The Influence Of Covid-19 On Patient Mobilization And Injury Attributes In The ICU: A Retrospective Analysis Of A Level II Trauma Center (preprint)

The objectives of this study were to determine the effect of COVID-19 on physical therapy (PT) mobilization of traumatically-injured patients and to determine if mobilization affected patient course in the ICU. This retrospective study included patients who were admitted to the ICU of a level II trauma center. The patients were divided into two groups, i.e., those admitted before (n=378) and after (n=499) April 1, 2020 when Georgia's COVID-19 Shelter-in-place order was mandated. The two groups were contrasted on nominal and ratio variables using Chi-square and Student's t-tests. A secondary analysis focused specifically on the after COVID patients examined the extent to which mobilization (n=328) or lack of mobilization (n=171) influenced ICU outcomes (e.g., mortality, readmission). The two groups were contrasted on nominal and ratio variables using Chi-square and Student's -tests. The after COVID patients had higher injury severity as a greater proportion was classified as severely injured (i.e., >15 on Injury Severity Score) compared to the before COVID patients. After COVID patients also had greater cumulative number of comorbidities and experienced greater complications in the ICU. Despite this, there was no difference between patients in receiving a PT consultation or day-to-mobilization. Within the after COVID cohort, those that were mobilized were older, a higher proportion were female, they had greater Glasgow Coma Scale scores, had longer total hospital days, and a lesser mortality rate. Despite shifting patient injury attributes post-COVID-19, a communicable disease, mobilization care remained consistent and effective.

Thinking Clearly: The History of Brain Dysfunction in Critical Illness.

Brain dysfunction during critical illness (ie, delirium and coma) is extremely common, and its lasting effect has only become increasingly understood in the last two decades. Brain dysfunction in the intensive care unit (ICU) is an independent predictor of both increased mortality and long-term impairments in cognition among survivors. As critical care medicine has grown, important insights regarding brain dysfunction in the ICU have shaped our practice including the importance of light sedation and the avoidance of deliriogenic drugs such as benzodiazepines. Best practices are now strategically incorporated in targeted bundles of care like the ICU Liberation Campaign's ABCDEF Bundle.

Urine Output and Mortality in Patients Resuscitated from out of Hospital Cardiac Arrest.

BACKGROUND: Limited data exist regarding urine output (UO) as a prognostic marker in out-of-hospital-cardiac-arrest (OHCA) survivors undergoing targeted temperature management (TTM). METHODS: We included 247 comatose adult patients who underwent TTM after OHCA between 2007 and 2017, excluding patients with end-stage renal disease. Three groups were defined based on mean hourly UO during the first 24 h: Group 1 (<0.5 mL/kg/h, n = 73), Group 2 (0.5-1 mL/kg/h, n = 81) and Group 3 (>1 mL/kg/h, n = 93). Serum creatinine was used to classify acute kidney injury (AKI). The primary and secondary outcomes respectively were in-hospital mortality and favorable neurological outcome at hospital discharge (modified Rankin Scale [mRS]<3). RESULTS: In-hospital mortality decreased incrementally as UO increased (adjusted OR 0.9 per 0.1 mL/kg/h higher; p = 0.002). UO < 0.5 mL/kg/h was strongly associated with higher in-hospital mortality (adjusted OR 4.2 [1.6-10.8], p = 0.003) and less favorable neurological outcomes (adjusted OR 0.4 [0.2-0.8], p = 0.007). Even among patients without AKI, lower UO portended higher mortality (40% vs 15% vs 9% for UO groups 1, 2, and 3 respectively, p < 0.001). CONCLUSION: Higher UO is incrementally associated with lower in-hospital mortality and better neurological outcomes. Oliguria may be a more sensitive early prognostic marker than creatinine-based AKI after OHCA.

