Coronavirus Disease 2019 Intensive Care Unit Patients Research Articles

Clinical phenotyping uncovers heterogeneous associations between corticosteroid treatment and survival in critically ill COVID-19 patients

PurposeDisease heterogeneity in coronavirus disease 2019 (COVID-19) may render the current one-size-fits-all treatment approach suboptimal. We aimed to identify and immunologically characterize clinical phenotypes among critically ill COVID-19 patients, and to assess heterogeneity of corticosteroid treatment effect.MethodsWe applied consensus k-means clustering on 21 clinical parameters obtained within 24 h after admission to the intensive care unit (ICU) from 13,279 COVID-19 patients admitted to 82 Dutch ICUs from February 2020 to February 2022. Derived phenotypes were reproduced in 6225 COVID-19 ICU patients from Spain (February 2020 to December 2021). Longitudinal immunological characterization was performed in three COVID-19 ICU cohorts from the Netherlands and Germany, and associations between corticosteroid treatment and survival were assessed across phenotypes.ResultsWe derived three phenotypes: COVIDICU1 (43% of patients) consisted of younger patients with the lowest Acute Physiology And Chronic Health Evaluation (APACHE) scores, highest body mass index (BMI), lowest PaO2/FiO2 ratio, and a 90-day in-hospital mortality rate of 18%. COVIDICU2 patients (37%) had the lowest BMI, were older and had higher APACHE scores and mortality rate (24%) than COVIDICU1. Patients with COVIDICU3 (20%) were the eldest with the most comorbidities, the highest APACHE scores, acute kidney injury and metabolic dysregulations, and the highest mortality rate (47%). These patients also displayed the most pronounced inflammatory response. Corticosteroid therapy started at day 5 [2–9] after ICU admission and administered for 5 [3–7] days was associated with an increased risk for 90-day mortality in patients with the COVIDICU1 and COVIDICU2 phenotypes (hazard ratio [HR] 1.59 [1.09–2.31], p = 0.015 and HR 1.79 [1.42–2.26], p < 0.001, respectively), but not in patients with the COVIDICU3 phenotype (HR 1.08 [0.76–1.54], p = 0.654).ConclusionOur multinational study identified three distinct clinical COVID-19 phenotypes, each exhibiting marked differences in demographic, clinical, and immunological features, and in the response to late and short-term corticosteroid treatment.

Dynamic associations between the respiratory tract and gut antibiotic resistome of patients with COVID-19 and its prediction power for disease severity

ABSTRACT The antibiotic resistome is the collection of all antibiotic resistance genes (ARGs) present in an individual. Whether an individual’s susceptibility to infection and the eventual severity of coronavirus disease 2019 (COVID-19) is influenced by their respiratory tract antibiotic resistome is unknown. Additionally, whether a relationship exists between the respiratory tract and gut ARGs composition has not been fully explored. We recruited 66 patients with COVID-19 at three disease stages (admission, progression, and recovery) and conducted a metagenome sequencing analysis of 143 sputum and 97 fecal samples obtained from them. Respiratory tract, gut metagenomes, and peripheral blood mononuclear cell (PBMC) transcriptomes are analyzed to compare the gut and respiratory tract ARGs of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between ARGs and immune response. Among the respiratory tract ARGs, we found that Aminoglycoside, Multidrug, and Vancomycin are increased in ICU patients compared with nICU patients. In the gut, we found that Multidrug, Vancomycin, and Fosmidomycin were increased in ICU patients. We discovered that the relative abundances of Multidrug were significantly correlated with clinical indices, and there was a significantly positive correlation between ARGs and microbiota in the respiratory tract and gut. We found that immune-related pathways in PBMC were enhanced, and they were correlated with Multidrug, Vancomycin, and Tetracycline ARGs. Based on the ARG types, we built a respiratory tract-gut ARG combined random-forest classifier to distinguish ICU COVID-19 patients from nICU patients with an AUC of 0.969. Cumulatively, our findings provide some of the first insights into the dynamic alterations of respiratory tract and gut antibiotic resistome in the progression of COVID-19 and disease severity. They also provide a better understanding of how this disease affects different cohorts of patients. As such, these findings should contribute to better diagnosis and treatment scenarios.

Reduced Mortality among COVID-19 ICU Patients after Treatment with HemoClear Convalescent Plasma in Suriname.

Convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), but its efficacy in intensive care unit (ICU) patients in low- and middle-income country settings such as Suriname is unknown. Bedside plasma separation using the HemoClear device made convalescent plasma therapy accessible as a treatment option in Suriname. Two hundred patients with severe SARS-CoV-2 infection requiring intensive care were recruited. Fifty eight patients (29%) received COVID-19 convalescent plasma (CCP) treatment in addition to standard of care (SOC). The CCP treatment and SOC groups were matched by age, sex, and disease severity scores. Mortality in the CCP treatment group was significantly lower than that in the SOC group (21% versus 39%; Fisher's exact test P = 0.0133). Multivariate analysis using ICU days showed that CCP treatment reduced mortality (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.18 to 0.66; P = 0.001), while complication of acute renal failure (creatinine levels, >110 mol/L; HR, 4.45; 95% CI, 2.54 to 7.80; P < 0.0001) was independently associated with death. Decrease in chest X-ray score in the CCP treatment group (median -3 points, interquartile range [IQR] -4 to -1) was significantly greater than that in the SOC group (median -1 point, IQR -3 to 1, Mann-Whitney test P = 0.0004). Improvement in the PaO2/FiO2 ratio was also significantly greater in the CCP treatment group (median 83, IQR 8 to 140) than in the SOC group (median 35, IQR -3 to 92, Mann-Whitney P = 0.0234). Further research is needed for HemoClear-produced CCP as a therapy for SARS-CoV-2 infection together with adequately powered, randomized controlled trials. IMPORTANCE This study compares mortality and other endpoints between intensive care unit COVID-19 patients treated with convalescent plasma plus standard of care (CCP), and a control group of patients hospitalized in the same medical ICU facility treated with standard of care alone (SOC) in a low- and middle-income country (LMIC) setting using bedside donor whole blood separation by gravity (HemoClear) to produce the CCP. It demonstrates a significant 65% survival improvement in HemoClear-produced CCP recipients (HR, 0.35; 95% CI, 0.19 to 0.66; P = 0.001). Although this is an exploratory study, it clearly shows the benefit of using the HemoClear-produced CCP in ICU patients in the Suriname LMIC setting. Additional studies could further substantiate our findings and their applicability for both LMICs and high-income countries and the use of CCP as a prepared readiness method to combat new viral pandemics.

Bacterial profiles and their antibiotic resistance background in superinfections caused by multidrug-resistant bacteria among COVID-19 ICU patients from southwest Iran.

This study investigated the bacterial causes of superinfections and their antibiotic resistance pattern in severe coronavirus disease 2019 (COVID-19) patients admitted to the intensive care unit (ICU) of Razi Hospital in Ahvaz, southwest Iran. In this cross-sectional study, endotracheal tube (ETT) secretion samples of 77 intubated COVID-19 patients, confirmed by reverse transcription-quantitative polymerase chain reaction, were investigated by standard microbiology test and analytical profile index kit. Antibiotic susceptibility testing was performed by disc diffusion. The presence of Haemophilus influenzae and Mycoplasma pneumoniae was investigated by the polymerase chain reaction (PCR). Using culture and PCR methods, 56 (72.7%) of the 77 COVID-19 patients (mean age of 55 years, 29 male and 27 female) had superinfections. Using culture, 67 isolates including 29 (43.2%) Gram-positive and 38 (56.7%) Gram-negative bacteria (GNB) were identified from 49 COVID-19 patients. The GNB were more predominant than the Gram-positive pathogens. Klebsiella pneumoniae (28.4%, n = 19/67) was the most common isolate followed by Staphylococcus aureus (22.4%, n = 15/67). Using PCR, 10.4% (8/77) and 11.7% (9/77) of ETT secretion specimens had H. influenzae and M. pneumoniae amplicons, respectively. Gram-positive and Gram-negative isolates showed high resistance rates (>70.0%) to majority of the tested antibiotics including fluoroquinolone, carbapenems, and cephalosporins and 68.7% (46/67) of isolates were multidrug-resistant (MDR). This study showed a high frequency rate of superinfections by MDR bacteria among COVID-19 patients in southwest Iran. The prevention of long-term consequences caused by COVID-19, demands continuous antibiotic surveillance particularly in management of bacterial superinfections.

Effect of Tocilizumab Use on Mortality in COVID-19 Patients Admitted to Intensive Care Unit

