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1.
Crit Care Explor ; 2(9): e0202, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1795075

ABSTRACT

OBJECTIVES: Patients with coronavirus disease 2019 acute respiratory distress syndrome appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (type 1) and a more conventional acute respiratory distress syndrome phenotype, displaying the typical characteristics of the "baby lung" (type 2). We aimed to test plausible hypotheses regarding the pathophysiologic mechanisms underlying coronavirus disease 2019 acute respiratory distress syndrome and to evaluate the resulting implications for ventilatory management. DESIGN: We adapted a high-fidelity computational simulator, previously validated in several studies of acute respiratory distress syndrome, to: 1) develop quantitative insights into the key pathophysiologic differences between the coronavirus disease 2019 acute respiratory distress syndrome and the conventional acute respiratory distress syndrome and 2) assess the impact of different positive end-expiratory pressure, Fio2, and tidal volume settings. SETTING: Interdisciplinary Collaboration in Systems Medicine Research Network. SUBJECTS: The simulator was calibrated to represent coronavirus disease 2019 acute respiratory distress syndrome patients with both normal and elevated body mass indices undergoing invasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An acute respiratory distress syndrome model implementing disruption of hypoxic pulmonary vasoconstriction and vasodilation leading to hyperperfusion of collapsed lung regions failed to replicate clinical data on type 1 coronavirus disease 2019 acute respiratory distress syndrome patients. Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis and heightened vascular resistance due to the emergence of microthrombi produced levels of ventilation perfusion mismatch and hypoxemia consistent with data from type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, while preserving close-to-normal lung compliance and gas volumes. Atypical responses to positive end-expiratory pressure increments between 5 and 15 cm H2O were observed for this type 1 coronavirus disease 2019 acute respiratory distress syndrome model across a range of measures: increasing positive end-expiratory pressure resulted in reduced lung compliance and no improvement in oxygenation, whereas mechanical power, driving pressure, and plateau pressure all increased. Fio2 settings based on acute respiratory distress syndrome network protocols at different positive end-expiratory pressure levels were insufficient to achieve adequate oxygenation. Incrementing tidal volumes from 5 to 10 mL/kg produced similar increases in multiple indicators of ventilator-induced lung injury in the type 1 coronavirus disease 2019 acute respiratory distress syndrome model to those seen in a conventional acute respiratory distress syndrome model. CONCLUSIONS: Our model suggests that use of standard positive end-expiratory pressure/Fio2 tables, higher positive end-expiratory pressure strategies, and higher tidal volumes may all be potentially deleterious in type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, and that a highly personalized approach to treatment is advisable.

2.
Crit Care Explor ; 2(9): e0220, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1795067

ABSTRACT

OBJECTIVES: To describe patients according to the maximum degree of respiratory support received and report their inpatient mortality due to coronavirus disease 2019. DESIGN: Analysis of patients in the Coracle registry from February 22, 2020, to April 1, 2020. SETTING: Hospitals in the Piedmont, Lombardy, Tuscany, and Lazio regions of Italy. PATIENTS: Nine-hundred forty-eight patients hospitalized for coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 948 patients, 122 (12.87%) received invasive ventilation, 637 (67.19%) received supplemental oxygen only, and 189 (19.94%) received no respiratory support. The median (quartile 1-quartile 3) age was 65 years (54-76.59 yr), and there was evidence of differential respiratory treatment by decade of life (p = 0.0046); patients greater than 80 years old were generally not intubated. There were 606 men (63.9%) in this study, and they were more likely to receive respiratory support than women (p < 0.0001). The rate of in-hospital death for invasive ventilation recipients was 22.95%, 12.87% for supplemental oxygen recipients, and 7.41% for those who received neither (p = 0.0004). A sensitivity analysis of the 770 patients less than 80 years old revealed a lower, but similar mortality trend (18.02%, 8.10%, 5.23%; p = 0.0008) among the 14.42%, 65.71%, and 19.87% of patients treated with mechanical ventilation, supplemental oxygen only, or neither. Overall, invasive ventilation recipients who died were significantly older than those who survived (median age: 68.5 yr [60-81.36 yr] vs 62.5 yr [55.52-71 yr]; p = 0.0145). CONCLUSIONS: Among patients hospitalized for coronavirus disease 2019, 13% received mechanical ventilation, which was associated with a mortality rate of 23%.

