Comparison of renal histopathology and gene expression profiles between severe COVID-19 and bacterial sepsis in critically ill patients

 

Comparison of renal histopathology and gene expression profiles between severe COVID-19 and bacterial sepsis in critically ill patients

 

by Meint Volbeda, Daniela Jou-Valencia, Marius C. van den Heuvel, Marjolein Knoester, Peter J. Zwiers, Janesh Pillay, Stefan P. Berger, Peter H. J. van der Voort, Jan G. Zijlstra, Matijs van Meurs and Jill Moser 

 

Critical Care volume 25, Article number: 202 (2021) 

 

Background

The mechanisms driving acute kidney injury (AKI) in critically ill COVID-19 patients are unclear. We collected kidney biopsies from COVID-19 AKI patients within 30 min after death in order to examine the histopathology and perform mRNA expression analysis of genes associated with renal injury.

Methods

This study involved histopathology and mRNA analyses of postmortem kidney biopsies collected from patients with COVID-19 (n = 6) and bacterial sepsis (n = 27). Normal control renal tissue was obtained from patients undergoing total nephrectomy (n = 12). The mean length of ICU admission-to-biopsy was 30 days for COVID-19 and 3–4 days for bacterial sepsis patients.

Results

We did not detect SARS-CoV-2 RNA in kidney biopsies from COVID-19-AKI patients yet lung tissue from the same patients was PCR positive. Extensive acute tubular necrosis (ATN) and peritubular thrombi were distinct histopathology features of COVID-19-AKI compared to bacterial sepsis-AKI. ACE2 mRNA levels in both COVID-19 (fold change 0.42, p = 0.0002) and bacterial sepsis patients (fold change 0.24, p < 0.0001) were low compared to control. The mRNA levels of injury markers NGAL and KIM-1 were unaltered compared to control tissue but increased in sepsis-AKI patients. Markers for inflammation and endothelial activation were unaltered in COVID-19 suggesting a lack of renal inflammation. Renal mRNA levels of endothelial integrity markers CD31, PV-1 and VE-Cadherin did not differ from control individuals yet were increased in bacterial sepsis patients (CD31 fold change 2.3, p = 0.0006, PV-1 fold change 1.5, p = 0.008). Angiopoietin-1 mRNA levels were downregulated in renal tissue from both COVID-19 (fold change 0.27, p < 0.0001) and bacterial sepsis patients (fold change 0.67, p < 0.0001) compared to controls. Moreover, low Tie2 mRNA expression (fold change 0.33, p = 0.037) and a disturbed VEGFR2/VEGFR3 ratio (fold change 0.09, p < 0.0001) suggest decreased microvascular flow in COVID-19.

Conclusions

In a small cohort of postmortem kidney biopsies from COVID-19 patients, we observed distinct histopathological and gene expression profiles between COVID-19-AKI and bacterial sepsis-AKI. COVID-19 was associated with more severe ATN and microvascular thrombosis coupled with decreased microvascular flow, yet minimal inflammation. Further studies are required to determine whether these observations are a result of true pathophysiological differences or related to the timing of biopsy after disease onset.

Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis

 

Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis

Intensive Care Medicine Published: 19 April 2021

Purpose

Corticosteroids are now recommended for patients with severe COVID-19 including those with COVID-related ARDS. This has generated renewed interest regarding whether corticosteroids should be used in non-COVID ARDS as well. The objective of this study was to summarize all RCTs examining the use of corticosteroids in ARDS.

Methods

The protocol of this study was pre-registered on PROSPERO (CRD42020200659). We searched online databases including MEDLINE, EMBASE, CDC library of COVID research, CINAHL, and COCHRANE. We included RCTs that compared the effect of corticosteroids to placebo or usual care in adult patients with ARDS, including patients with COVID-19. Three reviewers abstracted data independently and in duplicate using a pre-specified standardized form. We assessed individual study risk of bias using the revised Cochrane ROB-2 tool and rated certainty in outcomes using GRADE methodology. We pooled data using a random effects model. The main outcome for this review was 28-day-mortality.

Results

We included 18 RCTs enrolling 2826 patients. The use of corticosteroids probably reduced mortality in patients with ARDS of any etiology (2740 patients in 16 trials, RR 0.82, 95% CI 0.72–0.95, ARR 8.0%, 95% CI 2.2–12.5%, moderate certainty). Patients who received a longer course of corticosteroids (over 7 days) had higher rates of survival compared to a shorter course.

Conclusion

The use of corticosteroids probably reduces mortality in patients with ARDS. This effect was consistent between patients with COVID-19 and non-COVID-19 ARDS, corticosteroid types, and dosage.

Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies

 

Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies

 

by Eleni Papoutsi, Vassilis G. Giannakoulis, Eleni Xourgia, Christina Routsi, Anastasia Kotanidou and Ilias I. Siempos 

 

Critical Care volume 25, Article number: 121 (2021) 

 

Background

Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis.

