COVID-19 Patients In Intensive Care Unit Research Articles

EVIDENCE FROM FATAL COVID-19 FOR TARGETING THE BRADYKININ METABOLISM-A SINGLE-CENTER COHORT STUDY.

Background: Severe progression of COVID-19 to critical illness, with pulmonary failure, multiple organ failure, and death, is driven by systemic inflammatory responses with overproduction of inflammatory cytokines. In the past years, the potential role of bradykinin, leading to inappropriate immune responses in the pathogenesis of COVID-19, has been raised in a so-called bradykinin storm. However, clinical investigations of bradykinin, its metabolite des-Arg 9 -bradykinin, or substance P, are rare or completely lacking during intensive care of COVID-19 patients. A prospective prolonged cohort study was conducted, including 44 COVID-19 patients (09/2020-02/2021, prevalent wildtype SARS-CoV-2) from the intensive care unit. Plasma levels of bradykinin, des-Arg 9 -bradykinin, and substance P were measured daily by ELISA in survivors (n = 21) and nonsurvivors (n = 23) of COVID-19 from admission until discharge or death. Results: We found significantly higher plasma levels of des-Arg 9 -bradykinin in survivors and nonsurvivors of COVID-19 compared with healthy controls. In addition, plasma des-Arg 9 -bradykinin levels were higher ( P < 0.001, effect size = 0.79) in nonsurvivors compared with survivors of COVID-19 and correlated significantly with disease worsening, and clinical parameters of inflammation, like leukocyte count, IL-6 or lactate dehydrogenase, and outcome. Consequently, compared with healthy controls, bradykinin and substance P plasma levels were significantly reduced in survivors and nonsurvivors of COVID-19. Furthermore, plasma substance P levels were significantly reduced ( P < 0.001, effect size = 0.7) in nonsurvivors compared with survivors of COVID-19, whereas plasma bradykinin levels did not significantly differ between survivors and nonsurvivors of COVID-19. Conclusion: Our data demonstrates that des-Arg 9 -bradykinin is significantly elevated in COVID-19 intensive care unit patients and is associated with disease severity, clinical inflammatory parameters, and survival. These results indicate that des-Arg 9 -bradykinin, not bradykinin, is one of the pivotal peptides of concern for the lethal COVID-19 aggravation and outcome. Further investigations are necessary to evaluate whether des-Arg 9 -bradykinin exhibits potent blood biomarker properties in COVID-19 and offer new treatment approaches.

Machine learning algorithms for predicting determinants of COVID-19 mortality in South Africa.

COVID-19 has strained healthcare resources, necessitating efficient prognostication to triage patients effectively. This study quantified COVID-19 risk factors and predicted COVID-19 intensive care unit (ICU) mortality in South Africa based on machine learning algorithms. Data for this study were obtained from 392 COVID-19 ICU patients enrolled between 26 March 2020 and 10 February 2021. We used an artificial neural network (ANN) and random forest (RF) to predict mortality among ICU patients and a semi-parametric logistic regression with nine covariates, including a grouping variable based on K-means clustering. Further evaluation of the algorithms was performed using sensitivity, accuracy, specificity, and Cohen's K statistics. From the semi-parametric logistic regression and ANN variable importance, age, gender, cluster, presence of severe symptoms, being on the ventilator, and comorbidities of asthma significantly contributed to ICU death. In particular, the odds of mortality were six times higher among asthmatic patients than non-asthmatic patients. In univariable and multivariate regression, advanced age, PF1 and 2, FiO2, severe symptoms, asthma, oxygen saturation, and cluster 4 were strongly predictive of mortality. The RF model revealed that intubation status, age, cluster, diabetes, and hypertension were the top five significant predictors of mortality. The ANN performed well with an accuracy of 71%, a precision of 83%, an F1 score of 100%, Matthew's correlation coefficient (MCC) score of 100%, and a recall of 88%. In addition, Cohen's k-value of 0.75 verified the most extreme discriminative power of the ANN. In comparison, the RF model provided a 76% recall, an 87% precision, and a 65% MCC. Based on the findings, we can conclude that both ANN and RF can predict COVID-19 mortality in the ICU with accuracy. The proposed models accurately predict the prognosis of COVID-19 patients after diagnosis. The models can be used to prioritize COVID-19 patients with a high mortality risk in resource-constrained ICUs.

