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0 0.5 1 1.5 2+ Mortality, non-MV 45% Improvement Relative Risk Mortality, MV 76% Hospitalization time, non-MV 14% Hospitalization time, MV 18% Ibuprofen for COVID-19  Salva et al.  LATE TREATMENT Is late treatment with ibuprofen + alkalinization beneficial for COVID-19? Retrospective 501 patients in Argentina (April - October 2020) Lower mortality (p=0.0093) and shorter hospitalization (p<0.0001) c19early.org Salva et al., Infectious Diseases and .., Aug 2021 Favors ibuprofen Favors control

Reversal of SARS-CoV2-Induced Hypoxia by Nebulized Sodium Ibuprofenate in a Compassionate Use Program

Salva et al., Infectious Diseases and Therapy, doi:10.1007/s40121-021-00527-2, NCT04382768
Aug 2021  
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Retrospective 383 hospitalized COVID-19 patients in Argentina showing signifcantly lower mortality and shorter hospital stay with nebulized sodium ibuprofenate compared to 195 contemporaneous controls.
The treatment appears to be the same as detailed in Kalayan, which reports a pH of 8.5. Kreutzberger et al. showed that SARS-CoV-2 requires an acidic pH (between 6.2-6.8) for membrane fusion and cell entry, even when the viral spike protein is primed by proteases like TMPRSS2. Efficacy seen here may be more due to alkalinization, which shows more consistent higher efficacy than ibuprofen in studies to date.
Baseline SpO2 was significantly different for the patients on mechanical ventilation at baseline.
2 studies use direct respiratory tract administration Kalayan, Salva
Targeted administration to the respiratory tract provides treatment directly to the typical source of initial SARS-CoV-2 infection and replication, and allows for rapid onset of action, higher local drug concentration, and reduced systemic side effects (early treatment may be more beneficial).
This study is excluded in meta analysis: combined treatments may contribute more to the effect seen.
Study covers ibuprofen and alkalinization.
risk of death, 45.2% lower, RR 0.55, p = 0.009, treatment 35 of 327 (10.7%), control 34 of 174 (19.5%), NNT 11, patients not on mechanical ventilation at baseline.
risk of death, 75.7% lower, RR 0.24, p < 0.001, treatment 11 of 56 (19.6%), control 17 of 21 (81.0%), NNT 1.6, patients on mechanical ventilation at baseline.
hospitalization time, 13.5% lower, relative time 0.86, p < 0.001, treatment mean 11.5 (±0.3) n=327, control mean 13.3 (±0.9) n=174, patients not on mechanical ventilation at baseline.
hospitalization time, 17.8% lower, relative time 0.82, p < 0.001, treatment mean 14.8 (±1.4) n=56, control mean 18.0 (±5.6) n=21, patients on mechanical ventilation at baseline.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Salva et al., 30 Aug 2021, retrospective, Argentina, peer-reviewed, 26 authors, study period 4 April, 2020 - 31 October, 2020, this trial uses multiple treatments in the treatment arm (combined with alkalinization) - results of individual treatments may vary, trial NCT04382768 (history). Contact: garcia.nestor@conicet.gov.ar.
This PaperIbuprofenAll
Reversal of SARS-CoV2-Induced Hypoxia by Nebulized Sodium Ibuprofenate in a Compassionate Use Program
Oscar Salva, Pablo A Doreski, Celia S Giler, Dario C Quinodoz, Lucia G Guzmán, Sonia E Muñoz, Mariana N Carrillo, Daniela J Porta, Germán Ambasch, Esteban Coscia, Jorge L Tambini Diaz, Germán D Bueno, Jorge O Fandi, Miriam A Maldonado, Leandro E Peña Chiappero, Fernando Fournier, Hernán A Pérez, Mauro A Quiroga, Javier A Sala Mercado, Carlos Martínez Picco, Marcelo Alejandro Beltrán, Luis A Argañarás, Nicolás Martínez Ríos, Galia I Kalayan, Dante M Beltramo, Néstor H García
Infectious Diseases and Therapy, doi:10.1007/s40121-021-00527-2
Introduction: Sodium ibuprofenate in hypertonic saline (NaIHS) administered directly to the lungs by nebulization and inhalation has antibacterial and anti-inflammatory effects, with the potential to deliver these benefits to hypoxic patients. We describe a compassionate use program that offered this therapy to hospitalized COVID-19 patients. Methods: NaIHS (50 mg ibuprofen, tid) was provided in addition to standard of care (SOC) to hospitalized COVID-19 patients until oxygen saturation levels of[94% were achieved on ambient air. Patients wore a containment hood to diminish aerosolization. Outcome data from participating patients treated at multiple hospitals in Argentina between April 4 and October 31, 2020, are summarized.