Evaluation of Geriatric Falls in Emergency Department During the Early Coronavirus-2019 Pandemic and Pre-Pandemic Periods (preprint)

Purpose This study aimed to investigate the clinical characteristics, presentations, outcomes, and healthcare costs of older patients who presented at the emergency department (ED) with falls in the periods before and during the Coronavirus disease-2019 (COVID-19) pandemic.Methods Hospital records one year before and after the onset of the COVID-19 pandemic were retrospectively analyzed through “International Statistical Classification of Diseases-10th Revision” codes. Age, gender, falls, triage classification, length of stay (LOS) in the hospital and ED, COVID-19 status, Glasgow coma scale (GCS), consultations-comorbidities, injury status, outcomes in the ED, and costs were recorded.Results The study comprised of 3,187 patients aged ≥ 65 years admitted to the ED of a university hospital between March 2019 and 2021. In terms of pre-pandemic and pandemic periods; older patients presenting with falls to the ED, consultations, Charlson Comorbidity Index (CCI), and LOS in ED were lower in the pandemic period, but costs were higher (p = 0.03, p = 0.01, p = 0.01, p = 0.01 and p = 0.02, respectively). Hospitalization/mortality rates were higher in COVID-19-positive patients (77.2%) than in COVID-19-negative patients (4.6%) within the pandemic period and the patients in the pre-pandemic period (22.8%), likewise for the costs (both p = 0.01).Conclusion Though the number of geriatric fall presentations to ED, comorbidity burden, consultations, and LOS in the ED was lower, direct costs were higher during the pandemic period, particularly for COVID-19 positive older patients admitted to ED with falls than the pre-pandemic period, and those patients were with poorer outcomes.

Outcomes in Patients With COVID-19 With Acute Encephalopathy and Coma: An International Prospective Study.

BACKGROUND AND OBJECTIVES: To report the prevalence of acute encephalopathy and outcomes in patients with severe coronavirus disease 2019 (COVID-19) and to identify determinants of 90-day outcomes. METHODS: Data from adults with severe COVID-19 and acute encephalopathy were prospectively collected for patients requiring intensive care unit management in 31 university or university-affiliated intensive care units in 6 countries (France, United States, Colombia, Spain, Mexico, and Brazil) between March and September of 2020. Acute encephalopathy was defined, as recently recommended, as subsyndromal delirium or delirium or as a comatose state in case of severely decreased level of consciousness. Logistic multivariable regression was performed to identify factors associated with 90-day outcomes. A Glasgow Outcome Scale-Extended (GOS-E) score of 1-4 was considered a poor outcome (indicating death, vegetative state, or severe disability). RESULTS: Of 4,060 patients admitted with COVID-19, 374 (9.2%) experienced acute encephalopathy at or before the intensive care unit (ICU) admission. A total of 199/345 (57.7%) patients had a poor outcome at 90-day follow-up as evaluated by the GOS-E (29 patients were lost to follow-up). On multivariable analysis, age older than 70 years (odds ratio [OR] 4.01, 95% CI 2.25-7.15), presumed fatal comorbidity (OR 3.98, 95% CI 1.68-9.44), Glasgow coma scale score <9 before/at ICU admission (OR 2.20, 95% CI 1.22-3.98), vasopressor/inotrope support during ICU stay (OR 3.91, 95% CI 1.97-7.76), renal replacement therapy during ICU stay (OR 2.31, 95% CI 1.21-4.50), and CNS ischemic or hemorrhagic complications as acute encephalopathy etiology (OR 3.22, 95% CI 1.41-7.82) were independently associated with higher odds of poor 90-day outcome. Status epilepticus, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome were associated with lower odds of poor 90-day outcome (OR 0.15, 95% CI 0.03-0.83). DISCUSSION: In this observational study, we found a low prevalence of acute encephalopathy at ICU admission in patients with COVID-19. More than half of patients with COVID-19 presenting with acute encephalopathy had poor outcomes as evaluated by GOS-E. Determinants of poor 90-day outcome were dominated by older age, comorbidities, degree of impairment of consciousness before/at ICU admission, association with other organ failures, and acute encephalopathy etiology. TRIAL REGISTRATION INFORMATION: The study is registered with ClinicalTrials.gov, number NCT04320472.

Neuroimaging findings and neurological manifestations in hospitalized COVID-19 patients: Impact of cancer and ventilatory support status.

