Age-related influence on DNA damage, proteomic inflammatory markers and oxidative stress in hospitalized COVID-19 patients compared to healthy controls.

COVID-19 infections are accompanied by adverse changes in inflammatory pathways that are also partly influenced by increased oxidative stress and might result in elevated DNA damage. The aim of this case-control study was to examine whether COVID-19 patients show differences in oxidative stress-related markers, unconjugated bilirubin (UCB), an inflammation panel and DNA damage compared to healthy, age-and sex-matched controls. The Comet assay with and without the treatment of formamidopyrimidine DNA glycosylase (FPG) and H2O2 challenge was used to detect DNA damage in whole blood. qPCR was applied for gene expression, UCB was analyzed via HPLC, targeted proteomics were applied using Olink® inflammation panel and various oxidative stress as well as clinical biochemistry markers were analyzed in plasma. Hospitalized COVID-19 patients (n = 48) demonstrated higher serum levels of 55 inflammatory proteins (p < 0.001), including hs-C-reactive protein levels (p < 0.05), compared to healthy controls (n = 48). Interestingly, significantly increased age-related DNA damage (%-DNA in tail) after formamidopyrimidine DNA glycosylase (FPG) treatment was measured in younger (n = 24, average age 55.7 years; p < 0.05) but not in older COVID-19 patients (n = 24, average age 83.5 years; p > 0.05). Although various oxidative stress markers were not altered (e.g., FRAP, malondialdehyde, p > 0.05), a significant increased ratio of oxidized to reduced glutathione was detected in COVID-19 patients compared to healthy controls (p < 0.05). UCB levels were significantly lower in individuals with COVID-19, especially in younger COVID-19 patients (p < 0.05). These results suggest that COVID-19 infections exert effects on DNA damage related to age in hospitalized COVID-19 patients that might be driven by changes in inflammatory pathways but are not altered by oxidative stress parameters.

Evaluation of a novel, rapid antigen detection test for the diagnosis of SARS-CoV-2.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is currently finally determined in laboratory settings by real-time reverse-transcription polymerase-chain-reaction (rt-PCR). However, simple testing with immediately available results are crucial to gain control over COVID-19. The aim was to evaluate such a point-of-care antigen rapid test (AG-rt) device in its performance compared to laboratory-based rt-PCR testing in COVID-19 suspected, symptomatic patients. METHODS: For this prospective study, two specimens each of 541 symptomatic female (54.7%) and male (45.3%) patients aged between 18 and 95 years tested at five emergency departments (ED, n = 296) and four primary healthcare centres (PHC, n = 245), were compared, using AG-rt (positive/negative/invalid) and rt-PCR (positive/negative and cycle threshold, Ct) to diagnose SARS-CoV-2. Diagnostic accuracy, sensitivity, specificity, positive predictive values (PPV), negative predictive value (NPV), and likelihood ratios (LR+/-) of the AG-rt were assessed. RESULTS: Differences between ED and PHC were detected regarding gender, age, symptoms, disease prevalence, and diagnostic performance. Overall, 174 (32.2%) were tested positive on AG-rt and 213 (39.4%) on rt-PCR. AG correctly classified 91.7% of all rt-PCR positive cases with a sensitivity of 80.3%, specificity of 99.1%, PPV of 98.3, NPV of 88.6%, LR(+) of 87.8, and LR(-) of 0.20. The highest sensitivities and specificities of AG-rt were detected in PHC (sensitivity: 84.4%, specificity: 100.0%), when using Ct of 30 as cut-off (sensitivity: 92.5%, specificity: 97.8%), and when symptom onset was within the first three days (sensitivity: 82.9%, specificity: 99.6%). CONCLUSIONS: The highest sensitivity was detected with a high viral load. Our findings suggest that AG-rt are comparable to rt-PCR to diagnose SARS-CoV-2 in COVID-19 suspected symptomatic patients presenting both at emergency departments and primary health care centres.

Standard blood laboratory values as a clinical support tool to distinguish between SARS-CoV-2 positive and negative patients.

