Neuroimmune disorders in COVID-19

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the aetiologic agent of the coronavirus disease 2019 (COVID-19), is now rapidly disseminating throughout the world with 147,443,848 cases reported so far. Around 30–80% of cases (depending on COVID-19 severity) are reported to have neurological manifestations including anosmia, stroke, and encephalopathy. In addition, some patients have recognised autoimmune neurological disorders, including both central (limbic and brainstem encephalitis, acute disseminated encephalomyelitis [ADEM], and myelitis) and peripheral diseases (Guillain–Barré and Miller Fisher syndrome). We systematically describe data from 133 reported series on the Neurology and Neuropsychiatry of COVID-19 blog (https://blogs.bmj.com/jnnp/2020/05/01/the-neurology-and-neuropsychiatry-of-covid-19/) providing a comprehensive overview concerning the diagnosis, and treatment of patients with neurological immune-mediated complications of SARS-CoV-2. In most cases the latency to neurological disorder was highly variable and the immunological or other mechanisms involved were unclear. Despite specific neuronal or ganglioside antibodies only being identified in 10, many had apparent responses to immunotherapies. Although the proportion of patients experiencing immune-mediated neurological disorders is small, the total number is likely to be underestimated. The early recognition and improvement seen with use of immunomodulatory treatment, even in those without identified autoantibodies, makes delayed or missed diagnoses risk the potential for long-term disability, including the emerging challenge of post-acute COVID-19 sequelae (PACS). Finally, potential issues regarding the use of immunotherapies in patients with pre-existent neuro-immunological disorders are also discussed.

SARS-CoV-2 causes brain inflammation via impaired neuro-immune interactions

“…Also affecting the kidneys, brain, heart, liver and other organs, it can cause multi-organ failure 11 . Research on the etiology of SARS-CoV-2 has uncovered many neurological complications but many aspects of their pathogenesis mechanisms remain unknown 6,7 .…”

“… Abstract The brain inflammation that frequently occurs in SARS-CoV-2 is the cause of neurological complications 1,2 and long COVID 3,4,5 . However, many aspects of its pathogenesis mechanism remain unknown 6, 7 and no method of treatment has been established 8 . By administering a non-proliferating adenovirus vector expressing SARS-CoV-2 S1 protein into the nasal cavity of mice, we developed a mouse model (S1 mouse) reproducing brain inflammation, fatigue, depressive symptoms, and lung inflammation.…”

Immune-mediated and autoimmune disorders of central nervous system after new coronavirus disease

“…В частности, на модельных животных была продемонстрирована способность вируса SARS-CoV-2 длительно сохраняться в мозге животных, а также диссеминировать в различные области головного мозга, что может потенциально объяснить разнообразную клиническую картину у пациентов с COVID-19. Потенциальными путями проникновения вируса SARS-CoV-2 в ЦНС являются: ретроградный аксональный транспорт (входными воротами могут служить свободные нервные окончания, расположенные на коже или слизистой оболочке тонкого кишечника, а также обонятельный или тройничный нерв); гематогенная диссеминация с проникновением через гематоэнцефалический барьер (путем инфицирования эпителиальных клеток сосудистых сплетений или с использованием лейкоцитов в качестве вектора); через рецепторы ангиотензин-превращающего фермента-2 (АПФ-2), локализованные на поверхности многих клеток, включая нейроны, астроциты, олигодендроциты и эндотелиальные клетки [11].…”

“…Данный механизм может участвовать и в патогенезе неврологических осложнений COVID-19. Так, при исследовании цитокинов сыворотки пациентов с новой коронавирусной инфекцией были выявлены повышенные концентрации интерлейкина (ИЛ)-1β, ИЛ-6, IP-10, фактора некроза опухоли (ФНО), интерферона-γ, воспалительного белка макрофагов (macrophage inflammatory protein, MIP) 1α и 1β и cocудистого эндотелиального фактора роста [11]. Развитие цитокинового шторма может способствовать многим клиническим и лабораторным проявлениям, наблюдаемым при тяжелом течении COVID-19: цитопении, коагулопатии, эндотелиальному повреждению и повышению сосудистой проницаемости.…”

Response to Letter to the Editor: Spinomedullary Weston Hurst Syndrome After COVID-19 and Influenza Co-Infection

“…4-6 Other larger studies on post-COVID CNS inflammatory diseases share our interest in this particular issue of delayed latency to neurologic onset and have routinely documented cases occurring 30-60 days following viral infection. 7-10 At this stage of scientific discovery, however, we emphasize that neuroinflammatory diseases occurring in proximity to COVID-19 infection remain an interesting association and have not been definitively proven to be causally-linked.…”