Aim: Coronavirus disease 2019 (COVID-19) mostly proceeds with mild respiratory symptoms, but sometimes severe pneumonia, cytokine storm, and acute respiratory distress syndrome can develop. Anti-cytokine treatments are being tried for cytokine storm. In this study, we aimed to examine the effect of tocilizumab on mortality associated with COVID-19. Material and Methods: The study included 146 patients with moderate-to-severe acute respiratory distress syndrome diagnosed with COVID-19. The patients were divided into two groups, receiving only standard treatment (ST group, n=44), and tocilizumab treatment in addition to standard treatment (TCZ group, n=102). Groups were compared in terms of demographic, clinic, and laboratory data. Also, mortality rates were determined to detect the effect of tocilizumab on mortality. Results: Overall, 36.3% (n=53) of the patients were female, 63.7% (n=93) were male, and the mean age was 69.5±14.2 years. The mortality rate was 29.4% (n=30) in the TCZ group and 52.3% (n=23) in the ST group (p=0.009). While C-reactive protein, fibrinogen, and lactate levels on admission to the intensive care unit (ICU) were similar across the groups, the TCZ group had higher ferritin levels (p=0.006). On discharge from ICU, the TCZ group had a significant decrease in C-reactive protein (p&amp;lt;0.001), while their ferritin levels decreased to levels in the ST group (p=0.134). The absence of tocilizumab in the treatment regimen was associated with a 2.63-fold increase in the mortality risk. Conclusion: Tocilizumab reduces the mortality in COVID-19 patients in ICU. However, further studies are warranted to better elucidate the efficacy and side effects of tocilizumab.

Impact of the COVID-19 pandemic on critical care utilization in Japan: a nationwide inpatient database study

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has disrupted critical care services worldwide. Examining how critical care systems responded to the COVID-19 pandemic on a national level will be useful in setting future critical care plans. The present study aimed to describe the utilization of critical care services before and during the COVID-19 pandemic using a nationwide Japanese inpatient administrative database.MethodsAll patients admitted to an intensive care unit (ICU) or a high-dependency care unit (HDU) from February 9, 2019, to February 8, 2021, in the Japanese Diagnosis Procedure Combination inpatient database were included. February 9, 2020, was used as the breakpoint separating the periods before and during COVID-19 pandemic. Hospital and patient characteristics were compared before and during the COVID-19 pandemic. Change in ICU and HDU bed occupancy before and during the COVID-19 pandemic was evaluated using interrupted time-series analysis.ResultsThe number of ICU patients before and during the COVID-19 pandemic was 297,679 and 277,799, respectively, and the number of HDU patients was 408,005 and 384,647, respectively. In the participating hospitals (383 ICU-equipped hospitals and 460 HDU-equipped hospitals), the number of hospitals which increased the ICU and HDU beds capacity were 14 (3.7%) and 33 (7.2%), respectively. Patient characteristics and outcomes in ICU and HDU were similar before and during the COVID-19 pandemic except main etiology for admission of COVID-19. The mean ICU bed occupancy before and during the COVID-19 pandemic was 51.5% and 47.5%, respectively. The interrupted time-series analysis showed a downward level change in ICU bed occupancy during the COVID-19 pandemic (− 4.29%, 95% confidence intervals − 5.69 to − 2.88%), and HDU bed occupancy showed similar trends. Of 383 hospitals with ICUs, 232 (60.6%) treated COVID-19 patients in their ICUs. Their annual hospital case volume of COVID-19 ICU patients varied greatly, with a median of 10 (interquartile range 3–25, min 1, max 444).ConclusionsThe ICU and HDU bed capacity did not increase while their bed occupancy decreased during the COVID-19 pandemic in Japan. There was no change in clinicians’ decision-making to forego ICU/HDU care for selected patients, and there was no progress in the centralization of critically ill COVID-19 patients.

Influence of SARS-COV-2 Infection on Cytokine Production by Mitogen-Stimulated Peripheral Blood Mononuclear Cells and Neutrophils in COVID-19 Intensive Care Unit Patients.

We sought to investigate the influence of SARS-CoV-2 infection on the cytokine profiles of peripheral blood mononuclear cells (PBMCs) and neutrophils from coronavirus disease 2019 (COVID-19) intensive care unit (ICU) patients. Neutrophils and PBMCs were separated and stimulated with the mitogen phytohemagglutinin. Culture supernatants of mitogen-stimulated PBMCs and neutrophils from 88 COVID-19 ICU patients and 88 healthy controls were evaluated for levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-α, IFN-γ, interleukin (IL)-2, -4, -5, -6, -9, -10, -12, -17A, and tumor necrosis factor (TNF)-α using anti-cytokine antibody MACSPlex capture beads. Cytokine profiles of PBMCs showed significantly lower levels of GM-CSF, IFN-γ, IL-6, IL-9, IL-10, IL-17A, and TNF-α (p &lt; 0.0001) in COVID-19 ICU patients. In contrast, COVID-19 ICU patients showed higher median levels of IL-2 (p &lt; 0.001) and IL-5 (p &lt; 0.01) by PBMCs. As for neutrophils, COVID-19 ICU patients showed significantly lower levels of GM-CSF, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-17A, IL-12, TNF-α (p &lt; 0.0001), and IFN-α (p &lt; 0.01). T-helper (Th)1:Th2 cytokine ratios revealed lower inflammatory cytokine for PBMCs and neutrophils in COVID-19 ICU patients. Cytokine production profiles and Th1:Th2 cytokine ratios suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has an immunomodulatory effect on PBMCs and neutrophils. This study also suggests that the increased levels of several cytokines in the serum are not sourced from PBMCs and neutrophils.

