Criteria for Hyperinflammation Developing in COVID-19: Analysis of 2 Cohorts From Different Periods of the Pandemic.

OBJECTIVE: Hyperinflammation (HI) that develops in week 2 of COVID-19 contributes to a worse outcome. Because week 2 laboratory findings can be relatively mild, the available criteria for classification of hemophagocytic lymphohistiocytosis or macrophage activation syndrome are not helpful. METHODS: Our study included a discovery cohort of patients from Turkey with symptomatic COVID-19 who were followed up while hospitalized during the initial wave and a replication cohort of hospitalized patients from a later period, all of whom required oxygen support and received glucocorticoids. Diagnosis of HI was made by an expert panel; most patients with COVID-19-associated HI (HIC) received tocilizumab or anakinra. Clinical and laboratory data from start day of treatment with tocilizumab or anakinra in HIC patients were compared with the data from day 5-6 in patients without HIC. Values maximizing the sensitivity and specificity of each parameter were calculated to determine criteria items. RESULTS: The discovery cohort included 685 patients, and the replication cohort included 156 patients, with 150 and 61 patients receiving treatment for HI, respectively. Mortality rate in HI patients in the discovery cohort (23.3%) was higher than the rate in patients without HI (3.7%) and the rate in patients in the overall replication cohort (10.3%). The 12-item criteria that we developed for HIC showed that a score of 35 provided 85.3% sensitivity and 81.7% specificity for identification of HIC. In the replication cohort, the same criteria resulted in 90.0% sensitivity for HIC; however, lower specificity values were observed because of the inclusion of milder cases of HIC responding only to glucocorticoids. CONCLUSION: The use of the 12-item criteria for HIC can better define patients with HIC with reasonable sensitivity and specificity and enables an earlier treatment start.

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.

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.