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1.
Crit Care Med ; 48(6): e440-e469, 2020 06.
Article in English | MEDLINE | ID: covidwho-2152192

ABSTRACT

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.


Subject(s)
Coronavirus Infections/therapy , Intensive Care Units/organization & administration , Pneumonia, Viral/therapy , Practice Guidelines as Topic/standards , Betacoronavirus , COVID-19 , Critical Illness , Diagnostic Techniques and Procedures/standards , Humans , Infection Control/methods , Infection Control/standards , Intensive Care Units/standards , Pandemics , Respiration, Artificial/methods , Respiration, Artificial/standards , SARS-CoV-2 , Shock/therapy
2.
Ann Intern Med ; 173(2): 100-109, 2020 07 21.
Article in English | MEDLINE | ID: covidwho-1994454

ABSTRACT

BACKGROUND: The evolving outbreak of coronavirus disease 2019 (COVID-19) is requiring social distancing and other measures to protect public health. However, messaging has been inconsistent and unclear. OBJECTIVE: To determine COVID-19 awareness, knowledge, attitudes, and related behaviors among U.S. adults who are more vulnerable to complications of infection because of age and comorbid conditions. DESIGN: Cross-sectional survey linked to 3 active clinical trials and 1 cohort study. SETTING: 5 academic internal medicine practices and 2 federally qualified health centers. PATIENTS: 630 adults aged 23 to 88 years living with 1 or more chronic conditions. MEASUREMENTS: Self-reported knowledge, attitudes, and behaviors related to COVID-19. RESULTS: A fourth (24.6%) of participants were "very worried" about getting the coronavirus. Nearly a third could not correctly identify symptoms (28.3%) or ways to prevent infection (30.2%). One in 4 adults (24.6%) believed that they were "not at all likely" to get the virus, and 21.9% reported that COVID-19 had little or no effect on their daily routine. One in 10 respondents was very confident that the federal government could prevent a nationwide outbreak. In multivariable analyses, participants who were black, were living below the poverty level, and had low health literacy were more likely to be less worried about COVID-19, to not believe that they would become infected, and to feel less prepared for an outbreak. Those with low health literacy had greater confidence in the federal government response. LIMITATION: Cross-sectional study of adults with underlying health conditions in 1 city during the initial week of the COVID-19 U.S. outbreak. CONCLUSION: Many adults with comorbid conditions lacked critical knowledge about COVID-19 and, despite concern, were not changing routines or plans. Noted disparities suggest that greater public health efforts may be needed to mobilize the most vulnerable communities. PRIMARY FUNDING SOURCE: National Institutes of Health.


Subject(s)
Chronic Disease/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/psychology , Health Knowledge, Attitudes, Practice , Pneumonia, Viral/epidemiology , Pneumonia, Viral/psychology , Vulnerable Populations , Adult , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2 , Self Report , Surveys and Questionnaires , United States/epidemiology
3.
MMWR Morb Mortal Wkly Rep ; 70(14): 519-522, 2021 04 09.
Article in English | MEDLINE | ID: covidwho-1384037

ABSTRACT

CDC's National Vital Statistics System (NVSS) collects and reports annual mortality statistics using data from U.S. death certificates. Because of the time needed to investigate certain causes of death and to process and review data, final annual mortality data for a given year are typically released 11 months after the end of the calendar year. Daily totals reported by CDC COVID-19 case surveillance are timely but can underestimate numbers of deaths because of incomplete or delayed reporting. As a result of improvements in timeliness and the pressing need for updated, quality data during the global COVID-19 pandemic, NVSS expanded provisional data releases to produce near real-time U.S. mortality data.* This report presents an overview of provisional U.S. mortality data for 2020, including the first ranking of leading causes of death. In 2020, approximately 3,358,814 deaths† occurred in the United States. From 2019 to 2020, the estimated age-adjusted death rate increased by 15.9%, from 715.2 to 828.7 deaths per 100,000 population. COVID-19 was reported as the underlying cause of death or a contributing cause of death for an estimated 377,883 (11.3%) of those deaths (91.5 deaths per 100,000). The highest age-adjusted death rates by age, race/ethnicity, and sex occurred among adults aged ≥85 years, non-Hispanic Black or African American (Black) and non-Hispanic American Indian or Alaska Native (AI/AN) persons, and males. COVID-19 death rates were highest among adults aged ≥85 years, AI/AN and Hispanic persons, and males. COVID-19 was the third leading cause of death in 2020, after heart disease and cancer. Provisional death estimates provide an early indication of shifts in mortality trends and can guide public health policies and interventions aimed at reducing numbers of deaths that are directly or indirectly associated with the COVID-19 pandemic.


