Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression that suggest diverse host immune responses. We performed an integrated immune analysis on a cohort of ...50 COVID-19 patients with various disease severity. A distinct phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-β and low IFN-α production and activity), which was associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor nuclear factor-κB and characterized by increased tumor necrosis factor-α and interleukin-6 production and signaling. These data suggest that type I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.
The cholinergic system has been proposed as a potential regulator of COVID-19-induced hypercytokinemia. We investigated whole-blood expression of cholinergic system members and correlated it with ...COVID-19 severity. Patients with confirmed SARS-CoV-2 infection and healthy aged-matched controls were included in this non-interventional study. A whole blood sample was drawn between 9-11 days after symptoms onset, and peripheral leukocyte phenotyping, cytokines measurement, RNA expression and plasma viral load were determined. Additionally, whole-blood expression of native alpha-7 nicotinic subunit and its negative dominant duplicate (CHRFAM7A), choline acetyltransferase and acetylcholine esterase (AchE) were determined. Thirty-seven patients with COVID-19 (10 moderate, 11 severe and 16 with critical disease) and 14 controls were included. Expression of CHRFAM7A was significantly lower in critical COVID-19 patients compared to controls. COVID-19 patients not expressing CHRFAM7A had higher levels of CRP, more extended pulmonary lesions and displayed more pronounced lymphopenia. COVID-19 patients without CHRFAM7A expression also showed increased TNF pathway expression in whole blood. AchE was also expressed in 30 COVID-19 patients and in all controls. COVID-19-induced hypercytokinemia is associated with decreased expression of the pro-inflammatory dominant negative duplicate CHRFAM7A. Expression of this duplicate might be considered before targeting the cholinergic system in COVID-19 with nicotine.
Background
Microvascular, arterial and venous thrombotic events have been largely described during severe coronavirus disease 19 (COVID-19). However, mechanisms underlying hemostasis dysregulation ...remain unclear.
Methods
We explored two independent cross-sectional cohorts to identify soluble markers and gene-expression signatures that discriminated COVID-19 severity and outcomes.
Results
We found that elevated soluble (s)P-selectin at admission was associated with disease severity. Elevated sP-selectin was predictive of intubation and death (ROC AUC = 0.67,
p
= 0.028 and AUC = 0.74,
p
= 0.0047, respectively). An optimal cutoff value was predictive of intubation with 66% negative predictive value (NPV) and 61% positive predictive value (PPV), and of death with 90% NPV and 55% PPV. An unbiased gene set enrichment analysis revealed that critically ill patients had increased expression of genes related to platelet activation. Hierarchical clustering identified
ITG2AB
,
GP1BB
,
PPBP
and
SELPLG
to be upregulated in a grade-dependent manner. ROC curve analysis for the prediction of intubation was significant for
SELPLG
and
PPBP
(AUC = 0.8,
p
= 0.046 for both). An optimal cutoff value for
PBPP
was predictive of intubation with 100% NPV and 45% PPV, and for
SELPLG
with 100% NPV and 50% PPV.
Conclusion
We provide evidence that platelets contribute to COVID-19 severity. Plasma sP-selectin level was associated with severity and in-hospital mortality. Transcriptional analysis identified
PPBP/CXCL7
and
SELPLG
as biomarkers for intubation. These findings provide additional evidence for platelet activation in driving critical COVID-19. Specific studies evaluating the performance of these biomarkers are required.
PURPOSE Patients with hematologic malignancies are increasingly admitted to the intensive care unit (ICU) when life-threatening events occur. We sought to report outcomes and prognostic factors in ...these patients. PATIENTS AND METHODS Ours was a prospective, multicenter cohort study of critically ill patients with hematologic malignancies. Health-related quality of life (HRQOL) and disease status were collected after 3 to 6 months. Results Of the 1,011 patients, 38.2% had newly diagnosed malignancies, 23.1% were in remission, and 24.9% had received hematopoietic stem-cell transplantations (HSCT, including 145 allogeneic). ICU admission was mostly required for acute respiratory failure (62.5%) and/or shock (42.3%). On day1, 733 patients (72.5%) received life-supporting interventions. Hospital, day-90, and 1-year survival rates were 60.7%, 52.5%, and 43.3%, respectively. By multivariate analysis, cancer remission and time to ICU admission less than 24 hours were associated with better hospital survival. Poor performance status, Charlson comorbidity index, allogeneic HSCT, organ dysfunction score, cardiac arrest, acute respiratory failure, malignant organ infiltration, and invasive aspergillosis were associated with higher hospital mortality. Mechanical ventilation (47.9% of patients), vasoactive drugs (51.2%), and dialysis (25.9%) were associated with mortality rates of 60.5%, 57.5%, and 59.2%, respectively. On day 90, 80% of survivors had no HRQOL alterations (physical and mental health similar to that of the overall cancer population). After 6 months, 80% of survivors had no change in treatment intensity compared with similar patients not admitted to the ICU, and 80% were in remission. CONCLUSION Critically ill patients with hematologic malignancies have good survival, disease control, and post-ICU HRQOL. Earlier ICU admission is associated with better survival.
Background
The aim of this study is to determine whether severe COVID-19 patients harbour a higher risk of ICU-acquired pneumonia.
Methods
This retrospective multicentre cohort study comprised all ...consecutive patients admitted to seven ICUs for severe COVID-19 pneumonia during the first COVID-19 surge in France. Inclusion criteria were laboratory-confirmed SARS-CoV-2 infection and requirement for invasive mechanical ventilation for 48 h or more. Control groups were two historical cohorts of mechanically ventilated patients admitted to the ICU for bacterial or non-SARS-CoV-2 viral pneumonia. The outcome of interest was the development of ICU-acquired pneumonia. The determinants of ICU-acquired pneumonia were investigated in a multivariate competing risk analysis.
