Outcomes of Patients With Active Cancer and COVID-19 in the Intensive-Care Unit: A Multicenter Ambispective Study.

Background: Several studies report an increased susceptibility to SARS-CoV-2 infection in cancer patients. However, data in the intensive care unit (ICU) are scarce. Research Question: We aimed to investigate the association between active cancer and mortality among patients requiring organ support in the ICU. Study Design and Methods: In this ambispective study encompassing 17 hospitals in France, we included all adult active cancer patients with SARS-CoV-2 infection requiring organ support and admitted in ICU. For each cancer patient, we included 3 non cancer patients as controls. Patients were matched at the same ratio using the inverse probability weighting approach based on a propensity score assessing the probability of cancer at admission. Mortality at day 60 after ICU admission was compared between cancer patients and non-cancer patients using primary logistic regression analysis and secondary multivariable analyses. Results: Between March 12, 2020 and March 8, 2021, 2608 patients were admitted with SARS-CoV-2 infection in our study, accounting for 2.8% of the total population of patients with SARS-CoV-2 admitted in all French ICUs within the same period. Among them, 105 (n=4%) presented with cancer (51 patients had hematological malignancy and 54 patients had solid tumors). 409 of 420 patients were included in the propensity score matching process, of whom 307 patients in the non-cancer group and 102 patients in the cancer group. 145 patients (35%) died in the ICU at day 60, 59 (56%) with cancer and 86 (27%) without cancer. In the primary logistic regression analysis, the odds ratio for death associated to cancer was 2.3 (95%CI 1.24 - 4.28, p=0.0082) higher for cancer patients than for a non-cancer patient at ICU admission. Exploratory multivariable analyses showed that solid tumor (OR: 2.344 (0.87-6.31), p=0.062) and hematological malignancies (OR: 4.144 (1.24-13.83), p=0.062) were independently associated with mortality. Interpretation: Patients with cancer and requiring ICU admission for SARS-CoV-2 infection had an increased mortality, hematological malignancy harboring the higher risk in comparison to solid tumors.

Endothelial cell biomarkers in critically ill COVID-19 patients with encephalitis.

COVID-19 is associated with encephalitis in critically ill patients and endothelial dysfunction seems to contribute to this life-threatening complication. Our objective was to determine the hallmark of endothelial activation in COVID-19-related encephalitis. In an observational study in intensive care unit (ICU), we compared vascular biomarkers of critically ill COVID-19 patients with or without encephalitis. To be classified in the encephalitis group, patients had to have new onset of central neurologic symptom, and pathological findings on either brain magnetic resonance imaging (MRI) and/or electroencephalogram (EEG). Among the 32 critically ill COVID-19 consecutive patients, 21 were categorized in the control group and 11 in the encephalitis group. Encephalitis patients had a longer ICU stay than control patients (median length [25th-75th percentile] of 52 [16-79] vs. 20.5 [11-44] days, respectively, p = 0.04). Nine-month overall follow-up mortality reached 21% (7/32 patients), with mortality rates in the encephalitis group and the control group of 27% and 19%, respectively. Encephalitis was associated with significant higher release of soluble endothelial activation markers (sE-selectin, tumor necrosis factor-α (TNF-α), interleukin 6, placental growth factor, and thrombomodulin), but these increases were correlated with TNF-α plasmatic levels. The hypoxia-inducible protein angiopoietin-like 4 (ANGPTL4) was at significantly higher levels in encephalitis patients compared to control patients (p = 0.0099), and in contrary to the other increased factors, was not correlated with TNF-α levels (r = 0.2832, p = 0.1163). Our findings suggest that COVID-19-related encephalitis is a cytokine-associated acute brain dysfunction. ANGPTL4 was the only elevated marker found in encephalitis patients, which was not correlated with systemic inflammation, suggesting that ANGPTL4 might be a relevant factor to predict encephalitis in critically ill COVID-19 patients.

Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort.

BACKGROUND: Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. FINDINGS: Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. INTERPRETATION: VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov, number NCT04359693.

Distinct cytokine profiles associated with COVID-19 severity and mortality.

BACKGROUND: Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. METHODS: Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = 115), classified at hospitalization into 3 respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS), and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal-component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N = 86). RESULTS: At time of hospitalization, ECMO patients presented a dominant proinflammatory response with elevated levels of TNF-α, IL-6, IL-8, and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-ß was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at 1 month was associated with higher levels of proinflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients, and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (risk ratio, 24.3; P < .0001). Severe acute respiratory syndrome coronavirus 2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with proinflammatory response or severity. CONCLUSIONS: Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.

The cerebral network of COVID-19-related encephalopathy: a longitudinal voxel-based 18F-FDG-PET study.

