Consensus Clinical Guidance for Diagnosis and Management of Adult COVID-19 Encephalopathy Patients.

Encephalopathy, a common condition among patients hospitalized with COVID-19, can be a challenge to manage and negatively affect prognosis. While encephalopathy may present clinically as delirium, subsyndromal delirium, or coma and may be a result of systemic causes such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma (with or without cerebrovascular involvement), demyelination, or seizures, which may be disproportionate to COVID-19 severity and require specific management. Given the large number of patients hospitalized with severe acute respiratory syndrome coronavirus-2 infection, even these relatively unlikely complications are increasingly recognized and are particularly important because they require specific management. Therefore, the aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through consensus agreement of the Global COVID-19 Neuro Research Coalition. A systematic literature search of MEDLINE, medRxiv, and bioRxiv was conducted between January 1, 2020, and June 21, 2021, with additional review of references cited within the identified bibliographies. A modified Delphi approach was then undertaken to develop recommendations, along with a parallel approach to score the strength of both the recommendations and the supporting evidence. This review presents analysis of contemporaneous evidence for the definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and both acute and long-term management.

Management and Outcomes of COVID - 19 Associated Cerebral Venous Sinus Thrombosis.

BACKGROUND: Systemic hyper-coagulabilty leading to micro and macro thrombosis is a known complication of Coronavirus disease - 2019(COVID -19). The postulated mechanism appears to be the viral activation of endothelium, triggering the coagulation pathways. Thrombosis of the cerebral veins and sinuses (CVT), a potentially serious condition, has been increasingly reported with COVID - 19 infection. In this clinical study we attempt to describe the clinical profile, investigations and outcomes of patients with COVID- 19 associated CVT. METHODS: This is a single center prospective observational study from South India. The study included patients (aged >18 years) with concomitant COVID infection and CVT. The clinical, laboratory, imaging characteristics, management and outcomes were described and compared with COVID negative CVT patients. RESULTS: Out of 97 cases of CVT treated at our center during the first and second waves of the COVID pandemic 11/97 (11%) were COVID related CVT. Among these 11 patients, 9 (81%) had presented with only CVT related symptoms and signs and were tested positive for COVID - 19 infection during the pre-hospitalization screening. Respiratory symptoms were absent in 90% of the patients. Headache (100%) and seizures (90%) were the common presenting symptoms. The median time to diagnosis was 6 hours, from presentation to the emergency department. Transverse sinus was involved 10/11 (90%) and majority of them (9/11) had Haemorrhagic Venous Infarction (HVI). Acute inflammatory markers were elevated in comparison with non COVID CVT patients, with the mean serum D-dimer being 2462.75 ng/ml and the C-reactive protein was 64.5 mg/dl. Three patients (30%) underwent decompressive hemicraniectomy (DHC) because of large hemispheric HVI. All patients survived in the COVID CVT group while the mortality in the non COVID group was 4%. At 6 months follow up excellent outcome (modified Rankin Scale (mRS) score of 0-2) was noted equally in both groups. CONCLUSIONS: Symptoms and signs of CVT may be the only presentation of COVID-19 infection. Prompt recognition and aggressive medical management including DHC offers excellent outcomes.

Biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the humoral immunoresponse: a systematic review of evidence to support global policy-level actions and research.

BACKGROUND: Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019 (COVID-19) pandemic. Population-level data are widely available and efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a paucity of systemized data on this subject. OBJECTIVE: In this review, we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies. We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity, transmission potential, and prognosis. DATA SOURCES AND METHODS: Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications. Search terms included: "Novel Coronavirus" OR "COVID-19" OR "SARS-CoV-2" OR "2019-nCoV" AND "Immunity" OR "Immune Response" OR "Antibody Response" OR "Immunologic Response". Studies published from December 31, 2019 to December 31, 2020 were included. To ensure validity, papers in pre-print were excluded. RESULTS: Of 2 889 identified papers, 36 were included. Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2. Antibody titers appear to markedly increase two weeks after infection, followed by a plateau. A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations. This trend persists with regard to the length of antibody maintenance. However, overall immunity appears to wane within two to three months post-infection. CONCLUSION: Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection. Immunity generated through natural infection appears to be short, suggesting a need for long-term efforts to control the pandemic. Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention. Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity.