Characteristics, interventions, and longer term outcomes of COVID-19 ICU patients in Denmark-A nationwide, observational study.

BACKGROUND: Most data on intensive care unit (ICU) patients with COVID-19 originate in selected populations from stressed healthcare systems with shorter term follow-up. We present characteristics, interventions and longer term outcomes of the entire, unselected cohort of all ICU patients with COVID-19 in Denmark where the ICU capacity was not exceeded. METHODS: We identified all patients with SARS-CoV-2 admitted to any Danish ICU from 10 March to 19 May 2020 and registered demographics, chronic comorbidities, use of organ support, length of stay, and vital status from patient files. Risk factors for death were analyzed using adjusted Cox regression analysis. RESULTS: There were 323 ICU patients with confirmed COVID-19. Median age was 68 years, 74% were men, 50% had hypertension, 21% diabetes, and 20% chronic pulmonary disease; 29% had no chronic comorbidity. Invasive mechanical ventilation was used in 82%, vasopressors in 83%, renal replacement therapy in 26%, and extra corporeal membrane oxygenation in 8%. ICU stay was median 13 days (IQR 6-22) and hospital stay 19 days (11-30). Median follow-up was 79 days. At end of follow-up, 118 had died (37%), 15 (4%) were still in hospital hereof 4 in ICU as of 16 June 2020. Risk factors for mortality included male gender, age, chronic pulmonary disease, active cancer, and number of co-morbidities. CONCLUSIONS: In this nationwide, population-based cohort of ICU patients with COVID-19, longer term survival was high despite high age and substantial use of organ support. Male gender, age, and chronic co-morbidities, in particular chronic pulmonary disease, were associated with increased risk of death.

[Intracerebral haemorrhage twelve days after vaccination with ChAdOx1 nCoV-19].

The COVID-19-pandemic has had a huge impact on health and economics all over the world resulting in widespread vaccine development. Vaccine-induced immune thrombotic thrombocytropenia has been described, suggesting a link between the two adeno-vector vaccines ChAdOx1 nCoV-19 (Vaxzevria from AstraZeneca) and Ad26.COV2-S (Janssen from Johnson and Johnson). This rare clinical condition should be suspected in patients with headache, abdominal pain, suspected thrombosis or hemorrhage and thrombocytopenia within 3-30-day post vaccine. In this case report a previously healthy man had thrombocytopenia with fatal intracerebral haemorrhage which was suspected to be related to vaccine.

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.

Initial experiences from patients with COVID-19 on ventilatory support in Denmark.

INTRODUCTION: The coronavirus disease 2019 (COVID-19)pandemic reached Denmark in early 2020. This paper presents initial intensive-care unit (ICU) experiences with COVID-19 patients at Roskilde Hospital, which was the primary recipient of COVID-19 patients in need of intensive care in the Zealand Region, Denmark. METHODS: An evaluation was conducted of the COVID-19 patients admitted to the ICU due to respiratory failure from 11 March 2020 to 01 April 2020. The number of ICU beds was increased from eight to 22 beds during this period. RESULTS: Sixteen patients (four women) were evaluated. The median age was 69.5 years (range: 56-84 years). All the patients were admitted to the ICU for hypoxemic respiratory failure and all needed mechanical ventilation by orotracheal intubation. By 16 April, six patients were still admitted to the ICU, four patients had been discharged from the ICU and seven had died. At present, the average length of ICU stay is 14 ± 9 days (mean ± standard deviation). One patient has remained on ventilatory support for 31 days. The evaluation revealed four key themes. COVID-19 patients 1) had greatly increased C-reactive protein levels, 2) needed a significant inspiratory O2fraction, 3) were highly positive end-expiratory pressure (PEEP) dependent on ventilatory support and 4) suffered highly fluctuating respiratory failure requiring ventilatory support for a significantly longer period of time than non-COVID-19 patients. CONCLUSIONS: COVID-19 patients have characteristic reproducible laboratory findings and present a major challenge due to their illness severity and required treatment length. FUNDING: none. TRIAL REGISTRATION: not relevant.

Induced hypothermia in patients with septic shock and respiratory failure (CASS): a randomised, controlled, open-label trial.

