COVID-19 Acute Respiratory Distress Syndrome Research Articles

Transpulmonary Plasma Endothelin-1 Arterial:Venous Ratio Differentiates Survivors from Non-Survivors in Critically Ill Patients with COVID-19-Induced Acute Respiratory Distress Syndrome.

Endothelin-1 (ET-1) is a potent vasoconstrictor produced by endothelial cells and cleared from circulating blood mainly in the pulmonary vasculature. In a healthy pulmonary circulation, the rate of local production of ET-1 is less than its rate of clearance. In the present study, we aimed to investigate whether the abnormal pulmonary circulatory handling of ET-1 relates to poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS). To this end, central venous and systemic arterial ET-1 plasma levels were simultaneously measured on Days 1 and 3 following ICU admission in mechanically ventilated COVID-19 patients with ARDS (COVID-19 ARDS, N = 18). Central venous and systemic arterial ET-1 plasma levels were also measured in two distinct SARS-CoV-2-negative mechanically ventilated critically ill patient groups, matched for age, sex, and critical illness severity, with ARDS (non-COVID-19 ARDS, N = 14) or without ARDS (non-COVID-19 non-ARDS, N = 20). Upon ICU admission, COVID-19-induced ARDS patients had higher systemic arterial and central venous ET-1 levels compared to the non-COVID-19 ARDS and non-COVID-19 non-ARDS patients (p < 0.05), yet a normal systemic arterial:central venous (A:V) ET-1 ratio [0.63 (0.49-1.02)], suggesting that pulmonary ET-1 clearance is intact in these patients. On the other hand, the non-COVID-19 ARDS patients demonstrated abnormal ET-1 handling [A:V ET-1 ratio 1.06 (0.93-1.20)], while the non-COVID-19 non-ARDS group showed normal ET-1 handling [0.79 (0.52-1.11)]. On Day 3, the A:V ratio in all three groups was <1. When the COVID-19 ARDS patients were divided based on 28-day ICU mortality, while their systemic arterial and central venous levels did not differ, the A:V ET-1 ratio was statistically significantly higher upon ICU admission in the non-survivors [0.95 (0.78-1.34)] compared to the survivors [0.57 (0.48-0.92), p = 0.027]. Our results highlight the potential importance of ET-1 as both a biomarker and a therapeutic target in critically ill COVID-19 patients. The elevated A:V ET-1 ratio in non-survivors suggests that the early disruption of pulmonary ET-1 handling may be a key marker of poor prognosis.

Comparing the impact of targeting limited driving pressure to low tidal volume ventilation on mortality in mechanically ventilated adults with COVID-19 ARDS: an exploratory target trial emulation

BackgroundAn association between driving pressure (∆P) and the outcomes of invasive mechanical ventilation (IMV) may exist. However, the effect of a sustained limitation of ∆P on mortality in patients with...

Respiratory effects of prone position in COVID-19 acute respiratory distress syndrome differ according to the recruitment-to-inflation ratio: a prospective observational study

BackgroundImprovements in oxygenation and lung mechanics with prone position (PP) in patients with acute respiratory distress syndrome (ARDS) are inconstant. The objectives of the study were (i) to identify baseline variables, including the recruitment-to-inflation ratio (R/I), associated with a positive response to PP in terms of oxygenation (improvement of the ratio of arterial oxygen partial pressure over the inspired oxygen fraction (PaO2/FiO2) ≥ 20 mmHg) and lung mechanics; (ii) to evaluate whether the response to the previous PP session is associated with the response to the next session.MethodsIn this prospective, observational, single-center study in patients who underwent PP for ARDS due to COVID-19, respiratory variables were assessed just before PP and at the end of the session. Respiratory variables included mechanical ventilation settings and respiratory mechanics variables, including R/I, an estimate of the potential for lung recruitment compared to lung overinflation.ResultsIn 50 patients, 201 PP sessions lasting 19 ± 3 h were evaluated. Neuromuscular blockades were used in 116 (58%) sessions. The PaO2/FiO2 ratio increased from 109 ± 31 mmHg to 165 ± 65 mmHg, with an increase ≥ 20 mmHg in 142 (71%) sessions. In a mixed effect logistic regression, only pre-PP PaO2/FiO2 (OR 1.12 (95% CI [1.01–1.24])/every decrease of 10 mmHg, p = 0.034) in a first model and improvement in oxygenation at the previous PP session (OR 3.69 (95% CI [1.27–10.72]), p = 0.017) in a second model were associated with an improvement in oxygenation with PP. The R/I ratio (n = 156 sessions) was 0.53 (0.30–0.76), separating lower- and higher-recruiters. Whereas PaO2/FiO2 improved to the same level in both subgroups, driving pressure and respiratory system compliance improved only in higher-recruiters (from 14 ± 4 to 12 ± 4 cmH2O, p = 0.027, and from 34 ± 11 to 38 ± 13 mL/cmH2O, respectively, p = 0.014).ConclusionsA lower PaO2/FiO2 at baseline and a positive O2-response at the previous PP session are associated with a PP-induced improvement in oxygenation. In higher-recruiters, lung mechanics improved along with oxygenation. Benefits of PP could thus be greater in these patients.

