ICU without walls = ICU without Data? the Covid-19 deficit

Introduction: Northern Ireland (NI) has 5.5 ICU beds/100 000 population,1 amongst the lowest in Western Europe.2 Alongside ICU bed expansion the Covid-19 response required delivery of advanced Respiratory support (Continuous Positive Airway Pressure (CPAP) and High Flow Nasal Oxygen (HFNO)) outside ICU. ICNARC provides robust data for patients within ICU but this is unavailable for those receiving 'critical care' elsewhere. Objective(s): To evaluate delivery of CPAP/HFNO outside of ICU to Covid-19 patients - focusing on demographics and outcomes including ICU admission and mortality. Method(s): Ward-CPAP for acute hypoxaemic respiratory failure (AHRF) was not previously utilised.3 It was introduced for Covid-19 to Medical wards. Data was analysed using the NI Electronic Care Record, ward electronic note system (EDAMS) and ICU system (ICCA, Koninklijke Philips N.V.). Data was compared between Wave 1 (01/03/2020 - 12/12/2020) and Wave 2 (13/12/2020 - 01/04/2021). Result(s): 215 patients received CPAP/HFNO/Invasive Mechanical Ventilation (IMV) for Covid-19: 103 in Wave 1 and 112 in Wave 2. 75 Covid-19 patients were admitted to the ICU itself (comprising 44 of the study cohort, 11 direct from ED and 20 transferred from other Trusts). Table 1 shows demographics. Fewer patients were female as seen elsewhere,4 there were more young patients in Wave 2. The majority of patients would likely have been ICU candidates pre-pandemic,3 but a subset of 25% were deemed for a ward ceiling-of-care on admission by a Consultant and the proportion of elderly patients was higher than described by ICNARC.4 Comorbidities and obesity were common. Outcomes are shown in Table 2 and Figures 1-3. Close co-operation with ICU saw 61% of patients with a documented ICU review. Overall 20% of patients were admitted to ICU, and 15% received IMV. Mortality was 37%, but 22% if patients with an admission ward ceiling-of-care decision were excluded. Mortality correlated with frailty and age (fig 2&3). Outcomes were generally better in Wave 2. Conclusion(s): This Evaluation documents the huge contribution to the critical care Covid-19 response made by our Medical teams, not captured by ICNARC. Most patients avoided ICU admission and IMV and outcomes were likely at least comparable which undoubtedly freed up vital ICU beds. We thank the teams involved and believe it is vital to evaluate the outcome of all critically ill Covid-19 patients irrespective of their location.

Single centre, cross-sectional assessment of airway hemorrhage in a cohort of patients with COVID19-associated ARDS under Venovenous extracorporeal membrane oxygenation

Objectives: Airway hemorrhage (AH) frequently complicates extracorporeal membrane oxygenation (ECMO) treatment. Inflammation, coagulopathy and antithrombotic therapy are contributing factors. Patients with COVID-19- associated ARDS (CARDS) supported with ECMO present all these features. We aim to characterize the incidence and the clinical and prognostic impact of AH. Method(s): Review of a cohort of patients with CARDS treated with ECMO support at a single ECMO centre between March 2020-February 2022 (n=92). AH was defined as a clinically significant hemorrhage fit demanded interruption of anticoagulation, transfusional support or bronchoscopy. Univariate analysis was performed using GraphPadPrism. Result(s): One third (n= 31) of patients with CARDS treated with ECMO had clinically significant AH. Patients who developed AH had significantly longer ICU length-of-stay (LoS), ECMO run and invasive mechanical ventilation (IMV) duration. Significant differences in coagulation and inflammatory markers were detected between patients with early (<72h) versus late (>9 days) onset of AH (Table 1). Mortality at day 90, demographics, comorbidities, CT scan pattern and clinical severity indexes were similar between patients with and without AH (NAH). Conclusion(s): In patients with severe CARDS treated with ECMO support, the occurrence of airway hemorrhage leads to clinically important morbidity but does not increase mortality. Distinct pathways may be involved in the development of early v. late AH. (Table Presented).

Clinical characteristics and risk factors of patients with COVID-19 developing barotrauma

Background: At our hospital, people with COVID-19 (coronavirus disease 2019) had a high rate of pulmonary barotrauma. Therefore, the current study looked at barotrauma in COVID-19 patients getting invasive and non-invasive positive pressure ventilation to assess its prevalence, clinical results, and features. Methodology: Our retrospective cohort study comprised of adult COVID-19 pneumonia patients who visited our tertiary care hospital between April 2020 and September 2021 and developed barotrauma. Result(s): Sixty-eight patients were included in this study. Subcutaneous emphysema was the most frequent type of barotrauma, reported at 67.6%;pneumomediastinum, reported at 61.8%;pneumothorax, reported at 47.1%. The most frequent device associated with barotrauma was CPAP (51.5%). Among the 68 patients, 27.9% were discharged without supplemental oxygen, while 4.4% were discharged on oxygen. 76.5% of the patients expired because of COVID pneumonia and its complications. In addition, 38.2% of the patients required invasive mechanical breathing, and 77.9% of the patients were admitted to the ICU. Conclusion(s): Barotrauma in COVID-19 can pose a serious risk factor leading to mortality. Also, using CPAP was linked to a higher risk of barotrauma.Copyright © 2021 Muslim OT et al.

