A COVID-19-Related Retinopathy Case Report.

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 has been declared a worldwide pandemic by the WHO. Within various multi-organ involvements, several ocular manifestations have been described. We report the case of a patient diagnosed with COVID-19 who presented with a progressive increase of bilateral cotton wool spots over a 1-week period, despite quick and complete recovery of systemic signs of the disease and no ocular symptoms. We followed the evolution of such lesions over a 3-month period. Here, we underline the importance of retinal screening even if no ocular symptom is reported. Furthermore, we demonstrate the essential role of fundus examination as a reflection of systemic vascular changes.

A high-risk gut microbiota configuration associates with fatal hyperinflammatory immune and metabolic responses to SARS-CoV-2.

Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic and immune responses that limit viral spread and promote recovery of damaged systems. However, the role of the gut microbiota in regulating these responses has not been thoroughly investigated. In order to identify mechanisms underpinning microbiota interactions with host immune and metabolic systems that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalized COVID-19 patients and compared those with the most severe outcome (i.e. death, n = 41) to those with severe non-fatal disease (n = 89), or mild/moderate disease (n = 42), that recovered. A distinct subset of 8 cytokines (e.g. TSLP) and 140 metabolites (e.g. quinolinate) in sera identified those with a fatal outcome to infection. In addition, elevated levels of multiple pathobionts and lower levels of protective or anti-inflammatory microbes were observed in the fecal microbiome of those with the poorest clinical outcomes. Weighted gene correlation network analysis (WGCNA) identified modules that associated severity-associated cytokines with tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids with multiple pathobionts, such as Enterococcus. In contrast, less severe clinical outcomes are associated with clusters of anti-inflammatory microbes such as Bifidobacterium or Ruminococcus, short chain fatty acids (SCFAs) and IL-17A. Our study uncovered distinct mechanistic modules that link host and microbiome processes with fatal outcomes to SARS-CoV-2 infection. These features may be useful to identify at risk individuals, but also highlight a role for the microbiome in modifying hyperinflammatory responses to SARS-CoV-2 and other infectious agents.

Limitation of life-sustaining therapies in critically ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study.

BACKGROUND: Limitations of life-sustaining therapies (LST) practices are frequent and vary among intensive care units (ICUs). However, scarce data were available during the COVID-19 pandemic when ICUs were under intense pressure. We aimed to investigate the prevalence, cumulative incidence, timing, modalities, and factors associated with LST decisions in critically ill COVID-19 patients. METHODS: We did an ancillary analysis of the European multicentre COVID-ICU study, which collected data from 163 ICUs in France, Belgium and Switzerland. ICU load, a parameter reflecting stress on ICU capacities, was calculated at the patient level using daily ICU bed occupancy data from official country epidemiological reports. Mixed effects logistic regression was used to assess the association of variables with LST limitation decisions. RESULTS: Among 4671 severe COVID-19 patients admitted from February 25 to May 4, 2020, the prevalence of in-ICU LST limitations was 14.5%, with a nearly six-fold variability between centres. Overall 28-day cumulative incidence of LST limitations was 12.4%, which occurred at a median of 8 days (3-21). Median ICU load at the patient level was 126%. Age, clinical frailty scale score, and respiratory severity were associated with LST limitations, while ICU load was not. In-ICU death occurred in 74% and 95% of patients, respectively, after LST withholding and withdrawal, while median survival time was 3 days (1-11) after LST limitations. CONCLUSIONS: In this study, LST limitations frequently preceded death, with a major impact on time of death. In contrast to ICU load, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations.

Brain functional connectivity alterations associated with neuropsychological performance 6-9 months following SARS-CoV-2 infection.

Neuropsychological deficits and brain damage following SARS-CoV-2 infection are not well understood. Then, 116 patients, with either severe, moderate, or mild disease in the acute phase underwent neuropsychological and olfactory tests, as well as completed psychiatric and respiratory questionnaires at 223 ± 42 days postinfection. Additionally, a subgroup of 50 patients underwent functional magnetic resonance imaging. Patients in the severe group displayed poorer verbal episodic memory performances, and moderate patients had reduced mental flexibility. Neuroimaging revealed patterns of hypofunctional and hyperfunctional connectivities in severe patients, while only hyperconnectivity patterns were observed for moderate. The default mode, somatosensory, dorsal attention, subcortical, and cerebellar networks were implicated. Partial least squares correlations analysis confirmed specific association between memory, executive functions performances and brain functional connectivity. The severity of the infection in the acute phase is a predictor of neuropsychological performance 6-9 months following SARS-CoV-2 infection. SARS-CoV-2 infection causes long-term memory and executive dysfunctions, related to large-scale functional brain connectivity alterations.

