Refractory circulatory failure in COVID-19 patients treated with veno-arterial ECMO: A retrospective single-center experience

Objectives: Data about COVID-19 patients treated with veno-arterial-ECMO (VA-ECMO) is limited. Reported survival rates range from 27.9% to 77.8%, depending on VA-ECMO indication. A subgroup of patients suffers from circulatory failure due to a COVID-19 associated hyperinflammatory state (CovHI). In these patients, differentiation between inflammation and sepsis is difficult but important. In this retrospective case series, differential diagnoses of COVID-19 associated refractory circulatory failure and survival rates in different indications for VA-ECMO are investigated. Method(s): Retrospective analysis of 28 consecutive COVID-19 patients requiring VA-ECMO at the University Hospital Regensburg between March 2020 and May 2022. Specific treatment for COVID-19 was in accordance with respective guidelines. Mycotic infections were either invasive or met current definitions of COVID19-associated-pulmonary aspergillosis. Result(s): At VA-ECMO initiation, median age was 57.3 years (IQR: 51.4 - 61.8), SOFA score 16 (IQR: 13 - 17) and norepinephrine dosing 0.53mug/kg/min (IQR: 0.32 - 0.78). Virus-variants were: 61% wild-type, 14% Alpha, 18% Delta and 7% Omicron. Survival to hospital discharge was 39%. 17 patients were primarily supported with VA-ECMO only (survival 42%), 3 patients were switched from VV to VA-ECMO (survival 0%), and 8 patients were converted from VA to VAV or VV-ECMO (survival 50%). Indications for VA-ECMO support were pulmonary embolism (PE) (n=5, survival 80%), right heart failure due to secondary pulmonary hypertension (n=5, survival 20%), cardiac arrest (n=4, survival 25%), acute left heart failure (ALHF) (n=11, survival 36%) and refractory vasoplegia (n=3, survival 0%). Inflammatory markers at VA-ECMO initiation were higher in patients with ALHF or vasoplegia;in these patients a higher rate of invasive fungal infections (10/14, 71% vs. 4/14, 29%;p=0.023) compared to the other patients was found. Conclusion(s): Survival on VA-ECMO in COVID-19 depends on VA-ECMO indication, which should be considered in further studies and clinical decisions making. Circulatory failure due to vasoplegia should be considered very carefully as indication for VA-ECMO. A high rate of mycotic infections mandates an intense microbiological workup of these patients and must be considered as an important differential diagnosis to CovHI.

Long-term support of COVID-19 patients with veno-venous extracorporeal membrane oxygenation: Complications, predictors of mortality and long-term outcome

Objectives: Treatment of severe respiratory distress syndrome (ARDS) due to COVID-19 by veno-venous extracorporeal membrane oxygenation (VV-ECMO) had a mortality of up to 70% in Germany. Many patients with COVID-19 need VV-ECMO support longer than 28 days (long-term VV-ECMO). Evidence on mortality, complications during intensive care, functional status after discharge and mortality-predictors for patients supported with long-term VV-ECMO is lacking. Method(s): Retrospective study of 137 consecutive patients treated with VV-ECMO for ARDS due to COVID-19 at University Hospital Regensburg from March 2020 to March 2022. Result(s): 38% (n=52;87% male) of patients needed longterm VV-ECMO support. In these, SOFA score (median [IQR]) at ECMO initiation was 9 [8-11], age 58.2 [50.6- 62.5] years, PaO2/FiO2-ratio 67 [52-88] mmHg, pCO262 [52-74] mmHg, Murray-Score 3.3 [3.0-3.6] and PEEP 15 [13 - 16] cmH2O. Duration of long-term support was 45 [35-65] days. 26 (50%) patients were discharged from the ICU. Only one patient died after hospital discharge. At VVECMO initiation, baseline characteristics did not differ between deceased and survivors. Complications were frequent (acute kidney injury: 31/52, renal replacement therapy: 14/52, pulmonary embolism: 21/52, intracranial hemorrhage 8/52, major bleeding 34/52 and secondary sclerosing cholangitis: 5/52) and more frequent in the deceased. Karnofsky index (normal 100) after rehabilitation was 70 [57.5-82.5]. Twelve of the 18 patients discharged from rehabilitation had a satisfactory quality of life according to their own subjective assessment. Four patients required nursing support. Mortality-predictors within the first 30 days on VV-ECMO only observed in those who deceased later, were: Bilirubin >5mg/dl for > 7 days, pulmonary compliance <10ml/mbar for >14 days, and repeated serum concentrations of interleukin 8 >150ng/L. Conclusion(s): Long-term extracorporeal lung support in patients with COVID-19 resulted in 50 % survival and subsequently lead to a satisfactory quality of life and functionality in the majority of patients. It should preferably be performed in experienced centers because of a high incidence of complications. Several findings during the early course were associated with late mortality but need validation in large prospective studies.