Albumin Infusion May Improve the Prognosis of Critical COVID-19 Patients with Hypoalbuminemia in the Intensive Care Unit: A Retrospective Cohort Study.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has caused enormous mortality worldwide. Low albumin level is a risk factor for increasing mortality among patients in the intensive care unit (ICU). This study investigated the effect of albumin infusion on critical COVID-19 patients with hypoalbuminemia.MethodsA total of 114 COVID-19 ICU patients with hypoalbuminemia were recruited from Wuhan Leishenshan Hospital and Zhongnan Hospital of Wuhan University. Clinical features and laboratory variables were collected through electronic medical records. The cohorts were divided into two groups: albumin infusion and non-albumin infusion. Propensity-matched analysis was used to compare patients who received albumin to controls. Statistical analyses were used to investigate the survival time and inflammation-related blood biomarkers between groups.ResultsLactate dehydrogenase, interleukin (IL)-6, IL-2 receptor, and IL-8 levels were significantly downregulated in the albumin infusion group. Significant upregulations of lymphocyte counts and IL-10 were found in the albumin infusion group. There was a negative association between albumin level and D-dimer or procalcitonin levels after treatment. The albumin infusion group had a significantly longer survival time and shorter hospitalization time than control patients. Notably, a 1g increase in albumin level reduced the risk of death by approximately 7.3% after adjusting for age and sex. Patients with increased albumin levels after treatment had better prognoses than those without.ConclusionAlbumin administration can regulate COVID-19-related biomarkers and reduce the risk of death in critical patients with hypoalbuminemia. Clinicians should pay more attention to these risk factors. Targeted clinical interventions should be implemented to minimize the negative impacts of hypoalbuminemia and improve disease outcomes.

Increased Presence of Antibodies against Type I Interferons and Human Endogenous Retrovirus W in Intensive Care Unit COVID-19 Patients.

ABSTRACTIn this work, we observed an increased presence of antibodies (Abs) against type I interferon (IFN-I) in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care unit (ICU) compared to non-ICU COVID-19 patients and healthy control (HC) subjects. Human endogenous retrovirus W (HERV-W) can reactivate after viral infection; therefore, we also investigated the presence of antibodies against HERV-W envelope (HERV-W-env)-derived epitopes. A total of 113 subjects (41 female and 72 male subjects) were analyzed. A significant difference in autoantibodies against IFN-α, IFN-ω, and HERV-W was observed between HCs and ICU patients; indeed, the latter have higher levels of autoantibodies against IFN-α, IFN-ω, and HERV-W than subjects with mild COVID-19 and HCs. Neutralizing anti-IFN-I autoantibodies may affect the ability of IFN-I to bind to the type I interferon receptor (IFNAR), blocking the activation of the antiviral response.IMPORTANCE In this work, we report the increased presence of IFN autoantibodies in correlation with HERV-W-env autoantibodies in ICU COVID-19 patients. The novelty of the results is in the association of these IFN autoantibodies with autoantibodies against HERV-W-env, a protein recently discovered to be overexpressed in lymphocytes of COVID-19 patients and correlated with severe disease and pneumonia. Type I IFNs are part of a complex cross-regulatory network; however, in a small percentage of cases, the increase in autoantibodies against these proteins may lead to damage to the host instead of protection against infectious diseases.

Development and Internal Validation of a New Prognostic Model Powered to Predict 28-Day All-Cause Mortality in ICU COVID-19 Patients-The COVID-SOFA Score.