Comparative Efficacy of High-flow Nasal Cannula and Mechanical Ventilation in COVID-19 Intensive Care Unit Patients: A Saudi Arabian Retrospective Analysis

Abstract Introduction: The ongoing COVID-19 pandemic has profoundly affected respiratory care in intensive care units (ICUs) globally, necessitating an evaluation of various respiratory support methods to enhance patient care. This study compares the efficacy of high-flow nasal cannula (HFNC) and mechanical ventilation (MV) in treating COVID-19 patients in ICUs, aiming to refine treatment strategies in this critical setting. Methods: In this retrospective analysis, we examined a cohort of COVID-19 ICU patients who received either HFNC or MV. The study included patients with confirmed COVID-19, necessitating ICU admission and respiratory support. We collected comprehensive clinical data, including demographics, medical history, and treatment outcomes. Advanced statistical methods were applied to evaluate the effectiveness of HFNC versus MV, considering diverse clinical parameters. Results: The study’s findings highlight the key differences in the effectiveness of HFNC and MV among COVID-19 ICU patients. Our data showed distinct recovery patterns and respiratory support needs between patients treated with HFNC and those receiving MV, providing crucial insights into their management in ICU settings. Conclusion: This research illuminates the vital aspect of respiratory support in COVID-19 ICU patient care. The comparative analysis of HFNC and MV reveals differing clinical outcomes, emphasizing the need for personalized respiratory support strategies. These findings have broad implications, offering valuable guidance for clinical practices and future research in respiratory care during the COVID-19 pandemic and beyond.

Secondary Infections in Intensive Care Unit Patients in the COVID-19 Pandemic - Retrospective Study of the Incidence, Patterns, Risk Factors, and Outcomes

Introduction: The COVID-19 pandemic has raised significant concerns for secondary infections. In the second wave, there was an unprecedented epidemic of secondary invasive fungal infections. This study analyses the prevalence, details, risk factors, and outcomes of secondary infections in COVID-19 patients in a tertiary intensive care unit (ICU) in India. Materials and Methods: Retrospective analysis of secondary infections in ICU COVID-19 patients between April 2021 and June 2021. Demographic data, secondary bacterial and fungal infections, immunomodulator therapy, antimicrobial susceptibility data, and clinical outcomes were analyzed. Results: 71/238 (29.83%) ICU patients developed secondary bacterial and fungal infections. Mortality with secondary infections was significantly higher (80.28% [P &lt; 0.05]), compared to an overall ICU mortality of 51.68%. In patients with secondary infections, 59.66% were referred from other hospitals after receiving initial treatment and 52.10% had received various immunomodulatory therapies. Prolonged mechanical ventilation, indwelling central venous, and urinary catheters had higher secondary infection rates and higher mortality. Gram-negative bacteria were isolated in 85.91% and 32.39% had fungal isolates. Klebsiella pneumoniae, followed by Acinetobacter baumannii, were the predominant bacteria. Candida spp., followed by Mucormycosis, were the predominant fungal pathogens. Multi-drug resistant (MDR) infections were common (73.28%). 49.3% of secondary infection patients had polymicrobial infections, including fungal infections, with a higher mortality of 82.86%. Conclusions: There was a high incidence of secondary MDR bacterial and fungal infection, including Mucormycosis, in ICU COVID-19 patients, with higher mortality. Risk factors included immunomodulators such as tocilizumab, bevacizumab, and itolizumab, steroids, invasive tubes and catheters, and prolonged ICU and hospital stay. By uniform steroids, we meant the recommended use of moderate-to-high dose steroids for all patients with severe COVID-19 pneumonia (recovery trial), invasive tubes and catheters, and prolonged ICU and hospital stay.