Methylene blue for COVID-19 ARDS: insights from a randomized Clinical Trial.

Around the world, the COVID-19 pandemic has presented many difficulties, and acute respiratory distress syndrome (ARDS) has become a major worry. The antiviral and anti-inflammatory characteristics of methylene blue (MB) have garnered interest for potential medicinal applications. The object of the current study is to assess the effect of orally administered MB on the treatment of ARDS associated with COVID-19. A randomized clinical study was carried out on 122 hospitalized patients who had ARDS related to COVID-19. Patients who met the eligibility requirements were randomized at random to either the control group (CG) (n = 60) or the intervention group (IG) (n = 62). Standard treatments were administered to both groups, with the addition of oral MB to the IG. Clinical outcomes, including SpO2 levels, CRP levels were assessed on the third and fifth days. Additionally, at the time of discharge, patients' assessments were made in terms of APACHE II scores, SOFA scores, LDH and CRP levels, SpO2, and respiratory rate in comparison to the day prior to the intervention. Patients were followed for mortality outcomes at one month and three months after the intervention. Significant changes were observed in SpO2 levels over time (P < 0.001) and between groups (P = 0.022), with higher levels in the MB-treated group. The interaction between time and group (P = 0.019) indicated a stronger increase in SpO2 in the IG, with the IG's SpO2 level increasing by 6.42%. Furthermore, CRP levels showed significant changes over time (P < 0.001), but not between groups (P = 0.092). However, the interaction between group and CRP change over time (P = 0.019) suggested a distinct pattern of CRP decrease in the IG. Significant improvement in RR, SpO2, CRP, and APACHE II score were found according to discharge results. However, in terms of SpO2 and the APACHE II score, this improvement was noteworthy for IG. The length of hospitalization and mortality rates at one- and three-month follow-ups did not differ significantly. Oral administration of MB demonstrated positive effects on improving SpO2 levels and reducing inflammatory markers in COVID-19-related ARDS patients. Despite no significant impact on survival rates or hospitalization length, the study supports the potential efficacy of MB as an alternative treatment for COVID-19 ARDS. This study was registered with the Iranian Registry of Clinical Trials ( http://www.irct.ir ) under the registration code IRCT20200409047007N2 on 11/29/2021.

Therapeutic plasma exchange for COVID-19 acute respiratory distress syndrome complicated by myasthenia gravis

Abstract: The role and safety of therapeutic plasma exchange (TPE) in COVID-19-induced severe acute respiratory distress remains unclear, especially in the wake that a specific and effective treatment modality has not been discovered for the treatment of COVID-19. Here, we report a case where a patient presenting with severe COVID-19 acute respiratory distress syndromes (ARDS) complicated by myasthenia gravis showed significant improvement after the third session of TPE and was subsequently weaned off from the ventilator and shifted to the ward from intensive care unit. TPE can be considered an efficient and safe treatment modality in severe COVID-19 ARDS.

Longitudinal transcriptomic analysis reveals persistent enrichment of iron homeostasis and erythrocyte function pathways in severe COVID-19 ARDS.

