Post-COVID-19 Syndrome is Rarely Associated with Damage of the Nervous System: Findings from a Prospective Observational Cohort Study in 171 Patients.

INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs. Reports of persistent or newly emergent symptoms, including those related to the nervous system, have increased over the course of the pandemic, leading to the introduction of post-COVID-19 syndrome. However, this novel syndrome is still ill-defined and structured objectification of complaints is scarce. Therefore, we performed a prospective observational cohort study to better define and validate subjective neurological disturbances in patients with post-COVID-19 syndrome. METHODS: A total of 171 patients fulfilling the post-COVID-19 WHO Delphi consensus criteria underwent a comprehensive neurological diagnostic work-up including neurovascular, electrophysiological, and blood analysis. In addition, magnetic resonance imaging (MRI) and lumbar puncture were conducted in subgroups of patients. Furthermore, patients underwent neuropsychological, psychosomatic, and fatigue assessment. RESULTS: Patients were predominantly female, middle-aged, and had incurred mostly mild-to-moderate acute COVID-19. The most frequent post-COVID-19 complaints included fatigue, difficulties in concentration, and memory deficits. In most patients (85.8%), in-depth neurological assessment yielded no pathological findings. In 97.7% of the cases, either no diagnosis other than post COVID-19 syndrome, or no diagnosis likely related to preceding acute COVID-19 could be established. Sensory or motor complaints were more often associated with a neurological diagnosis other than post-COVID-19 syndrome. Previous psychiatric conditions were identified as a risk factor for developing post-COVID-19 syndrome. We found high somatization scores in our patient group that correlated with cognitive deficits and the extent of fatigue. CONCLUSIONS: Albeit frequently reported by patients, objectifiable affection of the nervous system is rare in post-COVID-19 syndrome. Instead, elevated levels of somatization point towards a pathogenesis potentially involving psychosomatic factors. However, thorough neurological assessment is important in this patient group in order to not miss neurological diseases other than post-COVID-19.

Observational cohort study of neurological involvement among patients with SARS-CoV-2 infection.

BACKGROUND: A growing number of reports suggest that infection with SARS-CoV-2 often leads to neurological involvement; however, data on the incidence and severity are limited to mainly case reports and retrospective studies. METHODS: This prospective, cross-sectional study of 102 SARS-CoV-2 PCR positive patients investigated the frequency, type, severity and risk factors as well as underlying pathophysiological mechanisms of neurological involvement (NIV) in COVID-19 patients. RESULTS: Across the cohort, 59.8% of patients had NIV. Unspecific NIV was suffered by 24.5%, mainly general weakness and cognitive decline or delirium. Mild NIV was found in 9.8%; most commonly, impaired taste or smell. Severe NIV was present in 23.5%; half of these suffered cerebral ischaemia. Incidence of NIV increased with respiratory symptoms of COVID-19. Mortality was higher with increasing NIV severity. Notably, 83.3% with severe NIV had a pre-existing neurological co-morbidity. All cerebrospinal fluid (CSF) samples were negative for SARS-CoV-2 RNA, and SARS-CoV-2 antibody quotient did not suggest intrathecal antibody synthesis. Of the patients with severe NIV, 50% had blood-brain barrier (BBB) disruption and showed a trend of elevated interleukin levels in CSF. Antibodies against neuronal and glial epitopes were detected in 35% of the patients tested. CONCLUSION: Cerebrovascular events were the most frequent severe NIV and severe NIV was associated with high mortality. Incidence of NIV increased with respiratory symptoms and NIV and pre-existing neurological morbidities were independent risk factors for fatality. Inflammatory involvement due to BBB disruption and cytokine release drives NIV, rather than direct viral invasion. These findings might help physicians define a further patient group requiring particular attention during the pandemic.

Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid.

Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache and neuroinflammatory or cerebrovascular disease. These conditions-termed here as Neuro-COVID-are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared with patients with non-inflammatory and autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells. Neuro-COVID CSF leukocytes featured an enriched interferon signature; however, this was less pronounced than in viral encephalitis. Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in severe compared with mild Neuro-COVID patients. Collectively, our findings document the CSF immune compartment in Neuro-COVID patients and suggest compromised antiviral responses in this setting.