COVID-19 Patients In Intensive Care Unit Research Articles

Recurrent myocardial injury is a strong predictor of ICU mortality in COVID-19

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial injury is common in COVID-19, and has been linked to disease severity and mortality.1 Its pathophysiology is not fully elucidated and suggested mechanisms include cytokine damage, endotheliitis, myocarditis, ferroptosis, acute coronary syndrome, oxygen supply-demand mismatch and pulmonary embolism.2-3 Elevated serum cardiac troponin (cTn) – as surrogate marker of myocardial injury – at admission and during hospitalisation is associated with poor outcome.4-5 Comparison of available trial data, however, is unfeasible, because of variable definition and sampling timing/intervals/assays.6 Peculiarly, prognostic cut-off cTn values are often – retrospectively – set much lower than recommended by the guidelines.6-8 Furthermore, robust intensive care unit (ICU) outcome data regarding cTn evolution over time is lacking. Purpose The aim of this study is to critically explore the correlation between myocardial injury and mortality in a tertiary ICU population, using both standard and high cTn cut-off values, and to scrutinise the impact of timing and recurrence. Methods All adult COVID-19 patients admitted to our tertiary ICU between 06/03/2020 and 27/09/2021 were enrolled in this large, retrospective, single centre, cohort study. Patients requiring extracorporeal membrane oxygenation (n=29) were excluded. Myocardial injury was defined – as per ESC guidelines - as high-sensitive cardiac troponin I (hs-cTnI) peak >45ng/L (99th percentile upper reference limit) and ‘major’ myocardial injury was defined as hs-cTnI >135ng/L (3x upper limit of normal).6-7 Recurrent myocardial injury was considered if a new hs-cTnI peak above cut-off point occurred after normalisation. Patients were categorised according to peak (‘standard’ >45ng/L vs ‘high’ >135ng/L), onset (‘on admission’ vs ‘during hospitalisation’) and recurrence (‘single’ vs ‘multiple’) of hs-cTnI rise. Statistical analysis was done by logistic regression, using IBM SPSS version 28. Results A total of 193 COVID-19 ICU patients were included. Patient characteristics, disease severity indices and treatment details are summarised in Table 1. The mean age was 62 years and ICU mortality was 22%. Myocardial injury overall occurred in 51% (n=99) and major myocardial injury occurred in 39% (n=75) of patients. Obtained results were consistent across standard (>45ng/L) and high (>135ng/L) hs-cTnI cut-off groups. Myocardial injury only present at ICU admission was not correlated with mortality in our cohort, contradicting prior (mostly non-ICU) trials. Single hs-cTnI peak during ICU hospitalisation, however, and, especially recurrent hs-cTnI peaks were strong predictors of ICU mortality. The respective incidence, odds ratio, 95% confidence intervals and p-values are displayed in Table 2. Conclusion Myocardial injury occurring during ICU hospitalisation and, especially, recurrent myocardial injury is strongly correlated with ICU mortality in COVID-19 patients.

Effect of the First Year of COVID-19 Pandemic on Ophthalmological Practice: A Multi-Centre Italian Study with a Focus on Medico-Legal Aspects

During the COVID-19 era, several restrictions on surgery have been imposed to reduce the infectious risk among patients and staff and further preserve the availability of critical care resources. The aim of the study was to assess their impact on the ophthalmological practice and its medico-legal implications. A retrospective review of electronic medical records of the ophthalmological departments of the University of Cagliari (SGD) and University Magna Græcia of Catanzaro (UMG), from 16 March 2020 to 14 March 2021 (52 weeks), were compared with data from the corresponding period of the previous year. Weekly data on the number and type of diagnoses and procedures performed were collected and analysed in relation to the weekly average of the total number of COVID-19 patients in intensive care units (ICUs) and inpatients in Sardinia and Calabria. Results showed a significant decrease in cataract surgery operations by 47% and 31%, respectively, in the SGD and UMG (p < 0.05) during the second semester of the year; this drop occurred at the same time as the increase in COVID-19 patients in ICU and those hospitalised in both regions. Additionally, anterior segment surgery decreased at the UMG by 30% (p < 0.05). Vitreoretinal surgery decreased by 27% at the SGD, differently increased amount 31.5% at UMG (p < 0.05). The pandemic had a dramatic impact on elective surgery in ophthalmology, quantifying the backlog is the first step in order to understanding the measures to be taken in near future.

