COVID-19 Patients In ICU Research Articles

P20 COVID-19-associated pulmonary aspergillosis (CAPA): review of utility of local CAPA guideline and MDT in directing diagnosis and antifungal stewardship

BackgroundCOVID-19-associated pulmonary aspergillosis (CAPA) is a recognized but incompletely characterized secondary fungal infection reported to be associated with increased mortality in patients in the ICU. Case definitions have been published but lack clarity: clinical and radiological features are non-specific and rely heavily on mycological tests for which both a timely availability and accuracy pose an issue contributing to the wide range of incidence reported of 4%–34%. In April 2021, we introduced a CAPA guideline for ICU patients at St George's University Hospital including when to suspect and how to investigate for CAPA (see Figure 1). The aim of this study was to evaluate its utility in identifying patients meeting ECMM_ISHAM criteria for possible/probable CAPA.Figure 1.St George's Hospital CAPA Guideline 2021.MethodsBetween March 2020 and May 2021 a retrospective audit was completed that identified all PCR-confirmed COVID-19 ICU patients prescribed either voriconazole, caspofungin, anidulafungin and AmBisome and reviewed their medical records, imaging and microbiology results categorizing patients into proven, probable, possible or unlikely CAPA based on ECMM/ISHAM criteria.ResultsTwenty-one patients were prescribed the specified antifungals. All had CT imaging and varying microbiological investigations. Real-time clinical decisions on empirical antifungal prescribing for CAPA (start or stop) were made by a multidisciplinary team (MDT) comprising Microbiology and ICU physicians in light of clinical, microbiology and radiology findings. Nine of 21 patients prescribed empirical antifungals had radiological evidence of CAPA. Aspergillus fumigatus was cultured in six patients from bronchoalveolar lavage and two patients from sputum/trachea. Of these, seven were deemed significant and one attributed to colonization. Two patients were diagnosed with ‘probable’ and five as ‘possible’ CAPA, of whom one died. All seven patients received antifungal treatment for CAPA of varying duration (range 18–49 days). Only one patient had an underlying host risk factor (B cell lymphoma). Of those defined with probable/possible CAPA, average time from intubation to treatment was 18.4 days (range 8–31) and from onset of COVID symptoms to treatment was 28.5 days (range 18–49). Three of 21 patients were treated empirically for CAPA and all 3 died prior to further investigation and 15 patients following an MDT were felt to have unlikely CAPA. Serum BDG and GM were negative in all patients with probable/possible CAPA.ConclusionsThe St George's CAPA guideline would have picked up two out of seven cases; two cases had antifungals started in another hospital so the utility of this guideline could not be assessed. Based on analysis of these cases the following changes were made to the guideline: (i) to assess patients ≥8 days post ICU admission (rather than ≥10 days) and (ii) assess patients following ≥3 days post appropriate antibiotic therapy (rather than following ≥5 days). Serum BDG and GM were negative in all patients with probable/possible CAPA prior to starting treatment therefore negative serum markers do not exclude diagnosis; this is consistent with experience reported elsewhere. Radiological presentations of CAPA were variable and wide ranging, and BAL sampling was not always possible, therefore we found the MDT approach including radiology, infection, respiratory and ICU invaluable in making decisions regarding treatment. This helped to reduce the use of fungal diagnostics, antifungal agents and appropriately manage patients with potential CAPA. The rationalization of antifungal use by the introduction of this guidelines was particularly important and also expedited the introduction of in-house fungal diagnostics.

CoCross: An ICT Platform Enabling Monitoring Recording and Fusion of Clinical Information Chest Sounds and Imaging of COVID-19 ICU Patients.

Monitoring and treatment of severely ill COVID-19 patients in the ICU poses many challenges. The effort to understand the pathophysiology and progress of the disease requires high-quality annotated multi-parameter databases. We present CoCross, a platform that enables the monitoring and fusion of clinical information from in-ICU COVID-19 patients into an annotated database. CoCross consists of three components: (1) The CoCross4Pros native android application, a modular application, managing the interaction with portable medical devices, (2) the cloud-based data management services built-upon HL7 FHIR and ontologies, (3) the web-based application for intensivists, providing real-time review and analytics of the acquired measurements and auscultations. The platform has been successfully deployed since June 2020 in two ICUs in Greece resulting in a dynamic unified annotated database integrating clinical information with chest sounds and diagnostic imaging. Until today multisource data from 176 ICU patients were acquired and imported in the CoCross database, corresponding to a five-day average monitoring period including a dataset with 3477 distinct auscultations. The platform is well accepted and positively rated by the users regarding the overall experience.

