Neurological Involvement in COVID-19 Among Non-Hospitalized Adolescents and Young Adults

Havdal, Lise Beier; Berven, Lise; Selvakumar, Joel; Stiansen-Sonerud, Tonje; Leegaard, Truls Michael; Tjade, Trygve; Zetterberg, Henrik; Blennow, Kaj; Wyller, Vegard Bruun

doi:10.3389/fneur.2022.915712

Cited by 14 publications

(26 citation statements)

References 56 publications

(65 reference statements)

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“…The lack of association of serum biomarkers of brain injury and infection status differs from previous studies, in which Ameres et al (Ameres et al 2020) found NfL to be elevated in adult health-care workers with a mild-to-moderate COVID infection and Havdal et al (Havdal et al 2022) found an increase in NfL and GFAP in non-hospitalized adolescents. This discrepant results to the latter study may be explained by the larger sample size, resulting in a more powered study and therefore, more likely to detect significant correlations.…”

Section: Discussioncontrasting

confidence: 66%

“…This discrepant results to the latter study may be explained by the larger sample size, resulting in a more powered study and therefore, more likely to detect significant correlations. Moreover, our study investigated brain injury biomarkers in post-acute infection stages (60 days after infection), whereas Havdal et al (Havdal et al 2022) investigated biomarkers in the acute phase of the SARS-CoV-2 infection (not more than 28 days since the first day of symptoms or positive PCR test).…”

Section: Discussionmentioning

confidence: 99%

“…However, despite the large number of patients with mild-to-moderate SARS-CoV-2 symptoms (Parasher 2021), only few studies investigated blood markers of brain injury in these groups during or even after resolution of the acute phase of the infection. One of these studies showed increased serum NfL (sNfL) and serum GFAP (sGFAP) levels in non-hospitalized adolescents (Havdal et al 2022), while another study reported increased sNfL levels in adult health-care workers with mild-to-moderate symptoms (Ameres et al 2020). To this date it is, however, still poorly understood whether the increase of the investigated biomarkers is associated with neurological symptoms in this groups.…”

Section: Introductionmentioning

confidence: 99%

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The role of serum brain injury biomarkers in individuals with a mild-to-moderate COVID infection and Long-COVID - results from the prospective population-based COVI-GAPP study

Telser

Grossmann

Weideli³

et al. 2023

Preprint

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Background: During and after mild (no hospitalization) or moderate (hospitalization without ICU) SARS-CoV-2 infections, a wide range of symptoms, including neurological disorders have been reported. It is, however, unknown if these neurological symptoms are associated with brain injury and whether brain injury and related symptoms also emerge in patients suffering from Long-COVID. Neuronal biomarkers such as serum neurofilament light chain and glial fibrillary acidic protein can be used to elucidate neuro-axonal and astroglial injuries. We therefore investigated whether these biomarkers are associated with the COVID-19 infection status (mild-to-moderate), the associated symptoms and Long-COVID. Methods: From 146 individuals of the general population with a post-acute, mild-to-moderate SARS-CoV-2 infection, serum neurofilament light chain (sNfL; marker of intra-axonal neuronal injury) and serum glial fibrillary acidic protein (sGFAP; marker of astrocytic activation/injury) were measured. Samples were taken before, during and after (five and ten months) a SARS-CoV-2 infection. Individual symptoms and Long-COVID status were assessed using questionnaires. Results: Neurological symptoms were described for individuals after a mild and moderate COVID-19 infection, however, serum markers of brain injury (sNfL/sGFAP) did not change after an infection (sNfL: P = 0.74; sGFAP: P = 0.24) and were not associated with headache (P = 0.51), fatigue (P = 0.93), anosmia (P = 0.77) and ageusia (P = 0.47). In participants with Long-COVID, sGFAP (P = 0.038), but not sNfL (P = 0.58) significantly increased but was not associated with neurological symptoms. Conclusion: Neurological symptoms in individuals after a mild-to-moderate SARS-CoV-2 infection with and without Long-COVID were not associated with brain injury, although there was some astroglial injury observed in Long-COVID patients. Funding: The COVI-GAPP study received grants from the Innovative Medicines Initiative (IMI grant agreement number 101005177), the Princely House of Liechtenstein, the government of the Principality of Liechtenstein, and the Hanela Foundation (Switzerland). None of the funders played a role in the study design, data collection, data analysis, data interpretation, writing of the report, or decision to publish.

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Section: Discussioncontrasting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The role of serum brain injury biomarkers in individuals with a mild-to-moderate COVID infection and Long-COVID - results from the prospective population-based COVI-GAPP study