References
Ackermann, Verleden, Kuehnel, Haverich, Welte et al., Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19, N Engl J Med
Baraniuk, Lundgren, Mizoguchi, Peden, Gawin et al., Bradykinin and respiratory mucous membranes: analysis of bradykinin binding site distribution and secretory responses in vitro and in vivo, Am Rev Respir Dis
Beigel, Tomashek, Dodd, Mehta, Zingman et al., Remdesivir for the treatment of COVID-19-final report, N Engl J Med
Brito-Azevedo, Pinto, Preta, Bouskela, SARS-CoV-2 infection causes pulmonary shunt by vasodilatation, J Med Virol
Cao, Wang, Wen, Liu, Wang et al., A Trial of Lopinavir-Ritonavir in adults hospitalized with severe COVID-19, N Engl J Med
Cavalcanti, Zampieri, Rosa, Azevedo, Veiga et al., Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate COVID-19, N Engl J Med
Das, Can bioactive lipids inactivate coronavirus (COVID-19)?, Arch Med Res
Dill, Patel, Yang, Bachoo, Powell et al., A molecular mechanism for ibuprofen-mediated RhoA inhibition in neurons, J Neurosci
Freeman, Peek, Becker, Smith, Denison, Coronaviruses induce entry-independent, continuous macropinocytosis, mBio, doi:10.1128/mBio.01340-14
Garcı ´a, Porta, Alasino, Mun ˜oz, Se et al., Ibuprofen, a traditional drug that may impact the course of COVID-19 new effective formulation in nebulizable solution, Med Hypotheses
Garvin, Alvarez, Miller, Prates, Walker et al., A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm, Elife
Gholamreza-Fahimi, Bisha, Hahn, Straßen, Krybus et al., Cyclooxygenase activity in bradykinin-induced dermal extravasation. A study in mice and humans, Biomed Pharmacother
Hammock, Gilligan, Panigrahy, Eicosanoids, Am J Pathol
Konstan, Byard, Hoppel, Davis, Effect of high-dose ibuprofen in patients with cystic fibrosis, N Engl J Med
Magro, Mulvey, Berlin, Nuovo, Salvatore et al., Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases, Transl Res
Mccullagh, Nelder, Generalized linear models (monographs on statistics and applied probability)
Mcfadyen, Stevens, Peter, The emerging threat of (Micro)thrombosis in COVID-19 and its therapeutic implications, Circ Res
Mcintyre, Philp, Inwood, Effect of ibuprofen on platelet function in normal subjects and hemophiliac patients, Clin Pharmacol Ther
Mun ˜oz, Alasino, Garro, Heredia, Garcı ´a et al., High concentrations of sodium chloride improve microbicidal activity of ibuprofen against common cystic fibrosis pathogens, Pharmaceuticals
Serhan, Systems approach to inflammation resolution: identification of novel anti-inflammatory and pro-resolving mediators, J Thromb Haemost
Shi, Han, Jiang, Cao, Alwalid et al., Radiological findings from 81 patients with COVID-study, Lancet Infect Dis
Simonovich, Pratx, Scibona, Beruto, Vallone et al., A randomized trial of convalescent plasma in COVID-19 severe pneumonia, N Engl J Med
Smith, Redfern, Pimentel, Collins, Malycha, The National Early Warning Score 2 (NEWS2), Clin Med
Stone, Frigault, Serling-Boyd, Fernandes, Harvey et al., Efficacy of tocilizumab in patients hospitalized with COVID-19, N Engl J Med
Swaine, Dittmar, CDC42 use in viral cell entry processes by RNA viruses, Viruses
Tsubouchi, Mukai, Kawahito, Yamada, Kohno et al., Meloxicam inhibits the growth of non-small cell lung cancer, Anticancer Res
Walsh, Low-dose aspirin: treatment for the imbalance of increased thromboxane and decreased prostacyclin in preeclampsia, Am J Perinatol
Zamudio-Meza, Castillo-Alvarez, Gonza ´lez-Bonilla, Meza, Cross-talk between Rac1 and Cdc42 GTPases regulates formation of filopodia required for dengue virus type-2 entry into HMEC-1 cells, J Gen Virol
Zhou, Nonsteroidal anti-inflammatory drugs can lower amyloidogenic A 42 by inhibiting rho, Science
{ 'DOI': '10.1007/s40121-021-00527-2', 'ISSN': ['2193-8229', '2193-6382'], 'URL': 'http://dx.doi.org/10.1007/s40121-021-00527-2', 'alternative-id': ['527'], 'assertion': [ { 'group': {'label': 'Article History', 'name': 'ArticleHistory'}, 'label': 'Received', 'name': 'received', 'order': 1, 'value': '14 April 2021'}, { 'group': {'label': 'Article History', 'name': 'ArticleHistory'}, 'label': 'Accepted', 'name': 'accepted', 'order': 2, 'value': '12 August 2021'}, { 'group': {'label': 'Article History', 'name': 'ArticleHistory'}, 'label': 'First Online', 'name': 'first_online', 'order': 3, 'value': '30 August 2021'}, { 'group': {'label': 'Funding', 'name': 'EthicsHeading'}, 'name': 'Ethics', 'order': 1, 'value': 'This work was supported by funds from the Química Luar SRL, who provided NaIHS ' 'under compassionate use. This funding body had no role in: the design of the ' 'study; the collection, analysis, or interpretation of data; and the writing of ' 'the manuscript. The journal’s Rapid Service Fee was funded by the Química Luar ' 'SRL.'