INTRODUCTION: Coronavirus 2019 (COVID-19) is known to affect the central nervous system. Neurologic morbidity associated with COVID-19 is commonly attributed to sequelae of some combination of thrombotic and inflammatory processes. The aim of this retrospective observational study was to evaluate neuroimaging findings in hospitalized COVID-19 patients with neurological manifestations in cancer versus non-cancer patients, and in patients with versus without ventilatory support (with ventilatory support defined as including patients with intubation and noninvasive ventilation). Cancer patients are frequently in an immunocompromised or prothrombotic state with side effects from chemotherapy and radiation that may cause neurological issues and increase vulnerability to systemic illness. We wanted to determine whether neurological and/or neuroimaging findings differed between patients with and without cancer. METHODS: Eighty adults (44 male, 36 female, 64.5 ±14 years) hospitalized in the Mount Sinai Health System in New York City between March 2020 and April 2021 with reverse-transcriptase polymerase chain reaction-confirmed COVID-19 underwent magnetic resonance imaging (MRI) during their admissions. The cohort consisted of four equal subgroups based on cancer and ventilatory support status. Clinical and imaging data were acquired and analyzed. RESULTS: Neuroimaging findings included non-ischemic parenchymal T2/FLAIR signal hyperintensities (36.3%), acute/subacute infarcts (26.3%), chronic infarcts (25.0%), microhemorrhages (23.8%), chronic macrohemorrhages (10.0%), acute macrohemorrhages (7.5%), and encephalitis-like findings (7.5%). There were no significant differences in neuroimaging findings between cancer and non-cancer subgroups. Clinical neurological manifestations varied. The most common was encephalopathy (77.5%), followed by impaired responsiveness/coma (38.8%) and stroke (26.3%). There were significant differences between patients with versus without ventilatory support. Encephalopathy and impaired responsiveness/coma were more prevalent in patients with ventilatory support (p = 0.02). Focal weakness was more frequently seen in patients without ventilatory support (p = 0.01). DISCUSSION: This study suggests COVID-19 is associated with neurological manifestations that may be visible with brain imaging techniques such as MRI. In our COVID-19 cohort, there was no association between cancer status and neuroimaging findings. Future studies might include more prospectively enrolled systematically characterized patients, allowing for more rigorous statistical analysis.

Protective down-regulated states in the human brain: A possible lesson from COVID-19.

The COVID-19 pandemic has created a large population of patients who are slow to recover consciousness following mechanical ventilation and sedation in the intensive care unit. Few clinical scenarios are comparable. Possible exceptions are the rare patients in post-cardiac arrest coma with minimal to no structural brain injuries who recovered cognitive and motor functions after prolonged delays. A common electroencephalogram (EEG) signature seen in these patients is burst suppression [8]. Biophysical modeling has shown that burst suppression is likely a signature of a neurometabolic state that preserves basic cellular function "during states of lowered energy availability." These states likely act as a brain protective mechanism [9]. Similar EEG patterns are observed in the anoxia resistant painted turtle [24]. We present a conceptual analysis to interpret the brain state of COVID-19 patients suffering prolonged recovery of consciousness. We begin with the Ching model and integrate findings from other clinical scenarios and studies of the anoxia-tolerant physiology of the painted turtle. We postulate that prolonged recovery of consciousness in COVID-19 patients could reflect the effects of modest hypoxic injury to neurons and the unmasking of latent neuroprotective mechanisms in the human brain. This putative protective down-regulated state appears similar to that observed in the painted turtle and suggests new approaches to enhancing coma recovery [12].

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses (preprint)