Unsupervised clustering reveals phenotypes of AKI in ICU COVID-19 patients.

Background: Acute Kidney Injury (AKI) is a very frequent condition, occurring in about one in three patients admitted to an intensive care unit (ICU). AKI is a syndrome defined as a sudden decrease in glomerular filtration rate. However, this unified definition does not reflect the various mechanisms involved in AKI pathophysiology, each with its own characteristics and sensitivity to therapy. In this study, we aimed at developing an innovative machine learning based method able to subphenotype AKI according to its pattern of risk factors. Methods: We adopted a three-step pipeline of analyses. First, we looked for factors associated with AKI using a generalized additive model. Second, we calculated the importance of each identified AKI related factor in the estimated AKI risk to find the main risk factor for AKI, at the single patient level. Lastly, we clusterized AKI patients according to their profile of risk factors and compared the clinical characteristics and outcome of every cluster. We applied this method to a cohort of severe COVID-19 patients hospitalized in the ICU of the Geneva University Hospitals. Results: Among the 248 patients analyzed, we found 7 factors associated with AKI development. Using the individual expression of these factors, we identified three groups of AKI patients, based on the use of Lopinavir/Ritonavir, baseline eGFR, use of dexamethasone and AKI severity. The three clusters expressed distinct characteristics in terms of AKI severity and recovery, metabolic patterns and hospital mortality. Conclusion: We propose here a new method to phenotype AKI patients according to their most important individual risk factors for AKI development. When applied to an ICU cohort of COVID-19 patients, we were able to differentiate three groups of patients. Each expressed specific AKI characteristics and outcomes, which probably reflect a distinct pathophysiology.

Retinal Manifestations in Patients with COVID-19: A Prospective Cohort Study.

The recent outbreak of the Coronavirus SARS-CoV-2 has been declared a worldwide pandemic. Within various multi-organ involvement, several ocular manifestations have been described, such as conjunctivitis and retinopathy. The prevalence and severity of retinal lesions and their relation to the severity of the systemic disease are unknown. We performed a prospective, observational study on 172 consecutively hospitalized patients with acute confirmed COVID-19 infection. All patients underwent screening widefield fundus photography at the time of hospital admission. Despite no ocular or vision-related symptoms, we found cotton wool spots (CWS) and/or hemorrhages in 19/172 patients (11%). Diabetes history, overweight, and elevated C-reactive protein were more frequently observed among patients with retinal abnormalities, while a history of systemic hypertension was more frequently observed among patients without retinal findings. At a 3-month follow-up visit, CWS had subsided in all patients.

Unsupervised clustering reveals phenotypes of AKI in ICU COVID-19 patients

Background Acute Kidney Injury (AKI) is a very frequent condition, occurring in about one in three patients admitted to an intensive care unit (ICU). AKI is a syndrome defined as a sudden decrease in glomerular filtration rate. However, this unified definition does not reflect the various mechanisms involved in AKI pathophysiology, each with its own characteristics and sensitivity to therapy. In this study, we aimed at developing an innovative machine learning based method able to subphenotype AKI according to its pattern of risk factors. Methods We adopted a three-step pipeline of analyses. First, we looked for factors associated with AKI using a generalized additive model. Second, we calculated the importance of each identified AKI related factor in the estimated AKI risk to find the main risk factor for AKI, at the single patient level. Lastly, we clusterized AKI patients according to their profile of risk factors and compared the clinical characteristics and outcome of every cluster. We applied this method to a cohort of severe COVID-19 patients hospitalized in the ICU of the Geneva University Hospitals. Results Among the 248 patients analyzed, we found 7 factors associated with AKI development. Using the individual expression of these factors, we identified three groups of AKI patients, based on the use of Lopinavir/Ritonavir, baseline eGFR, use of dexamethasone and AKI severity. The three clusters expressed distinct characteristics in terms of AKI severity and recovery, metabolic patterns and hospital mortality. Conclusion We propose here a new method to phenotype AKI patients according to their most important individual risk factors for AKI development. When applied to an ICU cohort of COVID-19 patients, we were able to differentiate three groups of patients. Each expressed specific AKI characteristics and outcomes, which probably reflect a distinct pathophysiology.

