1. confirmed or suspected immunosuppressive or immunodeficient state 2. prior or concomitant vaccine therapy for covid-19 3. significant disease, disorder, or finding 4. hypercholesterolemia 5. hypertriglyceridemia 6. liver disease 7. renal disease 8. sjögren syndrome 9. pregnancy 10. lactation 11. depressive disorder 12. body mass index less than 18 points or higher than 25 points 13. contraindications for hormonal contraception or intrauterine device. 14. autoimmune diseases a history of organ, bone marrow or hematopoietic stem cell transplantation 15. patients receiving anti-hcv treatment 16. permanent blindness in one eye 17. history of iritis, endophthalmitis, scleral inflammation or retinitis 15-90 days of retinal detachment or eye surgery 18. the competent physician considered it inappropriate to participate in the study ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- safety and promising features of isotretinoin in tne era of covid 2019 according principal investigator protocol: 1. this medication have the feature of aerosolized drug delivery to increase its efficacy beside oral administration, which makes it distinct from other medication in which should dose be only given orally. a study demonstrated that treating with 13 cis retinoic acid aerosolized via inhalation rout did not cause any damage in lung cells. 2. repeated high doses of 13 cis retinoic by inhalation resulted in moderate loss of body weight, but microscopic investigation of ten tissues including lung and oesophagus did not detect any significant aerosol-induced damage. the results suggest that administration of isotretinoin via powder aerosol inhalation is probably superior to its application via the oral route in terms of achieving efficacious drug concentrations in the lung. 3. inhaled isotretinoin might provide sufficient drug to the target cells for efficacy while avoiding systemic toxicity. 4. a study demonstrated that 13 cis retinoic is used in treating emphysema (emphysema is a lung condition that causes shortness of breath) 5. ra has been reported to induce formation of new alveoli and returns elastic recoil in the lung to approximately normal values in animal models of emphysema. 6. strong expectation of complete covid -19 blockade from cell entry and infection depending on strong ethics, researches and references. 7. availability of our compounds. 8. ease of application. 9. expectation of covid -19 treating by isotretinoin via more than one distinct mechanism. 10. inhibiting of thrombosis and platelet which is the most serious consequences caused by viral spike protein or vaccine spike protein:- co-incubation with 13-cis-ra and il-1 resulted in a synergic increase in the release of prostacyclin synthase (pgi2). pgi is a powerful vasodilator that inhibits platelet aggregation through activation of adenylate cyclase,consistently 13-cis-ra increased the ability of huvec to inhibit arachidonic acid -induced platelet aggregation. because of 13cra is a synthetic form that may function similar to the other produced isoforms, or by isomerization to atra and 9c ra. ra therapy has proven anti-platelet , anti- inflammatory, and fibrinolytic activities we suggest that 13cra may protect patients infected with covid-19 from pulmonary clots. 11. isotretinoin can induce innate immune response for recognition of cov in addition to , inhibiting il-6 the genome of middle east respiratory syndrome coronavirus is recognized by melanoma differentiation-associated protein-5 (mda5), retinoic acid inducible gene-1 (rig-1) and endosomal toll-like receptor 3 (tlr3) as pathogen-associated molecular patterns which recognize ssrna and dsrna intermediate of covid-19.this recognition resulted in the formation of type-1 interferon (ifn1) as in (fig 6).covid-19 synthesizes proteins that hinder the production ifn1 in its replication pathway, which is an evasion mechanism \[123\],\[124\],\[125\],\[126\],\[127\],\[128\],\[129\]. a study demonstrated that tlr3(-/-), tlr4(-/-), and tram(-/-) mice are more susceptible to sars-cov than wild-type mice but experience only transient weight loss with no mortality in response to infection. on the other hand, mice deficient in the tlr3/tlr4 adaptor trif are highly susceptible to sars-cov infection, showing increased weight loss, mortality, reduced lung function, increased lung pathology, and higher viral titers \[130\]. previous studies revealed that the high level of ifn- α/β produced via the tlr3-irf3/irf7 pathway and ifn-β is the reason for inhibiting dengue virus (denv) replication \[131\]. 13-cis retinoic acid induced significant upregulation of toll-like receptor 3 (tlr3), mitochondrial antiviral-signaling protein (mavs) and (rig-i) and ifn regulatory factor 1 expression in a time-dependent \[132\].furthermore, a study reported that 13-cis-retinoic acid and other retinoid analogs inhibit il-1-induced il-6 production and that this effect is analog-specific and, at least partially, transcriptionally mediated. this effect was dose-dependent with an ic50 of 10(-7) m ra and significant inhibition was found with doses of ra as low as 10(-8) m \[122\].