The effect of ABO blood types and mean platelet volume on mortality in COVID-19 patients in ICU

The effect of ABO blood types and mean platelet volume on mortality in COVID-19 patients in ICU

Comparison of Cytokine Hemadsorption as an Immunomodulator Therapy in COVID-19 Patients with and without Bacterial Sepsis.

In this retrospective study, we aimed to compare the laboratory and clinical results of cytokine hem-adsorption as an immunomodulation therapy in COVID-19 ICU patients with or without sepsis. The levels of PCT, CRP, and ferritin were determined as indicators of infection/sepsis; the levels of in-terleukins (IL-6, IL-8 and IL-10, and TNF-α) were determined as indicators of cytokine storm were compared. APACHE score, SOFA score, and mortality rates were compared for the progression of the disease in 23 COVID-19 patients. The therapy was generally successful in reducing the levels of IL-6, IL-8, IL-10, and TNF-α but the levels measured after the procedure did not differ among the patients with or without sepsis, suggesting that the presence of sepsis did not affect the efficacy and function of the cytokine hemadsorption procedure in COVID-19 patients. All parameters were reduced after the procedure except the levels of PCT and ferritin and mortality rates of patients diagnosed with sepsis. The level of PCT was significantly higher in these patients compared with the patients without sepsis while the ferritin and mortality did not show any significant difference between the two groups, suggesting that the cytokine hemadsorption may be safe in the treatment of critical COVID-19 patients. As a result, the progression of sepsis in COVID-19 may be avoided with cytokine hemadsorption applied as an immunomodulator therapy. However, this therapy should be further explored and validated prior to its introduction to everyday clinical practice when the epidemic conditions end.

Krebs von den Lungen 6 (KL-6) levels in COVID-19 ICU patients are associated with mortality

BackgroundKrebs von den Lungen 6 (KL-6) is a high-molecular-weight mucin-like glycoprotein, which is also known as MUC1. KL-6 is mainly produced by type 2 pneumocytes and bronchial epithelial cells, and, therefore, elevated circulating KL-6 levels may denote disorders of the alveolar epithelial lining.The objective of this study is to verify if KL-6 serum level might support ICU physicians in predicting mortality, risk stratifying and triaging severe COVID-19 patients.MethodsA retrospective cohort study, including all the COVID-19 patients who measured KL-6 serum values at least once during their ICU stay, was performed. The study sample, 122 patients, was divided in two groups, according to the median KL-6 value at ICU admission (median log-transformed KL-6 value: 6.73 U/ml; group A: KL-6 lower than the median and group B: KL-6 higher than the median). ResultsOne-hundred twenty-two ICU patients were included in this study. Mortality was higher in group B than in group A (80 versus 46%; p < 0.001); both linear and logistic multivariate analyses showed ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (P/F) significantly and inversely related to KL-6 values.ConclusionAt ICU admission, KL-6 serum level was significantly higher in the most hypoxic COVID-19 patients and independently associated with ICU mortality.

239: SCD TREATMENT IN COVID-19 ICU PATIENTS WITH ARDS AND AKI IS SAFE AND MAY IMPROVE OUTCOMES

239: SCD TREATMENT IN COVID-19 ICU PATIENTS WITH ARDS AND AKI IS SAFE AND MAY IMPROVE OUTCOMES

Study of Haematological and Biochemical Parameters of COVID-19 Patients in ICU and in Ward