Utility of the Brixia CXR score, C-Reactive Protein and Absolute Neutrophil Count in Predicting the Need for Invasive Mechanical Ventilation, Length of Hospital Stay, and Mortality in Moderate to Severe COVID-19 Patients

Background: The Brixia Chest X-ray (CXR) score, C-reactive protein (CRP), and the absolute neutrophil count (ANC) have been useful to predict outcomes in Coronavirus disease 2019 (COVID-19 patients). We studied the utility of the Brixia CXR score, CRP, and ANC in predicting the outcomes in terms of the need for invasive mechanical ventilation, length of stay, and mortality in moderate-severe COVID-19 patients. Material(s) and Method(s): This was a single-centre, retrospective, study on 122 COVID-19 patients. Brixia CXR score, CRP, and ANC on admission to the hospital and the fifth day of hospital stay were noted along with the need for invasive mechanical ventilation (IMV), prolonged length of stay (LOS) >= 14 days, and mortality. Result(s): 122 patients were included for analysis. The median and interquartile range (IQR) for baseline CRP was 81.50 (39-151) mg/L and 11.0 (4-30) mg/L (p < 0.001) on the fifth day. The median and IQR for baseline Brixia score was 10.0 (7-13), and on the fifth day was 7 (4-11) (p <0.001). The receiver operating characteristic curve (ROC) showed that the baseline CRP >= 52.5mg/L predicted both the need for IMV, with an area under the curve (AUC) of 0.628, and prolonged LOS with an AUC of 0.608. The ROC curve depicted that the baseline ANC >8500/muL predicted IMV requirement with an AUC of 0.657. The fifth day CRP >= 32 mg/L, ANC >= 11,000/ muL and Brixia CXR score >= 7 predicted a higher mortality in hospitalized patients. Conclusion(s): Baseline CRP (> 52.5mg/L) predicts the need for IMV and a prolonged LOS, but not mortality. Baseline ANC (> 8500/muL) predicted the need for IMV. CRP, Brixia CXR score, and ANC on the fifth day were not useful to predict LOS or mortality, though there was a significant reduction in CRP and Brixia CXR score on the fifth day compared to baseline after treatment. The fifth day CRP >= 32 mg/L, ANC >= 11,000/ muL and Brixia CXR score >= 7 predicted a higher mortality.Copyright © 2023, College of Anaesthesiologists of Sri Lanka. All rights reserved.

The impact of proning on nutritional therapy in mechanically ventilated COVID-19 patients

Introduction: Critically ill COVID-19-patients are at high risk of developing ICU-related malnutrition. This study aimed to examine the impact of proning on providing nutritional therapy for mechanically ventilated COVID-19-patients by comparing the achievement of nutritional goals and possible complications in patients who were proned vs. those who were not. Method(s): This is a single-center retrospective cohort study. We included all adult COVID-19 patients admitted to the ICU from 01/03/2020 until 31/05/2020 who required invasive mechanical ventilation (IMV), excluding those referred for ECMO. Data were extracted from electronic patient files. Weight-based nutrition targets were set in agreement with ESPEN guidelines [1]. Result(s): 32 patients were included (prone n = 16). Both groups were comparable in age, sex, comorbidities, biochemical markers and Nutrition Risk Screening on admission. Time on IMV was longer in the prone group (p = 0.032). The total time in prone position ranged from 19.5 h to 13.16 d. All patients received a NG tube, 1 proned patient received a jejunal tube. 6 received TPN (p = 0.654). Metoclopramide was used more often in the prone group (p = 0.028). The prevalence of vomiting (n = 4 vs. n = 5), large gastric residuals (n = 0 vs. n = 3) and VAP (n = 11 vs. n = 10) were comparable for the non-prone vs. prone group, resp. Table 1 shows the percentage of targets reached. These were lower in the prone group, though not statistically significant. However, when correcting for SAPS III-score, the impact of proning declined. Conclusion(s): These limited data suggest there is no significant difference in feeding COVID-19 patients on IMV that need proning vs. those who do not, except for metoclopramide use. Overall, reaching nutrition targets in these patients is challenging. This model suggests that disease impact is a greater influence on reaching nutritional goals than proning itself.