BACKGROUND: Animal models of serious infection suggest that 24 h of induced hypothermia improves circulatory and respiratory function and reduces mortality. We tested the hypothesis that a reduction of core temperature to 32-34°C attenuates organ dysfunction and reduces mortality in ventilator-dependent patients with septic shock. METHODS: In this randomised, controlled, open-label trial, we recruited patients from ten intensive care units (ICUs) in three countries in Europe and North America. Inclusion criteria for patients with severe sepsis or septic shock were a mean arterial pressure of less than 70 mm Hg, mechanical ventilation in an ICU, age at least 50 years, predicted length of stay in the ICU at least 24 h, and recruitment into the study within 6 h of fulfilling inclusion criteria. Exclusion criteria were uncontrolled bleeding, clinically important bleeding disorder, recent open surgery, pregnancy or breastfeeding, or involuntary psychiatric admission. We randomly allocated patients 1:1 (with variable block sizes ranging from four to eight; stratified by predictors of mortality, age, Acute Physiology and Chronic Health Evaluation II score, and study site) to routine thermal management or 24 h of induced hypothermia (target 32-34°C) followed by 48 h of normothermia (36-38°C). The primary endpoint was 30 day all-cause mortality in the modified intention-to-treat population (all randomly allocated patients except those for whom consent was withdrawn or who were discovered to meet an exclusion criterion after randomisation but before receiving the trial intervention). Patients and health-care professionals giving the intervention were not masked to treatment allocation, but assessors of the primary outcome were. This trial is registered with ClinicalTrials.gov, number NCT01455116. FINDINGS: Between Nov 1, 2011, and Nov 4, 2016, we screened 5695 patients. After recruitment of 436 of the planned 560 participants, the trial was terminated for futility (220 [50%] randomly allocated to hypothermia and 216 [50%] to routine thermal management). In the hypothermia group, 96 (44·2%) of 217 died within 30 days versus 77 (35·8%) of 215 in the routine thermal management group (difference 8·4% [95% CI -0·8 to 17·6]; relative risk 1·2 [1·0-1·6]; p=0·07]). INTERPRETATION: Among patients with septic shock and ventilator-dependent respiratory failure, induced hypothermia does not reduce mortality. Induced hypothermia should not be used in patients with septic shock. FUNDING: Trygfonden, Lundbeckfonden, and the Danish National Research Foundation.

Mild induced hypothermia: effects on sepsis-related coagulopathy--results from a randomized controlled trial.

INTRODUCTION: Coagulopathy associates with poor outcome in sepsis. Mild induced hypothermia has been proposed as treatment in sepsis but it is not known whether this intervention worsens functional coagulopathy. MATERIALS AND METHODS: Interim analysis data from an ongoing randomized controlled trial; The Cooling And Surviving Septic shock (CASS) study. Patients suffering severe sepsis/septic shock are allocated to either mild induced hypothermia (cooling to 32-34°C for 24hours) or control (uncontrolled temperature). TRIAL REGISTRATION: NCT01455116. Thrombelastography (TEG) is performed three times during the first day after study enrollment in all patients. Reaction time (R), maximum amplitude (MA) and patients' characteristics are here reported. RESULTS: One hundred patients (control n=50 and intervention n=50; male n=59; median age 68years) with complete TEG during follow-up were included. At enrollment, 3%, 38%, and 59% had a hypocoagulable, normocoagulable, and hypercoagulable TEG clot strength (MA), respectively. In the hypothermia group, functional coagulopathy improved during the hypothermia phase, measured by R and MA, in patients with hypercoagulation as well as in patients with hypocoagulation (correlation between ΔR and initial R: rho=-0.60, p<0.0001 and correlation between ΔMA and initial MA: rho=-0.50, p=0.0002). Similar results were not observed in the control group neither for R (rho=-0.03, p=0.8247) nor MA (rho=-0.15, p=0.3115). CONCLUSION: Mild induced hypothermia did seem to improve functional coagulopathy in septic patients. This improvement of functional coagulopathy parameters during the hypothermia intervention persisted after rewarming. Randomized trials are warranted to determine whether the positive effect on sepsis-related coagulopathy can be transformed to improved survival.