Evidence showing lipotoxicity worsens outcomes in covid-19 patients and insights about the underlying mechanisms

SummaryWe compared three hospitalized patient cohorts and conducted mechanistic studies to determine if lipotoxicity worsens COVID-19. Cohort-1 (n = 30) compared COVID-19 patients dismissed home to those requiring intensive-care unit (ICU) transfer. Cohort-2 (n = 116) compared critically ill ICU patients with and without COVID-19. Cohort-3 (n = 3969) studied hypoalbuminemia and hypocalcemia’s impact on COVID-19 mortality. Patients requiring ICU transfer had higher serum albumin unbound linoleic acid (LA). Unbound fatty acids and LA were elevated in ICU transfers, COVID-19 ICU patients and ICU non-survivors. COVID-19 ICU patients (cohort-2) had greater serum lipase, damage-associated molecular patterns (DAMPs), cytokines, hypocalcemia, hypoalbuminemia, organ failure and thrombotic events. Hypocalcemia and hypoalbuminemia independently associated with COVID-19 mortality in cohort-3. Experimentally, LA reacted with albumin, calcium and induced hypocalcemia, hypoalbuminemia in mice. Endothelial cells took up unbound LA, which depolarized their mitochondria. In mice, unbound LA increased DAMPs, cytokines, causing endothelial injury, organ failure and thrombosis. Therefore, excessive unbound LA in the circulation may worsen COVID-19 outcomes.

Impact of Isolation Time of COVID-19 Patients in Intensive Care Unit on Healthcare Workers Contamination and Nursing Care Intensity.

BackgroundThe optimal isolation time of COVID-19 patients in intensive care unit (ICU) is debated. We investigated the impact of two different COVID-19 patient isolation time strategies on healthcare workers (HCW) contamination, intensity of nursing care and potential associated adverse events.MethodsWe prospectively included all consecutive COVID-19 patients and HCW in our ICU in the first two pandemic waves (March to May 2020 and August to November 2020). Specific isolation measures for COVID-19 patients were released after two negative RT-PCR assays in the first wave and 14 days after the onset of symptoms in the second wave. Contamination of HCW was assessed at the end of each pandemic wave by combining both a RT-PCR assay and a serological test.ResultsOverall, 117 COVID-19 patients and 73 HCW were included. Despite an earlier release from isolation after ICU admission in the second than in the first wave [6 (4–8) vs. 15 (11–19) days, p < 0.01], the proportion of HCW with a positive serological test (16 vs. 17%, p = 0.94) or with a positive RT-PCR assay (3 vs. 5%, p = 0.58) was not different between the two waves. Although a lower nurse-to-bed ratio, the intensity of nursing care was higher in the second than in the first wave. A longer isolation time was associated with accidental extubation (OR = 1.18, 95%CI:1.07–1.35, p = 0.005) but neither with ventilator-associated pneumonia nor with dysglycemia.ConclusionA shorter isolation time of COVID-19 patients in ICU was not associated with higher HCW contamination, while a longer isolation time seemed to be associated with higher accidental extubation.

A Clustered Case Series of Mucorales Detection in Respiratory Samples from COVID-19 Patients in Intensive Care, France, August to September 2021.

While COVID-19-associated pulmonary aspergillosis is now well described in developed countries, COVID-19-associated mucormycosis (CAM) has seemed to remain quite rare in Europe. A retrospective study was performed between March 2020 to September 2021 among COVID-19 adult patients in the intensive care unit (ICU) at Toulouse Hospital (Southern France). PCR screening on respiratory samples, which target Aspergillus or Mucorales DNA, were performed, and the number of fungal detections was evaluated monthly during the study period. During the 19 months of the study, 44 (20.3%) COVID-19 ICU patients had a positive PCR for Aspergillus, an overall rate in keeping with the incidence of ICU COVID-19 patients. Ten patients (7.1%) had a positive Mucorales PCR over the same period. Surprisingly, 9/10 had a positive Mucor/Rhizopus PCR in August-September 2021, during the fourth Delta SARS-CoV-2 variant wave. Epidemic investigations have identified a probable environmental cause linked to construction works in the vicinity of the ICU (high levels of airborne spores due to the mistaken interruption of preventive humidification and summer temperature). Even if CAM are apparently rare in Europe, a cluster can also develop in industrialised countries when environmental conditions (especially during construction work) are associated with a high number of COVID-19 patients in the ICU.

COVID-19 mortality prediction in the intensive care unit with deep learning based on longitudinal chest X-rays and clinical data.