3.
Clin Infect Dis ; 74(3): 416-426, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1684537

ABSTRACT

BACKGROUND: We aimed to describe trends in adverse outcomes among patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between February and September 2020 within a national healthcare system. METHODS: We identified enrollees in the national United States Veterans Affairs healthcare system who tested positive for SARS-CoV-2 between 28 February 2020 and 30 September 2020 (n = 55 952), with follow-up extending to 19 November 2020. We determined trends over time in incidence of the following outcomes that occurred within 30 days of testing positive: hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death. RESULTS: Between February and July 2020, there were marked downward trends in the 30-day incidence of hospitalization (44.2% to 15.8%), ICU admission (20.3% to 5.3%), mechanical ventilation (12.7% to 2.2%), and death (12.5% to 4.4%), which subsequently plateaued between July and September 2020. These trends persisted after adjustment for sociodemographic characteristics, comorbid conditions, documented symptoms, and laboratory tests, including among subgroups of patients hospitalized, admitted to the ICU, or treated with mechanical ventilation. From February to September, there were decreases in the use of hydroxychloroquine (56.5% to 0%), azithromycin (48.3% to 16.6%), vasopressors (20.6% to 8.7%), and dialysis (11.6% to 3.8%) and increases in the use of dexamethasone (3.4% to 53.1%), other corticosteroids (4.9% to 29.0%), and remdesivir (1.7% to 45.4%) among hospitalized patients. CONCLUSIONS: The risk of adverse outcomes in SARS-CoV-2-positive patients decreased markedly between February and July, with subsequent stabilization from July to September. These trends were not explained by changes in measured baseline patient characteristics and may reflect changing treatment practices or viral pathogenicity.


Subject(s)
COVID-19 , Humans , Hydroxychloroquine , Intensive Care Units , Respiration, Artificial , SARS-CoV-2 , United States/epidemiology
4.
PLoS One ; 16(3): e0248029, 2021.
Article in English | MEDLINE | ID: covidwho-1574593

ABSTRACT

Many countries have seen a two-wave pattern in reported cases of coronavirus disease-19 during the 2020 pandemic, with a first wave during spring followed by the current second wave in late summer and autumn. Empirical data show that the characteristics of the effects of the virus do vary between the two periods. Differences in age range and severity of the disease have been reported, although the comparative characteristics of the two waves still remain largely unknown. Those characteristics are compared in this study using data from two equal periods of 3 and a half months. The first period, between 15th March and 30th June, corresponding to the entire first wave, and the second, between 1st July and 15th October, corresponding to part of the second wave, still present at the time of writing this article. Two hundred and four patients were hospitalized during the first period, and 264 during the second period. Patients in the second wave were younger and the duration of hospitalization and case fatality rate were lower than those in the first wave. In the second wave, there were more children, and pregnant and post-partum women. The most frequent signs and symptoms in both waves were fever, dyspnea, pneumonia, and cough, and the most relevant comorbidities were cardiovascular diseases, type 2 diabetes mellitus, and chronic neurological diseases. Patients from the second wave more frequently presented renal and gastrointestinal symptoms, were more often treated with non-invasive mechanical ventilation and corticoids, and less often with invasive mechanical ventilation, conventional oxygen therapy and anticoagulants. Several differences in mortality risk factors were also observed. These results might help to understand the characteristics of the second wave and the behaviour and danger of SARS-CoV-2 in the Mediterranean area and in Western Europe. Further studies are needed to confirm our findings.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Hospitalization/statistics & numerical data , Aged , Comorbidity , Female , Humans , Male , Middle Aged , Pandemics , Spain/epidemiology , Treatment Outcome
5.
PLoS One ; 16(3): e0248675, 2021.
Article in English | MEDLINE | ID: covidwho-1574573

