key: cord-0811377-acy6w71u authors: Aamodt, A. H.; Hogestol, E. A.; Popperud, T. H.; Holter, J. C.; Dyrhol-Riise, A. M.; Tonby, K.; Stiksrud, B.; Qvist-Paulsen, E.; Berge, T.; Barratt-Due, A.; Aukrust, P.; Heggelund, L.; Blennow, K.; Zetterberg, H.; Harbo, H. F. title: Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19 date: 2020-09-09 journal: nan DOI: 10.1101/2020.09.07.20189415 sha: c58f7fe54ad00b164a3a5323a6213e50758a292b doc_id: 811377 cord_uid: acy6w71u Objective To test the hypotheses that serum 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), NfL and GFAp. 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 (p<0.001) than patients who were discharged alive both in adjusted analyses (p=2.6 x 10-7) and unadjusted analyses (p=0.001). The concentrations of NfL 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. The GFAp concentration was also significantly higher in non-survivors than survivors (p=0.02). 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. Abstract 71 Objective 72 To test the hypotheses that blood concentrations of neurofilament light chain protein (NfL) and 73 glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-74 19 patients. In total, 21 % (n=10) of the patients were admitted to an intensive care unit, whereas the 85 overall mortality rate was 13 % (n=6). Non-survivors had higher serum concentrations of NfL 86 than patients who were discharged alive both in adjusted analyses (p=2.6 x 10 -7 ) and 87 unadjusted analyses (p=0.001). Serum concentrations of GFAp were significantly higher in is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. . https: //doi.org/10.1101 //doi.org/10. /2020 Conclusion 95 Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate 96 increased mortality risk. Measurement of blood biomarkers for nervous system injury can be 97 useful to detect and monitor CNS injury in COVID-19. . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Introduction 99 Emerging evidence suggest that respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 100 may affect the nervous system. NfL and GFAp. 19, 20 However, more studies are required to evaluate the 117 usefulness of these biomarkers in COVID-19 patients. The aim of this study was to explore the association between disease severity in 119 COVID-19 patients and blood concentrations of NfL and GFAp. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. . https://doi.org/10.1101/2020.09.07.20189415 doi: medRxiv preprint Ethical considerations 170 Informed consents were obtained from all patients or next-of-kin if patients were 171 incapacitated of giving consent. The study was approved by the South-Eastern 172 Norway Regional Health Authority (reference number: 106624). (Table 1) is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. . https://doi.org/10.1101/2020.09.07.20189415 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. . https://doi.org/10.1101/2020.09.07.20189415 doi: medRxiv preprint 195 On admission, NfL and GFAp concentrations above reference limits were measured 196 in 30 % (n=14) and 48 % (n=22) of the COVID-19 patients, respectively (Table 1) . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. . https://doi.org/10.1101/2020.09.07.20189415 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. . https://doi.org/10.1101/2020.09.07.20189415 doi: medRxiv preprint 226 Concentrations of NfL were significantly higher in non-survivors (n=6) compared to 227 survivors (p=2.6 x 10 -7 ) when adjusting for age and creatinine levels on admission 228 and in unadjusted analyses (p=0.001) (Figure 3) . Additionally, concentrations of 229 GFAp were significantly higher in non-survivors than survivors when adjusting for 230 age (p=0.02) ( Table 3) . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. . https: //doi.org/10.1101 //doi.org/10. /2020 This pilot study confirms the frequent observations of neurological symptoms in The identification of biomarkers in blood to assess nervous system 291 manifestation will be important in order to monitor the severity of the disease and is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. . https://doi.org/10.1101/2020.09.07.20189415 doi: medRxiv preprint easily be managed despite medical isolation procedures. Although NfL has been 295 shown to be useful as diagnostic, prognostic and monitoring biomarker in a wide 296 range of other neurological conditions, 23, 25-27 more studies are needed to assess the 297 applicability of NfL in One could claim that the high concentrations of NfL reflect medications used 299 in ICU. However, a recent study of NfL and other blood biomarkers in patients is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020 . . https://doi.org/10.1101 procedures at different units and several patients needed ventilatory support in ICUs. Thus, possible association between GFAp and NfL and specific CNS manifestations 320 may have been undetected in this study. In order to study further the questions raised 321 by our observations, we plan a follow-up study of COVID-19 patients up to a year 322 after diagnosis including a systematic neurological assessment. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 9, 2020. . https://doi.org/10.1101/2020.09.07.20189415 doi: medRxiv preprint Understanding the neurotropic characteristics of SARS-337 CoV-2: from neurological manifestations of COVID-19 to potential neurotropic mechanisms. 338 Nervous system involvement after infection with COVID-19 340 and other coronaviruses Immediate and long-term 342 consequences of COVID-19 infections for the development of neurological disease An Italian multicenter retrospective-prospective 345 observational study on neurological manifestations of COVID-19 (NEUROCOVID) Neurologic Manifestations of Hospitalized Patients With 348 Coronavirus Disease CoV-2): A Review Evidence of the COVID-19 Virus Targeting the 352 CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features Guillain-Barre syndrome as a 358 complication of SARS-CoV-2 infection SARS-CoV-2 can induce brain and spine 360 demyelinating lesions Severe acute respiratory 362 syndrome coronavirus infection causes neuronal death in the absence of encephalitis in 363 mice transgenic for human ACE2 A first case of meningitis/encephalitis associated 365 with SARS-Coronavirus-2 Potential neurological symptoms 367 of COVID-19 How does COVID-369 19 affect the brain? 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