COVID-19 Treatment: Real Time Analysis of more than 600 Studies (updated May 2021)

By Dr Frank Yap, MD -

This review article explores a superbly designed, highly navigable website that has continuously updated the evidence-based research on early COVID-19 treatments since June 2020. The website is so exhaustively comprehensive that it could be considered a journal in itself, produced by a team of competent, committed editors.

Although this singular resource site has been developed and posted anonymously, one observer commented on Reddit, “It doesn’t really matter who built it, imo. All studies are referenced/linked.”

The Website Itself: The Home Page is at c19early.com

The studies for Covid’s evidence-based early treatments are divided into sections: Ivermectin, Vitamin D, Hydroxychloroquine, Vitamin C, Zinc and more.

Methods and Study Results

Ongoing searches of PubMed, medRxiv, ClinicalTrials.gov, The Cochrane Library, Google Scholar, Collabovid, Research Square, ScienceDirect, Oxford University Press, the reference lists of other studies and meta-analyses. The site is updated regularly.

Here's the list of the most promising early treatments for COVID-19.

Ivermectin

Summary of Evidence

The site maintains an updated list of ivermectin COVID-19 treatment studies and outcomes, divided into prophylaxis, early treatment and late treatment results; complete with links and abstracts.


Hydroxychloroquine


A global list of hydroxychloroquine Covid-19 treatment studies and outcomes, divided into early treatment and late treatment results, and complete with links and abstracts, is available at https://hcqmeta.com/. The HCQ data alone can be downloaded as a pdf (more than 200 pages).

Vitamin D

The project has kept up with the encouraging work on Vitamin D and COVID-19. 


To view the updated and detailed list of vitamin D and COVID-19 studies, check out c19vitamind.com.

Proxalutamide


March 10, 2021: Late Cadegiani et al., Press Conference (Preprint) death, ↓91.4%, p<0.0001 The Proxa-Rescue AndroCoV Trial
RCT 590 hospitalized patients, 294 treated with proxalutamide showing significantly lower mortality and faster recovery.

Feb 22, 2021: Early Cadegiani et al., Cureus, doi:10.7759/cureus.13492 (Peer Reviewed) viral+, ↓92.1%, p<0.0001 Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, Double-Blinded, Placebo-Controlled Trial
RCT 234 mild-moderate COVID-19 patients with 171 treated with proxalutamide, showing significantly faster viral clearance and recovery.

Dec30, 2021: Early Cadegiani et al., Research Square, doi:10.21203/rs.3.rs-135303/v1 (Preprint) death, ↓81.1%, p=0.22 Proxalutamide (GT0918) Reduces the Rate of Hospitalization and Death in COVID-19 Male Patients: A Randomized Double-Blinded Placebo-Controlled Trial
RCT 214 male patients in Brazil, 114 treated with proxalutamide, showing significantly lower hospitalization and mechanical ventilation. NCT04446429.

Fluvoxamine


Apr 20, 2021
Review - Sukhatme et al., Front. Pharmacol., doi:10.3389/fphar.2021.652688 (Review) (Peer Reviewed)reviewFluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19. Review of mechanisms of action of fluvoxamine and other SSRIs that could be beneficial for COVID-19 treatment, including lower platelet aggregation, decreased mast cell degranulation, interference with endolysosomal viral trafficking, reg..

Mar 6, 2021
Review - Kirsch, S. (Review) (Preprint)reviewCOVID FAQCOVID FAQ from the founder of the COVID-19 Early Treatment Fund [1], including an extensive analysis of the fluvoxamine trials and other supporting evidence.

Feb 1, 2021
Early - Seftel et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofab050 (Peer Reviewed)death/ICU, ↓83.9%, p=0.15Prospective cohort of fluvoxamine for early treatment of COVID-19Prospective quasi-randomized (patient choice) study with 125 outpatients, 77 treated with fluvoxamine, showing lower death/ICU admission (0 of 77 vs. 2 of 48), lower hospitalization (0 of 77 vs. 6 of 48), and faster recovery with treatment

Nov 12, 2021
Early - Lenze et al., JAMA, doi:10.1001/jama.2020.22760 (Peer Reviewed)progression, ↓92.7%, p=0.009Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical TrialRCT 152 outpatients, 80 treated with fluvoxamine showing lower progression with treatment (0 of 80 versus 6 of 72 control).

