Impact of new lighting technology versus traditional fluorescent bulbs on sedation and delirium in the ICU.

BACKGROUND: Critically ill patients frequently encounter disruptions in their circadian rhythms in the intensive care unit (ICU) environment. New lighting systems have been developed to enhance daytime light levels and to promote circadian alignment. OBJECTIVES: To investigate the impact of implementing an innovative lighting technology that mimics natural light and reproduce the colour of the sky. DESIGN: Prospective, observational, non-randomized comparative trial. ICU patients were exposed to either a cutting-edge lighting system based on new technology (intervention group) or a conventional lighting system using fluorescent bulbs (control group). SETTING: An Italian intensive care unit with ten beds and five windowless rooms, thereby denying access to natural light. Three rooms had new lighting technology. MAIN OUTCOME MEASURES: The two groups were compared to assess the prevalence or absence of delirium and the need for sedatives during ICU stay. The secondary aim was to assess the presence of anxiety, depression, and post-traumatic stress disorder in patients at 3, 6, and 12 months after ICU discharge. RESULTS: 86 patients were included: 52 (60 %) in the intervention group and 34 (40 %) in the control group. Seventy-nine patients (82 %) were alive at ICU discharge. Fourteen patients (16 %) developed delirium (intervention group: n = 8 [15 %] vs. control group: n = 6 [18 %] in the control group, (P=0.781). The use of sedative drugs and neuromuscular blocking agents was similar in both the groups. No differences in the incidence of anxiety, depression, or post-traumatic stress disorders were observed among patients who underwent follow-up visits. CONCLUSIONS: Compared to traditional fluorescent tube lighting, the innovative lighting system did not provide any significant benefit in reducing the frequency of delirium or the necessity for sedative medications. IMPLICATIONS FOR CLINICAL PRACTICE: A single intervention, the use of lights that mimic sunny light and the sky, did not result in a statistically significant reduction in the incidence of delirium. Delirium has a multifactorial aetiology, necessitating interventions that are multifaceted and address different domains.

Mechanical ventilation settings during weaning from venovenous extracorporeal membrane oxygenation.

BACKGROUND: The optimal timing of weaning from venovenous extracorporeal membrane oxygenation (VV ECMO) and its modalities have been rarely studied. METHODS: Retrospective, multicenter cohort study over 7 years in two tertiary ICUs, high-volume ECMO centers in France and Italy. Patients with ARDS on ECMO and successfully weaned from VV ECMO were classified based on their mechanical ventilation modality during the sweep gas-off trial (SGOT) with either controlled mechanical ventilation or spontaneous breathing (i.e. pressure support ventilation). The primary endpoint was the time to successful weaning from mechanical ventilation within 90 days post-ECMO weaning. RESULTS: 292 adult patients with severe ARDS were weaned from controlled ventilation, and 101 were on spontaneous breathing during SGOT. The 90-day probability of successful weaning from mechanical ventilation was not significantly different between the two groups (sHR [95% CI], 1.23 [0.84-1.82]). ECMO-related complications were not statistically different between patients receiving these two mechanical ventilation strategies. After adjusting for covariates, older age, higher pre-ECMO sequential organ failure assessment score, pneumothorax, ventilator-associated pneumonia, and renal replacement therapy, but not mechanical ventilation modalities during SGOT, were independently associated with a lower probability of successful weaning from mechanical ventilation after ECMO weaning. CONCLUSIONS: Time to successful weaning from mechanical ventilation within 90 days post-ECMO was not associated with the mechanical ventilation strategy used during SGOT. Further research is needed to assess the optimal ventilation strategy during weaning off VV ECMO and its impact on short- and long-term outcomes.

Pressure Support Ventilation During Extracorporeal Membrane Oxygenation Support in Patients With Acute Respiratory Distress Syndrome.