Subject(s)
COVID-19/mortality , Mortality/trends , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/ethnology , Cause of Death/trends , Child , Child, Preschool , Female , Health Status Disparities , Humans , Infant , Male , Middle Aged , Mortality/ethnology , United States/epidemiology , Vital Statistics , Young Adult
4.
Aust Prescr ; 43(4): 110, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1912445
5.
Am J Speech Lang Pathol ; 30(1): 63-74, 2021 01 27.
Article in English | MEDLINE | ID: covidwho-1805676

ABSTRACT

Purpose Evaluation and management of voice and upper airway disorders in adults and children, by speech-language pathologists worldwide, have been significantly altered by the COVID-19 pandemic. Secondary to the pathogenic nature of the virus in the respiratory tract and upper airway, it is essential that speech-language pathologists who specialize in these disorders are knowledgeable of current practices to provide evidence-based care while minimizing viral transmission. Understanding how and when SARS-CoV-2 spreads is critical to the development of effective infection prevention within clinical practices. Method We established an evidence-based clinical practice guide for clinicians working with voice and upper airway through a comprehensive evaluation of peer-reviewed journals, non-peer-reviewed manuscripts on preprint servers, national health guidelines, and published and online consensus statements and emerging data. Emphasis was placed on risk mitigation for viral transmission via safe clinical practices, including evaluative procedures, therapy including telehealth, personal protective equipment, room, staffing, and distancing considerations. Results/Conclusions While knowledge relevant to viral transmission of SARS-CoV-2 is rapidly evolving, there is a paucity of literature specific to the evaluation and treatment of voice and upper airway disorders. Within these confines and given the potentially significant high risk of infection secondary to the nature of COVID-19, we summarize current considerations and recommend best practices that maximize risk mitigation whereby ensuring patient and provider safety.


Subject(s)
Airway Obstruction/diagnosis , COVID-19/diagnosis , Speech Disorders/diagnosis , Voice Disorders/diagnosis , Adult , Airway Obstruction/therapy , COVID-19/therapy , Child , Humans , Practice Guidelines as Topic , Risk Factors , Speech Disorders/therapy , Voice Disorders/therapy
6.
Pneumologe (Berl) ; 17(5): 357-364, 2020.
Article in German | MEDLINE | ID: covidwho-1797596

ABSTRACT

Background: At the beginning of the SARS-CoV­2 pandemic the focus of attention was on children and adolescents with chronic lung diseases. Due to a lack of epidemiological data and clinical experience, it was feared that children with respiratory diseases were a risk group for particularly severe courses of COVID-19, as has been reported for adults. Objective: The currently available (epidemiological) data on this patient group are presented as well as a description of our own experiences based on three selected cases. Material and methods: A review of the literature was carried out and three selected case reports and a discussion of current recommendations are presented. Results: The incidence of COVID-19 is significantly lower in children than in adults. Furthermore, the known risk factors in adults cannot be simply transferred to pediatric patients. In the majority of cases, children and adolescents with chronic lung diseases show a milder course of SARS-CoV­2 infections. Conclusion: Although the hitherto available data show that children and adolescents have a lower risk for COVID-19 courses than adults, it should not be ignored that fatal outcomes have also been reported in pediatric patients. Moreover, late effects, such as the pediatric inflammatory multisystem syndrome (PIMS) can sometimes lead to a fatal outcome. Nevertheless, care must be taken that this vulnerable patient group does not suffer from avoidable negative side effects of restriction and isolation measures. As an example, the no-show behavior in outpatient departments during the lockdown might have led to a relevant undertreatment of underlying chronic health conditions.

