Inosine pranobex was associated with a reduction in mortality in COVID-19 by over 22%, as reported in a retrospective study utilizing complete health data from the Czech national registry

Veselý et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2026.108519, Mar 2026
Mortality, 46% improvement lower risk ← → higher risk Mortality, pre-omicron 22% Mortality, omicron 65% Inosine Pranobex  Veselý et al.  EARLY TREATMENT Is early treatment with inosine pranobex beneficial for COVID-19? Retrospective 127,038 patients in Czech Republic (Mar 2020 - Dec 2021) Lower mortality with inosine pranobex (not stat. sig., p=0.11) c19early.org Veselý et al., Int. J. Infectious Dise.., Mar 2026 0 0.5 1 1.5 2+ RR
Retrospective 67,841 inosine pranobex recipients matched 1:2 with 135,682 controls from the Czech national registry, showing significantly reduced COVID-19 mortality with treatment.
Negative control outcome analyses (non-COVID mortality, cardiovascular mortality, external-cause mortality) showed no benefit, suggesting the effect is not purely a healthy-user bias. Authors note that treatment was prescribed preferentially to higher-risk patients, yet recipients still showed lower mortality, which strengthens the apparent benefit but cannot fully exclude unmeasured confounders.
risk of death, 46.3% lower, RR 0.54, p = 0.11, treatment 42,346, control 84,692.
risk of death, 22.0% lower, RR 0.78, p < 0.001, treatment 697 of 42,346 (1.6%), control 1,788 of 84,692 (2.1%), NNT 215, pre-omicon.
risk of death, 65.0% lower, RR 0.35, p < 0.001, treatment 32 of 25,495 (0.1%), control 181 of 50,990 (0.4%), NNT 436, omicron.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Veselý et al., 31 Mar 2026, retrospective, Czech Republic, peer-reviewed, 5 authors, study period 1 March, 2020 - 31 December, 2021. Contact: dalibor.vesely@lf3.cuni.cz, veselydalibor@seznam.cz.
Inosine pranobex is an orally administered small-molecule immunomodulator with broad antiviral activity. It enhances natural killer cell cytotoxicity and T-lymphocyte function and promotes Th1-type cytokine responses, thereby augmenting host antiviral defenses.
Abstract: ARTICLE IN PRESS [International Journal of Infectious Diseases xxx (xxxx) xxx](https://doi.org/10.1016/j.ijid.2026.108519) Contents lists available at ScienceDirect International Journal of Infectious Diseases journal homepage: [www.elsevier.com/locate/ijid](http://www.elsevier.com/locate/ijid) Inosine pranobex was associated with a reduction in mortality in COVID-19 by over 22%, as reported in a retrospective study utilizing complete health data from the Czech national registry Dalibor Veselý 1 , ∗ , Václav ˇ Capek 2 , Ondˇ rej Šanca 3 , Jiˇ rí Beran 4 , Jiˇ rí Slíva 1 - 1 Department of Pharmacology, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic - 2 Independent researcher - 3 Institute of Health Information and Statistics of the Czech Republic, Prague, Czech Republic - 4 Department for Tropical, Travel Medicine and Immunization, Institute for Postgraduate Medical Education, Prague, Czech Republic a r t i c l e i n f o Article history: Received 24 August 2025 Revised 17 February 2026 Accepted 28 February 2026 Available online xxx pranobex Keywords: COVID-19 Pandemic Inosine Isoprinosine Mortality Risk factor
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}, "publisher": "Elsevier BV", "reference": [ { "DOI": "10.2165/00003495-198632050-00001", "article-title": "Inosine pranobex", "author": "Campoli-Richards", "doi-asserted-by": "crossref", "first-page": "383", "journal-title": "Drugs", "key": "10.1016/j.ijid.2026.108519_bib0001", "volume": "32", "year": "1986" }, { "DOI": "10.1007/s12325-019-00995-6", "article-title": "Inosine pranobex: a key player in the game against a wide range of viral infections and non-infectious diseases", "author": "Sliva", "doi-asserted-by": "crossref", "first-page": "1878", "journal-title": "Adv Ther", "key": "10.1016/j.ijid.2026.108519_bib0002", "volume": "36", "year": "2019" }, { "DOI": "10.3390/v13112246", "article-title": "Inosine pranobex deserves attention as a potential immunomodulator to achieve early alteration of the COVID-19 disease