Neurological complications occur in a significant proportion of COVID-19 cases. In order to identify key biomarkers, we measured brain injury markers, inflammatory mediators, and autoantibodies in 203 participants admitted to hospital for management of COVID-19; 111 provided acute sera (1-11 days post admission) and 56 with COVID-19-associated neurological diagnoses provided convalescent sera (up to76 weeks post admission). Compared to 60 controls, brain injury biomarkers (total-Tau, GFAP, NfL, UCH-L1) were increased in acute sera, significantly more so for NfL and UCH-L1, in participants with altered consciousness. Total-Tau (tTau) and NfL remained elevated in convalescent sera, particularly following cerebrovascular and neuroinflammatory disorders. Acutely, inflammatory mediators (including IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) were higher in participants with altered consciousness and correlated with brain injury biomarker levels. Inflammatory mediators were lower in convalescent sera than acute sera. Levels of CCL2, CCL7, IL-1RA, IL-2Rα, M-CSF, SCF, IL-16 and IL-18 in individual participants correlated with tTau levels even at later time points. When compared to acute COVID-19 patients with a normal Glasgow Coma Scale score (GCS), network analysis showed significantly altered immune responses in patients with acute alteration of consciousness, and in convalescent patients who had suffered an acute neurological complication. The frequency and range of autoantibodies did not associate with neurological disorders. However, autoantibodies against specific antigens were more frequent in patients with altered consciousness in the acute phase (including MYL7, UCH-L1, GRIN3B, and DDR2), and in patients with neurological complications in the convalescent phase (including MYL7, GNRHR, and HLA antigens). In a novel low-inoculum mouse model of SARS-CoV-2, while viral replication was only consistently seen in mouse lungs, inflammatory responses were seen in both brain and lungs, with significant increases in CCL4, IFNγ, IL-17A, and microglial reactivity in the brain. Neurological injury is common in the acute phase of COVID-19 and we found brain injury markers persist during convalescence and may be driven by a para-infectious process involving a dysregulated host response.

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored. METHODS: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included. RESULTS: Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent. CONCLUSIONS: Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.

Characteristics of Delirium and Its Association with Sedation and In-Hospital Mortality in COVID-19 Patients on Veno-venous Extracorporeal Membrane Oxygenation (preprint)

Background Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used in patients with COVID-19 acute respiratory distress syndrome (ARDS). We aim to assess the characteristics of delirium and describe its association with sedation and in-hospital mortality. Methods We retrospectively reviewed adult patients on VV-ECMO for severe COVID-19 ARDS in the Johns Hopkins Hospital ECMO registry in 2020-2021. Delirium was assessed by the Confusion Assessment Method for the ICU when patients scored -3 or above on Richmond Agitation-Sedation Scale (RASS). Primary outcomes were delirium prevalence while on VV-ECMO and categorization of VV-ECMO days based on delirium status. Results Of 47 patients (median age=51) with 6 in a persistent coma, 40 of the remaining 41 patients (98%) had ICU delirium. Delirium in the survivors (n=21) and non-survivors (n=26) was first detected at a similar time point (day 9.5[5, 14] vs. 8.5[5, 21], p=0.56) with similar total delirium days (9.5[3.3, 16.8] vs. 9.0[4.3, 28.3], p=0.43), but the RASS scores on VV-ECMO were numerically lower in non-survivors (-3.72[-4.42, -2.96] vs. -3.10[-3.91, -2.21], p=0.06). Non-survivors had significantly prolonged median delirium days (27.3[17.4, 46.4] vs. 17.0[9.9, 28], p=0.04), delirium-unassessable days on VV-ECMO with a RASS of -4/-5 (23.0[16.3, 38.3] vs. 17.0[6, 23], p=0.03), and total VV-ECMO days (44.5[20.5, 74.3] vs. 27.0[21, 38], p=0.04). The proportion of delirium-present days correlated with RASS (r=0.64, p<0.001), proportion of days with a neuromuscular blocker (r=-0.59, p=0.001) and delirium-unassessable exams (r=-0.69, p<0.001), but not with overall ECMO duration (r=0.01, p=0.96). Average daily dosage of delirium-related medications on ECMO days did not differ significantly between survivors and non-survivors. On multivariable logistic regression, proportion of delirium days was not associated with mortality. Conclusions Longer duration of delirium was associated with lighter analgosedation and shorter paralysis, but the condition did not discern in-hospital mortality. Future studies should evaluate analgosedation and paralytic strategies to optimize delirium, sedation level, and outcomes.

Ischemic Stroke in a COVID-19-Infected Patient: A Case Report and Literature Review (preprint)

Ischemic stroke is a recognized neurological consequence of acute COVID-19 infection. A 61-year-old black African farmer with right-sided weakness was sent to the emergency hospital on September 19, 2022, within three hours of the onset of the impairment. He suffered a serious accident while working in the rural region fifteen years prior. Generalized body weakness, including weakness in the right upper and lower extremities while he was moving around, left facial paralysis, an inability to walk without assistance, difficulty swallowing, difficulty speaking, a two-day fever, a headache, and shortness of breath were all reasons why the patient was brought into the emergency room. An X-ray of the chest was taken, and it revealed scattered reticulations, coarse, somewhat bilateral crepitation, and diffuse bilateral infiltrates. The patient's cardiovascular checkup revealed nothing unusual. According to the Glasgow Coma Scale, the eye opening reaction was 1/4, the motor response was 3/6 (abnormal flexion), and the verbal response was 3/5 (inappropriate words). He started having trouble breathing and needed five intranasal doses of oxygen per minute to stay saturated. He began taking 81 mg of low-dose aspirin every day for a month. For ten days, he took 75 mg of clopidogrel orally once every day.