Health-Related Quality of Life Improves in Parallel with FEV1 and 6-Minute Walking Distance Test at Between 3 and 12 Months in Critical COVID-19 Survivors

BackgroundIn COVID-19 intensive care unit (ICU)–admitted patients, multiorgan acute complications lead to long-lasting sequelae. The aim of this study was to assess (1) changes in chest CT, pulmonary function test (PFT), functional capacity (6-minute walking distance test (6MWT)), and health-related quality of life (HR-QoL) among ICU COVID-19 survivors at 3, 6, and 12 months after ICU discharge and (2) predictors of persistent impairment/improvement in 6MWT and HR-QoL. MethodsICU COVID-19 survivors were prospectively included. Outcomes at 3, 6, and 12 months included PFT, 6MWT, respiratory muscle strength (RMS), HR-QoL (SF-36), Medical Research Council dyspnea scale (mMRC), and post-COVID Functional Status scale. ResultsEighty-seven survivors were included, from June 3, 2020, to September 2, 2021. At 12 months, 50% of PFT were normal, 46% were restrictive, and 22% showed reduced diffusing capacity for carbon monoxide (DLCO). Impaired DLCO was associated with ICU length of stay and age. In mixed linear model analysis, improvements in RMS and mMRC persisted over time regardless of the adjustments applied (P ≤ .050). SF-36 improved in parallel with FEV1 and 6MWT between 3 and 12 months (P ≤ .044), while increment in DLCO correlated with changes in FEV1 and total lung capacity (TLC) (p ≤ 0.026). ConclusionsThis longitudinal study demonstrated that improvements in SF-36 occur in parallel with improvements in FEV1 and 6MWT between 3 and 12 months post-ICU discharge in a sample of critically ill COVID-19 patients. However, PFT remained, however, abnormal in 50% of patients. Based on continued improvements observed from 3 to 12 months, it is anticipated that COVID-19 ICU patients will continue to recover similarly to ARDS patients.

Epidemiological Characteristics and Outcomes Predictors for Intensive Care Unit COVID-19 Patients in Al-Madinah, Saudi Arabia. Retrospective Cohort Study.

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) increased the demand for intensive care unit (ICU) services. Mortality and morbidity rates among ICU COVID-19 patients are affected by several factors, such as severity, comorbidities, and coinfections. In this study, we describe the demographic characteristics of COVID-19 patients admitted to an ICU in Saudi Arabia, and we determined the predictors for mortality and prolonged ICU length of stay. Additionally, we determined the prevalence of bacterial coinfection and its effect on the outcomes for ICU COVID-19 patients. We retrospectively studied the medical records of 142 COVID-19 patients admitted to the ICU at a tertiary hospital in Madinah, Saudi Arabia. Data on demographics, medical history, mortality, length of stay, and presence of coinfection were collected for each patient. Neutrophil-to-Lymphocyte ratio (NLR) and intubation were reliable predictors of mortality and ICU length of stay among these ICU COVID-19 patients. Moreover, bacterial coinfections were detected in 23.2% of the patients and significantly (p < 0.001) prolonged their ICU length of stay, explaining the 10% increase in the length of stay for these patients. Furthermore, mortality reached 70% among the coinfected patients, and 60.8% of the isolated coinfecting pathogens were multidrug-resistant (MDR) strains of Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus. Increased NLR and intubation are predictors of mortality and prolonged length of stay in COVID-19 patients admitted to the ICU. Coinfection with MDR bacterial strains potentially results in complications and is a high-risk factor for prolonged ICU length of stay.

The Activities and Roles of Trauma Surgeons in the Treatment of COVID-19 Patients

Trauma surgeons' roles in a national hospital in Korea changed during the COVID-19 pandemic. In this study, we report on their roles over a 15-month period (March 2020 to May 2021) including the eight months where the hospital was a COVID-19-only hospital. Despite shortages in medical resources including medical personnel, and intensive care unit (ICU) beds, the trauma surgeons helped to control the public health problem by assuming various roles including working in another COVID-19 ICU in Dae-gu, treating trauma patients with COVID-19 or those who needed self-quarantine, being in charge of care for some COVID-19 patients in the ICU (for two months), and performing the role of a rapid response team member for COVID-19 ICU patients. In this report, we emphasize how trauma surgeons, along with intensivists, played an active role in treatment of COVID-19 patients, and helped prevent the collapse of the healthcare system within the hospital during the pandemic.

