Liver biomarkers for prognosis in COVID-19

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).Mortality attributable to COVID-19 remains considerably high, with case fatality rates as high as 8-11%. Early medical intervention in patients who are seriously and critically ill with COVID-19 reduces fatal outcomes. Thus, there is an urgent need to identify biomarkers that could help clinicians determine which patients with SARS-CoV-2 infection are at a higher risk of developing the most adverse outcomes, which include intensive care unit (ICU) admission, invasive ventilation, and death. In COVID-19 patients experiencing the most severe form of the disease, tests of liver function are frequently abnormal and liver enzymes are found to be elevated. For this reason, we examine the most promising liver biomarkers for COVID-19 prognosis in an effort to help clinicians predict the risk of ARDS, ICU admission, and death at hospital admission. In patients meeting hospitalization criteria for COVID-19, serum albumin < 36 g/L is an independent risk factor for ICU admission, with an AUC of 0.989, whereas lactate dehydrogenase (LDH) values > 365 U/L accurately predict death with an AUC of 0.943.The clinical scores COVID-GRAM and SOFA that include measures of liver function such as albumin, LDH, and total bilirubin are also good predictors of pneumonia development, ICU admission, and death, with AUC values ranging from 0.88 to 0.978.Thus, serum albumin and LDH, together with clinical risk scores such as COVID-GRAM and SOFA, are the most accurate biomarkers in the prognosis of COVID-19.Copyright © 2021 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.

Disseminated Mucormycosis in a patient on long term immunosuppression: Severe fungal infections as multi-system disorders

Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.

Rehabilitation needs after critical illness: Referral outcomes from a ICU follow up clinic in Northern Ireland

Introduction: In 2019/20 a total of 171,900 people were admitted to adult general intensive care units (ICU) across England, Wales and Northern Ireland, with a survival rate of 79.6% at hospital discharge.1 Patients who survive critical illness and admission to ICU often experience ICU-related long-term physical and non-physical impairments and disability following hospital discharge.2 National guidance advocates multidisciplinary team (MDT) follow up to identify and manage the unmet health needs of this patient population.3-4 The UK has seen an increase in the number of follow up services available in the last 7 years.2 The Covid-19 pandemic further highlighted the need to provide this service, locally resulting in the establishment of the Belfast Health and Social Care Trust (BHSCT) ICU follow up clinic in July 2020. The follow up clinic is offered to patients aged = 18 years, an ICU length of stay of = 4 days, who have been discharged from an inpatient setting within the last 12 weeks and do not receive follow up from any other established care pathway. The clinic consists of an ICU Nurse, Doctor, Clinical Psychologist and Physiotherapist. Patients are offered either a virtual, face-to-face or telephone appointment. Objective(s): To identify unmet rehabilitation needs and onward referral requirements of patients presenting at an ICU follow-up clinic in Northern Ireland. Method(s): Data was gathered retrospectively using an excel database detailing patient demographics, appointment details and onward referrals generated from the clinic. Data was analysed for a set time period between the 01/12/2021 - 09/02/2022. The type of referral and the profession responsible were captured. Result(s): During the time period eight post ICU follow up clinics were completed. A total of 36 patient's attended (14 male and 22 female). Six appointments were attended virtually via MS Teams, 12 via telephone and 18 face-to-face. Twenty-three (64%) of the patients required at least one onward health referral. A total of 61 onward health referrals were generated from this population. Table 1 details the number of onwards referrals by speciality. Conclusion(s): Approximately 64% of patients who attended the post ICU follow up clinic, during a 10 week period, demonstrated unmet rehabilitation needs resulting in onward health referrals. This data supports the need for a post ICU follow up clinic at BHSCT to identify ongoing need, ensure transition of care to relevant services and optimise patient's physical and psychological outcomes. One limitation of this study is that not all recommended allied health professionals are commissioned for the clinic which may impact on the health needs identified. Future work should consider the impact of this and discussions regarding the need for a commissioned post ICU follow up clinic which is truly MDT for this patient population should be considered.

Relationship between neurological manifestations and severity of COVID-19. San Vicente de Paul Hospital. Ecuador 2021.

