Randomized controlled study to evaluate the safety and clinical impact of percutaneous auricular vagus nerve stimulation in patients with severe COVID-19.

Introduction: A severe course of COVID-19 is characterized by a hyperinflammatory state resulting in acute respiratory distress syndrome or even multi-organ failure along a derailed sympatho-vagal balance. Methods: In this prospective, randomized study, we evaluate the hypothesis that percutaneous minimally invasive auricular vagus nerve stimulation (aVNS) is a safe procedure and might reduce the rate of clinical complications in patients with severe course of COVID-19. In our study, patients with SARS-CoV-2 infection admitted to the intensive care unit with moderate-to-severe acute respiratory distress syndrome, however without invasive ventilation yet, were included and following randomization assigned to a group receiving aVNS four times per 24 h for 3 h and a group receiving standard of care (SOC). Results: A total of 12 patients were included (six in the aVNS and six in the SOC group). No side effects in aVNS were reported, especially no significant pain at device placement or during stimulation at the stimulation site or significant headache or bleeding after or during device placement or lasting skin irritation. There was no significant difference in the aVNS and SOC groups between the length of stay in the intensive care unit and at the hospital, bradycardia, delirium, or 90-day mortality. In the SOC group, five of six patients required invasive mechanical ventilation during their stay at hospital and 60% of them venovenous extracorporeal membrane oxygenation, compared to three of six patients and 0% in the aVNS group (p = 0.545 and p = 0.061). Discussion: Vagus nerve stimulation in patients with severe COVID-19 is a safe and feasible method. Our data showed a trend to a reduction of progression to the need of invasive ventilation and venovenous extracorporeal membrane oxygenation which encourages further research with larger patient samples.

The Role of Bacterial and Fungal Superinfection in Critical COVID-19.

BACKGROUND: The range of reported rates of bacterial and fungal superinfections in patients with a severe course of COVID-19 is wide, suggesting a lack of standardised reporting. METHODS: The rates of bacterial and fungal superinfection were assessed using predefined criteria to differentiate between infection and contamination. RESULTS: Overall, 117 patients admitted to the Intensive Care Unit due to severe COVID-19 were included. Overall, 55% of patients developed a superinfection and 13.6% developed a fungal superinfection (5.9% candidemia and 7.7% CAPA). The rate of ventilator-associated pneumonia was 65.2%. If superinfection was detected, the length of hospital stay was significantly longer and the mortality was especially increased if candidemia was detected. An increased risk of superinfection was observed in patients with pre-existing diabetes mellitus or chronic heart failure. The presence of immunomodulating therapy did not seem to have an impact on the frequency of superinfections. CONCLUSION: Increased awareness of high superinfection rates, fungal infections in particular, in patients suffering from severe COVID-19 is necessary.

Rapid Detection of Bacterial and Fungal Pathogens Using the T2MR versus Blood Culture in Patients with Severe COVID-19.

A high rate of bacterial and fungal superinfections was reported in critically ill patients with COVID-19. However, diagnosis can be challenging. The aim of this study is to evaluate the sensitivity and the clinical utility of the point-of-care method T2 magnetic resonance (T2MR) with the gold standard: the blood culture. T2MR can potentially detect five different Candida species and six common bacteria (so-called "ESKAPE" pathogens including Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinet`obacter baumanii, Pseudomonas aeruginosa, and Enterococcus faecium). If superinfection was suspected in patients with COVID-19 admitted to the intensive care unit, blood culture and two panels of T2MR were performed. Eighty-five diagnostic bundles were performed in 60 patients in total. T2MR detected an ESKAPE pathogen in 9 out of 85 (10.6%) samples, compared to BC in 3 out of 85 (3.5%). A Candida species was detected in 7 of 85 (8.2%) samples of T2MR compared to 1 out of 85(1.2%) in blood culture. The mean time to positive test result in samples with concordant positive results was 4.5 h with T2MR and 52.5 h with blood culture. The additional use of T2MR enables a highly sensitive and rapid detection of ESKAPE and Candida pathogens. IMPORTANCE Coronavirus disease 2019 (COVID-19) has led to a high number of deaths since the beginning of the pandemic worldwide. One of the reasons is the high number of bacterial and fungal superinfections in patients suffering from critical disease. However, diagnosis is often challenging. In this study we could show that the additional use of the culture-independent method T2MR did not only show a much higher detection rate of bacterial and fungal pathogens but also a significantly shorter time until detection and therapy change compared to the gold standard: the blood culture. The implementation of T2MRin the care of patients with severe course of COVID-19 might lead to an earlier sufficient antimicrobial therapy and as a result lower mortality and less use of broad-spectrum unnecessary therapy reducing the risk of resistance development.

Percutaneous Auricular Vagus Nerve Stimulation Reduces Inflammation in Critical Covid-19 Patients.

Covid-19 is an infectious disease associated with cytokine storms and derailed sympatho-vagal balance leading to respiratory distress, hypoxemia and cardiovascular damage. We applied the auricular vagus nerve stimulation to modulate the parasympathetic nervous system, activate the associated anti-inflammatory pathways, and reestablish the abnormal sympatho-vagal balance. aVNS is performed percutaneously using miniature needle electrodes in ear regions innervated by the auricular vagus nerve. In terms of a randomized prospective study, chronic aVNS is started in critical, but not yet ventilated Covid-19 patients during their stay at the intensive care unit. The results show decreased pro-inflammatory parameters, e.g. a reduction of CRP levels by 32% after 1 day of aVNS and 80% over 7 days (from the mean 151.9 mg/dl to 31.5 mg/dl) or similarly a reduction of TNFalpha levels by 58.1% over 7 days (from a mean 19.3 pg/ml to 8.1 pg/ml) and coagulation parameters, e.g. reduction of DDIMER levels by 66% over 7 days (from a mean 4.5 µg/ml to 1.5 µg/ml) and increased anti-inflammatory parameters, e.g. an increase of IL-10 levels by 66% over 7 days (from the mean 2.7 pg/ml to 7 pg/ml) over the aVNS duration without collateral effects. aVNS proved to be a safe clinical procedure and could effectively supplement treatment of critical Covid-19 patients while preventing devastating over-inflammation.