Long-term functional outcome of severe COVID19 pneumonia treated with venovenous extracorporeal membrane oxygenation support - learnings from a single centre

Objectives: Implementation of venovenous extracorporeal membrane oxygenation (VVECMO) allowed survival of patients with severe respiratory failure associated with SARS-CoV-2 infection. However, VVECMO treatment is usually associated with long ICU stays, prolonged sedation, and neuromuscular blockage days. Functional disability, due to delirium and acquired muscle weakness, is frequently an inevitable burden causing long term disability. This study aims to analyse main characteristics of patients under ECMO due to COVID-19 pneumonia, their outcomes and functional status six months after ICU discharge. Method(s): Retrospective review of a prospectively collected database in an ECMO referral centre. All patients receiving VVECMO for SARS-CoV-2 infection were included. Epidemiological and clinical data were reviewed. Functional status at 6 months after ICU discharge was assessed with modified Rankin Scale (mRS). Result(s): Ninety-three patients were included (29% female). Median age was 54+/-12 years, mean SOFA was 5.7+/-2.9, mean SAPS II was 35.6+/-13.6. Mean time from intubation to cannulation was 5+/-5.6 days in 91 patients;awake-ECMO was performed in 2 patients. Mean ECMO run duration was 33.1+/-30 days (longest ECMO run was 194 days). A period of awake-ECMO was performed on 36.5% of patients, during 16.4+/-21.2 days. ICU-acquired weakness was diagnosed on 64.5% of patients and delirium on 63.4%. Mortality was 24.7% (23 patients) with only 1 patient deceased in hospital after ICU discharge. At 6 months follow-up, all patients were still alive and most of them (65.1%) were independent on all daily activities (mRS <= 2). Conclusion(s): Patients with severe COVID-19 treated with VVECMO support had very good functional outcomes at six-month follow-up. Despite long ICU length-of-stay, high incidence of delirium and acquired muscle weakness, full recovery at six-month post-ICU discharge was achievable in most patients.

Association Between COVID-19 Pandemic and Serious Mental Illness: Systematic Review within Salutogenesis Model for Public Health Management

Background: The outbreak of the COVID-19 pandemic, the constant transformation of the SARS-COV-2 virus form, exposure to substantial psychosocial stress, environmental change, and isolation have led to the inference that the overall population's mental health could be affected, resulting in an increase in cases of psychosis. Objective(s): We initiated a systematic review to determine the impact of the SARS-COV-2 virus and its long-term effects-in both symptomatic and asymptomatic cases-on people with or without psychosis. We envisioned that this would give us an insight into effective clinical intervention methods for patients with psychosis during and after the pandemic. Method(s): We selected fifteen papers that met our inclusion criteria, i.e., those that considered participants with or without psychiatric illness and exposed to SARS-COV-2 infection, for this review and were retrieved via Google, Google Scholar, MEDLINE, PubMed, and PsychINFO Database. Key Gap: There is a dearth of research in understanding how COVID-19 affects people with or without a prior personal history of psychosis. Result(s): The systematic review summary provides insight into the state of knowledge. Insights from the systematic review have also been reviewed from the salutogenesis model's perspec-tive. There is moderate evidence of new-onset psychosis during the COVID-19 pandemic in which some antipsychotics treated the psychotic symptoms of patients while treating for COVID-19. Suggestions and recommendations are made for preventive and promotive public health strategies. Conclusion(s): The Salutogenesis model and Positive Psychology Interventions (PPI) provide another preventive and promotive public health management approach.Copyright © 2023 Bentham Science Publishers.

Mania: An Atypical Presentation of probable Streptococcus Agalactiae Meningoencephalitis

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a common pathogen in the neonatal period, causing meningitis and sepsis. In non-pregnant adults it is an unusual cause of meningitis. We report about an elderly female with several risk factors for invasive GBS infection who developed GBS meningoencephalitis one month after treatment for COVID-19 upper respiratory tract infection. The patient presented with mania, and the classic triad of headache, neck stiffness, and fever was absent which contributed to the delay in diagnosis. Following initiation of treatment with intravenous ceftriaxone she attained full recovery, and her behavior returned to baseline. This case illustrates an unusual presentation of an emerging infection and should alert clinicians about this presentation. By reporting this case we want to raise awareness about mania as a presenting feature of meningoencephalitis. This should lead to more timely diagnosis and better outcomes for future patients.

