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1.
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
2.
Clin Infect Dis ; 73(11): e4208-e4213, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1560475

ABSTRACT

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe adult respiratory syndrome coronavirus 2, occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. METHODS: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 1 January to 5 February. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy of treatment after hospitalization, and the differences between groups were compared. RESULTS: Compared with patients with general COVID-19 (45.2%), those with refractory disease were older, were more likely to be male, and had more underlying comorbid conditions, a lower incidence of fever, higher maximum temperatures among patients with fever, higher incidences of shortness of breath and anorexia, more severe disease assessment at admission, higher neutrophil, aspartate aminotransferase, lactate dehydrogenase, and C-reactive protein levels, lower platelet counts and albumin levels, and higher incidences of bilateral pneumonia and pleural effusion (P < .05). Patients with refractory COVID-19 were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment, including corticosteroids, antiviral drugs, and immune enhancers (P < .05). Considering the factors of disease severity at admission, mechanical ventilation, and intensive care unit transfer, patients with refractory COVID-19 were also more likely to be male, have manifestations of anorexia on admission, and receive oxygen, expectorant, and adjunctive agents (P < .05). CONCLUSION: In nearly 50% of patients with COVID-19 obvious clinical and radiological remission was not achieved within 10 days after hospitalization. Male, anorexia, and no fever at admission was predictive of poor treatment efficacy.


Subject(s)
COVID-19 , Adult , China/epidemiology , Female , Fever , Hospitalization , Humans , Male , Retrospective Studies , SARS-CoV-2
3.
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.

4.
Intensive Care Med ; 47(2): 188-198, 2021 02.
Article in English | MEDLINE | ID: covidwho-1384370

ABSTRACT

PURPOSE: Although patients with SARS-CoV-2 infection have several risk factors for ventilator-associated lower respiratory tract infections (VA-LRTI), the reported incidence of hospital-acquired infections is low. We aimed to determine the relationship between SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, and the incidence of VA-LRTI. METHODS: Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation > 48 h were eligible if they had: SARS-CoV-2 pneumonia, influenza pneumonia, or no viral infection at ICU admission. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. All VA-LRTI were prospectively identified, and chest-X rays were analyzed by at least two physicians. Cumulative incidence of first episodes of VA-LRTI was estimated using the Kalbfleisch and Prentice method, and compared using Fine-and Gray models. RESULTS: 1576 patients were included (568 in SARS-CoV-2, 482 in influenza, and 526 in no viral infection groups). VA-LRTI incidence was significantly higher in SARS-CoV-2 patients (287, 50.5%), as compared to influenza patients (146, 30.3%, adjusted sub hazard ratio (sHR) 1.60 (95% confidence interval (CI) 1.26 to 2.04)) or patients with no viral infection (133, 25.3%, adjusted sHR 1.7 (95% CI 1.2 to 2.39)). Gram-negative bacilli were responsible for a large proportion (82% to 89.7%) of VA-LRTI, mainly Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp. CONCLUSIONS: The incidence of VA-LRTI is significantly higher in patients with SARS-CoV-2 infection, as compared to patients with influenza pneumonia, or no viral infection after statistical adjustment, but residual confounding may still play a role in the effect estimates.


Subject(s)
COVID-19 , Pneumonia, Ventilator-Associated , Respiratory Tract Infections , Aged , COVID-19/epidemiology , Europe , Female , Humans , Incidence , Influenza, Human/epidemiology , Male , Middle Aged , Pneumonia, Ventilator-Associated/epidemiology , Respiratory Tract Infections/epidemiology , Retrospective Studies , Ventilators, Mechanical
5.
MMWR Morb Mortal Wkly Rep ; 69(25): 769-775, 2020 Jun 26.
Article in English | MEDLINE | ID: covidwho-1389845