Methods

PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147).

Results

A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08).

Conclusions

The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.

Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method

 

Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method

 

by Prashant Nasa, Elie Azoulay, Ashish K. Khanna, Ravi Jain, Sachin Gupta, Yash Javeri, Deven Juneja, Pradeep Rangappa, Krishnaswamy Sundararajan, Waleed Alhazzani, Massimo Antonelli, Yaseen M. Arabi, Jan Bakker, Laurent J. Brochard, Adam M. Deane, Bin Du… 

 

Critical Care volume 25, Article number: 106 (2021) 

 

Background

Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice.

Methods

Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p < 0·05 was considered as unstable).

Results

Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16–24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment.

Conclusion

Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited.

Trial registration: The study was registered with Clinical trials.gov Identifier: NCT04534569.

 

Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update

 

Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update

Critical Care Medicine: March 2021 - Volume 49 - Issue 3 - p e219-e234

 

BACKGROUND:

 The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU.

METHODS:

The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization’s definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility.

RESULTS:

The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning.

CONCLUSION:

The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.

Is Cardiopulmonary Resuscitation Futile in Coronavirus Disease 2019 Patients Experiencing In-Hospital Cardiac Arrest?*

 

Is Cardiopulmonary Resuscitation Futile in Coronavirus Disease 2019 Patients Experiencing In-Hospital Cardiac Arrest?*

 

by Shah, Priyank; Smith, Hallie; Olarewaju, Ayodeji; Jani, Yash; Cobb, Abigail; Owens, Jack; Moore, Justin; Chenna, Avantika; Hess, David 

 

Critical Care Medicine: February 2021 - Volume 49 - Issue 2 - p 201-208

 

Objectives: 

There is limited data regarding outcomes after in-hospital cardiac arrest among coronavirus disease 2019 patients. None of the studies have reported the outcomes of in-hospital cardiac arrest in coronavirus disease 2019 patients in the United States. We describe the characteristics and outcomes of in-hospital cardiac arrest in coronavirus disease 2019 patients in rural Southwest Georgia.

Design: 

Retrospective cohort study.

Setting: 

Single-center, multihospital.

PATIENTS: 

Consecutive coronavirus disease 2019 patients who experienced in-hospital cardiac arrest with attempted resuscitation.

Interventions: 

Attempted resuscitation with advanced cardiac life support.

Measurement and Main Results: 

Out of 1,094 patients hospitalized for coronavirus disease 2019 during the study period, 63 patients suffered from in-hospital cardiac arrest with attempted resuscitation and were included in this study. The median age was 66 years, and 49.2% were males. The majority of patients were African Americans (90.5%). The most common comorbidities were hypertension (88.9%), obesity (69.8%), diabetes (60.3%), and chronic kidney disease (33.3%). Eighteen patients (28.9%) had a Charlson Comorbidity Index of 0–2. The most common presenting symptoms were shortness of breath (63.5%), fever (52.4%), and cough (46%). The median duration of symptoms prior to admission was 14 days. During hospital course, 66.7% patients developed septic shock, and 84.1% had acute respiratory distress syndrome. Prior to in-hospital cardiac arrest, 81% were on ventilator, 60.3% were on vasopressors, and 39.7% were on dialysis. The majority of in-hospital cardiac arrest (84.1%) occurred in the ICU. Time to initiation of advanced cardiac life support protocol was less than 1 minute for all in-hospital cardiac arrest in the ICU and less than 2 minutes for the remaining patients. The most common initial rhythms were pulseless electrical activity (58.7%) and asystole (33.3%). Although return of spontaneous circulation was achieved in 29% patients, it was brief in all of them. The in-hospital mortality was 100%.

Conclusions: 

In our study, coronavirus disease 2019 patients suffering from in-hospital cardiac arrest had 100% in-hospital mortality regardless of the baseline comorbidities, presenting illness severity, and location of arrest.

 

Early Percutaneous Tracheostomy in Coronavirus Disease 2019: Association With Hospital Mortality and Factors Associated With Removal of Tracheostomy Tube at ICU Discharge. A Cohort Study on 121 Patients*

 

by Rosano, Antonio; Martinelli, Enrico; Fusina, Federica; Albani, Filippo; Caserta, Rosalba; Morandi, Alessandro; Dell’Agnolo, Piera; Dicembrini, Alessandra; Mansouri, Leila; Marchini, Andrea; Schivalocchi, Valeria; Natalini, Giuseppe 

Critical Care Medicine: February 2021 - Volume 49 - Issue 2 - p 261-270

 

Objectives: Early tracheotomy, defined as a procedure performed within 10 days from intubation, is associated with more ventilator free days, shorter ICU stay, and lower mortality than late tracheotomy. During the coronavirus disease 2019 pandemic, it was especially important to save operating room resources and to have a shorter ICU stay for patients, when ICUs had insufficient beds. In this context of limited resources, early percutaneous tracheostomy could be an effective way to manage mechanically ventilated patients. Nevertheless, current recommendations suggest delaying or avoiding the tracheotomy in coronavirus disease 2019 patients. Aim of the study was to analyze the hospital mortality of coronavirus disease 2019 patients who had received early percutaneous tracheostomy and factors associated with removal of tracheostomy cannula at ICU discharge.