Remdesivir Reduces Mortality in Hospitalized Covid-19 Patients across Variant Eras

Background: Clinical management of COVID-19 based on oxygenation requirements continues to change over time as variants of concern (VOC) evolve. We examine hospital all-cause mortality for early hospital RDV use vs. no RDV use across dominant VOC periods: pre-Delta (Dec'20-Apr'21), Delta (May-Nov'21) and Omicron (Dec'21-Apr'22). Method(s): We examined adults with a primary discharge diagnosis of COVID-19 (ICD-10: U07.1) using the Premier Healthcare Database. Patients treated with RDV in the first 2 days of admission vs. those not treated with RDV during the hospitalization were matched using a 1:1 preferential within-hospital propensity matching with replacement. Patients were excluded if discharged within 3 days of RDV initiation. Time to mortality at 14-and 28-days was examined for patients with no supplemental oxygen charges (NSOc), low-flow oxygen (LFO), high-flow oxygen/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) at baseline. Baseline was defined as first 2 days of hospitalization. Result(s): 164,791 RDV-treated patients were matched to 48,473 unique non-RDV patients. Post-matching balance was achieved across groups with different baseline oxygenation levels and VOC periods. In the matched weighted cohort, 35% required NSOc, 41% LFO, 21% HFO/NIV and 3% IMV/ECMO. During the overall study period (Dec'20-Apr'22), unadjusted mortality rate was significantly lower for RDV patients across all oxygenation levels at 14 days (NSOc: 5.4% vs. 7.3%, LFO: 6.4% vs. 8.8%, HFO/NIV: 16.8% vs. 19.4%, IMV/ECMO: 27.8% vs. 35.3%) and 28 days (NSOc: 8.0% vs. 9.8%, LFO: 9.8% vs. 12.3%, HFO/ NIV: 25.8% vs. 28.3%, IMV/ECMO: 41.4% vs. 50.6%). After adjusting for baseline and clinical covariates, 14-day mortality results showed that RDV significantly lower risk compared to non-RDV across all oxygenation levels at baseline [NSO (26%), LFO (28%), HFO/NIV (17%), IMV/ ECMO (27%)]. Similarly, 28-day mortality results showed that RDV significantly lower risk compared to non-RDV across all oxygenation levels at baseline [NSO (19%), LFO (21%), HFO/NIV (12%), IMV/ECMO (26%)]. This lower mortality risk associated with RDV was consistently observed across all variant periods (Figure). Conclusion(s): Timely initiation of RDV within first two days of hospital admission demonstrated significant mortality reduction in patients hospitalized for a primary diagnosis of COVID-19 across all oxygenation levels. Remdesivir demonstrated consistent benefit across all variant periods of the pandemic to-date.

Association between pulmonary extravascular water, dead space, and clinical outcome in intubated patients with COVID ARDS

Introduction: The aim of this study was to determine whether there is an association between extravascular lung water index (EVLWi) and physiological respiratory dead space (VDphys/VT) and to determine if these factors are associated with the possibility to being discharged alive on day 28. Method(s): We analyzed a prospective cohort of patients with COVID ARDS supported with invasive mechanical ventilation (IMV) admitted in our ICU who were monitored with volumetric capnography and transpulmonary thermodilution (TPTD). First day TDTP and VDphys/VT were considered. Bohr-Enghoff formula was used to obtain VDphys/ VT. This protocol was approved by the local IRB and informed consent was waived. Result(s): 31 patients with matched TPTD and VDphys/VT during the first 24 h were analyzed in who EVLWi correlated with VDphys/VT (r = 0.599 p = 0.002), however, EVLWi did not associated with PaFi. Patients with EVLWi > 10 ml/kg had higher APACHE II and VDphys/VT. These patients had a lower cumulative incidence to be discharged alive on day 28 with aHR 7.3 [1.4-39.1] p = 0.02 (adjusted by APACHE II and VDphys/VT, Fig. 1A). Remarkably, patients with EVLWi > 10 ml/ kg + VDphys/VT > 57% had worse outcome compared to those who had EVLWi > 10 ml/kg + VDphys/VT < 57% (25% vs 75%, p = 0.032, Fig. 1B). Conclusion(s): In patients with COVID ARDS supported with IMV, VDphys/VT give prognostic data additional to EVLWi.