How Can We Help Healthcare Workers during a Catastrophic Event Such as the COVID-19 Pandemic?

Healthcare workers (HCWs) have significantly suffered during the COVID-19 pandemic, reporting a high prevalence of anxiety, depression and post-traumatic stress disorder (PTSD). We investigated with this survey whether HCWs benefitted from supportive measures put in place by hospitals and how these measures were perceived. This cross-sectional survey, which was conducted during the first wave of COVID-19 at the Geneva University Hospitals, Switzerland, between May and July 2021, collected information on the use and perception of practical and mental health support measures provided by the hospital. In total, 3461 HCWs participated in the study. Regarding the practical support measures, 2896 (84%) participants found them useful, and 2650 (76%) used them. Regarding the mental health support measures, 3149 (90%) participants found useful to have the possibility of attending hypnosis sessions, 3163 (91%) to have a psychologist within hospital units, 3202 (93%) to have a medical nursing psychiatric permanence available seven days a week, and 3171 (92%) to have a hotline available seven days a week. In total, 436 (13%) HCWs used at least one of the available mental health support measures. During the COVID-19 pandemic, the support measures were valued by HCWs. Given the high prevalence of psychiatric issues among HCWs, these measures seem necessary and are likely to have alleviated the suffering of HCWs.

A COVID-19-Related Retinopathy Case Report

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 has been declared a worldwide pandemic by the WHO. Within various multi-organ involvements, several ocular manifestations have been described. We report the case of a patient diagnosed with COVID-19 who presented with a progressive increase of bilateral cotton wool spots over a 1-week period, despite quick and complete recovery of systemic signs of the disease and no ocular symptoms. We followed the evolution of such lesions over a 3-month period. Here, we underline the importance of retinal screening even if no ocular symptom is reported. Furthermore, we demonstrate the essential role of fundus examination as a reflection of systemic vascular changes.

Delayed intubation is associated with mortality in patients with severe COVID-19: A single-centre observational study in Switzerland.

INTRODUCTION: Switzerland experienced two waves of COVID-19 in 2020, but with a different ICU admission and treatment management strategy. The timing of ICU admission and intubation remains a matter of debate in severe patients. The aim of our study was to describe the characteristics of ICU patients between two subsequent waves of COVID-19 who underwent a different management strategy and to assess whether the timing of intubation was associated with differences in mortality. PATIENTS AND METHODS: We conducted a prospective observational study of all adult patients with acute respiratory failure due to COVID-19 who required intubation between the 9th of March 2020 and the 9th of January 2021 in the intensive care unit (ICU) at Geneva University Hospitals, Switzerland. RESULTS: Two hundred twenty-three patients were intubated during the study period; 124 during the first wave, and 99 during the second wave. Patients admitted to the ICU during the second wave had a higher SAPS II severity score (52.5 vs. 60; p = 0.01). The time from hospital admission to intubation was significantly longer during the second compared to the first wave (4 days [IQR, 1-7] vs. 2 days [IQR, 0-4]; p < 0.01). All-cause ICU mortality was significantly higher during the second wave (42% vs. 23%; p < 0.01). In a multivariate analysis, the delay between hospital admission and intubation was significantly associated with ICU mortality (OR 3.25 [95% CI, 1.38-7.67]; p < 0.05). CONCLUSIONS: In this observational study, delayed intubation was associated with increased mortality in patients with severe COVID-19. Further randomised controlled trials are needed.

Functional connectivity underlying cognitive and psychiatric symptoms in post-COVID-19 syndrome: is anosognosia a key determinant?