Design: Cohort study. Setting: Coronavirus disease 2019 ICU.

Patients: Adult patients with coronavirus disease 2019 3 days after ICU admission. Interventions: None.

Measurements and Main Results: Three days after ICU admission, 164 patients were present in ICU and included in the analysis. One-hundred and twenty-one patients (74%) were tracheostomized, whereas the other 43 (26%) were managed with translaryngeal intubation only. In multivariable analysis, early percutaneous tracheostomy was associated with lower hospital mortality. Sixty-six of tracheostomized patients (55%) were discharged alive from the hospital. Age and male sex were the only characteristics that were independently associated with mortality in the tracheostomized patients (45.5% and 62.8% in tracheostomized and nontracheostomized patients, respectively; p = 0.009). Tracheostomy tube was removed in 47 of the tracheostomized patients (71%). The only variable independently associated with weaning from tracheostomy at ICU discharge was a faster start of spontaneous breathing after tracheotomy was performed.

Conclusions: Early percutaneous tracheostomy was safe and effective in coronavirus disease 2019 patients, giving a good chance of survival and of weaning from tracheostomy cannula at ICU discharge.

 

 

 

 

Ventilator-associated pneumonia in critically ill patients with COVID-19

 Ventilator-associated pneumonia in critically ill patients with COVID-19

 

by Mailis Maes, Ellen Higginson, Joana Pereira-Dias, Martin D. Curran, Surendra Parmar, Fahad Khokhar, Delphine Cuchet-Lourenço, Janine Lux, Sapna Sharma-Hajela, Benjamin Ravenhill, Islam Hamed, Laura Heales, Razeen Mahroof, Amelia Solderholm, Sally Forrest, Sushmita Sridhar…

 

Critical Care volume 25, Article number: 25 (2021)

 

Background

Pandemic COVID-19 caused by the coronavirus SARS-CoV-2 has a high incidence of patients with severe acute respiratory syndrome (SARS). Many of these patients require admission to an intensive care unit (ICU) for invasive ventilation and are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP).

Objectives

To study the incidence of VAP and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients.

Methods

In this retrospective observational study, we compared the incidence of VAP and secondary infections using a combination of microbial culture and a TaqMan multi-pathogen array. In addition, we determined the lung microbiome composition using 16S RNA analysis in a subset of samples. The study involved 81 COVID-19 and 144 non-COVID-19 patients receiving invasive ventilation in a single University teaching hospital between March 15th 2020 and August 30th 2020.

Results

COVID-19 patients were significantly more likely to develop VAP than patients without COVID (Cox proportional hazard ratio 2.01 95% CI 1.14–3.54, p = 0.0015) with an incidence density of 28/1000 ventilator days versus 13/1000 for patients without COVID (p = 0.009). Although the distribution of organisms causing VAP was similar between the two groups, and the pulmonary microbiome was similar, we identified 3 cases of invasive aspergillosis amongst the patients with COVID-19 but none in the non-COVID-19 cohort. Herpesvirade activation was also numerically more frequent amongst patients with COVID-19.

Conclusion

COVID-19 is associated with an increased risk of VAP, which is not fully explained by the prolonged duration of ventilation. The pulmonary dysbiosis caused by COVID-19, and the causative organisms of secondary pneumonia observed are similar to that seen in critically ill patients ventilated for other reasons.

Comparison between first and second wave among critically ill COVID-19 patients admitted to a French ICU: no prognostic improvement during the second wave?

 

Comparison between first and second wave among critically ill COVID-19 patients admitted to a French ICU: no prognostic improvement during the second wave?

 

by Damien Contou, Megan Fraissé, Olivier Pajot, Jo-Anna Tirolien, Hervé Mentec and Gaëtan Plantefève 

 

Critical Care volume 25, Article number: 3 (2021)

 

As many countries in Europe, France faced a second wave COVID-19 pandemic since September, 2020. During the first wave, intensivists faced an unprecedented massive admission of patients with COVID-19 pneumonia requiring invasive mechanical ventilation, sometimes leading to ICUs saturation. They discovered the stereotypical course of this previously unknown disease with its own specificities including the need for deep sedation and neuromuscular blockade, the increased risk of thrombotic and hemorrhagic events [1, 2], and the prolonged duration of mechanical ventilation [3] with high rate of delirium [4]. Importantly, several randomized controlled trials conducted during this first wave highlighted the beneficial effects of early administration of glucocorticoids for critically ill COVID-19 patients [5, 6].