ABSTRACT

BACKGROUND: In December 2019, a new disease named coronavirus disease 2019 (COVID-19) was occurred. Patients who are critically ill with COVID-19 are more likely to die, especially elderly patients. We aimed to describe the effect of age on the clinical and immune characteristics of critically ill patients with COVID-19. METHODS: We retrospectively included 32 patients with COVID-19 who were confirmed to have COVID-19 by the local health authority and who were admitted to the first affiliated hospital of Zhengzhou University in Zhengzhou, China between January 3 and March 20, 2020. Clinical information and experimental test data were retrospectively collected for the patients. The 32 patients in this study were all in a critical condition and were classified as severe, according to the guidelines of 2019-nCoV infection from the National Health Commission of the People's Republic of China. Data were compared between those <60 years old and ≥60 years old. RESULTS: Of 32 patients, 13 were under 60 years old, and 19 patients were ≥60 years old. The most common symptom among all patients upon admission was fever (93.8%, 30/32). Compared to younger patients, older patients exhibited increased comorbidities. Among patients who were 60 years and older, platelet count, direct bilirubin (DBIL), indirect bilirubin(IBIL), lactate dehydrogenase (LDH), B-type natriuretic peptide (BNP), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-10 (IL-10) were significantly higher than in younger patients who were less than 60 years old. CD4+ T lymphocytes, CD8+ T lymphocytes, and NKT lymphocytes were decreased, CD4+/CD8+ T lymphocytes were significantly increased in all 32 patients, while there were no evident differences between younger and older patients. The CURB-65 (confusion, urea, respiratory, rate, blood pressure plus age ≥65 years), Acute Physiology and Chronic Health Evaluation (APACHE) II and pH value were significantly higher in older patients than in patients who were under 60 years old. However, the PaO2 and PaO2:FiO2 were lower in older patients than the younger. Compared to patients under 60 years old, patients who were 60 years and older tended to develop ARDS (15 [78.9%] vs 5 [38.5%]), septic shock (7 [36.8%] vs 0 [0.0%]) and were more likely to receive mechanical ventilation (13 [68.4%] vs 3[23.1%]). Dynamic trajectories of seven laboratory parameters were tracked on days 1, 3, 5 and 7, and significant differences in lymphocyte count (P = 0.026), D-dimer (P = 0.010), lactate dehydrogenase (P = 0.000) and C-reactive protein (P = 0.000) were observed between the two age groups. CONCLUSIONS: A high proportion of critically ill patients were 60 or older. Furthermore, rapid disease progression was noted in elderly patients. Therefore, close monitoring and timely treatment should be performed in elderly COVID-19 patients.


Subject(s)
COVID-19/epidemiology , Age Factors , Aged , CD4-CD8 Ratio , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Critical Illness , Female , Humans , Immunity , Lymphocyte Count , Male , Middle Aged , Preliminary Data , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index
6.
Indian J Crit Care Med ; 24(11): 1143-1144, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1575140

ABSTRACT

How to cite this article: Nair PR, Maitra S, Ray BR, Anand RK, Baidya DK, Subramaniam R. Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio as Predictors of the Early Requirement of Mechanical Ventilation in COVID-19 Patients. Indian J Crit Care Med 2020;24(11):1143-1144.

7.
Drugs Real World Outcomes ; 8(3): 417-425, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1540320

ABSTRACT

BACKGROUND: Critically ill patients are admitted to intensive care units so they can be comprehensively managed and provided with services not covered in general hospital wards, with the aim to increase their chances of survival. These procedures include invasive mechanical ventilation. OBJECTIVE: The aim of this study was to identify the factors associated with survival in critically ill patients who required invasive mechanical ventilation in an intensive care unit of a tertiary-level hospital in Colombia. METHODS: This was a retrospective follow-up study of a cohort of adult patients who required invasive mechanical ventilation in an intensive care unit in San José de Buga Hospital, between 2017 and 2018. Sociodemographic, clinical, and pharmacological variables were identified. Using Cox regression, variables associated with survival and complications were identified. RESULTS: A total of 357 patients were analyzed. The average age was 64.8 ± 18.9 years, and 52.9% were male. The most frequent diagnoses were sepsis/septic shock (38.4%) and trauma (17.4%). The main factors associated with shorter survival were advanced age (HR 0.97; 95% CI 0.96-0.99), a diagnosis of septic shock (HR 0.29; 95% CI 0.18-0.48) or diabetes mellitus at admission (HR 0.57; 95% CI 0.33-0.98), a healthcare-associated infection (HR 0.51; 95% CI 0.33-0.80), and the need for vasopressors (HR 0.36; 95% CI 0.22-0.59). The administration of systemic corticosteroids was associated with a higher probability of survival (HR 1.93; 95% CI 1.15-3.25). CONCLUSIONS: The use of systemic corticosteroids was associated with a greater probability of survival in critically ill patients who required invasive mechanical ventilation in an intensive care unit. The identification of the variables associated with a higher risk of dying should allow care protocols to be improved, thereby extending the life expectancy of these patients.