1. confirmed or suspected immunosuppressive or immunodeficient state 2. prior or concomitant vaccine therapy for covid-19 3. significant disease, disorder, or finding 4. hypercholesterolemia 5. hypertriglyceridemia 6. liver disease 7. renal disease 8. sjögren syndrome 9. pregnancy 10. lactation 11. depressive disorder 12. body mass index less than 18 points or higher than 25 points 13. contraindications for hormonal contraception or intrauterine device. 14. autoimmune diseases a history of organ, bone marrow or hematopoietic stem cell transplantation 15. patients receiving anti-hcv treatment 16. permanent blindness in one eye 17. history of iritis, endophthalmitis, scleral inflammation or retinitis 15-90 days of retinal detachment or eye surgery 18. the competent physician considered it inappropriate to participate in the study ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- safety and promising features of isotretinoin in tne era of covid 2019 according principal investigator protocol: 1. this medication have the feature of aerosolized drug delivery to increase its efficacy beside oral administration, which makes it distinct from other medication in which should dose be only given orally. a study demonstrated that treating with 13 cis retinoic acid aerosolized via inhalation rout did not cause any damage in lung cells. 2. repeated high doses of 13 cis retinoic by inhalation resulted in moderate loss of body weight, but microscopic investigation of ten tissues including lung and oesophagus did not detect any significant aerosol-induced damage. the results suggest that administration of isotretinoin via powder aerosol inhalation is probably superior to its application via the oral route in terms of achieving efficacious drug concentrations in the lung. 3. inhaled isotretinoin might provide sufficient drug to the target cells for efficacy while avoiding systemic toxicity. 4. a study demonstrated that 13 cis retinoic is used in treating emphysema (emphysema is a lung condition that causes shortness of breath) 5. ra has been reported to induce formation of new alveoli and returns elastic recoil in the lung to approximately normal values in animal models of emphysema. 6. strong expectation of complete covid -19 blockade from cell entry and infection depending on strong ethics, researches and references. 7. availability of our compounds. 8. ease of application. 9. expectation of covid -19 treating by isotretinoin via more than one distinct mechanism. 10. inhibiting of thrombosis and platelet which is the most serious consequences caused by viral spike protein or vaccine spike protein:- co-incubation with 13-cis-ra and il-1 resulted in a synergic increase in the release of prostacyclin synthase (pgi2). pgi is a powerful vasodilator that inhibits platelet aggregation through activation of adenylate cyclase,consistently 13-cis-ra increased the ability of huvec to inhibit arachidonic acid -induced platelet aggregation. because of 13cra is a synthetic form that may function similar to the other produced isoforms, or by isomerization to atra and 9c ra. ra therapy has proven anti-platelet , anti- inflammatory, and fibrinolytic activities we suggest that 13cra may protect patients infected with covid-19 from pulmonary clots. 11. isotretinoin can induce innate immune response for recognition of cov in addition to , inhibiting il-6 the genome of middle east respiratory syndrome coronavirus is recognized by melanoma differentiation-associated protein-5 (mda5), retinoic acid inducible gene-1 (rig-1) and endosomal toll-like receptor 3 (tlr3) as pathogen-associated molecular patterns which recognize ssrna and dsrna intermediate of covid-19.this recognition resulted in the formation of type-1 interferon (ifn1) as in (fig 6).covid-19 synthesizes proteins that hinder the production ifn1 in its replication pathway, which is an evasion mechanism \[123\],\[124\],\[125\],\[126\],\[127\],\[128\],\[129\]. a study demonstrated that tlr3(-/-), tlr4(-/-), and tram(-/-) mice are more susceptible to sars-cov than wild-type mice but experience only transient weight loss with no mortality in response to infection. on the other hand, mice deficient in the tlr3/tlr4 adaptor trif are highly susceptible to sars-cov infection, showing increased weight loss, mortality, reduced lung function, increased lung pathology, and higher viral titers \[130\]. previous studies revealed that the high level of ifn- α/β produced via the tlr3-irf3/irf7 pathway and ifn-β is the reason for inhibiting dengue virus (denv) replication \[131\]. 