The Effect of CRP/Albumin, Platelet/Lymphocyte, SOFA, and APACHE II in Predicting Mortality in Covid-19 Patients in Intensive Care Unit

Objectives: It is important to predict the prognosis during hospital admission of Covid-19 patients. The purpose of this study was to see how CRP/ Albumin (CAR) and Platelet/Lymphocyte (PLR) ratios, obtained from patients in the intensive care unit (ICU) within the first 24 hours of their hospitalization with a Covid-19 diagnosis, predictmortality and how they correlated with acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA). Method(s): Using hospital records, records of 83 patients hospitalized in the ICU with a diagnosis of Covid-19 between 11.03.2020 and 01.01.2021 were retrospectively analyzed . Patients were divided into two groups discharged (Group I) and exits (ex) group (Group II). CAR and PLR were recorded during the first 24 hours of ICU admission, and APACHE II and SOFA scores were computed. The calculated CAR and PLR were correlated with APACHE II and SOFA scores and their association with mortality was investigated. Result(s): SOFA, APACHE II, PLO, and age were higher, and albumin was lower in patients in the mortal course (p<0.05). ROC analysis revealed that APACHE II and SOFA scores could be employed to estimate mortality. Conclusion(s): We believe that APACHE II and SOFA scores can be used to predict mortality in patients admitted to the ICU due to Covid-19, whereas CRP/Albumin and Platelet/Lymphocyte ratios cannot. Copyright © 2023 by The Cardiovascular Thoracic Anaesthesia and Intensive Care.

Liver biomarkers for prognosis in COVID-19

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).Mortality attributable to COVID-19 remains considerably high, with case fatality rates as high as 8-11%. Early medical intervention in patients who are seriously and critically ill with COVID-19 reduces fatal outcomes. Thus, there is an urgent need to identify biomarkers that could help clinicians determine which patients with SARS-CoV-2 infection are at a higher risk of developing the most adverse outcomes, which include intensive care unit (ICU) admission, invasive ventilation, and death. In COVID-19 patients experiencing the most severe form of the disease, tests of liver function are frequently abnormal and liver enzymes are found to be elevated. For this reason, we examine the most promising liver biomarkers for COVID-19 prognosis in an effort to help clinicians predict the risk of ARDS, ICU admission, and death at hospital admission. In patients meeting hospitalization criteria for COVID-19, serum albumin < 36 g/L is an independent risk factor for ICU admission, with an AUC of 0.989, whereas lactate dehydrogenase (LDH) values > 365 U/L accurately predict death with an AUC of 0.943.The clinical scores COVID-GRAM and SOFA that include measures of liver function such as albumin, LDH, and total bilirubin are also good predictors of pneumonia development, ICU admission, and death, with AUC values ranging from 0.88 to 0.978.Thus, serum albumin and LDH, together with clinical risk scores such as COVID-GRAM and SOFA, are the most accurate biomarkers in the prognosis of COVID-19.Copyright © 2021 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.

Predictors of poor outcomes in patients with pandemic viral infections (influenza AH1N1pdm09, COVID-19) on a ventilator.

Considering the commonality of the pathogenetic links of the critical forms of COVID-19 and influenza AH1N1pdm09 (cytokine over-release syndrome), the question arises: will the predictors of an unfavorable outcome in patients on mechanical ventilation and, accordingly, the universal tactics of respiratory support in these diseases be identical? Objective. In a comparative aspect, to characterize patients with influenza AH1N1pdm09 and COVID-19 who were on mechanical ventilation, to identify additional clinical and laboratory risk factors for death, to determine the degree of influence of respiratory support (RP) tactics on an unfavorable outcome in the studied category of patients. Patients and methods. Patients treated on the basis of resuscitation and intensive care departments of the State Budgetary Healthcare Institution "SKIB" in Krasnodar and the State Budgetary Healthcare Institution "IB No 2" in Sochi were studied: group 1 - 31 people with influenza AH1N1pdm09 (21 people died - subgroup 1A;10 people survived - subgroup 1B) and group 2 - 50 people with COVID-19 (29 patients died - subgroup 2A;21 people survived - subgroup 2B). All patients developed hypoxemic ARF. All patients received step-by-step tactics of respiratory support, starting with oxygen therapy and ending with the use of "traditional" mechanical ventilation. Continuous variables were compared in subgroups of deceased and surviving patients for both nosologies at the stages: hospital admission;registration of hypoxemia and the use of various methods of respiratory therapy;development of multiple organ dysfunctions. With regard to the criteria for which a statistically significant difference was found (p < 0.05), we calculated a simple correlation, the relative risk of an event (RR [CI 25-75%]), the cut-off point, which corresponded to the best combination of sensitivity and specificity. Results. Risk factors for death of patients with influenza AH1N1pdm09 on mechanical ventilation: admission to the hospital later than the 8th day of illness;the fact of transfer from another hospital;leukocytosis >=10.0 x 109/l, granulocytosis >=5.5 x 109/l and LDH level >=700.0 U/l at admission;transfer of patients to mechanical ventilation on the 9th day of illness and later;SOFA score >=8;the need for pressor amines and replacement of kidney function. Predictors of poor outcome in ventilated COVID-19 patients: platelet count <=210 x 109/L on admission;the duration of oxygen therapy for more than 4.5 days;the use of HPNO and NIV as the 2nd step of RP for more than 2 days;transfer of patients to mechanical ventilation on the 14th day of illness and later;oxygenation index <=80;the need for pressors;SOFA score >=8. Conclusion. When comparing the identified predictors of death for patients with influenza and COVID-19 who needed mechanical ventilation, there are both some commonality and differences due to the peculiarities of the course of the disease. A step-by-step approach to the application of respiratory support methods is effective both in the case of patients with influenza AH1N1pdm09 and patients with COVID-19, provided that the respiratory support method used is consistent with the current state of the patient and his respiratory system, timely identification of markers of ineffectiveness of the respiratory support stage being carried out and determining the optimal moment escalation of respiratory therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Blood purification treatment and cytokine removal using Cytosorb device in critically ill patients with COVID-19 infection