Standard blood laboratory parameters may have diagnostic potential, if polymerase-chain-reaction (PCR) tests are not available on time. We evaluated standard blood laboratory parameters of 655 COVID-19 patients suspected to be infected with SARS-CoV-2, who underwent PCR testing in one of five hospitals in Vienna, Austria. We compared laboratory parameters, clinical characteristics, and outcomes between positive and negative PCR-tested patients and evaluated the ability of those parameters to distinguish between groups. Of the 590 patients (20-100 years, 276 females and 314 males), 208 were PCR-positive. Positive compared to negative PCR-tested patients had significantly lower levels of leukocytes, neutrophils, basophils, eosinophils, lymphocytes, neutrophil-to-lymphocyte ratio, monocytes, and thrombocytes; while significantly higher levels were detected with erythrocytes, hemoglobin, hematocrit, C-reactive-protein, ferritin, activated-partial-thromboplastin-time, alanine-aminotransferase, aspartate-aminotransferase, lipase, creatine-kinase, and lactate-dehydrogenase. From all blood parameters, eosinophils, ferritin, leukocytes, and erythrocytes showed the highest ability to distinguish between COVID-19 positive and negative patients (area-under-curve, AUC: 72.3-79.4%). The AUC of our model was 0.915 (95% confidence intervals, 0.876-0.955). Leukopenia, eosinopenia, elevated erythrocytes, and hemoglobin were among the strongest markers regarding accuracy, sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio, and post-test probabilities. Our findings suggest that especially leukopenia, eosinopenia, and elevated hemoglobin are helpful to distinguish between COVID-19 positive and negative tested patients.

Providing the best chest compression quality: Standard CPR versus chest compressions only in a bystander resuscitation model.

AIM OF THE STUDY: Bystander-initiated basic life support (BLS) for the treatment of prehospital cardiac arrest increases survival but is frequently not performed due to fear and a lack of knowledge. A simple flowchart can improve motivation and the quality of performance. Furthermore, guidelines do recommend a chest compression (CC)-only algorithm for dispatcher-assisted bystander resuscitation, which may lead to increased fatigue and a loss of compression depth. Consequently, we wanted to test the hypothesis that CCs are more correctly delivered in a flowchart-assisted standard resuscitation algorithm than in a CC-only algorithm. METHODS: With the use of a manikin model, 84 laypersons were randomized to perform either flowchart-assisted standard resuscitation or CC-only resuscitation for 5min. The primary outcome was the total number of CCs. RESULTS: The total number of correct CCs did not significantly differ between the CC-only group and the standard group (63 [±81] vs. 79 [±86]; p = 0.394; 95% CI of difference: 21-53). The total hand-off time was significantly lower in the CC-only group than in the standard BLS group. The relative number of correct CCs (the fraction of the total number of CCs achieving 5-6cm) and the level of exhaustion after BLS did not significantly differ between the groups. CONCLUSION: Standard BLS did not lead to an increase in correctly delivered CCs compared to CC-only resuscitation and exhibited significantly more hand-off time. The low rate of CCs in both groups indicates the need for an increased focus on performance during BLS training.

Early Antibiotic Prophylaxis Prior to Bypass Surgery Improves Tissue Penetration.

BACKGROUND: We previously identified preparation of the internal mammary artery as a risk factor significantly impairing antibiotic tissue penetration into the presternal subcutaneous tissue. We, therefore, adapted our dosing schema regarding preoperative timing to overcome this risk factor. METHODS: Eight patients who underwent coronary artery bypass grafting with a left internal mammary artery and vein grafts were included in this clinical trial. Cefazolin (4 g) was administered twice (3 hours and 1 hour) prior to skin incision and once during skin closure (2 g). Antibiotic concentrations were measured with subcutaneous microdialysis probes on both sternal sides. Results were directly compared with the previously published patient cohort receiving the standard schema (4 g cefazolin prior to skin incision and 2 g during closure). RESULTS: All patients (7 male, 1 female, 69 ± 7 years, 26.3 ± 3.9 kg/m2) survived the perioperative period. Mean area under the curve on the right and left sternal side was 117.0 ± 92.5 µg/mL and 114.5 ± 83.2 µg/mL, respectively (p = 0.95). This was well above the previously measured mean peak tissue concentrations without early preoperative antibiotic administration on the side of mammary artery harvesting (52.4 ± 48.5 µg/mL vs. 13.1 ± 5.8 µg/mL; p = 0.039). The %fT > minimal inhibitory concentration (MIC) for Staphylococcus epidermidis and Staphylococcus aureus during the first 10 hours in presternal tissue was ≥ 70% but did not differ compared with standard schema. CONCLUSIONS: Early, additional preoperative administration of cefazolin was able to significantly increase peak tissue concentrations during surgery compared with the standard protocol. No difference, however, could be achieved in the percentage of time during which the concentration exceeded the MIC.

