Management of Neurological Complications

Critically ill patients with COVID-19 pneumonia in the intensive care unit (ICU) may develop neurological complications of their central nervous system (CNS) or peripheral nervous system (PNS) that may arise directly from the COVID-19 virus, indirectly as a complication of the COVID-19-related hospitalization, or by mechanisms that have not yet been elucidated. These include encephalopathy, delirium, ischemic stroke, intracranial hemorrhage, peripheral nerve injury, and critical illness myopathy. As the evidence of neurological complications in COVID-19 patients accumulate, we aim to provide a concise review on optimal management strategies of these complications. For the purpose of our review, we are excluding patients in the ICU who develop new neurological symptoms and are found to have otherwise asymptomatic SARS-CoV-2 PCR positivity. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Neuropathogenesis and Neurological Manifestations of SARS-CoV-2

Neurological complications of COVID-19 contribute significantly to mortality in the intensive care unit (ICU). Preventive therapy, though discussed in literature, is limited for COVID-19 neurological manifestations and treatment algorithms continue to rely on evidence from previous pandemics. Thus, in this chapter we evaluate current in vitro, in vitro, histopathological studies to ascertain the most likely mechanisms of SARS-CoV-2 central nervous system entry. From this understanding, we determine probable mechanisms for neurological compilations observed in COVID-19 as relevant to the clinician. SARS-CoV-2 infection of nasal epithelium and the respiratory tract may allow for a systemic inflammatory response that results in neuroinflammation. While most neurological complications are inflammatory in etiology, rarely, SARS-CoV-2 may enter into the central nervous system and mediate neuronal damage. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Mid and Long-term Neurological and Neuropsychiatric Manifestations of PostCOVID-19 Syndrome: A Meta-analysis

Objective: To determine the prevalence of neurological and neuropsychiatric symptoms reported 12 weeks (3 months) or more after acute COVID-19 onset in adults. Background: Neurological and neuropsychiatric symptoms that persist or develop three months after the onset of COVID-19 pose a significant threat to the global healthcare system. These symptoms are yet to be synthesized and quantified via meta-analysis. Design/Methods: A systematic search of PubMed, EMBASE, Web of Science, Google Scholar and Scopus was conducted for studies published between January 1 , 2020 and August 1 , 2021. Studies were included if the length of follow-up satisfied the National Institute for Healthcare Excellence definition of post-COVID-19 syndrome. Additional criteria included reporting of neurological or neuropsychiatric symptoms in individuals with COVID-19. The primary outcome was the prevalence of neurological and neuropsychiatric symptoms reported ≥3 months post onset of COVID-19. Results: Of 1,458 articles, 19 studies, encompassing a total of 11,324 patients, were analysed. Overall prevalence for neurological post-COVID-19 symptoms were: fatigue (37%, 95% CI: 24%- 50%), brain fog (32%, 9%-55%), memory issues (27%, 18%-36%), attention disorder (22%, 10%- 34%), myalgia (18%, 4%-32%), anosmia (12%, 7%-17%), dysgeusia (11%, 4%-17%) and headache (10%, 1%-21%). Neuropsychiatric conditions included sleep disturbances (31%, 18%-43%), anxiety (23%, 13%-33%) and depression (12%, 7%-21%). Neuropsychiatric symptoms substantially increased in prevalence between mid- and long-term follow-up. Compared to non-hospitalised patients, patients hospitalised for acute COVID-19 had reduced risk of anosmia, anxiety, depression, dysgeusia, fatigue, headache, myalgia, and sleep disturbance at three (or more) months post-infection. Conversely, hospital admission was associated with higher frequency of memory issues (OR: 1.9, 95% CI: 1.4-2.3). Conclusions: Fatigue, brain fog and sleep disturbances appear to be key features of post-COVID19 syndrome. Psychiatric manifestations (sleep disturbances, anxiety, and depression) increase significantly in prevalence over time. Randomised controlled trials are necessary to develop intervention strategy to reduce disease burden.