Introduction: SARS-CoV-2 mainly affects the respiratory system, but the damage caused by this virus also extends to other systems, including the nervous system, and the mechanisms of neurological infection can be direct or indirect. Objective(s): To determine the relationship between neurological manifestations and disease severity in symptomatic COVID-19 positive patients at San Vicente de Paul Hospital in 2021. Material(s) and Method(s): A cross-sectional observational study was conducted using medical records of patients hospitalized with COVID-19 and neurological manifestations, which were classified into manifestations of the central nervous system and manifestations of the peripheral nervous system. Result(s): The results show that 74,1 % of patients presented neurological manifestations;the highest percentage was concentrated in patients who developed severe disease (15 [60 %], CNS;91 [77,1 %], PNS;125 [65,4 %], CNS and PNS). The joint presence of central and peripheral neurological manifestations was significantly associated with critical COVID-19 (P value= 0,011;OR: 2,005). The mortality rate reached 2,69 %. Conclusion(s): Neurological manifestations in hospitalized COVID-19 patients are very common, and critical COVID-19 is more likely to have neurological manifestations.Copyright © 2022 Universidad de Ciencias Medicas de La Hab. All rights reserved.

Extracorporeal cytokine hemadsorption in severe COVID-19 respiratory failure

Background: At least 20% of coronavirus disease 2019 (COVID-19) patients develop acute hypoxemic respiratory failure requiring admission to intensive care unit in 5-32% of the cases. Hyper-inflammatory activation characterized by immune cell infiltration and elevated levels of cytokines was reported as the main mechanism leading to critical illness and severe acute respiratory distress syndrome (ARDS). CytoSorb is currently used for all the conditions where elevated levels of cytokines are present. Along with the beneficial effect on systemic inflammation, CytoSorb can be easily integrated with all extracorporeal circulation systems. Case Presentation: Here, we present the laboratory and clinical outcomes of 11 patients with microbiological confirmed SARS-CoV-2 infection. These patients were treated with CytoSorb to remove the excess of cytokine. All patients were male, overweight and only 3 (27%) were over 70 years old. Median age was 62 years and median body mass index was 28. Best supportive care was provided according to hospital guidelines of that moment and included antibiotic therapy, antiretroviral therapy and protective ventilation. Result(s): Cytokines levels were evaluated before and after treatment. A significant reduction of IL-6, IL-8, IL-10 and IL-1beta was observed. A significant drop of C-reactive protein (CRP) median levels was observed starting from 48 hours after treatment start levels. The decrease in the inflammatory status was associated with a progressive improvement in the respiratory function, with a significant increase in P/F from the first day after the end of the therapy. A similar trend was observed for procalcitonin. Conclusion(s): CytoSorb therapy proved to be safe in COVID-19 patients. A clinical improvement was observed in most of the treated patients despite the severity of the disease. In this study CytoSorb was used empirically for 24- 48 hours based on previous experience in septic shock. The persistence of significant levels of IL-6 and CRP after CytoSorb treatment may suggest that a prolonged treatment can improve the efficacy in controlling COVID-19 hyperinflammatory status.

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.

ICU follow-up clinic provides the opportunity to recognise and address symptoms post critical illness, which may otherwise have been missed