ABSTRACT

As of June 16, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in 2,104,346 cases and 116,140 deaths in the United States.* During pregnancy, women experience immunologic and physiologic changes that could increase their risk for more severe illness from respiratory infections (1,2). To date, data to assess the prevalence and severity of COVID-19 among pregnant U.S. women and determine whether signs and symptoms differ among pregnant and nonpregnant women are limited. During January 22-June 7, as part of COVID-19 surveillance, CDC received reports of 326,335 women of reproductive age (15-44 years) who had positive test results for SARS-CoV-2, the virus that causes COVID-19. Data on pregnancy status were available for 91,412 (28.0%) women with laboratory-confirmed infections; among these, 8,207 (9.0%) were pregnant. Symptomatic pregnant and nonpregnant women with COVID-19 reported similar frequencies of cough (>50%) and shortness of breath (30%), but pregnant women less frequently reported headache, muscle aches, fever, chills, and diarrhea. Chronic lung disease, diabetes mellitus, and cardiovascular disease were more commonly reported among pregnant women than among nonpregnant women. Among women with COVID-19, approximately one third (31.5%) of pregnant women were reported to have been hospitalized compared with 5.8% of nonpregnant women. After adjusting for age, presence of underlying medical conditions, and race/ethnicity, pregnant women were significantly more likely to be admitted to the intensive care unit (ICU) (aRR = 1.5, 95% confidence interval [CI] = 1.2-1.8) and receive mechanical ventilation (aRR = 1.7, 95% CI = 1.2-2.4). Sixteen (0.2%) COVID-19-related deaths were reported among pregnant women aged 15-44 years, and 208 (0.2%) such deaths were reported among nonpregnant women (aRR = 0.9, 95% CI = 0.5-1.5). These findings suggest that among women of reproductive age with COVID-19, pregnant women are more likely to be hospitalized and at increased risk for ICU admission and receipt of mechanical ventilation compared with nonpregnant women, but their risk for death is similar. To reduce occurrence of severe illness from COVID-19, pregnant women should be counseled about the potential risk for severe illness from COVID-19, and measures to prevent infection with SARS-CoV-2 should be emphasized for pregnant women and their families.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Pandemics , Pneumonia, Viral/diagnosis , Pregnancy Complications, Infectious/virology , Adolescent , Adult , COVID-19 , Coronavirus Infections/epidemiology , Female , Humans , Laboratories , Pneumonia, Viral/epidemiology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Prevalence , Risk Assessment , SARS-CoV-2 , Severity of Illness Index , United States/epidemiology , Young Adult
7.
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
8.
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
9.
Medicine (Baltimore) ; 100(4): e24443, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1298407

ABSTRACT

ABSTRACT: The main aim of this study is to compare the use of non-invasive ventilation (NIV) via helmet versus face mask where different interfaces and masks can apply NIV. However, some of the limitations of the NIV face mask were air leak, face mask intolerance, and requirement of high positive end expiratory pressure, which could be resolved with the use of the helmet NIV. NIV facemask will be applied as per the facial contour of the patient. NIV helmet is a transparent hood and size will be measured as per the head size. Both groups will have a standard protocol for titration of NIV.Patients aged more than 18 years old and diagnosed with acute respiratory distress syndrome as per Berlin definition will be enrolled in the study after signing the informed consent. Subjects who met the inclusion criteria will receive 1 of the 2 interventions; blood gases, oxygenation status [Po2/Fio2] will be monitored in both groups. The time of intubation will be the main comparison factor among the 2 groups. The primary and secondary outcomes will be measured by the number of patients requiring endotracheal intubation after application of helmet device, Improvement of oxygenation defined as PaO2/FiO2 ≥ 200 or increase from baseline by 100, duration of mechanical ventilation via an endotracheal tube, intensive care unit length of stay, death from any cause during hospitalization at the time of enrolment, need for proning during the hospital stay, intensive care unit mortality, and the degree to which overt adverse effects of a drug can be tolerated by a patient including feeding tolerance. TRIAL REGISTRATION NUMBER: NCT04507802. PROTOCOL VERSION: May 2020.