ObjectivesWe aimed to develop deep learning models using longitudinal chest X-rays (CXRs) and clinical data to predict in-hospital mortality of COVID-19 patients in the intensive care unit (ICU).MethodsSix hundred fifty-four patients (212 deceased, 442 alive, 5645 total CXRs) were identified across two institutions. Imaging and clinical data from one institution were used to train five longitudinal transformer-based networks applying five-fold cross-validation. The models were tested on data from the other institution, and pairwise comparisons were used to determine the best-performing models.ResultsA higher proportion of deceased patients had elevated white blood cell count, decreased absolute lymphocyte count, elevated creatine concentration, and incidence of cardiovascular and chronic kidney disease. A model based on pre-ICU CXRs achieved an AUC of 0.632 and an accuracy of 0.593, and a model based on ICU CXRs achieved an AUC of 0.697 and an accuracy of 0.657. A model based on all longitudinal CXRs (both pre-ICU and ICU) achieved an AUC of 0.702 and an accuracy of 0.694. A model based on clinical data alone achieved an AUC of 0.653 and an accuracy of 0.657. The addition of longitudinal imaging to clinical data in a combined model significantly improved performance, reaching an AUC of 0.727 (p = 0.039) and an accuracy of 0.732.ConclusionsThe addition of longitudinal CXRs to clinical data significantly improves mortality prediction with deep learning for COVID-19 patients in the ICU.Key Points• Deep learning was used to predict mortality in COVID-19 ICU patients.• Serial radiographs and clinical data were used.• The models could inform clinical decision-making and resource allocation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00330-022-08588-8.

RETRACTED ARTICLE: Coronary arteries and aortic valve calcifications in COVID-19.

High coronary artery calcium score (CACS) and aortic valve calcifications (AC) increase cardiovascular risk. Our purpose is to evaluate CACS, measured by Weston score (WS), and the presence of AC in chest CT of COVID-19 patients and possibly investigate their prognostic role. This retrospective case-control study includes 150 hospitalized COVID-19 patients who underwent a chest CT at admission. The case group (group A) was formed by 50 in-patients in intensive care unit (ICU) under invasive ventilation (IV), while the control group (group B) was formed by 100 in-patients in non-ICU units, not under IV. After, a second case-control selection was originated from these two groups: the case group (group A1) composed by 30 patients, and the matching control group (group B1) composed by 60 patients. WS and the presence of AC were compared between groups A and B, and between groups A1 and B1. Moreover, lung severity score (LSS) and WS were correlated. LSS was 7.5 ± 3.9, and WS was 6.4 ± 3.0; AC was present in 97/150 (64.7%). WS was significantly higher in group A than in group B, respectively, 7.4 ± 4.0 and 5.7 ± 2.6 (p = 0.0146), and also the presence of AC, respectively, 41/50 (82.0%) vs 56/100 (56.0%) (p = 0.0016). Finally, WS and AC were significantly higher in group A1 compared to group B1. Both WS and AC were higher in ICU COVID-19 patients than in non-ICU COVID-19 patients.

CORONA (COre ultRasOund of covid in iNtensive care and Acute medicine) study: National service evaluation of lung and heart ultrasound in intensive care patients with suspected or proven COVID-19.

Combined Lung Ultrasound (LUS) and Focused UltraSound for Intensive Care heart (FUSIC Heart - formerly Focused Intensive Care Echocardiography, FICE) can aid diagnosis, risk stratification and management in COVID-19. However, data on its application and results are limited to small studies in varying countries and hospitals. This United Kingdom (UK) national service evaluation study assessed how combined LUS and FUSIC Heart were used in COVID-19 Intensive Care Unit (ICU) patients during the first wave of the pandemic. Twelve trusts across the UK registered for this prospective study. LUS and FUSIC Heart data were obtained, using a standardised data set including scoring of abnormalities, between 1st February 2020 to 30th July 2020. The scans were performed by intensivists with FUSIC Lung and Heart competency as a minimum standard. Data was anonymised locally prior to transfer to a central database. 372 studies were performed on 265 patients. There was a small but significant relationship between LUS score >8 and 30-day mortality (OR 1.8). Progression of score was associated with an increase in 30-day mortality (OR 1.2). 30-day mortality was increased in patients with right ventricular (RV) dysfunction (49.4% vs 29.2%). Severity of LUS score correlated with RV dysfunction (p < 0.05). Change in management occurred in 65% of patients following a combined scan. In COVID-19 patients, there is an association between lung ultrasound score severity, RV dysfunction and mortality identifiable by combined LUS and FUSIC Heart. The use of 12-point LUS scanning resulted in similar risk score to 6-point imaging in the majority of cases. Our findings suggest that serial combined LUS and FUSIC Heart on COVID-19 ICU patients may aid in clinical decision making and prognostication.

