Impact of immunosuppressive regimen on ICU acquired pneumonia in critically ill COVID-19.

BACKGROUND: Immunosuppressors (IS) such as Dexamethasone (DXM), Tocilizumab, and high-dose methylprednisolone boli (HDMB), are used in COVID-19-related acute respiratory distress syndrome (ARDS). This study aimed to determine whether COVID-19 ARDS-related combined IS therapy was associated with an increased incidence of ICU-acquired pneumonia (IAP). METHODS: We retrospectively analyzed COVID-19-ARDS admitted to ICU from March 2020 to April 2022. Patients' and IAP characteristics were analyzed according to five IS regimens: No IS, DXM alone, DXM+HDMB, DXM+tocilizumab, and DXM+tocilizumab+HDMB. To investigate the role of IS on IAP incidence, we performed a multivariate logistic regression and built a propensity score. Ultimately, we used a conditional logistic regression after pairing on the propensity score. RESULTS: The study included 496 COVID-19-ARDS. Regarding the IS therapy, 12.7% received no IS, 43% DXM alone, 21.6% DXM+HDMB, 15.5% DXM+tocilizumab and 5.4% DXM+tocilizumab+HDMB. 37% presented at least one IAP, and the IAP incidence was higher with DXM+HDMB (66.4%) compared to no IS (P<0.0001), DXM (P<0.0001) and DXM+tocilizumab (P<0.0001). HDMB and probabilistic antibiotherapy at admission were independent IAP predictors after adjustment on the propensity score (respectively OR:2.44; P<0.0001 and OR:2.85; P<0.001). CONCLUSIONS: In critically ill COVID-19, HDMB significantly increases the risk of IAP whereas DXM alone, nor in combination with tocilizumab, did not.

Impact of corticosteroids on the procoagulant profile of critically ill COVID-19 patients: a before-after study.

BACKGROUND: Several studies have reported an increased risk of thrombotic events in COVID-19 patients, but the pathophysiology of this procoagulant phenotype remains poorly understood. We hypothesized that corticosteroids may attenuate this procoagulant state through their anti-inflammatory effects. The aim of this study was to evaluate the impact of dexamethasone (DXM) on the coagulation profile of severely-ill COVID-19 patients METHODS: We conducted a retrospective, observational before/after bi-centric cohort study among ICU patients hospitalized for severe COVID-19 and receiving therapeutic anticoagulation by unfractionated heparin (UFH). Before and after the standardized use of DXM, we compared inflammatory and coagulation profiles, as well as the kinetics of heparin requirement, adjusted for weight and anti-Xa activity. RESULTS: Eighty-six patients were included, 35 in the no-DXM group, and 51 in the DXM group. At admission, CRP and fibrinogen levels were not different between groups, neither were UFH infusion rates. At day 3 after ICU admission, CRP (178 ± 94 mg/L vs 99± 68 mg/L, p<0.001) and fibrinogen (7.2 ± 1.4 g/L vs 6.1 ± 1.4 g/L, p=0.001) significantly decreased in the DXM group, but not in the no-DXM group. Over time, UFH infusion rates were lower in the DXM group (p<0.001) without any significant difference in plasma anti-Xa activity. CRP variations correlated with heparin dose variations between Day 0 and Day 3 (r=0.39, p=0.009). Finally, the incidence of venous thromboembolic events during in-ICU stay was significantly reduced in the DXM group (4 vs. 43%, p<0.0001). CONCLUSIONS: In critically ill COVID-19 patients, dexamethasone use was associated with a decrease in both pro-inflammatory and procoagulant profile.

Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19.

Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with rarer occurrence of severe disease requiring intensive care. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) is different from that in those infected with variant Delta (n = 111). We observe no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35-1.32]; p = 0.253). Among Omicron-infected patients, 43.2% are immunocompromised, most of whom have received two doses of vaccine or more (85.9%) but display a poor humoral response to vaccination. The mortality rate of immunocompromised patients infected with variant Omicron is significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there is no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms/mutational profile and 28-day mortality.

Endotracheal intubation rate is lower with additional face-mask noninvasive ventilation for critically-ill SARS-CoV-2 patients requiring high-flow nasal oxygen: a retrospective bicentric cohort with propensity score analysis.