Subject(s)
Head Protective Devices , Masks , Noninvasive Ventilation/instrumentation , Respiratory Distress Syndrome/therapy , Adolescent , Adult , Clinical Trials, Phase III as Topic , Critical Care Outcomes , Female , Humans , Intensive Care Units , Length of Stay , Male , Middle Aged , Randomized Controlled Trials as Topic , Treatment Outcome , Young Adult
10.
Ann Clin Biochem ; 58(5): 520-527, 2021 09.
Article in English | MEDLINE | ID: covidwho-1277833

ABSTRACT

BACKGROUND: The variability of Covid-19 severity between patients has driven efforts to identify prognosticating laboratory markers that could aid clinical decision-making. Procalcitonin is classically used as a diagnostic marker in bacterial infections, but its role in predicting Covid-19 disease severity is emerging. We aimed to identify the association between procalcitonin and Covid-19 disease severity in a critical care setting and whether bacterial co-infection is implicated. METHODS: We retrospectively reviewed Covid-19 patients with procalcitonin concentrations measured in a critical care setting at our institution between February and September 2020. Laboratory markers including peak procalcitonin values and a range of bacterial culture results were analysed. Outcomes were the requirement and duration of invasive mechanical ventilation as well as inpatient mortality. RESULTS: In total, 60 patients were included; 68% required invasive mechanical ventilation and 45% died as inpatient. Univariate analysis identified higher peak procalcitonin concentrations significantly associated with both the requirement for invasive mechanical ventilation (OR: 3.2, 95% CI 1.3-9.0, P = 0.02) and inpatient mortality (OR: 2.6, 95% CI 1.1-6.6, P = 0.03). Higher peak procalcitonin concentrations was an independent predictor of mortality on multivariate analysis (OR 3.7, 95% CI 1.1-12.4, P = 0.03). There was a significant positive correlation between increased peak procalcitonin concentrations and duration on invasive mechanical ventilation. No significant difference was found between peak procalcitonin concentrations of patients with positive and negative bacterial cultures. CONCLUSIONS: Elevated procalcitonin concentrations in Covid-19 patients are associated with respiratory failure requiring prolonged invasive mechanical ventilation and inpatient mortality. This association may be independent of bacterial co-infection.


Subject(s)
Bacterial Infections/blood , Bacterial Infections/complications , COVID-19/blood , COVID-19/complications , Procalcitonin/blood , SARS-CoV-2 , Adult , Aged , Bacterial Infections/diagnosis , Biomarkers/blood , COVID-19/epidemiology , Coinfection/blood , Critical Care , England/epidemiology , Female , Humans , Male , Middle Aged , Multivariate Analysis , Pandemics , Prognosis , Respiration, Artificial , Retrospective Studies , Risk Factors , Severity of Illness Index
11.
Aliment Pharmacol Ther ; 54(2): 160-166, 2021 07.
Article in English | MEDLINE | ID: covidwho-1263811

ABSTRACT

BACKGROUND: Recently, the SECURE-IBD study, based on a physician-reported registry, suggested that thiopurines, either alone or combined with anti-TNF, may increase risk of severe COVID-19. AIMS: To compare the risk of severe COVID-19 according to IBD medications in a large and unselected population. METHODS: Using the French national health data system, the risks of hospitalisation and of death or mechanical ventilation for COVID-19 from 15 February 2020 to 31 August 2020 in IBD patients were compared according to IBD treatment (immunomodulators and biologics), using multivariable Cox models adjusted for socio-demographic characteristics, budesonide/corticosteroids and aminosalicylates use, and comorbidities. RESULTS: Among 268 185 IBD patients, 600 were hospitalised for COVID-19 and 111 of them died or were mechanically ventilated (including 78 deaths). In multivariable analysis, the risk of hospitalisation for COVID-19 did not differ according to IBD treatment category, with adjusted Hazard Ratios (aHR, unexposed patients used as reference) of 0.94 (95%CI: 0.66-1.35) for immunomodulator monotherapy, 1.05 (0.80-1.38) for anti-TNF monotherapy, 0.80 (0.38-1.69) for anti-TNF combination therapy, 1.06 (0.55-2.05) for vedolizumab and 1.25 (0.64-2.43) for ustekinumab. Similarly, the risk of death or mechanical ventilation for COVID-19 did not differ according to IBD treatment. CONCLUSIONS: Immunomodulators and biologics prescribed in patients with IBD do not appear to increase the severity of COVID-19 infection.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Humans , Immunologic Factors , Inflammatory Bowel Diseases/drug therapy , SARS-CoV-2 , Tumor Necrosis Factor Inhibitors
12.
BMJ Open ; 11(5): e045041, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1259009