The acute respiratory distress syndrome (ARDS) is a common complication of severe COVID-19 and contributes to patient morbidity and mortality. ARDS is a heterogeneous syndrome caused by various insults, and results in acute hypoxemic respiratory failure. Patients with ARDS from COVID-19 may represent a subgroup of ARDS patients with distinct molecular profiles that drive disease outcomes. Here, we hypothesized that longitudinal transcriptomic analysis may identify distinct dynamic pathobiological pathways during COVID-19 ARDS. We identified a patient cohort from an existing ICU biorepository and established three groups for comparison: 1) patients with COVID-19 ARDS that survived hospitalization (COVID survivors, n = 4), 2) patients with COVID-19 ARDS that did not survive hospitalization (COVID non-survivors, n = 5), and 3) patients with ARDS from other causes as a control group (ARDS controls, n = 4). RNA was isolated from peripheral blood mononuclear cells (PBMCs) at 4 time points (Days 1, 3, 7, and 10 following ICU admission) and analyzed by bulk RNA sequencing. We first compared transcriptomes between groups at individual timepoints and observed significant heterogeneity in differentially expressed genes (DEGs). Next, we utilized the likelihood ratio test to identify genes that exhibit different patterns of change over time between the 3 groups and identified 341 DEGs across time, including hemoglobin subunit alpha 2 (HBA1, HBA2), hemoglobin subunit beta (HBB), von Willebrand factor C and EGF domains (VWCE), and carbonic anhydrase 1 (CA1), which all demonstrated persistent upregulation in the COVID non-survivors compared to COVID survivors. Of the 341 DEGs, 314 demonstrated a similar pattern of persistent increased gene expression in COVID non-survivors compared to survivors, associated with canonical pathways of iron homeostasis signaling, erythrocyte interaction with oxygen and carbon dioxide, erythropoietin signaling, heme biosynthesis, metabolism of porphyrins, and iron uptake and transport. These findings describe significant differences in gene regulation during patient ICU course between survivors and non-survivors of COVID-19 ARDS. We identified multiple pathways that suggest heme and red blood cell metabolism contribute to disease outcomes. This approach is generalizable to larger cohorts and supports an approach of longitudinal sampling in ARDS molecular profiling studies, which may identify novel targetable pathways of injury and resolution.

Inhaled nitric oxide in moderate-to-severe COVID-19 acute respiratory distress syndrome: a retrospective cohort study.

In this study, we present the findings from a cohort of patients with COVID-19 with acute respiratory distress syndrome who underwent standard therapy, including prone positioning, with or without adjunctive inhalation of nitric oxide. Our investigation sought to determine whether inhaled nitric oxide administration yielded clinical enhancement in this population. Remarkably, nitric oxide administration elevated the PaO2/FiO2 ratio, which is indicative of improved oxygenation. Despite this improvement, discernible mortality benefits did not emerge in association with the inhaled nitric oxide treatment. To evaluate the responsiveness of COVID-19 acute respiratory distress syndrome patients to inhaled nitric oxide as part of their standard therapy. This retrospective cohort study included critically ill adult patients with confirmed COVID-19 treated between March 2020 and May 2021. Eligible patients with moderate-to-severe acute respiratory distress syndrome due to COVID-19 were subsequently categorized into two groups based on inhaled nitric oxide use throughout their stay in the intensive care unit. The primary endpoints were overall mortality and improvement in oxygenation parameters 6 hours after inhaled nitric oxide use. A total of 481 patients admitted to the intensive care unit due to COVID-19 acute respiratory distress syndrome were screened, 105 of which were included. Among the 105 patients, inhaled nitric oxide therapy was used in 33 patients, will 72 did not undergo inhaled nitric oxide therapy. No significant difference in mortality was observed between the groups (67% for the treatment and 82% for the no-treatment groups respectively, p=0.173). Among the patients who used inhaled nitric oxide, 17 (51%) were considered responsive to therapy. There was no significant difference in the length of stay in the intensive care unit (p=0.324) or total hospitalization time (p=0.344). Inhaled nitric oxide rescue therapy improved oxygenation in patients with COVID-19 with moderate-to-severe acute respiratory distress syndrome but did not affect mortality.

Lung Protective Ventilation Adherence and Outcomes for Patients With COVID-19 Acute Respiratory Distress Syndrome Treated in an Intermediate Care Unit Repurposed to ICU Level of Care.

During the COVID-19 pandemic, some centers converted intermediate care units (IMCUs) to COVID-19 ICUs (IMCU/ICUs). In this study, we compared adherence to lung protective ventilation (LPV) and outcomes for patients with COVID-19-related acute respiratory distress syndrome (ARDS) treated in an IMCU/ICU versus preexisting medical ICUs (MICUs). Retrospective observational study using electronic medical record data. Two academic medical centers from March 2020 to September 2020 (period 1) and October 2020 to May 2021 (period 2), which capture the first two COVID-19 surges in this health system. Adults with COVID-19 receiving invasive mechanical ventilation who met ARDS oxygenation criteria (Pao2/Fio2 ≤ 300 mm Hg or Spo2/Fio2 ≤ 315). None. We defined LPV adherence as the percent of the first 48 hours of mechanical ventilation that met a restrictive definition of LPV of, tidal volume/predicted body weight (Vt/PBW) less than or equal to 6.5 mL/kg and plateau pressure (Pplat) less than or equal to 30 cm H2o. In an expanded definition, we added that if Pplat is greater than 30 cm H2o, Vt/PBW had to be less than 6.0 mL/kg. Using the restricted definition, period 1 adherence was lower among 133 IMCU/ICU versus 199 MICU patients (92% [95% CI, 50-100] vs. 100% [86-100], p = 0.05). Period 2 adherence was similar between groups (100% [75-100] vs. 95% CI [65-100], p = 0.68). A similar pattern was observed using the expanded definition. For the full study period, the adjusted hazard of death at 90 days was lower in IMCU/ICU versus MICU patients (hazard ratio [HR] 0.73 [95% CI, 0.55-0.99]), whereas ventilator liberation by day 28 was similar between groups (adjusted subdistribution HR 1.09 [95% CI, 0.85-1.39]). In patients with COVID-19 ARDS treated in an IMCU/ICU, LPV adherence was similar to, and observed survival better than those treated in preexisting MICUs. With adequate resources, protocols, and staffing, IMCUs provide an effective source of additional ICU capacity for patients with acute respiratory failure.