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 [NICE 2009]. Prior to 2020 University Hospitals Bristol and Weston 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. Objective(s): To provide a service that supports and empowers patients with their recovery from critical illness. Improving quality of life, speed of recovery and reducing longer term health care needs. Method(s): Referral criteria for the clinic included COVID-19 patients who received advanced respiratory support within intensive care and the high dependence unit. 8 weeks post discharge patients had a telephone appointment where ongoing symptoms could be identified. Advice around recovery, signposting to resources and onward referrals to appropriate specialities were provided. At 10 weeks post discharge patients had lung function tests and a chest X-ray which were reviewed by respiratory consultants. Based on the combination of these assessments, patients would be discharged or referred into the multidisciplinary team (MDT) follow-up clinic. The face to face clinic consisted of appointments with an intensivist, clinical psychologist, physiotherapist, and occupational therapist. Where needed patients would also be seen by a speech and language therapist or dietitian. Patients were seen only once in follow up clinic but again would be referred onto appropriate services within trust or the community, including but not exclusively community therapy services, secondary care services, SALT, dietetic or psychology clinics. Result(s): One of the key outcomes was the need for 147 onward referrals (an average of 1.13 referrals per patient). This included, 31 referrals to musculoskeletal physiotherapy outpatients for problems originating or made worse by their admission. 20 referrals to secondary care, including cardiology and ENT. 16 referrals to community occupational therapy, for provision of equipment, home adaptations and support in accessing the community. Subjectively, patient feedback was excellent. When asked what they felt was the most valuable thing they had taken from the clinic they reported: "Reassurance";"To know I'm not alone, others feel like this";"They listened to me and gave advice";"The ability to ask anything I wanted and the obvious kindness and support from all the clinicians I saw". Conclusion(s): Onward referral rates made by the follow-up clinic highlight the many issues faced by patients following discharge from ICU and hospital. With timely recognition and management, we can prevent a majority of these symptoms manifesting into chronic problems. This has the potential to lower the long-term burden on health care and improve quality of life for patients in both the short and long term. Without the follow-up clinic, these issues may have been missed or delayed. This reinforces the importance of the follow-up clinic and the need for ongoing investment.

Can eye movement desensitisation and reprocessing improve psychological recovery following COVID-19 related critical illness? the CovEMERALD feasibility trial

Introduction: Over 200,000 patients survive an intensive care admission each year in the United Kingdom (UK). For patients, survival is frequently beset by a range of chronic disabilities. Approximately 50% must navigate an often complex convalescence, while suffering serious and persistent symptoms of post-traumatic stress disorder (PTSD), anxiety and/or depression.1 Eye-movement desensitisation and reprocessing (EMDR) is a trauma-focussed psychological therapy, recommended for treating PTSD by the International Society for Traumatic Stress Studies2 and NICE.3 However, EMDR has never been systematically investigated for patient benefit following intensive care admission. Objective(s): CovEMERALD4 evaluated the feasibility of delivering a randomised controlled trial (RCT), testing the effect of EMDR on the psychological health of intensive care survivors, following COVID-19 related critical illness. We also provide preliminary evidence of the effect on clinically relevant outcomes. Findings will inform the design of a subsequent fully-powered RCT. Method(s): This feasibility RCT was conducted at a single-centre, teaching hospital in the UK (University Hospital Southampton). Patients were eligible if they were admitted to intensive care for over 24-hours with confirmed COVID-19, were above 18 years of age, were recruited within 3-months of hospital discharge, and had no cognitive impairment or pre-existing psychotic diagnosis. Participants were randomised (1:1) to receive either up to 8 sessions of remotely-delivered EMDR (Recent traumatic events protocol) or standard care alone as the control group (CG). Psychometric evaluation was undertaken at Baseline and 6-months after hospital discharge. Result(s): Seventy-five consecutive patients were screened at hospital discharge, from October 2020 to April 2021. 51 eligible patients approached. 26 (51%) provided consent. Reasons for declining participation were;no psychological distress (n=16), no internet access (n=7) and being physically unready (n=2). Demographic variables were balanced between groups. Of the 13 patients randomised to EMDR, one withdrew prior to intervention: the remaining attended all sessions recommended by the psychological therapists (mean of 3-4 sessions per patient), giving an overall adherence of 93%. One patient from each group declined the 6-month follow-up evaluation, so trial completion was possible in 23 of 26 (88%) participants. No reasons for trial withdrawal were given. There were no attributable adverse events. Mean change in PTSD score (PTSD Checklist-Civilian) from Baseline to 6-months, was -8 (SD=10.49) in the EMDR group vs. +0.75 (SD=15.17) in CG (p=0.126). Mean change in anxiety (Hospital Anxiety and Depression Scale-Anxiety) was -0.45 (SD=2.3) following EMDR vs. -0.83 (SD=4.0) in the CG (p=0.787), and median change in depression (HADS-D) was -2(IQR:-3.0,1.0) following EMDR vs. +1(IQR-1.5,2.0) in the CG (p=0.263). Figure 1. Box-plot of change in PTSD symptoms (PCL-C) from baseline to 6-months post-hospital discharge for control group and EMDR intervention group. Conclusion(s): EMDR can improve psychological recovery following an intensive care admission for COVID-19, and appeared feasible and safe. Although not powered to determine clinical effectiveness, this single-centre feasibility study returned a positive signal, in reducing PTSD and depressive symptoms. A full results manuscript will be submitted prior to congress. CovEMERALD has supported a successful NIHR doctoral fellowship application, during which protocol refinements will be tested, within existing, and recommended rehabilitation pathways. Trial activity and progression will be consistent with the Medical Research Council framework for developing and evaluating complex healthcare interventions.5.