Introduction: Acute kidney injury (AKI) is a complication of SARS-CoV-2 disease, associated with worse clinical outcomes. Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBPT) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions. Method(s): We retrospectively analyzed 20 patients admitted in ICU for ARDS and who developed moderate-to-severe AKI requiring RRT. Cytokine hemadsorption with Cytosorb was performed in association with CRRT. The main indication for this treatment was the worsening of hemodynamic and respiratory conditions and suspicion of cytokine storm. The protocol consisted in the use of 3-4 cartridges in total;among these, the first 2 were changed after 12 hours of treatment to maximize cytokine removal, while the others after 24 hours. We examined comorbidities, clinical and laboratory characteristics and the impact of treatment in terms of mortality rate and changes in data before and after treatment. Result(s): Nineteen patients (95%) had an AKI at any time during their ICU stay. Of these, 5 patients (25%) had AKI stage II and 14 patients (70%) had AKI stage III. All patients included in this subgroup were mechanical ventilated and required vasopressor's use. Mean prescribed CRRT dose was 31.2 +/- 11.7 ml/kg/h. The median time to strating RRT after ICU admission was 7 days (IQR 3.5-15 days) and the median duration was 7 days (IQR 2.5-12.5 days). Mean SOFA score at the time of RRT start was extremely high (14.5 +/- 2.8). Mortality rate was important (18 patients, 90%) in our cohort. Comparing clinical and laboratory data before and after treatment, a significant improvement of inflammatory markers was reported, with the reduction of C-reactive protein (CRP, 143 [62.1- 328.5] vs 83.5 [66.7-153.5] mg/L);however, no significant changes in IL-6, WBC and PCT values were observed. A slight increase of PaO2/FiO2 were described, although not statistically significant (PaO2/FiO2 ratio 144 [82.7-174.2] vs 183 [132-355.5] mmHg). Conclusion(s): Our experience supports the need of an adequate timing for the use of Cytosorb in critically ill patients with Covid-19. Although a discrete efficacy in improving inflammatory cascade, the late use of EBPT, when organ dysfunction was already ongoing, didn't impact survival.

Outcomes of cancer patients with Covid-19 admitted to the Intensive Care Unit: A retrospective study

Introduction: Active cancer increases the odds of death among patients with COVID-19.1 Cancer patients may be at increased risk of complications and mortality from COVID-19 owing to the systemic effects of malignancy, immune suppression after chemotherapy, treatment-related complications and presence of co-morbidities.2 They may develop serious complications necessitating ICU admission. In a meta-analysis, the pooled mortality in cancer patients with COVID-19 admitted to an ICU was 60.2%.3 Our hospital is a tertiary referral cancer centre, and the ICU admitted cancer patients with Covid-19 throughout the pandemic. Objective(s): To determine the 30-day in-hospital mortality of adult cancer patients with Covid-19 admitted to the ICU. We also aimed to determine the factors associated with mortality in cancer patients with Covid-19. Method(s): After approval from the Institutional Ethics Committee, data of all cancer patients (age = 16 years) with Covid-19 admitted to the ICU between March 2020 and March 2021 were retrieved from the hospital records. In case of multiple ICU admissions, data from the first admission was recorded. Data recorded included demographic details, type of cancer (solid, haematological), surgical status, APACHE-II and SOFA scores, C-reactive protein, and interventions in ICU. The primary outcome was 30-day in-hospital mortality. Data were analysed using Man-Whitney test and chi-square test. A multivariable regression analysis was carried out to determine factors associated with mortality. Result(s): Data of 127 cancer patients with Covid-19 was analysed. The median [interquartile range, IQR] age was 55 (43-62) years, and there were 50 females (39.3%). Comorbidities were present in 46 (36%) patients, the commonest being diabetes (29 patients) and hypertension (31 patients). The median [IQR] APACHE-II and SOFA scores were 15[8-20] and 4[2-7], respectively. Overall, 62/127 patients died, and 30-day hospital mortality was 49%. There were 30 patients with haematological malignancy and 97 with solid tumours with 30-day in-hospital mortality rates of 46.7% and 49.5%, respectively;p = 0.84). Amongst patients with solid tumours, there was no difference in mortality in surgical patients compared to non-surgical patients (43.3% vs. 52.2%;p = 0.42). Table 1 summarises the parameters and interventions in survivors and non-survivors. On multivariable analysis, only the change in SOFA score from Day 1 to Day 3 was independently associated with outcome (Odds ratio 1.36 (95% confidence interval 1.01-1.84, p-0.04). Conclusion(s): In patients with cancer and Covid-19 and age =16 years admitted to our ICU, the crude 30-day hospital mortality was 47%. There was no association of mortality with cancer type or surgical status. The only independent predictor of mortality was progression of organ failure. Cancer patients with Covid-19 have a reasonable outcome and should be given a trial of intensive care.