Chronic heart failure in a patient with SARS-CoV-2 infection: a case report and discussion (preprint)

The involvement of the heart in COVID-19 infection appears to have a major negative influence on patient prognosis and survival. Myocarditis is caused by COVID-19, which can lead to heart failure and arrhythmias. On October 11, 2022, a 60-year-old middle-aged black African female widow was admitted with history of muscular weakness for two days and lack of appetite, and occasional vomiting for one day. She arrived at the emergency room after complaining for two days of peeing less than usual, weakness, a fast heartbeat, swelling in the feet, pink blood-tinged mucus, fever, headache, dehydration, a non-productive cough, and shortness of breath. Her neurological assessment to determine her level of consciousness indicated a Glasgow coma rating of 10/15. Routine reverse transcription polymerase chain reaction (COVID-19) testing was performed in the emergency room; she tested positive. To treat her proven COVID-19 infection, she was received subcutaneous enoxaparin 80 mg every 12 hours as prophylaxis of deep venous thromboembolism. Because of a probable lung bacterial superinfection, 1 g of ceftriaxone and 500 mg of azithromycin were given orally once a day for five days to reduce her hospital-acquired infectious diseases.

A case report of critically ill COVID-19 ICU patient recovery from acute respiratory distress syndrome, acute heart failure, kidney disorder, and Churg-Strauss syndrome (preprint)

During the COVID-19 pandemic, a 32-year-old front line health-worker tested positive for COVID-19 in RT-PCR and was admitted to the Japan East West Medical College Hospital in Bangladesh. In the ICU, the patient was in coma for 5 days. The Patient’s condition was improved after taking fresh frozen plasma.

Trend and co-occurrence network study of symptoms through social media: an example of COVID-19 (preprint)

ImportanceCOVID-19 is a multi-organ disease with broad-spectrum manifestations. Clinical data-driven research can be difficult because many patients do not receive prompt diagnoses, treatment, and follow-up studies. Social medias accessibility, promptness, and rich information provide an opportunity for large-scale and long-term analyses, enabling a comprehensive symptom investigation to complement clinical studies. ObjectivePresent an efficient workflow to identify and study the characteristics and co-occurrences of COVID-19 symptoms using social media. Design, Setting, and ParticipantsThis retrospective cohort study analyzed 471,553,966 COVID-19-related tweets from February 1, 2020, to April 30, 2022. A comprehensive lexicon of symptoms was used to filter tweets through rule-based methods. 948,478 tweets with self-reported symptoms from 689,551 Twitter users were identified for analysis. Main Outcomes and MeasuresThe overall trends of COVID-19 symptoms reported on Twitter were analyzed (separately by the Delta strain and the Omicron strain) using weekly new numbers, overall frequency, and temporal distribution of reported symptoms. A co-occurrence network was developed to investigate relationships between symptoms and affected organ systems. ResultsThe weekly quantity of self-reported symptoms has a high consistency (0.8528, P<0.0001) and one-week leading trend (0. 8802, P<0.0001) with new infections in four countries. We grouped 201 common symptoms (mentioned [≥] 10 times) into 10 affected systems. The frequency of symptoms showed dynamic changes as the pandemic progressed, from typical respiratory symptoms in the early stage to more musculoskeletal and nervous symptoms at later stages. When comparing symptoms reported during the Delta strain versus the Omicron variant, significant changes were observed, with dropped odd ratios of coma (95%CI 0.55-0.49, P<0.01) and anosmia (95%CI, 0.6-0.56), and more pain in the throat (95%CI, 1.86-1.96) and concentration problems (95%CI, 1.58-1.70). The co-occurrence network characterizes relationships among symptoms and affected systems, both intra-systemic, such as cough and sneezing (respiratory), and inter-systemic, such as alopecia (integumentary) and impotence (reproductive). Conclusions and RelevanceWe found dynamic COVID-19 symptom evolution through self-reporting on social media and identified 201 symptoms from 10 affected systems. This demonstrates that social medias prevalence trends and co-occurrence networks can efficiently identify and study public health problems, such as common symptoms during pandemics. Key pointsO_ST_ABSQuestionsC_ST_ABSWhat are the epidemic characteristics and relationships of COVID-19 symptoms that have been extensively reported on social media? FindingsThis retrospective cohort study of 948,478 related tweets (February 2020 to April 2022) from 689,551 users identified 201 self-reported COVID-19 symptoms from 10 affected systems, mitigating the potential missing information in hospital-based epidemiologic studies due to many patients not being timely diagnosed and treated. Coma, anosmia, taste sense altered, and dyspnea were less common in participants infected during Omicron prevalence than in Delta. Symptoms that affect the same system have high co-occurrence. Frequent co-occurrences occurred between symptoms and systems corresponding to specific disease progressions, such as palpitations and dyspnea, alopecia and impotence. MeaningTrend and network analysis in social media can mine dynamic epidemic characteristics and relationships between symptoms in emergent pandemics.

