Thrombotic Events Related to Extracorporeal Membrane Oxygenation in COVID-19-Associated Severe Acute Respiratory Distress Syndrome.

Hypercoagulopathy associated with the novel coronavirus disease (COVID-19) is the leading cause of acute respiratory distress syndrome (ARDS), multiple organ failure, and mortality. Extracorporeal membrane oxygenation (ECMO) has been used to manage patients with COVID 19-associated severe respiratory or cardiac failure. In this report, we aim to summarise our experience with deadly thrombotic complications during venovenous ECMO (vvECMO) treatment in 6 patients with COVID-19-associated ARDS between March 19, 2020 and April 20, 2020. Based on our experience with 6 COVID-19-associated ARDS patients on ECMO, we intend to raise awareness regarding thrombotic complications leading to mortality.

[First Case of COVID-19 Positive Candida auris Fungemia in Turkey]. / Türkiye'de Ilk COVID-19 Pozitif Candida auris Fungemi Olgusu.

Candida auris is a species of fungus that has gained importance in recent years owing to its ability to cause hospital infections and epidemics, resistant to antifungal agents and disinfection processes and frequently misidentified by commercial systems. Hospital outbreaks caused by C.auris have been reported from some countries. It has been determined that C.auris has lower virulence than Candida albicans; however, it is associated with high mortality rates in immunocompromised individuals. An increase in the incidence of invasive fungal infections which can lead to serious complications and death, has been identified in severe coronavirus-2019 (COVID-19) patients or immunocompromised individuals with underlying disease. Studies demonstrated an increase in the frequency of C.auris isolation in COVID-19 patients with candidemia. In this report, the first case of COVID-19 positive C.auris fungemia detected in Turkey was presented. A 71-year-old male patient with a history of myocardial infarction, diabetes mellitus, donation of a single kidney and lobectomy surgery due to lung cancer was hospitalized in the pandemic thoracic surgery service due to the findings consistent with viral pneumonia on thoracic computed tomography. Favipiravir 2 x 600 mg and intravenous dexamethasone 1 x 6 mg therapy was administered. The patient tested positive for SARS-CoV-2 polymerase chain reaction, and severe involvement of the left lung was detected in the following days. Antibiotics were administered, followed by insertion of a right jugular vein catheter and initation of tocilizumab. The patient was transferred to the intensive care unit due to increased respiratory distress. Yeast growth was detected in the patient's hemoculture. The yeast strain could not be identified using API ID 32C (bioMerieux, France) (Sacchromyces kluyveri, Candida sake, unacceptable profile), but was identified as C.auris using the VITEK MALDI TOF MS (bioMerieux, France) (99.9%) system and confirmed by sequencing. The minimum inhibitor concentration values were detected as 3 µg/ml for amphotericin B; > 256 µg/ml for fluconazole; 0.19 µg/ml for voriconazole; 0.19 µg/ml for itraconazole; 0.016 µg/ml for posaconazole; 1 µg/ml for caspofungin and 0.094 µg/ml for anidulafungin by using the antibiotic gradient method. The patient's initial treatment comprised meropenem 3 x 1 g, vancomycin 2 x 1 g, caspofungin 1 x 70 mg, and continued as caspofungine 1 x 50 mg after the loading dose, and vancomycin 1 x 1 g/48 hours from the third day of treatment. The patient died on the ninth day after developing candidemia. The present case is the first case of fungemia caused by C.auris in a COVID-19 positive patient in Turkey, and it emphasizes the need of caution for fungemia due to C.auris in intensive care units in our country which has a high COVID-19 incidence.

Effects of adjunct treatment with intravenous immunoglobulins on the course of severe COVID-19: results from a retrospective cohort study.

OBJECTIVES: To evaluate the effect of adjunct treatment with Octagam, an intravenous immunoglobulin (IVIG) product, on clinical outcomes and biomarkers in critically ill COVID-19 patients. METHODS: Data from a single center was analyzed retrospectively. Patients had received preliminary standard intensive care (SIC) according to a local treatment algorithm, either alone or along with IVIG 5% at 30 g/day for 5 days. The two groups were compared regarding baseline characteristics, survival and changes in inflammation markers. Imbalance in baseline APACHE II scores was addressed by propensity score matching. Otherwise, Kaplan-Meier and multiple logistic regression models were used. RESULTS: Out of 93 patients, 51 had received IVIG and 42 had not. About 75% of patients were male and both groups had comparable body mass index and AB0 blood type distribution. IVIG-treated patients were younger (mean 65 ± 15 versus 71 ± 15 years, p = .066) and had slightly lower baseline disease scores (APACHE II: 20.6 versus 22.4, p = .281; SOFA: 5.0 versus 7.0, p = .006). Overall survival was 61% in the SIC + IVIG and 38% in the SIC only group (odds ratio: 2.2, 95% confidence interval: 0.9-5.4, p = .091 after controlling for baseline imbalances). IVIG significantly prolonged median survival time (68 versus 18 days, p = .014) and significantly reduced plasma levels of C-reactive protein (median change from baseline -71.5 versus -0.3 mg/L, p = .049). CONCLUSION: Clinically relevant benefits through adjunct IVIG treatment in COVID-19 need to be confirmed in a randomized, controlled trial.