7.
Crit Care Explor ; 2(6): e0139, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1795099

ABSTRACT

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 pandemic has stretched ICU resources in an unprecedented fashion and outstripped personal protective equipment supplies. The combination of a novel disease, resource limitations, and risks to medical personnel health have created new barriers to implementing the ICU Liberation ("A" for Assessment, Prevention, and Manage pain; "B" for Both Spontaneous Awakening Trials and Spontaneous Breathing Trials; "C" for Choice of Analgesia and Sedation; "D" for Delirium Assess, Prevent, and Manage; "E" for Early Mobility and Exercise; and "F" for Family Engagement and Empowerment [ABCDEF]) Bundle, a proven ICU care approach that reduces delirium, shortens mechanical ventilation duration, prevents post-ICU syndrome, and reduces healthcare costs. This narrative review acknowledges barriers and offers strategies to optimize Bundle performance in coronavirus disease 2019 patients requiring mechanical ventilation. DATA SOURCES STUDY SELECTION AND DATA EXTRACTION: The most relevant literature, media reports, and author experiences were assessed for inclusion in this narrative review including PubMed, national newspapers, and critical care/pharmacology textbooks. DATA SYNTHESIS: Uncertainty regarding coronavirus disease 2019 clinical course, shifts in attitude, and changes in routine behavior have hindered Bundle use. A domino effect results from: 1) changes to critical care hierarchy, priorities, and ICU team composition; 2) significant personal protective equipment shortages cause; 3) reduced/restricted physical bedside presence favoring; 4) increased depth of sedation and use of neuromuscular blockade; 5) which exacerbate drug shortages; and 6) which require prolonged use of limited ventilator resources. Other identified barriers include manageable knowledge deficits among non-ICU clinicians unfamiliar with the Bundle or among PICU specialists deploying pediatric-based Bundle approaches who are unfamiliar with adult medicine. Both groups have been enlisted to augment the adult ICU work force to meet demand. Strategies were identified to facilitate Bundle performance to liberate patients from the ICU. CONCLUSIONS: We acknowledge current challenges that interfere with comprehensive management of critically ill patients during the coronavirus disease 2019 pandemic. Rapid response to new circumstances precisely requires established safety mechanisms and protocols like the ABCDEF Bundle to increase ICU and ventilator capacity and help survivors maximize recovery from coronavirus disease 2019 as early as possible.

8.
Crit Care Explor ; 2(9): e0207, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1795073

ABSTRACT

OBJECTIVES: To determine whether placental cell therapy PLacental eXpanded (PLX)-PAD (Pluristem Therapeutics, Haifa, Israel) may be beneficial to treating critically ill patients suffering from acute respiratory distress syndrome due to coronavirus disease 2019. DESIGN: Retrospective case report of critically ill coronavirus disease 2019 patients treated with PLacental eXpanded (PLX)-PAD from March 26, 2020, to April 4, 2020, with follow-up through May 2, 2020. SETTING: Four hospitals in Israel (Rambam Health Care Campus, Bnai Zion Medical Center, and Samson Assuta Ashdod University Hospital), and Holy Name Medical Center in New Jersey. PATIENTS: Eight critically ill patients on invasive mechanical ventilation, suffering from acute respiratory distress syndrome due to coronavirus disease 2019. INTERVENTIONS: Intramuscular injection of PLacental eXpanded (PLX)-PAD (300 × 106 cells) given as one to two treatments. MEASUREMENTS AND MAIN RESULTS: Mortality, time to discharge, and changes in blood and respiratory variables were monitored during hospitalization to day 17 posttreatment. Of the eight patients treated (median age 55 yr, seven males and one female), five were discharged, two remained hospitalized, and one died. By day 3 postinjection, mean C-reactive protein fell 45% (240.3-131.3 mg/L; p = 0.0019) and fell to 77% by day 5 (56.0 mg/L; p < 0.0001). Pao2/Fio2 improved in 5:8 patients after 24-hour posttreatment, with similar effects 48-hour posttreatment. A decrease in positive end-expiratory pressure and increase in pH were statistically significant between days 0 and 14 (p = 0.0032 and p = 0.00072, respectively). A decrease in hemoglobin was statistically significant for days 0-5 and 0-14 (p = 0.015 and p = 0.0028, respectively), whereas for creatinine, it was statistically significant between days 0 and 14 (p = 0.032). CONCLUSIONS: Improvement in several variables such as C-reactive protein, positive end-expiratory pressure, and Pao2/Fio2 was observed following PLacental eXpanded (PLX)-PAD treatment, suggesting possible therapeutic effect. However, interpretation of the data is limited due to the small sample size, use of concomitant investigational therapies, and the uncontrolled study design. The efficacy of PLacental eXpanded (PLX)-PAD in coronavirus disease 2019 should be further evaluated in a controlled clinical trial.