Intensive Care Society State of the Art (SOA) 2022 Abstracts

The proceedings contain 117 papers. The topics discussed include: informing local policy through an audit of the assessment, management and outcomes of intermediate and high-risk patients with pulmonary embolism;an initial exploration into the use of a novel virtual reality system to aid rehabilitation in intensive care;surprising chest radiograph- air in mediastinum;exploring tissue donation as part of end-of-life wishes- a duty of care following death on ICU?;the impact of deprivation on respiratory support unit outcomes in COVID-19 patients, and highlights from wave 2 data in Portsmouth;survey of attitudes towards end of life care as a tool in identifying areas for improvement;a quality improvement project regarding family communication within critical care;sleep promotion in a busy inner city high dependency unit;findings from a regional survey of critical care nursing staff focusing on retention and factors that influence wellbeing;and tracking functional recovery post critical illness.

A Successful Treatment of a Critically Patient with SARS-CoV2

Background: The role of inflammatory cytokines is known in the pathogenesis of organ damage and is also confirmed in the context of COVID-19 disease. The modulation of the cytokine storm seems to determine endothelial protection, which can translate into a reduction of the "capillary leak syndrome", and, consequently, in a better control of the formation of edema and pulmonary infiltrates. CytoSorb stands in this context as a cartridge capable of adsorbing cytokines and allowing a better clinical course. Case Report: A 69 years-old woman with a history of arterial hypertension, diabetes mellitus and CKD, was admitted to ICU for SARS Cov 2 related critical illness staged with chest CT, blood gas analysis and PCR. At the admission, the patient presented with ubiquitous interstitial pneumonia, PaO2 60 mmHg with 90% Airvo2 and PCR 36.67. Therefore, in order to remove inflammatory cytokines, the patient underwent hemoperfusion treatment with the CytoSorb adsorbent cartridge. Method(s): The protocol used is approved by the FDA for the treatment of covid patients and consists of the use of 4 cartridges 12h, 12h, 24h, 24h with measurement for each cycle of PCR, PaO2 and chest CT control. Result(s): During the hemoperfusion whit CytoSorb, respiratory failure improved until the patient was discharged from the ICU on the tenth day, with oxygen support via simple facial mask. Below the progressive values of the PCR, PaO2 and the chest CT control on the twelfth day. Conclusion(s): The hemoperfusion treatment with the CytoSorb adsorbent cartridge proved to be a valid adjuvant therapy in determining a better clinical course both in terms of the need for invasive mechanical ventilation and survival.

Chest physiotherapy techniques administered by certified specialists to hospitalized patients with COVID-19 in Brazil: A look towards future practice.