Microcirculation disorders in patients with severe COVID-19 and development of bacterial sepsis

It is believed that microcirculation dysfunction in sepsis primarily caused by damage of the endothelium by infectious agents and pro-inflammatory cytokines. Mechanisms of impaired microcirculation in the severe course of COVID-19 and sepsis likely to be similar. However, there are few reports studied microcirculation disorders in patients with COVID-19, and their results are sometimes contradictory. Objective. To assess the microcirculation of patients with severe Covid-19 and the development of bacterial sepsis using nail bed microscopy and laser Doppler flowmetry. Materials and methods. 16 intensive care unit COVID-19 patients subsequently diagnosed with bacterial sepsis were examined. Patients underwent vital capillaroscopy and an occlusive test using laser Doppler flowmetry. The average rate of capillary blood flow, the size of the perivascular zone, the density of capillaries, the presence of intravascular aggregates, the increase in the amplitude of the maximum post-occlusive blood flow and the average value of postocclusive blood flow relative to the initial one were valuated. Additionally, the level of serum proadrenomedullin was evaluated. Studies were performed on the day of admission and in dynamics. Results. By the capillaroscopy analysis, microcirculation disorders were detected in the form of a decrease in the linear speed of capillary blood flow (&lt;400 μm/s), an extention of the perivascular zone (&gt;100 μm), the circulation of microaggregates; the absence of postocclusive hyperemia was determined by an occlusive test. Secondary bacterial infection led to an even greater aggravation of microcirculation disorders: an increase of the perivascular zone, the progression of intravascular aggregation resulting in microthrombosis with a decrease of the density of the capillary network (according to capillaroscopy), as well as a sharp decrease of amplitude maximal increment of blood flow of post-осclusive circulation at the time of an occlusive sample. We also revealed a trend of negative correlation between the level of serum proadrenomedullin and the maximum increase in blood flow during the occlusive test. Conclusion. The secondary bacterial infection in patients with COVID-19 leads to a significant aggravation of microcirculation disorders with the development of perfusion deficiency and interstitial edema. The increased plasma proadrenomedullin level supports the concept of the significant role of endothelial dysfunction in the pathogenesis of severe COVID-10 and bacterial sepsis.

Epidemiology of ventilator-associated pneumonia in ICU COVID-19 patients: an alarming high rate of multidrug-resistant bacteria

BackgroundCOVID‑19 is a novel cause of acute respiratory distress syndrome (ARDS) that leads patients to intensive care unit (ICU) admission requiring invasive ventilation, who consequently are at risk of developing of ventilator‑associated pneumonia (VAP). The aim of this study was to assess the incidence, antimicrobial resistance, risk factors, and outcome of VAP in ICU COVID-19 patients in invasive mechanical ventilation (MV).MethodsObservational prospective study including adult ICU admissions between January 1, 2021, and June 31, 2021, with confirmed COVID-19 diagnosis were recorded daily, including demographics, medical history, ICU clinical data, etiology of VAPs, and the outcome. The diagnosis of VAP was based on multi-criteria decision analysis which included a combination of radiological, clinical, and microbiological criteria in ICU patients in MV for at least 48 h.ResultsTwo hundred eighty-four COVID-19 patients in MV were admitted in ICU. Ninety-four patients (33%) had VAP during the ICU stay, of which 85 had a single episode of VAP and 9 multiple episodes. The median time of onset of VAP from intubation were 8 days (IQR, 5–13). The overall incidence of VAP was of 13.48 episodes per 1000 days in MV. The main etiological agent was Pseudomonas aeruginosa (39.8% of all VAPs) followed by Klebsiella spp. (16.5%); of them, 41.4% and 17.6% were carbapenem resistant, respectively. Patients during the mechanical ventilation in orotracheal intubation (OTI) had a higher incidence than those in tracheostomy, 16.46 and 9.8 episodes per 1000-MV day, respectively. An increased risk of VAP was reported in patients receiving blood transfusion (OR 2.13, 95% CI 1.26–3.59, p = 0.005) or therapy with Tocilizumab/Sarilumab (OR 2.08, 95% CI 1.12–3.84, p = 0.02). The pronation and PaO2/FiO2 ratio at ICU admission were not significantly associated with the development of VAPs. Furthermore, VAP episodes did not increase the risk of death in ICU COVID-19 patients.ConclusionsCOVID-19 patients have a higher incidence of VAP compared to the general ICU population, but it is similar to that of ICU ARDS patients in the pre-COVID-19 period. Interleukin-6 inhibitors and blood transfusions may increase the risk of VAP. The widespread use of empirical antibiotics in these patients should be avoided to reduce the selecting pressure on the growth of multidrug-resistant bacteria by implementing infection control measures and antimicrobial stewardship programs even before ICU admission.

Efficacy and safety of acetylcysteine for the prevention of liver injury in COVID-19 intensive care unit patients under treatment with remdesivir.