Result
One hundred and seventy-six patients with severe SARS-CoV-2 pneumonia admitted to the ICU between March 1st and 30th June of 2020 were included into the study. Historical control groups comprised 435 patients with bacterial pneumonia and 48 ones with viral pneumonia. ICU-acquired pneumonia occurred in 52% of COVID-19 patients, whereas in 26% and 23% of patients with bacterial or viral pneumonia, respectively (
p
< 0.001). Times from initiation of mechanical ventilation to ICU-acquired pneumonia were similar across the three groups. In multivariate analysis, the risk of ICU-acquired pneumonia remained independently associated with underlying COVID-19 (SHR = 2.18; 95 CI 1.2–3.98,
p
= 0.011).
Conclusion
COVID-19 appears an independent risk factor of ICU-acquired pneumonia in mechanically ventilated patients with pneumonia. Whether this is driven by immunomodulatory properties by the SARS-CoV-2 or this is related to particular processes of care remains to be investigated.
Managing patients with acute respiratory distress syndrome (ARDS) requires frequent changes in mechanical ventilator respiratory settings to optimize arterial oxygenation assessed by arterial oxygen ...partial pressure (PaO
) and saturation (SaO
). Pulse oxymetry (SpO
) has been suggested as a non-invasive surrogate for arterial oxygenation however its accuracy in COVID-19 patients is unknown. In this study, we aimed to investigate the influence of COVID-19 status on the association between SpO
and arterial oxygenation. We prospectively included patients with ARDS and compared COVID-19 to non-COVID-19 patients, regarding SpO
and concomitant arterial oxygenation (SaO
and PaO
) measurements, and their association. Bias was defined as mean difference between SpO
and SaO
measurements. Occult hypoxemia was defined as a SpO
≥ 92% while concomitant SaO
< 88%. Multiple linear regression models were built to account for confounders. We also assessed concordance between positive end-expiratory pressure (PEEP) trial-induced changes in SpO
and in arterial oxygenation. We included 55 patients, among them 26 (47%) with COVID-19. Overall, SpO
and SaO
measurements were correlated (r = 0.70; p < 0.0001), however less so in COVID-19 than in non-COVID-19 patients (r = 0.55, p < 0.0001 vs. r = 0.84, p < 0.0001, p = 0.002 for intergroup comparison). Bias was + 1.1%, greater in COVID-19 than in non-COVID-19 patients (2.0 vs. 0.3%; p = 0.02). In multivariate analysis, bias was associated with COVID-19 status (unstandardized β = 1.77, 95%CI = 0.38-3.15, p = 0.01), ethnic group and ARDS severity. Occult hypoxemia occurred in 5.5% of measurements (7.7% in COVID-19 patients vs. 3.4% in non-COVID-19 patients, p = 0.42). Concordance rate between PEEP trial-induced changes in SpO
and SaO
was 84%, however less so in COVID-19 than in non-COVID-19 patients (69% vs. 97%, respectively). Similar results were observed for PaO
regarding correlations, bias, and concordance with SpO
changes. In patients with ARDS, SpO
was associated with arterial oxygenation, but COVID-19 status significantly altered this association.
Whether to perform or not an immediate percutaneous coronary intervention (PCI) after out-of-hospital cardiac arrest is still debated. We aimed to evaluate the impact of PCI on short- and long-term ...survival in out-of-hospital cardiac arrest patients admitted after successful resuscitation.
Between 2000 and 2013, all nontrauma out-of-hospital cardiac arrest patients admitted in a Parisian cardiac arrest center after return of spontaneous circulation were prospectively included. The association between immediate PCI and short- and long-term mortality was analyzed using logistic regression and Cox multivariate analysis, respectively. Propensity score-matching method was used to assess the influence of PCI on short- and long-term survival. During the study period, 1722 patients (71.5% male, median age 60 49.6, 72.2 years) were analyzed: 628 (35.6%) without coronary angiography, 615 (35.7%) with coronary angiography without PCI, and 479 (27.8%) with both. Among these groups, day 30 and year-10 survival rates were 21% and 11.9%, 35% and 29%, 43% and 38%, respectively (P<0.01 for each). PCI as compared with no coronary angiography was associated with a lower day-30 and long-term mortality (adjORcoro with PCI versus no coro 0.71, 95% confidence interval 0.54, 0.92; P=0.02 and adjHRcoro with PCI versus no coro 0.44, 95% confidence interval 0.27, 0.71; P<0.01, respectively). PCI remained associated with a lower risk of long-term mortality (adjHR 0.29; 95% confidence interval 0.14, 0.61; P<0.01) in propensity score-matching analysis.
Immediate PCI after out-of-hospital cardiac arrest was associated with significant reduced risk of short- and long-term mortality. These findings should suggest physicians to consider immediate coronary angiography and PCI if indicated in these patients.
Purpose
Prognosis of solid organ transplant (SOT) recipients has improved, mainly because of better prevention of rejection by immunosuppressive therapies. However, SOT recipients are highly ...susceptible to conventional and opportunistic infections, which represent a major cause of morbidity, graft dysfunction and mortality.
Methods
Narrative review.
Results
We cover the current epidemiology and main aspects of infections in SOT recipients including risk factors such as postoperative risks and specific risks for different transplant recipients, key points on anti-infective prophylaxis as well as diagnostic and therapeutic approaches. We provide an up-to-date guide for management of the main syndromes that can be encountered in SOT recipients including acute respiratory failure, sepsis or septic shock, and central nervous system infections as well as bacterial infections with multidrug-resistant strains, invasive fungal diseases, viral infections and less common pathogens that may impact this patient population.
Conclusion
We provide state-of the art review of available knowledge of critically ill SOT patients with infections.
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