Hemoadsorption by CytoSorb in septic no-Covid and Covid patients: a case series

Background: Septic shock is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The reduction of pro-inflammatory and anti-inflammatory mediators by hemoadsorption represents a new tool in the treatment of sepsis. In the present case series, we evaluated the impact of CytoSorb on adult patients with septic shock. Method(s): Patients with septic shock, admitted to Intensive Care Unit (ICU) from March 1, 2021 to February 28, 2022 who received CytoSorb therapy within 72 hours of admission were enrolled in the study. The severity of clinical conditions at admission was assessed by the SAPS II and SOFA scores;The magnitude of the inflammatory response was estimated using the plasmatic levels of C reactive protein (CRP) and interleukin-6 (IL-6). The effect of CytoSorb therapy on the inflammatory state, was evaluated measuring the percentage reduction of IL-6 and CRP. Time elapsed from ICU admission and the start of CytoSorb therapy was also assessed. T-test was used to compare the means of the groups of Survivors and No survivors. Fisher's test was used to evaluated the difference in mortality between Covid and No covid patients. Result(s): Twelve patients were evaluated. Six patients tested positive for covid-19, while the other six did not. Table 1 shows the values of age, SAPSII, SOFA, IL-6, CRP, PCT and timing between the survivors and the no survivors. Overall, there was no significant difference between the two groups in terms of SAPSII, SOFA, age, CRP. There was a significant difference in the timing of Cytosorb start and percentage of IL-6 removal: In surviving patients the timing of intervention was shorter (3,3+/-1,8 vs 23,5+/-18,9 hours) than in non- survivors. The IL-6 removal rate was significantly higher in the survivor group (70,8+/-15,87 vs 33,2+/-12,26). Conclusion(s): In survivors the timing of CytoSorb therapy was shorter and the IL-6 removal rate was higher than in non-survivors. This suggest that the early applying of CytoSorb adsorber in combination with Continuous Renal Replacement Therapy (CRRT) techniques, could increase the survival rate of septic shock patients. Using CytoSorb was safe and well tolerated with no device-related adverse events during or after the treatment.

The Use of Acute-Phase Proteins Apache Ii and Sofa to Predict the Mortality of Covid-19 Patients

Objective: Acute-phase proteins are a family of proteins synthesized by the liver. With this study, we aimed to investigate the effects of COVID-19 infection on acute phase reactants (AFR) and determine the usability of AFRs as prognostic factors in COVID-19 disease. Material(s) and Method(s): Serum samples taken for routine analysis of the patients admitted to the Emergency Department and diagnosed with COVID-19, were used. AFR levels of 30 patients who resulted in mortality and 30 recovered patients were evaluated. C-reactive protein (CRP), ferritin (FER), ceruloplasmin (Cp), albumin (Alb), prealbumin (Prealb), transferrin (Trf), lactate, Acute Physiology and Chronic Health Evaluation (APACHE), and Sequential Organ Failure Assessment (SOFA) assessment was performed. Result(s): The hazard ratio and 95% confidence interval for FER, CRP, lactate, Alb, Cp, Prealb, Trf, Age, SOFA, and APACHE were 1.001 (1.000-1.001), 1.005 (1.001- 1.008), 1.141 (1.016-1.243), 1.016 (0.740-1.399), 1.016 (0.740-1.399), 1.056 (1.017-1.100), 0.978 (0.917-1.035), 1.000 (0.995-1.006), 1.032 (1.004- 1.064), 1.104 (0.971-1.247), and 1.012 (0.974-1.051), respectively, in univariable model. Only CRP, lactate, and FER found significant in multivariable model. In addition, patients in the nonsurvivors group had significantly higher FER, CRP, lactate, APACHE, age, and SOFA. Nonsurvivors also had lower Alb, Prealb, and serum Trf level compared to survivors. Conclusion(s): CRP, lactate, and FER, which we have shown to be significantly higher in severe COVID-19 patients, will be valuable parameters that will contribute to clinical improvement if they are used in the follow-up of patients due to their easy measurement and predictive values.Copyright © 2023, Nobelmedicus. All rights reserved.

Infections in Patients With Cirrhosis Have a Changing Profile Over Time and Are Linked to a Higher Risk of Death Compared to Patients Without Cirrhosis

Introduction: Intensive care outcomes in patients with cirrhosis are relatively poor. The comparison between outcomes, especially related to infections, remains unclear in those with and without cirrhosis. With the emergence of resistant and fungal organisms, the changes in infection profiles over time are important to analyze. The aim of this study is to determine the impact of cirrhosis and infections on inpatient death over time in a qSOFA-matched cohort of patients with and without cirrhosis. Method(s): Inpatients admitted to ICUs throughout 2015-2021 were analyzed. Patients with cirrhosis were matched 1:1 by age, gender, and admission qSOFA to patients without;COVID-positive patients were excluded. Admission demographics, labs, the reasons for ICU transfer, infections, and inpatient death or hospice referral were obtained for each patient. Comparisons were made between patients with and without cirrhosis and those who died/referred to hospice versus not. Logistic regression for death/hospice was performed. In patients with cirrhosis, the culture results were compared over the years. Result(s): 1669 patients;833 cirrhosis and 836 non-cirrhosis patients were included. Patients with cirrhosis had higher rates of infection, positive culture, abdominal infection, and bacteremia. They also had higher gram-positive and fungal infections with a higher rate of VRE. They showed a greater organ failure load, death, and hospice referral compared to patients without cirrhosis. Logistic regression showed that cirrhosis (OR 4.0, p< 0.0001), admission qSOFA (1.60, p< 0.0001), WBC (1.02, p=0.003), reasons for ICU (altered mental status 1.69, hypotension 1.79, renal support 2.77, respiratory failure 1.79, CVA 1.96, all p< 0.0001) with Infection (1.77, p< 0.0001, >1 microbe isolated 1.86, p=0.05) were risk factors for death/hospice. The infection trend in the cirrhosis group showed a significant decrease in positive cultures and gram-negative infections and an increase in fungal and gram-positive infections over time. Conclusion(s): Despite matching for demographics and qSOFA, patients with cirrhosis had higher risks of death and organ failures. They were more likely to develop gram-positive and fungal infections with multiple organisms and VRE. Time trends in cirrhosis showed lower rates of positive cultures and gram-negative infections and an increase in fungal and gram-positive infections over time, which should encourage re-evaluation of diagnostic and prophylactic strategies in cirrhosis-related infections. (Figure Presented).

