Study suggests potential therapeutic targets for COVID-19-related neurological pathologies

In a the latest research printed in the journal Molecular & Cellular Proteomics, researchers analyzed the proteins in cerebrospinal fluid (CSF) samples received from African green monkeys and rhesus macaques contaminated with serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2 to recognize the neurological manifestations of coronavirus condition 2019 (COVID-19).

Study: Cerebrospinal Fluid Protein Markers Indicate Neuro-Damage in SARS-CoV-2-Infected Nonhuman Primates. Image Credit: DOERS / ShutterstockAnalyze: Cerebrospinal Fluid Protein Markers Show Neuro-Destruction in SARS-CoV-2-Contaminated Nonhuman Primates. Picture Credit rating: DOERS / Shutterstock


The manifestations of SARS-CoV-2 infections range from asymptomatic or mildly symptomatic to intense respiratory infections foremost to pneumonia, lung harm, and even loss of life. Even so, a escalating entire body of evidence implies that scientific outcomes of COVID-19 are not limited to the respiratory program, neurological signs or symptoms, together with dizziness, anosmia, dysgeusia, and head aches in the early stages, and seizures, delirium, and meningoencephalitis in more serious situations, have been observed.

While more persistent neurological complications have been connected with serious COVID-19 scenarios, cognitive impairment has also been noticed in delicate conditions. The use of mass spectrometry in investigating the proteins in CSF has proven to be an efficient technique for comprehension the mechanisms of neurodegenerative ailments. Cerebrospinal fluid is an best sample alternative due to the fact obtaining it is comparatively much less dangerous and invasive than biopsies of the brain. It consists of the proteins secreted by all the regions and cell sorts of the central nervous technique (CNS), doing away with the challenge of sampling bias.

About the study

In the current research, the scientists made use of CSF samples from two non-human primate products — African green monkeys and rhesus macaques — infected with SARS-CoV-2 to perform mass spectrometric evaluation of the CSF proteins to comprehend the neurologic effects of COVID-19. The non-human primates were being infected with the 2019-nCoV/United states-WA1/2020 pressure of SARS-CoV-2 by using aerosol exposure or inoculation, and nasal swabs ended up tested for SARS-CoV-2 nucleocapsid protein to confirm infection institution.

Two African eco-friendly monkeys and two rhesus macaques ended up utilised as age-matched controls, and a negative SARS-CoV-2 take a look at for all the animals was ensured in advance of the commencement of the analyze. Whole blood and aseptic CSF were being attained from all the animals right after currently being contaminated with SARS-CoV-2.

The CSF samples had been subjected to protein extraction, digestion with trypsin, peptide enrichment, and powerful-cation trade chromatography fractionation to get ready the samples for mass spectrometry. Liquid chromatography-mass spectrometry acquisition of the samples was adopted by quantifying and pinpointing the CSF proteins. The dysregulated proteins ended up mapped to the human brain, and the diseased pathways ended up identified and analyzed.

Furthermore, sections of the cerebellum, brain stem, and basal ganglia ended up analyzed making use of immunohistochemistry, whilst added sections of the CNS, this sort of as the temporal, occipital, parietal, and frontal lobes and higher, decrease, intermediate, and center lobes of the lungs were employed to quantify the CNS and pulmonary pathologies in non-human primates contaminated with SARS-CoV-2. Enzyme-connected immunosorbent assays (ELISA) were also executed to evaluate the plasma matrix metalloproteinase-2.


The final results noted that the animals exhibited quite reduced ranges of pulmonary pathology, but the CNS pathology stages had been moderate to extreme. In addition, there ended up significant discrepancies in the CSF proteome of the contaminated animals and their uninfected controls, with the alterations corresponding to an abundance of bronchial virus in the early phases of the infection and a modify in the secretion of CNS components indicating neuropathy linked with the SARS-CoV-2 an infection.

On top of that, the scattered distribution of the information from the contaminated animals compared to the uninfected controls proposed that the CSF proteome alterations and the host’s response to the viral an infection were heterogeneous. In addition, the dysregulated proteins in the CSF have been found to be enriched preferentially in pathways linked with hemostasis, human neurodegenerative sickness, and innate pathways that could affect the inflammatory response subsequent COVID-19. Mapping of the dysregulated proteins making use of the Human Mind Protein Atlas also confirmed that these proteins have been enriched in the areas of the brain that exhibit personal injury commonly following COVID-19.


Over-all, the results advised that the adjustments in the CSF proteins detected in the non-human primate types contaminated with SARS-CoV-2 were connected to biochemical and purposeful pathways affiliated with innate immunity, thrombus formation, mobile infiltration, and progressive neurological conditions, and these pathways could perhaps be utilised as therapeutic targets to lower or avert the neurological outcomes of COVID-19.

Journal reference:

  • Maity, S., Mayer, M. G., Shu, Q., Linh, H., Bao, D., Blair, R. V., He, Y., Lyon, C. J., Hu, T. Y., Fischer, T., & Admirer, J. (2023). Cerebrospinal Fluid Protein Markers Indicate Neuro-Problems in SARS-CoV-2-Infected Non-human Primates. Molecular & Cellular Proteomics, 22(4), 100523.