Cerebrovascular injury associated with COVID-19 and non-COVID-19 acute respiratory distress syndrome

Background: Neurologic complications of Coronavirus Disease 2019 (COVID-19) may be associated with neurotropism of the virus or secondary brain injury from systemic inflammation. Acute respiratory distress syndrome (ARDS) is associated with cerebrovascular injury, including both ischemia and hemorrhage. We aimed to compare brain MRI findings of COVID-19 associated ARDS with non-COVID-19 ARDS. Methods: A registry of patients with COVID-19 from March 2020 through July 2021 from a hospital network was reviewed. Patients who met criteria for ARDS by Berlin definition and underwent MRI during their hospitalization were included. These patients were matched 1:1 by age and sex with patients who underwent MRI from another registry of patients of ARDS in the same hospital between 2010 and 2018. Cerebrovascular injury was classified as either acute cerebral ischemia (ischemic infarct or hypoxic ischemic brain injury) or intracranial hemorrhage (ICH) including intraparenchymal hemorrhage, subarachnoid hemorrhage, subdural hematoma, and cerebral microbleeds (CMBs). Results: Of 13,319 patients with COVID-19 infection, 26 patients had ARDS and MRI. Sixty-six of 678 non-COVID-19 ARDS patients had an MRI and were matched 1:1 by age and sex resulting in 23 matched pairs. The median age was 66 and 59% of patients were male. Patients with COVID-19 ARDS were more likely to have hypertension and chronic kidney disease but otherwise baseline medical characteristics were similar. ARDS severity as determined by PaO2/FiO2 ratio at ICU admission was similar between both groups. No difference was seen in the prevalence of cerebrovascular injury (52% vs 61%, p=0.8), cerebral ischemia (35% vs 43%, p=0.8), ICH (43% vs 48%, p=1.0), or CMBs (43% vs 39% p=1.0) on MRI between the COVID-19 and non-COVID-19 cohorts. However, two unique patterns of injury were seen only among COVID-19 patients: hemorrhagic leukoencephalitis (3 patients, 12%) and bilateral cerebral peduncular ischemia with microhemorrhage (2 patients, 8%). Conclusion: Cerebrovascular injury was common in both COVID-19 and non-COVID-19 ARDS without significant frequency difference. However, COVID-19 ARDS had unique neuroimaging patterns that may indicate distinct patterns of brain injury of COVID-19.

Long covid syndrome: Why efforts like aftercor are needed

Introduction: The AFTERCOR study was developed by the COVID-19 Critical Care Consortium (>7000 intensive care unit [ICU] and >400 extracorporeal membrane oxygenation [ECMO] patients currently) to enhance understanding of occurrence and progression of long-term dysfunction post-COVID-19. Design: Prospective longitudinal (24 months) study of ICU survivors of COVID-19 to describe recovery of the following aspects: a) health-related quality of life b) dynamics of organ dysfunction and recovery and c) pulmonary function. Countries involved Italy, Spain, Ireland, Austria, South Africa, Australia, USA, Argentina, Brazil, Colombia. Protocol specifics available at https://www.aftercorstudy.com. Inclusion Criteria: 1) COVID-19 infection requiring ICU admission;2) informed consent;3) age ≥18 years. Exclusion Criteria: 1) pregnancy;2) pre-COVID paralysis;3) history of pulmonary resection;4) prior lung transplant;5) inability to perform 6-min walk test or participate in interview. Methods: Goal enrollment is 1000 patients. Follow-up visits are at 3, 6, 12, 18 and 24-month post-ICU discharge. Assessments include: 1) Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36);2) Montreal Cognitive Assessment;3) any subsequent admission 4) St. George's Respiratory Questionnaire;5) Pulmonary function testing;6) chest radiography;7) 6-minute-walk test;8) Patient Health Questionnaire 9 (PHQ-9) and 9) full blood count and biochemistry. CT chest at 6 months and repeat ECHO at 3, 12 and 24 months if performed during COVID-19 hospitalization. If results are normal, subsequent testing will not be performed. Summary: The AFTERCOR study represents a comprehensive evaluation for long-term effects from COVID-19. Interested centers are sought and invited to participate.