A Joint Analysis of Two Randomized Controlled Trials on Enoxaparin for Covid-19

Background: COVID-19 carries a high risk of vascular thrombosis. This joint analysis of two randomized-controlled trials (RCTs) aims to assess the safety and efficacy of enoxaparin at therapeutic dose compared to prophylactic dose in people hospitalized with COVID-19. Method(s): A joint analysis of two RCTs, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), was performed. Both studies enrolled inpatients with COVID-19- associated respiratory compromise (as identified by respiratory rate >=25 breaths/min or arterial oxygen saturation <=93% at rest or PaO2/FiO2 <=300 mmHg for COVID-19 HD and by PaO2/FiO2 <=250 mmHg for EMOS-COVID) and/or coagulopathy (D-dimer > 2000 ng/ml for both RCTs or sepsis-Induced coagulopathy score >4 for COVIDHD). In both RCTs patients were randomly assigned to two arms: enoxaparin at prophylactic dose (standard 4.000 IU;in the EMOS-COVID 6000 IU if body weight >100 kg) and at therapeutic dose (70 U/Kg every 12 h). The primary efficacy endpoint of the joint analysis was clinical worsening, defined as the occurrence of at least one among: in-hospital death;acute myocardial infarction;symptomatic arterial or venous thromboembolism;need of either Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) in patients who were in standard oxygen therapy at randomization;need for IMV in any patient. The primary outcome was assessed as time-to-event, described with hazard ratio (HR) and with Kaplan-Meier survival estimate. The primary safety endpoint was major bleeding for both trials and for the joint analysis. Result(s): COVID-19 HD enrolled 142 people between July 2, 2020 and February 15, 2022, while EMOS-COVID enrolled 141 people from July 27, 2020 to June 5, 2021, resulting in 283 patients included in this joint analysis. Two-hundredseven (73.1%) were males, with a mean age of 61.1 years (SD +/-10.7), a mean BMI of 29.7 kg/m2 (SD +/-5.0), and 115 (40.6%) were on NIV or Cpap at randomization, with no significant difference between the study groups. 21/139 people in the high dose group reached the primary endpoint compared to 32/144 in the prophylactic group (HR 0.63, 95%CI 0.36 to 1.10). Figure 1 shows the Kaplan- Meier survival estimates of clinical worsening. No major bleeding was observed during the study time. Conclusion(s): The results of this joint analysis did not highlight significant differences in clinical worsening between COVID-19 patients that received enoxaparin at therapeutic compared to prophylactic dose. (Figure Presented).

D-dimer-driven versus standard prophylactic anticoagulation with fondaparinux in critically ill patients with COVID-19 and coagulopathy: An open-label, randomized controlled trial

Background: Anticoagulation with fondaparinux (FPX) has shown benefit to improve clinical outcomes in hospitalized patients with COVID-19. However, optimal thromboprophylaxis dosing in critically ill patients remains unknown. Purpose(s): To evaluate the effects of D-dimer-driven (DDD) FPX compared with standard prophylactic-dose (SPD) FPX in critically ill patients with COVID-19 and associated coagulopathy. Method(s): This was a single-center, open-label, two-arms, parallel-group, randomized controlled trial conducted between April 1, 2021 and Feb 28, 2022. The eligible COVID-19 patients who were critically ill (defined as a presence of critical care-level organ support at enrollment) and presented with coagulopathy were randomly assigned (1:1 ratio) to receive pragmatically defined regimens of either DDD FPX or SPD FPX throughout hospitalization. The primary efficacy outcome was a composite of all-cause mortality (ACM), acute myocardial infarction (MI), confirmed arterial (ATE) or venous thromboembolisms (VTE), assessed up to 30 days. The secondary efficacy outcomes were 30-day ACM, composite thrombotic events, progression to invasive mechanical ventilation (IMV) or ARDS, and acute kidney injury (AKI). The safety outcomes included major bleeding and clinically relevant non-major bleeding (CRNMB). Outcomes were blindly adjudicated and analysed on a 30-day intention-to-treat basis. Result(s): During allocated period, 270 (58%) of 465 patients were eligible and were equally assigned to DDD and SPD groups. The baseline characteristics were well-matched between groups (all p>0.05). At 30 days, the primary efficacy outcome was met in 49 of 135 patients (36.3%) with DDD FPX versus 47 of 135 patients (34.8%) with SPD FPX (hazard ratio [HR], 1.32;95% CI, 0.89-1.98;p=0.17). DDD group compared with SPD group revealed no significant difference in 30-day ACM (22.9% vs 31.8%;HR, 0.73;p=0.17). At 30 days, DDD group demonstrated no significant reduction in thromboembolism, i.e. acute MI (14.1% vs 11.8%;HR, 1.53;p=0.21);ATE (3.0% vs 3.0%;HR, 1.27;p=0.74);and VTE (2.2% vs 4.4%;HR, 0.69;p=0.59) when compared with SPD group. Among those not on IMV at randomization, DDD group showed no significant reduction in the proportion of patients meeting the need for IMV (18.5% vs 32.6%;HR, 0.72;p=0.18) or progression to ARDS (17.8% vs 27.4%;HR, 0.81;p=0.43). Allocation to DDD FPX had no significant effect on the proportion of patients experiencing AKI within 30 days (17.8% vs 14.8%;HR, 1.36;p=0.39). There was no significant difference between DDD and SPD groups in terms of major bleeding (2.2% vs 0%;HR, 8.35;p=0.35) or CRNMB (3.0% vs 2.2%;HR, 1.70;p=0.48) at 30 days. Conclusion(s): In critically ill patients with COVID-19 and coagulopathy, D-dimer-driven anticoagulation with fondaparinux did not significantly improve clinical outcomes at 30 days as compared to standard prophylacticdose. The risk of bleeding was not significantly increased in this trial. (Table Presented).