In the initial phases of veno-venous extracorporeal membrane oxygenation (VV ECMO) support for severe acute respiratory distress syndrome (ARDS), ultraprotective controlled mechanical ventilation (CMV) is typically employed to limit the progression of lung injury. As patients recover, transitioning to assisted mechanical ventilation can be considered to reduce the need for prolonged sedation and paralysis. This study aimed to evaluate the feasibility of transitioning to pressure support ventilation (PSV) during VV ECMO and to explore variations in respiratory mechanics and oxygenation parameters following the transition to PSV. This retrospective monocentric study included 191 adult ARDS patients treated with VV ECMO between 2009 and 2022. Within this population, 131 (69%) patients were successfully switched to PSV during ECMO. Pressure support ventilation was associated with an increase in respiratory system compliance (p = 0.02) and a reduction in pulmonary shunt fraction (p < 0.001). Additionally, improvements in the cardiovascular Sequential Organ Failure Assessment score and a reduction in pulmonary arterial pressures (p < 0.05) were recorded. Ninety-four percent of patients who successfully transitioned to PSV were weaned from ECMO, and 118 (90%) were discharged alive from the intensive care unit (ICU). Of those who did not reach PSV, 74% died on ECMO, whereas the remaining patients were successfully weaned from extracorporeal support. In conclusion, PSV is feasible during VV ECMO and potentially correlates with improvements in respiratory function and hemodynamics.

Impact of a 'Catheter Bundle' on Infection Rates and Economic Costs in the Intensive Care Unit: A Retrospective Cohort Study.

INTRODUCTION: Catheter-related infections (CBRSIs) are a widespread problem that increase morbidity and mortality in intensive care unit (ICU) patients and management costs. OBJECTIVE: The main aim of this study was to assess the prevalence of CBRSIs in an intensive care unit following international literature guidelines for managing vascular lines in critically ill patients. These guidelines include changing vascular lines every 7 days, using needle-free devices and port protectors, standardising closed infusion lines, employing chlorhexidine-impregnated dressings, and utilising sutureless devices for catheter securement. MATERIALS AND METHODS: This single-centre retrospective observational study was conducted in a general Italian ICU. This study included all eligible patients aged > 1 year who were admitted between January 2018 and December 2022. RESULTS: During the study period, 1240 patients were enrolled, of whom 9 were diagnosed with a CRBSI. The infection rate per 1000 catheters/day was as follows: femorally inserted central catheter, 1.04; centrally inserted central catheter, 0.77; pulmonary arterial catheter 0.71, arterial catheter, 0.1; and peripherally inserted central catheter and continuous veno-venous haemodialysis dialysis catheters equal to 0. No difference in CRBSI was observed between the years included in the study (p = 0.874). The multivariate analysis showed an association between the diagnosis of CBRSI and Nursing Activities Score (per single point increase ß = 0.04-95%CI: -0.01-0.09, p = 0.048), reason for ICU admission-trauma (ß = 0.77-95%CI: -0.03-1.49, p = 0.039), and use of therapeutic hypothermia (ß = 2.06, 95%CI: 0.51-3.20, p < 0.001). Implementing the study protocol revealed a cost of EUR 130.00/patient, equivalent to a daily cost of EUR 15.20 per patient. CONCLUSIONS: This study highlights the importance of implementing a catheter care bundle to minimise the risk of CRBSI and the associated costs in the ICU setting. A policy change for infusion set replacement every 7 days has helped to maintain the CRBSI rate below the recommended rate, resulting in significant cost reduction and reduced production of ICU waste.

