COVID-19 early treatment: real-time analysis of 1,044 studies

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Analysis of 28 COVID-19 early treatments, and database of 176 other potential treatments66 countries have approved early treatments.Treatments do not replace vaccines and other measures. All practical, effective, and safe means should be used. Elimination is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all variants. Denying efficacy increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage.
Levels Ramirez-Sandoval et al., Archives of Medical Research, doi:10.1016/j.arcmed.2021.09.006 (Peer Reviewed) death, ↓31.5%, p<0.0001 Very Low Vitamin D Levels are a Strong Independent Predictor of Mortality in Hospitalized Patients with Severe COVID-19
Details   Retrospective 2,908 hospitalized patients in Mexico with vitamin D levels measured on admission, showing significantly lower mortality for patients without vitamin D deficiency.
In Vitro Jitaboam et al., Research Square, doi:10.21203/ (Peer Reviewed) (In Vitro) in vitro Favipiravir and Ivermectin Showed in Vitro Synergistic Antiviral Activity against SARS-CoV-2
Details   In Vitro study showing a strong synergistic effect of ivermectin and favipiravir. Combining multiple antiviral drugs with different mechanisms of action helps to minimize drug resistance and toxicity.
Late Maghbooli et al., Endocrine Practice, doi:10.1016/j.eprac.2021.09.016 (Peer Reviewed) death, ↓40.0%, p=0.72 Treatment with 25-hydroxyvitamin D3 (calcifediol) is associated with a reduction in the blood neutrophil-to-lymphocyte ratio marker of disease severity in patients hospitalized with COVID-19: a pilot, multicenter, randomized, placebo-controlled double blind clinical trial
Details   RCT 106 hospitalized patients with vitamin D levels <30ng/ml in Iran, 53 treated with calcifediol, showing that treatment was able to correct vitamin D deficiency/insufficiency, resulting in improved immune system function. Hospitalizatio..
Late Ivashkin et al., Probiotics Antimicrob Proteins, doi:10.1007/s12602-021-09858-5 (Peer Reviewed) death, ↑2.0%, p=1.00 Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial
Details   RCT 200 patients, 99 treated with a probiotic (Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301). There was no sign..
Levels Afaghi et al., The Tohoku Journal of Experimental Medicine, doi:10.1620/tjem.255.127 (Peer Reviewed) death, ↓55.0%, p=0.002 Prevalence and Clinical Outcomes of Vitamin D Deficiency in COVID-19 Hospitalized Patients: A Retrospective Single-Center Analysis
Details   Retrospective 646 COVID-19+ hospitalized patients in Iran, showing higher mortality with vitamin D deficiency.
Late Hasan et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.10.012 (Peer Reviewed) death, ↓92.9%, p=0.0004 The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients
Details   RCT 158 severe condition patients in Iraq, 82 treated with melatonin, showing lower mortality, thrombosis, and sepsis with treatment.
Early Majeed et al., Evidence-Based Complementary and Alternative Medicine, doi:10.1155/2021/8447545 (Peer Reviewed) ventilation, ↓66.2%, p=1.00 A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of a Nutritional Supplement (ImmuActive) for COVID-19 Patients
Details   RCT 100 patients in India, 50 treated with ImmuActive (curcumin, andrographolides, resveratrol, zinc, selenium, and piperine), showing improved recovery with treatment.
Review Fordham et al., OSF Preprints, doi:10.31219/ (Review) (Preprint) review The uses and abuses of systematic reviews
Details   Analysis of defects in the Popp et al. meta analysis.
PrEP Wander et al., Diabetes Care, doi:10.2337/dc21-1351 (Peer Reviewed) death, ↓15.0%, p<0.0001 Prior Glucose-Lowering Medication Use and 30-Day Outcomes Among 64,892 Veterans With Diabetes and COVID-19
Details   Retrospective 64,892 veterans with diabetes in the USA, showing lower mortality with existing metformin use.
In Silico Francés-Monerris et al., Physical Chemistry Chemical Physics, doi:10.1039/D1CP02967C (Peer Reviewed) Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection
Details   In Silico molecular dynamics study showing that ACE2 and ACE2/RBD aggregates form persistent interactions with ivermectin.
Levels Mukherjee et al., FEBS Open Bio, doi:10.1002/2211-5463.13309 (Peer Reviewed) Seasonal UV exposure and vitamin D: Association with the dynamics of COVID-19 transmission in Europe
Details   Analysis of UV and temperature levels in 26 European countries, showing that low temperature, UV index, and cloud-free vitamin D UV dose levels are negatively correlated with COVID-19 prevalence. Authors suggest that low UV exposure can a..