Secondary infections in critically ill patients with COVID-19: effects of intravenous IgM-enriched immunoglobulin therapy

Introduction: Critically ill patients with severe COVID-19 have an increased risk of bacterial and fungal superinfections due to a dysregulated immune response characterized by lymphopenia and low immunoglobulins levels. The intravenous immunoglobulins are involved in pathogen/toxin scavenging and inhibition of inflammatory mediators gene transcription with anti-apoptotic effects on immune system cells. This research aimed to describe the effects of intravenous IgM-enriched immunoglobulins in COVID-19 patients with sepsis due to secondary infections and low IgM levels. Method(s): We performed an observational retrospective study, including patients admitted to our intensive care unit (ICU) between March 2020 and February 2021 with severe COVID-19 and sepsis due to a superinfection (known or suspected) treated with intravenous IgM-enriched immunoglobulins. We collected demographic data and comorbidities. We noted hemodinamic data, antimicrobial and adiuvant therapies, laboratory results at ICU admission (T0), at the beginning (T1) and at the end (T2) of the IgM-enriched immunoglobulins infusion and at ICU discharge (T3). Result(s): In our cohort of 36 patients (Table 1) the prevalence of documented secondary infections was 83%. We observed a significant reduction of leukocytes from T0 to T3 (10.4 [8.3-14.5] x 103/ mmc vs 7.1 [4.8-11.2] x 103/ mmc, p < 0.01) and the SOFA score from T0 to T2 (7 [6-19] vs 5 [3-7], p < 0.01) and from T0 to T3 (7 [6-10] vs 4 [2-9], p < 0.01);from T1 to T2 (7 [6-9] vs 5 [3-7], p < 0.01) and from T1 to T3 (7 [6-9] vs 4 [2-9], p < 0.01). Cardiovascular SOFA showed a statistically significant reduction from T1 to T2 (4 [3-4] vs 0 [0-3], p < 0.01). Conclusion(s): The IgM-enriched immunoglobulins could improve organ function, as evidenced by the reduction of the SOFA score. Although the latest Surviving Sepsis Campaign guidelines suggest against using of IgM-enriched immunoglobulins, our study supports its use as an adjunctive therapy in COVID-19 patients with septic shock.

The laboratory parameters-derived CoLab-score as an indicator of the host response in ICU COVID-19 patients decreases over time: the Maastricht intensive care COVID cohort

Introduction: The CoLab-score was originally developed and validated to rule out COVID-19 in suspected patients presenting in the emergency department [1, 2]. The CoLab-score includes the patient's age and ten blood parameters, reflecting the host response to SARSCoV-2 infection. Here, we investigated the CoLab-score over time in mechanically ventilated COVID-19 patients at the ICU. We hypothesized that the CoLab-score will decrease over time, independent of survival, disease severity and pandemic periods. This would create the opportunity to monitor COVID-19 patients and potentially ruling out the need for isolation when the host response decreases and the infection is overcome. Method(s): We used serial data of the Maastricht Intensive Care Covid (MaastrICCht) cohort of mechanically ventilated COVID-19 patients to investigate the association between time and daily CoLab-score using linear-mixed models. Crude models were adjusted for sex, APACHE II score, SOFA score, and stratified for intensive care mortality. Result(s): 324 patients (73% men), aged 64 +/- 12 years with 5959 daily CoLab-scores, were included. CoLab-score decreased with 0.31 points per day (95% CI -0.33 to -0.28). Adjustment for sex, APACHE II and stratification for mortality did not change this result. Conclusion(s): The CoLab-score decreased over time in mechanically ventilated ICU COVID-19 patients, with a point reduction per three days. This suggests that the CoLab-score eventually decreases to a normal state, reflecting a host response that has overcome infection. Future investigation is warranted to assess whether the need for isolation can be ruled out based on the CoLab-score.

