Neurological symptoms and axonal damage in COVID-19 survivors: are there sequelae?

Abstract

The persistence of neurological symptoms after SARS-CoV-2 infection, as well as the presence of late axonal damage, is still unknown. We performed extensive systemic and neurological follow-up evaluations in 107 out of 193 consecutive patients admitted to the COVID-19 medical unit, University Hospital of Verona, Italy between March and June 2020. We analysed serum neurofilament light chain (NfL) levels in all cases including a subgroup (n = 29) of patients with available onset samples. Comparisons between clinical and biomarker data were then performed. Neurological symptoms were still present in a significant number (n = 49) of patients over the follow-up. The most common reported symptoms were hyposmia (n = 11), fatigue (n = 28), myalgia (n = 14), and impaired memory (n = 11) and were more common in cases with severe acute COVID-19. Follow-up serum NfL values (15.2 pg/mL, range 2.4–62.4) were within normal range in all except 5 patients and did not differentiate patients with vs without persistent neurological symptoms. In patients with available onset and follow-up samples, a significant (p < 0.001) decrease of NfL levels was observed and was more evident in patients with a severe acute disease. Despite the common persistence of neurological symptoms, COVID-19 survivors do not show active axonal damage, which seems a peculiar feature of acute SARS-CoV-2 infection.

Plasma Markers of Neurologic Injury and Inflammation in People With Self-Reported Neurologic Postacute Sequelae of SARS-CoV-2 Infection

“… 19 , 29 , 34 Our findings are in line with studies that identified a correlation between NfL and/or GFAP with severity of reported neurologic symptoms during the acute phase, but found no association between the biomarker levels and persistence of neurologic symptoms after 6 months. 27 , 28 Further work exploring the dynamics of these markers in cohorts with measurements performed during the period of acute illness, as well as efforts to identify downstream markers which may persist and be identified during later recovery, will be informative.…”

“… 26 However, there are limited data on the relationship between biomarkers of immune activation, neurologic injury, and neurologic symptoms during the postacute period. 17 , 27 - 29 …”

Plasma markers of neurologic injury and systemic inflammation in individuals with self-reported neurologic post-acute sequelae of SARS-CoV-2 infection (PASC)

“…Our findings are in line with studies that identified a correlation between NfL and/or GFAP with neurologic symptoms during the acute phase, but found no association between the biomarker levels and persistence of neurologic symptoms after six months. 39,40 Further work exploring the dynamics of these markers in cohorts with measurements performed during the period of acute illness, as well as efforts to identify downstream markers which may persist during later recovery, will be informative.…”

“…14 However, there are limited data on the relationship between biomarkers of inflammation, neurologic injury, and neurologic symptoms during the post-acute period. 25,39,40…”

Serum neurofilament light chain levels in Covid-19 patients without major neurological manifestations

“…Elevated CSF NFL levels have been observed in the majority of Covid-19 patients with neurological symptoms [ 14 ]; however, a study reported increased CSF NFL concentrations in Covid-19 patients with CNS syndromes, but not in those with peripheral nervous system (PNS) involvement, whereas sNFL levels were similarly augmented in all hospitalized Covid-19 patients, suggesting—together with the lack of correlation between CSF and serum NFL levels—that increases of NFL in the blood are partly determined by peripheral mechanisms [ 15 ]. Notably, blood NFL levels have been reported to normalize within 6 months after acute Covid-19 in a large majority of patients [ 16 , 17 ].…”