Identification of risk factors and development of a predictive model for bloodstream infection in intensive care unit COVID-19 patients

To identify risk factors for nosocomial bloodstream infections (BSIs) in intensive care unit (ICU) patients with COVID-19 and to build a predictive model for BSIs. The retrospective case-control study included 236 ICU COVID-19 patients with BSIs group and 234 patients in the control group. Demographic and laboratory data, comorbidities, drug use, invasive procedures and identified pathogens were recorded separately for patients directly admitted and transferred to ICU. Fine and Gray's multi-variate competing risk model was used to build a predictive model for patients transferred to ICU. The risk factors were: interleukin inhibitors (HR= 6.1 (95% CI: 2.0-18.5)) and dexamethasone (HR= 3.0 (95% CI: 1.3-7.1)) use in previous hospitalization, glomerular filtration rate <60mL/min per 1.73m2 (HR= 4.0 (95% CI: 2.1-7.6)) and blood glucose >9mmol/L (HR= 2.5 (95% CI: 1.4-4.6)) in patients directly admitted to ICU; and dexamethasone use in previous hospitalization (HR= 4.5 (95% CI: 1.8-11)), the total dexamethasone dose before transfer to ICU (HR= 1.2 (95% CI: 1.06-1.37)), diabetes mellitus (HR= 1.4 (95% CI: 1.1-1.9)), alanine transaminase (ALT) ≥35.5 U/L on hospital admission (HR= 1.5 (95% CI: 1.1-2.1)), and the use of low-flow oxygen versus high-flow oxygen therapy or non-invasive mechanical ventilation on admission to ICU ((HR= 2.7 (95% CI: 5.6-11.1)) in patients transferred to ICU. A predictive model had sensitivity of 63-73% and specificity of 71-83% at different times of ICU stay. Our findings may help clinicians detect patients at high risk of developing BSIs.

Point-of-care pancreatic stone protein measurement in critically ill COVID-19 patients

IntroductionPancreatic stone protein (PSP) is a novel biomarker that is reported to be increased in pneumonia and acute conditions. The primary aim of this study was to prospectively study plasma levels of PSP in a COVID-19 intensive care unit (ICU) population to determine how well PSP performed as a marker of mortality in comparison to other plasma biomarkers, such as C reactive protein (CRP) and procalcitonin (PCT).MethodsWe collected clinical data and blood samples from COVID-19 ICU patients at the time of admission (T0), 72 h later (T1), five days later (T2), and finally, seven days later. The PSP plasma level was measured with a point-of-care system; PCT and CRP levels were measured simultaneously with laboratory tests. The inclusion criteria were being a critical COVID-19 ICU patient requiring ventilatory mechanical assistance.ResultsWe enrolled 21 patients and evaluated 80 blood samples; we found an increase in PSP plasma levels according to mixed model analysis over time (p < 0.001), with higher levels found in the nonsurvivor population (p < 0.001). Plasma PSP levels achieved a statistically significant result in terms of the AUROC, with a value higher than 0.7 at T0, T1, T2, and T3. The overall AUROC of PSP was 0.8271 (CI (0.73–0.93), p < 0.001). These results were not observed for CRP and PCT.ConclusionThese first results suggest the potential advantages of monitoring PSP plasma levels through point-of-care technology, which could be useful in the absence of a specific COVID-19 biomarker. Additional data are needed to confirm these results.Graphical

The relationship between the PRE-DELIRIC score and the prognosis in COVID-19 ICU patients