13-cis retinoic acid induced significant upregulation of toll-like receptor 3 (tlr3), mitochondrial antiviral-signaling protein (mavs) and (rig-i) and ifn regulatory factor 1 expression in a time-dependent \[132\].furthermore, a study reported that 13-cis-retinoic acid and other retinoid analogs inhibit il-1-induced il-6 production and that this effect is analog-specific and, at least partially, transcriptionally mediated. this effect was dose-dependent with an ic50 of 10(-7) m ra and significant inhibition was found with doses of ra as low as 10(-8) m \[122\].

confirmed or suspected immunosuppressive or immunodeficient state prior or concomitant vaccine therapy for covid-19 significant disease, disorder, or finding hypercholesterolemia hypertriglyceridemia liver disease renal disease sjögren syndrome pregnancy lactation depressive disorder body mass index less than 18 points or higher than 25 points contraindications for hormonal contraception or intrauterine device. autoimmune diseases a history of organ, bone marrow or hematopoietic stem cell transplantation patients receiving anti-hcv treatment permanent blindness in one eye history of iritis, endophthalmitis, scleral inflammation or retinitis 15-90 days of retinal detachment or eye surgery the competent physician considered it inappropriate to participate in the study ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- safety and promising features of isotretinoin in tne era of covid 2019 according principal investigator protocol: this medication have the feature of aerosolized drug delivery to increase its efficacy beside oral administration, which makes it distinct from other medication in which should dose be only given orally. a study demonstrated that treating with 13 cis retinoic acid aerosolized via inhalation rout did not cause any damage in lung cells. repeated high doses of 13 cis retinoic by inhalation resulted in moderate loss of body weight, but microscopic investigation of ten tissues including lung and oesophagus did not detect any significant aerosol-induced damage. the results suggest that administration of isotretinoin via powder aerosol inhalation is probably superior to its application via the oral route in terms of achieving efficacious drug concentrations in the lung. inhaled isotretinoin might provide sufficient drug to the target cells for efficacy while avoiding systemic toxicity. a study demonstrated that 13 cis retinoic is used in treating emphysema (emphysema is a lung condition that causes shortness of breath) ra has been reported to induce formation of new alveoli and returns elastic recoil in the lung to approximately normal values in animal models of emphysema. strong expectation of complete covid -19 blockade from cell entry and infection depending on strong ethics, researches and references. availability of our compounds. ease of application. expectation of covid -19 treating by isotretinoin via more than one distinct mechanism. inhibiting of thrombosis and platelet which is the most serious consequences caused by viral spike protein or vaccine spike protein:- co-incubation with 13-cis-ra and il-1 resulted in a synergic increase in the release of prostacyclin synthase (pgi2). pgi is a powerful vasodilator that inhibits platelet aggregation through activation of adenylate cyclase,consistently 13-cis-ra increased the ability of huvec to inhibit arachidonic acid -induced platelet aggregation. because of 13cra is a synthetic form that may function similar to the other produced isoforms, or by isomerization to atra and 9c ra. ra