One can legitimately assume that the experience gained during the first wave may have contributed to a better management and outcome among critically ill COVID-19 patients admitted during the second wave.

We therefore compared the characteristics and the outcome between patients admitted to our 41-bed COVID-19 ICU for acute respiratory failure due to COVID-19 (RT-PCR positive for SARS-CoV-2) during the first wave (from March 13th to May 27th, 2020) and those admitted to our 18-bed ICU during the second wave (from August 19th to December 7th, 2020).

COVID-19 patients without acute respiratory failure, those transferred to other ICUs or still hospitalized in ICU were not included.

Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study

 

Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study

 

by Pablo Monedero, Alfredo Gea, Pedro Castro, Angel M. Candela-Toha, María L. Hernández-Sanz, Egoitz Arruti, Jesús Villar and Carlos Ferrando 

 

Critical Care volume 25, Article number: 2 (2021)

 

Background

Critically ill patients with coronavirus disease 19 (COVID-19) have a high fatality rate likely due to a dysregulated immune response. Corticosteroids could attenuate this inappropriate response, although there are still some concerns regarding its use, timing, and dose.

Methods

This is a nationwide, prospective, multicenter, observational, cohort study in critically ill adult patients with COVID-19 admitted into Intensive Care Units (ICU) in Spain from 12th March to 29th June 2020. Using a multivariable Cox model with inverse probability weighting, we compared relevant outcomes between patients treated with early corticosteroids (before or within the first 48 h of ICU admission) with those who did not receive early corticosteroids (delayed group) or any corticosteroids at all (never group). Primary endpoint was ICU mortality. Secondary endpoints included 7-day mortality, ventilator-free days, and complications.

Results

A total of 691 patients out of 882 (78.3%) received corticosteroid during their hospital stay. Patients treated with early-corticosteroids (n = 485) had lower ICU mortality (30.3% vs. never 36.6% and delayed 44.2%) and lower 7-day mortality (7.2% vs. never 15.2%) compared to non-early treated patients. They also had higher number of ventilator-free days, less length of ICU stay, and less secondary infections than delayed treated patients. There were no differences in medical complications between groups. Of note, early use of moderate-to-high doses was associated with better outcomes than low dose regimens.

Conclusion

Early use of corticosteroids in critically ill patients with COVID-19 is associated with lower mortality than no or delayed use, and fewer complications than delayed use.

Protracted viral shedding and viral load are associated with ICU mortality in Covid-19 patients with acute respiratory failure

 

Protracted viral shedding and viral load are associated with ICU mortality in Covid-19 patients with acute respiratory failure

 

by L. Bitker, F. Dhelft, L. Chauvelot, E. Frobert, L. Folliet, M. Mezidi, S. Trouillet-Assant, A. Belot, B. Lina, F. Wallet and J. C. Richard

 

Annals of Intensive Care volume 10, Article number: 167 (2020) Published: 10 December 2020

Background

Protracted viral shedding is common in hospitalized patients with COVID-19 pneumonia, and up to 40% display signs of pulmonary fibrosis on computed tomography (CT) after hospital discharge. We hypothesized that COVID-19 patients with acute respiratory failure (ARF) who die in intensive care units (ICU) have a lower viral clearance in the respiratory tract than ICU patients discharged alive, and that protracted viral shedding in respiratory samples is associated with patterns of fibroproliferation on lung CT. We, therefore, conducted a retrospective observational study, in 2 ICU of Lyon university hospital.

Results

129 patients were included in the study, of whom 44 (34%) died in ICU. 432 RT-PCR for SARS-CoV-2 were performed and 137 CT scans were analyzed. Viral load was significantly higher in patients deceased as compared to patients alive at ICU discharge (p < 0.001), after adjustment for the site of viral sampling and RT-PCR technique. The median time to SARS-CoV-2 negativation on RT-PCR was 19 days [CI95 %:15–21] in patients alive at ICU discharge and 26 days [CI95 %:17-infinity] in non-survivors at ICU discharge. Competitive risk regression identified patients who died in ICU and age as independent risk factors for longer time to SARS-CoV-2 negativation on RT-PCR, while antiviral treatment was independently associated with shorter time. None of the CT scores exploring fibroproliferation (i.e., bronchiectasis and reticulation scores) were significantly associated with time to SARS-CoV-2 negativation.

Conclusions

Viral load in respiratory samples is significantly lower and viral shedding significantly shorter in ICU survivors of COVID-19 associated acute respiratory failure. Protracted viral shedding is unrelated to occurrence of fibrosis on lung CT.