BACKGROUND: Chest physiotherapy for hospitalized patients with COVID-19 has been poorly reported. Although recommendations were published to guide physiotherapists, practice might have differed depending on education and training. OBJECTIVE: To analyze the differences in chest physiotherapy applied for hospitalized patients with COVID-19 between certified specialists and non-certified specialists. METHODS: An online questionnaire survey was developed for physiotherapists involved in the management of hospitalized patients with COVID-19. The questionnaire inquired about professional information and characteristics of physiotherapy practice. RESULTS: There were 485 respondents, yielding a completion rate of 76%. Of these, 61 were certified specialists and 424 non-certified specialists. The certified specialists were older, had more years of professional experience, were more qualified, and had better job conditions. For mechanically ventilated patients, the certified specialists used the ventilator hyperinflation maneuver more frequently (50.4% vs 35.1%, p = 0.005), and the hard/brief expiratory rib cage compression (ERCC) (26.9% vs 48.3%, p = 0.016), soft/long ERCC (25.2% vs 39.1%, p = 0.047), and manual chest compression-decompression (MCCD) maneuver (22.4% vs 35.6%, p = 0.001) less often. For spontaneously breathing patients, the certified specialists used the active cycle of breathing technique (30.8% vs 67.1%, p<0.001), autogenic drainage (7.7% vs 20.7%, p = 0.017), and MCCD maneuver (23.1% vs 41.4%, p = 0.018) less frequently. CONCLUSIONS: Certified specialists with higher levels of expertise seem to prefer the use of chest physiotherapy techniques that are applied with the mechanical ventilator over manual techniques. Furthermore, they use techniques that could potentially increase the work of breathing less frequently, mitigating the risk of exacerbating respiratory conditions in patients with COVID-19.

A Pathology-based Case Series of Influenza- and COVID-19-associated Pulmonary Aspergillosis: The Proof Is in the Tissue.

RATIONALE: Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe COVID-19, similarly to influenza; yet the clinical invasiveness is more debated. OBJECTIVES: We investigated the invasive nature of pulmonary aspergillosis in histology specimens of influenza and COVID-19 intensive care unit (ICU) fatalities in a tertiary care center. METHODS: In this monocentric, descriptive, retrospective case series we included adult ICU patients with PCR-proven influenza/COVID-19 respiratory failure that underwent postmortem examination and/or tracheobronchial biopsy during ICU admission from September 2009 until June 2021. Diagnosis of probable/proven viral-associated pulmonary aspergillosis (VAPA) was made based on the ICM-IAPA and ECMM/ISHAM-CAPA consensus criteria. All respiratory tissues were independently reviewed by two experienced pathologists. MEASUREMENTS AND MAIN RESULTS: In the 44 patients of the autopsy-verified cohort, 6 proven influenza-associated and 6 proven COVID-19-associated pulmonary aspergillosis diagnoses were identified. Fungal disease was identified as missed-diagnosis upon autopsy in 8% of proven cases (n=1/12), yet most frequently found as confirmation of probable antemortem diagnosis (n=11/21, 52%) despite receiving antifungal treatment. Bronchoalveolar lavage galactomannan testing showed highest sensitivity for VAPA diagnosis. Among both viral entities, an impeded fungal growth was the predominant histologic pattern of pulmonary aspergillosis. Fungal tracheobronchitis was histologically indistinguishable in influenza (n=3) and COVID-19 (n=3) cases, yet macroscopically more extensive at bronchoscopy in influenza setting. CONCLUSIONS: Proven invasive pulmonary aspergillosis diagnosis was found regularly and with a similar histological pattern in influenza and in COVID-19 ICU case-fatalities. Our findings highlight an important need for VAPA awareness with an emphasis on mycological bronchoscopic work-up. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

COVID-19-Induced Myopathy and Diaphragmatic Weakness: A Case Report.

Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that can induce myopathy, which can evolve into potentially life-threatening muscle weakness, including diaphragmatic paralysis. We present a case report of a 57-year-old female treated in the medical ICU for acute respiratory distress syndrome (ARDS) triggered by active COVID-19 infection, who subsequently developed worsening respiratory weakness from underlying COVID-19 myopathy manifesting as respiratory muscle weakness. Our patient's muscle biopsy highlights the development of muscle atrophy without evidence of inflammatory myopathy, making the presence of pre-existing autoimmune myopathy unlikely. While literature cites different biochemical etiologies for the development of myopathy, the exact mechanism behind this phenomenon is not yet defined.

In critically ill adult patients with COVID-19, lower energy and higher protein intake are associated with fewer mechanical ventilation and antibiotic days but not with ICU length of stay.