PrEP Pérez-Segura et al., Medicina Clínica, doi:10.1016/j.medcle.2021.02.010 (Peer Reviewed) death, ↑49.1%, p<0.0001 Prognostic factors at admission on patients with cancer and COVID-19: Analysis of HOPE registry data
Details   Retrospective 770 COVID-19 patients with cancer, showing increased mortality with aspirin use in unadjusted results.
PrEP Sisinni et al., International Journal of Cardiology, doi:10.1016/j.ijcard.2021.09.058 (Peer Reviewed) death, ↑7.1%, p=0.65 Pre-admission acetylsalicylic acid therapy and impact on in-hospital outcome in COVID-19 patients: The ASA-CARE study
Details   Retrospective 984 COVID-19 patients, 253 taking aspirin prior to admission, showing lower risk of respiratory support upgrade with treatment.
Levels Abdollahzadeh et al., Infection, Genetics and Evolution, doi:10.1016/j.meegid.2021.105098 (Peer Reviewed) Association of Vitamin D receptor gene polymorphisms and clinical/severe outcomes of COVID-19 patients
Details   Analysis of 500 hospitalized patients in Iran, showing associations between specific vitamin D receceptor gene polymorphisms and COVID-19 outcomes.
PrEP Basheer et al., Metabolites, doi:10.3390/metabo11100679 (Peer Reviewed) death, ↑13.0%, p=0.0003 Clinical Predictors of Mortality and Critical Illness in Patients with COVID-19 Pneumonia
Details   Retrospective 390 hospitalized patients in Israel, showing higher risk of mortality with prior aspirin use. Details of the analysis are not provided.
N/A TrialSite News (News) news Committed to Medical Evidence, a Prominent Ivermectin Group is Eradicated from the Memories of Cyberspace
Details   Report on Twitter’s censorship of the British Ivermectin Recommendation Development group.
Late Mozaffari et al., Clinical Infectious Diseases, doi:10.1093/cid/ciab875 (Peer Reviewed) death, ↓12.0%, p=0.003 Remdesivir treatment in hospitalized patients with COVID-19: a comparative analysis of in-hospital all-cause mortality in a large multi-center observational cohort
Details   Retrospective 28,855 remdesivir patients with PSM matched controls, showing lower mortality with treatment.
Late Zhao et al., Anesthesiology, doi:10.1097/ALN.0000000000003999 (Peer Reviewed) death, ↓43.0%, p=0.0006 Treatments Associated with Lower Mortality among Critically Ill COVID-19 Patients: A Retrospective Cohort Study
Details   Retrospective 2,070 hospitalized patients in the USA, showing lower mortality with aspirin treatment.
Early Merck News Release (News) death, ↓94.2%, p=0.003 Merck and Ridgeback’s Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study
Details   News release reporting interim analysis of the MOVe-OUT trial, showing significantly lower risk of hospitalization or death. NCT04575597.
Late Babalola et al., Research Square, doi:10.21203/ (Preprint) no disch., ↑54.5%, p=0.20 A Randomized Controlled Trial of Ivermectin Monotherapy Versus Hydroxychloroquine, Ivermectin, and Azithromycin Combination Therapy in Covid-19 Patients in Nigeria
Details   Small RCT with 61 patients in Nigeria, all patients treated with ivermectin, zinc, and vitamin C, showing no significant improvements in recovery with the addition of HCQ+AZ. PACTR202108891693522.
PrEP Fung et al., medRxiv, doi:10.1101/2021.09.28.21264186 (Preprint) death, ↓15.0%, p=0.10 Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients
Details   Retrospective database analysis of 374,229 patients in the USA, showing no significant difference with HCQ use, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research sh..
Late Menardi et al., PharmAdvances, doi:10.36118/pharmadvances.2021.15 (Peer Reviewed) death, ↓35.2%, p=0.12 A retrospective analysis on pharmacological approaches to COVID-19 patients in an Italian hub hospital during the early phase of the pandemic
Details   Retrospective 277 hospitalized patients in Italy, showing lower mortality with HCQ treatment, not reaching statistical significance, and subject to confounding by indication.
Animal Cecon et al., Journal of Pineal Research, doi:10.1111/jpi.12772 (Peer Reviewed) animal study Therapeutic potential of melatonin and melatonergic drugs on K18-hACE2 mice infected with SARS-CoV-2
Details   Study of melatonin and melatonergic compounds with mice expressing the human ACE2 receptor (K18-hACE2). Daily administration of melatonin, agomelatine or ramelteon delayed the occurrence of severe clinical outcome with improvement of surv..
In Silico Şimşek et al., Journal of Molecular Graphics and Modelling, doi:10.1016/j.jmgm.2021.108038 (Peer Reviewed) In silico identification of SARS-CoV-2 cell entry inhibitors from selected natural antivirals
Details   In SIlico study identifying quercetin derivatives as SARS-CoV-2 spike protein, ACE2, and neuropilin inhibitors.