9.
Thromb J ; 18: 22, 2020.
Article in English | MEDLINE | ID: covidwho-1793931

ABSTRACT

BACKGROUND: Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted. CASE PRESENTATION: In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence. CONCLUSIONS: In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.

10.
Nutrients ; 12(6)2020 Jun 02.
Article in English | MEDLINE | ID: covidwho-1725881

ABSTRACT

The COVID-19 pandemic has dramatically increased food insecurity in the United States (US). The objective of this study was to understand the early effects of the COVID-19 pandemic among low-income adults in the US as social distancing measures began to be implemented. On 19-24 March 2020 we fielded a national, web-based survey (53% response rate) among adults with <250% of the federal poverty line in the US (N = 1478). Measures included household food security status and COVID-19-related basic needs challenges. Overall, 36% of low-income adults in the US were food secure, 20% had marginal food security, and 44% were food insecure. Less than one in five (18.8%) of adults with very low food security reported being able to comply with public health recommendations to purchase two weeks of food at a time. For every basic needs challenge, food-insecure adults were significantly more likely to report facing that challenge, with a clear gradient effect based on severity of food security. The short-term effects of the COVID-19 pandemic are magnifying existing disparities and disproportionately affecting low-income, food-insecure households that already struggle to meet basic needs. A robust, comprehensive policy response is needed to mitigate food insecurity as the pandemic progresses.


Subject(s)
Coronavirus Infections/epidemiology , Food Supply/statistics & numerical data , Pneumonia, Viral/epidemiology , Adolescent , Adult , Betacoronavirus , COVID-19 , Family Characteristics , Female , Humans , Male , Middle Aged , Pandemics , Poverty , SARS-CoV-2 , Surveys and Questionnaires , United States/epidemiology , Young Adult
11.
J Clin Rheumatol ; 28(2): e348-e352, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1703196

ABSTRACT

OBJECTIVES: The aim of this study was to examine the incidence of coronavirus disease 2019 (COVID-19) among patients with immunomediated inflammatory diseases (IMIDs) treated with biologic or targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) and to evaluate the influence of either IMIDs or related therapies on the incidence and evolution of COVID-19. METHODS: This observational, cross-sectional study was conducted from January 31, 2020, to May 15, 2020. Data of 902 patients were obtained from clinical records in hospitals, primary care units, and community pharmacies. Inclusion criteria were adults with IMIDs treated with bDMARDs or tsDMARDs who started therapy 3 months prior to study commencement. Patients with poor adherence to treatments were excluded. COVID-19 was classified as "definitive" (severe acute respiratory syndrome coronavirus 2 polymerase chain reaction [PCR]-positive), "possible" (characteristic symptoms and negative PCR), and "suspected" (characteristic symptoms but PCR not performed). RESULTS: COVID-19 was diagnosed in 70 patients (11 definitive, 19 possible, and 40 suspected). The cumulative incidence of definitive COVID-19 was 1.2%. When considering all cases, the incidence was 7.8%. Patients on biosimilars tumor necrosis factor blockers were more likely to have a diagnosis of COVID-19 (odds ratio, 2.308; p < 0.001). Patients on anti-B-cell therapies had a lower incidence of infections (p = 0.046). Low rates of hospitalization (14.3%), pneumonia (14.3%), death (2.9%), or thrombosis (2.9%) were observed, and 94.3% of patients recovered. CONCLUSIONS: The cumulative incidence of confirmed cases of COVID-19 was similar to the general population, with generally low hospitalization, intensive care management, and mortality rates. COVID-19 incidence was less frequent in patients with more severe immunosuppression.