8.
J Clin Med ; 10(8)2021 Apr 10.
Article in English | MEDLINE | ID: covidwho-1526831

ABSTRACT

A clinical interpretation of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study was performed to provide a useful tool to understand whether, when, and to whom dexamethasone should be administered during hospitalization for COVID-19. A post hoc analysis of data published in the preliminary report of the RECOVERY study was performed to calculate the person-based number needed to treat (NNT) and number needed to harm (NNH) of 6 mg dexamethasone once daily for up to 10 days vs. usual care with respect to mortality. At day 28, the NNT of dexamethasone vs. usual care was 36.0 (95%CI 24.9-65.1, p < 0.05) in all patients, 8.3 (95%CI 6.0-13.1, p < 0.05) in patients receiving invasive mechanical ventilation, and 34.6 (95%CI 22.1-79.0, p < 0.05) in patients receiving oxygen only (with or without noninvasive ventilation). Dexamethasone increased mortality compared with usual care in patients not requiring oxygen supplementation, leading to a NNH value of 26.7 (95%CI 18.1-50.9, p < 0.05). NNT of dexamethasone vs. usual care was 17.3 (95%CI 14.9-20.6) in subjects <70 years, 27.0 (95%CI 18.5-49.8) in men, and 16.2 (95%CI 13.2-20.8) in patients in which the onset of symptoms was >7 days. Dexamethasone is effective in male subjects < 70 years that require invasive mechanical ventilation experiencing symptoms from >7 days and those patients receiving oxygen without invasive mechanical ventilation; it should be avoided in patients not requiring respiratory support.

9.
J Clin Med ; 9(12)2020 Dec 21.
Article in English | MEDLINE | ID: covidwho-1463718

ABSTRACT

Patients receiving mechanical ventilation for coronavirus disease 2019 (COVID-19) related, moderate-to-severe acute respiratory distress syndrome (CARDS) have mortality rates between 76-98%. The objective of this retrospective cohort study was to identify differences in prone ventilation effects on oxygenation, pulmonary infiltrates (as observed on chest X-ray (CXR)), and systemic inflammation in CARDS patients by survivorship and to identify baseline characteristics associated with survival after prone ventilation. The study cohort included 23 patients with moderate-to-severe CARDS who received prone ventilation for ≥16 h/day and was segmented by living status: living (n = 6) and deceased (n = 17). Immediately after prone ventilation, PaO2/FiO2 improved by 108% (p < 0.03) for the living and 150% (p < 3 × 10-4) for the deceased. However, the 48 h change in lung infiltrate severity in gravity-dependent lung zones was significantly better for the living than for the deceased (p < 0.02). In CXRs of the lower lungs before prone ventilation, we observed 5 patients with confluent infiltrates bilaterally, 12 patients with ground-glass opacities (GGOs) bilaterally, and 6 patients with mixed infiltrate patterns; 80% of patients with confluent infiltrates were alive vs. 8% of patients with GGOs. In conclusion, our small study indicates that CXRs may offer clinical utility in selecting patients with moderate-to-severe CARDS who will benefit from prone ventilation. Additionally, our study suggests that lung infiltrate severity may be a better indicator of patient disposition after prone ventilation than PaO2/FiO2.

10.
Crit Care Med ; 49(10): 1684-1693, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1452742

ABSTRACT

OBJECTIVES: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators. DESIGN: A 2-day in-person meeting was held in Washington, DC, on March 28-29, 2019, followed by a three-round, online modified Delphi consensus process. PARTICIPANTS: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process. MEASUREMENTS AND MAIN RESULTS: The final recommendations were iteratively refined based on the survey results, participants' reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization. CONCLUSIONS: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials.


Subject(s)
Hypnotics and Sedatives/pharmacokinetics , Hypnotics and Sedatives/therapeutic use , Congresses as Topic , Consensus , Delphi Technique , District of Columbia , Humans , Hypnotics and Sedatives/pharmacology , Respiration, Artificial/instrumentation , Respiration, Artificial/methods , Time Factors
11.
N Engl J Med ; 382(18): 1708-1720, 2020 04 30.
Article in English | MEDLINE | ID: covidwho-1428982

ABSTRACT

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).