Aim:The present double-blinded placebo-controlled randomized clinical trial evaluated prophylactic use of acetylcysteine for the prevention of liver injury in patients with severe COVID-19 pneumonia under treatment with remdesivir.Background:Liver injury is reportedly common in patients with severe COVID-19 pneumonia and can occur not only as a result of disease progression, but as an iatrogenic reaction to remdesivir.Methods:A total of 83 adult patients with severe COVID-19 pneumonia were randomly assigned in parallel groups to receive either acetylcysteine or placebo. All the patients received standard care according to institutional protocols, including remdesivir for a total of five days. One gram acetylcysteine was administered intravenously every 12 hours for 42 patients, and 41 patients received the same volume of 0.9% sodium chloride as placebo (Trial Registration: www.irct.ir identifier, IRCT20210726051995N1). Results:After 5 days, median aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly lower in the acetylcysteine than in the placebo group. Of those who received the placebo, 30 (73.2%), 4 (9.7%), and 3 (7.3%) patients had serum AST levels elevated between 1-2.5, 2.5-5, and over 5 times the upper limit of normal (ULN), respectively; while in the acetylcysteine group, 33 (78.6%) and 0 patients had AST levels between 1-2.5 and over 2.5 times ULN, respectively (p-value=0.037). In the acetylcysteine group, 23 (54.8%), 1 (2.4%), and 1 (2.4%) patient had serum ALT levels elevated between 1-2.5, 2.5-5, and over 5 times ULN, respectively; in the placebo group, however, 24 (58.5%), 7 (17.1%), and 1 (2.4%) patient had serum ALT levels between 1-2.5, 2.5-5, and over 5 times ULN, respectively (p-value=0.073). Conclusion:Intravenous administration of acetylcysteine significantly prevents liver transaminases elevation and liver injury in seriously ill COVID-19 patients treated with remdesivir.

Yoğun Bakım Ünitesindeki Geriatrik COVID-19 Hastalarının Özellikleri ve Mortalite Prodüktörleri: Retrospektif Klinik Çalışma

Objective: Although coronavirus disease-2019 (COVID- 19) is seen in all age groups, the disease may progress more severely in adults with geriatric patients and comorbidities. We aimed to determine mortality rates and factors that may affect mortality by comparing the demographic, clinical, laboratory and radiological characteristics of different geriatric age groups. Material and Methods: A total of 444 COVID-19 intensive care unit (ICU) patients aged ≥65 years who were diagnosed with COVID-19 (real-time polymerase chain reaction positive) were included in the study. The patients were classified into 3 groups according to their age: younger-aged (65-74 years old), middle-aged (75-84 years old) and advanced-aged (≥85 years old) and the groups were compared. Results: The most common hospital admission symptom of total of 444 (73.2%) patients was dyspnoea. There was a statistical difference between genders in three groups (p<0.001). There was no difference between the mortality rates of the 3 groups (p=0.097). According to multiple logistic regression analysis, age ≥85 years, lactate dehydrogenase (LDH), procalcitonin and myalgia/joint pain were determined to be the risk factors that may affect mortality (p values 0.01, 0.025, 0.033 and 0.01, respectively). Conclusion: In geriatric COVID-19 ICU patients, advanced-age (≥85 years), male gender, laboratory parameters (e.g., interleukin-6, ferritin, procalcitonin, LDH) and, dyspnoea are the risk factors that increased mortality. Mortality rate was similar in geriatric groups.

Factores relacionados con la neumonía bacteriana en pacientes con COVID-19 en una unidad de cuidados intensivos de Barranquilla, Colombia

ObjectiveTo determine the factors related to bacterial pneumonia in patients with COVID-19 in an intensive care unit in Barranquilla, Colombia. DesignNested, single-center case-control study, conducted between March and August 2020. PatientsPatients over 18 years of age, a hospital stay greater than 72h, with invasive mechanical ventilation support admitted to the intensive care unit. InterventionsNone. MeasurementsClinical variables were grouped for both cases and controls. Means and standard deviation were calculated in quantitative variables and proportions in categorical variables. Fisher's exact test was used to evaluate the differences between proportions, and the Mann-Whitney U test was used for differences in means. Variables with statistically significant differences were run in an explanatory model based on binary logistic regression. ResultsThe frequency of bacterial pneumonia was 10.07%, finding a high consumption of empirical antibiotic therapy. A statistical association was found between the time of dexamethasone use (OR 1.520; 95% CI 1.131-2.042) with the development of bacterial pneumonia. The rest of the variables were not statistically significant after adjusting the model with logistic regression. ConclusionLow rates of bacterial pneumonia were found, with Klebsiella pneumoniae prevailing as the most frequent bacterium. Overuse of dexamethasone in intensive care unit COVID-19 patients could increase the risk of bacterial pneumonia. For this reason, it must be evaluated in greater depth to explain causality and effect.

Data and Network Analytics for COVID-19 ICU Patients: A Case Study for a Spanish Hospital.

