Abstract
Objective To test the hypotheses that blood concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients.
Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa). Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects.
Results In total, 21 % (n = 10) of the patients were admitted to an intensive care unit, whereas the overall mortality rate was 13 % (n = 6). Non-survivors had higher serum concentrations of NfL than patients who were discharged alive both in adjusted analyses (p = 2.6 × 10−7) and unadjusted analyses (p = 0.001). Serum concentrations of GFAp were significantly higher in non-survivors than survivors in adjusted analyses (p = 0.02). The NfL concentrations in non-survivors increased over repeated measurements, whereas the concentrations in survivors were stable. Significantly higher concentrations of NfL were found in patients reporting fatigue, while reduced concentrations were found in patients experiencing cough, myalgia and joint pain.
Conclusion Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.
Competing Interest Statement
A.H. Aamodt has received travel support, honoraria for advice or lecturing from Bayer, Boehringer Ingelheim, BMS, Allergan, Teva, Sanofi-Genzyme, Novartis, Roche, and Teva and research grant from Medtronic and Boehringer Ingelheim. T.H. Popperud has received honoraria for lecturing from Alexion and unrestricted research support from Octapharma. E. A. Høgestøl has received honoraria for lecturing from Biogen, Merck and Sanofi-Genzyme, and unrestricted research support from Merck and Sanofi-Genzyme. H.F. Harbo has received travel support, honoraria for advice or lecturing from Biogen Idec, Sanofi-Genzyme, Merck, Novartis, Roche, and Teva and an unrestricted research grant from Novartis. Kaj Blennow has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. 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. H. Zetterberg 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 (outside submitted work).
Funding Statement
Supported by Oslo University Hospital, Research Council of Norway grant no 312780, Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Informed consents were obtained from all patients or next-of-kin if patients were incapacitated of giving consent. The study was approved by the South-Eastern Norway Regional Health Authority (reference number: 106624).
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Data Availability
The data that support the findings of this study are available on request from the corresponding author, AHA. The data are not publicly available due to ethical restrictions.
Abbreviations used in this paper
- CNS
- central nervous system;
- SARS-CoV-2
- severe acute respiratory syndrome coronavirus 2;
- ACE-2
- angiotensin-converting enzyme 2;
- NfL
- neurofilament light protein;
- GFAp
- glial fibrillary acidic protein