Background: The sequential organ failure assessment (SOFA) score has poor discriminative ability for death in severely or critically ill patients with Coronavirus disease 2019 (COVID-19) requiring intensive care unit (ICU) admission. Our aim was to create a new score powered to predict 28-day mortality. Methods: Retrospective, observational, bicentric cohort study including 425 patients with COVID-19 pneumonia, acute respiratory failure and SOFA score ≥ 2 requiring ICU admission for ≥72 h. Factors with independent predictive value for 28-day mortality were identified after stepwise Cox proportional hazards (PH) regression. Based on the regression coefficients, an equation was computed representing the COVID-SOFA score. Discriminative ability was tested using receiver operating characteristic (ROC) analysis, concordance statistics and precision-recall curves. This score was internally validated. Results: Median (Q1–Q3) age for the whole sample was 64 [55–72], with 290 (68.2%) of patients being male. The 28-day mortality was 54.58%. After stepwise Cox PH regression, age, neutrophil-to-lymphocyte ratio (NLR) and SOFA score remained in the final model. The following equation was computed: COVID-SOFA score = 10 × [0.037 × Age + 0.347 × ln(NLR) + 0.16 × SOFA]. Harrell’s C-index for the COVID-SOFA score was higher than the SOFA score alone for 28-day mortality (0.697 [95% CI; 0.662–0.731] versus 0.639 [95% CI: 0.605–0.672]). Subsequently, the prediction error rate was improved up to 16.06%. Area under the ROC (AUROC) was significantly higher for the COVID-SOFA score compared with the SOFA score for 28-day mortality: 0.796 [95% CI: 0.755–0.833] versus 0.699 [95% CI: 0.653–0.742, p < 0.001]. Better predictive value was observed with repeated measurement at 48 h after ICU admission. Conclusions: The COVID-SOFA score is better than the SOFA score alone for 28-day mortality prediction. Improvement in predictive value seen with measurements at 48 h after ICU admission suggests that the COVID-SOFA score can be used in a repetitive manner. External validation is required to support these results.

Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality.

PurposeCytomegalovirus (CMV) reactivation in immunocompetent critically ill patients is common and relates to a worsening outcome. In this large observational study, we evaluated the incidence and the risk factors associated with CMV reactivation and its effects on mortality in a large cohort of patients affected by coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU).MethodsConsecutive patients with confirmed SARS-CoV-2 infection and acute respiratory distress syndrome admitted to three ICUs from February 2020 to July 2021 were included. The patients were screened at ICU admission and once or twice per week for quantitative CMV-DNAemia in the blood. The risk factors associated with CMV blood reactivation and its association with mortality were estimated by adjusted Cox proportional hazards regression models.ResultsCMV blood reactivation was observed in 88 patients (20.4%) of the 431 patients studied. Simplified Acute Physiology Score (SAPS) II score (HR 1031, 95% CI 1010–1053, p = 0.006), platelet count (HR 0.0996, 95% CI 0.993–0.999, p = 0.004), invasive mechanical ventilation (HR 2611, 95% CI 1223–5571, p = 0.013) and secondary bacterial infection (HR 5041; 95% CI 2852–8911, p < 0.0001) during ICU stay were related to CMV reactivation. Hospital mortality was higher in patients with (67.0%) than in patients without (24.5%) CMV reactivation but the adjusted analysis did not confirm this association (HR 1141, 95% CI 0.757–1721, p = 0.528).ConclusionThe severity of illness and the occurrence of secondary bacterial infections were associated with an increased risk of CMV blood reactivation, which, however, does not seem to influence the outcome of COVID-19 ICU patients independently.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00134-022-06716-y.

Neurophysiological Aspects in SARS-CoV-2-Induced Acute Respiratory Distress Syndrome.

Patients with coronavirus disease 2019 (COVID-19) often develop acute respiratory failure and acute respiratory distress syndrome (ARDS) that requires intensive care unit (ICU) hospitalization and invasive mechanical ventilation, associated with a high mortality rate. In addition, many patients fail early weaning attempts, further increasing ICU length of stay and mortality. COVID-19 related ARDS can be complicated by neurological involvement with mechanisms of direct central nervous system (CNS) infection and with overlapping para-infective mechanisms of the peripheral nervous system (PNS). We aimed to evaluate the possible involvement of the brainstem and PNS in patients with COVID-19 related ARDS and difficulty in weaning from mechanical ventilation. We evaluated electroencephalogram (EEG), brainstem auditory evoked potentials (BAEPs), electroneurography of the four limbs and the phrenic nerve in 10 patients with respiratory insufficiency due to SARS-CoV-2. All were admitted to intensive care unit and were facing prolonged weaning from mechanical ventilation. All ten patients showed a mild diffuse non-specific slowing of brain electrical activity on the EEG. Four patients had an acute motor axonal neuropathy with absent or reduced amplitude phrenic nerve CMAP while four patients showed impairment of the BAEPs. A patient with peripheral nerve impairment suggestive of Guillain-Barré syndrome (GBS) underwent an intravenous immunoglobulin (IVIg) cycle that led to an improvement in the weaning process and progressive motor improvement. The inclusion of a comprehensive neurological evaluation in COVID-19 patients in ICU facilitated the early identification and effective management of Nervous System involvement.