The COVID-19 pandemic presents unprecedented challenges to the healthcare systems around the world. In 2020, Spain was among the countries with the highest Intensive Care Unit (ICU) hospitalization and mortality rates. This work analyzes data of COVID-19 patients admitted to a Spanish ICU during the first wave of the pandemic. The patients in our study either died (deceased patients) or were discharged from the ICU (non-deceased patients) and underwent the following landmarks: beginning of symptoms; arrival at the emergency department; beginning of the hospital stay; and ICU admission. Our goal is to create a graph-based data-science methodology to find associations among patients' comorbidities, previous medication, symptoms, and the COVID-19 treatment, and to analyze their evolution across landmarks. Towards that end, we first perform a hypothesis test based on bootstrap to identify discriminative features among deceased and non-deceased patients. Then, we leverage graph-based representations and network analytics to determine pairwise associations and complex relations among clinical features. The descriptive statistical analysis confirms that deceased patients exhibit multiple comorbidities with stronger levels of association and are treated with a wider range of drugs during the ICU stay. We also observe that the most common treatment was the simultaneous administration of lopinavir/ritonavir with hydroxychloroquine, regardless of the patients' outcome. Our results illustrate how graph tools and representations yield insights on the relations among comorbidities, drug treatments, and patients' evolution. All in all, the approach puts forth a new data-analysis tool for clinicians that can be applied to analyze (post-COVID) symptom/patient evolution.

Incidence of Pneumothorax and Pneumomediastinum in 497 COVID-19 Patients with Moderate-Severe ARDS over a Year of the Pandemic: An Observational Study in an Italian Third Level COVID-19 Hospital.

(1) Background: COVID-19 is a novel cause of acute respiratory distress syndrome (ARDS). Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, there has also been an increase in the incidence of cases with pneumothorax (PNX) and pneumomediastinum (PNM). However, the incidence and the predictors of PNX/PMN in these patients are currently unclear and even conflicting. (2) Methods: The present observational study analyzed the incidence of barotrauma (PNX/PNM) in COVID-19 patients with moderate–severe ARDS hospitalized in a year of the pandemic, also focusing on the three waves occurring during the year, and treated with positive-pressure ventilation (PPV). We collected demographic and clinical data. (3) Results: During this period, 40 patients developed PNX/PNM. The overall incidence of barotrauma in all COVID-19 patients hospitalized in a year was 1.6%, and in those with moderate–severe ARDS in PPV was 7.2% and 3.8 events per 1000 positive-pressure ventilator days. The incidence of barotrauma in moderate–severe ARDS COVID-19 patients during the three waves was 7.8%, 7.4%, and 8.7%, respectively. Treatment with noninvasive respiratory support alone was associated with an incidence of barotrauma of 9.1% and 2.6 events per 1000 noninvasive ventilator days, of which 95% were admitted to the ICU after the event, due to a worsening of respiratory parameters. The incidence of barotrauma of ICU COVID-19 patients in invasive ventilation over a year was 5.8% and 2.7 events per 1000 invasive ventilator days. There was no significant difference in demographics and clinical features between the barotrauma and non-barotrauma group. The mortality was higher in the barotrauma group (17 patients died, 47.2%) than in the non-barotrauma group (170 patients died, 37%), although this difference was not statistically significant (p = 0.429). (4) Conclusions: The incidence of PNX/PNM in moderate–severe ARDS COVID-19 patients did not differ significantly between the three waves over a year, and does not appear to be very different from that in ARDS patients in the pre-COVID era. The barotrauma does not appear to significantly increase mortality in COVID-19 patients with moderate–severe ARDS if protective ventilation strategies are applied. Attention should be paid to the risk of barotrauma in COVID-19 patients in noninvasive ventilation because the event increases the probability of admission to the intensive care unit (ICU) and intubation.

Association of cardiometabolic microRNAs with COVID-19 severity and mortality.

AimsCoronavirus disease 2019 (COVID-19) can lead to multiorgan damage. MicroRNAs (miRNAs) in blood reflect cell activation and tissue injury. We aimed to determine the association of circulating miRNAs with COVID-19 severity and 28 day intensive care unit (ICU) mortality.Methods and resultsWe performed RNA-Seq in plasma of healthy controls (n = 11), non-severe (n = 18), and severe (n = 18) COVID-19 patients and selected 14 miRNAs according to cell- and tissue origin for measurement by reverse transcription quantitative polymerase chain reaction (RT–qPCR) in a separate cohort of mild (n = 6), moderate (n = 39), and severe (n = 16) patients. Candidates were then measured by RT–qPCR in longitudinal samples of ICU COVID-19 patients (n = 240 samples from n = 65 patients). A total of 60 miRNAs, including platelet-, endothelial-, hepatocyte-, and cardiomyocyte-derived miRNAs, were differentially expressed depending on severity, with increased miR-133a and reduced miR-122 also being associated with 28 day mortality. We leveraged mass spectrometry-based proteomics data for corresponding protein trajectories. Myocyte-derived (myomiR) miR-133a was inversely associated with neutrophil counts and positively with proteins related to neutrophil degranulation, such as myeloperoxidase. In contrast, levels of hepatocyte-derived miR-122 correlated to liver parameters and to liver-derived positive (inverse association) and negative acute phase proteins (positive association). Finally, we compared miRNAs to established markers of COVID-19 severity and outcome, i.e. SARS-CoV-2 RNAemia, age, BMI, D-dimer, and troponin. Whilst RNAemia, age and troponin were better predictors of mortality, miR-133a and miR-122 showed superior classification performance for severity. In binary and triplet combinations, miRNAs improved classification performance of established markers for severity and mortality.ConclusionCirculating miRNAs of different tissue origin, including several known cardiometabolic biomarkers, rise with COVID-19 severity. MyomiR miR-133a and liver-derived miR-122 also relate to 28 day mortality. MiR-133a reflects inflammation-induced myocyte damage, whilst miR-122 reflects the hepatic acute phase response.