ABSTRACT

INTRODUCTION: International guidelines include early nutritional support (≤48 hour after admission), 20-25 kcal/kg/day, and 1.2-2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets. METHODS AND ANALYSIS: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2-0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0-1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes. ETHICS AND DISSEMINATION: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03573739.


Subject(s)
COVID-19 , Diet, Protein-Restricted , Adult , Critical Illness , Humans , Respiration, Artificial , SARS-CoV-2
13.
Clin Infect Dis ; 72(11): e736-e741, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1249285

ABSTRACT

BACKGROUND: A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in patients with coronavirus disease 2019 (COVID-19). METHODS: This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an oxyhemoglobin saturation <94% or respiratory rate >24 breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality. RESULTS: Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was observed in secondary endpoints. CONCLUSIONS: Administration of NAC in high doses did not affect the evolution of severe COVID-19. CLINICAL TRIALS REGISTRATION: Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 (http://www.ensaiosclinicos.gov.br/rg/RBR-8969zg/).


Subject(s)
COVID-19 , Acetylcysteine/therapeutic use , Brazil , COVID-19/drug therapy , Double-Blind Method , Humans , Respiration, Artificial , SARS-CoV-2 , Treatment Outcome
14.
JAMA Otolaryngol Head Neck Surg ; 147(7): 646-655, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1245338

ABSTRACT

Importance: Approximately 5% to 15% of patients with COVID-19 require invasive mechanical ventilation (IMV) and, at times, tracheostomy. Details regarding the safety and use of tracheostomy in treating COVID-19 continue to evolve. Objective: To evaluate the association of tracheostomy with COVID-19 patient outcomes and the risk of SARS-CoV-2 transmission among health care professionals (HCPs). Data Sources: EMBASE (Ovid), Medline (Ovid), and Web of Science from January 1, 2020, to March 4, 2021. Study Selection: English-language studies investigating patients with COVID-19 who were receiving IMV and undergoing tracheostomy. Observational and randomized clinical trials were eligible (no randomized clinical trials were found in the search). All screening was performed by 2 reviewers (P.S. and M.L.). Overall, 156 studies underwent full-text review. Data Extraction and Synthesis: We performed data extraction in accordance with Meta-analysis of Observational Studies in Epidemiology guidelines. We used a random-effects model, and ROBINS-I was used for the risk-of-bias analysis. Main Outcomes and Measures: SARS-CoV-2 transmission between HCPs and levels of personal protective equipment, in addition to complications, time to decannulation, ventilation weaning, and intensive care unit (ICU) discharge in patients with COVID-19 who underwent tracheostomy. Results: Of the 156 studies that underwent full-text review, only 69 were included in the qualitative synthesis, and 14 of these 69 studies (20.3%) were included in the meta-analysis. A total of 4669 patients were included in the 69 studies, and the mean (range) patient age across studies was 60.7 (49.1-68.8) years (43 studies [62.3%] with 1856 patients). We found that in all studies, 1854 patients (73.8%) were men and 658 (26.2%) were women. We found that 28 studies (40.6%) investigated either surgical tracheostomy or percutaneous dilatational tracheostomy. Overall, 3 of 58 studies (5.17%) identified a small subset of HCPs who developed COVID-19 that was associated with tracheostomy. Studies did not consistently report the number of HCPs involved in tracheostomy. Among the patients, early tracheostomy was associated with faster ICU discharge (mean difference, 6.17 days; 95% CI, -11.30 to -1.30), but no change in IMV weaning (mean difference, -2.99 days; 95% CI, -8.32 to 2.33) or decannulation (mean difference, -3.12 days; 95% CI, -7.35 to 1.12). There was no association between mortality or perioperative complications and type of tracheostomy. A risk-of-bias evaluation that used ROBINS-I demonstrated notable bias in the confounder and patient selection domains because of a lack of randomization and cohort matching. There was notable heterogeneity in study reporting. Conclusions and Relevance: The findings of this systematic review and meta-analysis indicate that enhanced personal protective equipment is associated with low rates of SARS-CoV-2 transmission during tracheostomy. Early tracheostomy in patients with COVID-19 may reduce ICU stay, but this finding is limited by the observational nature of the included studies.