therapy has proven anti-platelet , anti- inflammatory, and fibrinolytic activities we suggest that 13cra may protect patients infected with covid-19 from pulmonary clots. isotretinoin can induce innate immune response for recognition of cov in addition to , inhibiting il-6 the genome of middle east respiratory syndrome coronavirus is recognized by melanoma differentiation-associated protein-5 (mda5), retinoic acid inducible gene-1 (rig-1) and endosomal toll-like receptor 3 (tlr3) as pathogen-associated molecular patterns which recognize ssrna and dsrna intermediate of covid-19.this recognition resulted in the formation of type-1 interferon (ifn1) as in (fig 6).covid-19 synthesizes proteins that hinder the production ifn1 in its replication pathway, which is an evasion mechanism [123],[124],[125],[126],[127],[128],[129]. a study demonstrated that tlr3(-/-), tlr4(-/-), and tram(-/-) mice are more susceptible to sars-cov than wild-type mice but experience only transient weight loss with no mortality in response to infection. on the other hand, mice deficient in the tlr3/tlr4 adaptor trif are highly susceptible to sars-cov infection, showing increased weight loss, mortality, reduced lung function, increased lung pathology, and higher viral titers [130]. previous studies revealed that the high level of ifn- α/β produced via the tlr3-irf3/irf7 pathway and ifn-β is the reason for inhibiting dengue virus (denv) replication [131]. 13-cis retinoic acid induced significant upregulation of toll-like receptor 3 (tlr3), mitochondrial antiviral-signaling protein (mavs) and (rig-i) and ifn regulatory factor 1 expression in a time-dependent [132].furthermore, a study reported that 13-cis-retinoic acid and other retinoid analogs inhibit il-1-induced il-6 production and that this effect is analog-specific and, at least partially, transcriptionally mediated. this effect was dose-dependent with an ic50 of 10(-7) m ra and significant inhibition was found with doses of ra as low as 10(-8) m [122].

confirmed or suspected immunosuppressive or immunodeficient state prior or concomitant vaccine therapy for covid-19 significant disease, disorder, or finding hypercholesterolemia hypertriglyceridemia liver disease renal disease sjögren syndrome pregnancy lactation depressive disorder body mass index less than 18 points or higher than 25 points contraindications for hormonal contraception or intrauterine device. autoimmune diseases a history of organ, bone marrow or hematopoietic stem cell transplantation patients receiving anti-hcv treatment permanent blindness in one eye history of iritis, endophthalmitis, scleral inflammation or retinitis 15-90 days of retinal detachment or eye surgery the competent physician considered it inappropriate to participate in the study ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- safety and promising features of isotretinoin in tne era of covid 2019 according principal investigator protocol: this medication have the feature of aerosolized drug delivery to increase its efficacy beside oral administration, which makes it distinct from other medication in which should dose be only given orally. a study demonstrated that treating with 13 cis retinoic acid aerosolized via inhalation rout did not cause any damage in lung cells. repeated high doses of 13 cis retinoic by inhalation resulted in moderate loss of body weight, but microscopic investigation of ten tissues including lung and oesophagus did not detect any significant aerosol-induced damage. the results suggest that administration of isotretinoin via powder aerosol inhalation is probably superior to its application via the oral route in terms of achieving efficacious drug concentrations in the lung. inhaled isotretinoin might provide sufficient drug to the target cells for efficacy while avoiding systemic toxicity. a study demonstrated that 13 cis retinoic is used in treating emphysema (emphysema is a lung condition that causes shortness of breath) ra has been reported to induce formation of new alveoli and returns elastic recoil in the