Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: A prospective study

Robert Frithiof, Elham Rostami, Eva Kumlien, Johan Virhammar, David Fällmar, Michael Hultström, Miklós Lipcsey, Nicholas Ashton, Kaj Blennow, Henrik Zetterberg, Anna Rostedt Punga, Robert Frithiof, Elham Rostami, Eva Kumlien, Johan Virhammar, David Fällmar, Michael Hultström, Miklós Lipcsey, Nicholas Ashton, Kaj Blennow, Henrik Zetterberg, Anna Rostedt Punga

Abstract

Objective: The aim was to characterize the electrophysiological features and plasma biomarkers of critical illness polyneuropathy (CIN) and myopathy (CIM) in coronavirus disease 2019 (COVID-19) patients with intensive care unit acquired weakness (ICUAW).

Methods: An observational ICU cohort study including adult patients admitted to the ICU at Uppsala University Hospital, Uppsala, Sweden, from March 13th to June 8th 2020. We compared the clinical, electrophysiological and plasma biomarker data between COVID-19 patients who developed CIN/CIM and those who did not. Electrophysiological characteristics were also compared between COVID-19 and non-COVID-19 ICU patients.

Results: 111 COVID-19 patients were included, 11 of whom developed CIN/CIM. Patients with CIN/CIM had more severe illness; longer ICU stay, more thromboembolic events and were more frequently treated with invasive ventilation for longer than 2 weeks. In particular CIN was more frequent among COVID-19 patients with ICUAW (50%) compared with a non-COVID-19 cohort (0%, p = 0.008). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) levels were higher in the CIN/CIM group compared with those that did not develop CIN/CIM (both p = 0.001) and correlated with nerve amplitudes.

Conclusions: CIN/CIM was more prevalent among COVID-19 ICU patients with severe illness.

Significance: COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care, suggesting their potential as predictive biomarkers for CIN/CIM.

Keywords: COVID-19; Critical illness neuropathy; Myopathy; NFL; SARS-CoV-2.

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (all outside submitted work). The other authors report no disclosures.

Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
Flow chart of the screening and inclusion of patients in the study.
Fig. 2
Fig. 2
Levels of plasma A) neurofilament light chain (NfL), B) glial fibrillary acidic protein (GFAp) and C) Tau in pg/ml (logarithmic scale) comparing patients with critical illness neuropathy/myopathy (CIN/CIM; filled circles) with the patients without CIN/CIM (open triangles) at the early (median: 4 days, range: 3–9 days) and late timepoint (median: 16 days, range: 11–42 days).
Fig. 3
Fig. 3
A) Combined motor amplitude (CMA) of all examined motor nerves (ulnar, median, fibular and tibial) and B) combined sensory amplitude (CSA) of all examined sensory nerves (ulnar, radial, sural) in the group of patients without critical illness neuropathy (CIN) or myopathy (CIM) (N = 3) and among patients with CIN/CIM (N = 11).
Fig. 4
Fig. 4
A) Correlation between compound motor amplitude score (CMA) and glial fibrillary acidic protein (GFAp). Spearman R = -0.72; p = 0.007. B) Correlation between compound sensory amplitude score (CSA) and Tau. Spearman R = -0.63; p = 0.024.

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