Unique vascular complication following extended VV-ECMO support

Objectives: To present an unusual complication related to prolonged ECMO support in a patient with COVID19 induced acute respiratory syndrome (ARDS). Method(s): Clinical chart review of the care process after obtaining the informed consent from the patient. Result(s): A 48-year-old female with COVID-19 infection during second wave of pandemic in August 2021 progressed to severe ARDS. She was put on VV-ECMO support after failing conventional therapy for refractory hypoxemia. Her cannulation configuration included a 25 F venous drainage cannula in the right femoral vein and a 21 F venous return cannula in the right Internal Jugular (IJ) vein. Cannulations were performed using the ;Seldinger technique;under USG guidance, and no difficulties or complications were reported. Her hospital course was notable for delirium, and intermittent bleeding from the cannula sites. After 80 days of support, she showed adequate respiratory improvement which allowed ECMO decannulation. She continued to show improvement, and was eventually discharged after 102 days of total hospital stay. During her 6 weeks follow-up clinic visit a palpable thrill was noted at the jugular ECMO cannula site. A CT angiogram of the neck demonstrated a large venous varix connecting the right IJ and the left common carotid artery with filling from the left common carotid artery. ECMO cannulation site complications such as aneurysm, clots, infections and stenosis are well known. What was unusual in this case is the nature of the aneurysm given that there were no arterial procedures performed on the left side of the neck. She was managed by an ;Amplatzer plug;to the carotid artery at the level of the connection to the varix without any complications. Conclusion(s): Longer duration of ECMO support needs careful follow-up for timely recognition and management of vascular complications. (Figure Presented).

Is COVID-19 a risk for postoperative delirium and death in elderly patients after emergency surgery?

Aim: While recent evidence describes atypical outcomes of coronavirus disease 2019 (COVID-19) in elderly patients, the frequency of delirium and associated outcomes in elderly patients with COVID-19 (coronavirus disease 2019) infection undergoing emergency surgery are not well defined. This study aims to determine the effect of COVID-19 on postoperative delirium and postoperative death in elderly patients undergoing emergency surgery. Material(s) and Method(s): This descriptive and cross-sectional study was conducted in general surgery, orthopedics, and cardiovascular surgery clinics of a public hospital, including 30 days of follow-up between April 1 and May 1, 2021. All patients who were admitted to these clinics for emergency surgery intervention on these dates constituted the study population, while a total of 140 patients aged >=65 years, who met the study criteria, formed the sample of the study. Descriptive Characteristics Form and Nursing Delirium Screening Scale (Nu-DESC) were used as data collection tools in the study. SPSS 25.0 statistical program was used for data analysis. Result(s): Thirty (42.85%) of the SARS-CoV-2 positive (n=70) patients developed delirium in the study. 12.9% (n=18) of the patients died within 30 days of follow-up after surgery. There were 30 (69.8) of 70 SARS-CoV-2 positive patients who developed delirium, and 12 patients (25.5) died after testing positive for COVID-19, with a mean of 8.08T1.56 days within 30 days of admission. Discussion(s): These findings may lead to a poor clinical prognosis for COVID-19 infection delirium and postoperative death in patients over 65 years of age undergoing emergency surgery.Copyright © 2023, Derman Medical Publishing. All rights reserved.

Similar symptoms at 3 months post discharge in ICU, COVID-19 ICU, and COVID-19 patients that received non-invasive ventilation in high dependency areas

Introduction: It is well documented that survivors of ICU admissions struggle to return to pre-admission level of function because of both physical and psychological burden. Current guidance therefore recommends a follow-up service to review patients 2-3 months post discharge from ICU [NICE 2009]. Prior to 2020 University Hospitals Bristol and Weston (UHBW) had no such service. With the increase in patient numbers seen during the COVID-19 pandemic, funding was received to provide a follow-up clinic to COVID-19 survivors. Spare clinic spaces were used for non COVID ICU patients. Objective(s): To review symptoms reported by patients in the following 3 groups, COVID-19 patients treated in ICU (COVID ICU), COVID-19 patients treated with continuous positive airway pressure ventilation in high dependency areas (COVID CPAP) and non COVID-19 ICU patients (ICU), at 2-3 months post discharge from UHBW. Method(s): Referred patients had an initial phone call at 8 weeks post discharge. The call identified both physical and psychological symptoms. Advice regarding recovery, signposting to resources and onwards referrals to appropriate specialities were provided. If symptoms indicated, patients would then be referred into the multidisciplinary team follow up clinic. Here they met with an intensivist, clinical psychologist, physiotherapist, occupational therapist, speech and language therapist and dietitian. Result(s): As Graph 1 shows all 3 patient groups had a wide variety of ongoing symptoms at 2-3 months post discharge. Fatigue was the most common symptom reported in all 3 groups. Breathlessness was the second most common symptom reported by COVID patients but was less frequently reported in the ICU population who had a variety of non-respiratory related reasons for admission. COVID ICU patients more commonly reported ongoing problems with their swallowing, voice and communication compared to the COVID CPAP group, most probably due to invasive ventilation. Psychological burden post critical illness was high in all 3 groups. More than 20% of all patients scored =10 on a PHQ-9 depression scale showing moderate to severe depression. More than 15% of all patients scored =10 on a GAD-7 showing moderately severe to severe anxiety. COVID ICU group had the highest incidence of post-traumatic stress disorder (PTSD). This may be linked to the higher level of delirium we saw in this group, as a result of change in practice, such as full PPE and absence of visiting during the pandemic. ICU patients presented with a significantly higher percentage of physiotherapy needs. This is likely because patients with the longest and most complex ICU admissions were selected for the clinic. Sleep likely goes under reported in these results as we only began questioning specifically about this later on in the clinic. Conclusion(s): This data goes some way in supporting current literature that the rehabilitation needs of COVID ICU patients equal that of ICU patients (Puthucheary et al 2021). It also shows the need to follow up patients who receive advanced respiratory support outside of the ICU environment, as their symptoms, and therefore rehabilitation needs are very similar to ICU patients at 2-3 months post discharge.

Characteristics of delirium and its association with sedation and in-hospital mortality in patients with COVID-19 on veno-venous extracorporeal membrane oxygenation.

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 (CAM-ICU) when patients scored-3 or above on the Richmond Agitation-Sedation Scale (RASS). Primary outcomes were delirium prevalence and duration in the proportion of days on VV-ECMO. Results: Of 47 patients (median age = 51), 6 were in a persistent coma and 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 (VV-ECMO day 9.5(5,14) vs. 8.5(5,21), p = 0.56) with similar total delirium days on VV-ECMO (9.5[3.3, 16.8] vs. 9.0[4.3, 28.3] days, p = 0.43). Non-survivors had numerically lower RASS scores on VV-ECMO days (-3.72[-4.42, -2.96] vs. -3.10[-3.91, -2.21], p = 0.06) and significantly prolonged 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), the proportions of days on VV-ECMO with a neuromuscular blocker (r = -0.59, p = 0.001), and with delirium-unassessable exams (r = -0.69, p < 0.001) but not with overall ECMO duration (r = 0.01, p = 0.96). The average daily dosage of delirium-related medications on ECMO days did not differ significantly. On an exploratory multivariable logistic regression, the proportion of delirium days was not associated with mortality. Conclusion: Longer duration of delirium was associated with lighter sedation and shorter paralysis, but it did not discern in-hospital mortality. Future studies should evaluate analgosedation and paralytic strategies to optimize delirium, sedation level, and outcomes.

Clinicians' Perceptions of a Modified Hospital Elder Life Program for Delirium Prevention During COVID-19.

The Hospital Elder Life Program (HELP) is a multicomponent delirium prevention program targeting delirium risk factors of cognitive impairment, vision and hearing impairment, malnutrition and dehydration, immobility, sleep deprivation, and medications. We created a modified and extended version of the program, HELP-ME, deployable under COVID-19 conditions, for example, patient isolation and restricted staff and volunteer roles. We explored perceptions of interdisciplinary clinicians who implemented HELP-ME to inform its development and testing. Qualitative descriptive study of HELP-ME among older adults on medical and surgical services during the COVID-19 pandemic. HELP-ME staff at 4 pilot sites across the United States who implemented HELP-ME.We held five 1-hour video focus groups (5-16 participants/group) to review specific intervention protocols and the overall program. We asked participants open-endedly about positive and challenging aspects of protocol implementation. Groups were recorded and transcribed. We used directed content analysis to analyze data. Participants identified general, technology-related, and protocol-specific positive and challenging aspects of the program. Overarching themes included the need for enhanced customization and standardization of protocols, need for increased volunteer staffing, digital access to family members, patient technological literacy and comfort, variation in the feasibility of remote delivery among intervention protocols, and preference for a hybrid program model. Participants offered related recommendations. Participants felt that HELP-ME was successfully implemented, with some modifications needed to address limitations of remote implementation. A hybrid model combining remote and in-person aspects was recommended as the preferred option.

