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Clin Pharmacol Ther ; 110(6): 1498-1511, 2021 12.
Article in English | MEDLINE | ID: covidwho-1245382


Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the ASM/ceramide system may be central to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe coronavirus disease 2019 (COVID-19) in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking an FIASMA medication at the time of their hospital admission. The primary end point was a composite of intubation and/or death. We compared this end point between patients taking vs. not taking an FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD = 12.5), the primary end point occurred in 104 patients (37.5%) receiving an FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.58-0.87, P < 0.001) and primary IPW (HR = 0.58, 95%CI = 0.46-0.72, P < 0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one particular FIASMA class or medication. These results show the potential importance of the ASM/ceramide system in COVID-19 and support the continuation of FIASMA medications in these patients. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.

COVID-19/enzymology , COVID-19/mortality , Hospitalization/trends , Intubation, Intratracheal/mortality , Intubation, Intratracheal/trends , Sphingomyelin Phosphodiesterase/antagonists & inhibitors , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 Testing/trends , Cohort Studies , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Female , Humans , Male , Middle Aged , Mortality/trends , Retrospective Studies , Sphingomyelin Phosphodiesterase/metabolism , Young Adult , COVID-19 Drug Treatment
Crit Care Med ; 48(11): e1097-e1101, 2020 11.
Article in English | MEDLINE | ID: covidwho-998502


OBJECTIVES: To characterize the impact of obesity on disease severity in patients with coronavirus disease 2019. DESIGN: This was a retrospective cohort study designed to evaluate the association between body mass index and risk of severe disease in patients with coronavirus disease 2019. Data were abstracted from the electronic health record. The primary endpoint was a composite of intubation or death. SETTING: Two hospitals in Massachusetts (one quaternary referral center and one affiliated community hospital). PATIENTS: Consecutive patients hospitalized with confirmed coronavirus disease 2019 admitted between March 13, 2020, and April 3, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 305 patients were included in this study. We stratified patients by body mass index category: < 25 kg/m (54 patients, 18%), ≥ 25 kg/m to < 30 kg/m (124 patients, 41%), ≥ 30 kg/m to < 35 kg/m (58 patients, 19%), and ≥ 35 kg/m (69 patients, 23%). In total, 128 patients (42%) had a primary endpoint (119 patients [39%] were intubated and nine died [3%] without intubation). Sixty-five patients (51%) with body mass index greater than or equal to 30 kg/m were intubated or died. Adjusted Cox models demonstrated that body mass index greater than or equal to 30 kg/m was associated with a 2.3-fold increased risk of intubation or death (95% CI, 1.2-4.3) compared with individuals with body mass index less than 25 kg/m. Diabetes was also independently associated with risk of intubation or death (hazard ratio, 1.8; 95% CI, 1.2-2.7). Fifty-six out of 127 patients (44%) with body mass index greater than or equal to 30 kg/m had diabetes, and the combination of both diabetes and body mass index greater than or equal to 30 kg/m was associated with a 4.5-fold increased risk of intubation or death (95% CI, 2.0-10.2) compared with patients without diabetes and body mass index less than 25 kg/m. CONCLUSIONS: Among consecutive patients hospitalized with coronavirus disease 2019, obesity was an independent risk factor for intubation or death.

Betacoronavirus , Coronavirus Infections/mortality , Critical Illness/mortality , Intubation, Intratracheal/mortality , Obesity/mortality , Pneumonia, Viral/mortality , Adult , Aged, 80 and over , Body Mass Index , COVID-19 , Coronavirus Infections/therapy , Humans , Intensive Care Units , Male , Middle Aged , Obesity/complications , Pandemics , Pneumonia, Viral/therapy , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index
Tohoku J Exp Med ; 252(2): 103-107, 2020 10.
Article in English | MEDLINE | ID: covidwho-757142


Coronavirus disease 2019 (COVID-19) is a global public health concern that can be classified as mild, moderate, severe, or critical, based on disease severity. Since the identification of critical patients is crucial for developing effective management strategies, we evaluated clinical characteristics, laboratory data, treatment provided, and oxygenation to identify potential predictors of mortality among critical COVID-19 pneumonia patients. We retrospectively utilized data from seven critical patients who were admitted to our hospital during April 2020 and required mechanical ventilation. The primary endpoint was to clarify potential predictor of mortality. All patients were older than 70 years, five were men, six had hypertension, and three ultimately died. Compared with survivors, non-survivors tended to be never smokers (0 pack-years vs. 30 pack-years, p = 0.08), to have higher body mass index (31.3 kg/m2 vs. 25.3 kg/m2, p = 0.06), to require earlier tracheal intubation after symptom onset (2.7 days vs. 5.5 days, p = 0.07), and had fewer lymphocytes on admission (339 /µL vs. 518 /µL, p = 0.05). During the first week after tracheal intubation, non-survivors displayed lower values for minimum ratio of the partial pressure of oxygen to fractional inspiratory oxygen concentration (P/F ratio) (44 mmHg vs. 122 mmHg, p < 0.01) and poor response to intensive therapy compared with survivors. In summary, we show that obesity and lymphopenia could predict the severity of COVID-19 pneumonia and that the trend of lower P/F ratio during the first week of mechanical ventilation could provide useful prognostic information.

Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Critical Illness/therapy , Intubation, Intratracheal , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Smoking , Aged , Betacoronavirus/physiology , COVID-19 , Cohort Studies , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Critical Illness/epidemiology , Critical Illness/mortality , Female , Hospitalization , Humans , Intubation, Intratracheal/mortality , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Prognosis , Radiography, Thoracic , Retrospective Studies , Risk Factors , SARS-CoV-2 , Smoking/adverse effects , Smoking/epidemiology , Smoking/mortality , Smoking/therapy , Tomography, X-Ray Computed