course", "author": "Beran", "doi-asserted-by": "crossref", "first-page": "2246", "journal-title": "Viruses", "key": "10.1016/j.ijid.2026.108519_bib0003", "volume": "13", "year": "2021" }, { "DOI": "10.1146/annurev-immunol-032712-100001", "article-title": "Control of human viral infections by natural killer cells", "author": "Jost", "doi-asserted-by": "crossref", "first-page": "163", "journal-title": "Annu Rev Immunol", "key": "10.1016/j.ijid.2026.108519_bib0004", "volume": "31", "year": "2013" }, { "DOI": "10.1016/j.intimp.2016.11.023", "article-title": "Inosine acedoben dimepranol promotes an early and sustained increase in the natural killer cell component of circulating lymphocytes: a clinical trial supporting anti-viral indications", "author": "Rumel Ahmed", "doi-asserted-by": "crossref", "first-page": "108", "journal-title": "Int Immunopharmacol", "key": "10.1016/j.ijid.2026.108519_bib0005", "volume": "42", "year": "2017" }, { "DOI": "10.1002/eji.201847948", "article-title": "Inosine pranobex enhances human NK cell cytotoxicity by inducing metabolic activation and NKG2D ligand expression", "author": "McCarthy", "doi-asserted-by": "crossref", "first-page": "130", "journal-title": "Eur J Immunol", "key": "10.1016/j.ijid.2026.108519_bib0006", "volume": "50", "year": "2020" }, { "DOI": "10.3390/pathogens9121055", "article-title": "Inosine pranobex significantly decreased the case-fatality rate among PCR positive elderly with SARS-CoV-2 at three nursing homes in the Czech Republic", "author": "Beran", "doi-asserted-by": "crossref", "first-page": "1055", "journal-title": "Pathogens", "key": "10.1016/j.ijid.2026.108519_bib0007", "volume": "9", "year": "2020" }, { "article-title": "Efficacy and safety of inosine pranobex in COVID-19 patients: a multicenter phase 3 randomized double-blind, placebo-controlled trial", "author": "C", "journal-title": "Adv Ther", "key": "10.1016/j.ijid.2026.108519_bib0008", "volume": "5", "year": "2022" }, { "DOI": "10.1016/j.ijid.2024.01.017", "article-title": "Case fatality rates of COVID-19 during epidemic periods of variants of concern: a meta-analysis by continents", "author": "Xia", "doi-asserted-by": "crossref", "journal-title": "Int J Infect Dis", "key": "10.1016/j.ijid.2026.108519_bib0009", "volume": "141", "year": "2024" }, { "DOI": "10.3389/fpubh.2022.884121", "article-title": "Risk of SARS-CoV-2 reinfection 18 months after primary infection: population-level observational study", "author": "Flacco", "doi-asserted-by": "crossref", "journal-title": "Front Public Health", "key": "10.1016/j.ijid.2026.108519_bib0010", "volume": "10", "year": "2022" }, { "DOI": "10.1038/s41586-020-2918-0", "article-title": "Age-specific mortality and immunity patterns of SARS-CoV-2", "author": "O’Driscoll", "doi-asserted-by": "crossref", "first-page": "140", "journal-title": "Nature", "key": "10.1016/j.ijid.2026.108519_bib0011", "volume": "590", "year": "2021" }, { "DOI": "10.1136/bmj.m4509", "article-title": "Infection fatality risk for SARS-CoV-2 in community dwelling population of Spain: nationwide seroepidemiological study", "author": "Pastor-Barriuso", "doi-asserted-by": "crossref", "first-page": "m4509", "journal-title": "BMJ", "key": "10.1016/j.ijid.2026.108519_bib0012", "volume": "371", "year": "2020" }, { "DOI": "10.1016/j.ijid.2020.07.029", "article-title": "Comorbidities and the risk of severe or fatal outcomes associated with coronavirus disease 2019: a systematic review and meta-analysis", "author": "Zhou", "doi-asserted-by": "crossref", "first-page": "47", "journal-title": "Int J Infect Dis", "key": "10.1016/j.ijid.2026.108519_bib0013", "volume": "99", "year": "2020" }, { "DOI": "10.3389/fmed.2021.588013", "article-title": "Chronic diseases as a predictor for severity and mortality of COVID-19: a systematic review with cumulative meta-analysis", "author": "Geng", "doi-asserted-by": "crossref", "journal-title": "Front Med", "key": "10.1016/j.ijid.2026.108519_bib0014", "volume": "8", "year": "2021" }, { "key": "10.1016/j.ijid.2026.108519_bib0015", "unstructured": "Šanca O, Jarkovský J, Klika P, Davidová H, Klimeš D, Mužík J, et al. Přehled vykázaných tříznakových diagnóz dle MKN-10. 