Prevalence of the Risk Factors of Delirium Among COVID-19 Patients in the Intensive Care Unit at King Abdullah Medical City, Makkah: A Single-Center Study.

Background Coronavirus disease 2019 (COVID-19) patients admitted to the intensive care unit (ICU) are at a higher risk of developing delirium. In this study, we estimated the incidence of delirium and its risk factors in ICU patients with COVID-19 at King Abdullah Medical City (KAMC), Makkah, Saudi Arabia. Methodology We conducted a retrospective, analytical, cohort study of adult COVID-19 patients admitted to the ICU of KAMC between May 2020 and July 2021. Data were collected from electronic medical records. Results Of the 406 examined patients with COVID-19 aged >18 years, 55 developed delirium in the ICU setting. The incidence rate was 0.59% per 100 ICU days in these 55 patients; the mean age was 62.36 ± 17.9 years, and 65.5% were men. Binary logistic regression showed that age (p = 0.027), nationality (p = 0.045), presence of infectious diseases other than COVID-19 (p = 0.047), and ICU outcome (p = 0.013) were significant risk factors for developing delirium. The clinical presentation and prognosis of patients who developed delirium were assessed using the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, and the mean scores were 16.13 ± 7.96 and 5.25 ± 3.48, respectively. The mean length of ICU stay was 22.2 ± 33.3 days; 39 (70.9%) patients were discharged and 16 (29.1%) died. Conclusions Older age, nationality, infections, and ICU outcomes were risk factors for developing delirium in hospitalized COVID-19 patients at KAMC. Early detection of cognitive comorbidities and delirium in these patients is important.

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.

Incidence Rate and Factors Associated with Delirium and Subsyndromal Delirium in Patients with COVID-19 in an Intensive Care Unit.

BACKGROUND: Delirium subsyndrome (SSD) and delirium (DL) are known complications in the intensive care unit (ICU) and are associated with worse clinical outcomes. The aim of this study was to screen for SSD and DL in individuals with COVID-19 admitted to the ICU and to study the associated factors and clinical outcomes. METHOD: An observational, longitudinal study was conducted in the reference ICU for COVID-19. All admitted individuals with COVID-19 were screened for SSD and DL during their ICU stay using the Intensive Care Delirium Screening Checklist (ICDSC). Individuals with SSD and/or DL were compared to those without SSD and/or DL. RESULTS: Ninety-three patients were evaluated, of which 46.7% had SSD and/or DL. The incidence rate was 4.17 cases/100 person-days. Individuals with SSD and/or DL had higher severity of illness on admission to the ICU, as measured by the APACHE II score (median 16 versus 8 points, p < 0.001). SSD and/or DL were associated with longer ICU and hospital stays (median 19 versus 6 days, p < 0.001 and median 22 versus 7 days, p < 0.001, respectively). CONCLUSION: Individuals with SSD and/or DL had greater disease severity and longer ICU and hospital stays when compared to those without SSD and/or DL. This reinforces the importance of screening for consciousness disorders in the ICU.

Key elements of an evidence-based clinical psychology service within adult critical care.

The COVID-19 pandemic has generated renewed interest in the psychological rehabilitation needs of patients admitted to intensive care units. While the availability of embedded practitioner psychologists within adult critical care teams remains inconsistent, post numbers have increased in response to the clinical needs of the pandemic. As psychology services within adult critical care become more widely established, models for service provision will be required. We describe our experience of developing a model for the delivery of a clinical psychology service within critical care in a District General Hospital with specialist tertiary surgical and cancer services. The current paper describes a service design that is firmly rooted in psychological theory and the broader clinical health psychology evidence base. We hope that our learning will be helpful to others.