lung to approximately normal values in animal models of emphysema. strong expectation of complete covid -19 blockade from cell entry and infection depending on strong ethics, researches and references. availability of our compounds. ease of application. expectation of covid -19 treating by isotretinoin via more than one distinct mechanism. inhibiting of thrombosis and platelet which is the most serious consequences caused by viral spike protein or vaccine spike protein:- co-incubation with 13-cis-ra and il-1 resulted in a synergic increase in the release of prostacyclin synthase (pgi2). pgi is a powerful vasodilator that inhibits platelet aggregation through activation of adenylate cyclase,consistently 13-cis-ra increased the ability of huvec to inhibit arachidonic acid -induced platelet aggregation. because of 13cra is a synthetic form that may function similar to the other produced isoforms, or by isomerization to atra and 9c ra. ra therapy has proven anti-platelet , anti- inflammatory, and fibrinolytic activities we suggest that 13cra may protect patients infected with covid-19 from pulmonary clots. isotretinoin can induce innate immune response for recognition of cov in addition to , inhibiting il-6 the genome of middle east respiratory syndrome coronavirus is recognized by melanoma differentiation-associated protein-5 (mda5), retinoic acid inducible gene-1 (rig-1) and endosomal toll-like receptor 3 (tlr3) as pathogen-associated molecular patterns which recognize ssrna and dsrna intermediate of covid-19.this recognition resulted in the formation of type-1 interferon (ifn1) as in (fig 6).covid-19 synthesizes proteins that hinder the production ifn1 in its replication pathway, which is an evasion mechanism [123],[124],[125],[126],[127],[128],[129]. a study demonstrated that tlr3(-/-), tlr4(-/-), and tram(-/-) mice are more susceptible to sars-cov than wild-type mice but experience only transient weight loss with no mortality in response to infection. on the other hand, mice deficient in the tlr3/tlr4 adaptor trif are highly susceptible to sars-cov infection, showing increased weight loss, mortality, reduced lung function, increased lung pathology, and higher viral titers [130]. previous studies revealed that the high level of ifn- α/β produced via the tlr3-irf3/irf7 pathway and ifn-β is the reason for inhibiting dengue virus (denv) replication [131]. 13-cis retinoic acid induced significant upregulation of toll-like receptor 3 (tlr3), mitochondrial antiviral-signaling protein (mavs) and (rig-i) and ifn regulatory factor 1 expression in a time-dependent [132].furthermore, a study reported that 13-cis-retinoic acid and other retinoid analogs inhibit il-1-induced il-6 production and that this effect is analog-specific and, at least partially, transcriptionally mediated. this effect was dose-dependent with an ic50 of 10(-7) m ra and significant inhibition was found with doses of ra as low as 10(-8) m [122].

1. confirmed or suspected immunosuppressive or immunodeficient state 2. prior or concomitant vaccine therapy for covid-19 3. significant disease, disorder, or finding 4. hypercholesterolemia 5. hypertriglyceridemia 6. liver disease 7. renal disease 8. sjögren syndrome 9. pregnancy 10. lactation 11. depressive disorder 12. body mass index less than 18 points or higher than 25 points 13. contraindications for hormonal contraception or intrauterine device. 14. autoimmune diseases a history of organ, bone marrow or hematopoietic stem cell transplantation 15. patients receiving anti-hcv treatment 16. permanent blindness in one eye 17. history of iritis, endophthalmitis, scleral inflammation or retinitis 15-90 days of retinal detachment or eye surgery 18. the competent physician considered it inappropriate to participate in the study -------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------- --------------------------------------------------------------- safety and promising features of isotretinoin in tne era of covid 2019 according principal investigator protocol: 1. this medication have the feature of aerosolized drug delivery to increase its efficacy beside oral administration, which makes it distinct from other medication in which should dose be only given orally. a study demonstrated that treating with 13 cis retinoic acid aerosolized via inhalation rout did not cause any damage in lung cells. 