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We read with great interest the recent article by Sutter and colleagues reporting increased serum neurofilament light chain (NfL) levels in COVID-19 patients compared to non-COVID-19 intensive care unit (ICU) patients without infectious disease. 1 They postulated that infection with SARS-CoV-2 leads to neuronal injury in ICU-patients and that NfL might be used to identify patients at risk for neurological complications.We evaluated these findings in the broader context of infectious disorders by comparing the plasma NfL levels of critically ill patients with similar disease severity and pneumonia induced by SARS-CoV-2 versus bacterial pathogens. We excluded patients with neurological comorbidities or trauma and matched the study population investigated by Sutter et al for sex, age, and disease severity (COVID-19 pneumonia vs bacterial pneumonia: mean age = 65 years, range = 42-89, 78% male, Sequential Organ Failure Assessment [SOFA] score = 4, range = 2-11 vs mean age = 67 years, range = 50-89, 90% male, SOFA score = 3, range = 0-5). Most notably, we observed that patients with COVID-19 pneumonia had considerably lower NfL levels compared to patients with bacterial pneumonia at day 3 AE 1 after onset of sepsis (defined as infection-related acute change in total SOFA score ≥ 2 points), which did not significantly increase over time (Fig A). Consistently with previous reports, we found a positive correlation between NfL levels and age as well as SOFA score in COVID-19 patients (see Fig B , C).FIGURE: Neurofilament light chain (NfL) assay by Quanterix (Billerica, MA) HD-X was used to measure NfL levels according to manufacturer's instructions. (A) Comparison of NfL levels in patients with COVID-19 pneumonia at day 3 AE 1 and day 7 AE 1 (n = 18) and bacterial pneumonia at day 3 AE 1 (scatter dot blot with mean; n = 10) after onset of sepsis (analysis of variance on ranks, p < 0.001; Dunn multiple comparison test, ***p < 0.001). (B, C) Pearson correlation was used to assess correlations between neurofilaments and Sequential Organ Failure Assessment (SOFA) score (n = 36; day 3 AE 1 and 7 AE 1) or age (n = 18; day 3 AE 1) in COVID-19 patients.

IntroductionSepsis is one of the most prevalent life-threatening conditions in the intensive care unit. Patients suffer from impaired organ function, reduced physical functional capacity and decreased quality of life even after surviving sepsis. The identification of prognostic factors for the medium-term and long-term outcomes of this condition is necessary to develop personalised theragnostic approaches. Sepsis can cause cardiac impairment. The impact of this septic cardiomyopathy on patient’s long-term outcome remains unclear. This study aims to evaluate cardiovascular risk factors, particularly the occurrence of septic cardiomyopathy, regarding their suitability as prognostic factors for the short-term and long-term outcomes of septic patients. Additionally, the study seeks to validate preclinical pathophysiological findings of septic cardiomyopathy in the clinical setting.Methods and analysisIn this prospective monocentric cohort study, patients will be clinically assessed during the acute and postacute phase of sepsis and two follow-ups after 6 and 12 months. To determine the effect of septic cardiomyopathy and concomitant cellular and molecular changes on patient mortality and morbidity, a comprehensive cardiovascular and molecular deep phenotyping of patients will be performed. This includes an echocardiographic and electrocardiographic assessment, and the evaluation of heart rate variability, body composition, mitochondrial oxygen metabolism, macrocirculation and microcirculation, and endothelial barrier function. These analyses are complemented by routine immunological, haematological and biochemical laboratory tests and analyses of the serum metabolome and lipidome, microbiome and epigenetic modifications of immune cells. The reversibility of patients’ organ dysfunction, their quality of life and physical functional capacity will be investigated in the follow-ups. Patients with cardiomyopathy without infection and healthy subjects will serve as control groups.Ethics and disseminationApproval was obtained from the Ethics Committee of the Friedrich Schiller University Jena (5276-09/17). The results will be published in peer-reviewed journals and presented at appropriate conferences.Trial registration numbersDRKS00013347; NCT03620409.