Evaluation of COVID-19 risk in patients on systemic retinoid therapy

Background and Design: Systemic retinoids are commonly used medications in dermatology and indicated in various skin disorders such as acne vulgaris and psoriasis. Data about the risk of Coronavirus disease-2019 (COVID-19) in patients using systemic retinoids are limited. Thus, this study aimed to investigate the risk of COVID-19 in patients undergoing systemic retinoid therapy. Materials and Methods: A total of 186 patients who have undergone systemic isotretinoin and acitretin therapy were recruited. Patients who presented to the dermatology clinic for various skin diseases, such as eczema, vitiligo, tinea, etc., who were not on systemic retinoid therapy, and who received topical medications comprised the control group. The development of COVID-19 in the retinoid therapy group and the control group was retrospectively reviewed using hospital database. Results: The mean age of the patients in the retinoid therapy group was 25.72+or-0.67 and that in the control group was 25.4+or-0.62. Moreover,165 patients received isotretinoin, and 21 patients received acitretin treatment. The isotretinoin dosage ranged from 0.5 to 0.8 mg/kg wheras the acitretin dosage ranged between 10 and 25 mg/day. Two patients (1.07%) in the retinoid therapy group and 8 (4.3%) patients in the control group were diagnosed with COVID-19. None of the patients receiving acitretin was diagnosed with COVID-19. COVID-19 diagnosis was established in the 2nd and 3rd months of isotretinoin treatment, and lung involvement was not observed. No significant difference regarding the number of COVID-19 cases and disease severity was found between the two groups (p=0.105;p=0.258, respectively). Conclusion: Isotretinoin and acitretin use was not associated with increased COVID-19 risk or disease severity. Systemic retinoids appear to be a safe treatment modality in the COVID-19 era.

Cardiovascular side effects of medications for skin diseases

Although many conditions can be successfully managed using the wide range of locally applied physical and pharmacological therapies, systemic administration of drugs is often necessary in dermatology. This chapter gives a brief survey of some of the most important systemic agents used by dermatologists, agents that may induce cardiovascular side effects or, sometimes, may benefit cardiovascular function. © Springer Nature Switzerland AG 2021.

[Pityriasis rubra pilaris after COVID-19 vaccination: causal relationship or coincidence?] / Pityriasis rubra pilaris nach COVID-19-Impfung: Kausaler Zusammenhang oder Koinzidenz?

Numerous cutaneous side effects associated with COVID-19 vaccines have been described since their clinical approval. These include, among others, injection site reactions, urticarial, maculopapular and pityriasiform rashes or temporary exacerbations of a pre-existing chronic inflammatory skin disease. Herein we report about three cases of pityriasis rubra pilaris that occurred for the first time in close temporal relationship with the administration of a COVID-19 vaccine.

Molecular Simulations suggest Vitamins, Retinoids and Steroids as Ligands of the Free Fatty Acid Pocket of the SARS-CoV-2 Spike Protein*.

We investigate binding of linoleate and other potential ligands to the recently discovered fatty acid binding site in the SARS-CoV-2 spike protein, using docking and molecular dynamics simulations. Simulations suggest that linoleate and dexamethasone stabilize the locked spike conformation, thus reducing the opportunity for ACE2 interaction. In contrast, cholesterol may expose the receptor-binding domain by destabilizing the closed structure, preferentially binding to a different site in the hinge region of the open structure. We docked a library of FDA-approved drugs to the fatty acid site using an approach that reproduces the structure of the linoleate complex. Docking identifies steroids (including dexamethasone and vitamin D); retinoids (some known to be active in vitro, and vitamin A); and vitamin K as potential ligands that may stabilize the closed conformation. The SARS-CoV-2 spike fatty acid site may bind a diverse array of ligands, including dietary components, and therefore provides a promising target for therapeutics or prophylaxis.

Liver Damage and Exposure to Toxic Concentrations of Endogenous Retinoids in the Pathogenesis of COVID-19 Disease: Hypothesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a marked tropism for the biliary tract; it damages the bile ducts and hepatocytes and can lead to liver decompensation, cirrhosis, and sepsis. The pathogenesis of liver damage and its association with damage to the lung, heart, and brain and to the other protean manifestations of COVID-19 disease are not fully understood. In particular, tissue damage from thinning and leaky blood vessels appears to result from an inflammatory response to the virus rather than the virus itself. This article outlines a new hypothesis of the nature of the inflammatory factor responsible for tissue damage in COVID-19. Review of the literature reveals that COVID-19 disease closely resembles an endogenous form of hypervitaminosis A. We propose that SARS-CoV-2 virus-induced liver damage causes retinoic acid and stored retinyl esters to be released into the circulation in toxic concentrations, unbound to protein, with resulting damage to organs including the lungs, heart, blood vessels, and skin. Several lines of evidence support this model of disease causation. Subject to testing, strategies for the effective treatment and prevention of COVID-19 could include targeting the action and accumulation of retinoids.

Multiple Vaccinations and the Enigma of Vaccine Injury.

A growing number of vaccines are administered at the same time or in close succession, increasing the complexity of assessing vaccine safety. Individual vaccines are assumed to have no other effect than protection against the targeted pathogen, but vaccines also have nonspecific and interactive effects, the outcomes of which can be beneficial or harmful. To date, no controlled trials and very few observational studies have determined the impact of vaccination schedules on overall health. The balance of the risks and benefits from mass vaccination therefore remains uncertain. Recent studies worryingly suggest links between multiple vaccinations and increased risks of diverse multisystem health problems, including allergies, infections, and neuropsychiatric or neurodevelopmental disorders. Here, we propose that, in susceptible persons, multiple vaccinations activate the retinoid cascade and trigger apoptotic hepatitis, leading to cholestatic liver dysfunction, in which stored vitamin A compounds (retinyl esters and retinoic acid) enter the circulation in toxic concentrations; this induces endogenous forms of hypervitaminosis A, with the severity of adverse outcomes being directly proportional to the concentration of circulating retinoids. In very low concentrations, vitamin A and its major metabolite retinoic acid contribute to immune function and to the process of immunization, whereas excess vitamin A increases the risk of adverse events, including common "side-effects" as well as chronic adverse outcomes. The increasing rates of allergy, ear infections, and neurodevelopmental disorders (NDDs) in countries with high rates of vaccination could be related to mass vaccination and to its impact on liver function and vitamin A metabolism, collectively representing endogenous manifestations of hypervitaminosis A. Further studies of health outcomes in vaccinated and unvaccinated groups are urgently needed, to increase understanding of the pathophysiology and treatment of vaccine injury, to identify the risk factors and screen for vaccine injury, to inform public health policy on potential hazards related to vaccination schedules, and to optimize the safety and benefits of vaccines.

A role for retinoids in the treatment of COVID-19?

The 2020 global outbreak of the novel coronavirus (SARS-CoV-2 or COVID-19) is a serious threat to international health, and thus, there is an urgent need for discovery of novel therapies or use of repurposed drugs that can make a significant impact on slowing the spread of the virus. Type 1 interferons (IFN-I) are a family cytokines of the early innate immune response to viruses that are being tested against SARS-CoV-2. However, coronaviruses similar to SARS-CoV-2 can suppress host IFN-I antiviral responses. Retinoids are a family molecules related to vitamin A that possess robust immune-modulating properties, including the ability to increase and potentiate the actions of IFN-I. Therefore, adjuvants such as retinoids, capable of increasing IFN-I-mediated antiviral responses, should be tested in combinations of IFN-I and antiviral drugs in pre-clinical studies of SARS-CoV-2.