2. repeated high doses of 13 cis retinoic by inhalation resulted in moderate loss of body weight, but microscopic investigation of ten tissues including lung and oesophagus did not detect any significant aerosol-induced damage. the results suggest that administration of isotretinoin via powder aerosol inhalation is probably superior to its application via the oral route in terms of achieving efficacious drug concentrations in the lung. 3. inhaled isotretinoin might provide sufficient drug to the target cells for efficacy while avoiding systemic toxicity. 4. a study demonstrated that 13 cis retinoic is used in treating emphysema (emphysema is a lung condition that causes shortness of breath) 5. ra has been reported to induce formation of new alveoli and returns elastic recoil in the lung to approximately normal values in animal models of emphysema. 6. strong expectation of complete covid -19 blockade from cell entry and infection depending on strong ethics, researches and references. 7. availability of our compounds. 8. ease of application. 9. expectation of covid -19 treating by isotretinoin via more than one distinct mechanism. 10. inhibiting of thrombosis and platelet which is the most serious consequences caused by viral spike protein or vaccine spike protein:- co-incubation with 13-cis-ra and il-1 resulted in a synergic increase in the release of prostacyclin synthase (pgi2). pgi is a powerful vasodilator that inhibits platelet aggregation through activation of adenylate cyclase,consistently 13-cis-ra increased the ability of huvec to inhibit arachidonic acid -induced platelet aggregation. because of 13cra is a synthetic form that may function similar to the other produced isoforms, or by isomerization to atra and 9c ra. ra therapy has proven anti-platelet , anti- inflammatory, and fibrinolytic activities we suggest that 13cra may protect patients infected with covid-19 from pulmonary clots. 11. isotretinoin can induce innate immune response for recognition of cov in addition to , inhibiting il-6 the genome of middle east respiratory syndrome coronavirus is recognized by melanoma differentiation-associated protein-5 (mda5), retinoic acid inducible gene-1 (rig-1) and endosomal toll-like receptor 3 (tlr3) as pathogen-associated molecular patterns which recognize ssrna and dsrna intermediate of covid-19.this recognition resulted in the formation of type-1 interferon (ifn1) as in (fig 6).covid-19 synthesizes proteins that hinder the production ifn1 in its replication pathway, which is an evasion mechanism [123],[124],[125],[126],[127],[128],[129]. a study demonstrated that tlr3(-/-), tlr4(-/-), and tram(-/-) mice are more susceptible to sars-cov than wild-type mice but experience only transient weight loss with no mortality in response to infection. on the other hand, mice deficient in the tlr3/tlr4 adaptor trif are highly susceptible to sars-cov infection, showing increased weight loss, mortality, reduced lung function, increased lung pathology, and higher viral titers [130]. previous studies revealed that the high level of ifn- α/β produced via the tlr3-irf3/irf7 pathway and ifn-β is the reason for inhibiting dengue virus (denv) replication [131]. 13-cis retinoic acid induced significant upregulation of toll-like receptor 3 (tlr3), mitochondrial antiviral-signaling protein (mavs) and (rig-i) and ifn regulatory factor 1 expression in a time-dependent [132].furthermore, a study reported that 13-cis-retinoic acid and other retinoid analogs inhibit il-1-induced il-6 production and that this effect is analog-specific and, at least partially, transcriptionally mediated. this effect was dose-dependent with an ic50 of 10(-7) m ra and significant inhibition was found with doses of ra as low as 10(-8) m [122].