Sepsis and Coronavirus Disease 2019: Common Features and Anti-Inflammatory Therapeutic Approaches

 

Sepsis and Coronavirus Disease 2019: Common Features and Anti-Inflammatory Therapeutic Approaches

 

by Beltrán-García, Jesús; Osca-Verdegal, Rebeca; Pallardó, Federico V.; Ferreres, José; Rodríguez, María; Mulet, Sandra; Ferrando-Sánchez, Carolina; Carbonell, Nieves; García-Giménez, José Luis

 

Critical Care Medicine: December 2020 - Volume 48 - Issue 12 - p 1841-1844

 

Great efforts are being made worldwide to identify the specific clinical characteristics of infected critically ill patients that mediate the associated pathogenesis, including vascular dysfunction, thrombosis, dysregulated inflammation, and respiratory complications. Recently, coronavirus disease 2019 has been closely related to sepsis, which suggests that most deaths in ICUs in infected patients are produced by viral sepsis. Understanding the physiopathology of the disease that lead to sepsis after severe acute respiratory syndrome coronavirus 2 infection is a current clinical need to improve intensive care–applied therapies applied to critically ill patients. Although the whole representative data characterizing the immune and inflammatory status in coronavirus disease 2019 patients are not completely known, it is clear that hyperinflammation and coagulopathy contribute to disease severity. Here, we present some common features shared by severe coronavirus disease 2019 patients and sepsis and describe proposed anti-inflammatory therapies for coronavirus disease 2019 which have been previously evaluated in sepsis.

Plasma Exchange: An Effective Rescue Therapy in Critically Ill Patients With Coronavirus Disease 2019 Infection

 

Plasma Exchange: An Effective Rescue Therapy in Critically Ill Patients With Coronavirus Disease 2019 Infection

 

by Fernandez, Javier; Gratacos-Ginès, Jordi; Olivas, Pol; Costa, Montserrat; Nieto, Susana; Mateo, Dolors; Sánchez, María Belén; Aguilar, Ferran; Bassegoda, Octavi; Ruiz, Pablo; Caballol, Berta; Pocurull, Anna; Llach, Joan; Mustieles, María Jesús; Cid, Joan; Reverter, Enric; Toapanta, Nestor David; Hernández-Tejero, María; Martínez, José Antonio; Claria, Joan; Fernández, Carlos; Mensa, José; Arroyo, Vicente; Castro, Pedro; Lozano, Miquel; for the Covid Clinic Critical Care (CCCC) Group

 

Objectives: 

Infection by severe acute respiratory syndrome coronavirus-2 can induce uncontrolled systemic inflammation and multiple organ failure. The aim of this study was to evaluate if plasma exchange, through the removal of circulating mediators, can be used as rescue therapy in these patients.

Design: 

Single center case series.

Setting: 

Local study.

Subjects: 

Four critically ill adults with coronavirus disease 19 pneumonia that failed conventional interventions.

Interventions: 

Plasma exchange. Two to six sessions (1.2 plasma volumes). Human albumin (5%) was used as the main replacement fluid. Fresh frozen plasma and immunoglobulins were administered after each session to avoid coagulopathy and hypogammaglobulinemia.

Measurements and Main Results: 

Serum markers of inflammation and macrophage activation. All patients showed a dramatic reduction in inflammatory markers, including the main cytokines, and improved severity scores after plasma exchange. All survived to ICU admission.

Conclusions: 

Plasma exchange mitigates cytokine storm, reverses organ failure, and could improve survival in critically ill patients with coronavirus disease 2019 infection.

Right ventricular-arterial uncoupling independently predicts survival in COVID-19 ARDS

 

Right ventricular-arterial uncoupling independently predicts survival in COVID-19 ARDS

 

by Michele D’Alto, Alberto M. Marra, Sergio Severino, Andrea Salzano, Emanuele Romeo, Rosanna De Rosa, Francesca Maria Stagnaro, Gianpiero Pagnano, Raffaele Verde, Patrizia Murino, Andrea Farro, Giovanni Ciccarelli, Maria Vargas, Giuseppe Fiorentino, Giuseppe Servillo, Ivan Gentile

 

Aim

To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS).

Methods

Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio

Results

The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01–0.579; p: 0.019) and PaO2/FIO2 (HR: 0.988; 95%CI 0.988–0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively.

Conclusions

COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19.