BACKGROUND: SARS-CoV-2 pneumonia is responsible for unprecedented numbers of acute respiratory failure requiring invasive mechanical ventilation (IMV). This work aimed to assess whether adding face-mask noninvasive ventilation (NIV) to high-flow nasal oxygen (HFNO) was associated with a reduced need for endotracheal intubation. METHODS: This retrospective cohort study was conducted from July 2020 to January 2021 in two tertiary care intensive care units (ICUs) in Paris, France. Patients admitted for laboratory confirmed SARS-CoV-2 infection with acute hypoxemic respiratory failure requiring HFNO with or without NIV were included. The primary outcome was the rate of endotracheal intubation. Secondary outcomes included day-28 mortality, day-28 respiratory support and IMV free days, ICU and hospital length-of-stay. Sensitivity analyses with both propensity score matching and overlap weighting were used. RESULTS: One hundred twenty-eight patients were included, 88 (69%) received HFNO alone and 40 (31%) received additional NIV. Additional NIV was associated with a reduced rate of endotracheal intubation in multivariate analysis (53 [60%] vs. 15 [38%], HR=0.46 [95% CI: 0.23-0.95], P=0.04). Sensitivity analyses by propensity score matching (HR=0.45 [95% CI: 0.24-0.84], P=0.01) and overlap weighting (HR=0.52 [95% CI: 0.28-0.94], P=0.03) were consistent. Day-28 mortality was 25 (28%) in the HFNO group and 8 (20%) in the NIV group (HR=0.75 [95% CI: 0.15-3.82], P=0.72). NIV was associated with higher IMV free days (20 [0-28] vs. 28 [14-28], P=0.015). All sensitivity analyses were consistent regarding secondary outcomes. CONCLUSIONS: Need for endotracheal intubation was lower in critically-ill SARS-CoV-2 patients receiving face-mask noninvasive mechanical ventilation in addition to high-flow oxygen therapy.

Impaired skin microvascular endothelial reactivity in critically ill COVID-19 patients.

BACKGROUND: Some clinical and histological studies have reported that SARS-CoV-2 infection may damage the endothelium. However, the impact of this virus on endothelial function in vivo remains poorly characterized. In this single-center pilot observational study, we performed iontophoresis of acetylcholine coupled with Laser doppler to investigate microvascular endothelial reactivity in COVID-19 patients compared to patients with non-COVID-19 bacterial pneumonia (NCBP) patients. RESULTS: During three consecutive months, 32 COVID-19 patients and 11 control NCBP patients with acute respiratory failure were included. The median age was 59 [50-68] and 69 [57-75] years in COVID-19 and NCBP groups, respectively (P = 0.11). There was no significant difference in comorbidities or medications between the two groups, except for body mass index, which was higher in COVID-19 patients. NCBP patients had a higher SAPS II score compared to COVID-19 patients (P < 0.0001), but SOFA score was not different between groups (P = 0.51). Global hemodynamic and peripheral tissue perfusion parameters were not different between groups. COVID-19 patients had significantly lower skin microvascular basal blood flow than NCBP patients (P = 0.02). In addition, endothelium-dependent microvascular reactivity was threefold lower in COVID-19 patients than NCBP patients (P = 0.008). CONCLUSIONS: Both baseline skin microvascular blood flow and skin endothelial-dependent microvascular reactivity were impaired in critically ill COVID-19 patients compared to NCBP patients, despite a lower disease severity score supporting a specific pathogenic role of SARS-CoV-2 on the endothelium.

Acute kidney injury in critically ill patients with COVID-19.

Acute kidney injury (AKI) has been reported in up to 25% of critically-ill patients with SARS-CoV-2 infection, especially in those with underlying comorbidities. AKI is associated with high mortality rates in this setting, especially when renal replacement therapy is required. Several studies have highlighted changes in urinary sediment, including proteinuria and hematuria, and evidence of urinary SARS-CoV-2 excretion, suggesting the presence of a renal reservoir for the virus. The pathophysiology of COVID-19 associated AKI could be related to unspecific mechanisms but also to COVID-specific mechanisms such as direct cellular injury resulting from viral entry through the receptor (ACE2) which is highly expressed in the kidney, an imbalanced renin-angotensin-aldosteron system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. Non-specific mechanisms include haemodynamic alterations, right heart failure, high levels of PEEP in patients requiring mechanical ventilation, hypovolemia, administration of nephrotoxic drugs and nosocomial sepsis. To date, there is no specific treatment for COVID-19 induced AKI. A number of investigational agents are being explored for antiviral/immunomodulatory treatment of COVID-19 and their impact on AKI is still unknown. Indications, timing and modalities of renal replacement therapy currently rely on non-specific data focusing on patients with sepsis. Further studies focusing on AKI in COVID-19 patients are urgently warranted in order to predict the risk of AKI, to identify the exact mechanisms of renal injury and to suggest targeted interventions.