. Res.'},
{ 'key': 'B28',
'doi-asserted-by': 'publisher',
'first-page': '4694',
'DOI': '10.1172/jci138554',
'article-title': 'Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent',
'volume': '130',
'author': 'Mazzoni',
'year': '2020',
'journal-title': 'J. Clin. Invest.'},
{ 'key': 'B29',
'doi-asserted-by': 'publisher',
'first-page': '145',
'DOI': '10.1038/s41584-020-00571-1',
'article-title': 'Immune cartography of macrophage activation syndrome in the COVID-19 '
'ERA',
'volume': '17',
'author': 'McGonagle',
'year': '2021',
'journal-title': 'Nat. Rev. Rheumatol.'},
{ 'key': 'B30',
'doi-asserted-by': 'publisher',
'first-page': '102537',
'DOI': '10.1016/j.autrev.2020.102537',
'article-title': 'The role of cytokines including interleukin-6 in COVID-19 induced '
'pneumonia and macrophage activation syndrome-like disease',
'volume': '19',
'author': 'McGonagle',
'year': '2020',
'journal-title': 'Autoimmun. Rev.'},
{ 'key': 'B31',
'doi-asserted-by': 'publisher',
'first-page': '325',
'DOI': '10.1002/npr2.12194',
'article-title': 'SSRIs: Applications in inflammatory lung disease and implications for '
'Covid‐19',
'volume': '41',
'author': 'Meikle',
'year': '2021',
'journal-title': 'Neuropsychopharmacol. Rep.'},
{ 'key': 'B32',
'doi-asserted-by': 'publisher',
'first-page': '355',
'DOI': '10.1038/s41577-020-0331-4',
'article-title': 'Pathological inflammation in patients with COVID-19: A key role for '
'monocytes and macrophages',
'volume': '20',
'author': 'Merad',
'year': '2020',
'journal-title': 'Nat. Rev. Immunol.'},
{ 'key': 'B33',
'doi-asserted-by': 'publisher',
'first-page': '574862',
'DOI': '10.3389/fimmu.2020.574862',
'article-title': 'Mast cells in alveolar septa of COVID-19 patients: A pathogenic pathway '
'that may link interstitial edema to immunothrombosis',
'volume': '11',
'author': 'Motta Junior',
'year': '2020',
'journal-title': 'Front. Immunol.'},
{ 'key': 'B34',
'doi-asserted-by': 'publisher',
'first-page': '80',
'DOI': '10.1080/07853890.2021.2017474',
'article-title': 'Use of serotonin reuptake inhibitor antidepressants and the risk of '
'bleeding complications in patients on anticoagulant or antiplatelet '
'agents: A systematic review and meta-analysis',
'volume': '54',
'author': 'Nochaiwong',
'year': '2021',
'journal-title': 'Ann. Med.'},
{ 'key': 'B35',
'doi-asserted-by': 'publisher',
'DOI': '10.23880/eij-16000217',
'article-title': 'Early multidrug treatment of SARS-COV-2 (COVID-19) and decreased case '
'fatality rates in Honduras',
'volume': '6',
'author': 'Ontai',
'year': '2022',
'journal-title': 'Epidemiol. Int. J.'},
{ 'key': 'B37',
'doi-asserted-by': 'publisher',
'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': 'Reis',
'year': '2022',
'journal-title': 'Lancet. Glob. Health'},
{ 'key': 'B38',
'doi-asserted-by': 'publisher',
'first-page': '1233',
'DOI': '10.1007/s10067-020-05569-4',
'article-title': 'Haemophagocytic syndrome and Covid-19',
'volume': '40',
'author': 'Retamozo',
'year': '2021',
'journal-title': 'Clin. Rheumatol.'},
{ 'key': 'B39',
'doi-asserted-by': 'publisher',
'first-page': '226',
'DOI': '10.1177/1060028016677309',
'article-title': 'Risk of bleeding in patients on full-dose enoxaparin with venous '
'thromboembolism and selective serotonin reuptake inhibitors',
'volume': '51',
'author': 'Samuel',
'year': '2016',
'journal-title': 'Ann. Pharmacother.'},
{ 'key': 'B40',
'doi-asserted-by': 'publisher',
'first-page': '1201',
'DOI': '10.3389/fimmu.2020.01201',
