COVID-19 early treatment: real-time analysis of 3,328 studies
Analysis of 56 COVID early treatments,
approvals in 102 countries, database of
5,033 treatments
Ziaei | Systematic review and meta analysis of 5 studies, showing significantly lower mortality, ICU admission, and hospitalization with quercetin treatment. |
Burhan | 559 patients remdesivir ICU: 15% higher mortality (p=0.23) |
Marikawa | Analysis of molnupiravir active metabolite N4-hydroxycytidine's effects on mouse preimplantation embryos in vitro, showing embryotoxicity at.. |
Sanderson | Identification of SARS-CoV-2 variants created by molnupiravir treatment, including cases of onwards transmission. Authors find a class of long.. |
Alves | In Vitro study showing that iron-free and iron-saturated bovine lactoferrin inhibited SARS-CoV-2 ancestral and omicron Vero cell infection... |
Treatment cost times median NNT - details and limitations.
0.7% of treatments show efficacy.
Timeline for when studies showed efficacy - details and limitations.
0.7% of treatments show efficacy.
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All clinical results for selected treatments. 0.7% of treatments show efficacy.
Random effects meta-analysis of all studies (pooled effects, all stages). Treatments with ≤3 studies with distinct authors or with <50 control events are shown in grey. Pooled results across all stages and outcomes depend on the distribution of stages and outcomes tested - for example late stage treatment may be less effective and if the majority of studies are late stage this may obscure the efficacy of early treatment. Please see the specific stage and outcome analyses. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments. 0.7% of proposed treatments show efficacy in clinical studies. | |||||
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Random effects meta-analysis of early treatment studies (pooled effects). Treatments with ≤3 studies with distinct authors or with <50 control events are shown in grey. Pooled results across all outcomes are affected by the distribution of outcomes tested, please see detail pages for specific outcome analysis. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments. 0.7% of proposed treatments show efficacy in clinical studies. | |||||
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Random effects meta-analysis of all mortality results (all stages). Treatments with ≤3 studies with distinct authors or with <25 control events are shown in grey. Pooled results across all stages depend on the distribution of stages tested - for example late stage treatment may be less effective and if the majority of studies are late stage this may obscure the efficacy of early treatment. Please see the specific stage analyses. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments. 0.7% of proposed treatments show efficacy in clinical studies. | |||||
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Random effects meta-analysis of early treatment mortality results. Treatments with ≤3 studies with distinct authors or with <25 control events are shown in grey. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments. 0.7% of proposed treatments show efficacy in clinical studies. | |||||
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Random effects meta-analysis of prophylaxis studies (pooled effects). Treatments with ≤3 studies with distinct authors or with <50 control events are shown in grey. Pooled results across all outcomes are affected by the distribution of outcomes tested, please see detail pages for specific outcome analysis. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments. 0.7% of proposed treatments show efficacy in clinical studies. | |||||
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Random effects meta-analysis of prophylaxis mortality results. Treatments with ≤3 studies with distinct authors or with <25 control events are shown in grey. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments. 0.7% of proposed treatments show efficacy in clinical studies. |