BACKGROUND: Coronavirus disease 2019 (COVID-19) nutrition management guidelines recommend hypocaloric, high-protein feeding in the acute phase of critical illness. This study aimed to determine, among critically ill adults with COVID-19, whether nutrition support affects outcomes in nonobese patients when providing a mean energy intake of ≥20 kcal/kg/day vs <20 kcal/kg/day and protein intake of ≥1.2 g/kg/day vs <1.2 g/kg/day, using actual body weight, and in patients with obesity when providing ≥20 kcal/kg/day vs <20 kcal/kg/day and a protein intake of ≥2 g/kg/day vs <2 g/kg/day using ideal body weight. METHODS: This retrospective study included adults with COVID-19 on mechanical ventilation (MV) admitted to the intensive care unit (ICU) from 2020 to 2021. Clinical and nutrition parameters were recorded the first 14 days of ICU stay. RESULTS: One hundred four patients were included: 79 (75.96%) were male and had a median age of 51 years and body mass index of 29.65 kg/m2 . ICU length of stay (LOS) was not affected by nutrition intake, but patients receiving <20 kcal/kg/day had fewer MV days (P = 0.029). In a subgroup analysis, MV days were lower in the nonobese group receiving <20 kcal/kg/day (P = 0.012). In the obese group, those receiving higher protein intake had fewer antibiotic days (P = 0.013). CONCLUSION: In critically ill patients with COVID-19, lower energy and higher protein intake were respectively associated with fewer MV days and, in patients with obesity, fewer antibiotic days, but they had no effect on ICU LOS.

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.

Recovery from Covid-19 critical illness: A secondary analysis of the ISARIC4C CCP-UK cohort study and the RECOVER trial.

Background: We aimed to compare the prevalence and severity of fatigue in survivors of Covid-19 versus non-Covid-19 critical illness, and to explore potential associations between baseline characteristics and worse recovery. Methods: We conducted a secondary analysis of two prospectively collected datasets. The population included was 92 patients who received invasive mechanical ventilation (IMV) with Covid-19, and 240 patients who received IMV with non-Covid-19 illness before the pandemic. Follow-up data were collected post-hospital discharge using self-reported questionnaires. The main outcome measures were self-reported fatigue severity and the prevalence of severe fatigue (severity >7/10) 3 and 12-months post-hospital discharge. Results: Covid-19 IMV-patients were significantly younger with less prior comorbidity, and more males, than pre-pandemic IMV-patients. At 3-months, the prevalence (38.9% [7/18] vs. 27.1% [51/188]) and severity (median 5.5/10 vs 5.0/10) of fatigue were similar between the Covid-19 and pre-pandemic populations, respectively. At 6-months, the prevalence (10.3% [3/29] vs. 32.5% [54/166]) and severity (median 2.0/10 vs. 5.7/10) of fatigue were less in the Covid-19 cohort. In the total sample of IMV-patients included (i.e. all Covid-19 and pre-pandemic patients), having Covid-19 was significantly associated with less severe fatigue (severity <7/10) after adjusting for age, sex and prior comorbidity (adjusted OR 0.35 (95%CI 0.15-0.76, p=0.01). Conclusion: Fatigue may be less severe after Covid-19 than after other critical illness.

Characteristics of Critically Ill COVID-19 Patients in Busan, Republic of Korea.

BACKGROUND: This study aimed to improve the clinical course of patients through rapid response by analyzing the characteristics of critically ill patients with confirmed coronavirus disease 2019 (COVID-19) in Busan between December 1, 2020, and December 31, 2021. METHODS: We divided patients diagnosed with COVID-19 into mild-to-moderate and critical groups based on their clinical severity. The critically ill patients were further sub-divided into delta and delta variant non-epidemic group. RESULTS: The following factors were significantly more frequent in critically ill patients than in patients with mild-tomoderate symptoms: male sex, age ≥60 years, symptoms at the time of diagnosis, and those with underlying diseases. The following factors were significantly more common in the non-delta variant epidemic group than in the delta variant epidemic group in critically ill patients: male sex, age ≥60 years, underlying diseases, and not being vaccinated. In the delta variant epidemic group, the duration between confirmation of disease and its progression to critically ill status was significantly shorter than that in the non-delta variant epidemic group. CONCLUSION: COVID-19 is characterized by the emergence of new variants and repeated epidemics. Therefore, it is necessary to analyze the characteristics of critically ill patients to efficiently distribute and manage medical resources.