Discriminating between CPAP success and failure in COVID-19 patients with severe respiratory failure

 

Discriminating between CPAP success and failure in COVID-19 patients with severe respiratory failure

 

By: Pietro Arina, Beatrice Baso, Valeria Moro, Hemani Patel, Gareth Ambler on behalf of the UCL Critical Care COVID-19 Research Group

Intensive Care Medicine (2020) Published: 16 November 2020

 

Research letter

Continuous positive airways pressure (CPAP) treatment was used increasingly in the UK and elsewhere for coronavirus disease 2019 (COVID-19) to avoid the need for mechanical ventilation [1,2,3]. Early identification of patients benefitting from CPAP would assist decision making however we found that intensive care unit (ICU) admission respiratory parameters (rate, PaO2/FiO2 ratio) were poorly discriminatory. Using electronic healthcare records we retrospectively studied COVID-19 patients admitted to the University College London Hospital ICU between 8 March and 5 June 2020 in moderate-to-severe respiratory failure who received initial management with CPAP to see whether better prognosticators could be identified.

Comparison of demographic, clinical and biochemical parameters measured on ICU admission was made between patients adjudged CPAP success (hospital survival with CPAP alone) or failure (either death where CPAP was a ceiling of treatment, or need for mechanical ventilation regardless of hospital outcome). Requirement for other organ support was also compared. Patients managed on CPAP in non-ICU wards were excluded as detailed clinical and lab data were often lacking.

Of 108 within-hospital admissions, 93 (86%) received CPAP as initial respiratory failure management (median[IQR] PaO2/FiO2 ratio 13 [10–18] kPa) (Supplementary Fig. 1). Thirty-two (34%) were adjudged CPAP successes and 61 (66%) failures (14 deaths (23%) with CPAP as the ceiling of treatment, 47 (77%) requiring invasive ventilation of whom 26 died). Demographics and ICU admission values of respiratory rate, inspired oxygen concentration (FiO2) and PaO2/FiO2 ratio were similar between groups (Supplementary data). Admission values of C-reactive protein (CRP) (p < 0.0001), N Terminal-pro-B-type natriuretic peptide (NT-proBNP) (p < 0.001), troponin-T (p < 0.001) and D-dimers (p < 0.05) were significantly higher in CPAP failure patients (Fig. 1). Other organ support was only required for CPAP failure patients receiving invasive ventilation (46 vasopressors, 28 renal replacement therapy), but none for CPAP successes. At 6 h post-CPAP the PaO2/FiO2 ratio rose by 76.7% (37.9 to 99.8%) in CPAP success patients but only by 38.1% (−24.4 to 100.5) in the failure group (p = 0.015)…

Weak anti-SARS-CoV-2 antibody response is associated with mortality in a Swedish cohort of COVID-19 patients in critical care

 

Weak anti-SARS-CoV-2 antibody response is associated with mortality in a Swedish cohort of COVID-19 patients in critical care

 

by Sana Asif, Robert Frithiof, Miklos Lipcsey, Bjarne Kristensen, Kjell Alving and Michael Hultström 

 

Critical Care volume 24, Article number: 639 (2020)

Research Letter

Profiling of the antibody responses to SARS-CoV-2 may be crucial to understand the immunological reaction and to design successful treatment strategies. Studies have confirmed the development of a typical antibody response to an acute viral infection in COVID-19 patients [1]. A robust generation and a dynamic pattern of IgA, IgM and IgG antibodies can be detected 2–3 weeks following the first symptoms of COVID-19 [2, 3]. An early robust antibody response in patients hospitalized with severe COVID-19 was reported in survivors, versus a weak antibody production in non-survivors [4, 5]. However, antibody responses to SARS-CoV-2 in critically ill patients is largely unknown.

We investigated the antibody response to SARS-Cov-2 Spike-1 protein in adult patients (n = 19) admitted to the intensive care unit (ICU) at a tertiary care hospital in Uppsala, Sweden. Plasma samples were collected at two different time points; (a) early, day 0–3 and (b) late, day 10–13, and concentrations of IgA, IgG and IgM antibodies were quantified by FluoroEnzymeImmunoassay (FEIA), Phadia AB, Uppsala, Sweden.

The median age of our cohort was 57 years, and 93% were males. The most common co-morbidities were obesity (93%), hypertension (42%) and diabetes mellitus type-2 (32%). The median COVID-19 day at ICU admission was 10 (6–14) days, the median length of ICU stay was 18 (11–38) days, and 30 days mortality was 21% (Table 1). In our cohort, a IgA, IgG and IgM antibody response could be detected as early as day 0–3 post-ICU admission, and this increase in antibodies was persistent up to day 10–13 (Fig. 1). A significant change in antibody concentrations over time was detected in patients who survived till day 30 in comparison with those who did not (Fig. 1). No associations were seen between antibody levels and patient age, or any other clinical or laboratory parameters. At both early and late timepoints, plasma concentrations of IgA, IgG and IgM antibodies tend to be higher in patients who survived compared to those who had died at 30 days (Fig. 1). This suggests that SARS-CoV-2 antibody response, similar to other virus illnesses, is important for virus protection and recovery. A limitation of the present dataset is the relatively low number of patients…