Subject(s)
Betacoronavirus , Coronavirus Infections , Disease Outbreaks , Pandemics , Pneumonia, Viral , Adolescent , Adult , Aged , COVID-19 , Child , China/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Female , Fever/etiology , Humans , Male , Middle Aged , Patient Acuity , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , SARS-CoV-2 , Young Adult
12.
Respir Care ; 66(5): 814-821, 2021 May.
Article in English | MEDLINE | ID: covidwho-1395146

ABSTRACT

BACKGROUND: The growing proportion of elderly intensive care patients constitutes a public health challenge. The benefit of critical care in these patients remains unclear. We compared outcomes in elderly versus very elderly subjects receiving mechanical ventilation. METHODS: In total, 5,557 mechanically ventilated subjects were included in our post hoc retrospective analysis, a subgroup of the VENTILA study. We divided the cohort into 2 subgroups on the basis of age: very elderly subjects (age ≥ 80 y; n = 1,430), and elderly subjects (age 65-79 y; n = 4,127). A propensity score on being very elderly was calculated. Evaluation of associations with 28-d mortality was done with logistic regression analysis. RESULTS: Very elderly subjects were clinically sicker as expressed by higher SAPS II scores (53 ± 18 vs 50 ± 18, P < .001), and their rates of plateau pressure < 30 cm H2O were higher, whereas other parameters did not differ. The 28-d mortality was higher in very elderly subjects (42% vs 34%, P < .001) and remained unchanged after propensity score adjustment (adjusted odds ratio 1.31 [95% CI 1.16-1.49], P < .001). CONCLUSIONS: Age was an independent and unchangeable risk factor for death in mechanically ventilated subjects. However, survival rates of very elderly subjects were > 50%. Denial of critical care based solely on age is not justified. (ClinicalTrials.gov registration NCT02731898.).


Subject(s)
Critical Illness , Respiration, Artificial , Aged , Humans , Intensive Care Units , Retrospective Studies , Risk Factors , Simplified Acute Physiology Score
13.
Hepatology ; 74(1): 322-335, 2021 07.
Article in English | MEDLINE | ID: covidwho-1384170

ABSTRACT

BACKGROUND AND AIMS: Whether patients with cirrhosis have increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the extent to which infection and cirrhosis increase the risk of adverse patient outcomes remain unclear. APPROACH AND RESULTS: We identified 88,747 patients tested for SARS-CoV-2 between March 1, 2020, and May 14, 2020, in the Veterans Affairs (VA) national health care system, including 75,315 with no cirrhosis-SARS-CoV-2-negative (C0-S0), 9,826 with no cirrhosis-SARS-CoV-2-positive (C0-S1), 3,301 with cirrhosis-SARS-CoV-2-negative (C1-S0), and 305 with cirrhosis-SARS-CoV-2-positive (C1-S1). Patients were followed through June 22, 2020. Hospitalization, mechanical ventilation, and death were modeled in time-to-event analyses using Cox proportional hazards regression. Patients with cirrhosis were less likely to test positive than patients without cirrhosis (8.5% vs. 11.5%; adjusted odds ratio, 0.83; 95% CI, 0.69-0.99). Thirty-day mortality and ventilation rates increased progressively from C0-S0 (2.3% and 1.6%) to C1-S0 (5.2% and 3.6%) to C0-S1 (10.6% and 6.5%) and to C1-S1 (17.1% and 13.0%). Among patients with cirrhosis, those who tested positive for SARS-CoV-2 were 4.1 times more likely to undergo mechanical ventilation (adjusted hazard ratio [aHR], 4.12; 95% CI, 2.79-6.10) and 3.5 times more likely to die (aHR, 3.54; 95% CI, 2.55-4.90) than those who tested negative. Among patients with SARS-CoV-2 infection, those with cirrhosis were more likely to be hospitalized (aHR, 1.37; 95% CI, 1.12-1.66), undergo ventilation (aHR, 1.61; 95% CI, 1.05-2.46) or die (aHR, 1.65; 95% CI, 1.18-2.30) than patients without cirrhosis. Among patients with cirrhosis and SARS-CoV-2 infection, the most important predictors of mortality were advanced age, cirrhosis decompensation, and high Model for End-Stage Liver Disease score. CONCLUSIONS: SARS-CoV-2 infection was associated with a 3.5-fold increase in mortality in patients with cirrhosis. Cirrhosis was associated with a 1.7-fold increase in mortality in patients with SARS-CoV-2 infection.