Subject(s)
COVID-19/transmission , Infectious Disease Transmission, Patient-to-Professional , Pneumonia, Viral/transmission , Tracheostomy , COVID-19/prevention & control , Humans , Personal Protective Equipment , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , SARS-CoV-2
15.
Respir Care ; 66(9): 1406-1415, 2021 09.
Article in English | MEDLINE | ID: covidwho-1244287

ABSTRACT

BACKGROUND: ARDS in patients with coronavirus disease 2019 (COVID-19) is characterized by microcirculatory alterations in the pulmonary vascular bed, which could increase dead-space ventilation more than in non-COVID-19 ARDS. We aimed to establish if dead-space ventilation is different in patients with COVID-19 ARDS when compared with patients with non-COVID-19 ARDS. METHODS: A total of 187 subjects with COVID-19 ARDS and 178 subjects with non-COVID-19 ARDS who were undergoing invasive mechanical ventilation were included in the study. The association between the ARDS types and dead-space ventilation, compliance of the respiratory system, subjects' characteristics, organ failures, and mechanical ventilation was evaluated by using data collected in the first 24 h of mechanical ventilation. RESULTS: Corrected minute ventilation (V˙E), a dead-space ventilation surrogate, was higher in the subjects with COVID-19 ARDS versus in those with non-COVID-19 ARDS (median [interquartile range] 12.6 [10.2-15.8] L/min vs 9.4 [7.5-11.6] L/min; P < .001). Increased corrected V˙E was independently associated with COVID-19 ARDS (odds ratio 1.24, 95% CI 1.07-1.47; P = .007). The best compliance of the respiratory system, obtained after testing different PEEPs, was similar between the subjects with COVID-19 ARDS and the subjects with non-COVID-19 ARDS (mean ± SD 38 ± 11 mL/cm H2O vs 37 ± 11 mL/cm H2O, respectively; P = .61). The subjects with COVID-19 ARDS received higher median (interquartile range) PEEP (12 [10-14] cm H2O vs 8 [5-9] cm H2O; P < .001) and lower median (interquartile range) tidal volume (5.8 [5.5-6.3] mL/kg vs 6.6 [6.1-7.3] mL/kg; P < .001) than the subjects with non-COVID-19 ARDS, being these differences maintained at multivariable analysis. In the multivariable analysis, the subjects with COVID-19 ARDS showed a lower risk of anamnestic arterial hypertension (odds ratio 0.18, 95% CI 0.07-0.45; P < .001) and lower neurologic sequential organ failure assessment score (odds ratio 0.16, 95% CI 0.09-0.27; P < .001) than the subjects with non-COVID-19 ARDS. CONCLUSIONS: Indirect measurements of dead space were higher in subjects with COVID-19 ARDS compared with subjects with non-COVID-19 ARDS. The best compliance of the respiratory system was similar in both ARDS forms provided that different PEEPs were applied. A wide range of compliance is present in every ARDS type; therefore, the setting of mechanical ventilation should be individualized patient by patient and not based on the etiology of ARDS.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Microcirculation , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , Tidal Volume
16.
Pediatr Hematol Oncol ; 38(8): 695-706, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1242072