2024. https://www.nzip.cz/clanek/1760-prehled-vykazane-triznakove-diagnozy-mkn-10-nrhzs-datovy-souhrn [accessed 30 April 2025]." }, { "DOI": "10.1093/eurheartj/ehaa433", "article-title": "Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study", "author": "Gao", "doi-asserted-by": "crossref", "first-page": "2058", "journal-title": "Eur Heart J", "key": "10.1016/j.ijid.2026.108519_bib0016", "volume": "41", "year": "2020" }, { "DOI": "10.2337/dci21-0001", "article-title": "Diabetes and COVID-19: population impact 18 months into the pandemic", "author": "Gregg", "doi-asserted-by": "crossref", "first-page": "1916", "journal-title": "Diabetes Care", "key": "10.1016/j.ijid.2026.108519_bib0017", "volume": "44", "year": "2021" }, { "DOI": "10.1016/j.medcli.2020.12.017", "article-title": "Coronary heart disease and COVID-19: a meta-analysis", "author": "Liang", "doi-asserted-by": "crossref", "first-page": "547", "journal-title": "Med Clín", "key": "10.1016/j.ijid.2026.108519_bib0018", "volume": "156", "year": "2021" }, { "DOI": "10.1016/j.ajem.2020.07.009", "article-title": "Effect of heart failure on the outcome of COVID-19 — a meta analysis and systematic review", "author": "Yonas", "doi-asserted-by": "crossref", "first-page": "204", "journal-title": "Am J Emerg Med", "key": "10.1016/j.ijid.2026.108519_bib0019", "volume": "46", "year": "2021" }, { "DOI": "10.20892/j.issn.2095-3941.2020.0559", "article-title": "Effects of cancer on patients with COVID-19: a systematic review and meta-analysis of 63,019 participants", "author": "Yang", "doi-asserted-by": "crossref", "first-page": "298", "journal-title": "Cancer Biol Med", "key": "10.1016/j.ijid.2026.108519_bib0020", "volume": "18", "year": "2021" }, { "DOI": "10.1111/jce.14770", "article-title": "Outcomes and mortality associated with atrial arrhythmias among patients hospitalized with COVID-19", "author": "Peltzer", "doi-asserted-by": "crossref", "first-page": "3077", "journal-title": "J Cardiovasc Electrophysiol", "key": "10.1016/j.ijid.2026.108519_bib0021", "volume": "31", "year": "2020" }, { "DOI": "10.1016/j.jstrokecerebrovasdis.2020.104949", "article-title": "Impact of cerebrovascular and cardiovascular diseases on mortality and severity of COVID-19–systematic review, meta-analysis, and meta-regression", "author": "Pranata", "doi-asserted-by": "crossref", "journal-title": "J Stroke Cerebrovasc Dis", "key": "10.1016/j.ijid.2026.108519_bib0022", "volume": "29", "year": "2020" }, { "DOI": "10.1038/s41598-023-36208-y", "article-title": "Anemia as a risk factor for disease progression in patients admitted for COVID-19: data from a large, multicenter cohort study", "author": "Veronese", "doi-asserted-by": "crossref", "first-page": "9035", "journal-title": "Sci Rep", "key": "10.1016/j.ijid.2026.108519_bib0023", "volume": "13", "year": "2023" }, { "DOI": "10.1097/MCP.0000000000000834", "article-title": "Chronic obstructive pulmonary disease and COVID-19: interrelationships", "author": "Singh", "doi-asserted-by": "crossref", "first-page": "76", "journal-title": "Curr Opin Pulm Med", "key": "10.1016/j.ijid.2026.108519_bib0024", "volume": "28", "year": "2022" }, { "DOI": "10.1016/j.cpcardiol.2021.101007", "article-title": "Peripheral artery disease and COVID-19 outcomes: insights from the Yale DOM-CovX registry", "author": "Smolderen", "doi-asserted-by": "crossref", "journal-title": "Curr Probl Cardiol", "key": "10.1016/j.ijid.2026.108519_bib0025", "volume": "47", "year": "2022" }, { "DOI": "10.1038/s41598-022-06276-7", "article-title": "Mortality and readmission rates among hospitalized COVID-19 patients with varying stages of chronic kidney disease: a multicenter retrospective cohort", "author": "Appelman", "doi-asserted-by": "crossref", "first-page": "2258", "journal-title": "Sci Rep", "key": "10.1016/j.ijid.2026.108519_bib0026", "volume": "12", "year": "2022" }, { "DOI": "10.1007/s11684-020-0822-5", "article-title": "Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection", "author": "Tan", "doi-asserted-by": "crossref", "first-page": "746", "journal-title": "Front Med", "key": "10.1016/j.ijid.2026.108519_bib0027", "volume": "14", "year": "2020" }, { "DOI": "10.1016/j.isci.2022.103743", "article-title": "Immunity to