Lack of awareness of cognitive impairment (i.e. anosognosia) could be a key factor for distinguishing between neuropsychological post-COVID-19 condition phenotypes. In this context, the 2-fold aim of the present study was to (i) establish the prevalence of anosognosia for memory impairment, according to the severity of the infection in the acute phase and (ii) determine whether anosognosic patients with post-COVID syndrome have a different cognitive and psychiatric profile from nosognosic patients, with associated differences in brain functional connectivity. A battery of neuropsychological, psychiatric, olfactory, dyspnoea, fatigue and quality-of-life tests was administered 227.07 ± 42.69 days post-SARS-CoV-2 infection to 102 patients (mean age: 56.35 years, 65 men, no history of neurological, psychiatric, neuro-oncological or neurodevelopmental disorder prior to infection) who had experienced either a mild (not hospitalized; n = 45), moderate (conventional hospitalization; n = 34) or severe (hospitalization with intensive care unit stay and mechanical ventilation; n = 23) presentation in the acute phase. Patients were first divided into two groups according to the presence or absence of anosognosia for memory deficits (26 anosognosic patients and 76 nosognosic patients). Of these, 49 patients underwent an MRI. Structural images were visually analysed, and statistical intergroup analyses were then performed on behavioural and functional connectivity measures. Only 15.6% of patients who presented mild disease displayed anosognosia for memory dysfunction, compared with 32.4% of patients with moderate presentation and 34.8% of patients with severe disease. Compared with nosognosic patients, those with anosognosia for memory dysfunction performed significantly more poorly on objective cognitive and olfactory measures. By contrast, they gave significantly more positive subjective assessments of their quality of life, psychiatric status and fatigue. Interestingly, the proportion of patients exhibiting a lack of consciousness of olfactory deficits was significantly higher in the anosognosic group. Functional connectivity analyses revealed a significant decrease in connectivity, in the anosognosic group as compared with the nosognosic group, within and between the following networks: the left default mode, the bilateral somatosensory motor, the right executive control, the right salient ventral attention and the bilateral dorsal attention networks, as well as the right Lobules IV and V of the cerebellum. Lack of awareness of cognitive disorders and, to a broader extent, impairment of the self-monitoring brain system, may be a key factor for distinguishing between the clinical phenotypes of post-COVID syndrome with neuropsychological deficits.

Long COVID Neuropsychological Deficits after Severe, Moderate, or Mild Infection

There is growing awareness that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, even in its mild or moderate respiratory forms, can include long-term neuropsychological deficits. Standardized neuropsychological, psychiatric, neurological, and olfactory tests were administered to 45 patients 236.51 ±22.54 days after hospital discharge following severe, moderate, or mild respiratory severity from SARS-CoV-2 infection (severe = intensive care unit hospitalization, moderate = conventional hospitalization, mild = no hospitalization). Deficits were found in all domains of cognition, and the prevalence of psychiatric symptoms was relatively high in the three groups. The severe infection group performed more poorly on long-term episodic memory tests and exhibited greater anosognosia than did the other two groups. Those with moderate infection had poorer emotion recognition, which was positively correlated with persistent olfactory dysfunction. Individuals with mild infection were more stressed, anxious, and depressed. The data support the hypothesis that the virus targets the central nervous system (notably the limbic system) and the notion that there are different neuropsychological phenotypes.

Retinal Manifestations in Patients with COVID-19: A Prospective Cohort Study

The recent outbreak of the Coronavirus SARS-CoV-2 has been declared a worldwide pandemic. Within various multi-organ involvement, several ocular manifestations have been described, such as conjunctivitis and retinopathy. The prevalence and severity of retinal lesions and their relation to the severity of the systemic disease are unknown. We performed a prospective, observational study on 172 consecutively hospitalized patients with acute confirmed COVID-19 infection. All patients underwent screening widefield fundus photography at the time of hospital admission. Despite no ocular or vision-related symptoms, we found cotton wool spots (CWS) and/or hemorrhages in 19/172 patients (11%). Diabetes history, overweight, and elevated C-reactive protein were more frequently observed among patients with retinal abnormalities, while a history of systemic hypertension was more frequently observed among patients without retinal findings. At a 3-month follow-up visit, CWS had subsided in all patients.

Hypophosphatemia on ICU Admission Is Associated with an Increased Length of Stay in the ICU and Time under Mechanical Ventilation.

Hypophosphatemia is frequently observed in the ICU and is associated with several impairments such as respiratory failure or infections. We hypothesized that hypophosphatemia on ICU admission is associated with a prolonged duration of mechanical ventilation and ICU length of stay (LOS), particularly in COVID-19 patients. This cross-sectional study analyzed data from 1226 patients hospitalized in the ICU of the Geneva University Hospitals from August 2020 to April 2021. Patients were categorized as having hypophosphatemia (phosphatemia ≤ 0.8 mmol/L) or non-hypophosphatemia (phosphatemia > 0.8 mmol/L) on ICU admission. Linear regressions were performed to investigate the association between hypophosphatemia on ICU admission and ICU LOS and duration of mechanical ventilation. Overall, 250 (20%) patients presented hypophosphatemia on ICU admission. In the univariable analysis, hypophosphatemic patients had longer ICU LOS than non-hypophosphatemic patients, 7.4 days (±10.4) versus 5.6 days (±8.3), (p < 0.01). Hypophosphatemia on ICU admission was associated with a prolonged duration of mechanical ventilation, 7.4 days (±11.2) versus 5.6 days (±8.9), (p < 0.01). These associations were confirmed in the multivariable analysis (p < 0.01). In the subgroup of COVID-19 patients, a significant association between hypophosphatemia and ICU LOS and duration of mechanical ventilation was also observed. In conclusion, hypophosphatemia on ICU admission is associated with a longer ICU LOS and time under mechanical ventilation, both in the general ICU population and in COVID-19 patients.

