Impact of sex differences on cardiac injury in critically ill patients with COVID-19.

BACKGROUND: COVID-19 infections are associated with accrued inflammatory responses which may result in cardiac injury. Immune response to infection appears different between men and women, suggesting that COVID-19 patients' outcomes may differ according to biological sex. However, the impact of biological sex on the occurrence of cardiac injury during intensive care unit (ICU) stay in COVID-19 patients remain unclear. METHODS: In this multicenter and prospective study, we included consecutive patients admitted to ICU for severe COVID-19 pneumonia, during the first two pandemic waves. Biological, electrocardiogram (ECG) and echocardiographic variables were collected on ICU admission. Cardiac injury was defined by increased troponin above 99th percentile of upper norm value and newly diagnosed ECG and/or echocardiographic abnormalities. The primary endpoint was the proportion of patients with cardiac injury during ICU stay according to biological sex. The impact of biological sex on other subsequent clinical outcomes was also evaluated. RESULTS: We included 198 patients with a median age of 66 (56-73) years, 147 (74%) patients were men and 51 (26%) were women. Overall, 119 (60%) patients had cardiac injury during ICU stay and the proportion of patients with cardiac injury during ICU stay was not different between men and women (60% vs. 61%, p = 1.00). Patients with cardiac injury during ICU stay showed more cardiovascular risk factors and chronic cardiac disease and had a higher ICU mortality rate. On ICU admission, they had a more marked lymphopenia (0.70 (0.40-0.80) vs. 0.80 (0.50-1.10) × 109/L, p < 0.01) and inflammation (C-Reactive Protein (155 (88-246) vs. 111 (62-192) mg/L, p = 0.03); D-Dimers (1293 (709-2523) vs. 900 (560-1813) µg/L, p = 0.03)). Plasmatic levels of inflammatory biomarkers on ICU admission correlated with SAPS-2 and SOFA scores but not with the different echocardiographic variables. Multivariate analysis confirmed cardiovascular risk factors (OR = 2.31; 95%CI (1.06-5.02), p = 0.03) and chronic cardiac disease (OR = 8.58; 95%CI (1.01-73.17), p = 0.04) were independently associated with the occurrence of cardiac injury during ICU stay, whereas biological sex (OR = 0.88; 95%CI (0.42-1.84), p = 0.73) was not. Biological sex had no impact on the occurrence during ICU stay of other clinical outcomes. CONCLUSIONS: Most critically ill patients with COVID-19 were men and experienced cardiac injury during ICU stay. Nevertheless, biological sex had no impact on the occurrence of cardiac injury during ICU stay or on other clinical outcomes. Clinical trial registration NCT04335162.

Prognostic value of right ventricular dilatation in patients with low-risk pulmonary embolism.

The prognosis of multidetector computed tomography (MDCT) assessed right ventricular dilatation (RVD) is unclear in patients with pulmonary embolism (PE) and a simplified Pulmonary Embolism Severity Index (sPESI) of 0. We investigated in these patients whether MDCT-assessed RVD, defined by a right to left ventricular ratio (RV/LV) ≥0.9 or ≥1.0, is associated with worse outcomes.We combined data from three prospective cohorts of patients with PE. The main study outcome was the composite of 30-day all-cause mortality, haemodynamic collapse or recurrent PE in patients with sPESI of 0.Among 779 patients with a sPESI 0, 420 (54%) and 299 (38%) had a RV/LV ≥0.9 and ≥1.0 respectively. No difference in primary outcome was observed, 0.95% (95% CI 0.31-2.59) versus 0.56% (95% CI 0.10-2.22; p=0.692) and 1.34% (95% CI 0.43-3.62) versus 0.42% (95% CI 0.07-1.67; p=0.211) with RV/LV ≥0.9 and ≥1.0 respectively. Increasing the RV/LV threshold to ≥1.1, the outcome occurred more often in patients with RVD (2.12%, 95% CI 0.68-5.68 versus 0.34%, 95% CI 0.06-1.36; p=0.033).MDCT RV/LV ratio of ≥0.9 and ≥1.0 in sPESI 0 patients is frequent but not associated with a worse prognosis but higher cut-off values might be associated with worse outcome in these patients.

