ABSTRACT
SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. SARS-CoV-2 infection is necessary but not sufficient for development of clinical COVID-19 disease. Currently, there are no approved pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We have investigated several plausible hypotheses for famotidine activity including antiviral and host-mediated mechanisms of action. We propose that the principal mechanism of action of famotidine for relieving COVID-19 symptoms involves on-target histamine receptor H2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release. Based on these findings and associated hypothesis, new COVID-19 multi-drug treatment strategies based on repurposing well-characterized drugs are being developed and clinically tested, and many of these drugs are available worldwide in inexpensive generic oral forms suitable for both outpatient and inpatient treatment of COVID-19 disease.
ABSTRACT
BACKGROUND: Patients with critical coronavirus disease 2019 (COVID-19), characterized by respiratory failure requiring mechanical ventilation (MV), are at high risk of mortality. An effective and practical MV weaning protocol is needed for these fragile cases. CASE SUMMARY: Here, we present two critical COVID-19 patients who presented with fever, cough and fatigue. COVID-19 diagnosis was confirmed based on blood cell counts, chest computed tomography (CT) imaging, and nuclei acid test results. To address the patients' respiratory failure, they first received noninvasive ventilation (NIV). When their condition did not improve after 2 h of NIV, each patient was advanced to MV [tidal volume (Vt), 6 mL/kg ideal body weight (IBW); 8-10 cmH2O of positive end-expiratory pressure; respiratory rate, 20 breaths/min; and 40%-80% FiO2] with prone positioning for 12 h/day for the first 5 d of MV. Extensive infection control measures were conducted to minimize morbidity, and pharmacotherapy consisting of an antiviral, immune-enhancer, and thrombosis prophylactic was administered in both cases. Upon resolution of lung changes evidenced by CT, the patients were sequentially weaned using a weaning screening test, spontaneous breathing test, and airbag leak test. After withdrawal of MV, the patients were transitioned through NIV and high-flow nasal cannula oxygen support. Both patients recovered well. CONCLUSION: A MV protocol attentive to intubation/extubation timing, prone positioning early in MV, infection control, and sequential withdrawal of respiratory support, may be an effective regimen for patients with critical COVID-19.
ABSTRACT
We report the clinical and laboratory findings and successful management of seven patients with critical coronavirus disease 2019 (COVID-19) requiring mechanical ventilation (MV). The patients were diagnosed based on epidemiological history, clinical manifestations, and nucleic acid testing. Upon diagnosis with COVID-19 of critical severity, the patients were admitted to the intensive care unit, where they received early noninvasive-invasive sequential ventilation, early prone positioning, and bundle pharmacotherapy regimen, which consists of antiviral, anti-inflammation, immune-enhancing, and complication-prophylaxis medicines. The patients presented fever (n = 7, 100%), dry cough (n = 3, 42.9%), weakness (n = 2, 28.6%), chest tightness (n = 1, 14.3%), and/or muscle pain (n = 1, 14.3%). All patients had normal or lower than normal white blood cell count/lymphocyte count, and chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs. Nucleic acid testing confirmed COVID-19 in all seven patients. The median MV duration and intensive care unit stay were 9.9 days (interquartile range, 6.5-14.6 days; range, 5-17 days) and 12.9 days (interquartile range, 9.7-17.6 days; range, 7-19 days), respectively. All seven patients were extubated, weaned off MV, transferred to the common ward, and discharged as of the writing of this report. Thus, we concluded that good outcomes for patients with critical COVID-19 can be achieved with early noninvasive-invasive sequential ventilation and bundle pharmacotherapy.
Subject(s)
Antiviral Agents/administration & dosage , Coronavirus Infections , Critical Illness/therapy , Noninvasive Ventilation/methods , Pandemics , Pneumonia, Viral , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Chemoprevention/methods , Clinical Laboratory Techniques/methods , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Critical Care/methods , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged , Outcome and Process Assessment, Health Care , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , SARS-CoV-2 , Tomography, X-Ray Computed/methods , Ventilator Weaning/methods , COVID-19 Drug TreatmentABSTRACT
SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We explore several plausible avenues of activity including antiviral and host-mediated actions. We propose that the principal famotidine mechanism of action for COVID-19 involves on-target histamine receptor H 2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release.