Heparan sulfate mimetic fucoidan restores the endothelial glycocalyx and protects against dysfunction induced by serum of COVID-19 patients in the intensive care unit

Accumulating evidence proves that endothelial dysfunction is involved in coronavirus disease 2019 (COVID-19) progression. We previously demonstrated that the endothelial surface glycocalyx has a critical role in maintenance of vascular integrity. Here, we hypothesised that serum factors of severe COVID-19 patients affect the glycocalyx and result in endothelial dysfunction.We included blood samples of 32 COVID-19 hospitalised patients at the Leiden University Medical Center, of which 26 were hospitalised in an intensive care unit (ICU) and six on a non-ICU hospital floor; 18 of the samples were obtained from convalescent patients 6 weeks after hospital discharge, and 12 from age-matched healthy donors (control) during the first period of the outbreak. First, we determined endothelial (angiopoietin 2 (ANG2)) and glycocalyx degradation (soluble thrombomodulin (sTM) and syndecan-1 (sSDC1)) markers in plasma.In the plasma of COVID-19 patients, circulating ANG2 and sTM were elevated in patients in the ICU. Primary lung microvascular endothelial cell (HPMEC) and human glomerular microvascular endothelial cell (GEnC) cultured in the presence of these sera led to endothelial cell glycocalyx degradation, barrier disruption, inflammation and increased coagulation on the endothelial surface, significantly different compared to healthy control and non-ICU patient sera. These changes could all be restored in the presence of fucoidan.In conclusion, our data highlight the link between endothelial glycocalyx degradation, barrier failure and induction of a procoagulant surface in COVID-19 patients in ICU which could be targeted earlier in disease by the presence of heparan sulfate mimetics.

Prognostic Impact of Bronchoalveolar Lavage Fluid Galactomannan and Aspergillus Culture Results on Survival in COVID-19 Intensive Care Unit Patients: a Post Hoc Analysis from the European Confederation of Medical Mycology (ECMM) COVID-19-Associated Pulmonary Aspergillosis Study.

ABSTRACTCritically ill patients with coronavirus disease 2019 (COVID-19) may develop COVID-19-associated pulmonary aspergillosis (CAPA), which impacts their chances of survival. Whether positive bronchoalveolar lavage fluid (BALF) mycological tests can be used as a survival proxy remains unknown. We conducted a post hoc analysis of a previous multicenter, multinational observational study with the aim of assessing the differential prognostic impact of BALF mycological tests, namely, positive (optical density index of ≥1.0) BALF galactomannan (GM) and positive BALF Aspergillus culture alone or in combination for critically ill patients with COVID-19. Of the 592 critically ill patients with COVID-19 enrolled in the main study, 218 were included in this post hoc analysis, as they had both test results available. CAPA was diagnosed in 56/218 patients (26%). Most cases were probable CAPA (51/56 [91%]) and fewer were proven CAPA (5/56 [9%]). In the final multivariable model adjusted for between-center heterogeneity, an independent association with 90-day mortality was observed for the combination of positive BALF GM and positive BALF Aspergillus culture in comparison with both tests negative (hazard ratio, 2.53; 95% CI confidence interval [CI], 1.28 to 5.02; P = 0.008). The other independent predictors of 90-day mortality were increasing age and active malignant disease. In conclusion, the combination of positive BALF GM and positive BALF Aspergillus culture was associated with increased 90-day mortality in critically ill patients with COVID-19. Additional study is needed to explore the possible prognostic value of other BALF markers.

Cumulative Radiation Exposure in Covid-19 Patients Admitted to the Intensive Care Unit.

Medical imaging plays a major role in coronavirus disease-2019 (COVID-19) patient diagnosis and management. However, the radiation dose received from medical procedures by these patients has been poorly investigated. We aimed to estimate the cumulative effective dose (CED) related to medical exposure in COVID-19 patients admitted to the intensive care unit (ICU) in comparison to the usual critically ill patients. We designed a descriptive cohort study including 90 successive ICU COVID-19 patients admitted between March and May 2020 and 90 successive non-COVID-19 patients admitted between March and May 2019. In this study, the CED resulting from all radiological examinations was calculated and clinical characteristics predictive of higher exposure risk identified. The number of radiological examinations was 12.0 (5.0-26.0) [median (interquartile range) in COVID-19 vs. 4.0 (2.0-8.0) in non-COVID-19 patient (P < 0.001)]. The CED during a four-month period was 4.2 mSv (1.9-11.2) in the COVID-19 vs. 1.2 mSv (0.13-6.19) in the non-COVID-19 patients (P < 0.001). In the survivors, the CED in COVID-19 vs. non-COVID-19 patients was ≥100 mSv in 3% vs. 0%, 10-100 mSv in 23% vs. 15%, 1-10 mSv in 56% vs. 30% and <1 mSv in 18% vs. 55%. The CED (P < 0.001) and CED per ICU hospitalization day (P = 0.004) were significantly higher in COVID-19 than non-COVID-19 patients. The CED correlated significantly with the hospitalization duration (r = 0.45, P < 0.001) and the number of conventional radiological examinations (r = 0.8, P < 0.001). To conclude, more radiological examinations were performed in critically ill COVID-19 patients than non-COVID-19 patients resulting in higher CED. In COVID-19 patients, contribution of strategies to limit CED should be investigated in the future.