Clinical efficacy and safety of ivermectin (400 mug/kg, single dose) in patients with severe COVID-19: a randomized clinical trial

Purpose: To evaluate the clinical efficacy of including Ivermectin (single dose on day 1 of 400 mug/kg PO) in the standard of care in hospitalized adults with severe COVID-19. Method(s): Double-blinded, parallel, placebo-controlled, single-center, randomized clinical trial. Seventy-five patients were randomly assigned (1:1) to receive standard of care plus ivermectin or placebo and were followed up for 21 days. Primary outcome measure was admission to ICU and secondary outcomes were the requirement of intensive mechanical ventilation (IMV) and in-hospital death. Intention-to-treat analyses, estimated risk differences (RD), and Hazard ratios (HR) with Cox regression were performed. Result(s): Enrollment stopped due to the lack of eligible patients. Thirty-seven patients were assigned to intervention and 38 to placebo. Patients in the ivermectin group were 54.5 years on average, 62.2% were male. Comorbidities were more prevalent in the control group (78.9% vs. 56.8%). There was no difference in the 21-day risk of admission to the ICU between ivermectin (21.6%) and placebo (15.8%) (RD= 5.8%;95%CI: -11.8%-23.5%);neither in the risk of requirement of IMV (18.9% vs 13.2%), mortality (5.4% vs 10.5%) or in adverse events (32.4% vs. 28.9%). Discussion(s): Ivermectin showed no significant benefit in reducing the requirement of ICU, IMV, or mortality for severe COVID-19 patients.Copyright © 2022 Asociacion Colombiana de Infectologia. All rights reserved.

Proteomic determinants of disease, mortality and sequelae in COVID-19 patients requiring invasive mechanical ventilation

Introduction: The molecular mechanisms linked to the pathology of severe COVID-19 and its outcomes are poorly described. Aim(s): To analyze the proteomic profile of bronchial aspirates (BAS) samples from critically ill COVID-19 patients in order to identify factors associated with the disease and its prognosis. Method(s): Multicenter study including 74 critically ill non-COVID-19 and COVID-19 patients. BAS was obtained by bronchoaspiration after invasive mechanical ventilation (IMV) initiation. Proximity extension assay (PEA) technology was used for proteomic profiling. Random forest (RF) statistical models were used to predict the variable importance. Result(s): After adjusting for confounding factors, CST5, NADK, SRPK2 and TGF-alpha showed differences between COVID-19 and non-COVID-19 patients. Reduced levels of ENTPD2 and PTN were observed in non-survivors, even after adjustment. AGR2, NQO2, IL-1alpha, OSM and TRAIL, were the top five strongest predictors for ICU mortality and were used to build a prediction model. PTN (HR=4.00) ENTPD2 (HR=2.14) and the prediction model (HR=6.25) were associated with higher risk of death. In survivors, FCRL1, NTF4 and THOP1 correlated with lung function (DLCO levels) 3-months after hospital discharge. Similar findings were observed for Flt3L and THOP1 and radiological features (TSS). The proteins identified are expressed in immune and non-immune lung cells. A poor control of viral infectivity and an inappropriate reparative response seems to be linked to the disease and fatal outcomes, respectively. Conclusion(s): In critically ill COVID-19 patients, specific proteomic profiles are associated with the pathology, mortality and lung sequelae.