Background/Aim: The PRE-DELIRIC score is a test to detect delirium in the intensive care unit (ICU). Delirium has been studied as a factor associated with the clinical course of patients in COVID-19 intensive care. Our study aimed to investigate the relationship between the PRE-DELIRIC score and prognosis in patients followed in the COVID-19 ICU. Methods: Patients hospitalized in the COVID-19 ICU between March 2020 and May 2021 were retrospectively analyzed, and 461 patients were included in the study. The PRE-DELIRIC scores of the patients were calculated using data obtained from the hospital information system. Patients with a PRE-DELIRIC score ≥50 were considered Group 1, and those with a score &lt;50 were considered Group 2. The groups were compared in terms of gender, Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE II) score, Sequential Organ Failure Evaluation Score (SOFA), length of hospital stay, and mortality rates. Results: Of the 461 patients included in the study, 153 were female, and 308 were male. A high PRE-DELIRIC score was determined in 157 (34.1%) patients (Group 1), while 304 patients (65.9%) had lower scores (Group 2). The hospitalization duration was 9.6 (6.7) days, and the mortality rate was 87.2% in Group 1, compared to 8.2 (6.03) days and 38.1% in Group 2, respectively. A significant difference was observed in the length of hospital stay and mortality between the groups (P&lt;0.001). The rate of patients who were intubated and followed up on an invasive mechanical ventilator (MV) was 81.5% in Group 1, whereas it was 16.4% in Group 2 (P&lt;0.001). Conclusion: Our study found that patients with a high PRE-DELIRIC score indicating delirium had higher mortality rates and longer hospital and MV stays. Delirium is one of the factors affecting mortality in COVID-19 disease. We believe that the PRE-DELIRIC score, as one of these factors, can serve as an important prognostic test in COVID-19 ICU patients.

Pulmonary Functional Outcomes at 3 Months in Critical COVID-19 Survivors Hospitalized during the First, Second, and Third Pandemic Waves.

Despite improved management of patients with COVID-19, we still ignore whether pharmacologic treatments and improved respiratory support have modified outcomes for intensive care unit (ICU) surviving patients of the three first consecutive waves (w) of the pandemic. The aim of this study was to evaluate whether developments in the management of ICU COVID-19 patients have positively impacted respiratory functional outcomes, quality of life (QoL), and chest CT scan patterns in ICU COVID-19 surviving patients at 3 months, according to pandemic waves. We prospectively included all patients admitted to the ICU of two university hospitals with acute respiratory distress syndrome (ARDS) related to COVID-19. Data related to hospitalization (disease severity, complications), demographics, and medical history were collected. Patients were assessed 3 months post-ICU discharge using a 6 min walking distance test (6MWT), a pulmonary function test (PFT), a respiratory muscle strength (RMS) test, a chest CT scan, and a Short Form 36 (SF-36) questionnaire. We included 84 ARDS COVID-19 surviving patients. Disease severity, complications, demographics, and comorbidities were similar between groups, but there were more women in wave 3 (w3). Length of stay at the hospital was shorter during w3 vs. during wave 1 (w1) (23.4 ± 14.2 days vs. 34.7 ± 20.8 days, p = 0.0304). Fewer patients required mechanical ventilation (MV) during the second wave (w2) vs. during w1 (33.3% vs. 63.9%, p = 0.0038). Assessment at 3 months after ICU discharge revealed that PFTs and 6MWTs scores were worse for w3 > w2 > w1. QoL (SF-36) deteriorated (vitality and mental health) more for patients in w1 vs. in w3 (64.7 ± 16.3 vs. 49.2 ± 23.2, p = 0.0169). Mechanical ventilation was associated with reduced forced expiratory volume (FEV1), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO), and respiratory muscle strength (RMS) (w1,2,3, p < 0.0500) on linear/logistic regression analysis. The use of glucocorticoids, as well as tocilizumab, was associated with improvements in the number of affected segments in chest CT, FEV1, TLC, and DLCO (p < 0.01). With better understanding and management of COVID-19, there was an improvement in PFT, 6MWT, and RMS in ICU survivors 3 months after ICU discharge, regardless of the pandemic wave during which they were hospitalized. However, immunomodulation and improved best practices for the management of COVID-19 do not appear to be sufficient to prevent significant morbidity in critically ill patients.

Is Gastrointestinal Bleeding a Problem for COVID-19 Intensive Care Unit Patients?