Risk factors for delirium among patients with advanced cancer in palliative care: a multicenter, patient-based registry cohort in South Korea

OBJECTIVE: Previous studies have comprehensively investigated the preva-lence and various potential risk factors for de-lirium among patients with advanced cancer ad-mitted to the acute palliative care unit (APCU). Our objective was to evaluate the comprehen-sive association between delirium and various risk factors among patients with advanced can-cer in an acute palliative care setting using a pa-tient-based multicenter registry cohort.PATIENTS AND METHODS: We performed a multicenter, patient-based registry cohort study collected in South Korea between January 1, 2019, and December 31, 2020. Delirium was identified using a medical record review based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.RESULTS: In total, 2,124 eligible patients with advanced cancer in the APCU met the inclu-sion criteria. There were 127 out of 2,124 pa-tients (prevalence, 6.0%;95% CI, 5.0 to 7.1) with delirium during admission. Delirium in patients with advanced cancer was associated with age >70 years (OR, 1.793;95% CI, 1.246 to 2.581), male sex (OR, 1.675;95% CI, 1.131 to 2.479), no chemotherapy during hospitalization (OR, 2.019;95% CI, 1.236 to 3.298), hearing impairment (OR, 3.566;95% CI, 1.176 to 10.810), underweight (OR, 1.826;95% CI, 1.067 to 3.124), current use of opioid medication (OR, 1.942;95% CI, 1.264 to 2.982), previous history of delirium (OR, 12.497;95% CI, 6.920 to 22.568), and mental illness (OR, 2.333;95% CI, 1.251 to 4.352).CONCLUSIONS: In a large-scale multicenter patient-based registry cohort, delirium was asso-ciated with old age, male sex, no chemotherapy during hospitalization, hearing impairment, un-derweight, current use of opioid medication, and a history of delirium and mental illness. Our find-ings suggest physicians should pay attention to delirium in patients with advanced cancer admit-ted to the APCU with the above risk factors.

Experimental and Clinical Evaluation of Mefloquine Effectiveness against the Infection Caused by Sars-Cov-2

The efficacy of mefloquine has not been studied in the in vivo experiments and clinical trials involving COVID-19 patients. The study was aimed to assess the effects of mefloquine on the SARS-CoV-2 accumulation in the lungs of infected animals and to study the efficacy and safety of mefloquine compared to hydroxychloroquine in patients with COVID-19. During the experiment, a total of 96 Syrian hamsters were infected with SARS-CoV-2. Accumulation of the virus in lungs was compared in the groups of animals treated with mefloquine and ribavirin and in the control group. During the clinical trial, the mefloquine and hydroxychloroquine safety and efficacy in patients with mild and moderate COVID-19 (172 individuals) was assessed based on the symptom changes over time and the computed tomography results. The experiment showed that the SARS-CoV-2 accumulation in the lungs of Syrian hamsters 6 days after infection and mefloquine treatment was 2.2 +/- 0.18 lg PFU/g, which was lower (p < 0.05) than in the control group (3.5 +/- 0.21 lg PFU/g) and ribavirin group (5.2 +/- 0.05 lg PFU/g). During the clinical trial, it was found that 50.0% of patients in the mefloquine group and 32.4% in the hydroxychloroquine group (p < 0.05) developed a mild disease, and the completely resolved respiratory failure was registered in 76.5% and 44.6%, respectively (p < 0.001). Adverse events were observed in 86.7 % and 77% of patients in the mefloquine and hydroxychloroquine groups, respectively (p > 0.05). Thus, during the experiment, mefloquine contributed to the faster virus titer reduction in the lungs. During the clinical trial, the mefloquine efficacy was non-inferiority or, based on a number of indicators, higher compared to hydroxychloroquine, with comparable safety.Copyright © Extreme Medicine.All right reserved.

COVID-19 psychosis versus psychosis due to cytotoxic lesion of the corpus callosum (CLOCC): A case report and review.

Background: Cytotoxic lesions of the corpus callosum syndrome (CLOCC) is an inflammatory disorder caused by various etiologies such as medications, malignancies, seizure, metabolic abnormalities, and infections, especially COVID-19. It presents on MRI as an area of restricted diffusion in the corpus callosum. We present a case of psychosis and CLOCC in a patient with mild active COVID-19 infection. Case: A 25-year-old male with a history of asthma and unclear past psychiatric history presented to the emergency room with shortness of breath, chest pain, and disorganized behavior. His-COVID-19 PCR was negative, and he was voluntarily admitted to psychiatry for management of unspecified psychosis. Overnight, he spiked a fever and was diaphoretic with headache and altered mental status. Repeat COVID-19 PCR at this time was positive and cycle threshold indicated infectivity. A brain MRI showed a new restricted diffusion within the midline of the splenium of the corpus callosum. Lumbar puncture was unremarkable. He continued to have flat affect and exhibit disorganized behavior with unspecified grandiosity, unclear auditory hallucinations, echopraxia, and poor attention and working memory. He was started on risperidone, with an MRI after 8 days showing complete resolution of the lesion in the corpus callosum and symptoms. Conclusion: This case discusses diagnostic difficulties and treatment options for a patient presenting with psychotic symptoms and disorganized behavior in the context of active COVID-19 infection and CLOCC and highlights differences between delirium, COVID-19 psychosis and neuropsychiatric symptoms of CLOCC. Future research directions are also discussed.

