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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality 86% Improvement Relative Risk ICU admission 67% Recovery time 35% Time to viral- 44% Isotretinoin  Elkazzaz et al.  LATE TREATMENT  RCT Is late treatment with antiandrogens beneficial for COVID-19? RCT 40 patients in Egypt (June - August 2020) Faster recovery (p<0.0001) and viral clearance (p<0.0001) Elkazzaz et al., medRxiv, March 2022 Favors isotretinoin Favors control

13 cis retinoic acid improved the outcomes of COVID-19 patients. A randomized clinical trial

Elkazzaz et al., medRxiv, doi:10.1101/2022.03.05.22271959, NCT04353180
Mar 2022  
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7th treatment shown to reduce risk in September 2020
*, now known with p = 0.000000056 from 49 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,200+ studies for 70+ treatments.
RCT with 20 13-cis-retinoic acid patients and 20 control patients, showing faster recovery and viral clearance with treatment. Aerosolized 13-cis-retinoic acid with increasing dose from 0.2 mg/kg/day to 4 mg/kg/day for 14 days, plus oral 13-cis-retinoic acid 20 mg/day. 13-cis retinoic acid, also known as isotretinoin, is a synthetic vitamin A derivative that has been shown to have antiandrogenic effects.
risk of death, 85.7% lower, RR 0.14, p = 0.23, treatment 0 of 20 (0.0%), control 3 of 20 (15.0%), NNT 6.7, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of ICU admission, 66.7% lower, RR 0.33, p = 0.24, treatment 2 of 20 (10.0%), control 6 of 20 (30.0%), NNT 5.0.
recovery time, 35.4% lower, relative time 0.65, p < 0.001, treatment mean 16.3 (±4.5) n=20, control mean 25.23 (±4.72) n=20.
time to viral-, 44.0% lower, relative time 0.56, p < 0.001, treatment mean 13.36 (±1.49) n=20, control mean 23.85 (±4.0) n=20.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Elkazzaz et al., 8 Mar 2022, Randomized Controlled Trial, Egypt, preprint, 4 authors, study period June 2020 - August 2020, trial NCT04353180 (history).
This PaperAntiandrogensAll
STRA6 (vitamin A receptor), as a Novel binding receptor of COVID-19 (A breakthrough)
Mahmoud Elkazzaz, Tamer Haydara, Yousry Esam-Eldin Abo-Amer, Israa M Shamkh, Mohammed . F Abo El Magd, Amr Ahmed
Background A global pandemic of pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, at the end of 2019. Although, the ACE2 receptor has been demonstrated to be the main entry receptor of COVID-19, but our docking analysis , predicted and discovered a novel receptor termed STRA6 that may play a critical role in the pathogenicity of COVID-19 and explain the common pre and post COVID-19 symptoms with unknown etiology. STRA6 receptor expressed in many organs and immune cells, upregulated by retinoic acid jm6 (STRA6) was the rst protein to be identi ed in a novel category of proteins, cytokine signaling transporters, due to its ability to function as both a cell surface receptor and a membrane protein that binds to retinol binding protein facilitating cellular uptake of retinol. The primary ligand of STRA6 (vitamin/retinol) was shown to be drastically reduced during COVID-19 infection, which agrees with our ndings. Methods The STRA6 receptor protein were submitted to the server for functional interaction associated network between partners for the STRING (Research Online of Interacting Genes/Proteins Data Basis version 10.0)13 .Docking study of each Spike -ACE 2 and STRA6 receptor protein were carried out using HDOCK server ( The binding mode of Spike -ACE 2 and STRA6 receptor protein is retrieved form the PDB with accession number (7DMU , 5sy1) Results Surprisingly, our molecular docking based analysis showed that spike protein Receptor Binding Domain(RDB) of COVID-19 strongly and e ciently binds to STRA6 receptor, de nitely to the RDB vital residues of RBP-binding motif located in STRA6 receptor. STRA6 receptor is a membrane receptor responsible for signaling and transporting of Vitamin A(Retinol) from plasma retinol binding protein (RBP) to our cells. In an outstanding manner, COVID-19 Spike protein exhibited high docking score with human STRA6 with low binding energy . The docking score of COVID-19 spike protein was stronger than the docking score of spike protein with ACE2.The surface view of complex reveals that the binding pocket of STRA6-Spike protein and Spike ACE 2 complexes with RMSD (189.44 Å , 1.00 Å ) representatively and docking score (-341.21 ,-354.68) kcal/mol the quality of the receptor and the ligand are LGscore and MaxSub ( 2.416 , 0.147 ). The spike to bind to RDB of the STRA 6 protein in the ILE 131C , MET 145C , HIS 86A with interface residue( 4.961 , 4.953 and 3.271) representatively. In conclusion STRA6 mutations results in a broad spectrum of complication related to malformations including congenital heart defects , anophthalmia, alveolar capillary dysplasia, diaphragmatic hernia, lung hypoplasia and mental retardation. Moreover, Retinoic acid metabolism is defective in COVID-19 (cytokine storm), sepsis, ARDS and SIRS. Therefore, we believe that this novel discovery that STRA6 receptor acts as a novel binding..