Subject(s)
Antirheumatic Agents , Biosimilar Pharmaceuticals , COVID-19 , Antirheumatic Agents/therapeutic use , Cross-Sectional Studies , Humans , Incidence , SARS-CoV-2
12.
PM R ; 14(2): 198-201, 2022 02.
Article in English | MEDLINE | ID: covidwho-1694679

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) survivors are at risk of functional decline. To address the current gap in knowledge about post-acute needs of those infected by COVID-19, we examined discharge function data to better prepare patients, providers, and health systems to return patients to optimal levels of functioning. OBJECTIVE: To examine the prevalence of functional decline and related rehabilitation needs at hospital discharge. DESIGN: Prospective chart review. SETTING: Academic tertiary care hospital. PARTICIPANTS: Hospitalized adults with a laboratory confirmed COVID-19 diagnosis, with admission dates between March 4, 2020 and May 1, 2020. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Discharge location; need for outpatient physical, occupational, or speech therapy; need for durable medical equipment at discharge; presence of dysphagia at discharge; functional decline. RESULTS: Three hundred eleven potential cases were reviewed. The final number of cases included in analysis was N = 288; patient ages ranged from 20 to 95 years old (mean 66.80 ± 15.31 years). Nearly 20 % of COVID-19 survivors were discharged to a location other than their home. Forty-five percent of survivors experienced functional decline impacting their discharge. Eighty-seven survivors (80.6%) who showed functional change during hospitalization were referred for additional therapy at discharge. At least 73 (67.6%) of these patients required durable medical equipment at discharge (in 12 cases this was not clearly documented). Twenty-nine (26.7%) of the survivors who showed functional changes had ongoing dysphagia at the time of hospital discharge. Ninety-seven of the survivors (40.6%) were never assessed by a PM&R physician, physical therapist, occupational therapist, or speech language pathologist during their hospitalization. CONCLUSIONS: COVID-19 mortality rates are frequently reported in the media, whereas the effects on function are not as well described. The information provided here highlights the need for rehabilitative services during and after hospitalization for COVID-19.


Subject(s)
COVID-19 , Adult , Aged , Aged, 80 and over , COVID-19 Testing , Humans , Middle Aged , Pandemics , Patient Discharge , Prospective Studies , SARS-CoV-2 , Young Adult
13.
Clin Infect Dis ; 74(1): 66-73, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1633721

ABSTRACT

BACKGROUND: Understanding the role of children in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is critical to guide decision-making for schools in the pandemic. We aimed to describe the transmission of SARS-CoV-2 among children and adult staff in summer schools. METHODS: During July 2020, we prospectively recruited children and adult staff attending summer schools in Barcelona who had SARS-CoV-2 infection. Primary SARS-CoV-2 infections were identified through (1) a surveillance program in 22 summer schools of 1905 participants, involving weekly saliva sampling for SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) during 2-5 weeks; and (2) cases identified through the Catalonian Health Surveillance System of children diagnosed with SARS-CoV-2 infection by nasopharyngeal RT-PCR. All centers followed prevention protocols: bubble groups, handwashing, face masks, and conducting activities mostly outdoors. Contacts of a primary case within the same bubble were evaluated by nasopharyngeal RT-PCR. Secondary attack rates and the effective reproduction number in summer schools (Re*) were calculated. RESULTS: Among the >2000 repeatedly screened participants, 30 children and 9 adults were identified as primary cases. A total of 253 close contacts of these primary cases were studied (median, 9 [interquartile range, 5-10] for each primary case), among which 12 new cases (4.7%) were positive for SARS-CoV-2. The Re* was 0.3, whereas the contemporary rate in the general population from the same areas in Barcelona was 1.9. CONCLUSIONS: The transmission rate of SARS-CoV-2 infection among children attending school-like facilities under strict prevention measures was lower than that reported for the general population. This suggests that under preventive measures schools are unlikely amplifiers of SARS-CoV-2 transmission, supporting current recommendations for school opening.