Non-invasive ventilation in >= 70 year old COVID-19 patients in a level two unit: retrospective cohort analysis, comparison with COVIP substudy and defense of a multifaceted work of breathing control driven strategy

Introduction: The debate about optimal management of patients with COVID-19 ARDS remains, including medical treatment, ventilatory strategies, awake proning and others. COVIP is a multicentric observational study with over 3000 patients under NIV. A substudy by Polok and al. evaluated patients (PTS) >= 70 years old. At our intermediate care unit (IU) we used a strategy of high dose corticosteroid started when the work of breathing (WOB) increased, prolonged awake prone positioning (> 12 h) and high CPAP ventilatory strategy. We describe our cohort of >= 70 years old NIV PTS and compare it to COVIP substudy results. Method(s): Descriptive retrospective study. Data were collected from electronic medical records of 95 COVID-19 PTS aged 70 years old or above under NIV at the IU between September/20 and March/21. Categorical data are presented as frequency (percentage) and were compared using chi2-test. Continuous variables were compared using Mann-Whitney U test. Cohort results were compared with those from Polok et al. COVIP substudy (COVIPss). Result(s): 95 of PTS were submitted to NIV. Median age was 76 years and 49.5% were male, versus 75.7 and 71.4% in COVIPss. Median admission SOFA score was 4 and CFS was 3 with 14% considered frail (CFS > 5). In COVIPss median SOFA was 5 and 17% of PTS were frail. The preferred mode was CPAP with median maximum pressure of 13. Mean PaO2/fiO2 ratio after start of NIV was 125, 30% < 100. NIV failure occurred in 46.3% versus 74,7% in COVIPss. Our intra-unit mortality was 31.6%. 14 PTS (14.7%) were submitted to invasive mechanical ventilation and 57% of those died. In COVIPss mortality at 30d was 52.9% in NIV and 47.7 in IMV groups. Conclusion(s): We argue that NIV is a valid option for COVID ARDS management if supported by a multifaceted strategy such as ours, using prone and CPAP for WOB control. We agree with COVIPss authors as NIV trial should be short and intubation promptly if WOB not controlled. Comparison with COVIP substudy NIV failure and mortality results, support our belief.

A new score to predict severe respiratory failure and guide anakinra treatment in COVID-19 pneumonia: analysis of the randomized SAVE-MORE trial

Introduction: Anakinra treatment is approved for the treatment of COVID-19 pneumonia in hospitalized adults in need of oxygen and at risk for progression into severe respiratory failure (SRF) defined as circulating concentrations of the biomarker suPAR (soluble urokinase plasminogen activator receptor) >= 6 ng/mL by the EMA and has been authorized for emergency use by FDA under an EUA [1]. This is based on the results of the randomized SAVE-MORE trial where suPAR >= 6 ng/ mL was used to select patients at risk for SRF [2]. The suPAR test is not commercially available in the USA and an alternative method of patient selection was needed. Method(s): In collaboration with the US FDA, an alternative method to select patients most likely to have suPAR >= 6 ng/mL based on commonly measured patient characteristics was developed. Patients with at least 3 of the following criteria are considered likely to have suPAR >= 6 ng/ ml: age >= 75 years, severe pneumonia by WHO criteria, current/previous smoking status, Sequential Organ Failure Assessment score >= 3, neutrophil-to-lymphocyte ratio >= 7, hemoglobin <= 10.5 g/dl, history of ischemic stroke, blood urea >= 50 mg/dl and/or history of renal disease. Result(s): The positive predictive value of this new score was 95.4% in SAVE-MORE population. However, a lower sensitivity meant a small proportion of patients with suPAR >= 6 ng/ml will not be identified by the new score. The adjusted hazard ratio for survival at 60 days for patients meeting this score and who receive anakinra is 0.45 (Fig. 1). Conclusion(s): The developed score predicts accurately patients with suPAR levels >= 6 ng/mL and may be used as an alternative to guide anakinra treatment in patients with COVID-19 pneumonia. Based on these subgroup results, patients in SAVE-MORE who met the new score appeared to show beneficial efficacy results with treatment of anakinra consistent with the overall studied population.

An observational study on the use of oral vitamin C in critically ill stage-5 patients with COVID-19 infection

Introduction: The evidence-based use of the oral form of Vitamin C as adjuvant treatment for critically ill COVID-19 patients is lacking worldwide despite its intravenous preparation form being demonstrated to be potentially beneficial in some studies. The present study objective was to evaluate the effects of oral Vitamin C in the treatment of severe COVID-19. Method(s): This was an open-label observational study with propensity score matching on unvaccinated, similar medication history, hospitalized stage-5 severe COVID-19 patients, who were treated with daily 2g, 4g, or 6g of oral Vitamin C respectively from November 2020 to December 2021. The clinical data were collected retrospectively for analysis. The study outcomes were 28-day in-hospital mortality, the proportion of mechanical ventilation-free days (MVFD), the Day 1, Day 3, and Day 7 of both the inflammation progression (c-reactive protein) and the Sequential Organ Failure Assessment score (SOFA). Result(s): A total of 147 patients were recruited. The number of subjects in the 2g, 4g, and 6g Vitamin C groups was 43, 44, and 60 respectively. There was no significant difference in the 28-day mortality (p=0.336), the MVFD (p=0.486), the c-reactive protein level on Day 1 (p=0.856), Day 3 (p=0.977), Day 7 (p=0.462), and the SOFA score on Day 1(p=0.540), Day 3 (p=0.149) and Day 7 (p=0.754) between the three Vitamin C dosing groups. Conclusion(s): The present study showed that the oral form of Vitamin C provided no benefit in reducing stage-5 COVID-19 patients' hospital mortality, the mechanical ventilation requirement, or the overall inflammation progression.