Subject(s)
COVID-19/etiology , Liver Cirrhosis/complications , SARS-CoV-2 , Veterans/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/mortality , COVID-19/therapy , Female , Hospitalization/statistics & numerical data , Humans , Liver Cirrhosis/virology , Male , Middle Aged , Proportional Hazards Models , Respiration, Artificial/statistics & numerical data , Risk Factors , United States/epidemiology , Young Adult
14.
Clin Infect Dis ; 74(3): 416-426, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1387822

ABSTRACT

BACKGROUND: We aimed to describe trends in adverse outcomes among patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between February and September 2020 within a national healthcare system. METHODS: We identified enrollees in the national United States Veterans Affairs healthcare system who tested positive for SARS-CoV-2 between 28 February 2020 and 30 September 2020 (n = 55 952), with follow-up extending to 19 November 2020. We determined trends over time in incidence of the following outcomes that occurred within 30 days of testing positive: hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death. RESULTS: Between February and July 2020, there were marked downward trends in the 30-day incidence of hospitalization (44.2% to 15.8%), ICU admission (20.3% to 5.3%), mechanical ventilation (12.7% to 2.2%), and death (12.5% to 4.4%), which subsequently plateaued between July and September 2020. These trends persisted after adjustment for sociodemographic characteristics, comorbid conditions, documented symptoms, and laboratory tests, including among subgroups of patients hospitalized, admitted to the ICU, or treated with mechanical ventilation. From February to September, there were decreases in the use of hydroxychloroquine (56.5% to 0%), azithromycin (48.3% to 16.6%), vasopressors (20.6% to 8.7%), and dialysis (11.6% to 3.8%) and increases in the use of dexamethasone (3.4% to 53.1%), other corticosteroids (4.9% to 29.0%), and remdesivir (1.7% to 45.4%) among hospitalized patients. CONCLUSIONS: The risk of adverse outcomes in SARS-CoV-2-positive patients decreased markedly between February and July, with subsequent stabilization from July to September. These trends were not explained by changes in measured baseline patient characteristics and may reflect changing treatment practices or viral pathogenicity.


Subject(s)
COVID-19 , Humans , Hydroxychloroquine , Intensive Care Units , Respiration, Artificial , SARS-CoV-2 , United States/epidemiology
16.
Anaesth Crit Care Pain Med ; 39(5): 553-561, 2020 10.
Article in English | MEDLINE | ID: covidwho-1384795

ABSTRACT

PURPOSE: Community transmission of SARS-CoV-2 was detected in Spain in February 2020, with 216% intensive care unit (ICU) capacity expanded in Vitoria by March 18th, 2020. METHODS: We identified patients from the two public hospitals in Vitoria who were admitted to ICU with confirmed infection by SARS-CoV-2. Data reported here were available in April 6th, 2020. Mortality was assessed in those who completed 15-days of ICU stay. RESULTS: We identified 48 patients (27 males) with confirmed SARS-CoV-2. Median [interquartile range (IQR)] age of patients was 63 [51-75] years. Symptoms began a median of 7 [5-12] days before ICU admission. The most common comorbidities identified were obesity (48%), arterial hypertension (44%) and chronic lung disease (37%). All patients were admitted by hypoxemic respiratory failure and none received non-invasive mechanical ventilation. Forty-five (94%) underwent intubation, 3 (6%) high flow nasal therapy (HFNT), 1 (2%) extracorporeal membrane oxygenation (ECMO) and 22 (46%) required prone position. After 15 days, 14/45 (31%) intubated patients died (13% within one week), 10/45 (22%) were extubated, and 21/45 (47%) underwent mechanical ventilation. Six patients had documented super-infection. Procalcitonin plasma above 0.5µg/L was associated with 16% vs. 19% (p=0.78) risk of death after 7 days. CONCLUSION: This early experience with SARS-CoV-2 in Spain suggests that a strategy of right oxygenation avoiding non-invasive mechanical ventilation was life-saving. Seven-day mortality in SARS-CoV-2 requiring intubation was lower than 15%, with 80% of patients still requiring mechanical ventilation. After 15 days of ICU admission, half of patients remained intubated, whereas one third died.