Monitoring of sedation in mechanically ventilated patients using remote technology.

PURPOSE OF REVIEW: Two years of coronavirus disease 2019 (COVID-19) pandemic highlighted that excessive sedation in the ICU leading to coma and other adverse outcomes remains pervasive. There is a need to improve monitoring and management of sedation in mechanically ventilated patients. Remote technologies that are based on automated analysis of electroencephalogram (EEG) could enhance standard care and alert clinicians real-time when severe EEG suppression or other abnormal brain states are detected. RECENT FINDINGS: High rates of drug-induced coma as well as delirium were found in several large cohorts of mechanically ventilated patients with COVID-19 pneumonia. In patients with acute respiratory distress syndrome, high doses of sedatives comparable to general anesthesia have been commonly administered without defined EEG endpoints. Continuous limited-channel EEG can reveal pathologic brain states such as burst suppression, that cannot be diagnosed by neurological examination alone. Recent studies documented that machine learning-based analysis of continuous EEG signal is feasible and that this approach can identify burst suppression as well as delirium with high specificity. SUMMARY: Preventing oversedation in the ICU remains a challenge. Continuous monitoring of EEG activity, automated EEG analysis, and generation of alerts to clinicians may reduce drug-induced coma and potentially improve patient outcomes.

Short- and long-term outcome and predictors in an international cohort of patients with neuro-COVID-19.

BACKGROUND AND PURPOSE: Despite the increasing number of reports on the spectrum of neurological manifestations of COVID-19 (neuro-COVID), few studies have assessed short- and long-term outcome of the disease. METHODS: This is a cohort study enrolling adult patients with neuro-COVID seen in neurological consultation. Data were collected prospectively or retrospectively in the European Academy of Neurology NEuro-covid ReGistrY ((ENERGY). The outcome at discharge was measured using the modified Rankin Scale and defined as 'stable/improved' if the modified Rankin Scale score was equal to or lower than the pre-morbid score, 'worse' if the score was higher than the pre-morbid score. Status at 6 months was also recorded. Demographic and clinical variables were assessed as predictors of outcome at discharge and 6 months. RESULTS: From July 2020 to March 2021, 971 patients from 19 countries were included. 810 (83.4%) were hospitalized. 432 (53.3%) were discharged with worse functional status. Older age, stupor/coma, stroke and intensive care unit (ICU) admission were predictors of worse outcome at discharge. 132 (16.3%) died in hospital. Older age, cancer, cardiovascular complications, refractory shock, stupor/coma and ICU admission were associated with death. 262 were followed for 6 months. Acute stroke or ataxia, ICU admission and degree of functional impairment at discharge were predictors of worse outcome. 65/221 hospitalized patients (29.4%) and 10/32 non-hospitalized patients (24.4%) experienced persisting neurological symptoms/signs. 10/262 patients (3.8%) developed new neurological complaints during the 6 months of follow-up. CONCLUSIONS: Neuro-COVID is a severe disease associated with worse functional status at discharge, particularly in older subjects and those with comorbidities and acute complications of infection.