Airway management in the critically ill patient with COVID-19.

Critically ill Coronavirus disease 2019 (COVID-19) patients needing endotracheal intubation are on the verge of rapid decompensation. The aims of this review were to assess the risks, the preoxygenation, the device and the hemodynamic management of a patient with COVID-19. The proceduralist performing endotracheal intubation with the entire team are at an increased risk for exposure to COVID-19. Appropriate personal protective equipment and other measures remain essential. For preoxygenation, noninvasive ventilation allows higher oxygen saturation during intubation in severely hypoxemic patients and can be associated with apneic oxygenation and mask ventilation during apnea in selected cases. The COVID-19 pandemic has further highlighted the place of videolaryngoscopy during intubation in intensive care unit (ICU). Hemodynamic optimization is mandatory to limit hypotension and cardiac arrest associated with airway management. Future trials will better define the role of videolaryngoscopy, apneic oxygenation and mask ventilation during apnea for intubation of COVID-19 patients in ICU. The use of fluid loading and vasopressors remains to be investigated in large randomized controlled studies. Choosing the right time for intubation remains uncertain in clinical practice, and future works will probably help to identify earlier the patients who will need intubation.

One year health-related quality of life after discharge: a prospective cohort study among COVID-19 ICU survivors

Considering the paucity of data on long-term Health-Related Quality of Life (HRQoL) in coronavirus disease 2019 (COVID-19) intensive care unit (ICU) survivors, we present one-year follow-up results on patients’ HRQoL and compare them with those of the already reported 6-month follow-up. We conducted a prospective cohort study of patients in COVID-19 ICU between March and June 2020. A HRQoL analysis was performed six months and 1 year after discharge by means of a short-form-36 (SF-36) questionnaire. Hospital mortality in 403 ICU COVID-19 patients was 44.9%; further 4.0% died between hospital discharge and 6-month follow-up and only 0.5% died in the next six months. The median physical component of HRQoL increased from 43.7 (interquartile range (IQR): 31.7–52.7) at 6 months to 46.0 (IQR: 38.0–53.0) 1 year after hospital discharge (p = 0.007). In multivariable regression analysis, age &gt;50 (odds ratio (OR) 0.270) and female sex (OR 0.144) were independently associated with reduced physical HRQoL 1 year after discharge. The median mental component of HRQoL increased from 50.6 (IQR: 42.0–55.8) at 6 months to 53.0 (IQR: 47.0–56.0) 1 year after discharge (p = 0.035), with no significant predictors. Increased HRQoL was associated with an improvement in patients’ physical status, role functioning, emotional well-being (all p &lt; 0.001) and social functioning (p = 0.007). ICU COVID-19 patients’ HRQoL slightly improved 1 year after discharge, when compared to results of the 6-month follow-up. Medications received during ICU stay had no effect on physical or mental HRQoL.

Pattern of Conventional Coagulation and Thromboelastographic Parameters in Patients with COVID-19 Diseases and Association of COVID-Associated Coagulopathy with Mortality in Intensive Care Unit.

Background:Knowledge of underlying pathophysiology of coagulopathy is evolving and the pattern of coagulation parameters in coronavirus disease 2019 (COVID-19)–associated diseases is still not very clear.Aims:In the present study, we aimed to find out the pattern and distribution of conventional coagulation parameters and thromboelastographic (TEG) parameters in COVID-19–associated coagulopathy (CAC) in survivors and nonsurvivors at 28 days.Setting and Design:The present prospective observational study was conducted at a tertiary care COVID-19 intensive care unit (ICU) facility from March 21, 2020, to July 15, 2021.Materials and Methods:Admission clinical and laboratory data (conventional coagulation, inflammatory and TEG parameters, and disease severity parameters) of 64 COVID-19 patients admitted to the ICU were collected. Patients were divided into two groups, i.e., survivors and nonsurvivors.Statistical Analysis:Data were compared between two groups, i.e., survivors versus no survivors on 28 days using Student's t-test/Mann–Whitney U-test or Chi-square test/Fisher's exact test.Results:Admission mean plasma fibrinogen levels (474.82 ± 167.41 mg.dL−1) and D-dimer were elevated (1.78 [0.66, 3.62] mg.mL−1) in the COVID-19 ICU patients. Overall, COVID-19 patients had mean lower normal platelet count (150 ± 50 × 103 cells.mm−3), with marginally elevated prothrombin time (16.25 ± 3.76 s) and activated partial thromboplastin time (38.22 ± 16.72 s). A 65.6% (42/64) TEG profile analysis showed a normal coagulation profile, and the rest 21.9% (14/64) and 12.5% (8/64) had hypercoagulable and hypocoagulable states, respectively. Plasma D-dimer level was markedly elevated in nonsurvivors compared to survivors (P < 0.05), while no other conventional coagulation parameters and TEG profile demonstrated statistically significant between the two groups.Conclusion:Markedly elevated plasma D-dimer level was observed in nonsurvivors of COVID-19 ICU patients. A large portion of COVID-19 ICU patients had a normal TEG profile. Conventional coagulation parameters and TEG profile were similar between survivors and nonsurvivors.