Hospitalised patients with COVID-19: the impact of nosocomial infections

Introduction: COVID-19 is a disease caused by the SARS-CoV-2 virus. Healthcare-associated infections (HCAI) are infections acquired during a stay in a hospital or other healthcare setting that were not incubating at the time of admission. Objective(s): To describe the impact of HCAI in hospitalised patients with COVID-19. Method(s): A retrospective and descriptive study of hospitalised patients with COVID-19 in a Portuguese hospital in 2020 was conducted. Result(s): The sample consisted of 1110 patients of whom 229 acquired HCAI. The main comorbidities were hypertension 62.45% (n=143), obesity 24.01% (n=55), arrhythmias 20.52% (n=47), ischaemic heart 11.35% (n=26) and heart failure 16.16%. Infectious agents were isolated in 27.95% (n=64), with Escherichia coli and Klebsiella pneumoniae being the most frequent. HCAI's classification were: 5.68% (n=13) nosocomial bacteraemia 31.89% (n=73);urinary tract infection 54.15% (n=124);hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia 8.28% (n=19). Ventilatory support required: 14.85% (n=34) didn't require, 49.34% (n=113) conventional oxygen therapy (COT);2.62% (n=6) high flow therapy, 3.06% (n=7) non-invasive ventilation, 16.16% (n=37) HelmetCPAP, 12.66% (n=29) invasive mechanical ventilation (IMV) and 1.31% (n=3) ECMO. The mean number of days of admission was 14.84 (+/-13.67). The probability of death HCAI's patients was OR 1.63, 95% CI 1.154-2.304. Conclusion(s): The sample shows a high incidence of nosocomial infections. The most frequent HCAI were HAP mainly with clinical diagnosis. Clinical stabilisation of comorbidities and COT were effective for most patients but IMV and Helmet-CPAP for the most severe. HCAI are a high risk factor for mortality.

Posttraumatic-stress disorder, and others psychological impairment in COVID-19 surviving patients

Background: The post-COVID syndrome generates physical and respiratory complications that can be accompanied by psychological impairments, which can affect long-term mental and physical health. Objective(s): Know the prevalence and severity of PTSD, anxiety, and depression in surviving COVID-19 patients in a follow-up evaluation. Method(s): A cross-sectional descriptive study was conducted. 227 survivors COVID-19 patients participated, were assessed three months following discharge hospital. The following questionnaires were used: The Brief Davidson Trauma Scale, the General Anxiety Disorder Questionnaire, and the Patient Health Questionnaire. A descriptive and statically analysis was performed using the statistical software SPSS version 26. Result(s): The 64.5% of the patients were men, 60.9% required of invasive mechanical ventilation (IMV) during the hospitalization, the average age was about 48.23+/-14.33 years old. The 40% of the patients showed symptoms associated with PTSD, 38.4% anxiety symptoms, 36.6% depression symptoms. There were statistically significant differences between the type of treatment during hospitalization (IMV vs without IMV), in PTSD (t=2.482, df=223, p=.014, XIMV = 5.21, XWIMV = 6.08) and anxiety (t= -2.006, df=223, p=.046, XIMV = 4.05, XWIMV =5.44). Conclusion(s): Survivors of COVID-19 experience a high prevalence of PTSD, anxiety, and depression even three months after discharge from hospital. Patients who did not require IMV during hospitalization experienced a high prevalence and severity of PTSD and anxiety symptoms. Screening for PTSD and other emotional disturbances should be considered in follow-up evaluations in patients discharged from the hospital.

Interstitial changes after severe SARS-CoV-2 Infection

Introduction and aim: COVID19 pandemic caused by SARS-CoV-2 is associated with high morbidity and mortality rate worldwide,producing inflammation that can lead to persistent parenchymal lesions. The aim was to analyse the medium-long term evolution of patients with severe COVID19. Method(s): Follow-up of a cohort of 97 COVID19 patients admitted to intensive care unit from March 2020 to June 2021,requiring invasive/non-invasive mechanical ventilation (IMV/NIMV) and/or high-flow nasal cannula (HFNC). They were clinically evaluated in the Interstitial Diseases consult at 4-6 weeks after discharge with spirometry (SP),CO diffusion capacity (DLCO) and thoracic ultrasound (TU);those suggestive of mild interstitial changes (IC) were evaluated at 3 months and moderate-severe ones at 6 months with HRCT,SP and DLCO. Result(s): Mean age was 61+/-15 years (61% male) and hospital stay was 26+/-17 days.93% used HFNC,57% NIMV and 31% IMV. At 4-6 week after discharge assessment showed 45% dyspnea and 33% crackles. SP was normal in 63%,with mild DLCO disorders in 36% and 77% pathological TU. The most frequent abnormality on HRCT was ground glass. After clinical-functional and ultrasound-radiological evaluation at 4-6 weeks after COVID19,37% of cases were discharged,another 2% at 3 months,22% at 6 months and 7% at 12 months. The remaining 32% are still being followed up for persistent IC(6 receiving home oxygen therapy,6 treated with steroids and 4 with antifibrotic). Conclusion(s): Most patients with severe COVID19 infection have after discharge IC with mild clinical-functional impact at 4-6 weeks,although one third have persistent changes after 12 months. Medium to long-term follow-up of postCOVID19 patients is necessary to identify those with permanent abnormalities.