'article-title': 'Fighting the host reaction to SARS-COV-2 in critically ill patients: '
'The possible contribution of off-label drugs',
'volume': '11',
'author': 'Scala',
'year': '2020',
'journal-title': 'Front. Immunol.'},
{ 'key': 'B41',
'unstructured': 'AIDS and Covid-19 are two diseases separated by a common '
'lymphocytopenia\n'
' SciacchitanoS.\n'
' GiovagnoliS.\n'
' AmodeoR.\n'
' SantinoI.\n'
' SimmacoM.\n'
' AnibaldiP.\n'
' 10.21203/rs.3.rs-43462/v12020'},
{ 'key': 'B36',
'unstructured': 'Protocolo de Manejo Clinico de Pacientes con segun estadios clinico Y '
'nivel de atencion Covid-192020'},
{ 'key': 'B42',
'doi-asserted-by': 'publisher',
'first-page': 'ofab050',
'DOI': '10.1093/ofid/ofab050',
'article-title': 'Prospective cohort of fluvoxamine for early treatment of coronavirus '
'disease 19',
'volume': '8',
'author': 'Seftel',
'year': '2021',
'journal-title': 'Open Forum Infect. Dis.'},
{ 'key': 'B43',
'doi-asserted-by': 'publisher',
'first-page': '519',
'DOI': '10.1007/s10517-012-1567-1',
'article-title': 'Effect of antiserotonin drug on the development of lung fibrosis and '
'blood system reactions after intratracheal administration of Bleomycin',
'volume': '152',
'author': 'Skurikhin',
'year': '2012',
'journal-title': 'Bull. Exp. Biol. Med.'},
{ 'key': 'B44',
'doi-asserted-by': 'publisher',
'article-title': 'Signatures of mast cell activation are associated with severe COVID-19',
'author': 'Tan',
'year': '2021',
'DOI': '10.1101/2021.05.31.21255594'},
{ 'key': 'B45',
'doi-asserted-by': 'publisher',
'DOI': '10.23880/eij-16000234',
'article-title': 'Repurposing drugs for Covid-19 by a developing country',
'volume': '6',
'author': 'Valerio Pascua',
'year': '2022',
'journal-title': 'Epidemiol. Int. J.'},
{ 'key': 'B46',
'doi-asserted-by': 'publisher',
'first-page': 'e0245025',
'DOI': '10.1371/journal.pone.0245025',
'article-title': 'A multi-mechanism approach reduces length of stay in the ICU for severe '
'COVID-19 patients',
'volume': '16',
'author': 'Valerio Pascua',
'year': '2021',
'journal-title': 'PLOS ONE'},
{ 'key': 'B47',
'doi-asserted-by': 'publisher',
'first-page': '1061',
'DOI': '10.1001/jama.2020.1585',
'article-title': 'Clinical characteristics of 138 hospitalized patients with 2019 novel '
'coronavirus–infected pneumonia in Wuhan, China',
'volume': '323',
'author': 'Wang',
'year': '2020',
'journal-title': 'JAMA'},
{ 'key': 'B48',
'doi-asserted-by': 'publisher',
'first-page': '635',
'DOI': '10.1182/bloodadvances.2020003513',
'article-title': 'Platelet reactivity to thrombin differs between patients with COVID-19 '
'and those with Ards unrelated to COVID-19',
'volume': '5',
'author': 'Zaid',
'year': '2021',
'journal-title': 'Blood Adv.'}],
'container-title': 'Frontiers in Pharmacology',
'original-title': [],
'link': [ { 'URL': 'https://www.frontiersin.org/articles/10.3389/fphar.2022.1054644/full',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2022, 11, 30]],
'date-time': '2022-11-30T06:16:29Z',
'timestamp': 1669788989000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fphar.2022.1054644/full'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2022, 11, 30]]},
'references-count': 48,
'alternative-id': ['10.3389/fphar.2022.1054644'],
'URL': 'http://dx.doi.org/10.3389/fphar.2022.1054644',
'relation': {},
'ISSN': ['1663-9812'],
'subject': ['Pharmacology (medical)', 'Pharmacology'],
'container-title-short': 'Front. Pharmacol.',
'published': {'date-parts': [[2022, 11, 30]]}}