Does Fibrin Structure Contribute to the Increased Risk of Thrombosis in COVID-19 ICU Patients?

Introduction: SARS-CoV-2 is responsible for a global pandemic, with almost 200 million confirmed cases. SARS-CoV-2 infection can lead to various disease states, from only mild symptoms in the majority of cases to severe disease, which is associated with an increased incidence of venous thromboembolism (VTE). We hypothesized that an altered fibrin network structure contributes to VTE in COVID-19 patients by affecting thrombus stability and fibrinolysis sensitivity. By studying the fibrin network of COVID-19 patients, we aimed to unravel the mechanisms that contribute to the increased risk of VTE in COVID-19 patients.Methods: Between April 2020 and December 2020, we collected plasma samples from patients with COVID-19 admitted to the intensive care unit (ICU) of the Erasmus Medical Center. We included patients with confirmed VTE diagnosed on CT-angiography, and COVID-19 patients without confirmed VTE during ICU admission. Samples were collected on admission to the ICU and after confirmed VTE or at similar time points in ICU patients without confirmed VTE. In addition, we collected plasma from COVID-19 patients at admission to general wards without confirmed VTE and from healthy controls. Clots were formed by mixing citrated plasma with thrombin (final concentration 1 U/ml) and calcium (17 mM). We imaged the clots using stimulated emission depletion (STED) microscopy, a super-resolution technique in which a depletion laser is used to selectively switch off fluorophores surrounding the focal point, thereby increasing the resolution. In these images, fibrin fiber diameters were measured using the Local Thickness plugin of ImageJ. Fiber density was quantified as percentage of area in Z-stacks of confocal microscopy images. Finally, a clot lysis assay based on turbidity was used to determine sensitivity to fibrinolysis (clot lysis time) and clot density (difference between maximum and baseline absorbance). Differences in fibrin network properties between groups were tested using One-Way ANOVA with Bonferroni post-hoc tests and linear regression with and without adjustment for fibrinogen levels.Results: We included 21 COVID-19 ICU patients with confirmed VTE, 20 COVID-19 ICU patients without confirmed VTE, 10 COVID-19 ward patients and 7 healthy controls. Mean age was comparable between the groups, while BMI was higher in COVID-19 patients than in healthy controls (Table 1). Levels of fibrinogen, D-dimer and anti-Xa were significantly higher in COVID-19 ICU patients than in COVID-19 ward patients and healthy controls. FVIII levels were significantly higher in COVID-19 ICU patients than in healthy controls, while FXIII levels were significantly lower.On admission to the ICU, clot density was significantly higher in COVID-19 ICU patients with and without confirmed VTE than in healthy controls (Figure 1 and Table 2). However, after adjustment for fibrinogen levels, this difference disappears. Clot lysis time was significantly longer in clots from COVID-19 ICU patients than in clots from healthy controls, regardless of fibrinogen levels (Table 2). COVID-19 ICU patients with confirmed VTE also showed a significant longer clot lysis time than COVID-19 ward patients. Interestingly, in the clot lysis assay, fibrinolysis did not occur in 25% of COVID-19 ICU patients with VTE versus 9.5% of COVID-19 ICU patients without VTE (Figure 2). This fibrinolysis shutdown was never observed in clots from healthy controls and COVID-19 ward patients. Fibrin fiber diameters were comparable between the groups.In the clots from plasma samples collected at admission to the ICU, there were no differences between COVID-19 ICU patients with and without VTE (Figure 2). However, when comparing clots prepared from plasma collected at the second time point (after VTE or at a similar time point for patients without VTE), we observed significant longer clot lysis times in patients with confirmed VTE (97.4 [88.5-158.8] min) than in patients without confirmed VTE (80.0 [76.0-97.8] min) (p=0.03).Finally, there were no significant changes between clots from plasma before and after VTE or between the two time points in patients without VTE, except for a decreased clot lysis time over time for COVID-19 ICU patients without confirmed VTE.Conclusion: Our results suggest that SARS-CoV-2 infection increases clot density and decreases clot susceptibility to fibrinolysis, and that these changes relate to the severity of the disease. [Display omitted] DisclosuresKruip: Daiichi Sankyo: Research Funding; Bayer: Honoraria, Research Funding.