Risk factors for mortality in COPD patients with COVID19 admitted to Intensive Care Unit

Background and aim: Patients with Chronic obstructive pulmonary disease (COPD) and COVID-19 have increased risk of hospitalization and Instensive Care Unit (ICU) admission (1). Aims and objectives: To indentify risk factors for intrahospital mortality in COPD patients with COVID-19 admitted to Spanish ICUs. Method(s): Demographic and clinical data during ICU admission were recorded using REDCap on all patients hospitalized for COVID-19 in 70 Spanish ICUs (2). We described the baseline clinical characteristics of COPD compared to other chronic respiratory disease (CRD) and to the overall population. We identified the risk factors for intrahospital mortality of COPD patients receiving invasive mechanical ventilation (IMV) and for those COPD receiving noninvasive respiratory support (NIRS). Result(s): Two hundred and sixty-eight ICU patients (5%) had COPD out of 5196 included. No differences were found between COPD, CRD or the overall population in the rates of IMV (76-78%) vs NIRS (22-24%). COPD intrahospital mortality was much higher in the IMV subgroup (58%). Independent risk factors for intrahospital mortality in the COPD+IMV or COPD+NIRS were: age and chronic Kidney disease or hypertension, respectively. Previous NIRS in COPD+IMV group was protective for intrahospital mortality (Figure). Conclusion(s): New strategies are needed to reduce the high intrahospital and 90-days mortality of COPD COVID-19 patients admitted to ICU.

Serum markers of endothelial dysfunction and invasive mechanical ventilation in COVID-19

Introduction: Sars-Cov-2 infection induces vascular endothelium damage at pulmonary and systemic level. Alterations on immunity response generate inappropriate endothelial activation through pro-inflammatory cytokines release, up-regulated expression of adhesion molecules, leukocyte migration, increased nitric oxide requirements and oxidative stress. Endothelial function is a key feature in the pathogenesis of COVID-19. Objective(s): To evaluate circulating markers associated with endothelial activation in hospitalized patients with COVID-19 and determine the difference between patients who required invasive mechanical ventilation (IMV) and those who did not. Method(s): Cross-sectional study. Subjects with a confirmed diagnosis of COVID-19 and >18 years old were included. Patients who did not require hospitalization were excluded. Serum markers of endothelial function were tested during hospitalization and protein adjustment was performed. Result(s): A total of 390 patients were studied, with an average age of 57+/-13 years old. Patients who required invasive mechanical ventilation had higher prevalence of diabetes (34.53% vs 11.54%;p=0.020), higher serum nitrite levels (0.028 mmol/L [0.094-0.647] vs 0.07 [0.03-0.24];p=0.003), nitrates (0.363mmol/L [0.100- 0.591] vs 0.130[0.003-0.374];p=0.004) and E-selectin (1.00 ng/mg [0.79-1.32] vs 0.84 [0.55-1.09];p=0.019) when compared to non-IMV patients. Higher levels of nitrites adjusted by proteins were associated with an increased risk for IMV (OR 5.59, CI 95 1.15-27.00, p=0.032). Conclusion(s): Patients with increased nitrites and E-selectin levels had worse endothelial dysfunction and a higher risk for IMV during hospitalization.

COVID-19 treatment and outcomes: trends over 20 months in 338,930 US hospital patients with COVID-19 and pneumonia

Methods: This retrospective study included adults with COVID-19 (ICD-10: U07.1) and pneumonia (ICD-10 subcodes within J11.x - J16.x, J18.x) May 2020-December 2021 in the Premier Healthcare Database, analyzing severity, treatment patterns and clinical outcomes. Result(s): Between May 2020 and December 2021: N=338,930 patients in 856 hospitals 79% of patients received any dexamethasone(DEX);>50% received any remdesivir(RDV) Combination therapy use increased: DEX+RDV only from <1% of patients to 29%;DEX+RDV with baricitinib or tocilizumab from <1% to 19% RDV initiation in the first 2 days of hospitalization increased 41% to 88% Overall all-cause mortality increased 19% to 24% with large differences between severity subgroups: in December 2021, 20%, 32%, 46% and 60%, respectively, in no supplementary oxygen(NSOc), low-flow(LFO), highflow/non-invasive(HFO/NIV) and invasive mechanical ventilation/ECMO(IMV/ECMO) Overall median hospital LOS and ICU LOS remained between 6-10 days, with notable variation by severity subgroup and over time Overall ICU use was 35%-38%, with large differences by severity subgroups: in December 2021, 28%, 47%, 67% and 94%, respectively, in NSOc, LFO, HFO/NIV and IMV/EC Conclusion(s): COVID-19 can result in severe outcomes;understanding treatment and severity trends can improve prognosis.

