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

Elkazzaz, Mahmoud; Abo-Amer, Yousry Esam-Eldin; Ahmed, Amr; Haydara, Tamer

doi:10.1101/2022.03.05.22271959

Cited by 4 publications

(5 citation statements)

References 134 publications

(60 reference statements)

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“…Aerosolized retinoic acid may have an effective role in treating post-COVID-19 anosmia through upregulating ACE2 and STRA6 and regenerating OSNs expressing olfactory receptors. Elkazzaz’s study group investigated the potential role of aerosolized retinoic acid in treating COVID-19 anosmia [ 48 ]. They divided the patients into three groups: (1) the first group of patients received a daily dose of 13-cis-retinoic acid aerosol with gradual increases in two doses from 0.2 mg/kg/day to 4 mg/kg/day for 3 weeks.…”

Section: Resultsmentioning

confidence: 99%

“…Other drugs that have been tested in clinical trials reached the last stage and are represented by local and systemic corticosteroids, Retinoic acid, and Imupret [ 12 , 13 , 26 , 48 ]. Corticosteroids can also be effective in treating olfactory loss and are commonly used by clinicians without knowing the cause of anosmia.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding the use of aerosolized retinoic acid, the authors suggested that STRA6 function was lost due to a blockade by the COVID-19 spike protein, which binds to it with high affinity, hijacking the signaling pathway, leading to disruption of retinoic acid synthesis and vitamin A deficiency. This is because Elkazzaz et al indicated that the administrated retinoic acid would facilitate cellular uptake of retinol in immune cells through the impaired transport function of the STRA6 receptor by binding to the RBD of the SARS-CoV-2 spike protein, leading to an improvement in immune system homeostasis [ 48 , 69 ]. This may also be applicable to olfactory epithelial homeostasis because retinoic acid insufficiency in the olfactory epithelium causes cell failure in progenitor cells and, consequently, olfactory neuron differentiation is not maintained.…”

Section: Discussionmentioning

confidence: 99%

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Post-COVID-19 Anosmia and Therapies: Stay Tuned for New Drugs to Sniff Out

et al. 2023

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Background: Anosmia is defined as the complete absence of olfactory function, which can be caused by a variety of causes, with upper respiratory tract infections being among the most frequent causes. Anosmia due to SARS-CoV-2 infection has attracted attention given its main role in symptomatology and the social impact of the pandemic. Methods: We conducted systematic research in a clinicaltrials.gov database to evaluate all active clinical trials worldwide regarding drug therapies in adult patients for anosmia following SARS-CoV-2 infection with the intention of identifying the nearby prospects to treat Anosmia. We use the following search terms: “Anosmia” AND “COVID-19” OR “SARS-CoV-2” OR “2019 novel coronavirus”. Results: We found 18 active clinical trials that met our criteria: one phase 1, one phase 1–2, five phases 2, two phases 2–3, three phases 3, and six phases 4 studies were identified. The drug therapies that appear more effective and promising are PEA-LUT and Cerebrolysin. The other interesting drugs are 13-cis-retinoic acid plus aerosolized Vitamin D, dexamethasone, and corticosteroid nasal irrigation. Conclusions: COVID-19 has allowed us to highlight how much anosmia is an important and debilitating symptom for patients and, above all, to direct research to find a therapy aimed at curing the symptom, whether it derives from SARS-CoV-2 infection or other infections of the upper airways. Some of these therapies are very promising and are almost at the end of experimentation. They also provide hope in this field, which not addressed until recently.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Post-COVID-19 Anosmia and Therapies: Stay Tuned for New Drugs to Sniff Out

et al. 2023

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“…Vigorous screening of the 595 available records yielded a total of 14 RCTs for inclusion, encompassing a sample size of 2593. [11][12][13][14][15][16][17][18][19][20][21][22][23][24] A PRISMA flowchart demonstrates the selection process in Figure 1.…”

Section: Study Selection and Quality Assessmentmentioning

confidence: 99%

Antiandrogens for the treatment of COVID‐19 patients: A meta‐analysis of randomized controlled trials

Cheema

Rehman

Elrashedy

et al. 2023

Journal of Medical Virology

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Antiandrogens may carry a potential benefit as a therapeutic agent against COVID-19. However, studies have been yielding mixed results, thus hindering any objective recommendations. This necessitates a quantitative synthesis of data to quantify the benefits of antiandrogens. We systematically searched PubMed/ MEDLINE, Cochrane Library, clinical trial registers, and reference lists of included studies to identify relevant randomized controlled trials (RCTs). Results from the trials were pooled using a random-effects model and outcomes were reported as risk ratios (RR) and mean differences (MDs) with 95% confidence intervals (CIs).Fourteen RCTs with a total sample size of 2593 patients were included.Antiandrogens yielded a significant mortality benefit (RR 0.37; 95% CI; 0.25-0.55).However, on subgroup analysis, only proxalutamide/enzalutamide and sabizabulin were found to significantly reduce mortality (RR 0.22, 95% CI: 0.16-0.30 and RR 0.42, 95% CI: 0.26-0.68, respectively), while aldosterone receptor antagonists and antigonadotropins did not show any benefit. No significant between-group difference was found in the early or late initiation of therapy. Antiandrogens also reduced hospitalizations and the duration of hospital stay, and improved recovery rates. Proxalutamide and sabizabulin may be effective against COVID-19, however, further large-scale trials are needed to confirm these findings.

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“… Active studies of drugs that interfere with cell signaling triggered by sex hormones 37‐154 . Adapted from 105 …”

Section: Active Clinical Trialsmentioning

confidence: 99%

Crosstalk between estrogen, dendritic cells, and SARS‐CoV‐2 infection

Mateus

Sebastião

Carrascal

et al. 2021

Reviews in Medical Virology

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The novel coronavirus disease 2019 (Covid‐19) first appeared in Wuhan and has so far killed more than four million people worldwide. Men are more affected than women by Covid‐19, but the cellular and molecular mechanisms behind these differences are largely unknown. One plausible explanation is that differences in sex hormones could partially account for this distinct prevalence in both sexes. Accordingly, several papers have reported a protective role of 17β‐estradiol during Covid‐19, which might help explain why women appear less likely to die from Covid‐19 than men. 17β‐estradiol is the predominant and most biologically active endogenous estrogen, which signals through estrogen receptor α, estrogen receptor β, and G protein‐coupled estrogen receptor 1. These receptors are expressed in mature cells from the innate and the adaptive immune system, particularly on dendritic cells (DCs), suggesting that estrogens could modulate their effector functions. DCs are the most specialized and proficient antigen‐presenting cells, acting at the interface of innate and adaptive immunity with a powerful capacity to prime antigen‐specific naive CD8+ T cells. DCs are richly abundant in the lung where they respond to viral infection. A relative increase of mature DCs in broncho‐alveolar lavage fluids from Covid‐19 patients has already been reported. Here we will describe how SARS‐CoV‐2 acts on DCs, the role of estrogen on DC immunobiology, summarise the impact of sex hormones on the immune response against Covid‐19, and explore clinical trials regarding Covid‐19

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

Cited by 4 publications

References 134 publications

Post-COVID-19 Anosmia and Therapies: Stay Tuned for New Drugs to Sniff Out

Post-COVID-19 Anosmia and Therapies: Stay Tuned for New Drugs to Sniff Out

Antiandrogens for the treatment of COVID‐19 patients: A meta‐analysis of randomized controlled trials

Crosstalk between estrogen, dendritic cells, and SARS‐CoV‐2 infection

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