Early Clinical and Electrophysiological Brain Dysfunction Is Associated With ICU Outcomes in COVID-19 Critically Ill Patients With Acute Respiratory Distress Syndrome: A Prospective Bicentric Observational Study.

OBJECTIVES: Describe the prevalence of acute cerebral dysfunction and assess the prognostic value of an early clinical and electroencephalography (EEG) assessment in ICU COVID-19 patients. DESIGN: Prospective observational study. SETTING: Two tertiary critical care units in Paris, France, between April and December 2020. PATIENTS: Adult critically ill patients with COVID-19 acute respiratory distress syndrome. INTERVENTIONS: Neurologic examination and EEG at two time points during the ICU stay, first under sedation and second 4-7 days after sedation discontinuation. MEASUREMENTS AND MAIN RESULTS: Association of EEG abnormalities (background reactivity, continuity, dominant frequency, and presence of paroxystic discharges) with day-28 mortality and neurologic outcomes (coma and delirium recovery). Fifty-two patients were included, mostly male (81%), median (interquartile range) age 68 years (56-74 yr). Delayed awakening was present in 68% of patients (median awakening time of 5 d [2-16 d]) and delirium in 74% of patients who awoke from coma (62% of mixed delirium, median duration of 5 d [3-8 d]). First, EEG background was slowed in the theta-delta range in 48 (93%) patients, discontinuous in 25 patients (48%), and nonreactive in 17 patients (33%). Bifrontal slow waves were observed in 17 patients (33%). Early nonreactive EEG was associated with lower day-28 ventilator-free days (0 vs 16; p = 0.025), coma-free days (6 vs 22; p = 0.006), delirium-free days (0 vs 17; p = 0.006), and higher mortality (41% vs 11%; p = 0.027), whereas discontinuous background was associated with lower ventilator-free days (0 vs 17; p = 0.010), coma-free days (1 vs 22; p < 0.001), delirium-free days (0 vs 17; p = 0.001), and higher mortality (40% vs 4%; p = 0.001), independently of sedation and analgesia. CONCLUSIONS: Clinical and neurophysiologic cerebral dysfunction is frequent in COVID-19 ARDS patients. Early severe EEG abnormalities with nonreactive and/or discontinuous background activity are associated with delayed awakening, delirium, and day-28 mortality.

COVID-19 Time of Intubation Mortality Evaluation (C-TIME): A System for Predicting Mortality of Patients with COVID-19 Pneumonia at the Time They Require Mechanical Ventilation. (preprint)

Background: An accurate system to predict mortality in patients requiring intubation for COVID-19 could help to inform consent, frame family expectations and assist end-of-life decisions. Research objective: To develop and validate a mortality prediction system called C-TIME (COVID-19 Time of Intubation Mortality Evaluation) using variables available before intubation, determine its discriminant accuracy, and compare it to APACHE IVa and SOFA. Methods: A retrospective cohort was set in 18 medical-surgical ICUs, enrolling consecutive adults, positive by SARS-CoV 2 RNA by reverse transcriptase polymerase chain reaction or positive rapid antigen test, and undergoing endotracheal intubation. All were followed until hospital discharge or death. The combined outcome was hospital mortality or terminal extubation with hospice discharge. Twenty-five clinical and laboratory variables available 48 hours prior to intubation were entered into multiple logistic regression (MLR) and the resulting model was used to predict mortality of validation cohort patients. AUROC was calculated for C-TIME, APACHE IVa and SOFA. Results: The median age of the 2,440 study patients was 66 years; 61.6 percent were men, and 50.5 percent were Hispanic, Native American or African American. Age, gender, COPD, minimum mean arterial pressure, Glasgow Coma scale score, and PaO2/FiO2 ratio, maximum creatinine and bilirubin, receiving factor Xa inhibitors, days receiving non-invasive respiratory support and days receiving corticosteroids prior to intubation were significantly associated with the outcome variable. The validation cohort comprised 1,179 patients. C-TIME had the highest AUROC of 0.75 (95%CI 0.72-0.79), vs 0.67 (0.64-0.71) and 0.59 (0.55-0.62) for APACHE and SOFA, respectively (Chi2 P<0.0001). Conclusions: C-TIME is the only mortality prediction score specifically developed and validated for COVID-19 patients who require mechanical ventilation. It has acceptable discriminant accuracy and goodness-of-fit to assist decision-making just prior to intubation. The C-TIME mortality prediction calculator can be freely accessed on-line at https://phoenixmed.arizona.edu/ctime.