Spontaneous hemothorax in 4 COVID-19 ARDS patients on VV-ECMO revealing pulmonary artery aneurysms

 

Spontaneous hemothorax in 4 COVID-19 ARDS patients on VV-ECMO revealing pulmonary artery aneurysms

 

by Cyrielle Desnos, Samia Boussouar, Guillaume Hekimian, Alban Redheuil and Alain Combes 

 

Critical Care volume 24, Article number: 638 (2020)

 

COVID-19 pneumonia is a cause of severe ARDS. Its pathophysiology involves endothelial dysfunction and angiogenesis related to ACE-2 receptor, the host-cell receptor for SARS-CoV-2, expressed by endothelial cells, which may lead to thrombosis or hemorrhage [1].

This case series describes the presentation of COVID-19 patients who had unusual spontaneous hemothorax while on veno-venous extra corporeal membrane oxygenation (VV-ECMO) for severe ARDS. In accordance with French legislation, only non-opposition of patient’s surrogate for utilization of the deidentified data was obtained. The ICU database was registered with the national data protection authority (CNIL 1950673). From February to September 2020, 62 patients with confirmed COVID-19-related severe ARDS requiring VV-ECMO were transferred and treated in our tertiary care ICU, of whom 4 had spontaneous hemothorax.

Ages were 33, 63, 48 and 46 years; 2 patients were women. None of them had pulmonary embolism on previous CT angiography, and they had received continuous infusion of unfractionated heparin at high preventive dose according to international expert guidelines [2]. They were on VV-ECMO for 3, 9, 22 and 28 days at the time of the hemothorax onset. In all four patients, hemothorax was revealed by shock, both hemorrhagic and obstructive by compression of the mediastinum, requiring high doses of catecholamine and massive packed red blood cells transfusion. One patient experienced cardiac arrest shortly after shock onset, resuscitated after chest drainage. On chest CT scan, vascular lung abnormalities were very similar in the 4 patients, including peripheral medium and small pulmonary artery branches aneurysms, one of them also having renal and diaphragmatic artery aneurysms (Fig. 1). Three of the patients underwent salvage radioembolization, one of them survived to this episode without relapse, and hemothorax was fatal for the 3 others…

Corticosteroids in severe COVID-19: a critical view of the evidence

 

Corticosteroids in severe COVID-19: a critical view of the evidence

 

by Daniel De Backer, Elie Azoulay and Jean-Louis Vincent 

 

Critical Care volume 24, Article number: 627 (2020)

 

Since December 2019, SARS-CoV-2 has infected millions of people worldwide, causing excess deaths and a surge in demand for ICU beds. With no effective therapies against SARS-CoV-2, randomized trials of several potential therapeutic agents, including steroids, have been conducted. Although use of steroids in patients with ARDS [1] and severe viral pneumonia [2, 3] has been challenged, several arguments support the biological plausibility of steroid use in patients with severe COVID-19. First, autopsy studies in COVID-19 patients showed lymphocyte alveolitis, acute fibrinous injury and organizing pneumonia [4], which are all probably steroid-sensitive. Second, COVID-19 leads to activation of endothelial cells causing not only systemic inflammation but also microvascular thrombosis, pulmonary infarcts and venous thromboembolism [4, 5]. Admittedly, there are also arguments against steroid use. First, viral particles are often found at autopsy [4], and steroids may decrease viral clearance. Second, steroids only influence the inflammatory component of the inflammation–thrombosis–hypoxia interaction [6], suggesting that steroids may be less effective once thrombi have developed.

The RECOVERY trial compared administration of 6 mg/day dexamethasone for 10 days to usual care in 6425 hospitalized patients with SARS-CoV-2 infection. Survival was significantly higher in the dexamethasone-treated patients, especially in the subgroup of 1007 patients receiving invasive mechanical ventilation [7]. As a result of the RECOVERY findings, three further steroid trials, focusing on ICU patients, were stopped prematurely after inclusion of 384 [8], 299 [9] and 149 [10] patients, respectively. A meta-analysis of the available data concluded that administration of systemic steroids was associated with a decrease in 28-day mortality [11]. Nevertheless, although administration of steroids appears promising, several limitations must be considered when interpreting the results

High-Flow Nasal Oxygen in Coronavirus Disease 2019 Patients With Acute Hypoxemic Respiratory Failure: A Multicenter, Retrospective Cohort Study*

 

High-Flow Nasal Oxygen in Coronavirus Disease 2019 Patients With Acute Hypoxemic Respiratory Failure: A Multicenter, Retrospective Cohort Study*

 

by Xia, Jingen; Zhang, Yi; Ni, Lan; Chen, Lei; Zhou, Changzhi; Gao, Chang; Wu, Xiaojing; Duan, Jun; Xie, Jungang; Guo, Qiang; Zhao, Jianping; Hu, Yi; Cheng, Zhenshun; Zhan, Qingyuan