Introduction: Covid-19 is 65 nm to 125 nm in diameter and contains single-stranded RNA as nuclei content. Covid-19's global scale transmission, frequent occurrence, large number of deaths, infection and mortality among care providers, and multiplicative impact in vulnerable or sensitive groups are all major causes of concern. The clinical presentations of coronavirus disease are diverse, ranging from asymptomatic carriers to manifestations of respiratory collapse requiring mechanical ventilation and ICU support, as well as multi-organ and systemic symptoms such as sepsis, septic shock, and multiple organ dysfunction syndromes (MODS).&#x0D; Aim: Comparison of Haematological and Biochemical Parameters of Covid-19 Patients in ICU and in Ward.&#x0D; Materials and Methods: 25 patients were ICU and 25 patients were ward. Patients went directly to the Observed Treatment in the Dept. of Medicine and Dept. of Respiratory.&#x0D; Datta Meghe Medical College and Shalinitai Meghe Hospital and Research Centre.&#x0D; Results: Serum urea and creatinine significantly raised in ICU patients as compare to ward patients while sodium, potassium and chloride were insignificantly increased in ICU patients.&#x0D; Table 1 shows the D-dimer was also increased in ICU patients (3.45±2.76) as compare to the ward patients (1.49±2.13). D-Dimer is significantly increased in ICU patients (P=0.0071). As we can see in above table the level of Pro-BNP were highly significantly raised in ICU patients as compare to the ward patients (P = 0.0001). While level of Trop T insignificantly increased in ICU patients (P=0.8732).&#x0D; Conclusion: Several indicators, such as elevated leukocyte and CRP, LDH, and deranged urea/creatinine, were identified to be most likely correlated factors with disease incidence and mortality in our study. So are lower bicarbonate levels. However, acute liver and kidney injury are more common in COVID-19 patients.

Vital Signs Prediction for COVID-19 Patients in ICU.

This study introduces machine learning predictive models to predict the future values of the monitored vital signs of COVID-19 ICU patients. The main vital sign predictors include heart rate, respiration rate, and oxygen saturation. We investigated the performances of the developed predictive models by considering different approaches. The first predictive model was developed by considering the following vital signs: heart rate, blood pressure (systolic, diastolic and mean arterial, pulse pressure), respiration rate, and oxygen saturation. Similar to the first approach, the second model was developed using the same vital signs, but it was trained and tested based on a leave-one-subject-out approach. The third predictive model was developed by considering three vital signs: heart rate (HR), respiration rate (RR), and oxygen saturation (SpO). The fourth model was a leave-one-subject-out model for the three vital signs. Finally, the fifth predictive model was developed based on the same three vital signs, but with a five-minute observation rate, in contrast with the aforementioned four models, where the observation rate was hourly to bi-hourly. For the five models, the predicted measurements were those of the three upcoming observations (on average, three hours ahead). Based on the obtained results, we observed that by limiting the number of vital sign predictors (i.e., three vital signs), the prediction performance was still acceptable, with the average mean absolute percentage error (MAPE) being , and for heart rate, oxygen saturation, and respiration rate, respectively. Moreover, increasing the observation rate could enhance the prediction performance to be, on average, , and for heart rate, oxygen saturation, and respiration rate, respectively. It is envisioned that such models could be integrated with monitoring systems that could, using a limited number of vital signs, predict the health conditions of COVID-19 ICU patients in real-time.

Correlation of Patient Profiles and Biomarkers with Outcomes in Covid-19 Icu Patients: A Retrospective Analysis.

COVID-19 is a novel disease with a highly variable and unpredictable clinical course. Various clinicodemographic factors and numerous biomarkers have been identified in studies from the West and marked as possible predictors of severe illness and mortality which may be used to triage patients for early aggressive care. This triaging becomes even more significant in resource-limited critical care settings of the Indian subcontinent. This retrospective observational study recruited 99 cases of COVID-19 admitted to intensive care from 1 May to 1 August 2020. Demographic, clinical and baseline laboratory data were collected and analysed for association with clinical outcomes, including survival and need for mechanical ventilatory support. Male gender (p=0.044) and diabetes mellitus (p=0.042) were associated with increased mortality. Binomial logistic regression analysis revealed Interleukin-6 (IL6) (p=0.024), D-dimer (p=0.025) and CRP (p<0.001) as significant predictors of need of ventilatory support and IL6 (p=0.036), CRP (p=0.041), D-dimer (p=0.006) and PaO2FiO2 ratio (p=0.019) as significant predictors of mortality. CRP >40 mg/L predicted mortality with sensitivity of 93.3% and specificity of 88.9% (AUC 0.933) and IL6> 32.5 pg/ml with a sensitivity of 82.2% and specificity of 70.4% (AUC 0.821). Our results suggest that a baseline CRP >40 mg/L, IL6 >32.5 pg/ml or D-dimer >810 ng/ml are early accurate predictors of severe illness and adverse outcomes and may be used to triage patients for early intensive care.