Distal Lung Inflammation Assessed by Alveolar Concentration of Nitric Oxide Is an Individualised Biomarker of Severe COVID-19 Pneumonia.

Pulmonary sequelae as assessed by pulmonary function tests (PFTs) are often reported in patients infected by SARS-CoV-2 during the post-COVID-19 period. Little is known, however, about the status of pulmonary inflammation during clinical recovery after patients' discharge from the hospitals. We prospectively measured PFTs coupled with the exhaled nitric oxide (NO) stemming from the proximal airways (FeNO) and the distal lung (CaNO) in 169 consecutive patients with varying degrees of the severity of COVID-19 six weeks to one year after acute infection by SARS-CoV-2. The proportions of patients with abnormal PFTs, defined as the presence of either obstructive/restrictive patterns or impaired lung gas transfer, or both, increased with the severity of the initial lung disease (15, 30, and 52% in patients with mild, moderate, and severe COVID-19). FeNO values remained within normal ranges and did not differ between the three groups of patients. CaNO, however, was significantly higher in patients with severe or critical COVID-19, compared with patients with milder forms of the disease. There was also an inverse relationship between CaNO and DLCO. We conclude that the residual inflammation of the distal lung is still present in the post-COVID-19 follow-up period, in particular, in those patients with an initially severe form of COVID-19. This long-lasting alveolar inflammation might contribute to the long-term development of pulmonary fibrosis and warrants the regular monitoring of exhaled NO together with PFTs in patients with COVID-19.

Seasonal burden of severe influenza virus infection in the critically ill patients, using the Assistance Publique-Hôpitaux de Paris clinical data warehouse: a pilot study.

PURPOSE: At the critical care level, the flu surveillance system is limited in France, with heterogeneous regional modalities of implementation. MATERIALS, PATIENTS AND METHODS: We aimed at assessing the relevance of the Assistance Publique-Hôpitaux de Paris (AP-HP) clinical data warehouse for estimating the burden of the influenza epidemic on medical adult critical care units of the AP-HP, and outcome of patients during the flu season 2017-2018. This exploratory multi-site epidemiological study comprised all consecutive adult stays (n = 320) in 18 medical intensive care units (ICU) or intermediate care wards (ICW) for probable or confirmed Influenza virus infection during the 2017-2018 flu season. RESULTS: Patients admitted to ICU/ICW had low vaccination coverage (21%), required life support in 60% of cases, stayed in the ICU for a median of 8 days, and had high 28-day mortality rate (19.7%; 95% confidence interval 15.5-24.5). Early prognostic factors included age, core temperature, the acute organ failures score, and the early administration of antiviral therapy. CONCLUSIONS: Data directly extracted from the electronic medical records stored in the data warehouse provide detailed clinical, care pathway and prognosis information. The real-time availability should enable to detect and assess the burden of the most severe cases. By a firmer and more acute monitoring and adjustment of care and patient management, hospitals could generate more ICU/ICW capacities, sensitize their emergency department and contribute to the recommendations from health authorities. This pilot study is of particular relevance in the context of emerging epidemics of severe acute respiratory diseases.

Determining extent of COVID-19 pneumonia on CT based on biological variables.

