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Neurological injury biomarkers in acute COVID-19 normalise in the long term – Swedish study

The normalisation of central nervous system (CNS) injury biomarkers in all individuals, regardless of previous disease severity or persisting neurological symptoms, indicates that post COVID-19 neurological sequelae are not accompanied by ongoing CNS injury, found a Swedish study.

Central nervous system involvement and signs of brain injury have been described since the beginning of the SARS-CoV-2 pandemic. A previous study from the same group showed that hospitalised patients receiving oxygen therapy or ICU care often had signs of brain damage by measuring blood-based biomarker of brain injury.

In addition, in recent months it has been increasingly evident that after the acute phase of COVID-19, many patients still suffer from persisting neurologic disability. This often includes lethargy, fatigue, or impaired cognitive function. This consequence is now termed post-COVID condition.

The mechanism behind how COVID-19 causes persisting neurological symptoms is still not fully understood. In a follow-up study, the researchers aimed to investigate the longitudinal trajectories of the same plasma biomarkers in patients who have recovered from COVID-19, with and without persisting neurological symptoms.

Normalisation of markers

The study presented in EBioMedicine recruited 100 COVID-19 patients from the Sahlgrenska University Hospital in Gothenburg, Sweden. The study population was divided into groups according to disease severity: mild, moderate, and severe COVID-19. Blood samples were collected at an interval of acute phase of the disease, three- and six-months post-infection.

At the acute phase, patients who required hospitalisation and were receiving oxygen therapy or mechanical ventilation showed an increase of NfL (neurofilament light chain protein), a biomarker that increases with neuronal injury, and GFAp (glial fibrillary acidic protein), a biomarker that indicates astrocytic injury or overactivation. At follow-up, all biomarkers returned to their normal baseline values.

In addition, at three- and six-month clinical follow-ups, 50 patients out of the 100 recruited individuals reported one or more neurological symptoms, the most common being fatigue, "brain-fog". and cognitive impairment, such as memory loss and lack of concentration. Remarkably, there was no difference in frequency of any symptoms among the disease severity groups.

Further research important
"The findings in this study emphasise the importance of further research that needs to validate the scale of persisting neurological symptoms and recovery, but also to investigate the true cause of this condition. This is of high importance from a scientific and public health point of view in search for better care of this patient group," says first author Nelly Kanberg, PhD student at the Infectious Disease at Sahlgrenska Academy, University of Gothenburg and resident medical doctor at the Department of Infectious Disease, Sahlgrenska University Hospital.

Magnus Gisslén, professor of Infectious Diseases at the Sahlgrenska Academy and chief physician at the Department of Infectious Diseases, Sahlgrenska University Hospital, leads the Academy's clinical research on COVID-19. The results of this study are, in his view, of great importance and encouraging for patients with long-lasting symptoms after COVID-19.

"Neurological complications are common in COVID-19 and can, in some patients, continue several months after the acute phase. It is reassuring that elevated concentrations of brain-injury markers return to normal three to six months after the acute phase of COVID-19 indicating that no continuous brain damage is present and that there is a good chance for recovery also in patients with remaining post-acute neurologic and cognitive symptoms," he said.

Study details

Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up

Nelly Kanberg, Joel Simrén, Arvid Edén, Lars-Magnus Andersson, Staffan Nilsson, Nicholas J. Ashton, Pär-Daniel Sundvall, Bengt Nellgård, Kaj Blennow, Henrik Zetterberg, Magnus Gisslén

Published in eBioMedicine on 29 July 2021

Abstract

Background
Neurologic manifestations are well-recognised features of COVID-19. However, the longitudinal association of biomarkers reflecting CNS impact and neurological symptoms is not known. We sought to determine whether plasma biomarkers of CNS injury were associated with neurologic sequelae after COVID-19.

Methods
Patients with confirmed acute COVID-19 were studied prospectively. Neurological symptoms were recorded during the acute phase of the disease and at six months follow-up, and blood samples were collected longitudinally. Healthy age-matched individuals were included as controls. We analysed plasma concentrations of neurofilament light-chain (NfL), glial fibrillary acidic protein (GFAp), and growth differentiation factor 15 (GDF-15).

Findings
One hundred patients with mild (n = 24), moderate (n = 28), and severe (n = 48) COVID-19 were followed for a median (IQR) of 225 (187–262) days. In the acute phase, patients with severe COVID-19 had higher concentrations of NfL than all other groups (all p < 0·001), and higher GFAp than controls (p < 0·001). GFAp was also significantly increased in moderate disease (p < 0·05) compared with controls. NfL (r = 0·53, p < 0·001) and GFAp (r = 0·39, p < 0·001) correlated with GDF-15 during the acute phase.

After six months, NfL and GFAp concentrations had normalized, with no persisting group differences. Despite this, 50 patients reported persistent neurological symptoms, most commonly fatigue (n = 40), “brain-fog” (n = 29), and changes in cognition (n = 25). We found no correlation between persistent neurological symptoms and CNS injury biomarkers in the acute phase.

Interpretation
The normalisation of CNS injury biomarkers in all individuals, regardless of previous disease severity or persisting neurological symptoms, indicates that post COVID-19 neurological sequelae are not accompanied by ongoing CNS injury.

 

BioMed article – Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up (Open access)

 

See more from MedicalBrief archives:

 

SARS-CoV-2: No brain infection but can inflict significant damage — 40 autopsies

 

COVID-19's cognitive cost may be equivalent to 10-years ageing — UK intelligence test data

 

Answers to 'long COVID' may lie in Chronic Fatigue Syndrome research

 

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