Nutritional evaluation scenery on Covid-19 ICU patients on Brazil’s state of paraiba

Nutritional evaluation scenery on Covid-19 ICU patients on Brazil’s state of paraiba

COVID-19 associated infections in the ICU setting: A retrospective analysis in a tertiary-care hospital

IntroductionOur work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections. MethodsRetrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors. ResultsTwo-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, p<0.01). In multivariate analysis use of corticosteroids (OR 4.9, 95% CI 1.4–16.9, p 0.01), tocilizumab (OR 2.4, 95% CI 1.1–5.9, p 0.03) and broad-spectrum antibiotics within first 7 days of admission (OR 2.5, 95% CI 1.2–5.1, p<0.01) were associated with superinfections. Patients with superinfections presented respect to controls prolonged ICU stay (35 vs. 12 days, p<0.01) but not higher in-hospital mortality (45.3% vs. 39.7%, p 0.13). ConclusionsSuperinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.

Predictors of Mortality for Critically Ill COVID-19 Patients: Systematic Review

Objective: To identify mortality predictors of critically ill COVID-19 patients in ICU based on current available literatures.Methods: Systematic literature search was conducted in open-access databases. Data extraction was conducted for publication date, methodology employed, sample size, and results of multivariate analysis. Eligibility criteria for analysis was observational analytic design, sample size of 100 or more, and availability of multivariate results. Primary measures assessed was risk ratio, presented as odds ratio or hazard ratio. Data was analyzed qualitatively for themes that emerged for mortality predictors.Results: Several mortality predictors were identified, which included demographic, clinical history, laboratory results, and oxygenation profile at ICU admission. Several of the most consistently reported mortality predictors was older age, one or more comorbidities that constitute metabolic syndrome, chronic pulmonary disorder, low lymphocyte and platelet count, elevated d-dimer, and low PaO2/FiO2 ratio.Conclusions: Mortality predictors identified in this review were similar to previously known mortality and severity predictors of COVID-19 patients in general. This consistency may point to the potential of developing a scoring system to predict COVID-19 severity and mortality for clinical practice use.

Bioelectric impedance body composition and phase angle in relation to 90-day adverse outcome in hospitalized COVID-19 ward and ICU patients: The prospective BIAC-19 study.

Background & aimsGaining insight into readily obtainable baseline characteristics that allow prediction of adverse outcome in COVID-19 aids both treatment and healthcare planning. Bioelectric impedance (BIA) Phase Angle (PhA) is correlated with outcome in a multitude of diseases and may be of added value in predicting adverse outcome of COVID-19. We aimed to associate baseline body composition parameters with 90-day adverse outcome of COVID-19 including ICU-admission and to explore the added predictive value of baseline PhA.MethodsWe performed a prospective observational study, conducting BIA amongst COVID-19 patients within 24 hours of hospital admission, with a follow-up of 90 days. Data were compared between ward-only and ICU-patients. Regression models were used to assess the associations between baseline characteristics, body composition and 90-day adverse outcome, including a composite outcome score of morbidity, ICU-admission, and mortality. An ROC-curve was used to explore the added predictive value of PhA to other clinical parameters at baseline for the prediction of adverse outcome.ResultsOne-hundred-and-fifty patients were included. Mean age was 68 (66–70) years, 67% were male. Forty-one (27%) patients were admitted to ICU and 77 (51%) met the criteria of the composite outcome score. In multiple regression, PhA was independently, inversely correlated with risk of ICU-admission (OR .531, p = .021), complications (OR .579, p = .031), hospital length of stay (OR .875, p = .037) and the composite outcome score (OR .502, p = .012). An ROC-curve showed that the incorporation of PhA in a composite risk-score improved the discriminative power for the composite outcome from poor to fair, compared to individual predictors (AUC 0.79 (95% CI 0.71–0.87)).ConclusionBIA measurements including Phase Angle are independently correlated with an adverse outcome of COVID-19. Interpretation of Phase Angle can be a valuable addition to risk assessment of adverse outcome of COVID-19 at hospital admission.Clinical Trial RegistrationNetherlands Trial Register number NL8562, registered 2020-04-21.