Critical illness in patients with omicron variant COVID-19: different but crucial

Introduction: During the COVID-19 pandemic, various virus variants evolved worldwide. COVID-19 omicron (CO) was associated with a decrease in length of hospital stay, ICU admission and death [1] as compared to COVID-19 delta (CD). To estimate impact of CO on ICUs worldwide, we investigated characteristics, disease course and outcome of critically ill CO patients. Method(s): Of 8562 critically ill COVID-19 patients included in the prospective international multicenter RISC-19-ICU registry [2,3], characteristics and outcome were compared for 1890 CD and 272 CO patients admitted to ICU between 1-2021 and 9-2022. Mixed model analysis corrected for individual center effects and adjusted for age, sex, vaccination status, use of steroids and anticoagulants was used. Result(s): There was no difference in age, sex and BMI between groups. CO patients had more comorbidities [mean difference (MD) 0.7, 95% CI (0.5-1.0), p = 0.02], especially arterial hypertension, and higher SAPS II score [MD 0.0 (0-0.1), p < 0.001], SOFA score [MD 0.1 (0.1-0.3), p < 0.0001]. CO patients presented with higher cardiovascular system SOFA subscore, but better PF-ratio at ICU admission and smaller risk for intubation and mechanical ventilation throughout their ICU stay [OR 0.5 (0.3-0.8)]. There was no difference in ECMO treatments, ICU length of stay [MD 0.6 (0-11.4), p = 0.72] or ICU survival [HR 1 (0.7-1.5), p = 0.88] between the two groups. Conclusion(s): We show that critically ill CO patients present with more comorbidities, less severe respiratory disease but more severe hemodynamic instability at ICU admission as compared to CD patients, although the ICU length of stay and mortality was similar. These differences could be explained by differences in disease characteristics caused by CO, or by the increasing prevalence of CO as co-factor to preexisting disease. Continued monitoring of critically ill CO patients in ICUs worldwide is warranted.

Predictors of poor outcomes in patients with pandemic viral infections (influenza AH1N1pdm09, COVID-19) on a ventilator.

Considering the commonality of the pathogenetic links of the critical forms of COVID-19 and influenza AH1N1pdm09 (cytokine over-release syndrome), the question arises: will the predictors of an unfavorable outcome in patients on mechanical ventilation and, accordingly, the universal tactics of respiratory support in these diseases be identical? Objective. In a comparative aspect, to characterize patients with influenza AH1N1pdm09 and COVID-19 who were on mechanical ventilation, to identify additional clinical and laboratory risk factors for death, to determine the degree of influence of respiratory support (RP) tactics on an unfavorable outcome in the studied category of patients. Patients and methods. Patients treated on the basis of resuscitation and intensive care departments of the State Budgetary Healthcare Institution "SKIB" in Krasnodar and the State Budgetary Healthcare Institution "IB No 2" in Sochi were studied: group 1 - 31 people with influenza AH1N1pdm09 (21 people died - subgroup 1A;10 people survived - subgroup 1B) and group 2 - 50 people with COVID-19 (29 patients died - subgroup 2A;21 people survived - subgroup 2B). All patients developed hypoxemic ARF. All patients received step-by-step tactics of respiratory support, starting with oxygen therapy and ending with the use of "traditional" mechanical ventilation. Continuous variables were compared in subgroups of deceased and surviving patients for both nosologies at the stages: hospital admission;registration of hypoxemia and the use of various methods of respiratory therapy;development of multiple organ dysfunctions. With regard to the criteria for which a statistically significant difference was found (p < 0.05), we calculated a simple correlation, the relative risk of an event (RR [CI 25-75%]), the cut-off point, which corresponded to the best combination of sensitivity and specificity. Results. Risk factors for death of patients with influenza AH1N1pdm09 on mechanical ventilation: admission to the hospital later than the 8th day of illness;the fact of transfer from another hospital;leukocytosis >=10.0 x 109/l, granulocytosis >=5.5 x 109/l and LDH level >=700.0 U/l at admission;transfer of patients to mechanical ventilation on the 9th day of illness and later;SOFA score >=8;the need for pressor amines and replacement of kidney function. Predictors of poor outcome in ventilated COVID-19 patients: platelet count <=210 x 109/L on admission;the duration of oxygen therapy for more than 4.5 days;the use of HPNO and NIV as the 2nd step of RP for more than 2 days;transfer of patients to mechanical ventilation on the 14th day of illness and later;oxygenation index <=80;the need for pressors;SOFA score >=8. Conclusion. When comparing the identified predictors of death for patients with influenza and COVID-19 who needed mechanical ventilation, there are both some commonality and differences due to the peculiarities of the course of the disease. A step-by-step approach to the application of respiratory support methods is effective both in the case of patients with influenza AH1N1pdm09 and patients with COVID-19, provided that the respiratory support method used is consistent with the current state of the patient and his respiratory system, timely identification of markers of ineffectiveness of the respiratory support stage being carried out and determining the optimal moment escalation of respiratory therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.

