Coronavirus disease 2019 (COVID‐19) is associated with endothelial dysfunction. Pharmacologically targeting the different mechanisms of endothelial dysfunction may improve clinical outcomes and lead to reduced morbidity and mortality. In this pilot, double‐blind, placebo‐controlled, randomized clinical trial, we assigned patients who were admitted to the hospital with mild, moderate, or severe COVID‐19 infection to receive, on top of optimal medical therapy, either an endothelial protocol consisting of (Nicorandil, L‐arginine, folate, Nebivolol, and atorvastatin) or placebo for up to 14 days. The primary outcome was time to recovery, measured by an eight category ordinal scale and defined by the time to being discharged from the hospital or hospitalized for infection‐control or other nonmedical reasons. Secondary outcomes included the composite outcome of intensive care unit (ICU) admission or the need for mechanical ventilation, all‐cause mortality, and the occurrence of side effects. Of 42 randomized patients, 37 were included in the primary analysis. The mean age of the patients was 57 years; the mean body mass index of study participants was 29.14. History of hypertension was present in 27% of the patients, obesity in 45%, and diabetes mellitus in 21.6%. The median (interquartile range) time to recovery was not significantly different between the endothelial protocol group (6 [4–12] days) and the placebo group (6 [5–8] days; p value = 0.854). Furthermore, there were no statistically significant differences in the need for mechanical ventilation or ICU admission, all‐cause mortality, or the occurrence of side effects between the endothelial protocol group and the placebo group. Among patients hospitalized with mild, moderate, or severe COVID‐19 infection, targeting endothelial dysfunction by administering Nicorandil, L‐arginine, Folate, Nebivolol, and Atorvastatin on top of optimal medical therapy did not decrease time to recovery. Based on this study’s findings, targeting endothelial dysfunction did not result in a clinically significant improvement in outcome and, as such, larger trials targeting this pathway are not recommended.
Background: Coronavirus disease 2019 (Covid-19) is associated with endothelial dysfunction. Pharmacologically targeting the different mechanisms of endothelial dysfunction may improve clinical outcomes and lead to reduced morbidity and mortality Methods: In this pilot, double-blind, placebo-controlled, randomized clinical trial we assigned patients who were admitted to the hospital with mild, moderate, or severe COVID-19 infection to receive, on top of optimal medical therapy, either an endothelial protocol consisting of (Nicorandil, L-arginine, Folate, Nebivolol, and Atorvastatin) or placebo for up to 14 days. The primary outcome was time to recovery, measured by an 8 category ordinal scale and defined by the time to being discharged from the hospital or hospitalized for infection-control or other nonmedical reasons. Secondary outcomes included the composite outcome of ICU admission or the need for mechanical ventilation, all-cause mortality, and the occurrence of side effects Results: Of 42 randomized patients, 37 were included in the primary analysis. The mean age of the patients was 57 years; the mean BMI of study participants was 29.14. History of hypertension was present in 27% of the patients, obesity in 45%, and Diabetes Mellitus in 21.6%. The median(Interquartile range) time to recovery was not significantly different between the endothelial protocol group (6 [4-12] days) and the placebo group (6 [5-8]days)(p-value = 0.854). Furthermore, there were no statistically significant differences in the need for mechanical ventilation or ICU admission, all-cause mortality, and the occurrence of side effects between the endothelial protocol group and the placebo group. Conclusion: Among patients hospitalized with mild, moderate, or severe COVID-19 infection, targeting endothelial dysfunction by administering Nicorandil, L-arginine, Folate, Nebivolol, and Atorvastatin on top of optimal medical therapy did not decrease time to recovery. However, this treatment protocol was associated with an excellent safety profile. Adequately sized prospective randomized controlled trials are needed for the evaluation of the role of treating endothelial dysfunction in COVID-19 infection.
Background: Mucormycosis is a rare fatal infection caused by a ubiquitous fungus from the order of Mucorales, which can have varying clinical presentations. Immunocompromised patients are particularly susceptible to mucormycosis and can suffer fatal consequences if not treated adequately. COVID-19 infection with its immunomodulatory properties has been associated with a wide range of secondary bacterial and fungal infections. We present a case of rapidly progressive rhinocerebral mucormycosis post-COVID-19 infection with the subsequent development of several complications associated with the disease. Case Report: A 62-year-old male patient with a history of hypertension and diabetes mellitus type II, presented 14 days post-COVID-19 recovery with right facial swelling, erythema, and right eye proptosis. Throughout his disease, the patient developed blindness and cranial nerve palsies. He was also found to have palatal necrotic lesions, consistent with the diagnosis of mucormycosis. The patient’s disease was complicated by Garcin syndrome, meningitis, orbital apex syndrome, cavernous sinus thrombosis, brain infarction, and hemorrhage. Despite all measures and interventions, the patient died. Conclusion: COVID-19 infection and its treatments are associated with an increased risk of secondary fungal infections like mucormycosis. As such, a high index of suspicion is needed amongst healthcare workers for the early diagnosis and treatment of such opportunistic infections since prompt treatment is associated with a marked improvement in outcome. Furthermore, optimal glucose control and judicious use of corticosteroids in COVID-19 patients decreases the risk of developping such life threatening superinfections.
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