Declarations Con ict of Interest Statement The author declares that the research was conducted in the absence of any commercial or nancial relationships that could be construed as a potential con ict of interest. The spike to bind to RD8 of the STRA 6 protein
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{ 'DOI': '10.1101/2022.03.05.22271959', 'URL': '', 'abstract': '<jats:p>The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 ' '(SARS-CoV-2) has infected over 100 million people causing over 2.4 million deaths over the ' 'world, and it is still expanding. Given the urgency of the COVID-19 pandemic, the clinical ' 'investigation of approved drugs is a promising alternative to find a timely effective ' 'treatment. In this randomized trial, we investigated the activity of both oral and ' 'aerosolized 13 cis retinoic acid in the treatment of SARS-COV-2 added to standard of care ' 'treatment in patients with COVID-19 versus standard of care treatment alone. This was a ' 'randomized controlled trial conducted at Kafrelsheikh Universitys Quarantine Hospitals, ' 'Egypt. After obtaining informed consent, forty patients with a confirmed diagnosis of ' 'COVID-19 were enrolled in the study. They were randomly assigned to one of two groups: Group ' 'I; 20 patients received aerosolized and oral 13 cis retinoic acid plus standard of care ' 'treatment (13 cis RA group) and Group II; 20 patients received only standard care treatment ' 'as a control group. The two groups were age and gender matched. There was no statistically ' 'significant difference between them in any of the baseline characteristics or laboratory ' 'parameters. The results showed that there was a high significant difference between the two ' 'groups regarding intensive care unit (ICU) admission, mortality and improvement ' '(P&lt;0.05). Only 10.52 % of patients in the 13 cis retinoic acid group needed ICU ' 'admission compared to 28.57 % in the control arm. There was no mortality in the 13 cis ' 'retinoic acid group, whereas about 14.35% were died in the group II. All patients who ' 'received 13 cis retinoic acid noticed a high improvement (P&lt;0.001), and the mean value for ' 'clinical improvement was 16 days. There was no significant difference regarding the ' 'laboratory parameters before and after 14 days of treatment in the group of patients received ' 'the standard of care treatment (P=0.66). Univariate logistic regression analysis showed ' 'overall mortality was significantly related to the patients age, serum ferritin, C-reactive ' 'protein, oxygen saturation, the presence of diabetes mellitus, obesity, and abdominal pain. ' 'We conclude that 13 cis retinoic acid is a promising drug in the treatment of patients ' 'with COVID-19 infection, when added to the standard of care treatment.</jats:p>', 'accepted': {'date-parts': [[2022, 3, 8]]}, 'author': [ {'affiliation': [], 'family': 'Elkazzaz', 'given': 'Mahmoud R', 'sequence': 'first'}, { 'affiliation': [], 'family': 'Esam-Eldin Abo-Amer', 'given': 'Yousry', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Ahmed', 'given': 'Amr', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Hayadar', 'given': 'Tamer', 'sequence': 'additional'}], 'container-title': [], 'content-domain': {'crossmark-restriction': False, 'domain': []}, 'created': {'date-parts': [[2022, 3, 9]], 'date-time': '2022-03-09T01:40:54Z', 'timestamp': 1646790054000}, 'deposited': { 'date-parts': [[2022, 3, 9]], 'date-time': '2022-03-09T01:40:54Z', 'timestamp': 1646790054000}, 'group-title': 'Respiratory Medicine', 'indexed': {'date-parts': [[2022, 3, 9]], 'date-time': '2022-03-09T16:40:32Z', 'timestamp': 1646844032037}, 'institution': [{'name': 'medRxiv'}], 'is-referenced-by-count': 0, 'issued': {'date-parts': [[2022, 3, 8]]}, 'link': [ { 'URL': '', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'member': '246', 'original-title': [], 'posted': {'date-parts': [[2022, 3, 8]]}, 'prefix': '10.1101', 'published': {'date-parts': [[2022, 3, 8]]}, 'publisher': 'Cold Spring Harbor Laboratory', 'reference-count': 0, 'references-count': 0, 'relation': {}, 'resource': {'primary': {'URL': ''}}, 'score': 1, 'short-container-title': [], 'short-title': [], 'source': 'Crossref', 'subtitle': [], 'subtype': 'preprint', 'title': ['13 cis retinoic acid improved the outcomes of COVID-19 patients. A randomized clinical trial'], 'type': 'posted-content'}
Late treatment
is less effective
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