Post by Nadica (She/Her) on Jul 20, 2024 21:34:41 GMT
Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications - Published July 13, 2024
Highlights
•Neurological symptoms are dissociated from pulmonary involvement in COVID-19.
•Despite disease heterogeneity, COVID-19 patients shared a single altered CSF proteomic profile.
•Deregulated CSF proteomic pathways related to the innate immune system and hemostasis.
•Mild and severe COVID-19 patients with neurological symptoms display systemic and central nervous system hyper-inflammation.
•Disease severity is associated with increases in CSF IL6.
•Neuroimaging abnormalities are connected to elevated CSF IL6 and TNFα levels.
Abstract
COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored. To illuminate possible mechanisms leading to COVID-19 neurological disease, we retrospectively investigated in detail a cohort of 35 COVID-19 mild and severe hospitalized patients presenting neurological alterations subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigation, brain imaging, viral sequencing, and cerebrospinal CSF analyses were carried out. We found that COVID-19 patients presented heterogeneous neurological symptoms dissociated from lung burden. Nasal swab viral sequencing revealed a dominant strain at the time of the study, and we could not detect traces of SARS-CoV-2's spike protein in patients' CSF by multiple reaction monitoring analysis. Patients presented ubiquitous systemic hyper-inflammation and broad alterations in CSF proteomics related to inflammation, innate immunity, and hemostasis, irrespective of COVID-19 severity or neuroimaging alterations. Elevated CSF interleukin-6 (IL6) correlated with disease severity (sex-, age-, and comorbidity-adjusted mean Severe 24.5 pg/ml, 95% confidence interval (CI) 9.62–62.23 vs. Mild 3.91 pg/mL CI 1.5–10.3 patients, p = 0.019). CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients presenting pronounced neuroimaging alterations compared to those who did not (sex-, age-, and comorbidity-adjusted mean TNFα Pronounced 3.4, CI 2.4–4.4 vs. Non-Pronounced 2.0, CI 1.4–2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89–123.31 vs Non-Pronounced 6.22, CI 2.9–13.34, p = 0.046). Collectively, our findings put neuroinflammation as a possible driver of COVID-19 acute neurological disease in mild and severe cases.
Highlights
•Neurological symptoms are dissociated from pulmonary involvement in COVID-19.
•Despite disease heterogeneity, COVID-19 patients shared a single altered CSF proteomic profile.
•Deregulated CSF proteomic pathways related to the innate immune system and hemostasis.
•Mild and severe COVID-19 patients with neurological symptoms display systemic and central nervous system hyper-inflammation.
•Disease severity is associated with increases in CSF IL6.
•Neuroimaging abnormalities are connected to elevated CSF IL6 and TNFα levels.
Abstract
COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored. To illuminate possible mechanisms leading to COVID-19 neurological disease, we retrospectively investigated in detail a cohort of 35 COVID-19 mild and severe hospitalized patients presenting neurological alterations subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigation, brain imaging, viral sequencing, and cerebrospinal CSF analyses were carried out. We found that COVID-19 patients presented heterogeneous neurological symptoms dissociated from lung burden. Nasal swab viral sequencing revealed a dominant strain at the time of the study, and we could not detect traces of SARS-CoV-2's spike protein in patients' CSF by multiple reaction monitoring analysis. Patients presented ubiquitous systemic hyper-inflammation and broad alterations in CSF proteomics related to inflammation, innate immunity, and hemostasis, irrespective of COVID-19 severity or neuroimaging alterations. Elevated CSF interleukin-6 (IL6) correlated with disease severity (sex-, age-, and comorbidity-adjusted mean Severe 24.5 pg/ml, 95% confidence interval (CI) 9.62–62.23 vs. Mild 3.91 pg/mL CI 1.5–10.3 patients, p = 0.019). CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients presenting pronounced neuroimaging alterations compared to those who did not (sex-, age-, and comorbidity-adjusted mean TNFα Pronounced 3.4, CI 2.4–4.4 vs. Non-Pronounced 2.0, CI 1.4–2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89–123.31 vs Non-Pronounced 6.22, CI 2.9–13.34, p = 0.046). Collectively, our findings put neuroinflammation as a possible driver of COVID-19 acute neurological disease in mild and severe cases.