ABSTRACT
One third of COVID-19 patients develop significant neurological symptoms, yet SARS-CoV-2 is rarely detected in central nervous system (CNS) tissue, suggesting a potential role for parainfectious processes, including neuroimmune responses. We therefore examined immune parameters in cerebrospinal fluid (CSF) and blood samples from a cohort of patients with COVID-19 and significant neurological complications. We found divergent immunological responses in the CNS compartment, including increased levels of IL-12 and IL-12-associated innate and adaptive immune cell activation. Moreover, we found increased proportions of B cells in the CSF relative to the periphery and evidence of clonal expansion of CSF B cells, suggesting a divergent intrathecal humoral response to SARS-CoV-2. Indeed, all COVID-19 cases examined had anti-SARS-CoV-2 IgG antibodies in the CSF whose target epitopes diverged from serum antibodies. We directly examined whether CSF resident antibodies target self-antigens and found a significant burden of CNS autoimmunity, with the CSF from most patients recognizing neural self-antigens. Finally, we produced a panel of monoclonal antibodies from patients CSF and show that these target both anti-viral and anti-neural antigens--including one mAb specific for the spike protein that also recognizes neural tissue. This exploratory immune survey reveals evidence of a compartmentalized and self-reactive immune response in the CNS meriting a more systematic evaluation of neurologically impaired COVID-19 patients. One Sentence SummaryA subset of COVID-19 patients with neurologic impairment show cerebrospinal fluid-specific immune alterations that point to both neuroinvasion and anti-neural autoimmunity as potential causes of impairment.
ABSTRACT
PURPOSE: To study the demographic characteristics of ocular trauma in Central Sarawak and identify the determinant factors of poor visual outcome. DESIGN: A retrospective study of ocular trauma cases presenting at the referral hospital in 2013. METHODS: Patients were identified and recruited from hospital records. Those presenting for follow-up review were excluded. Case records were retrieved and reviewed after recruitment. RESULTS: We studied 168 patients with 179 ocular injuries, of which 44% were work related. Compared with non-work-related cases, work-related cases were more likely to be male [odds ratio (OR), 19.7; 95% confidence interval (CI), 2.6-150.9] and foreign (OR, 18.0; 95% CI, 2.3-142.0). Open globe injuries constituted a higher percentage of impaired visual acuity (VA) during the first visit: 84.6% compared with 18.1% for closed globe injuries (OR, 25.0; 95% CI, 5.3-118.4; P < 0.001). Of the open globe injuries, 61.5% worsened or showed no improvement in VA after 3 months compared with closed globe injuries (28.9%) (OR, 3.9; 95% CI, 1.2-12.7; P = 0.015). Of cases presenting 7 or more days after trauma, 76.9% worsened or showed no improvement in VA after 3 months compared with those presenting in less than 7 days (27.7%) (OR, 8.7; 95% CI, 2.3-33.0; P < 0.001). Among those with work-related injuries, 23.1% had used eye protective devices (EPDs). CONCLUSIONS: Ocular injuries in Central Sarawak were predominantly work related, occurring at industrial premises, and involving males and foreigners. Both open globe injuries and a delay in seeking treatment resulted in significantly poorer visual outcomes.