ABSTRACT

An understanding of the behavior of SARS-CoV-2 in pediatric hematology-oncology patients is essential to the optimal management of these patients during the COVID-19 pandemic. This study describes the characteristics and outcomes of COVID-19 disease in children with cancer or hematologic disorders treated at a large children's hospital. A retrospective cohort study was conducted at Texas Children's Cancer and Hematology Center from January 1, 2020 to September 30, 2020. All patients with a primary hematology-oncology diagnosis and SARS-CoV-2 positivity by reverse transcription polymerase chain reaction were identified. Clinical and laboratory data were obtained from the medical record. Descriptive analyses were performed to evaluate COVID-19-related outcomes and risk factors for severe disease in this population. We identified 109 patients with COVID-19 disease, including 52 hematology, 51 oncology, and 6 HSCT patients; median age was 10.3 years (IQR 4.4-15.9), and 58.7% were male. Seventy-four percent of the patients were managed in the outpatient setting. Patients with sickle cell disease were more likely to require hospitalization. ICU care was needed in 8% (n = 9) of the entire cohort, and mechanical ventilation was required in 6.4% (6 oncology patients, 1 hematology patient). COVID-19 contributed to the deaths of two cancer patients. No deaths occurred in hematology or HSCT patients. In conclusion, the risk of severe COVID-19 complications is slightly higher in pediatric hematology-oncology patients than in the general pediatric population but lower than initially feared. For most asymptomatic patients, primary disease management may continue as planned, but treatment decisions must be individualized.


Subject(s)
COVID-19 , Hematologic Diseases , Neoplasms , COVID-19/complications , Child , Hematologic Diseases/epidemiology , Humans , Male , Neoplasms/epidemiology , Pandemics , Retrospective Studies , Texas/epidemiology
17.
Front Endocrinol (Lausanne) ; 12: 633767, 2021.
Article in English | MEDLINE | ID: covidwho-1241166

ABSTRACT

Background: Although hyperuricemia frequently associates with respiratory diseases, patients with severe coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) can show marked hypouricemia. Previous studies on the association of serum uric acid with risk of adverse outcomes related to COVID-19 have produced contradictory results. The precise relationship between admission serum uric acid and adverse outcomes in hospitalized patients is unknown. Methods: Data of patients affected by laboratory-confirmed COVID-19 and admitted to Leishenshan Hospital were retrospectively analyzed. The primary outcome was composite and comprised events, such as intensive care unit (ICU) admission, mechanical ventilation, or mortality. Logistic regression analysis was performed to explore the association between serum concentrations of uric acid and the composite outcome, as well as each of its components. To determine the association between serum uric acid and in-hospital adverse outcomes, serum uric acid was also categorized by restricted cubic spline, and the 95% confidence interval (CI) was used to estimate odds ratios (OR). Results: The study cohort included 1854 patients (mean age, 58 years; 52% women). The overall mean ± SD of serum levels of uric acid was 308 ± 96 µmol/L. Among them, 95 patients were admitted to ICU, 75 patients received mechanical ventilation, and 38 died. In total, 114 patients reached composite end-points (have either ICU admission, mechanical ventilation or death) during hospitalization. Compared with a reference group with estimated baseline serum uric acid of 279-422 µmol/L, serum uric acid values ≥ 423 µmol/L were associated with an increased risk of composite outcome (OR, 2.60; 95% CI, 1.07- 6.29) and mechanical ventilation (OR, 3.01; 95% CI, 1.06- 8.51). Serum uric acid ≤ 278 µmol/L was associated with an increased risk of the composite outcome (OR, 2.07; 95% CI, 1.18- 3.65), ICU admission (OR, 2.18; 95% CI, 1.17- 4.05]), and mechanical ventilation (OR, 2.13; 95% CI, 1.06- 4.28), as assessed by multivariate analysis. Conclusions: This study shows that the association between admission serum uric acid and composite outcome of COVID-19 patients was U-shaped. In particular, we found that compared with baseline serum uric acid levels of 279-422 µmol/L, values ≥ 423 µmol/L were associated with an increased risk of composite outcome and mechanical ventilation, whereas levels ≤ 278 µmol/L associated with increased risk of composite outcome, ICU admission and mechanical ventilation.