Mortality and bleeding complications of COVID-19 critically ill patients with venous thromboembolism.

Venous thromboembolism (VTE) disease in COVID-19 patients is a remarkable issue, especially its relationship with bleeding events and mortality. The objective of this study was to describe the outcomes of critically ill patients with COVID-19, hospitalized in the Intensive Care Unit (ICU), in relationship with VTE during their stay. This is a prospective cohort study of critically ill COVID-19 patients in two hospitals that underwent a venous ultrasound at the beginning of follow-up of both lower limbs in April 2020. In case of clinical suspicion of new VTE during the 30-day follow-up, additional ultrasound or thoracic CT were performed. Global VTE frequency, major bleeding events and survival were collected, and their predictors were studied. We included 230 patients. After 30 days of follow-up, there were 95 VTE events in 86 patients (37.4%). Thirteen patients (5.7%) developed major bleeding complications and 42 patients (18.3%) died. None of the comorbidities or previous treatments were related with bleeding events. D-Dimer at admission was significantly related with VTE development and mortality. Independent predictors of mortality in the regression model were older age (>66 years), D-Dimer at admission (>1.500 ng/mL) and low lymphocyte count (<0.45×109/L) with an AUC in the ROC curve of 0.81 (95% CI: 0.73-0.89). Patients presenting these three conditions presented a mortality of 100% in the predictive model. VTE frequency in ICU COVID-19 patients is high and risk of major bleeding is low. Comorbidities and laboratory parameters of admission in these patients can be a useful tool to predict mortality.

The Use of Nasogastric Tube Bridle Kits in COVID-19 Intensive Care Unit Patients

The Use of Nasogastric Tube Bridle Kits in COVID-19 Intensive Care Unit Patients

Coronary arteries and aortic valve calcifications in COVID-19: Not only lungs at chest CT

Objectives: Cardiovascular diseases cause worse outcomes in patients affected by COVID-19. High coronary artery calcium score (CACS) and aortic valve calcifications (AC) increase cardiovascular risk. Our purpose is to evaluate CACS, measured by Weston Score (WS), and presence of AC in chest CT of COVID-19 patients and possibly to investigate their prognostic role. Material and methods: This retrospective case-control study includes 150 hospitalized COVID-19 patients who underwent a chest CT at admission. The case group (Group A) was formed by 50 in-patients in Intensive Care Unit (ICU) under invasive ventilation (IV), while the matching control group for sex, age and BMI (Group B) was formed by 100 in-patients in non-ICU units, not under IV. After, a second case-control selection was originated from these two Groups: the case group (Group A1) composed by 30 patients selected from Group A, and the matching control group for age, sex, BMI and CT lung severity score (LSS) (Group B1) composed by 60 patients selected from Group B. WS and the presence of AC were compared between Groups A and B, and between Groups A1 and B1. Moreover, LSS and WS were correlated. Parametric tests were used for statistical analysis. Material and methods: This retrospective case-control study includes 150 hospitalized COVID-19 patients who underwent a chest CT at admission. The case group (Group A) was formed by 50 in-patients in Intensive Care Unit (ICU) under invasive ventilation (IV), while the matching control group for sex, age and BMI (Group B) was formed by 100 in-patients in non-ICU units, not under IV. After, a second case-control selection was originated from these two Groups: the case group (Group A1) composed by 30 patients selected from Group A, and the matching control group for age, sex, BMI and CT lung severity score (LSS) (Group B1) composed by 60 patients selected from Group B. WS and the presence of AC were compared between Groups A and B, and between Groups A1 and B1. Moreover, LSS and WS were correlated. Parametric tests were used for statistical analysis. Results: Among the 150 patients, 105 (70.0%) were male and 45 (30.0%) female. The age was 70.2 ± 13.3 years. LSS was 7.5 ± 3.9, WS was 6.4 ± 3.0; AC was present in 97/150 (64.7%). WS was significantly higher in Group A than in Group B, respectively, 7.4 ± 4.0 and 5.7 ± 2.6 (p=0.0146), and also the presence of AC, respectively, 41/50 (82.0%) vs 56/100 (56.0%) (p=0.0016). In Group B, LSS and WS had a linear positive correlation (r=0.2240, p=0.0405). Finally, WS and AC were significantly higher in Group A1 compared to Group B1. Conclusions: Both WS and AC were higher in ICU COVID-19 patients than in non-ICU COVID-19 patients: they could have a predictive role in the pejorative evolution of the disease.