Lung Transplantation in the United States for COVID-19 Related Lung Disease During the Pandemic.

Lung transplantation (LTx) is a potential intervention for end-stage COVID-19 lung disease. Current literature is sparse regarding the outcomes of LTx for COVID-19 related acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). This study aims to characterize outcomes and patterns of LTx for COVID-19 related lung disease throughout the pandemic. Patients who underwent LTx during the pandemic for COVID-19 related lung disease were retrospectively identified using the UNOS registry. Demographics, as well as outcomes measures and nationwide patterns of care were collected and analyzed. A total of 510 adult cases of LTx for COVID-19 (259 ARDS, 251 PF) were compared to 4,031 without COVID-19 (3,994 PF, 37 ARDS). Patients who received LTx for COVID-19 ARDS did not differ in 2-year survival when compared to those with COVID-19 PF (81.9% vs 77.2%, p = 0.4428). Compared to non-COVID-19 etiologies, COVID-19 ARDS patients had higher rates of stroke (2.3% vs 0%, p = 0.0005), lower rates of graft failure (12.8% vs 36.1%, p = 0.0003) and post-transplant ECMO (29.6% vs 41.7%, p = 0.0002), and improved 2-year survival following LTx (81.9% vs 61.7%, p = 0.0064). No difference in 2-year survival following LTx was observed between patients with COVID-19 and non-COVID-19 PF (77.2% vs 71.8%, p = 0.34). Rates of LTx spiked with variant emergence and declined with rounds of vaccination. Our results are consistent with early reports of survival outcomes following LTx for COVID-19 ARDS and PF while providing an increased layer of granularity. LTx may be considered as a safe and effective intervention for COVID-19 lung disease.

ECMO is associated with decreased hospital mortality in COVID-19 ARDS

This study determined whether compared to conventional mechanical ventilation (MV), extracorporeal membrane oxygenation (ECMO) is associated with decreased hospital mortality or fibrotic changes in patients with COVID-19 acute respiratory distress syndrome. A cohort of 72 patients treated with ECMO and 390 with conventional MV were analyzed (February 2020–December 2021). A target trial was emulated comparing the treatment strategies of initiating ECMO vs no ECMO within 7 days of MV in patients with a PaO2/FiO2 < 80 or a PaCO2 ≥ 60 mmHg. A total of 222 patients met the eligibility criteria for the emulated trial, among whom 42 initiated ECMO. ECMO was associated with a lower risk of hospital mortality (hazard ratio [HR], 0.56; 95% confidence interval [CI] 0.36–0.96). The risk was lower in patients who were younger (age < 70 years), had less comorbidities (Charlson comorbidity index < 2), underwent prone positioning before ECMO, and had driving pressures ≥ 15 cmH2O at inclusion. Furthermore, ECMO was associated with a lower risk of fibrotic changes (HR, 0.30; 95% CI 0.11–0.70). However, the finding was limited due to relatively small number of patients and differences in observability between the ECMO and conventional MV groups.

Impact of extended lung protection during mechanical ventilation on lung recovery in patients with COVID-19 ARDS: a phase II randomized controlled trial