Post-COVID-19 syndrome mimicking cholangiocarcinoma: A case report.

Key Clinical Message: The differential diagnosis of post-COVID-19 syndrome is important in patients with symptoms of biliary obstruction. This patient had severe COVID-19 who underwent ERCP and mimicked cholangiocarcinoma. Abstract: Patients with severe coronavirus disease 2019 (COVID-19) manifest liver injuries with pathological changes because of lowered blood oxygen saturation, cardiac malfunction, hepatotoxic drugs during treatment, and cellular injury. This paper reports a patient with a history of severe COVID-19 who mimics cholangiocarcinoma after undergoing endoscopic retrograde cholangiopancreatography (ERCP). It was shown that differential diagnosis of post-COVID-19 syndrome is greatly important mostly in patients with symptoms of biliary obstruction.

Critical Illness-Related Corticosteroid Insufficiency (CIRCI) Among Patients with COVID-19 at a Tertiary Hospital: Clinical Characteristics and Outcomes.

Objectives: Among critically ill patients, there is usually impairment of the hypothalamic-pituitary-adrenal axis, leading to a condition known as critical illness-related corticosteroid insufficiency (CIRCI). This investigation aims to determine the incidence of and characterize CIRCI among patients with COVID-19 as well as to analyze the outcomes of these critically ill patients. Methodology: This is a single-center, retrospective cohort study that investigated the occurrence of CIRCI among critically ill patients infected with COVID-19. Results: In this cohort, there were 145 COVID-19-positive patients with refractory shock, which reflects that 22.94% of the COVID-19 admissions have probable CIRCI.Patients who were given corticosteroids were found to have statistically significant longer median days on a ventilator (p=0.001). However, those on the corticosteroid arm were at higher risk of morbidity and mortality and a greater proportion had organ dysfunction. Multivariable logistic regression analysis revealed that SOFA score was a significant predictor of mortality in CIRCI (p=0.013). Conclusion: CIRCI has a unique presentation among patients with COVID-19 because of the presence of a high level of inflammation in this life-threatening infection. It is possibly a harbinger of a markedly increased risk of mortality in these patients.

Impact of the First Year of the COVID-19 Pandemic on Pediatric Emergency Department Attendance in a Tertiary Center in South Italy: An Interrupted Time-Series Analysis.

BACKGROUND: The evidence shows a reduction in pediatric emergency department (PED) flows during the early stages of the COVID-19 pandemic. Using interrupted time-series analysis, we evaluated the impact of different stages of the pandemic response on overall and cause-specific PED attendance at a tertiary hospital in south Italy. Our methods included evaluations of total visits, hospitalizations, accesses for critical illnesses and four etiological categories (transmissible and non-transmissible infectious diseases, trauma and mental-health) during March-December 2020, which were compared with analogous intervals from 2016 to 2019; the pandemic period was divided into three segments: the "first lockdown" (FL, 9 March-3 May), the "post-lockdown" (PL, 4 May-6 November) and the "second lockdown" (SL, 7 November-31 December). Our results showed that attendance dropped by a mean of 50.09% during the pandemic stages, while hospitalizations increased. Critical illnesses decreased during FL (incidence rate ratio -IRR- 0.37, 95% CI 0.13, 0.88) e SL (IRR 0.09, 95% CI 0.01, 0.74) and transmissible disease related visits reduced more markedly and persistently (FL: IRR 0.18, 95% CI 0.14, 0.24; PL: IRR 0.20, 95% CI 0.13, 0.31, SL: IRR 0.17, 95% CI 0.10, 0.29). Non-infectious diseases returned to pre-COVID-19 pandemic levels by PL. We concluded that that the results highlight the specific effect of the late 2020 containment measures on transmissible infectious diseases and their burden on pediatric emergency resources. This evidence can inform resource allocation and interventions to mitigate the impact of infectious diseases on pediatric populations and the health-care system.