Differences in delirium presentation in non-intubated COVID-19 and non-COVID-19 patients in the ICU

Introduction: Delirium in intensive care unit (ICU) patients is a common disorder which is characterized by non-specific brain dysfuncion and is associated with increased mortality [1]. Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-COV-2 is associated with increased delirium rates through various mechanisms including hypoxaemia, circulation of inflammatory mediators and direct central nervous system damage [2]. Due to life-threatening respiratory manifestations in COVID-19 patients delirium is often underestimated. Aim of the study was to record the pharmacologic treatment of delirium in ICU patients treated with non-invasive ventilation and the differences in delirium treatment between COVID-19 and non-COVID-19 patients. Method(s): Consecutive patients with respiratory failure were retrospectively included. All patients were hospitalized in the ICU and noninvasive ventilation was applied. Patient characteristics, length of ICU stay and medication were recorded. Result(s): Totally 64 patients were included (33 patients with COVID- 19). Pharmacologic management of delirium included administration of remifentanyl, dexmedetomidine, propofol and combinations of the above. COVID-19 patients were younger (61 vs 70.4 years, p = 0.02), had longer ICU hospitalization (p < 0.001) and needed longer intravenous medication administration (p = 0.001). Additionally, the proportion of patients with COVID-19 treated with intravenous medication due to delirium was higher than non-COVID-19 patients (81.8% vs 48.4%, p = 0.008). COVID-19 seemed to have worse outcomes than non-COVID-19 patients and this difference tended to be statistically significant (p = 0.09). Conclusion(s): Delirium is quite common and requires aggressive treatment among COVID-19 patients, despite being younger than non- COVID-19 patients. Physicians should be vigilant to assess and manage delirium to improve the long-term outcomes of COVID-19 patients.

Pathogenesis of encephalopathy and delirium: neocortical neuronal membrane potential and action potential firing are changed by coronavirus-associated cytokines

Introduction: Encephalopathy and delirium are common following coronavirus infection [1], and the associated neuroinflammation often results in long-term behavioral and cognitive impairment. Neurovirulent cytokines (NVC) are strongly implicated in the pathogenesis of coronavirus encephalopathy [2]. We hypothesized that characterizing the abnormal signaling in NVC exposed neurons will enable us to identify targets to treat encephalopathy and prevent its downstream effects. Method(s): We incubated primary mouse neocortical cultures in NVC known to be increased in coronavirus encephalopathy (TNF-alpha, IL-1beta, IL-6, IL-12 and IL-15). Using whole-cell patch clamp methods, we tested how neuronal function was impacted by 22-28-h exposure to NVC. Result(s): We found that NVC depolarized the resting membrane potential (RMP), reduced the firing threshold of neocortical neurons, and increased baseline spontaneous action potential (AP) firing. NVC altered the sensitivity (or input-output properties) of single neurons to changes in their microenvironment. Specifically, decreasing external Ca2+ and Mg2+ from physiological to low (1.1-0.2 mM) levels increased evoked AP firing in control, but not following exposure to NVC. AP firing threshold and spontaneous firing rates returned to control levels 1 h after NVC wash-out. However, the RMP and attenuated sensitivity of evoked APs to changes in the microenvironment remained persistently abnormal suggesting two distinct mechanisms were at play. Interestingly, hyperpolarizing the RMP reversed this altered response. Conclusion(s): Sustained exposure to NVC reversibly depolarizes neocortical neuronal RMP, altering excitability and the ability of neurons to respond to microenvironment changes. By characterizing the pathogenesis of the underlying changes in neuronal function in our model of coronavirus encephalopathy we will identify intervenable drug targets.