The objective of this study was to describe the COVID-19 intensive care unit population and analyze the characteristics and outcomes of gastrointestinal bleeding patients. An observational prospective study design was used following the STROBE checklist. All patients admitted between February and April 2020 to the intensive care unit were included. Main outcome measures were first bleeding event timing, sociodemographic and clinical data before admission, and gastrointestinal symptoms. A total of 116 COVID-19 patients were included; 16 (13.8%) developed gastrointestinal bleeding, 15 were males (93.7%), and the median age was 65.64 ± 7.33 years. All 16 patients were mechanically ventilated, one (6.3%) already had gastrointestinal symptoms, 13 (81.3%) had at least one concomitant disease, and six (37.5%) died. Bleeding episodes occurred on a mean of 16.9 ± 9.5 days after admission. Nine cases (56.3%) had effects on their hemodynamics, hemoglobin levels, or transfusion requirements; six (37.5%) required diagnostic imaging; and two (12.5%) underwent endoscopy procedures. The Mann-Whitney test showed statistically significant differences between the two groups of patients concerning comorbidities. Gastrointestinal bleeding can occur in critically ill patients with COVID-19. Having a solid tumor or chronic liver disease seems to increase that risk. Nurses caring for COVID-19 patients are urged to individualize patients at higher risk in order to improve safety.

Echocardiogram in Critically ill Patients with COVID-19: ECOVID Study

Background Literature is scarce on echocardiographic characteristics of COVID-19 patients admitted to the intensive care unit (ICU). Objectives To describe echocardiographic characteristics of ICU COVID-19 patients and associate them with clinical signals/symptoms, laboratory findings and outcomes. Methods Patients with RT-PCR-confirmed COVID-19, admitted to the ICU, who underwent echocardiography were included. Clinical characteristics associated with an abnormal echocardiogram (systolic ventricular dysfunction of any degree — left and/or right ventricle — and/or high filling pressures and/or moderate to severe pericardial effusion) [...]

The outcome of COVID‐19 patients in the intensive care unit in Sudan: A cross‐sectional study

A major outbreak of coronavirus spread all over the world and gave rise to high mortality rate and high admission rate to intensive care unit (ICU). This cohort study aims to assess the outcome of COVID-19 patients in ICU and to investigate the factors associated with mortality. This is a multicentered retrospective cohort study that was conducted among confirmed cases of COVID-19 patients, who were admitted to ICU in Sudan during March 2021. The data collection was done manually from the medical records of patients. Mortality rate and association and prediction of factors associated with mortality were obtained using Statistical Package for the Social Sciences software (SPSS) version 22. The mortality rate among patients in this study was 70%. Using the chi-square test we found that age, needing intubation, developing Systemic inflammatory response syndrome, neurological complications, hematological complications, and cardiac complications have a significant association with the outcome. Majority of COVID-19 patients who were admitted to the ICU died. 55.8% of patients developed at least one complication during their stay in ICU. The age, the need for intubation, and developing of systematic inflammatory response syndrome (SIRS) are the factors that predict the mortality.

Plasma Apolipoprotein Concentrations Are Highly Altered in Severe Intensive Care Unit COVID-19 Patients: Preliminary Results from the LIPICOR Cohort Study.

SARS-CoV-2 infection goes beyond acute pneumonia, as it also impacts lipid metabolism. Decreased HDL-C and LDL-C levels have been reported in patients with COVID-19. The lipid profile is a less robust biochemical marker than apolipoproteins, components of lipoproteins. However, the association of apolipoprotein levels during COVID-19 is not well described and understood. The objective of our study is to measure plasma levels of 14 apolipoproteins in patients with COVID-19 and to evaluate the relationships between apolipoprotein levels, severity factors and patient outcomes. From November to March 2021, 44 patients were recruited on admission to the intensive care unit because of COVID-19. Fourteen apolipoproteins and LCAT were measured by LC-MS/MS in plasma of 44 COVID-19 patients on admission to the ICU and 44 healthy control subjects. Absolute apolipoprotein concentrations were compared between COVID-19 patients and controls. Plasma apolipoproteins (Apo) A (I, II, IV), C(I, II), D, H, J and M and LCAT were lower in COVID-19 patients, whereas Apo E was higher. COVID-19 severity factors such as PaO2/FiO2 ratio, SO-FA score and CRP were correlated with certain apolipoproteins. Lower Apo B100 and LCAT levels were observed in non-survivors of COVID-19 versus survivors. To conclude, in this study, lipid and apolipoprotein profiles are altered in COVID-19 patients. Low Apo B100 and LCAT levels may be predictive of non-survival in COVID-19 patients.