Subject(s)
COVID-19 , Adult , Child , Humans , Pandemics , SARS-CoV-2 , Schools , Spain/epidemiology
14.
Trials ; 22(1): 172, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-1622253

ABSTRACT

OBJECTIVES: The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. TRIAL DESIGN: REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. PARTICIPANTS: The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. INCLUSION CRITERIA: Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria: • Moderate - PaO2/FiO2 100-200 mmHg; • Severe - PaO2/FiO2 < 100 mmHg; 5. Admission to ICU in the last 24 hours. EXCLUSION CRITERIA: Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history: a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days; b) Systemic corticosteroid use before hospitalization; c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment; d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g. • intractable hyperglycaemia; • active gastrointestinal bleeding; • adrenal gland disorders; • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. INTERVENTION AND COMPARATOR: Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10. Patients in the control group will receive dexamethasone 6 mg day 1-10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. MAIN OUTCOMES: Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. SECONDARY ENDPOINTS: a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index. RANDOMISATION: Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. BLINDING (MASKING): This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. TRIAL STATUS: This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. TRIAL REGISTRATION: The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. FULL PROTOCOL: The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19/therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Respiration, Artificial , Respiratory Distress Syndrome/therapy , COVID-19/complications , Clinical Trials, Phase II as Topic , Disease Progression , Dose-Response Relationship, Drug , Equivalence Trials as Topic , Humans , Length of Stay , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/etiology , SARS-CoV-2
15.
Ann Clin Biochem ; 59(1): 15-22, 2022 01.
Article in English | MEDLINE | ID: covidwho-1622156

ABSTRACT

BACKGROUND: There is limited information regarding the role of biomarker levels at predicting mortality in patients with the coronavirus disease (COVID-19) pandemic. The purpose of this study is to determine the differences in serum biomarker levels in adults with COVID-19 who survived hospitalization from those who did not. METHODS: A comprehensive search was completed on PubMed, EMBASE and Cochrane libraries to identify studies of interest. Endpoints of interest were blood counts, hepatic function test, acute phase reactants, cytokines and cardiac biomarkers. RESULTS: A total of 10 studies with 1584 patients were included in the pooled analyses. Biomarkers that were noted to be significantly higher in those who died from coronavirus disease included: white blood cell count, neutrophil count, C-reactive protein, high sensitivity C-reactive protein, procalcitonin, ferritin, D-dimer, interleukin-6, lactate dehydrogenase, creatine kinase, prothrombin time, aspartate aminotransferase, alanine aminotransferase, total bilirubin and creatinine. Lymphocyte count, platelet count and albumin were significantly lower in patients who died. CONCLUSION: This pooled analysis of 10 studies including 1584 patients identified significant differences in biomarkers on admission in patients who survived from those who did not. Further research is needed to develop risk stratification models to help with judicious use of limited health-care resources.


Subject(s)
COVID-19 , Biomarkers , C-Reactive Protein/analysis , Humans , Leukocyte Count , Pandemics , Retrospective Studies , SARS-CoV-2
16.
J Immunotoxicol ; 18(1): 23-29, 2021 12.
Article in English | MEDLINE | ID: covidwho-1593522