INTRODUCTION: Covid-19 pneumonia CT extent correlates well with outcome including mortality. However, CT is not widely available in many countries. This study aimed to explore the relationship between Covid-19 pneumonia CT extent and blood tests variations. The objective was to determine for the biological variables correlating with disease severity the cut-off values showing the best performance to predict the parenchymal extent of the pneumonia. METHODS: Bivariate correlations were calculated between biological variables and grade of disease extent on CT. Receiving Operating Characteristic curve analysis determined the best cutoffs for the strongest correlated biological variables. The performance of these variables to predict mild (<10%) or severe pneumonia (>50% of parenchyma involved) was evaluated. RESULTS: Correlations between biological variables and disease extent was evaluated in 168 patients included in this study. LDH, lymphocyte count and CRP showed the strongest correlations (with 0.67, -0.41 and 0.52 correlation coefficient, respectively). Patients were split into a training and a validation cohort according to their centers. If one variable was above/below the following cut-offs, LDH>380, CRP>80 or lymphocyte count <0.8G/L, severe pneumonia extent on CT was detected with 100% sensitivity. Values above/below all three thresholds were denoted in 73% of patients with severe pneumonia extent. The combination of LDH<220 and CRP<22 was associated with mild pneumonia extent (<10%) with specificity of 100%. DISCUSSION: LDH showed the strongest correlation with the extent of Covid-19 pneumonia on CT. Combined with CRP±lymphocyte count, it helps predicting parenchymal extent of the pneumonia when CT scan is not available.

Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling.

Heterozygous missense mutations in coatomer protein subunit α, COPA, cause a syndrome overlapping clinically with type I IFN-mediated disease due to gain-of-function in STING, a key adaptor of IFN signaling. Recently, increased levels of IFN-stimulated genes (ISGs) were described in COPA syndrome. However, the link between COPA mutations and IFN signaling is unknown. We observed elevated levels of ISGs and IFN-α in blood of symptomatic COPA patients. In vitro, both overexpression of mutant COPA and silencing of COPA induced STING-dependent IFN signaling. We detected an interaction between COPA and STING, and mutant COPA was associated with an accumulation of ER-resident STING at the Golgi. Given the known role of the coatomer protein complex I, we speculate that loss of COPA function leads to enhanced type I IFN signaling due to a failure of Golgi-to-ER STING retrieval. These data highlight the importance of the ER-Golgi axis in the control of autoinflammation and inform therapeutic strategies in COPA syndrome.

Determinants and prognostic implication of diagnostic delay in patients with a first episode of pulmonary embolism.

Signs and symptoms of pulmonary embolism (PE) are not specific and this can lead to a diagnostic delay. Little is known about the determinants of this delay and its prognostic implication. We conducted a retrospective analysis of a prospective cohort involving 514 patients with a first episode of PE. The diagnostic delay was defined as a time from first symptom onset to diagnosis of >3 days, corresponding of the median time in the population. Multivariable logistic regression analysis was performed to identify determinants of diagnostic delay. Prognostic implication was measured as the occurrence of 30-day all-cause mortality, haemodynamic collapse or recurrent PE. A total of 240 (47%) among 514 patients had a time from first symptom to diagnosis > 3 days. Previous deep vein thrombosis (OR 0.55, 95% Confidence Interval (CI), 0.32-0.93), immobilization (OR 0.52, 95% CI, 0.28-0.96), surgery (OR 0.31, 95% CI, 0.16-0.62), chest pain (OR 0.58, 95% CI, 0.39-0.86), syncope (OR 0.48, 95% CI, 0.23-1.01), dyspnea (OR 2.48, 95% CI, 1.57-3.91) and hemoptysis (OR 3.57, 95% CI, 1.40-9.07) were associated with diagnostic delay. Twenty-two patients (4.3%, 95%CI, 2.8-6.5) experienced an outcome event within 30 days. Among them, 15 patients (6.2% 95%CI, 3.7-10.3) had a diagnostic delay and 7 (2.6%, 95% CI 1.1-5.4) did not (p = 0.039). In this cohort, diagnostic delay is associated with the absence of major risk factors for PE or clinical features such as chest pain or syncope and the presence of dyspnea or hemoptysis. Diagnostic delay is associated with a worse 30-day prognosis.