TWO CASES OF ARTERIAL THROMBUS IN COVID-19 INFECTION

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Several studies have observed thrombotic complications in COVID-19 patients with rates as high as 30%. We present two COVID-19 cases of arterial and venous thrombotic complications. CASE PRESENTATION: A 64-year-old African American female was admitted for worsening respiratory failure due to COVID-19. HIT panel was obtained due to worsening thrombocytopenia, as the patient was on heparin for venous thrombosis prophylaxis, which was negative. Duplex of the lower extremities performed on hospital day 12 showed an acute non-occlusive deep vein thrombosis of the left common femoral vein, for which therapeutic heparin was initiated. On hospital day 25, the patient was found to have right digit ischemia with no flow to the right ulnar artery secondary to an occlusive arterial thrombus. Hematology was consulted for severe thrombocytopenia and considered to treat empirically for ITP with IVIG;however, the patient continued to decompensate and the family elected for comfort care measures. The patient expired on hospital day 30.Our second case report is a 64-year-old African American male presented from a local prison with worsening shortness of breath and was found to have COVID-19. Shortly after arrival from the ED to ICU, the patient went into cardiac arrest, ACLS was initiated and ROSC was achieved. The patient was in torsades and Vfib rhythm. He underwent left heart catheterization on hospital day 1 and was found to have 100% occlusion of obtuse marginal and underwent successful percutaneous coronary intervention with a drug-eluting stent to OM2. On hospital day 8, the patient was found to have digit ischemia of the right first through third digits. Arterial and venous duplex showed thrombotic occlusion of the right radial artery from the mid-forearm to the wrist and an acute deep vein thrombus of the left subclavian and axillary veins. DISCUSSION: COVID-19 can be associated with arterial and venous thrombosis as highlighted by our two cases. Even though the pathophysiology of thromboembolic complications in COVID-19 is not reported in the literature, it is implicated due to inflammation, hypoxia, immobilization, and DIC. In a study done by Klok et al in COVID-19 ICU patients, 27% of the study population had CTPE/Ultrasonography confirmed venous thromboembolism and 3.7% had arterial thrombosis compared to 12% of venous thrombosis in the ICU. The mechanism for hyper-coagulability in COVID infection is not known, it has been linked to the inflammatory response rather than specific properties of the virus. This association of excess inflammation and COVID-19 with subsequent activation of coagulation has been implicated in the pathogenesis of thrombosis. CONCLUSIONS: Intermediate to therapeutic anticoagulation may be necessary to prevent venous and arterial thromboembolic events in ICU patients admitted with COVID-19 given their excessive inflammatory state. REFERENCE #1: Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood, The Journal of the American Society of Hematology. 2020 Jun 4;135(23):2033-40. REFERENCE #2: Leisman DE, Deutschman CS, Legrand M. Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation. Intensive Care Medicine. 2020 Apr 28:1-4. REFERENCE #3: Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Muller MC, Bouman CC, Beenen LF, Kootte RS, Heijmans J, Smits LP. Incidence of venous thromboembolism in hospitalized patients with COVID-19. Journal of Thrombosis and Haemostasis. 2020 May 5. DISCLOSURES: No relevant relationships by Sarenthia Epps, source=Web Response No relevant relationships by Harmeen Goraya, source=Web Response No relevant relationships by Raga Deepak Reddy Palagiri, source=Web Response

Managing critical care during COVID-19 pandemic: The experience of an ICU of a tertiary care hospital

BackgroundThe COVID-19 pandemic has strained ICUs worldwide. To learn from our experience, we described the critical care response to the outbreak. MethodsThis is a case study of the response of the Intensive Care Department (75-bed capacity) at a tertiary-care hospital to COVID-19 pandemic, which resulted in a high number of critically ill patients. ResultsBetween March 1 and July 31, 2020, 822 patients were admitted to the adult non-cardiac ICUs with suspected (72%)/confirmed (38%) COVID-19. At the peak of the surge, 125 critically ill patients with COVID-19 were managed on single day. To accommodate these numbers, the bed capacity of 4 ICUs was increased internally from 58 to 71 beds (+40%) by cohorting 2 patients/room in selected rooms; forty additional ICUs beds were created in 2 general wards; one cardiac ICU was converted to managed non-COVID-19 general ICU patients and one ward was used as a stepdown for COVID-19 patients. To manage respiratory failure, 53 new ICU ventilators, 90 helmets for non-invasive ventilation and 47 high-flow nasal cannula machines were added to the existing capacity. Dedicated medical teams cared for the COVID-19 patients to prevent cross-contamination. The nurse-to-patient and RT-to-patient ratio remained mostly 1:1 and 1:6, respectively. One-hundred-ten ward nurses were up-skilled to care for COVID-19 and other ICU patients using tiered staffing model. Daily executive rounds were conducted to identify patients for transfer and at least 10 beds were made available for new COVID-19 admissions/day. The consumption of PPE increased multiple fold compared with the period preceding the pandemic. Regular family visits were not allowed and families were updated daily by videoconferencing and phone calls. ConclusionsOur ICU response to the COVID-19 pandemic required almost doubling ICU bed capacity and changing multiple aspects of ICU workflow to be able to care for high numbers of affected patients.

Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients.

Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.92, 95% CI = 2.49–14.1). MAIT cell activation correlates with several other mortality-associated immunologic measures including broad activation of CD8+ T cells and non-Vδ2 γδT cells, and elevated levels of cytokines and chemokines, including GM-CSF, CXCL10, CCL2, and IL-6. MAIT cell activation is also a predictor of disease severity in influenza (ECMO/death HR = 4.43, 95% CI = 1.08–18.2). Single-cell RNA-sequencing reveals a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 –a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.

Continuation of therapeutic anticoagulation before and during hospitalization is associated with reduced mortality in COVID-19 ICU patients

Background: Literature has well established COVID-19 associated coagulopathy with resulting thrombotic complications including microthrombi as an underlying mechanism leading to severe respiratory disease. Therapeutic anticoagulation (TAC) for COVID-19 patients has therefore been widely trialed to combat COVID-19’s coagulopathic effects. However, literature has yet to define which population of patients TAC benefits; the most current randomized controlled trials (RCTs) reveal TAC to be possibly beneficial to moderately-ill hospitalized COVID-19 patients, whereas benefits did not outweigh risks in critically-ill ICU patients. Importantly, these studies excluded patients who received prehospital TAC. We examined outcomes in critically ill COVID-19 ICU patients who received TAC vs prophylactic anticoagulation (PAC) and specifically whether prehospital TAC effected outcomes. Methods: Retrospective cohort study of 132 COVID-19 ICU patients admitted March-June, 2020. Initial clinical practice provided PAC, as literature demonstrating COVID-19 associated coagulopathy and increased thromboembolic complications emerged, a TAC protocol was initiated. Results: 130 patients were included in the study, 95 of whom received TAC and 35 PAC. There was 50.8% overall mortality, with lower mortality in the TAC vs PAC group (46.3% vs 62.9%, p=0.094). There were few thromboembolic and hemorrhagic complications, with no significant difference between TAC and PAC patients. Of 24 patients anticoagulated prior to and during hospitalization, only 1 (4.2%) died, whereas the mortality was 60.6% among patients therapeutically anticoagulated during hospitalization only (p&lt;0.001). Multivariable analysis revealed patients who received prehospital and in hospital TAC had a 92% lower risk of death (p=0.008) compared to in hospital only TAC and PAC patients. Conclusions: Overall, therapeutic anticoagulation did not result in mortality benefit to COVID-19 ICU patients compared to prophylactic anticoagulation. However, a sub-population of patients who received TAC both prior to and during hospitalization had a 12-fold lower risk of death. This suggests a protective effect of TAC when it is continued before and during hospitalization. RCTs are needed to specifically examine this subset of COVID-19 patients.

Pharmacokinetics of enoxaparin in COVID-19 critically ill patients

BackgroundIn intensive-care unit (ICU) patients, pathophysiological changes may affect the pharmacokinetics of enoxaparin and result in underdosing. ObjectivesTo develop a pharmacokinetic model of enoxaparin to predict the time-exposure profiles of various thromboprophylactic regimens in COVID-19 ICU-patients. MethodsThis was a retrospective study in ICUs of two French hospitals. Anti-Xa activities from consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated with enoxaparin for the prevention or the treatment of venous thrombosis were used to develop a population pharmacokinetic model using non-linear mixed effects techniques. Monte Carlo simulations were then performed to predict enoxaparin exposure at steady-state after three days of administration. ResultsA total of 391 anti-Xa samples were measured in 95 patients. A one-compartment model with first-order kinetics best fitted the data. The covariate analysis showed that enoxaparin clearance (typical value 1.1 L.h-1) was related to renal function estimated by the CKD-EPI formula and volume of distribution (typical value 17.9 L) to actual body weight.Simulation of anti-Xa activities with enoxaparin 40 mg qd indicated that 64% of the patients had peak levels within the range 0.2 to 0.5 IU.mL-1 and 75% had 12-hour levels above 0.1 IU.mL-1. Administration of a total daily dose of at least 60 mg per day improved the probability of target attainment. ConclusionIn ICU COVID-19 patients, exposure to enoxaparin is reduced due to an increase in the volume of distribution and clearance. Consequently, enoxaparin 40 mg qd is suboptimal to attain thromboprophylactic anti-Xa levels.