SARS-CoV-2 infection as a trigger of humoral response against apolipoprotein A-1.

BACKGROUND: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights into the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We aimed at determining (a) the association between anti-SARS-CoV-2 and anti-apoA-1 humoral response and (b) the degree of linear homology between SARS-CoV-2, apoA-1 and Toll-like receptor 2 (TLR2) epitopes. DESIGN: Bioinformatics modelling coupled with mimic peptides engineering and competition experiments were used to assess epitopes sequence homologies. Anti-SARS-CoV-2 and anti-apoA-1 IgG as well as cytokines were assessed by immunoassays on a case-control (n = 101), an intensive care unit (ICU; n = 126) and a general population cohort (n = 663) with available samples in the pre and post-pandemic period. RESULTS: Using bioinformatics modelling, linear sequence homologies between apoA-1, TLR2 and Spike epitopes were identified but without experimental evidence of cross-reactivity. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (P < .0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-day kinetics, reaching 82% for anti-apoA-1 seropositivity. In the general population, SARS-CoV-2-exposed individuals displayed higher anti-apoA-1 IgG seropositivity rates than nonexposed ones (34% vs 16.8%; P = .004). CONCLUSION: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.

Mental health outcomes of ICU and non-ICU healthcare workers during the COVID-19 outbreak: a cross-sectional study.

BACKGROUND: Intensive care workers are known for their stressful work environment and for a high prevalence of mental health outcomes. The aim of this study was to evaluate the mental health, well-being and changes in lifestyle among intensive care unit (ICU) healthcare workers (HCW) during the first wave of the COVID-19 pandemic and to compare these results with those of HCW in other hospital units. Another objective was to understand which associated factors aggravate their mental health during the COVID-19 outbreak. METHODS: This cross-sectional survey collected socio-demographic data, lifestyle changes and mental health evaluations as assessed by the Generalized Anxiety Disorder 7 items (GAD-7), the Patient Health Questionnaire 9 items (PHQ-9), the Peritraumatic Distress Inventory (PDI) and the World Health Organization Well-Being Index (WHO-5) from the 28th May to 7th July 2020. The study was carried out at Geneva University Hospitals, a group of eight public hospitals in Switzerland. ICU HCW were analyzed for mental health outcomes and lifestyles changes and then compared to non-ICU HCW. A series of linear regression analyses were performed to assess factors associated with mental health scores. RESULTS: A total of 3461 HCW were included in the study, with 352 ICU HCW. Among ICU HCW, 145 (41%) showed low well-being, 162 (46%) symptoms of anxiety, 163 (46%) symptoms of depression and 76 (22%) had peritraumatic distress. The mean scores of GAD-7, PHQ-9 and WHO-5 were worse in ICU HCW than in non-ICU HCW (p < 0.01). Working in the ICU rather than in other departments resulted in a change of eating habits, sleeping patterns and alcohol consumption (p < 0.01). Being a woman, the fear of catching and transmitting COVID-19, anxiety of working with COVID-19 patients, work overload, eating and sleeping disorders as well as increased alcohol consumption were associated with worse mental health outcomes. CONCLUSION: This study confirms the suspicion of a high prevalence of anxiety, depression, peritraumatic distress and low well-being during the first COVID-19 wave among HCW, especially among ICU HCW. This allows for the identification of associated risk factors. Long-term psychological follow-up should be considered for HCW.

Impact of nutritional therapy during the first wave of the COVID-19 pandemic in intensive care patients: A retrospective observational study.