BackgroundProtective ventilation seems crucial during early Acute Respiratory Distress Syndrome (ARDS), but the optimal duration of lung protection remains undefined. High driving pressures (ΔP) and excessive patient ventilatory drive may hinder lung recovery, resulting in self-inflicted lung injury. The hidden nature of the ΔP generated by patient effort complicates the situation further. Our study aimed to assess the feasibility of an extended lung protection strategy that includes a stepwise protocol to control the patient ventilatory drive, assessing its impact on lung recovery.MethodsWe conducted a single-center randomized study on patients with moderate/severe COVID-19-ARDS with low respiratory system compliance (CRS < 0.6 (mL/Kg)/cmH2O). The intervention group received a ventilation strategy guided by Electrical Impedance Tomography aimed at minimizing ΔP and patient ventilatory drive. The control group received the ARDSNet low-PEEP strategy. The primary outcome was the modified lung injury score (mLIS), a composite measure that integrated daily measurements of CRS, along with oxygen requirements, oxygenation, and X-rays up to day 28. The mLIS score was also hierarchically adjusted for survival and extubation rates.ResultsThe study ended prematurely after three consecutive months without patient enrollment, attributed to the pandemic subsiding. The intention-to-treat analysis included 76 patients, with 37 randomized to the intervention group. The average mLIS score up to 28 days was not different between groups (P = 0.95, primary outcome). However, the intervention group showed a faster improvement in the mLIS (1.4 vs. 7.2 days to reach 63% of maximum improvement; P < 0.001), driven by oxygenation and sustained improvement of X-ray (P = 0.001). The intervention group demonstrated a sustained increase in CRS up to day 28 (P = 0.009) and also experienced a shorter time from randomization to room-air breathing (P = 0.02). Survival at 28 days and time until liberation from the ventilator were not different between groups.ConclusionsThe implementation of an individualized PEEP strategy alongside extended lung protection appears viable. Promising secondary outcomes suggested a faster lung recovery, endorsing further examination of this strategy in a larger trial.Clinical trial registration This trial was registered with ClinicalTrials.gov (number NCT04497454) on August 04, 2020.

Association between emergency department disposition and mortality in patients with COVID-19 acute respiratory distress syndrome.

Patients hospitalized for COVID-19 frequently develop hypoxemia and acute respiratory distress syndrome (ARDS) after admission. In non-COVID-19 ARDS studies, admission to hospital wards with subsequent transfer to intensive care unit (ICU) is associated with worse outcomes. We hypothesized that initial admission to the ward may affect outcomes in patient with COVID-19 ARDS. This was a retrospective study of consecutive adults admitted for COVID-19 ARDS between March 2020 and March 2021 at Stanford Health Care. Mortality scores at hospital admission (Coronavirus Clinical Characterization Consortium Mortality Score [4C score]) and ICU admission (Simplified Acute Physiology Score III [SAPS-III]) were calculated, as well as ROX index for patients on high flow nasal oxygen. Patients were classified by emergency department (ED) disposition (ward-first vs. ICU-direct), and 28- and 60-day mortality and highest level of respiratory support within 1 day of ICU admission were compared. A second cohort (April 2021‒July 2022, n=129) was phenotyped to validate mortality outcome. A total of 157 patients were included, 48% of whom were first admitted to the ward (n=75). Ward-first patients had more comorbidities, including lung disease. Ward-first patients had lower 4C and similar SAPS-III score, yet increased mortality at 28 days (32%vs. 17%, hazard ratio [HR] 2.0, 95% confidence interval [95% CI] 1.0‒3.7, p=0.039) and 60 days (39%vs. 23%, HR 1.83, 95% CI 1.04‒3.22, p=0.037) compared to ICU-direct patients. More ward-first patients escalated to mechanical ventilation on day 1 of ICU admission (36%vs. 14%, p=0.002) despite similar ROX index. Ward-first patients who upgraded to ICU within 48h of ED presentation had the highest mortality. Mortality findings were replicated in a sensitivity analysis. Despite similar baseline risk scores, ward-first patients with COVID-19 ARDS had increased mortality and escalation to mechanical ventilation compared to ICU-direct patients. Ward-first patients requiring ICU upgrade within 48h were at highest risk, highlighting a need for improved identification of this group at ED admission.

Medium-Term Disability and Long-Term Functional Impairment Persistence in Survivors of Severe COVID-19 ARDS: Clinical and Physiological Insights