Telser

Grossmann

Weideli³

et al. 2023

Preprint

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“…We were able to show that women more often suffered from persistent fatigue, not caused by an effort and not alleviated by rest, within 12 weeks since the onset of the SARS‐CoV‐2 infection. So far, it has been known that among patients with mild COVID‐19, fatigue (Miyazato et al., 2022 ) and malaise after exertion were correlated with female sex (Havdal et al., 2022 ). In relation to the post‐COVID fatigue, these sex differences were also found significant in studies with similar to ours cross‐sectional design (Fugazzaro et al., 2022 ), and in cohorts consisting of medical workers of whom most did not require hospitalization due to COVID‐19 (Sultana et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Fatigue after COVID‐19 in non‐hospitalized patients according to sex

et al. 2023

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Background Limited evidence exists on sex differences in post‐COVID fatigue among non‐hospitalized patients. Therefore, aim of the study was to evaluate the course of chronic fatigue symptoms in non‐hospitalized subjects with the SARS‐CoV‐2 infection, according to sex. Methods Patients and staff from the University Hospital in Krakow anonymously and retrospectively completed neuropsychological questionnaire that included eight symptoms of chronic fatigue syndrome. The presence of these symptoms was assessed before COVID‐19 and 0–4, 4–12, and >12 weeks postinfection. The inclusion criteria were as follows: age 18 or more years, >12 weeks since the onset of the SARS‐CoV‐2 infection, and diagnosis confirmed by the RT‐PCR from anasopharyngeal swab. Results We included 303 patients (79.53% women, 47.52% medical personnel) assessed retrospectively after a median of 30 (interquartile range: 23–35) weeks since the onset of symptoms. A higher prevalence of at least one chronic fatigue symptom was found in females in all time intervals after the onset of COVID‐19 compared to males (p < .036). Women, compared to men, more often experienced persistent fatigue, not caused by effort and persisting after rest (for <4 weeks, odds ratio [OR] = 2.31, 95% confidence interval [CI]: 1.13–4.73; for 4–12 weeks, OR = 1.95, 95% CI: 1.06–3.61), non‐restorative sleep (for <4 weeks, OR = 2.17, 95% CI: 1.23–3.81; for >12 weeks, OR = 1.95, 95% CI: 1.03–3.71), and sore throat (for <4 weeks, OR = 1.97, 95% CI: 1.03–3.78; for 4–12 weeks, OR = 2.76, 95% CI: 1.05–7.27). Sex differences in headache, arthralgia, and prolonged postexercise fatigue were observed only during the first 4 weeks (OR = 2.59, 95% CI: 1.45–4.60, OR = 2.97, 95% CI: 1.02–8.64, and OR = 1.87, 95% CI: 1.01–3.51, respectively). There were no differences between women and men in myalgia and self‐reported lymph node enlargement. Conclusions The course of post‐COVID fatigue differs significantly between sexes in non‐hospitalized individuals with COVID‐19, with women more often suffering from persistent fatigue, not caused by effort and persisting after rest, non‐restorative sleep, and sore throat.

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“…Studies have shown glial activation and neuronal injury in patients with COVID-19 [17,18] with elevated biomarkers related to neuronal injury detected in the cerebrospinal fluid (CSF) and blood of COVID-19 patients [19]. The concentrations of NfL and GFAP were found to be elevated in 405 non-hospitalized COVID-19 patients [20], with plasma GFAP levels observed to be significantly two-fold higher in critically ill patients with COVID-19 when compared to healthy controls [17]. Serum GFAP showed a significant association with the severity of COVID-19 infection [21], and both NfL and GFAP predicted COVID-19associated mortality in hospitalized patients [18].…”

Section: Introductionmentioning

confidence: 99%

Blood Biomarkers as Prognostic Indicators for Neurological Injury in COVID-19 Patients: A Systematic Review and Meta-Analysis

Huang,

Haile,

Gedefaw

et al. 2023

IJMS

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Coronavirus disease 2019 (COVID-19) has been linked to various neurological complications. This meta-analysis assessed the relationship between glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels in the blood and neurological injury in COVID-19 patients. A comprehensive search of various databases was conducted until 18 August 2023, to find studies reporting GFAP and NfL blood levels in COVID-19 patients with neurological complications. GFAP and NfL levels were estimated between COVID-19 patients and healthy controls, and meta-analyses were performed using RevMan 5.4 software for analysis. In the 21 collected studies, it was found that COVID-19 patients had significantly higher levels of pooled GFAP (SMD = 0.52; 95% CI: 0.31, 0.73; p ≤ 0.001) and NfL (SMD = 0.60; 95% CI: 0.37, 0.82; p ≤ 0.001) when compared to the healthy controls. The pooled GFAP (SMD = 0.86; 95% CI: 0.26, 1.45; p ≤ 0.01) and NfL (SMD = 0.87; 95% CI: 0.48, 1.26; p ≤ 0.001) were significantly higher in non-survivors. These findings indicate a significant association between COVID-19 severity and elevated levels of GFAP and NfL, suggesting that GFAP and NfL could serve as potential diagnostic and prognostic markers for the early detection and monitoring of COVID-19-related neurological injuries.

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Neurological Involvement in COVID-19 Among Non-Hospitalized Adolescents and Young Adults

Cited by 14 publications

References 56 publications

The role of serum brain injury biomarkers in individuals with a mild-to-moderate COVID infection and Long-COVID - results from the prospective population-based COVI-GAPP study

The role of serum brain injury biomarkers in individuals with a mild-to-moderate COVID infection and Long-COVID - results from the prospective population-based COVI-GAPP study

Fatigue after COVID‐19 in non‐hospitalized patients according to sex

Blood Biomarkers as Prognostic Indicators for Neurological Injury in COVID-19 Patients: A Systematic Review and Meta-Analysis

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