Subject(s)
Betacoronavirus , Coronavirus Infections/mortality , Hospitals, Public/statistics & numerical data , Intensive Care Units/statistics & numerical data , Pandemics , Pneumonia, Viral/mortality , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , COVID-19 , Combined Modality Therapy , Comorbidity , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Disease Outbreaks , Female , Hospital Mortality , Humans , Influenza, Human/epidemiology , Kaplan-Meier Estimate , Length of Stay , Male , Middle Aged , Oxygen Inhalation Therapy , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Procalcitonin/blood , Respiration, Artificial , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , Spain/epidemiology
17.
J Acquir Immune Defic Syndr ; 85(1): 6-10, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-1373693

ABSTRACT

BACKGROUND: SARS-CoV-2 infection continues to cause significant morbidity and mortality worldwide. Preliminary data on SARS-CoV-2 infection suggest that some immunocompromised hosts experience worse outcomes. We performed a retrospective matched cohort study to characterize outcomes in HIV-positive patients with SARS-CoV-2 infection. METHODS: Leveraging data collected from electronic medical records for all patients hospitalized at NYU Langone Health with COVID-19 between March 2, 2020, and April 23, 2020, we matched 21 HIV-positive patients with 42 non-HIV patients using a greedy nearest-neighbor algorithm. Admission characteristics, laboratory test results, and hospital outcomes were recorded and compared between the 2 groups. RESULTS: Although there was a trend toward increased rates of intensive care unit admission, mechanical ventilation, and mortality in HIV-positive patients, these differences were not statistically significant. Rates for these outcomes in our cohort are similar to those previously published for all patients hospitalized with COVID-19. HIV-positive patients had significantly higher admission and peak C-reactive protein values. Other inflammatory markers did not differ significantly between groups, although HIV-positive patients tended to have higher peak values during their clinical course. Three HIV-positive patients had superimposed bacterial pneumonia with positive sputum cultures, and all 3 patients died during hospitalization. There was no difference in frequency of thrombotic events or myocardial infarction between these groups. CONCLUSIONS: This study provides evidence that HIV coinfection does not significantly impact presentation, hospital course, or outcomes of patients infected with SARS-CoV-2, when compared with matched non-HIV patients. A larger study is required to determine whether the trends we observed apply to all HIV-positive patients.


Subject(s)
Betacoronavirus , Coinfection/virology , Coronavirus Infections/complications , HIV Infections/complications , Pneumonia, Viral/complications , Adult , Aged , Aged, 80 and over , COVID-19 , Case-Control Studies , Cohort Studies , Coinfection/mortality , Coronavirus Infections/mortality , Critical Care , Female , HIV Infections/mortality , Hospitalization , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
18.
Clin Hemorheol Microcirc ; 78(2): 199-207, 2021.
Article in English | MEDLINE | ID: covidwho-1352794

ABSTRACT

INTRODUCTION: Coronavirus disease-19 (COVID-19) is a new type of epidemic pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The population is generally susceptible to COVID-19, which mainly causes lung injury. Some cases may develop severe acute respiratory distress syndrome (ARDS). Currently, ARDS treatment is mainly mechanical ventilation, but mechanical ventilation often causes ventilator-induced lung injury (VILI) accompanied by hypercapnia in 14% of patients. Extracorporeal carbon dioxide removal (ECCO2R) can remove carbon dioxide from the blood of patients with ARDS, correct the respiratory acidosis, reduce the tidal volume and airway pressure, and reduce the incidence of VILI. CASE REPORT: Two patients with critical COVID-19 combined with multiple organ failure undertook mechanical ventilation and suffered from hypercapnia. ECCO2R, combined with continuous renal replacement therapy (CRRT), was conducted concomitantly. In both cases (No. 1 and 2), the tidal volume and positive end-expiratory pressure (PEEP) were down-regulated before the treatment and at 1.5 hours, one day, three days, five days, eight days, and ten days after the treatment, together with a noticeable decrease in PCO2 and clear increase in PO2, while FiO2 decreased to approximately 40%. In case No 2, compared with the condition before treatment, the PCO2 decreased significantly with down-regulation in the tidal volume and PEEP and improvement in the pulmonary edema and ARDS after the treatment. CONCLUSION: ECCO2R combined with continuous blood purification therapy in patients with COVID-19 who are criti-cally ill and have ARDS and hypercapnia might gain both time and opportunity in the treatment, down-regulate the ventilator parameters, reduce the incidence of VILI and achieve favorable therapeutic outcomes.