BackgroundAlthough the medium- and long-term sequelae of survivor of acute respiratory distress syndrome (ARDS) of any cause have been documented, little is known about the way in which COVID-19-induced ARDS affects functional disability and exercise components. Our aims were to examine the medium-term disability in severe COVID-19-associated ARDS survivors, delineate pathophysiological changes contributing to their exercise intolerance, and explore its utility in predicting long-term functional impairment persistence. MethodsWe studied 108 consecutive subjects with severe COVID-19 ARDS who remained alive 6 months after intensive care unit (ICU) discharge. Lung morphology was assessed with chest non-contrast CT scans and CT angiography. Functional evaluation included spirometry, plethysmography, muscle strength, and diffusion capacity, with assessment of gas exchange components through diffusing capacity of nitric oxide. Disability was assessed through an incremental exercise test, and measurements were repeated 12 and 24 months later in patients with functional impairments. ResultsAt 6 months after ICU discharge, a notable dissociation between morphological and clinical-functional sequelae was identified. Moderate-severe disability was present in 47% of patients and these subjects had greater limitation of ventilatory mechanics and gas exchange, as well as greater symptomatic perception during exercise and a probable associated cardiac limitation. Female sex, hypothyroidism, reduced membrane diffusion component, lower functional residual capacity, and high-attenuation lung volume were independently associated with the presence of moderate-severe functional disability, which in turn was related to higher frequency and greater intensity of dyspnea and worse quality of life. Out of the 71 patients with reduced lung volumes or diffusion capacity at 6 months post-ICU discharge, only 19 maintained a restrictive disorder associated with gas exchange impairment at 24 months post-discharge. In these patients, 6-month values for diffusion membrane component, maximal oxygen uptake, ventilatory equivalent for CO2, and dead space to tidal volume ratio were identified as independent risk factors for persistence of long-term functional sequelae. ConclusionsLess than half of survivors of COVID-19 ARDS have moderate-severe disability in the medium term, identifying several risk factors. In turn, diffusion membrane component and exercise tolerance at 6-month ICU discharge are independently associated with the persistence of long-term functional sequelae.

Racial and ethnic disparities post-hospitalization for COVID-19: barriers to access to care for survivors of COVID-19 acute respiratory distress syndrome

Racial and ethnic health disparities in the incidence and severity of Coronavirus Disease 2019 (COVID-19) have been observed globally and in the United States. Research has focused on transmission, hospitalization, and mortality among racial and ethnic minorities, but Long COVID-19 health disparities research is limited. This study retrospectively evaluated 195 adults who survived COVID-19 associated acute respiratory distress syndrome (C-ARDS) in New York City from March–April 2020. Among survivors, 54% met the criteria for Long COVID syndrome. Hispanic/Latinx patients, were more likely to be uninsured (p = 0.027) and were less frequently discharged to rehabilitation facilities (p < 0.001). A cross-sectional telephone survey and interview were conducted with a subset of survivors (n = 69). Among these, 11% reported a lack of follow-up primary care post-discharge and 38% had subsequent emergency room visits. Notably, 38% reported poor treatment within the health care system, with 67% attributing this to racial or ethnic bias. Thematic analysis of interviews identified four perceived challenges: decline in functional status, discrimination during hospitalization, healthcare system inequities, and non-healthcare-related structural barriers. Sources of resilience included survivorship, faith, and family support. This study highlights structural and healthcare-related barriers rooted in perceived racism and poverty as factors impacting post-COVID-19 care.

Echocardiographic assessment of right ventricular performance in COVID-19 related acute respiratory distress syndrome: the importance of systo-diastolic interaction.

The cardiac manifestations of COVID-19 have been described in patients with acute respiratory distress syndrome (ARDS) admitted to intensive care unit (ICU). The presence and impact of right ventricular (RV) diastolic function and performance has not been studied in this population yet. We describe the prevalence of RV diastolic dysfunction, assessed by the pulmonary valve pre-ejection A wave (PV A wave), and the RV systo-diastolic interaction, using the RV total isovolumic time (t-IVT), in COVID-19 ARDS. Prospective observational study enrolling patients with moderate to severe COVID-19 ARDS admitted to ICU who underwent a transthoracic echocardiogram within 24h of ICU admission and at least a second one during the ICU stay. Respiratory, hemodynamic and biochemistry parameters were collected. 163 patients (age 61.0 ± 9.3years, 72% males) were enrolled. 36 patients (22.1%) had RV dysfunction, 45 (27.1%) LV systolic dysfunction. 73 patients (44.7%) had PV A wave. The RV t-IVT correlated with TAPSE at ICU admission (p < 0.002; r -0.61), presence of PV A wave (p < 0.001; r 0.78), peak inspiratory pressure (PIP) (p < 0.001; r 0.42), PEEP (p < 0.001; r 0.68), dynamic driving pressure (DDP) (p < 0.001; r 0.58), and PaO2/FiO2 ratio (p < 0.01; r -0.35). The presence of PV A wave was associated with higher PIP (p < 0.001; r 0.45), higher PEEP (p < 0.001; r 0.56), higher DDP (p < 0.01, r 0.51), and lower PaO2/FiO2 ratio (p < 0.001; r -0.49). RV t-IVT and the presence of PV A wave are non-invasive means to describe a significant RV diastolic dysfunction and may be consider descriptive signs of RV performance in COVID-19 ARDS.