ABSTRACT

The coronavirus SARS-CoV-2 of 2019 (COVID-19) causes a pandemic that has been diagnosed in more than 70 million people worldwide. Mild-to-moderate COVID-19 symptoms include coughing, fever, myalgia, shortness of breath, and acute inflammatory lung injury (ALI). In contrast, acute respiratory distress syndrome (ARDS) and respiratory failure occur in patients diagnosed with severe COVID-19. ARDS is mediated, at least in part, by a dysregulated inflammatory response due to excessive levels of circulating cytokines, a condition known as the "cytokine-storm syndrome." Currently, there are FDA-approved therapies that attenuate the dysregulated inflammation that occurs in COVID-19 patients, such as dexamethasone or other corticosteroids and IL-6 inhibitors, including sarilumab, tocilizumab, and siltuximab. However, the efficacy of these treatments have been shown to be inconsistent. Compounds that activate the vagus nerve-mediated cholinergic anti-inflammatory reflex, such as the α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuate ARDS/inflammatory lung injury by decreasing the extracellular levels of high mobility group box-1 (HMGB1) in the airways and the circulation. It is possible that HMGB1 may be an important mediator of the "cytokine-storm syndrome." Notably, high plasma levels of HMGB1 have been reported in patients diagnosed with severe COVID-19, and there is a significant negative correlation between HMGB1 plasma levels and clinical outcomes. Nicotine can activate the cholinergic anti-inflammatory reflex, which attenuates the up-regulation and the excessive release of pro-inflammatory cytokines/chemokines. Therefore, we hypothesize that low molecular weight compounds that activate the cholinergic anti-inflammatory reflex, such as nicotine or GTS-21, may represent a potential therapeutic approach to attenuate the dysregulated inflammatory responses in patients with severe COVID-19.


Subject(s)
Benzylidene Compounds/pharmacology , COVID-19/drug therapy , Cholinergic Agents/pharmacology , Inflammation/drug therapy , Nicotine/metabolism , Pyridines/pharmacology , SARS-CoV-2/physiology , Tobacco Use Disorder/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Cigarette Smoking/adverse effects , Dexamethasone/therapeutic use , HMGB1 Protein/blood , Humans , Pandemics , alpha7 Nicotinic Acetylcholine Receptor/agonists
17.
J Ultrasound Med ; 41(1): 89-96, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1574799

ABSTRACT

OBJECTIVES: Lung ultrasound (LUS) can accurately diagnose several pulmonary diseases, including pneumothorax, effusion, and pneumonia. LUS may be useful in the diagnosis and management of COVID-19. METHODS: This study was conducted at two United States hospitals from 3/21/2020 to 6/01/2020. Our inclusion criteria included hospitalized adults with COVID-19 (based on symptomatology and a confirmatory RT-PCR for SARS-CoV-2) who received a LUS. Providers used a 12-zone LUS scanning protocol. The images were interpreted by the researchers based on a pre-developed consensus document. Patients were stratified by clinical deterioration (defined as either ICU admission, invasive mechanical ventilation, or death within 28 days from the initial symptom onset) and time from symptom onset to their scan. RESULTS: N = 22 patients (N = 36 scans) were included. Eleven (50%) patients experienced clinical deterioration. Among N = 36 scans, only 3 (8%) were classified as normal. The remaining scans demonstrated B-lines (89%), consolidations (56%), pleural thickening (47%), and pleural effusion (11%). Scans from patients with clinical deterioration demonstrated higher percentages of bilateral consolidations (50 versus 15%; P = .033), anterior consolidations (47 versus 11%; P = .047), lateral consolidations (71 versus 29%; P = .030), pleural thickening (69 versus 30%; P = .045), but not B-lines (100 versus 80%; P = .11). Abnormal findings had similar prevalences between scans collected 0-6 days and 14-28 days from symptom onset. DISCUSSION: Certain LUS findings may be common in hospitalized COVID-19 patients, especially for those that experience clinical deterioration. These findings may occur anytime throughout the first 28 days of illness. Future efforts should investigate the predictive utility of these findings on clinical outcomes.