A nationwide cohort study of pregnant and postpartum patients with severe COVID-19 pneumonitis in ICU in Israel

Introduction: This study included pregnant patients with severe COVID to test the hypothesis that the impact of delivery on maternal outcome depends upon illness severity at the time of delivery;we hypothesized that patients not yet requiring IPPV would improve following delivery (due to improvement in respiratory mechanics), while patients already on IPPV, or close to requiring ventilation, would deteriorate (due to maternal cardiovascular intolerance to autotransfusion). Method(s): This multicenter, prospective/retrospective cohort study evaluated Israeli ICU admissions of pregnant women with COVID-19 pneumonitis from 1-Feb-2020 to 31-Jan-2022. We assessed maternal, neonatal outcomes and longitudinal maternal clinical data. The primary outcome was maternal outcome (no-IPPV, IPPV, ECMO, death). The primary longitudinal outcome was SOFA score, the secondary longitudinal outcome was the novel PORCH score (PEEP, Oxygenation, Respiratory-support, Chest-X-ray, Haemodynamic-support). Patients were classified into: no-delivery, postpartum admission, deliverycritical and delivery-not-critical groups. Result(s): 84 patients in 13 ICUs were analysed;there were 34 nodelivery, 4 postpartum, 32 delivery-critical, 14 delivery-not-critical patients. Delivery-critical and postpartum had worse outcomes with, 26/32(81%) and 4/4(100%) requiring IPPV;12/32(38%) and 3/4(75%) requiring ECMO;1/32(3%) and 2/4(50%) dying. Deliverynot- critical and no-delivery had far better outcomes with, respectively, 6/34(18%) and 2/14(14%) requiring mechanical ventilation;no patients required ECMO or died. SpO2, S/F ratio, P/F ratio in Deliverycritical deteriorated on the day of delivery, continued to deteriorate, and took longer to recover;delivery-not-critical improved rapidly following delivery. The day of delivery was a highly significant covariate for PORCH (p < 0.0001), not SOFA (p = 0.09). Conclusion(s): Interventional delivery should be considered for maternal indications before patients deteriorate and require IPPV.

Continuous renal replacement therapy with oXiris filter in critically ill COVID-19 patients

Introduction: COVID-19 causes a major inflammatory response, which may progress to shock and multiple organ failure. We explored whether continuous renal replacement therapy (CRRT) using adsorption membrane (oXiris) could reduce the inflammatory response in critically ill COVID-19 patients with acute renal failure (ARF) [1, 2]. Method(s): Case-control study including 24 critically ill COVID-2019 patients requiring RRT using an oXiris filter. We measured cytokines before and during treatment as well as relevant clinical endpoints. The control group was selected among COVID-19 patients included into our ongoing RECORDS trial (NCT04280497) who received RRT without adsorbing filters. Result(s): 24 severe COVID-19 patients, admitted to the intensive care unit (ICU) and treated with CRRT using the oXiris filter between March and April 2020 (20 males and 4 females);median age 67. The average time from COVID-19 symptoms to initiation of oXiris treatment was 18 +/- 7 days, and from ICU admission to initiation of oXiris treatment 9.5 +/- 7.8 days and from ARF to oXiris treatment was 3 +/- 5 days. The average length of treatment was 152.8 +/- 92.3 h. Treatment was associated with cytokine decreases for IL-1beta (p = 0.00022), MCP-1 (p = 0.03), and MIP-1 alpha (p = 0.03). The SOFA scores also showed a reduction over 48 h of therapy without reaching statistical significance. Our study found no significant effect of hemodynamic status. The average ICU stay length was 14 +/- 5 days and the mortality rate was 79% in the Oxiris group. We compared the mortality across the two matched groups, there was no evidence of any difference in mortality (Fig. 1). Conclusion(s): In our study, CRRT using the oXiris filter seemed to effectively remove IL-1 beta, MCP-1, and MIP-1 alpha in COVID-19 patients. These exploratory results should be confirmed in a randomized controlled study.

Medication regimen complexity (MRC-ICU) for in-hospital mortality prediction in COVID-19 patients

Purpose: The medication regimen complexity-intensive care unit (MRC-ICU) score was developed prior to the existence of COVID-19. The purpose of this study was to assess if MRC-ICU could predict in-hospital mortality in patients with COVID-19. Method(s): A single-center, observational study was conducted from August 2020 to January 2021. The primary outcome of this study was the area under the receiver operating characteristic (AUROC) for in-hospital mortality for the 48-hour MRC-ICU. Age, sequential organ failure assessment (SOFA), and World Health Organization (WHO) COVID-19 Severity Classification were assessed. Logistic regression was performed to predict in-hospital mortality as well as WHO Severity Classification at 7 days. Result(s): A total of 149 patients were included. The median SOFA score was 8 (IQR 5-11) and median MRC-ICU score at 48 hours was 15 (IQR 7-21). The in-hospital mortality rate was 36% (n = 54). The AUROC for MRC-ICU was 0.71 (95% Confidence Interval (CI), 0.62-0.78) compared to 0.66 for age, 0.81 SOFA, and 0.72 for the WHO Severity Classification. In univariate analysis, age, SOFA, MRC-ICU, and WHO Severity Classification all demonstrated significant association with in-hospital mortality, while SOFA, MRC-ICU, and WHO Severity Classification demonstrated significant association with WHO Severity Classification at 7 days. In univariate analysis, all 4 characteristics showed significant association with mortality;however, only age and SOFA remained significant following multivariate analysis. Conclusion(s): In the first analysis of medication-related variables as a predictor of severity and in-hospital mortality in COVID-19, MRC-ICU demonstrated acceptable predictive ability as represented by AUROC;however, SOFA was the strongest predictor in both AUROC and regression analysis.Copyright © The Author(s) 2023.