LATE TREATMENT | ||||||
Physician / Team | Location | Patients | HospitalizationHosp. | MortalityDeath | ||
Dr. David Uip (*) | Brazil | 2,200 | 38.6% (850) | Ref. | 2.5% (54) | Ref. |
EARLY TREATMENT - 39 physicians/teams | ||||||
Physician / Team | Location | Patients | HospitalizationHosp. | ImprovementImp. | MortalityDeath | ImprovementImp. |
Dr. Roberto Alfonso Accinelli 0/360 deaths for treatment within 3 days |
Peru | 1,265 | 0.6% (7) | 77.5% | ||
Dr. Mohammed Tarek Alam patients up to 84 years old |
Bangladesh | 100 | 0.0% (0) | 100.0% | ||
Dr. Oluwagbenga Alonge | Nigeria | 310 | 0.0% (0) | 100.0% | ||
Dr. Raja Bhattacharya up to 88yo, 81% comorbidities |
India | 148 | 1.4% (2) | 44.9% | ||
Dr. Flavio Cadegiani | Brazil | 3,450 | 0.1% (4) | 99.7% | 0.0% (0) | 100.0% |
Dr. Alessandro Capucci | Italy | 350 | 4.6% (16) | 88.2% | ||
Dr. Shankara Chetty | South Africa | 8,000 | 0.0% (0) | 100.0% | ||
Dr. Deborah Chisholm | USA | 100 | 0.0% (0) | 100.0% | ||
Dr. Ryan Cole | USA | 400 | 0.0% (0) | 100.0% | 0.0% (0) | 100.0% |
Dr. Marco Cosentino vs. 3-3.8% mortality during period; earlier treatment better |
Italy | 392 | 6.4% (25) | 83.5% | 0.3% (1) | 89.6% |
Dr. Jeff Davis | USA | 6,000 | 0.0% (0) | 100.0% | ||
Dr. Dhanajay | India | 500 | 0.0% (0) | 100.0% | ||
Dr. Bryan Tyson & Dr. George Fareed | USA | 20,000 | 0.0% (6) | 99.9% | 0.0% (4) | 99.2% |
Dr. Raphael Furtado | Brazil | 170 | 0.6% (1) | 98.5% | 0.0% (0) | 100.0% |
Dr. Heather Gessling | USA | 1,500 | 0.1% (1) | 97.3% | ||
Dr. Ellen Guimarães | Brazil | 500 | 1.6% (8) | 95.9% | 0.4% (2) | 83.7% |
Dr. Syed Haider | USA | 4,000 | 0.1% (5) | 99.7% | 0.0% (0) | 100.0% |
Dr. Mark Hancock | USA | 24 | 0.0% (0) | 100.0% | ||
Dr. Sabine Hazan | USA | 1,000 | 0.0% (0) | 100.0% | ||
Dr. Mollie James | USA | 3,500 | 1.1% (40) | 97.0% | 0.0% (1) | 98.8% |
Dr. Roberta Lacerda | Brazil | 550 | 1.5% (8) | 96.2% | 0.4% (2) | 85.2% |
Dr. Katarina Lindley | USA | 100 | 5.0% (5) | 87.1% | 0.0% (0) | 100.0% |
Dr. Ben Marble | USA | 150,000 | 0.0% (4) | 99.9% | ||
Dr. Edimilson Migowski | Brazil | 2,000 | 0.3% (7) | 99.1% | 0.1% (2) | 95.9% |
Dr. Abdulrahman Mohana | Saudi Arabia | 2,733 | 0.0% (0) | 100.0% | ||
Dr. Carlos Nigro | Brazil | 5,000 | 0.9% (45) | 97.7% | 0.5% (23) | 81.3% |
Dr. Benoit Ochs | Luxembourg | 800 | 0.0% (0) | 100.0% | ||
Dr. Ortore | Italy | 240 | 1.2% (3) | 96.8% | 0.0% (0) | 100.0% |
Dr. Valerio Pascua one death for a patient presenting on the 5th day in need of supplemental oxygen |
Honduras | 415 | 6.3% (26) | 83.8% | 0.2% (1) | 90.2% |
Dr. Sebastian Pop | Romania | 300 | 0.0% (0) | 100.0% | ||
Dr. Brian Proctor | USA | 869 | 2.3% (20) | 94.0% | 0.2% (2) | 90.6% |
Dr. Anastacio Queiroz | Brazil | 700 | 0.0% (0) | 100.0% | ||
Dr. Didier Raoult | France | 8,315 | 2.6% (214) | 93.3% | 0.1% (5) | 97.6% |
Dr. Karin Ried up to 99yo, 73% comorbidities, av. age 63 |
Turkey | 237 | 0.4% (1) | 82.8% | ||
Dr. Roman Rozencwaig patients up to 86 years old |
Canada | 80 | 0.0% (0) | 100.0% | ||
Dr. Vipul Shah | India | 8,000 | 0.1% (5) | 97.5% | ||
Dr. Silvestre Sobrinho | Brazil | 116 | 8.6% (10) | 77.7% | 0.0% (0) | 100.0% |
Dr. Unknown | Brazil | 957 | 1.7% (16) | 95.7% | 0.2% (2) | 91.5% |
Dr. Vladimir Zelenko | USA | 2,200 | 0.5% (12) | 98.6% | 0.1% (2) | 96.3% |
Mean improvement with early treatment protocols | 237,521 | HospitalizationHosp. | 94.1% | MortalityDeath | 94.7% |
Physician results with early treatment protocols compared to
no early treatment. These results are subject to selection and ascertainment
bias and more accurate analysis requires details of the patient populations
and followup, however results are consistently better across many teams, and consistent
with the extensive controlled trial evidence that shows a significant
reduction in risk with many early treatments, and improved results with the
use of multiple treatments in combination.