Hemorrhage and thrombosis in COVID-19-patients supported with extracorporeal membrane oxygenation: an international study based on the COVID-19 critical care consortium

BackgroundExtracorporeal membrane oxygenation (ECMO) is a rescue therapy in patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19. While bleeding and thrombosis complicate ECMO, these events may also occur secondary to COVID-19. Data regarding bleeding and thrombotic events in COVID-19 patients on ECMO are sparse.MethodsUsing the COVID-19 Critical Care Consortium database, we conducted a retrospective analysis on adult patients with severe COVID-19 requiring ECMO, including centers globally from 01/2020 to 06/2022, to determine the risk of ICU mortality associated with the occurrence of bleeding and clotting disorders.ResultsAmong 1,248 COVID-19 patients receiving ECMO support in the registry, coagulation complications were reported in 469 cases (38%), among whom 252 (54%) experienced hemorrhagic complications, 165 (35%) thrombotic complications, and 52 (11%) both. The hazard ratio (HR) for Intensive Care Unit mortality was higher in those with hemorrhagic-only complications than those with neither complication (adjusted HR = 1.60, 95% CI 1.28–1.99, p < 0.001). Death was reported in 617 of the 1248 (49.4%) with multiorgan failure (n = 257 of 617 [42%]), followed by respiratory failure (n = 130 of 617 [21%]) and septic shock [n = 55 of 617 (8.9%)] the leading causes.ConclusionsCoagulation disorders are frequent in COVID-19 ARDS patients receiving ECMO. Bleeding events contribute substantially to mortality in this cohort. However, this risk may be lower than previously reported in single-nation studies or early case reports.Trial registration ACTRN12620000421932 (https://covid19.cochrane.org/studies/crs-13513201).

Pregnant women with COVID-19 ARDS on the intensive care unit

Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk of severe disease progression. Comorbidities, such as chronic arterial hypertension, diabetes mellitus, advanced maternal age and high body mass index, may predispose to severe disease. The management of pregnant COVID-19patients on the intensive care unit (ICU) is challenging and requires careful consideration of maternal, fetal and ethical issues. Description and discussion of intensive care treatment strategies and perinatal anesthesiological management in patients with COVID-19 acute respiratory distress syndrome (CARDS). We analyzed the demographic data, maternal medical history, clinical intensive care management, complications, indications and management of extracorporeal membrane oxygenation (ECMO) and infant survival of all pregnant patients treated for severe CARDS in the anesthesiological ICU of aGerman university hospital between March and November 2021. The cohort included 9 patients with amean age of 30.3 years (range 26-40years). The gestational age ranged from 21 + 3 weeks to 37 + 2 weeks. None of the patients had been vaccinated against SARS-CoV‑2. Of the nine patients seven were immigrants and communication was hampered by inadequate Central European language skills. Of the patients five had aPaO2/FiO2 index < 150 mm Hg despite escalated invasive ventilation (FiO2 > 0.9 and a positive end-expiratory pressure [PEEP] of 14 mbar) and were therefore treated with repeated prolonged prone positioning maneuvers (5-14 prone positions for 16 h each, atotal of 47prone positioning treatments) and 2 required treatment with inhaled nitric oxide and venovenous ECMO. The most common complications were bacterial superinfection of the lungs, urinary tract infection and delirium. All the women and five neonates survived. All newborns were delivered by cesarean section, two patients were discharged home with an intact pregnancy and two intrauterine fetal deaths were observed. None of the newborns tested positive for SARS-CoV‑2 at birth. High survival rates are possible in pregnant patients with CARDS. The peripartum management of pregnant women with CARDS requires close interdisciplinary collaboration and should prioritize maternal survival in early pregnancy. In our experience, prolonged prone positioning, an essential evidence-based cornerstone in the treatment of ARDS, can also be safely used in advanced stages of pregnancy. Inhaled nitric oxide (iNO) and ECMO should be considered as life-saving treatment options for carefully selected patients. For cesarean section, neuraxial anesthesia can be safely performed in patients with mild CARDS if well planned but the therapeutic anticoagulation recommended for COVID-19 may increase the risk of bleeding complications, making general anesthesia amore viable alternative, especially in severe disease.

Extracorporeal membrane oxygenation versus invasive ventilation in patients with COVID-19 acute respiratory distress syndrome and pneumomediastinum: A cohort trial.