Aug 17, 2021
Late - Hoertel et al., Molecular Psychiatry, doi:10.1038/s41380-021-01021-4 (Peer Reviewed)Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational studyRetrospective 7,230 hospitalized COVID-19 patients in France, 345 receiving an antidepressant medication within 48 hours of admission. There was a significant association between antidepressant use and reduced risk of intubation or death ..

Povidone-Iodine


2021 Povidone-Iodine Studies

Apr 14, 2021: PEP - Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 (Peer Reviewed) severe case, ↓44.7%, p=0.05 Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin ..

Mar 17, 2021: Early - Elzein et al., medRxiv, doi:10.1101/2021.03.07.21252302 (Preprint) In vivo evaluation of the virucidal efficacy of Chlorhexidine and Povidone-iodine mouthwashes against salivary SARS-CoV-2
Small RCT comparing mouthwashing with PVP-I, Chlorhexidine, and water, showing both PVP-I and Chlorhexidine were effective, with PVP-I increasing Ct by a mean of 4.45 (p < 0.0001) and Chlorhexidine by a mean of 5.69 (p < 0.0001), compared..

Mar 15, 2021: Review - Chopra et al., Japanese Dental Science Review, doi:10.1016/j.jdsr.2021.03.001 (Review) (Peer Reviewed) review Can povidone Iodine gargle/mouthrinse inactivate SARS-CoV-2 and decrease the risk of nosocomial and community transmission during the COVID-19 pandemic? An evidence-based update
Review discussing the rationale, safety, recommendations, and dosage of PVP-I gargle/mouthwash as an effective method to decrease the viral load of SARS-CoV-2.

Mar 1, 2021: In Vitro - Xu et al., Pathogens, doi:10.3390/pathogens10030272 (Peer Reviewed) (In Vitro) in vitro Differential Effects of Antiseptic Mouth Rinses on SARS-CoV-2 Infectivity In Vitro. In Vitro study showing that PVP-I and other mouthwashes inactivated replication-competent SARS-CoV-2.

Mar 1, 2021: Early - Jayaraman et al., medRxiv, doi:10.1101/2021.02.25.21252488 (Preprint) Povidone iodine, hydrogen peroxide and chlorhexidine mouthwashes reduce SARS-CoV2 burden in whole mouth fluid and respiratory droplets
Study of SARS-CoV2 burden in whole mouth fluid and respiratory droplets with povidone iodine, hydrogen peroxide, and chlorhexidine mouthwashes in 36 hospitalized COVID-19 patients using PCR and rapid antigen testing. There were significan..

Feb 4, 2021: Early - Guenezan et al., JAMA Otolaryngol Head Neck Surg., doi:10.1001/jamaoto.2020.5490 (Peer Reviewed) viral load, ↓63.2%, p=0.25 Povidone Iodine Mouthwash, Gargle, and Nasal Spray to Reduce Nasopharyngeal Viral Load in Patients With COVID-19: A Randomized Clinical Trial
RCT of PCR+ patients with Ct<=20 with 12 treatment and 12 control patients, concluding that nasopharyngeal decolonization may reduce the carriage of infectious SARS-CoV-2 in adults with mild to moderate COVID-19. All patients but 1 had ne..

Feb 1, 2021: In Vitro - Tucker et al., bioRxiv, doi:10.1101/2021.01.31.426979 (Preprint) (In Vitro) in vitro In vitro inactivation of SARS-CoV-2 with 0.5% povidone iodine nasal spray (Nasodine) at clinically relevant concentrations and timeframes using tissue culture and PCR based assays
In Vitro study showing that PVP-I eliminated the viability of SARS-CoV-2 with short exposure times. Authors find that PCR alone may not be adequate for viral quantification and recommend incorporating cell culture to assess viral viability.

Jan 3, 2021: Early - Khan et al., American Journal of Otolaryngology, doi:10.1016/j.amjoto.2020.102880 (Peer Reviewed) Tolerability and usability of 0.5% PVP-I gargles and nasal drops in 6692 patients: Observational study
Study of the use of PVP-I gargles and nasal drops before and after ENT examinations with a total of 6,692 patients, finding high usability and good tolerance for


UPDATE: COVID-19 is a highly dynamic topic. Please refer to the latest FLCCC protocol (April 26, 2021 version) for treatment recommendations.

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