Changes in PD-1- and CTLA-4-bearing blood lymphocytes in ICU COVID-19 patients treated with Favipiravir/Kaletra or Dexamethasone/Remdesivir: a pilot study.

COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.e., severe) or infection ward (i.e., moderate) and after 7 days of antiviral therapy. COVID-19 patients were treated with either favipiravir or Kaletra (FK group, 11 severe and 11 moderate) or dexamethasone plus remdesivir (DR group, 7 severe and 10 moderate) for 7 days in a pilot study. Eight healthy control subjects were also enrolled. The frequency of PD-1+ and CTLA-4+ lymphocytes in whole blood was evaluated by flow cytometry. Patients on DR therapy had shorter hospital stays than those on FK therapy. The frequency of PD-1+ lymphocytes in the FK group at baseline differed between COVID-19 patients and healthy controls, while the frequency of both PD-1+ and CTLA-4+ cells increased significantly 7 days of FK therapy. The response was similar in both moderate and severe patients. In contrast,the frequency of PD-1+ and CTLA-4+ lymphocytes varied significantly between patients and healthy controls before DR treatment. DR therapy enhanced PD-1+ but not the CTLA-4+ frequency of these cells after 7 days. We show that the frequency of PD-1 and CTAL-4-bearing lymphocytes during hospitalization was increased in Iranian ICU COVID-19 patients who received FK treatment, but that the frequency of CTLA-4+ cells was higher at baseline and did not increase in patients who received DR. The effectiveness of DR treatment may reflect differences in T-cell activation or exhaustion status, particularly in CTLA-4-expressing cells.

Coagulopathy is Initiated with Endothelial Dysfunction and Disrupted Fibrinolysis in Patients with COVID-19 Disease.

The online version contains supplementary material available at 10.1007/s12291-023-01118-3.

Population pharmacokinetics of nadroparin for thromboprophylaxis in COVID-19 intensive care unit patients.

Nadroparin is administered to COVID-19 intensive care unit (ICU) patients as thromboprophylaxis. Despite existing population pharmacokinetic (PK) models for nadroparin in literature, the population PK of nadroparin in COVID-19 ICU patients is unknown. Moreover, optimal dosing regimens achieving anti-Xa target levels (0.3-0.7IU/mL) are unknown. Therefore, a population PK analysis was conducted to investigate different dosing regimens of nadroparin in COVID-19 ICU patients. Anti-Xa levels (n= 280) from COVID-19 ICU patients (n= 65) receiving twice daily (BID) 5700 IU of subcutaneous nadroparin were collected to perform a population PK analysis with NONMEM v7.4.1. Using Monte Carlo simulations (n= 1000), predefined dosing regimens were evaluated. A 1-compartment model with an absorption compartment adequately described the measured anti-Xa levels with interindividual variability estimated for clearance (CL). Inflammation parameters C-reactive protein, D-dimer and estimated glomerular filtration rate based on the Chronic Kidney Disease Epidemiology Collaboration equation allowed to explain the interindividual variability of CL. Moreover, CL was decreased in patients receiving corticosteroids (22.5%) and vasopressors (25.1%). Monte Carlo simulations demonstrated that 5700 IU BID was the most optimal dosing regimen of the simulated regimens for achieving prespecified steady-state t= 4h anti-Xa levels with 56.7% on target (0.3-0.7IU/mL). In our study, clearance of nadroparin is associated with an increase in inflammation parameters, use of corticosteroids, vasopression and renal clearance in critically ill patients. Furthermore, of the simulated regimens, targeted anti-Xa levels were most adequately achieved with a dosing regimen of 5700 IU BID. Future studies are needed to elucidate the underlying mechanisms of found covariate relationships.