Patients with severe respiratory failure due to COVID-19 who are not under mechanical ventilation may develop severe hypoxemia when complicated with spontaneous pneumomediastinum (PM). These patients may be harmed by invasive ventilation. Alternatively, veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) may be applied. We report on the efficacy of V-V ECMO and invasive ventilation as initial advanced respiratory support in patients with COVID-19 and acute respiratory failure due to spontaneous PM. This was a retrospective cohort study performed between March 2020 and January 2022. Enrolled patients had COVID-19 and acute respiratory failure due to spontaneous PM and were not invasively ventilated. Patients were treated in the intensive care unit (ICU) with invasive ventilation (invasive ventilation group) or V-V ECMO support (V-V ECMO group) as the main therapeutic option. The primary outcomes were mortality and ICU discharge at 90 days after ICU admission. Twenty-two patients were included in this study (invasive ventilation group: 13 [59%]; V-V ECMO group: 9 [41%]). The V-V ECMO strategy was significantly associated with lower mortality (hazard ratio [HR] 0.33 [95% CI 0.12-0.97], p = 0.04). Five (38%) patients in the V-V ECMO group were intubated and eight (89%) patients in the invasive ventilation group required V-V ECMO support within 30 days from ICU admission. Three (33%) patients in the V-V ECMO group were discharged from ICU within 90 days compared to one (8%) patient in the invasive ventilation group (HR 4.71 [95% CI 0.48-45.3], p = 0.18). Preliminary data suggest that V-V ECMO without invasive ventilation may improve survival in COVID-19-related acute respiratory failure due to spontaneous PM. The study's retrospective design and limited sample size underscore the necessity for additional investigation and warrant caution.

Driving pressure, as opposed to tidal volume based on predicted body weight, is associated with mortality: results from a prospective cohort of COVID-19 acute respiratory distress syndrome patients.

To evaluate the association between driving pressure and tidal volume based on predicted body weight and mortality in a cohort of patients with acute respiratory distress syndrome caused by COVID-19. This was a prospective, observational study that included patients with acute respiratory distress syndrome due to COVID-19 admitted to two intensive care units. We performed multivariable analyses to determine whether driving pressure and tidal volume/kg predicted body weight on the first day of mechanical ventilation, as independent variables, are associated with hospital mortality. We included 231 patients. The mean age was 64 (53 - 74) years, and the mean Simplified Acute and Physiology Score 3 score was 45 (39 - 54). The hospital mortality rate was 51.9%. Driving pressure was independently associated with hospital mortality (odds ratio 1.21, 95%CI 1.04 - 1.41 for each cm H2O increase in driving pressure, p = 0.01). Based on a double stratification analysis, we found that for the same level of tidal volume/kg predicted body weight, the risk of hospital death increased with increasing driving pressure. However, changes in tidal volume/kg predicted body weight were not associated with mortality when they did not lead to an increase in driving pressure. In patients with acute respiratory distress syndrome caused by COVID-19, exposure to higher driving pressure, as opposed to higher tidal volume/kg predicted body weight, is associated with greater mortality. These results suggest that driving pressure might be a primary target for lung-protective mechanical ventilation in these patients.

Quantitative SARS-CoV-2 RT-PCR and Bronchoalveolar Cytokine Concentrations Redefine the COVID-19 Phenotypes in Critically Ill Patients.

Recent studies suggest that both hypo- and hyperinflammatory acute respiratory distress syndrome (ARDS) phenotypes characterize severe COVID-19-related pneumonia. The role of lung Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) viral load in contributing to these phenotypes remains unknown. To redefine COVID-19 ARDS phenotypes when considering quantitative SARS-CoV-2 RT-PCR in the bronchoalveolar lavage of intubated patients. To compare the relevance of deep respiratory samples versus plasma in linking the immune response and the quantitative viral loads. Eligible subjects were adults diagnosed with COVID-19 ARDS who required mechanical ventilation and underwent bronchoscopy. We recorded the immune response in the bronchoalveolar lavage and plasma and the quantitative SARS-CoV-2 RT-PCR in the bronchoalveolar lavage. Hierarchical clustering on principal components was applied separately on the 2 compartments' datasets. Baseline characteristics were compared between clusters. Twenty subjects were enrolled between August 2020 and March 2021. Subjects underwent bronchoscopy on average 3.6 days after intubation. All subjects were treated with dexamethasone prior to bronchoscopy, 11 of 20 (55.6%) received remdesivir and 1 of 20 (5%) received tocilizumab. Adding viral load information to the classic 2-cluster model of ARDS revealed a new cluster characterized by hypoinflammatory responses and high viral load in 23.1% of the cohort. Hyperinflammatory ARDS was noted in 15.4% of subjects. Bronchoalveolar lavage clusters were more stable compared to plasma. We identified a unique group of critically ill subjects with COVID-19 ARDS who exhibit hypoinflammatory responses but high viral loads in the lower airways. These clusters may warrant different treatment approaches to improve clinical outcomes.