Nov 23 |
Antihistamine H1RAs for COVID-19: real-time meta analysis of 15 studies | |
| Statistically significant lower risk is seen for mortality, recovery, and cases. 8 studies from 7 independent teams in 4 countries show significant improvements. Meta analysis using the most serious outcome reported shows 39% [23R.. | ||
Jul 2 |
et al., mBio, doi:10.1128/mbio.01088-24 | The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2 |
| In Vitro and mouse study showing that antihistamine drugs targeting the histamine receptor H1 (HRH1) inhibit SARS-CoV-2 infection. Authors find that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the N-terminal.. | ||
Oct 29 2023 |
et al., International Journal of Molecular Sciences, doi:10.3390/ijms242115718 | Sigma Receptor Ligands Prevent COVID Mortality In Vivo: Implications for Future Therapeutics |
| Mouse study showing the combination of lactoferrin and diphenhydramine resulted in slower weight loss, improved survival, and faster weight recovery in SARS-CoV-2 infected animals compared to controls. The study authors propose the.. | ||
Aug 29 2023 |
et al., bioRxiv, doi:10.1101/2023.08.28.554806 | Chlorpheniramine Maleate Displays Multiple Modes of Antiviral Action Against SARS-CoV-2: A Mechanistic Study |
| In Vitro study showing that chlorpheniramine maleate (CPM) inhibits SARS-CoV-2 infection by affecting viral adsorption, replication, and having a direct virucidal effect in Vero E6 cells. Molecular docking analysis revealed that CPM inter.. | ||
Aug 4 2023 |
et al., Pharmaceuticals, doi:10.3390/ph16081107 | Medications Modulating the Acid Sphingomyelinase/Ceramide System and 28-Day Mortality among Patients with SARS-CoV-2: An Observational Study |
| Retrospective 72,105 COVID+ hospitalized patients in France, showing no significant difference in mortality with antihistamine H1RAs desloratadine and hydroxyzine. | ||
Jul 17 2023 |
et al., Frontiers in Cardiovascular Medicine, doi:10.3389/fcvm.2023.1202696 | Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation |
| 29% lower PASC (p=0.1). Retrospective 14 patients with long-COVID symptoms attributed to mast cell activation treated with H1 and H2 antihistamines compared to 13 control patients, showing significant improvements in several symptoms in the treatment group compa.. | ||
Dec 31 2022 |
et al., Medical Research Archives, doi:10.18103/mra.v10i3.2752 | Intranasal Chlorpheniramine Maleate for the treatment of COVID-19: Translational and Clinical Evidence |
| 87% lower hospitalization (p=0.08). Small RCT showing significantly improved recovery with intranasal chlorpheniramine maleate. Authors also perform an In Vitro study showing efficacy with a highly differentiated three-dimensional model of normal, human-derived tracheal/bro.. | ||
Dec 6 2022 |
et al., Scientific Reports, doi:10.1038/s41598-022-25399-5 | Desloratadine, an FDA-approved cationic amphiphilic drug, inhibits SARS-CoV-2 infection in cell culture and primary human nasal epithelial cells by blocking viral entry |
| In Vitro study showing that desloratadine inhibits SARS-CoV-2 infection in Vero E6 cells, Calu-3 cells, and primary human nasal epithelial cells (HNECs) by blocking viral entry through the endosomal pathway. Authors screened 8 FDA-approve.. | ||
Oct 18 2022 |
et al., Research Square, doi:10.21203/rs.3.rs-2167465/v1 | Chlorpheniramine Intranasal Spray to Accelerate COVID-19 Clinical Recovery in an Outpatient Setting: The ACCROS Trials |
| 54% faster recovery (p<0.0001). RCT and retrospective study of chlorpheniramine nasal spray for COVID-19. The retrospective study included 660 outpatients showing fewer days with general COVID-19 symptoms, cough, anosmia, and ageusia compared to standard of care alone. .. | ||
Oct 18 2022 |
et al., Research Square, doi:10.21203/rs.3.rs-2167465/v1 | Chlorpheniramine Intranasal Spray to Accelerate COVID-19 Clinical Recovery in an Outpatient Setting: The ACCROS Trials |
| 61% improved recovery (p=0.0002). RCT and retrospective study of chlorpheniramine nasal spray for COVID-19. The RCT included 101 outpatients showing significantly faster recovery with treatment. The retrospective study results are listed separately [Valerio-Pascua]. | ||
Aug 16 2022 |
et al., Virology Journal, doi:10.1186/s12985-023-02195-9 (date from preprint) | Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments |
| 40% lower mortality (p=0.003). Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with antihistamine H1RAs, without statistical significance. Since only hospitalized patients are included, results do not reflect different probabilitie.. | ||
Jun 29 2022 |
et al., Journal of General Internal Medicine, doi:10.1007/s11606-022-07701-3 | Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans |
| 43% lower mortality (p<0.0001). Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including antihistamines. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a .. | ||
Jan 8 2022 |
et al., Pharmaceuticals, doi:10.3390/ph15010078 | A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis |
| 80% lower mortality (p=0.05). PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of loratadine. | ||
Jan 6 2022 |
, S., Cureus, doi:10.7759/cureus.20980 | Molecular Modeling and Preliminary Clinical Data Suggesting Antiviral Activity for Chlorpheniramine (Chlorphenamine) Against COVID-19 |
| In Silico study suggesting that the over-the-counter antihistamine chlorpheniramine may have antiviral activity against SARS-CoV-2. Using structural database searches and molecular modeling, authors found that chlorpheniramine shares simi.. | ||
Dec 15 2021 |
et al., Journal of Clinical Medicine, doi:10.3390/jcm10245891 | Hydroxyzine Use and Mortality in Patients Hospitalized for COVID-19: A Multicenter Observational Study |
| 46% lower mortality (p=0.02). Retrospective 15,103 hospitalized COVID-19 patients in France showing lower mortality with hydroxyzine use. | ||
Apr 30 2021 |
et al., Chemico-Biological Interactions, doi:10.1016/j.cbi.2021.109420 | Testing of the inhibitory effects of loratadine and desloratadine on SARS-CoV-2 spike pseudotyped virus viropexis |
| In Vitro study showing that histamine H1 antagonists loratadine (LOR) and desloratadine (DES) inhibit SARS-CoV-2 spike pseudovirus entry into ACE2-overexpressing HEK293T cells, with DES showing greater efficacy. Using cell membrane chroma.. | ||
Apr 30 2021 |
et al., Pulmonary Pharmacology & Therapeutics, doi:10.1016/j.pupt.2021.101989 | Antihistamines and azithromycin as a treatment for COVID-19 on primary health care – A retrospective observational study in elderly patients |
| Retrospective 84 elderly nursing home residents in Spain showing no mortality, hospitalization, or ICU admission with early treatment with antihistamines alone or in combination with azithromycin. | ||
Mar 31 2021 |
et al., Signal Transduction and Targeted Therapy, doi:10.1038/s41392-021-00689-y (date from preprint) | Real-world evidence for improved outcomes with histamine antagonists and aspirin in 22,560 COVID-19 patients |
| 25% lower mortality (p=0.4). PSM retrospective TriNetX database analysis of 1,379 severe COVID-19 patients requiring respiratory support, showing lower mortality with H1RAs+H2RAs versus famotidine alone, without statistical significance. | ||
Feb 22 2021 |
et al., BMC Medicine, doi:10.1186/s12916-021-01907-8 | Relation of severe COVID-19 to polypharmacy and prescribing of psychotropic drugs: the REACT-SCOT case-control study |
| 30% higher severe cases (p=0.0004). Retrospective 4,251 severe COVID-19 cases and 36,738 matched controls in Scotland showing increased risk of severe COVID-19 with PPI use and antihistamine H1RA use. Adjusted results are only provided for the patients not in care homes (2,.. | ||
Jan 31 2021 |
et al., Biochemical and Biophysical Research Communications, doi:10.1016/j.bbrc.2020.11.095 | Identification of antiviral antihistamines for COVID-19 repurposing |
| 34% fewer cases (p<0.0001). Retrospective 219,000 patients showing lower risk of COVID-19 with antihistamine H1RA use. In Vitro study showing these drugs exhibit direct antiviral activity against SARS-CoV-2. Molecular docking suggests hydroxyzine and azelastine may .. | ||
Jan 5 2021 |
et al., bioRxiv, doi:10.1101/2021.01.04.424792 | Hydroxyzine inhibits SARS-CoV-2 Spike protein binding to ACE2 in a qualitative in vitro assay |
| In Vitro study showing that hydroxyzine inhibits the binding of SARS-CoV-2 Spike protein receptor-binding domain (RBD) to ACE2 in a qualitative assay. Hydroxyzine inhibited RBD binding to ACE2 in a dose-dependent manner, while labetalol, .. | ||
Dec 10 2020 |
et al., BMJ Open, doi:10.1136/bmjopen-2020-041577 | Influence of prior comorbidities and chronic medications use on the risk of COVID-19 in adults: a population-based cohort study in Tarragona, Spain |
| 53% fewer cases (p=0.05). Retrospective 79,083 adults aged ≥50 years in Spain showing lower with of PCR-confirmed COVID-19 with antihistamine use, close to statistical significance. | ||
Oct 27 2020 |
et al., medRxiv, doi:10.1101/2020.10.23.20154302 | Association between Hydroxyzine Use and Reduced Mortality in Patients Hospitalized for Coronavirus Disease 2019: Results from a multicenter observational study |
| 58% lower mortality (p=0.001). Retrospective 7,345 hospitalized COVID-19 patients in France showing lower mortality with hydroxyzine use, with a significant dose-response relationship. Hydroxyzine was also associated with a faster decrease in inflammatory markers. | ||
Jul 25 2020 |
et al., The Journal of Clinical Hypertension, doi:10.1111/jch.13948 | Use of distinct anti‐hypertensive drugs and risk for COVID‐19 among hypertensive people: A population‐based cohort study in Southern Catalonia, Spain |
| 61% fewer cases (p=0.1). Retrospective 34,936 hypertensive outpatients in Spain showing no significant difference in COVID-19 cases with PPIs and antihistamine H1RAs. | ||
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.
Thanks for your feedback! Please search before submitting papers and note
that studies are listed under the date they were first available, which may be
the date of an earlier preprint.