Distribution of sequelae in post-covid patients according to previous need of respiratory support

Introduction: "Long COVID" is defined by the persistence of symptoms after 4-12 weeks from COVID-19 disease. Data comparing different clinical phenotypes according to COVID-19 severity are still scanty. Aims and objectives: We aimed to identify different clinical phenotypes of post-COVID syndrome according to the level of respiratory support used. Method(s): We enrolled 309 patients who previously suffered from COVID-19 disease. All patients performed routine blood tests, arterial blood gas analysis, 6 minute walking test and body plethysmography. Then, we assigned each patient to a "severity group" according to the respiratory support needed during COVID-19 disease. Severity group 0: no respiratory support needed Severity group 1: oxygen only Severity group 2: positive airway pressure (CPAP or NIV) Severity group 3: Invasive Mechanical Ventilation (IMV) Results: Patients belonging to Group 0 experienced less fatigue (p=0.004) and mood disorders (p=0.007) compared to the other groups. Group 0 and 3 reported less frequently insomnia (p<0.0001). Hospitalized patients developed sleep and mood disorders during hospitalization due to several factors (fear, acoustic/visual triggers ect.). Patients who underwent IMV, instead, were completely sedated for the entire course of the acute phase of the disease, not being exposed to these triggers. Among blood markers, only Galectin-3 (p=0.004) and IL6 (p=0.004) had significant lower serum concentrations in patients belonging to Group 0, confirming their lower inflammatory status Conclusion(s): Awake hospitalization seems to deeply affect post-COVID sequelae in several patients.

Pneumomediastinum in COVID-19 critically ill patients

Pneumomediastinum in COVID-19 critically ill patients Introduction: Pneumomedisatinum(PM) is an uncommon potentially life-threatening complication of COVID-19 and can be an aggravating factor. This study aimed to determine the incidence and outcomes of PM in critically ill COVI19 patients. Method(s): A retrospective study carried out in a 9-bed intensive care unit from October 1st, 2020 to February 28, 2021 including patients with confirmed COVID19 related acute respiratory distress syndrome (ARDS) with confirmed PM on Chest computed tomography (CT). Were recorded patients characteristics, management and outcomes. Result(s): 7 cases of PM were reported : 5 men, 2 women, aged between 47 and 70 years-old. None of them had underlying lung disease. 4 patients were under invasive mechanical ventilation (IMV), 2 under non-invasive ventilation (NIV) and one had a spontaneous PM at the time of the event. Chest CT scan showed : pulmonary involvement, moderate (n=4/7) to severe (n=3/7), PM (n=7/7), subcutaneous emphysema (n=5/7) and pneumothorax (n=2/7). The highest positive end-expiratory pressure (PEEP) for patients receiving IMV and NIV were respectively 10cmH2O and 6cmH2O. Urgent mediastinal decompression wasn't immediately indicated, conservative therapy with reduced airway pressure was adopted. Patients with NIV were intubated after NIV failure. Despite protective ventilation with lower pressure, needle aspiration and chest drainage, all patients expired during their hospital stay. Conclusion(s): Our findings suggest that PM is secondary to inflammatory response due to COVID-19 and mostly triggered by the use of positive pressure ventilation and it is associated with poor outcome in critically ill COVID-19 patients.

Real-world effectiveness of remdesivir for hospitalized patients with COVID-19: systematic review and metaanalysis

Introduction: Trials of remdesivir (RDV) for COVID-19 have provided evidence for regulatory approval. This is the first meta-analysis (MA) to evaluate the real-world effectiveness of RDV in patients hospitalized with COVID-19. Objective(s): To synthesize RDV observational data. Method(s): A systematic literature review identified observational studies of RDV. Outcomes were all-cause mortality and progression to invasive mechanical ventilation (IMV) assessed at early (day 14/15) and late (day 28/29/30) timepoints. MAs were conducted using standard random effects models;analyses were performed with R statistical software. Result(s): Of 1,069 studies identified, 29 met inclusion criteria for mortality data, 18 were excluded for low quality based on the ROBINS-I tool;11 studies from the United Kingdom, European Union, United States and Japan were included in the MA (N=166,399 patients). RDV was associated with a significant improvement in mortality at early (5 studies;risk ratio [RR] 0.71, 95% confidence interval [CI] 0.64-0.79) and late (10 studies, RR 0.82, 95%CI 0.71-0.95;Figure) timepoints. No significant effect was shown on the proportion of patients requiring IMV (evaluable only in the 3 studies denoted by asterisk in Figure, RR 1.07, 95%CI 0.84-1.34). Results were robust to scenario analyses. Conclusion(s): In a real-world setting, RDV is effective in reducing mortality in hospitalized COVID-19 patients.