Dynamic Hemostasis and Fibrinolysis Assays in Intensive Care COVID-19 Patients and Association with Thrombosis and Bleeding-A Systematic Review and a Cohort Study.

Patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19), the infectious pathology caused by severe acute respiratory syndrome coronavirus 2, have a high risk of thrombosis, though the precise mechanisms behind this remain unclarified. A systematic literature search in PubMed and EMBASE identified 18 prospective studies applying dynamic coagulation assays in ICU COVID-19 patients. Overall, these studies revealed normal or slightly reduced primary hemostasis, prolonged clot initiation, but increased clot firmness. Thrombin generation assay parameters generally were equivalent to the control groups or within reference range. Fibrinolysis assays showed increased clot resistance. Only six studies related their findings to clinical outcome. We also prospectively included 51 COVID-19 patients admitted to the ICU. Blood samples were examined on day 1, 3-4, and 7-8 with platelet function tests, rotational thromboelastometry (ROTEM), in vivo and ex vivo thrombin generation, and clot lysis assay. Data on thrombosis, bleeding, and mortality were recorded during 30 days. Primary hemostasis was comparable to healthy controls, but COVID-19 patients had longer ROTEM-clotting times and higher maximum clot firmness than healthy controls. Ex vivo thrombin generation was similar to that of healthy controls while in vivo thrombin generation markers, thrombin-antithrombin (TAT) complex, and prothrombin fragment 1 + 2 (F1 + 2) were higher in ICU COVID-19 patients than in healthy controls. Impaired fibrinolysis was present at all time points. TAT complex and F1 + 2 levels were significantly higher in patients developing thrombosis (n = 16) than in those without. In conclusion, only few previous studies employed dynamic hemostasis assays in COVID-19 ICU-patients and failed to reveal a clear association with development of thrombosis. In ICU COVID-19 patients, we confirmed normal platelet aggregation, while in vivo thrombin generation was increased and fibrinolysis decreased. Thrombosis may be driven by increased thrombin formation in vivo.

Physical recovery of COVID-19 pneumosepsis intensive care survivors compared with non-COVID pneumosepsis intensive care survivors during post-intensive care hospitalization: The RECOVID retrospective cohort study.

BackgroundCoronavirusdisease 2019 (COVID‐19) pneumosepsis survivors are at a high risk of developing intensive care unit (ICU)–acquired weakness (ICUAW) because of high incidence of acute respiratory distress syndrome and the common need for prolonged invasive ventilation. It remains unknown whether regular postpneumosepsis physical rehabilitation strategies are suitable for this extraordinary patient category.MethodsWe retrospectively compared the physical recovery of COVID‐19 and non‐COVID pneumosepsis ICU survivors during post‐ICU hospitalization, defined as the difference in performance on the Medical Research Council Sum‐Score (MRC‐SS), Chelsea Critical Care Physical Assessment tool (CPAx), and percentage of predicted handgrip strength (POP‐HGS). An analysis of covariance model was built using age, sex, Barthel index, body mass index, admission Acute Physiology And Chronic Health Evaluation II score, adequacy of protein delivery during ICU stay, and ward length of stay as covariates.ResultsThirty‐five COVID‐19 ICU patients could be compared with 21 non‐COVID pneumosepsis ICU survivors. All patients scored ≤48 on the MRC‐SS at ICU discharge, indicating ICUAW. When controlling for covariates, COVID‐19 patients performed worse on all physical assessments upon ICU discharge, but had improved more at hospital discharge on the MRC‐SS (ɳ2 = 0.214, P =.002) and CPAx (ɳ2 = 0.153, P =.011). POP‐HGS remained lower in COVID‐19 patients throughout hospital stay.ConclusionCOVID‐19 ICU survivors are vulnerable to ICUAW, but they show better tendency towards physical rehabilitation than non‐COVID pneumosepsis ICU survivors during the post‐ICU hospitalization period regarding MRC‐SS and CPAx. COVID‐19 ICU patients might benefit from early, more intensive physical therapy.