}, { 'group': {'label': 'Authorship', 'name': 'EthicsHeading'}, 'name': 'Ethics', 'order': 2, 'value': 'All named authors meet the International Committee of Medical Journal Editors ' '(ICMJE) criteria for authorship for this article, take responsibility for the ' 'integrity of the work as a whole, and have given their approval for this ' 'version to be published.'}, { 'group': {'label': 'Authorship Contributions', 'name': 'EthicsHeading'}, 'name': 'Ethics', 'order': 3, 'value': 'Conceptualization: Pablo Alexis Doreski, Germán Ambasch, Luis Alberto ' 'Argañarás, Nicolás Martínez Ríos, Dante Miguel Beltramo and Néstor Horacio ' 'García. Data curation: Sonia Edith Muñoz, Mariana Natalia Carrillo, Daniela ' 'Josefina Porta, Hernán Alejandro Pérez, Néstor Horacio García. Formal analysis: ' 'Pablo Alexis Doreski, Sonia Edith Muñoz, Mariana Natalia Carrillo, Daniela ' 'Josefina Porta, Hernán Alejandro Pérez, Dante Miguel Beltramo, Néstor Horacio ' 'García. Funding acquisition: Luis Alberto Argañarás, Nicolás Martínez Ríos and ' 'Galia Ines Kalayan. Investigation: Oscar Salva, Celia Sara Giler, Dario Conrado ' 'Quinodoz, Lucia Guadalupe Guzmán, Germán Ambasch, Esteban Coscia, Jorge Luis ' 'Tambini Díaz, Germán David Bueno, Jorge Oscar Fandi, Miriam Angélica Maldonado, ' 'Leandro Eugenio Peña Chiappero, Fernando Fournier, Hernán Alejandro Pérez, ' 'Mauro Andrés Quiroga, Javier Agustín Sala Mercado, Marcelo Alejandro Beltrán, ' 'Carlos Martínez Picco, Methodology: Luis Alberto Argañarás, Nicolás Martínez ' 'Ríos, Dante Miguel Beltramo, Néstor Horacio García. Project administration: ' 'Luis Alberto Argañarás, Nicolás Martínez Ríos, Galia Inés Kalayan. Resources: ' 'Luis Alberto Argañarás and Nicolás Martínez Ríos. Supervision: Luis Alberto ' 'Argañarás, Nicolás Martínez Ríos, Néstor Horacio García. Software: Hernán ' 'Alejandro Pérez. Validation: Oscar Salva, Pablo Alexis Doreski, Néstor Horacio ' 'García. Visualization: Néstor Horacio García. Writing—original draft: Néstor ' 'Horacio García. Writing—review and editing: Pablo Alexis Doreski, Dario Conrado ' 'Quinodoz, Luis Alberto Argañarás, Nicolás Martínez Ríos, Dante Miguel Beltramo, ' 'Néstor Horacio García.'}, { 'group': {'label': 'Disclosures', 'name': 'EthicsHeading'}, 'name': 'Ethics', 'order': 4, 'value': 'All named authors confirm that they have no conflicts of interest to declare.'}, { 'group': {'label': 'Compliance with Ethics Guidelines', 'name': 'EthicsHeading'}, 'name': 'Ethics', 'order': 5, 'value': 'Ethical approval was obtained from the Institutional Independent Ethics ' 'Committees and district regulatory agencies of Córdoba and Mendoza Provinces ' 'for the compassionate use of Luarprofeno<sup>®</sup> (sodium ibuprofenate in ' 'hypertonic saline, or NaIHS, for nebulization). The program was carried out in ' 'accordance with the principles of the Declaration of Helsinki for Buenos Aires. 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' '2010;30(3):963–72.', 'volume': '30', 'year': '2010'}, { 'DOI': '10.1016/j.mehy.2020.110079', 'author': 'NH García', 'doi-asserted-by': 'publisher', 'first-page': '110079', 'journal-title': 'Med Hypotheses', 'key': '527_CR27', 'unstructured': 'García NH, Porta DJ, Alasino RV, Muñoz SE, Beltramo DM. Ibuprofen, a ' 'traditional drug that may impact the course of COVID-19 new effective ' 'formulation in nebulizable solution. Med Hypotheses. 2020;144:110079.', 'volume': '144', 'year': '2020'}, { 'DOI': '10.7861/clinmedicine.19-3-260', 'author': 'GB Smith', 'doi-asserted-by': 'publisher', 'first-page': '260', 'issue': '3', 'journal-title': 'Clin Med', 'key': '527_CR28', 'unstructured': 'Smith GB, Redfern OC, Pimentel MA, Gerry S, Collins GS, Malycha J, et ' 'al. The National Early Warning Score 2 (NEWS2). Clin Med. ' '2019;19(3):260–260.', 'volume': '19', 'year': '2019'}, { 'author': 'P McCullagh', 'edition': '2', 'key': '527_CR29', 'unstructured': 'McCullagh P, Nelder JA. 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Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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