Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1175175 (SARS)
 19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article summarizes the likely attenuation properties of RRx-001 in COVID-19 based on its mechanism of action and the putative pathogenesis of the disease, which appears to activate inflammatory, oxidative, and immune cascades with the potential to culminate in acute respiratory distress syndrome, cytokine storm and death. An ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 appears to present with 3 major patterns of clinical symptomatology: (1) mild upper respiratory tract infection, (2) non-life-threatening pneumonia, and (3) severe pneumonia and acute respiratory distress syndrome that initially manifest as a mild prodrome lasting for 7-8 days before rapid clinical and radiological deterioration requiring ICU transfer. RRx-001 is a targeted nitric oxide donor. This small molecule, which has been evaluated in multiple Phase 1-2 clinical trials for cancer as well as a Phase 3 clinical trial for the treatment of small cell lung cancer called REPLATINUM (NCT03699956), is minimally toxic and demonstrates clear evidence of antitumor activity. During the course of these clinical trials it was noted that the rate of chronic obstructive pulmonary disease exacerbation and pneumonia in actively smoking small cell lung cancer patients treated with RRx-001 is less than 1%. Due to extensive history of tobacco use, 40%-70% of patients with lung cancer have chronic obstructive pulmonary disease and the expected rate of pulmonary infection in this population is 50%-70%, which was not observed in RRx-001 clinical trials. Moreover, in preclinical studies of pulmonary hypertension, RRx-001 was found to be comparable with or more effective than the FDA approved agent, Bosentan. The potential pulmonary protective effects of RRx-001 in patients with recurrent lung infections coupled with preclinical models demonstrating RRx-001-mediated reversal of pulmonary hypertension suggests RRx-001 may have therapeutic activity in patients with acute respiratory symptoms due to COVID 19. Clinical trials have been initiated to confirm the hypothesis that RRx-001 may be repurposed to treat SARS-CoV-2 infection.
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PMID:Desperate Times, Desperate Measures: The Case for RRx-001 in the Treatment of COVID-19. 3271 60

SARS-CoV-2 infection is associated with significant lung and cardiac morbidity but there is a limited understanding of the endocrine manifestations of coronavirus disease 2019 (COVID-19). Although thyrotoxicosis due to subacute thyroiditis has been reported in COVID-19, it is unknown whether SARS-CoV-2 infection can also lead to decompensated hypothyroidism. We present the first case of myxedema coma (MC) in COVID-19 and we discuss how SARS-CoV-2 may have precipitated multiorgan damage and sudden cardiac arrest in our patient. A 69-year-old woman with a history of small cell lung cancer presented with hypothermia, hypotension, decreased respiratory rate, and a Glasgow Coma Scale score of 5. The patient was intubated and administered vasopressors. Laboratory investigation showed elevated thyrotropin, very low free thyroxine, elevated thyroid peroxidase antibody, and markedly elevated inflammatory markers. SARS-CoV-2 test was positive. Computed tomography showed pulmonary embolism and peripheral ground-glass opacities in the lungs. The patient was diagnosed with myxedema coma with concomitant COVID-19. While treatment with intravenous hydrocortisone and levothyroxine were begun the patient developed a junctional escape rhythm. Eight minutes later, the patient became pulseless and was eventually resuscitated. Echocardiogram following the arrest showed evidence of right heart dysfunction. She died 2 days later of multiorgan failure. This is the first report of SARS-CoV-2 infection with MC. Sudden cardiac arrest likely resulted from the presence of viral pneumonia, cardiac arrhythmia, pulmonary emboli, and MC-all of which were associated with the patient's SARS-CoV-2 infection.
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PMID:Sudden Cardiac Arrest in a Patient With Myxedema Coma and COVID-19. 3298 43