Treatment |
Improvement (early) |
Studies (early) |
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PXProxalutamide | 71% | 3 |
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(H)CQHydroxychlor.. | 62% | 38 |
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IVMIvermectin | 62% | 37 |
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V.DVitamin D | 60% | 11 |
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BLBamlaniv../e.. | 59% | 11 |
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BUBudesonide | 49% | 2 |
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CICasirivimab/i.. | 47% | 21 |
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FVFluvoxamine | 42% | 10 |
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RDRemdesivir | 41% | 7 |
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ZnZinc | 41% | 6 |
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V.CVitamin C | 37% | 6 |
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PLPaxlovid | 32% | 32 |
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SSotrovimab | 29% | 19 |
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NACN-acetylcys.. | 21% | 2 |
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FPVFavipiravir | 20% | 19 |
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MPMolnupiravir | 16% | 29 |
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ACEAcetaminophen | -17% | 3 |
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TCTixagev../c.. | -29% | 2 |
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IBIbuprofen | -52% | 2 |
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Early treatments approved by >2 countries. 102 countries have officially approved treatments.
Details.
Ziaei | Systematic review and meta analysis of 5 studies, showing significantly lower mortality, ICU admission, and hospitalization with quercetin treatment. |
Burhan | 559 patients ICU: 15% higher mortality (p=0.23) |
Hagman | 318 patients late treatment: no change in mortality (p=0.97), 40% higher progression (p=0.31), and 29% improved viral clearance (p=0.11) |
Marikawa | Analysis of molnupiravir active metabolite N4-hydroxycytidine's effects on mouse preimplantation embryos in vitro, showing embryotoxicity at.. |
Sanderson | Identification of SARS-CoV-2 variants created by molnupiravir treatment, including cases of onwards transmission. Authors find a class of long.. |
Alpizar | 1,527 patient prophylaxis RCT: 24% fewer symptomatic cases (p=0.06) |
Alves | In Vitro study showing that iron-free and iron-saturated bovine lactoferrin inhibited SARS-CoV-2 ancestral and omicron Vero cell infection... |
Yuan | Review of cell death pathways in SARS-CoV-2 infection. Authors note that studies show lower selenium levels are associated with higher COVID-19.. |
Yuan | Review of cell death pathways in SARS-CoV-2 infection. Authors note that N-acetylcysteine (NAC) is a precursor to glutathione that may inhibit.. |
Sanecka | Prospective study of 171 hospitalized COVID-19 patients in Ireland, showing significantly lower mortality and ICU admission with sufficient vitamin.. |
Qiu | Retrospective 399 hospitalized patients in China, showing that lower vitamin D levels and higher IL-5 levels were independent risk factors for COVID.. |
Graydon | Analysis of 88 COVID+ patients in the USA showing that a higher frequency of natural killer (NK) cells was associated with asymptomatic infection... |
Ogasawara | 312 patients late treatment: 78% lower progression (p=0.05) and 75% lower need for oxygen therapy (p=0.09) |
Albóniga | Plasma metabolomic analysis showing significantly lower threonic acid levels for severe and mild COVID-19 cases compared with moderate cases... |
Graydon | Analysis of 88 COVID+ patients in the USA showing that a higher frequency of natural killer (NK) cells was associated with asymptomatic infection... |
Liu | In Vitro study showing that ivermectin and meclizine mitigated cardiac cell death and dysfunction caused by SARS-CoV-2 viral genes. Authors found.. |
Naggie | Late treatment low risk population RCT showing lower progression to hospitalization or urgent care/ER visits with fluvoxamine, without statistical.. |
Graydon | Analysis of 88 COVID+ patients in the USA showing that a higher frequency of natural killer (NK) cells was associated with asymptomatic infection... |
Rolles | In Vitro study showing improved natural killer (NK) cell function with zinc. - showed that a lower frequency of natural killer cells was associated.. |
Graydon | Analysis of 88 COVID+ patients in the USA showing that a higher frequency of natural killer (NK) cells was associated with asymptomatic infection... |
Finamore | RCT 98 adults, showing that probiotics improved immune function including increased natural killer (NK) cell activity. - showed that a lower.. |
Graydon | Analysis of 88 COVID+ patients in the USA showing that a higher frequency of natural killer (NK) cells was associated with asymptomatic infection... |
