German study finds lack of association between SARS-CoV-2 infection and neuroaxonal damage

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the virus that causes coronavirus disease 2019 (COVID-19) – is not associated with neuroaxonal damage, according to a new study from researchers in Germany.

Neurological symptoms have been observed in about one-third of coronavirus cases. However, the full extent of the virus’s impact on the brain remains unclear. In the current study, the researchers found that changes in plasma neurofilament light chain (NfL) — a marker of neuroaxonal damage — levels did not correlate with COVID-19–induced neurological symptoms such as loss of smell and taste and headaches.

The researchers write:

Our findings indicate that mild-to-moderate COVID-19 is unlikely to be associated with a clinically relevant degree of neuroaxonal damage, even in those cases associated with neurological symptoms like olfactory and gustatory dysfunction, headache and myalgia.”

The article “The association between SARS-CoV-2 infection and neuronal damage: A population-based nested case-control study” is published on the preprint medRxiv* server.

How they did it

The study consisted of administering a survey measuring antibody levels in people living in Bonn, Germany, from April 24 to June 30, 2020. People who tested positive for SARS-CoV-2 antibodies were labeled cases. Plasma NfL levels were also measured during the survey period and also from samples collected from the same individuals from 2016 to 2019.

In total, there were 22 individuals with positive serological confirmation of a COVID-19 infection. One of the 22 individuals was excluded from the final analysis because of insufficient plasma levels needed to measure NfL levels. The study controls were randomly selected individuals who did not show evidence of antibodies after recovering from SARS-CoV-2.

NfL levels are not correlated with SARS-CoV-2 infection

There was no change in NfL levels before and after the pandemic. Self-reported neurological symptoms such as loss of smell or taste, headache, muscle weakness, and fever, did not correlate with altered NfL levels in patients who previously had a SARS-CoV-2 infection.

The results indicate neuroaxonal damage is not associated with SARS-CoV-2 infection.

Given the lack of association, the researchers predict that neuroaxonal damage in hospitalized patients with severe COVID-19 infection may likely come from an indirect viral neuroinvasion. While more research is needed to explore this hypothesis, neuronal injury may be coming from dyshomeostasis and hypercoagulation produced from systemic infection and inflammation.

Study limitations

The study had a small sample size of individuals with serologically confirmed SARS-CoV-2 infection. While the survey confirmed infection, it does not provide information on when the infection occurred and the severity of the illness, which may increase the possibility of neurological effects.

However, the researchers note that NfL has a long half-life of up to a few weeks and samples were collected at the start of the pandemic, making it unlikely they missed any COVID-19–induced increases in NfL levels.

“By implementing a serosurvey with a rigorous multi-tiered testing approach in an ongoing large prospective population-based cohort study, we were able to minimize the risk of false positives and take advantage of existing bio-samples collected before the start of the pandemic.”

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Jocelyn Solis-Moreira

Jocelyn Solis-Moreira graduated with a Bachelor's in Integrative Neuroscience, where she then pursued graduate research looking at the long-term effects of adolescent binge drinking on the brain's neurochemistry in adulthood.