Subject(s)
COVID-19 , Pneumonia , Adult , Humans , Lung/diagnostic imaging , SARS-CoV-2 , Ultrasonography
18.
Ann Med ; 53(1): 410-412, 2021 12.
Article in English | MEDLINE | ID: covidwho-1573909

ABSTRACT

OBJECTIVE: Cytokine release syndrome is suggested to be the most important mechanism triggering acute respiratory distress syndrome and end organ damage in COVID-19. The severity of disease may be measured by different biomarkers. METHODS: We studied markers of inflammation and coagulation as recorded in 29 patients on admission to the hospital in order to identify markers of severe COVID-19 and need of ICU. RESULTS: Patients who were eventually admitted to ICU displayed significantly higher serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. No statistical differences were found between the groups in median levels of lymphocytes, D-dimer or ferritin. CONCLUSIONS: IL-6 and CRP were the strongest predictors of severity in hospitalized patients with COVID-19.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Interleukin-6/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Female , Humans , Male , Middle Aged , Severity of Illness Index , Young Adult
19.
Clin Infect Dis ; 73(11): e4005-e4011, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1562130

ABSTRACT

BACKGROUND: Racial disparities are central in the national conversation about coronavirus disease 2019 (COVID-19) , with Black/African Americans being disproportionately affected. We assessed risk factors for death from COVID-19 among Black inpatients at an urban hospital in Detroit, Michigan. METHODS: This was a retrospective, single-center cohort study. We reviewed the electronic medical records of patients positive for severe acute respiratory syndrome coronavirus 2 (the COVID-19 virus) on qualitative polymerase chain reaction assay who were admitted between 8 March 2020 and 6 May 2020. The primary outcome was in-hospital mortality. RESULTS: The case fatality rate was 29.1% (122/419). The mean duration of symptoms prior to hospitalization was 5.3 (3.9) days. The incidence of altered mental status on presentation was higher among patients who died than those who survived, 43% vs 20.0%, respectively (P < .0001). From multivariable analysis, the odds of death increased with age (≥60 years), admission from a nursing facility, Charlson score, altered mental status, higher C-reactive protein on admission, need for mechanical ventilation, presence of shock, and acute respiratory distress syndrome. CONCLUSIONS: These demographic, clinical, and laboratory factors may help healthcare providers identify Black patients at highest risk for severe COVID-19-associated outcomes. Early and aggressive interventions among this at-risk population may help mitigate adverse outcomes.


Subject(s)
COVID-19 , African Americans , Cohort Studies , Hospital Mortality , Hospitalization , Humans , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2
20.
Clin Infect Dis ; 73(11): e4189-e4196, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1562059

ABSTRACT

BACKGROUND: Lung ultrasonography (LUS) is a promising pragmatic risk-stratification tool in coronavirus disease 2019 (COVID-19). This study describes and compares LUS characteristics between patients with different clinical outcomes. METHODS: Prospective observational study of polymerase chain reaction-confirmed adults with COVID-19 with symptoms of lower respiratory tract infection in the emergency department (ED) of Lausanne University Hospital. A trained physician recorded LUS images using a standardized protocol. Two experts reviewed images blinded to patient outcome. We describe and compare early LUS findings (≤24 hours of ED presentation) between patient groups based on their 7-day outcome (1) outpatients, (2) hospitalized, and (3) intubated/dead. Normalized LUS score was used to discriminate between groups. RESULTS: Between 6 March and 3 April 2020, we included 80 patients (17 outpatients, 42 hospitalized, and 21 intubated/dead). Seventy-three patients (91%) had abnormal LUS (70% outpatients, 95% hospitalized, and 100% intubated/dead; P = .003). The proportion of involved zones was lower in outpatients compared with other groups (median [IQR], 30% [0-40%], 44% [31-70%], 70% [50-88%]; P < .001). Predominant abnormal patterns were bilateral and there was multifocal spread thickening of the pleura with pleural line irregularities (70%), confluent B lines (60%), and pathologic B lines (50%). Posterior inferior zones were more often affected. Median normalized LUS score had a good level of discrimination between outpatients and others with area under the ROC of .80 (95% CI, .68-.92). CONCLUSIONS: Systematic LUS has potential as a reliable, cheap, and easy-to-use triage tool for the early risk stratification in patients with COVID-19 presenting to EDs.


Subject(s)
COVID-19 , Adult , Humans , Lung/diagnostic imaging , Prospective Studies , Risk Assessment , SARS-CoV-2 , Ultrasonography
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