Critical Care Medicine: November 2020 - Volume 48 - Issue 11 - p e1079-e1086

Objectives:  

An ongoing outbreak of coronavirus disease 2019 is spreading globally. Acute hypoxemic respiratory failure is the most common complication of coronavirus disease 2019. However, the clinical effectiveness of early high-flow nasal oxygen treatment in patients with coronavirus disease 2019 with acute hypoxemic respiratory failure has not been explored. This study aimed to analyze the effectiveness of high-flow nasal oxygen treatment and to identify the variables predicting high-flow nasal oxygen treatment failure in coronavirus disease 2019 patients with acute hypoxemic respiratory failure.

Design:

A multicenter, retrospective cohort study. Setting: Three tertiary hospitals in Wuhan, China. Patients: Forty-three confirmed coronavirus disease 2019 adult patients with acute hypoxemic respiratory failure treated with high-flow nasal oxygen. Interventions: None.

Measurements and Main Results:

Mean age of the enrolled patients was 63.0 ± 9.7 years; female patients accounted for 41.9%. High-flow nasal oxygen failure (defined as upgrading respiratory support to positive pressure ventilation or death) was observed in 20 patients (46.5%), of which 13 (30.2%) required endotracheal intubation. Patients with high-flow nasal oxygen success had a higher median oxygen saturation (96.0% vs 93.0%; p < 0.001) at admission than those with high-flow nasal oxygen failure. High-flow nasal oxygen failure was more likely in patients who were older (p = 0.030) and male (p = 0.037), had a significant increase in respiratory rate and a significant decrease in the ratio of oxygen saturation/Fio2 to respiratory rate index within 3 days of high-flow nasal oxygen treatment. In a multivariate logistic regression analysis model, male and lower oxygen saturation at admission remained independent predictors of high-flow nasal oxygen failure. The hospital mortality rate of the cohort was 32.5%; however, the hospital mortality rate in patients with high-flow nasal oxygen failure was 65%.

Conclusions:

High-flow nasal oxygen may be effective for treating coronavirus disease 2019 patients with mild to moderate acute hypoxemic respiratory failure. However, high-flow nasal oxygen failure was associated with a poor prognosis. Male and lower oxygenation at admission were the two strong predictors of high-flow nasal oxygen failure.

Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study

 

Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study

 

by Carlos Ferrando, Ricard Mellado-Artigas, Alfredo Gea, Egoitz Arruti, César Aldecoa, Ramón Adalia, Fernando Ramasco, Pablo Monedero, Emilio Maseda, Gonzalo Tamayo, María L. Hernández-Sanz, Jordi Mercadal, Ascensión Martín-Grande, Robert M. Kacmarek, Jesús Villar and Fernando Suárez-Sipmann

 

Critical Care volume 24, Article number: 597 (2020) Published: 06 October 2020

Background

Awake prone positioning (awake-PP) in non-intubated coronavirus disease 2019 (COVID-19) patients could avoid endotracheal intubation, reduce the use of critical care resources, and improve survival. We aimed to examine whether the combination of high-flow nasal oxygen therapy (HFNO) with awake-PP prevents the need for intubation when compared to HFNO alone.

Methods

Prospective, multicenter, adjusted observational cohort study in consecutive COVID-19 patients with acute respiratory failure (ARF) receiving respiratory support with HFNO from 12 March to 9 June 2020. Patients were classified as HFNO with or without awake-PP. Logistic models were fitted to predict treatment at baseline using the following variables: age, sex, obesity, non-respiratory Sequential Organ Failure Assessment score, APACHE-II, C-reactive protein, days from symptoms onset to HFNO initiation, respiratory rate, and peripheral oxyhemoglobin saturation. We compared data on demographics, vital signs, laboratory markers, need for invasive mechanical ventilation, days to intubation, ICU length of stay, and ICU mortality between HFNO patients with and without awake-PP.

Results

A total of 1076 patients with COVID-19 ARF were admitted, of which 199 patients received HFNO and were analyzed. Fifty-five (27.6%) were pronated during HFNO; 60 (41%) and 22 (40%) patients from the HFNO and HFNO + awake-PP groups were intubated. The use of awake-PP as an adjunctive therapy to HFNO did not reduce the risk of intubation [RR 0.87 (95% CI 0.53–1.43), p = 0.60]. Patients treated with HFNO + awake-PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0–2.5) vs 2 IQR 1.0–3.0] days (p = 0.055), but awake-PP did not affect 28-day mortality [RR 1.04 (95% CI 0.40–2.72), p = 0.92].

Conclusion

In patients with COVID-19 ARF treated with HFNO, the use of awake-PP did not reduce the need for intubation or affect mortality.