MDR BACTERIAL INFECTIONS IN CRITICALLY ILL COVID-19 PATIENTS IN A TERTIARY CARE HOSPITAL (OF PAKISTAN)

Objective: To identify antimicrobial susceptibility pattern of multidrug resistant bacteria causing secondary infections in COVID-19 patients in ICU’ sofa tertiary care hospital.&#x0D; Study Design: Cross–sectional study.&#x0D; Place and Duration of Study: Department of Microbiology, Pak Emirates Military Hospital, Rawalpindi, from Apr to Jul 2020.&#x0D; Methodology: This study included blood samples and endotracheal aspirates from 114 critically ill COVID-19 patients. Peripheral blood specimens were collected fromthe patients with secondary bacterial blood stream infections and endotracheal aspirates were collected from patients with ventilator associated pneumonia for culture and sensitivity. The results were interpreted according to Clinical &amp; Laboratory Standard Institute (CLSI) 2020.&#x0D; Results: A total of 114 COVID-19 patients were admitted in ICU during that time period. Fourteen (12.28%) were female and 100 (87.71%) were male, age distribution was between 36-82 years. Sixty six paired blood samples were sent to the microbiology lab out of which 51 (77.2%) showed bacterial growth while 15 (22.7%) samples were negative. Out of 50 endotracheal aspirates, 42 showed bacterial growth (84%) and 8 samples did not show any significant bacterial growth (16%). Most of the endotracheal aspirates showed growth of &gt;1 bacterial isolates. The most common gram-negative organisms were Acinetobacter baumannii (n=54) and Klebsiella pneumonia (n=26) and most common gram-positive organism isolated was Enterococcus faecium (n=9). All isolated organisms were multidrug resistant.&#x0D; Conclusion: Poor antimicrobial stewardship particularly in critical care units resulted in secondary bacterial infections in COVID-19 patients. The pathogens isolated were multidrug resistant including Acinetobacter baumannii, Klebsiella pneumonia and Enterococcus faecium.

Extensive microbiological respiratory tract specimen characterization in critically ill COVID-19 patients.

Microbial co‐infections may contribute to the pulmonary deterioration in COVID‐19 patients needing intensive care treatment. The present study portrays the extent of co‐infections in COVID‐19 ICU patients. Conventional culture, molecular detections for atypical aetiologies, QiaStat‐Dx® respiratory panel V2 detecting 21 respiratory pathogens and ribosomal DNA genes 16S/18S amplicon‐based microbiome analyses were performed on respiratory samples from 34 COVID‐19 patients admitted to the ICU. Potential pathogens were detected in seven patients (21%) by culturing, in four patients (12%) by microbiome analysis and in one patient (3%) by respiratory panel. Among 20 patients receiving antibiotics prior to ICU admission, fungi (3 Candida albicans, 1 C. tropicalis, 1 C. dubliniensis) were cultured in 5 (15%) endotracheal aspirates. Among 14 patients who were antibiotic‐naive at ICU admission, two patients (6%) had bacterial respiratory pathogens (Staphylococcus aureus, Streptococcus pseudopneumoniae) cultured in their endotracheal aspirates. Microbiome analysis recognized four potential respiratory pathogens (3 Haemophilus influenza, 1 Fusobacterium necrophorum) isolated in samples from four other patients (12%). QiaStat‐Dx® respiratory panel V2 detected adenovirus in one patient (3%). The prevalence of pulmonary microbial co‐infections is modest among COVID‐19 patients upon admission to ICU. Microbiome analysis complements conventional microbial diagnostics in characterization of respiratory co‐infections.