Haemodynamic response at double lumen bronchial tube placement - Airtraq vs. MacIntosh laryngoscope, a randomised controlled trial.

INTRODUCTION: Tracheal intubation causes a haemodynamic response that might be harmful for patients. The Airtraq® laryngoscope has been shown to decrease the haemodynamic response to single-lumen tube intubation. We hypothesised that double-lumen bronchial tube placement with the Double-lumen Airtraq® laryngoscope would cause a reduced haemodynamic response and decreased catecholamine release compared with the MacIntosh laryngoscope. METHODS: Forty adult patients were randomly assigned to the Airtraq® group or to the MacIntosh group. Intubation with either the Airtraq® or the MacIntosh laryngoscope was performed two minutes after standardised induction of anaesthesia. Arterial blood pressure, heart rate, catecholamine levels, bispectral index and duration of the intubation procedure were measured. RESULTS: Mean (standard deviation [95% confidence interval]) systolic arterial blood pressure at laryngoscopy with the Airtraq® laryngoscope was 124 (34 [106 to 141]) mmHg and, with the MacIntosh laryngoscope, it was 110 (25 [99 to 122]) mmHg (p=1.0). Heart rate at laryngoscopy with the Airtraq® laryngoscope was 75 beats·min-1 (16 [67 to 83]) and, with the MacIntosh laryngoscope, it was 64 beats·min-1 (14 [58 to 71]) (p=0.71). Adrenaline levels post-intubation were 54.3 ng·l-1 (41.5) [29.3 to 79.4] in the Airtraq® group and 30.5 ng·l-1 (25.6) [15.1 to 46.0] in the MacIntosh group (p=0.016). The duration of intubation with the Airtraq® laryngoscope was 88 s (31 [72-104]) while, with the MacIntosh laryngoscope, the duration was 75 s (35 [59-92]) (p=0.26). CONCLUSIONS: The use of the Double-lumen Airtraq® laryngoscope provides no benefit regarding stress response compared to the MacIntosh laryngoscope.

Comparison of a conventional tracheal airway with the Combitube in an urban emergency medical services system run by physicians.

This prospective randomised study was performed to compare the use of the Esophageal-Tracheal Combitube(R) (ETC; Tyco Healthcare, Mansfield, MA; http://www.combitube.org) with a conventional tracheal airway (ETA) for airway management by experienced physicians of the Emergency Medical Services System of the City of Vienna in the prehospital setting. Access to the patient's head, time of arrival of the ambulance, ease of insertion, time of insertion, potential substitution by the alternate airway, efficacy of adrenaline (epinephrine) administered via the airway, survival to the intensive care unit (ICU) ward and survival to discharge from the hospital were evaluated. One hundred and seventy-two non-traumatic cardiac arrest patients (131 males, 41 females) were enrolled in this study during a 12 months period. In 83 patients (48.3%), the conventional ETA (group 1) was used for the initial intubation attempt which was successful in 78 patients (94%). The remaining five patients of group 1 could not be intubated with an ETA, but were successfully managed with the ETC. Eighty-nine patients (51.7%) were intubated with the ETC (group 2) as first choice (79 in oesophageal position (89%); eight in tracheal position: (9%)), which was successful in 87 (98%) patients. The remaining two patients in group 2 (2%) were successfully managed with the ETA. Success of intubation and ventilation with ETC was comparable to the ETA. Recorded time of insertion was shorter with the ETC versus ETA (P<0.05). The Combitube worked well in cases of difficult access to the patient's head and in bleeding and vomiting patients. Both devices served as successful substitutes for each other. Adrenaline (epinephrine) applied via ETC with a 10-fold dosage was as effective as via the conventional ETA. To our knowledge this is the first study using physicians comparing ETC and ETA in the prehospital setting.