Recent studies (see the individual treatment pages for all studies):
Sep 22 |
et al., BMJ Open, doi:10.1136/bmjopen-2023-073761 | Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial |
14% improved recovery (p=0.41). Early terminated low-risk population (no hospitalization) very late treatment (mean 8 days) RCT with 44 patients treated with vitamin C, D, K, and zinc, and 46 control patients, showing no significant differences. Authors acknowledge that.. | ||
Sep 22 |
et al., Advances in Medical Sciences, doi:10.1016/j.advms.2023.09.007 | Safety and efficacy of melatonin as an adjuvant therapy in COVID-19 patients: Systematic review and meta-analysis |
Systematic review and meta analysis of 11 COVID-19 studies showing significantly higher clinical improvement and shorter hospitalization and mechanical ventilation time with melatonin treatment. | ||
Sep 20 |
et al., Signal Transduction and Targeted Therapy, doi:10.1038/s41392-023-01580-8 | The role of cell death in SARS-CoV-2 infection |
Review of cell death pathways in SARS-CoV-2 infection. Authors note that studies show lower selenium levels are associated with higher COVID-19 mortality. Through preserving glutathione peroxidase 4 activity and countering oxidative stres.. | ||
Sep 19 |
et al., Makara Journal of Science, doi:10.7454/mss.v27i3.1609 | In-silico Approach for Predicting the Inhibitory Effect of Home Remedies on Severe Acute Respiratory Syndrome Coronavirus-2 |
In Silico analysis showing that curcumin and quercetin may be beneficial for COVID-19 by binding to the main protease (Mpro), spike protein, and ACE2 receptor. Both compounds had suitable ADME properties and minimal predicted toxicity. | ||
Sep 13 |
et al., Stem Cell Research & Therapy, doi:10.1186/s13287-023-03485-3 | SARS-CoV-2 viral genes Nsp6, Nsp8, and M compromise cellular ATP levels to impair survival and function of human pluripotent stem cell-derived cardiomyocytes |
In Vitro study showing that ivermectin and meclizine mitigated cardiac cell death and dysfunction caused by SARS-CoV-2 viral genes. Authors found that SARS-CoV-2 viral genes Nsp6, Nsp8, and M had harmful effects on human cardiomyocytes (h.. | ||
Sep 13 |
et al., Scientific Reports, doi:10.1038/s41598-023-40999-5 | Differential abundance of lipids and metabolites related to SARS-CoV-2 infection and susceptibility |
Plasma metabolomic analysis showing significantly lower threonic acid levels for severe and mild COVID-19 cases compared with moderate cases. Threonic acid is a metabolite of vitamin C. The expected relationship in non-linear and depends .. | ||
Sep 13 |
et al., medRxiv, doi:10.1101/2023.09.12.23295424 | Effect of Higher-Dose Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial |
Late treatment low risk population RCT showing lower progression to hospitalization or urgent care/ER visits with fluvoxamine, without statistical significance. There was no mortality and only three hospitalizations. Authors provide no de.. | ||
Sep 13 |
et al., Virology Journal, doi:10.1186/s12985-023-02165-1 | Vitamin D status in hospitalized COVID‑19 patients is associated with disease severity and IL-5 production |
Retrospective 399 hospitalized patients in China, showing that lower vitamin D levels and higher IL-5 levels were independent risk factors for COVID-19 severity. | ||
Sep 8 |
et al., Nutrition Reviews, doi:10.1093/nutrit/nuad105 | Therapeutic effects of high-dose vitamin C supplementation in patients with COVID-19: a meta-analysis |
66% lower progression (p=0.03). Meta analysis of 14 studies showing lower COVID-19 progression with high-dose vitamin C treatment. | ||
Sep 8 |
et al., Journal of Infection, doi:10.1016/j.jinf.2023.08.016 | Molnupiravir for Intra-Household Prevention of COVID-19: the MOVe-AHEAD Randomized, Placebo-Controlled Trial |
24% fewer symptomatic cases (p=0.06). PEP RCT 1,527 patients showing lower COVID-19 cases with molnupiravir, without statistical significance. | ||
Sep 6 |
et al., Crohn's & Colitis 360, doi:10.1093/crocol/otad047 | Tixagevimab and Cilgavimab (Evusheld) as Pre-exposure Prophylaxis for COVID-19 in Patients With Inflammatory Bowel Disease: A Propensity Matched Cohort Study |
12% lower hospitalization (p=0.81) and 35% more cases (p=0.18). TriNetX PSM retrospective 408 IBD patients receiving tixagevimab/cilgavimab and matched controls, showing no significant difference in COVID-19 cases or hospitalization. | ||
Sep 5 |
et al., Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2309870120 | Reply to Yan et al.: Quercetin possesses a fluorescence quenching effect but is a weak inhibitor against SARS-CoV-2 main protease |
In Vitro study [Yan] and associated response from the original authors [Xu], collectively showing that quercetin and echinatin had weak SARS-CoV-2 protease inhibition in SDS-PAGE assays [Xu], despite false positive FRET results from MCA-A.. | ||
Sep 5 |