241. Antibiotic Prescription in COVID Intensive Care Unit (ICU): Empiric Treatment vs. FilmArray Pneumonia (FAP) Panel Guided Treatment

Abstract Background The empiric prescription of antibiotics in COVID 19 ICU patients is frequent due to the severity of disease and presentation of patients with septic shock. In this study we compared two approaches of antimicrobial prescription: empiric use vs. FilmArray pneumonia (FAP) panel guided treatment. We evaluated costs of intervention, clinical outcomes as development of hospital acquired infections (HAI), length of stay and mortality. Methods Retrospective study. Patients with severe COVID-19 infection hospitalized in ICU of two institutions in Pereira were included. The prescription of antibiotic without FAP panel was defined as empiric. The prescription according to FAP panel results was defined as guided. Data analysis was performed in Epiinfo version 7.5.2.0. The study protocol was approved by the ethics committee of Universidad Tecnologica de Pereira. Results 252 patients were included, 180 received empiric therapy and 72 were FAP panel guided. The median age was 65 years (IQR 53-73), the PaO2/FiO2 ratio mean was 108 (IQR 64-130). In the group of empiric treatment, 21 (11.67%) patients presented confirmed bacterial infection. Patients on guided antimicrobial therapy presented less HAI (RR 0,54 (IC 95% 0.30-0.95) p 0.02). The median length of stay in ICU was 16 days for both groups. Klebsiella pneumoniae was the most frequent bacteria identified during the first episode of infection followed of Pseudomonas aeruginosa. Mortality on guided group was 54% Vs. 42% on empiric group (p&amp;lt; 0,3). Meropenem was the main antibiotic prescribed (DDD empiric 3.17 Vs. 1.8 DDD guided) followed of cefepime (DDD empiric 0.9 Vs. DDD guided 0.12). The median cost of antimicrobial treatment in the empiric group was US$530 (US$30-US$1579) per patient compared to the median cost of guided prescription that was US$292 (US$16-US$8767). When including the cost of FAP panel, the median cost per patient treatment course was US$429 (US$153-US$8904) p&amp;lt; 0.7. Conclusion Implementation of a guided antimicrobial therapy using FAP panel could be useful and cost effective in COVID-19 ICU patients to reduce antimicrobial consumption and adverse outcomes related to the inappropriate use of antibiotics without significant impact on mortality or length of stay. Disclosures Karen M. Ordonez, MD, AstraZeneca: Expert Testimony|Biomerieux: Expert Testimony|Farma de Colombia: Expert Testimony|MSD: Expert Testimony|Pfizer: Expert Testimony.

Serum inflammatory and brain injury biomarkers in COVID-19 patients admitted to intensive care unit: A pilot study.

The aim of this study was to measure serum brain injury biomarkers in patients with COVID-19 admitted to intensive care unit (ICU), without evidence of brain impairment, and to determine potential correlations with systemic inflammatory markers, illness severity, and outcome. In patients admitted to the ICU with COVID-19, without clinical evidence of brain injury, blood S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE) and interleukin-6 (IL-6) were measured on admission. Clinical, routine laboratory data and illness severity were recorded. Comparisons between 28-day survivors and non-survivors and correlations of neurological biomarkers to other laboratory data and illness severity, were analyzed. We included 50 patients, median age 64 [IQR 58-78] years, 39 (78%) males, 39 (78%) mechanically ventilated and 11 (22%) under high flow nasal oxygen treatment. S100B and NSE were increased in 19 (38%) and 45 (90%) patients, respectively. S100B was significantly elevated in non-survivors compared to survivors: 0.15 [0.10-0.29] versus 0.11 [0.07-0.17] μg/L, respectively, (p=0.03), and significantly correlated with age, IL-6, arterial lactate, noradrenaline dose, illness severity and lymphocyte count. IL-6 was significantly correlated with C-reactive protein, noradrenaline dose and organ failure severity. NSE was correlated only with lactate dehydrogenase. Brain injury biomarkers were frequently elevated in COVID-19 ICU patients, in the absence of clinical evidence of brain injury. S100B was significantly correlated with IL-6, low lymphocyte count, hypoperfusion indices, illness severity, and short-term outcome. These findings indicate a possible brain astrocytes and neurons involvement, also suggesting a broader role of S100B in systemic inflammatory response.