Subject(s)
COVID-19/complications , Carbon Dioxide/isolation & purification , Extracorporeal Circulation/methods , Hemofiltration/methods , Hypercapnia/therapy , Respiratory Distress Syndrome/therapy , SARS-CoV-2/isolation & purification , Aged , COVID-19/transmission , COVID-19/virology , Humans , Hypercapnia/physiopathology , Hypercapnia/virology , Male , Positive-Pressure Respiration , Respiration, Artificial , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/virology
19.
BMC Pulm Med ; 20(1): 317, 2020 Dec 07.
Article in English | MEDLINE | ID: covidwho-1331939

ABSTRACT

BACKGROUND: The COVID-19 pandemic reached Europe in early 2020. Convalescent plasma is used without a consistent evidence of efficacy. Our hypothesis is that passive immunization with plasma collected from patients having contracted COVID-19 and developed specific neutralizing antibodies may alleviate symptoms and reduce mortality in patients treated with mechanical ventilation for severe respiratory failure during the evolution of SARS-CoV-2 pneumonia. METHODS: We plan to include 500 adult patients, hospitalized in 16 Belgian intensive care units between September 2020 and 2022, diagnosed with SARS-CoV-2 pneumonia, under mechanical ventilation for less than 5 days and a clinical frailty scale less than 6. The study treatment will be compared to standard of care and allocated by randomization in a 1 to 1 ratio without blinding. The main endpoint will be mortality at day 28. We will perform an intention to treat analysis. The number of patients to include is based on an expected mortality rate at day 28 of 40 percent and an expected relative reduction with study intervention of 30 percent with α risk of 5 percent and ß risk of 20 percent. DISCUSSION: This study will assess the efficacy of plasma in the population of mechanically ventilated patients. A stratification on the delay from mechanical ventilation and inclusion will allow to approach the optimal time use. Selecting convalescent plasmas with a high titer of neutralizing antibodies against SARS-CoV-2 will allow a homogeneous study treatment. The inclusion in the study is based on the consent of the patient or his/her legal representative, and the approval of the Investigational Review Board of the University hospital of Liège, Belgium. A data safety monitoring board (DSMB) has been implemented. Interim analyses have been planned at 100, 2002, 300 and 400 inclusions in order to decide whether the trail should be discontinued prematurely for ethical issues. We plan to publish our results in a peer-reviewed journal and to present them at national and international conferences. FUNDING AND REGISTRATION: The trial is funded by the Belgian Health Care Knowledge Center KCE # COV201004 TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT04558476. Registered 14 September 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04558476.


Subject(s)
COVID-19/therapy , Respiration, Artificial , Severe Acute Respiratory Syndrome/therapy , Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , Belgium , COVID-19/mortality , Clinical Trials, Phase II as Topic , Humans , Immunization, Passive , Intensive Care Units , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Severe Acute Respiratory Syndrome/mortality , Time Factors , Treatment Outcome
20.
Pharmacol Res ; 158: 104899, 2020 08.
Article in English | MEDLINE | ID: covidwho-1318934

ABSTRACT

SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged ≥18 years undergoing mechanical ventilation or with an oxygen saturation level of ≤94 % in air or a National Early Warning Score 2 of ≥4. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63 %) and discontinued by 13, of whom eight (22.8 %) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3 %) patients from IDW were discharged, two were still hospitalized and one died (5.9 %), whereas in ICU 6 (33.3 %) were discharged, 8 (44.4 %) patients died, three (16.7 %) were still mechanically ventilated and one (5.6 %) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8 % and 22.8 % of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Betacoronavirus , Compassionate Use Trials/statistics & numerical data , Coronavirus Infections/drug therapy , Hospitalization/statistics & numerical data , Intensive Care Units/statistics & numerical data , Pneumonia, Viral/drug therapy , Acute Kidney Injury/chemically induced , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Aged , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/blood , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , SARS-CoV-2 , Transaminases/blood , Treatment Outcome
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