COVID-19 in chronic kidney disease: a retrospective, propensity score-matched cohort study.

BACKGROUND: The prognostic factors for COVID-19 in patients with chronic kidney disease (CKD) are uncertain. We conducted a study to compare clinical and prognostic features between hospitalized COVID-19 patients with and without CKD. METHODS: Fifty-six patients with stage 3-5 CKD and propensity score-matched fifty-six patients without CKD were included in the study. Patients were followed-up at least fifteen days or until death after COVID-19 diagnosis. The endpoints were death from all causes, development of acute kidney injury (AKI) or cytokine release syndrome or respiratory failure, or admission to the intensive care unit (ICU). RESULTS: All patients were reviewed retrospectively over a median follow-up of 44 days (IQR, 36-52) after diagnosis of COVID-19. Patients with CKD had higher intensive care unit admission and mortality rates than the patients without CKD, but these results did not reach statistical significance (16 vs. 19; p = 0.54 and 11 vs. 16, p = 0.269, respectively). The frequency of AKI development was significantly higher in predialysis patients with CKD compared to the other group (8 vs. 5; p < 0.001), but there was no significant difference between the groups in terms of cytokine release syndrome (13 vs. 8; p = 0.226), follow-up in the ICU (19 vs. 16; p = 0.541), and respiratory failure (25 vs. 22, p = 0.566). Multivariate logistic regression analysis revealed that respiratory failure and AKI were independent risk factors for mortality. CONCLUSION: The mortality rates of COVID-19 patients with CKD had higher than COVID-19 patients without CKD. Also, AKI and respiratory failure were independently related to mortality.

Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study.

BACKGROUND: To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae. METHODS: This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression. FINDINGS: Between Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation-Sedation Scale score while on invasive mechanical ventilation was -4 (-5 to -3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). During the 21-day study period, patients were alive without delirium or coma for a median of 5·0 days (0·0 to 14·0). At baseline, older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). 601 (28·8%) of 2088 patients died within 28 days of admission, with most of those deaths occurring in the ICU. INTERPRETATION: Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19. FUNDING: None. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Prognostic Value of Antithrombin Levels in COVID-19 Patients and Impact of Fresh Frozen Plasma Treatment: A Retrospective Study

Objective: The defective interplay between coagulation and inflammation may be the leading cause of intravascular coagulation and organ dysfunction in coronavirus disease-19 (COVID-19) patients. Abnormal coagulation profiles were reported to be associated with poor outcomes. In this study, we assessed the prognostic values of antithrombin (AT) activity levels and the impact of fresh frozen plasma (FFP) treatment on outcome. Materials and Methods: Conventional coagulation parameters as well as AT activity levels and outcomes of 104 consecutive critically ill acute respiratory distress syndrome (ARDS) patients with laboratory-confirmed COVID-19 disease were retrospectively analyzed. Patients with AT activity below 75% were treated with FFP. Maximum AT activity levels achieved in those patients were recorded. Results: AT activity levels at admission were significantly lower in nonsurvivors than survivors (73% vs. 81%). The cutoff level for admission AT activity was 79% and 58% was the lowest AT for survival. The outcome in those patients who had AT activity levels above 75% after FFP treatment was better than that of the nonresponding group. As well as AT, admission values of D-dimer, C-reactive protein, and procalcitonin were coagulation and inflammatory parameters among the mortality risk factors. Conclusion: AT activity could be used as a prognostic marker for survival and organ failure in COVID-19-associated ARDS patients. AT supplementation therapy with FFP in patients with COVID-19-induced hypercoagulopathy may improve thrombosis prophylaxis and thus have an impact on survival.

Fatal SARS-CoV-2 infection in a renal transplant recipient.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) caused a pandemic that first discovered in Wuhan, China. While 10% of the patients have asymptomatic infection, 15-20% have lung involvement, 5-10% have multiple organ failure, and macrophage activation syndrome. Chronic respiratory diseases, diabetes mellitus, hypertension, and cancer are risk factors for mortality. Prognosis or optimal treatment strategy for renal transplant recipients in SARS-CoV-2 infection is still unknown. Besides fatal cases, there were also milder case reports. In addition, COVID-19 treatment and the maintenance immunosuppression strategy is still under debate. Antiviral therapies and drug interactions are special topics for these patients. To the best of our knowledge, favipiravir and anti-cytokine treatments have not been previously reported in a kidney transplant recipient with SARS-CoV-2 infection before. We report a case of SARS-CoV-2 infection in a kidney transplant recipient with fatal outcomes.