et al., Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2309289120 | Reframing quercetin as a promiscuous inhibitor against SARS-CoV-2 main protease |
In Vitro study [Yan] and associated response from the original authors [Xu], collectively showing that quercetin and echinatin had weak SARS-CoV-2 protease inhibition in SDS-PAGE assays [Xu], despite false positive FRET results from MCA-A.. | ||
Sep 4 |
et al., Frontiers in Immunology, doi:10.3389/fimmu.2023.1197752 | Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis |
In Silico study identifying IGF1 as a shared gene between pulmonary fibrosis and hypertension that promotes inflammation, fibrosis, and cell proliferation when overactivated. Molecular docking analysis demonstrated ivermectin directly bin.. | ||
Sep 1 |
et al., Frontiers in Immunology, doi:10.3389/fimmu.2023.1231813 | Association of serum vitamin D concentration with the final course of hospitalization in patients with COVID-19 |
Retrospective 474 hospitalized COVID-19 patients in Poland, showing lower vitamin D levels associated with mortality. | ||
Sep 1 |
et al., Clinical Nutrition, doi:10.1016/j.clnu.2023.08.021 | The effect of 1-hydroxy-vitamin D treatment in hospitalized patients with COVID-19: A retrospective study |
78% lower progression (p=0.05) and 75% lower need for oxygen therapy (p=0.09). PSM retrospective 312 hospitalized patients in Japan, showing lower progression with vitamin D (alfacalcidol) treatment, statistically significant via KM log-rank. | ||
Aug 31 |
et al., iScience, doi:10.1016/j.isci.2023.107786 | N4-hydroxycytidine, the active compound of Molnupiravir, promotes SARS-CoV-2 mutagenesis and escape from a neutralizing nanobody |
In Vitro study showing that NHC, the active compound molnupiravir, can promote rapid selection of immune escape mutants. NHC treatment enabled selection of nanobody-resistant mutants much faster than without NHC. While an in vitro model w.. | ||
Aug 31 |
et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2023.08.022 | Local budesonide therapy in the management of persistent hyposmia in suspected non-severe COVID-19 patients: Results of a randomized controlled trial |
RCT 123 post-COVID-19 hyposmia patients, showing no significant difference in smell recovery with budesonide. 2 patients experienced improvement of more than two points on the ODORATEST score compared with 0 in the control group. | ||
Aug 30 |
et al., Stresses, doi:10.3390/stresses3030043 | Paradigm of Well-Orchestrated Pharmacokinetic Properties of Curcuminoids Relative to Conventional Drugs for the Inactivation of SARS-CoV-2 Receptors: An In Silico Approach |
In Silico analysis of curcuminoids showing similar drug-like properties and strong binding to the main protease and spike receptor binding domain proteins. Curcuminoid binding was comparable or better than existing drugs favipiravir, remd.. | ||
Aug 30 |
et al., Acta Biomedica Atenei Parmensis, doi:10.23750/abm.v94iS3.14405 | Metformin and Covid-19: a systematic review of systematic reviews with meta-analysis |
31% lower mortality (p<0.0001) and 20% lower severe cases (p=0.03). Systematic review and meta analysis of 36 studies showing significantly lower COVID-19 mortality and severity with metformin use. | ||
Aug 28 |
et al., BMJ Open Respiratory Research, doi:10.1136/bmjresp-2023-001674 | Repurposed drug studies on the primary prevention of SARS-CoV-2 infection during the pandemic: systematic review and meta-analysis |
Meta analysis with many errors/limitations/biases, including many missing studies, use of unadjusted results, use of non-symptomatic results, and use of all-cause instead of COVID-19 hospitalization. For HCQ, there are , including . Note .. | ||
Aug 25 |
et al., Journal of Clinical Medicine, doi:10.3390/jcm12175520 | Is Serum 25-Hydroxyvitamin D Level Associated with Severity of COVID-19? A Retrospective Study |
Retrospective 763 hospitalized COVID-19 patients showing no significant difference in outcomes based on serum levels. Unadjusted results show non-significantly lower risk of critical severity, death, and complications with vitamin D suffi.. |
We aim to cover the most promising early treatments for
COVID-19. We use pre-specified effect extraction criteria that prioritizes
more serious outcomes, for details see methods. For specific
outcomes and different treatment stages see the individual pages. Not all
treatments are covered here, effectiveness has been reported for many other treatments in studies.
Of the 3,328 studies,
1,931 present results comparing with a control group,
1,747 are treatment studies, and
184 analyze outcomes based on serum levels. There are
42 animal studies,
85 in silico studies,
169 in vitro studies,
201 reviews,
and 144 meta analyses.
Please send us corrections, updates, or comments. Vaccines and
treatments are complementary. All practical, effective, and safe means should
be used based on risk/benefit analysis. No treatment, vaccine, 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.