Late Simsek et al., Annals of Medical Research, doi:10.5455/annalsmedres.2020.10.1043 (Peer Reviewed) death, ↓44.1%, p=0.18 Effects of high dose vitamin C administration in Covid-19 patients
Details   Retrospective 139 hospitalized patients in Turkey, 58 treated with high dose vitamin C, showing improved kidney functioning with treatment. Mortality was lower with treatment, but not reaching statistical significance with the small sampl..
Late Yildiz et al., Bratislava Medical Journal, doi:10.4149/BLL_2021_119 (Peer Reviewed) death, ↓80.9%, p=0.04 The prognostic significance of vitamin D deficiency in patients with COVID-19 pneumonia
Details   Retrospective 207 hospitalized patients in Turkey, 37 with vitamin D levels <30ng/ml treated with a 300,000IU vitamin D, showing lower mortality with treatment.
Meta Borsche et al., medRxiv, doi:10.1101/2021.09.22.21263977 (Preprint) (meta analysis) meta-analysis COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3: Results of a systematic review and meta-analysis
Details   Meta analysis of 8 studies with vitamin D levels measured pre-infection or on the day of hospital admission, showing a correlation between the levels and mortality. Authors recommend combining vaccination with vitamin D supplementation to..
PrEP Arroyo-Díaz et al., Frontiers in Public Health, doi:10.3389/fpubh.2021.758347 (Peer Reviewed) death, ↑12.4%, p=0.51 Previous Vitamin D Supplementation and Morbidity and Mortality Outcomes in People Hospitalised for COVID19: A Cross-Sectional Study
Details   Retrospective 1,267 hospitalized patients in Spain, 189 on vitamin D supplementation before admission, showing lower ICU admission with supplementation, and no statistically significant difference for mortality or ventilation.
Early Mayer et al., Zenodo, doi:10.5281/zenodo.5525362 (Preprint) death, ↓55.1%, p<0.0001 Safety and efficacy of a MEURI Program for the use of high dose ivermectin in COVID-19 patients
Details   Retrospective 21,232 patients in Argentina, 3,266 assigned to ivermectin treatment, showing lower mortality with treatment. Greater benefits were seen for patients >40, and a dose dependent response was found.
Late Dorward et al., medRxiv, doi:2021.09.20.21263828 (Preprint) hosp./death, ↑29.8%, p=0.65 Colchicine for COVID-19 in adults in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial
Details   Late treatment RCT with 156 colchicine patients in the UK, showing no significant differences. ISRCTN86534580.
Review Castle et al., Journal of Inflammation Research, doi:10.2147/JIR.S323356 (Review) (Peer Reviewed) review Implications for Systemic Approaches to COVID-19: Effect Sizes of Remdesivir, Tocilizumab, Melatonin, Vitamin D3, and Meditation
Details   Review of the effects of COVID-19 on inflammatory markers, and the effects on those markers of standard treatments vs. vitamin D, melatonin, and meditation, showing comparable or superior effects with the non-standard treatments. The stan..
Levels Laing et al., Nutrients, doi:10.3390/nu13103304 (Peer Reviewed) death, ↓79.0%, p=0.01 Course and Survival of COVID-19 Patients with Comorbidities in Relation to the Trace Element Status at Hospital Admission
Details   Retrospective 79 hospitalized patients in Belgium, showing mortality associated with zinc and selenium deficiency.
Levels Marino-Ramirez et al., medRxiv, doi:10.1101/2021.09.20.21263865 (Preprint) Vitamin D and socioeconomic deprivation mediate COVID-19 ethnic health disparities
Details   UK Biobank retrospective showing that vitamin supplements, including vitamin D, mediate the Asian disparity in COVID-19 susceptibility, and vitamin D levels mediate Asian and Black COVID-19 severity disparities. Authors conclude that the ..
Levels Derakhshanian et al., Food Science & Nutrition, doi:10.1002/fsn3.2591 (Peer Reviewed) death, ↓44.8%, p=0.02 The predictive power of serum vitamin D for poor outcomes in COVID-19 patients
Details   Retrospective 290 hospitalized patients in Iran, showing higher mortality with vitamin D deficiency.
Late Hassaniazad et al., Phytotherapy Research, doi:10.1002/ptr.7294 (Peer Reviewed) no recov., ↑45.7%, p=0.90 A triple-blind, placebo-controlled, randomized clinical trial to evaluate the effect of curcumin-containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID-19 patients
Details   Small RCT with 40 low risk patients in Iran, 20 treated with nano-curcumin, showing no significant difference in outcomes with treatment. Authors note that treatment can improve peripheral blood inflammatory indices and modulate immune re..

Source: COVID-19 early treatment: real-time analysis of 1,044 studies