Frequency and burden of neurological manifestations in hospitalized patients with COVID-19: findings from a large Brazilian cohort (preprint)

Background: Scientific data regarding the prevalence of COVID-19 neurological manifestations and prognosis in Latin America countries is still lacking. Therefore, the study aims to understand neurological manifestations of SARS-CoV 2 infection in the Brazilian population and its association with patient outcomes, such as in-hospital mortality. Methods This study is part of the Brazilian COVID-19 Registry, a multicentric COVID-19 cohort, including data from 37 Brazilian hospitals. For the analysis, patients were grouped according to the presence of self-reported vs. clinically-diagnosed neurological manifestations and matched with patients without neurological manifestations by age, sex, number of comorbidities, hospital, and whether or not patients ha neurological underlying disease. Results From 7,232 hospitalized patients with COVID-19, 27.8% presented self-reported neurological manifestations, 9.9% were diagnosed with a clinically-defined neurological syndrome and 1.2% did not show any neurological symptoms. In patients with self-reported symptoms, the most common ones were headache (19.3%), ageusia (10.4%) and anosmia (7.4%). Meanwhile, in the group with clinically-defined neurological syndromes, acute encephalopathy was the most common diagnosis (10.5%), followed by coma (0.6%1) and seizures (0.4%). Men and younger patients were more likely to self-report neurological symptoms, while women and older patients were more likely to develop a neurological syndrome. Patients with clinically-defined neurological syndromes presented a higher prevalence of comorbidities, as well as lower oxygen saturation and blood pressure at hospital admission. In the paired analysis, it was observed that patients with clinically-defined neurological syndromes were more likely to require ICU admission (46.9 vs. 37.9%), mechanical ventilation (33.4 vs. 28.2%), to develop acute heart failure (5.1 vs. 3.0%, p=0.037) and to die (40.7 vs. 32.3%, p<0.001) when compared to controls. Conclusion Neurological manifestations are an important cause of morbidity in COVID-19 patients. More specifically, patients with clinically defined neurological syndromes presented a poorer prognosis for the disease when compared to matched controls.

Evaluation of Prognosis of Coma Patients With Acute Brain Injury by Electroencephalogram Bispectral Index Monitoring.

BACKGROUND: The high mortality rate of comatose patients with traumatic brain injury is a prominent public health issue that negatively impacts patients and their families. Objective, reliable tools are needed to guide treatment decisions and prioritize resources. OBJECTIVE: This study aimed to evaluate the prognostic value of the bispectral index (BIS) in comatose patients with severe brain injury. METHODS: This was a retrospective cohort study of 84 patients with severe brain injury and Glasgow Coma Scale (GCS) scores of 8 and less treated from January 2015 to June 2017. Sedatives were withheld at least 24 hr before BIS scoring. The BIS value, GCS scores, and Full Outline of UnResponsiveness (FOUR) were monitored hourly for 48 hr. Based on the Glasgow Outcome Scale (GOS) score, the patients were divided into poor (GOS score: 1-2) and good prognosis groups (GOS score: 3-5). The correlation between BIS and prognosis was analyzed by logistic regression, and the receiver operating characteristic curves were plotted. RESULTS: The mean (SD) of the BIS value: 54.63 (11.76), p = .000; and GCS score: 5.76 (1.87), p = .000, were higher in the good prognosis group than in the poor prognosis group. Lower BIS values and GCS scores were correlated with poorer prognosis. Based on the area under the curve of receiver operating characteristic curves, the optimal diagnostic cutoff value of the BIS was 43.6, and the associated sensitivity and specificity were 85.4% and 74.4%, respectively. CONCLUSION: Taken together, our study indicates that BIS had good predictive value on prognosis. These findings suggested that BIS could be used to evaluate the severity and prognosis of severe brain injury.