BACKGROUND & AIMS: The COVID-19 pandemic has caused major organizational challenges to healthcare systems concerning staff, material and bed availability. Nutrition was not a priority in the intensive care unit (ICU) at the beginning of the pandemic with the need for simplified protocols. We aimed to assess the impact of a simplified nutritional protocol for critically ill COVID-19 patients during the pandemic first wave. METHODS: We included all patients with SARS-CoV-2 infections, admitted to the ICU of the Geneva University Hospitals for at least 4 days from March 9 to May 19, 2020. Data on the route and solution of nutritional therapy, prescribed and received volume, calorie and protein intake, amount of insulin, propofol and glucose administered were collected daily during the entire ICU stay. We compared nutritional outcomes between patients admitted to the ICU before and after implementing the simplified nutritional protocol using unpaired t-test. RESULTS: Out of 119 patients, 48 were hospitalized in the ICU before, 47 across and 24 after the implementation of the nutritional protocol. The mean age was 63.2 (±12.7) years and 76% were men without significant difference between before and after group. The nutritional protocol implementation led to an increase in caloric intake (1070 vs. 1357 kcal/day, p = 0.018) and in the percentage of days within 80-100% of the energy target (11 vs. 20%, p = 0.021). The protein debt decreased significantly from 48 g/day to 37 g/day (p = 0.015). No significant difference in the percentage of days within the protein target (80-100%) was observed. CONCLUSIONS: Calorie and protein coverage improved after the implementation of the simplified nutritional protocol in critically ill COVID-19 patients. Further studies are needed to assess the impact of such an approach on patients' clinical outcomes.

Decreased CRRT Filter Lifespan in COVID-19 ICU Patients.

(1) Background: Increased thromboembolic events and an increased need for continuous renal replacement therapy (CRRT) have been frequently reported in COVID-19 patients. Our aim was to investigate CRRT filter lifespan in intensive care unit (ICU) COVID-19 patients. (2) Methods: We compared CRRT adjusted circuit lifespan in COVID-19 patients admitted for SARS-CoV-2 infection to a control group of patients admitted for septic shock of pulmonary origin other than COVID-19. Both groups underwent at least one session of CRRT for AKI. (3) Results: Twenty-six patients (13 in each group) were included. We analysed 117 CRRT circuits (80 in the COVID-19 group and 37 in the control group). The adjusted filter lifespan was shorter in the COVID-19 group (17 vs. 39 h, p < 0.001). This trend persisted after adjustment for confounding factors (-14 h, p = 0.037). Before CRRT circuit clotting, the COVID-19 group had a more procoagulant profile despite higher heparin infusion rates. Furthermore, we reported a decreased relation between activated partial thromboplastin time (aPTT) and cumulative heparin dose in COVID-19 patients when compared to historical data of 23,058 patients, suggesting a heparin resistance. (4) Conclusion: COVID-19 patients displayed a shorter CRRT filter lifespan that could be related to a procoagulant profile and heparin resistance.

COVID-19 encephalopathy: Clinical and neurobiological features.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has been associated with neurological complications, including acute encephalopathy. To better understand the neuropathogenesis of this acute encephalopathy, we describe a series of patients with coronavirus disease 2019 (COVID-19) encephalopathy, highlighting its phenomenology and its neurobiological features. On May 10, 2020, 707 patients infected by SARS-CoV-2 were hospitalized at the Geneva University Hospitals; 31 (4.4%) consecutive patients with an acute encephalopathy (64.6 ± 12.1 years; 6.5% female) were included in this series, after exclusion of comorbid neurological conditions, such as stroke or meningitis. The severity of the COVID-19 encephalopathy was divided into severe and mild based on the Richmond Agitation Sedation Scale (RASS): severe cases (n = 14, 45.2%) were defined on a RASS < -3 at worst presentation. The severe form of this so-called COVID-19 encephalopathy presented more often a headache. The severity of the pneumonia was not associated with the severity of the COVID-19 encephalopathy: 28 of 31 (90%) patients did develop an acute respiratory distress syndrome, without any difference between groups (p = .665). Magnetic resonance imaging abnormalities were found in 92.0% (23 of 25 patients) with an intracranial vessel gadolinium enhancement in 85.0% (17 of 20 patients), while an increased cerebrospinal fluid/serum quotient of albumin suggestive of blood-brain barrier disruption was reported in 85.7% (6 of 7 patients). Reverse transcription-polymerase chain reaction for SARS-CoV-2 was negative for all patients in the cerebrospinal fluid. Although different pathophysiological mechanisms may contribute to this acute encephalopathy, our findings suggest the hypothesis of disturbed brain homeostasis and vascular dysfunction consistent with a SARS-CoV-2-induced endotheliitis.