1. confirmed or suspected immunosuppressive or immunodeficient state 2. prior or concomitant vaccine therapy for covid-19 3. significant disease, disorder, or finding 4. hypercholesterolemia 5. hypertriglyceridemia 6. liver disease 7. renal disease 8. sjögren syndrome 9. pregnancy 10. lactation 11. depressive disorder 12. body mass index less than 18 points or higher than 25 points 13. contraindications for hormonal contraception or intrauterine device. 14. autoimmune diseases a history of organ, bone marrow or hematopoietic stem cell transplantation 15. patients receiving anti-hcv treatment 16. permanent blindness in one eye 17. history of iritis, endophthalmitis, scleral inflammation or retinitis 15-90 days of retinal detachment or eye surgery 18. the competent physician considered it inappropriate to participate in the study -------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------- --------------------------------------------------------------- safety and promising features of isotretinoin in tne era of covid 2019 according principal investigator protocol: 1. this medication have the feature of aerosolized drug delivery to increase its efficacy beside oral administration, which makes it distinct from other medication in which should dose be only given orally. a study demonstrated that treating with 13 cis retinoic acid aerosolized via inhalation rout did not cause any damage in lung cells. 2. repeated high doses of 13 cis retinoic by inhalation resulted in moderate loss of body weight, but microscopic investigation of ten tissues including lung and oesophagus did not detect any significant aerosol-induced damage. the results suggest that administration of isotretinoin via powder aerosol inhalation is probably superior to its application via the oral route in terms of achieving efficacious drug concentrations in the lung. 3. inhaled isotretinoin might provide sufficient drug to the target cells for efficacy while avoiding systemic toxicity. 4. a study demonstrated that 13 cis retinoic is used in treating emphysema (emphysema is a lung condition that causes shortness of breath) 5. ra has been reported to induce formation of new alveoli and returns elastic recoil in the lung to approximately normal values in animal models of emphysema. 6. strong expectation of complete covid -19 blockade from cell entry and infection depending on strong ethics, researches and references. 7. availability of our compounds. 8. ease of application. 9. expectation of covid -19 treating by isotretinoin via more than one distinct mechanism. 10. inhibiting of thrombosis and platelet which is the most serious consequences caused by viral spike protein or vaccine spike protein:- co-incubation with 13-cis-ra and il-1 resulted in a synergic increase in the release of prostacyclin synthase (pgi2). pgi is a powerful vasodilator that inhibits platelet aggregation through activation of adenylate cyclase,consistently 13-cis-ra increased the ability of huvec to inhibit arachidonic acid -induced platelet aggregation. because of 13cra is a synthetic form that may function similar to the other produced isoforms, or by isomerization to atra and 9c ra. ra therapy has proven anti-platelet , anti- inflammatory, and fibrinolytic activities we suggest that 13cra may protect patients infected with covid-19 from pulmonary clots. 11. isotretinoin can induce innate immune response for recognition of cov in addition to , inhibiting il-6 the genome of middle east respiratory syndrome coronavirus is recognized by melanoma differentiation-associated protein-5 (mda5), retinoic acid inducible gene-1 (rig-1) and endosomal toll-like receptor 3 (tlr3) as pathogen-associated molecular patterns which recognize ssrna and dsrna intermediate of covid-19.this recognition resulted in the formation of type-1 interferon (ifn1) as in (fig 6).covid-19 synthesizes proteins that hinder the production ifn1 in its replication pathway, which is an evasion mechanism [123],[124],[125],[126],[127],[128],[129]. a study demonstrated that tlr3(-/-), tlr4(-/-), and tram(-/-) mice are more susceptible to sars-cov than wild-type mice but experience only transient weight loss with no mortality in response to infection. on the other hand, mice deficient in the tlr3/tlr4 adaptor trif are highly susceptible to sars-cov infection, showing increased weight loss, mortality, reduced lung function, increased lung pathology, and higher viral titers [130]. previous studies revealed that the high level of ifn- α/β produced via the tlr3-irf3/irf7 pathway and ifn-β is the reason for inhibiting dengue virus (denv) replication [131]. 13-cis retinoic acid induced significant upregulation of toll-like receptor 3 (tlr3), mitochondrial antiviral-signaling protein (mavs) and (rig-i) and ifn regulatory factor 1 expression in a time-dependent [132].furthermore, a study reported that 13-cis-retinoic acid and other retinoid analogs inhibit il-1-induced il-6 production and that this effect is analog-specific and, at least partially, transcriptionally mediated. this effect was dose-dependent with an ic50 of 10(-7) m ra and significant inhibition was found with doses of ra as low as 10(-8) m [122].