Subject(s)
COVID-19/blood , Uric Acid/blood , Adult , Aged , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Prognosis , Respiration, Artificial , Retrospective Studies , Survival Rate
18.
Immunol Rev ; 302(1): 228-240, 2021 07.
Article in English | MEDLINE | ID: covidwho-1241009

ABSTRACT

The COVID-19 pandemic rapidly spread around the world following the first reports in Wuhan City, China in late 2019. The disease, caused by the novel SARS-CoV-2 virus, is primarily a respiratory condition that can affect numerous other bodily systems including the cardiovascular and gastrointestinal systems. The disease ranges in severity from asymptomatic through to severe acute respiratory distress requiring intensive care treatment and mechanical ventilation, which can lead to respiratory failure and death. It has rapidly become evident that COVID-19 patients can develop features of interstitial pulmonary fibrosis, which in many cases persist for as long as we have thus far been able to follow the patients. Many questions remain about how such fibrotic changes occur within the lung of COVID-19 patients, whether the changes will persist long term or are capable of resolving, and whether post-COVID-19 pulmonary fibrosis has the potential to become progressive, as in other fibrotic lung diseases. This review brings together our existing knowledge on both COVID-19 and pulmonary fibrosis, with a particular focus on lung epithelial cells and fibroblasts, in order to discuss common pathways and processes that may be implicated as we try to answer these important questions in the months and years to come.


Subject(s)
COVID-19/pathology , Epithelial Cells/pathology , Fibroblasts/pathology , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/virology , Respiratory Mucosa/pathology , COVID-19/complications , Humans , SARS-CoV-2
19.
Sci Rep ; 11(1): 10727, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1238019

ABSTRACT

Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score-matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January-April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388-0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323-2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841-2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347-5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).


Subject(s)
Adrenal Cortex Hormones/administration & dosage , COVID-19/therapy , Hospitalization , Respiration, Artificial , SARS-CoV-2 , COVID-19/diagnostic imaging , COVID-19/pathology , Critical Illness , Female , Humans , Male , Middle Aged , Retrospective Studies
20.
Pulm Pharmacol Ther ; 69: 102039, 2021 08.
Article in English | MEDLINE | ID: covidwho-1237861

ABSTRACT

BACKGROUND AND AIM: Cytokine release syndrome is a dangerous complication of the coronavirus disease 2019 (COVID-19). This study aimed to evaluate the efficacy and safety of tofacitinib in the management of this complication. METHODS: The retrospective study included COVID-19 patients with C-reactive protein (CRP) levels of 60-150 mg/L. RESULTS: Thirty-two patients who received tofacitinib (TOF group) and 30 patients who did not receive any anti-cytokine drugs (control [CON] group) were enrolled. Mortality and the incidence of admission to the intensive care unit were lower in the TOF group than in the CON group (16.6% vs. 40.0%, p = 0.009; and 15.6% vs. 50.0%, p = 0.004). There was a significant decrease in the volume of the affected part of the lungs (p = 0.022) and a significant increase in oxygen saturation (p = 0.012) in the TOF group than in the CON group 7-10 days after the beginning tofacitinib administration. CRP level was lower in the TOF group than in the CON group (7 [3-22] vs. 20 [5-52] mg/L; p = 0.048) 7-10 days after the start of the administration of tofacitinib. During this period, the number of patients requiring mechanical ventilation or those in the prone position increased in the CON group compared to those in the TOF group (26.7% vs. 0.0%, p = 0.002; 33.3% vs. 6.7%, p = 0.020). There was no significant difference in the development of secondary infections, liver or kidney injury, and cytopenia between the two groups. CONCLUSION: Tofacitinib was effective and safe for managing the cytokine release syndrome in COVID-19. Randomized controlled double-blind trials with tofacitinib with and without the simultaneous use of glucocorticoids are required to confirm our findings.


Subject(s)
COVID-19 , Humans , Piperidines , Pyrimidines , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
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