SARS-CoV-2 up to 15 months after infection", "author": "Marcotte", "doi-asserted-by": "crossref", "journal-title": "iScience", "key": "10.1016/j.ijid.2026.108519_bib0028", "volume": "25", "year": "2022" }, { "article-title": "Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells", "author": "Cohen", "journal-title": "Cell Rep Med", "key": "10.1016/j.ijid.2026.108519_bib0029", "volume": "2", "year": "2021" }, { "DOI": "10.1056/NEJMoa2118691", "article-title": "Protection against SARS-CoV-2 after Covid-19 vaccination and previous infection", "author": "Hall", "doi-asserted-by": "crossref", "first-page": "1207", "journal-title": "N Engl J Med", "key": "10.1016/j.ijid.2026.108519_bib0030", "volume": "386", "year": "2022" }, { "DOI": "10.1016/j.envres.2022.112911", "article-title": "SARS-CoV-2 reinfections: overview of efficacy and duration of natural and hybrid immunity", "author": "Pilz", "doi-asserted-by": "crossref", "journal-title": "Env Res", "key": "10.1016/j.ijid.2026.108519_bib0031", "volume": "209", "year": "2022" }, { "DOI": "10.1186/s12879-022-07418-y", "article-title": "SARS-CoV-2 vaccine effectiveness against infection, symptomatic and severe COVID-19: a systematic review and meta-analysis", "author": "Ssentongo", "doi-asserted-by": "crossref", "first-page": "439", "journal-title": "BMC Infect Dis", "key": "10.1016/j.ijid.2026.108519_bib0032", "volume": "22", "year": "2022" }, { "DOI": "10.1016/S0140-6736(22)00152-0", "article-title": "Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression", "author": "Feikin", "doi-asserted-by": "crossref", "first-page": "924", "journal-title": "Lancet", "key": "10.1016/j.ijid.2026.108519_bib0033", "volume": "399", "year": "2022" }, { "DOI": "10.1001/jama.2021.19499", "article-title": "Association between mRNA vaccination and COVID-19 hospitalization and disease severity", "author": "Tenforde", "doi-asserted-by": "crossref", "first-page": "2043", "journal-title": "JAMA", "key": "10.1016/j.ijid.2026.108519_bib0034", "volume": "326", "year": "2021" }, { "DOI": "10.1016/S0140-6736(20)32661-1", "article-title": "AZ - safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomized controlled trials in Brazil, South Africa, and the UK", "author": "Voysey", "doi-asserted-by": "crossref", "first-page": "99", "journal-title": "Lancet", "key": "10.1016/j.ijid.2026.108519_bib0035", "volume": "397", "year": "2021" }, { "DOI": "10.1056/NEJMoa2101544", "article-title": "Jansen safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19", "author": "Sadoff", "doi-asserted-by": "crossref", "first-page": "2187", "journal-title": "N Engl J Med", "key": "10.1016/j.ijid.2026.108519_bib0036", "volume": "384", "year": "2021" }, { "key": "10.1016/j.ijid.2026.108519_bib0037", "unstructured": "Ewopharma International, s.r.o. Isoprinosine 500 mg tablety SmPC. State Institute for Drug Control (SÚKL); 2019. https://prehledy.sukl.cz/prehledy/v1/dokumenty/12916 [accessed 10 August 2025]." }, { "key": "10.1016/j.ijid.2026.108519_bib0038", "unstructured": "Themis Medicare Limited. Viralex SmPC. Rwanda Food and Drug Authority; 2024. https://rwandafda.gov.rw/wp-content/uploads/2025/04//VIRALEX-InosinePranobex500mgTablets-SmPC.pdf [accessed 10 August 2025]." }, { "DOI": "10.1016/S1473-3099(22)00507-2", "article-title": "Real-world effectiveness of early molnupiravir or nirmatrelvir–ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong’s omicron BA.2 wave: a retrospective cohort study", "author": "Wong", "doi-asserted-by": "crossref", "first-page": "1681", "journal-title": "Lancet Infect Dis", "key": "10.1016/j.ijid.2026.108519_bib0039", "volume": "22", "year": "2022" } ], "reference-count": 39, "references-count": 39, "relation": {}, "resource": { "primary": { "URL": "https://linkinghub.elsevier.com/retrieve/pii/S1201971226001542" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Inosine pranobex was associated with a reduction in mortality in COVID-19 by over 22%, as reported in a retrospective study utilizing complete health data from the Czech national registry", "type": "journal-article", "update-policy": "https://doi.org/10.1016/elsevier_cm_policy" }
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