PURPOSE: Little is known about the neuronal substrates of neuropsychiatric symptoms associated with COVID-19 and their evolution during the course of the disease. We aimed at describing the longitudinal brain metabolic pattern in COVID-19-related encephalopathy using 18F-FDG-PET/CT. METHODS: Seven patients with variable clinical presentations of COVID-19-related encephalopathy were explored thrice with brain 18F-FDG-PET/CT, once in the acute phase, 1 month later and 6 months after COVID-19 onset. PET images were analysed with voxel-wise and regions-of-interest approaches in comparison with 32 healthy controls. RESULTS: Patients' neurological manifestations during acute encephalopathy were heterogeneous. However, all of them presented with predominant cognitive and behavioural frontal disorders. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. MRI revealed no specific abnormalities for most of the subjects. All patients had a consistent pattern of hypometabolism in a widespread cerebral network including the frontal cortex, anterior cingulate, insula and caudate nucleus. Six months after COVID-19 onset, the majority of patients clinically had improved but cognitive and emotional disorders of varying severity remained with attention/executive disabilities and anxio-depressive symptoms, and lasting prefrontal, insular and subcortical 18F-FDG-PET/CT abnormalities. CONCLUSION: The implication of this widespread network could be the neural substrate of clinical features observed in patients with COVID-19, such as frontal lobe syndrome, emotional disturbances and deregulation of respiratory failure perception. This study suggests that this network remains mildly to severely impaired 6 months after disease onset.

Coronavirus disease 2019 crisis in Paris: A differential psychological impact between regular intensive care unit staff members and reinforcement workers.

BACKGROUND: Intensive care unit (ICU) healthcare workers (HCWs) are at the forefront of the coronavirus disease 2019 pandemic. To overcome the lack of human resources during this crisis, some ICUs had to mobilise staff from a reinforcement pool, with no or outdated ICU experience. This study aimed to investigate and to compare the psychological impact of the pandemic on regular ICU staff members and reinforcement workers. MATERIAL AND METHODS: Self-assessment questionnaires were completed by HCWs who worked from March 1 to April 30, 2020, in our 16-bed neurological ICU at La Pitié-Salpêtrière Hospital in Paris, France, which was converted to a COVID ICU. The Hospital Anxiety and Depression Scale, the Post-traumatic Stress Disorder Checklist for DSM-5, McGill Quality of Life Questionnaire-Revised, and 10-item Connor-Davidson Resilience Scale were used to assess anxiety, depression and post-traumatic stress disorder, quality of life, and resilience, respectively. RESULTS: Sixty-nine ICU HCWs completed the survey (37 from the team of regular staff members, i.e., from the public health service, and 32 from a reinforcement pool, either from non-ICU public health service or from private healthcare interim employment agencies). Prevalence of anxiety, depression, and post-traumatic stress disorder symptoms was high, at 19%, 9%, and 16%, respectively, with limited impairment in quality of life or resilience scores. Depression symptoms were observed more in regular staff members than in welcomed reinforcement workers, at 16% and 0%, respectively. CONCLUSIONS: These results revealed that during the pandemic, HCWs from the team of regular staff members were at greater risk of developing psychological disorder compared with reinforcement workers, with higher levels of depressive symptoms.

Therapeutic plasma exchange in a critically ill Covid-19 patient.

Here we describe the effect of therapeutic plasma exchange with 5% albumin as sole replacement solution for the management of Covid-19. A 74-year-old man was admitted for severe Covid-19 acute respiratory distress syndrome. Based on the growing body of evidence that cytokine release syndrome, and especially interleukin-6, plays a key role in critically ill Covid-19 patients, we decided to implement therapeutic plasma exchange as a rescue therapy. The patient's clinical status rapidly improved, and biological records showed convincing results of decrease in interleukin-6 and inflammatory parameters under treatment. This case presents a proof-of-concept for the use of therapeutic plasma exchange with 5% albumin as sole replacement solution in a critically ill Covid-19 patient with cytokine release syndrome. This could constitute a major benefit in terms of security compared to long-lasting immunosuppressive monoclonal antibodies, or to therapeutic plasma exchange with plasma as replacement fluid. Hence, we think that a further evaluation of risk-benefit balance of this therapy in severe cases of Covid-19 should rapidly be undertaken.

Orbitofrontal involvement in a neuroCOVID-19 patient.

Neurological manifestations of coronavirus disease 19 (COVID-19) such as encephalitis and seizures have been reported increasingly, but our understanding of COVID-19-related brain injury is still limited. Herein we describe prefrontal involvement in a patient with COVID-19 who presented prior anosmia, raising the question of a potential trans-olfactory bulb brain invasion.