Retrospective ANalysis of multi-drug resistant Gram-nEgative bacteRia on veno-venous extracorporeal membrane oxygenation. The multicenter RANGER STUDY.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a rapidly expanding life-support technique worldwide. The most common indications are severe hypoxemia and/or hypercapnia, unresponsive to conventional treatments, primarily in cases of acute respiratory distress syndrome. Concerning potential contraindications, there is no mention of microbiological history, especially related to multi-drug resistant (MDR) bacteria isolated before V-V ECMO placement. Our study aims to investigate: (i) the prevalence and incidence of MDR Gram-negative (GN) bacteria in a cohort of V-V ECMOs; (ii) the risk of 1-year mortality, especially in the case of predetected MDR GN bacteria; and (iii) the impact of annual hospital V-V ECMO volume on the probability of acquiring MDR GN bacteria. METHODS: All consecutive adults admitted to the Intensive Care Units of 5 Italian university-affiliated hospitals and requiring V-V ECMO were screened. Exclusion criteria were age < 18 years, pregnancy, veno-arterial or mixed ECMO-configuration, incomplete records, survival < 24 h after V-V ECMO. A standard protocol of microbiological surveillance was applied and MDR profiles were identified using in vitro susceptibility tests. Cox-proportional hazards models were applied for investigating mortality. RESULTS: Two hundred and seventy-nine V-V ECMO patients (72% male) were enrolled. The overall MDR GN bacteria percentage was 50%: 21% (n.59) detected before and 29% (n.80) after V-V ECMO placement. The overall 1-year mortality was 42%, with a higher risk observed in predetected patients (aHR 2.14 [1.33-3.47], p value 0.002), while not in 'V-V ECMO-acquired MDR GN bacteria' group (aHR 1.51 [0.94-2.42], p value 0.090), as compared to 'non-MDR GN bacteria' group (reference). Same findings were found considering only infections. A larger annual hospital V-V ECMO volume was associated with a lower probability of acquiring MDR GN bacteria during V-V ECMO course (aOR 0.91 [0.86-0.97], p value 0.002). CONCLUSIONS: 21% of MDR GN bacteria were detected before; while 29% after V-V ECMO connection. A history of MDR GN bacteria, isolated before V-V ECMO, was an independent risk factor for mortality. The annual hospital V-V ECMO volume affected the probability of acquiring MDR GN bacteria. Trial Registration ClinicalTrial.gov Registration Number NCTNCT06199141, date 12.26.2023.

Prone-position decreases airway closure in a patient with ARDS undergoing venovenous extracorporeal membrane oxygenation.

PURPOSE: Airway closure is a interruption of communication between larger and smaller airways. The presence of airway closure during mechanical ventilation may lead to the overestimation of driving pressure (DP), introducing errors in the assessment of respiratory mechanics and in positive end-expiratory pressure (PEEP) setting on the ventilator. Patients with severe acute respiratory distress syndrome (ARDS) may exhibit the airway closure phenomenon, which can be easily diagnosed with a low-flow inflation. Prone positioning is a therapeutic manoeuver proven to reduce mortality in ARDS patients, and has been widely implemented also in patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). To date, the impact of prone positioning on changes in airway closure has not been described. METHODS: We present an image analysis of the pressure waveform during volume-controlled ventilation and low-flow inflations before and after prone positioning in an ARDS patient on VV ECMO. RESULTS: A high airway opening pressure level (23 cmH2O) was detected in the supine position during tidal ventilation. Airway closure was confirmed by using a low-flow inflation. Prone positioning significantly attenuated airway closure, with the airway opening pressure decreasing to 13 cmH2O. After re-supination, airway closure was lower as compared with supine position at baseline (17 cmH2O). CONCLUSION: Prone positioning reduced airway closure in an ARDS patient on VV ECMO support.

Perioperative Care for Children With Syndromic Craniofacial Synostosis Undergoing Le Fort III Surgery: A Retrospective Cohort Study.

OBJECTIVE: To present characteristics, surgical variables, complications, and postoperative care in pediatric patients with craniofacial synostosis undergoing Le Fort III osteotomy. BACKGROUND: Craniofacial synostoses are a group of genetic syndromes that result in premature fusion of cranial and facial sutures, leading to craniofacial deformities and associated complications. Midface advancement through Le Fort III osteotomy is the most frequent surgical option for these conditions. METHODS: Retrospective monocentric cohort study including patients with syndromic craniofacial synostosis who underwent Le Fort III osteotomy between 2009 and 2022 in a specialized referral center. Data collection encompassed surgical time, blood loss, intraoperative transfusions, fluid balance, and postoperative parameters such as duration of invasive mechanical ventilation and intensive care unit (ICU) length of stay. RESULTS: Twenty-six children were included in the analysis. The median surgical time was 345 minutes (300-360), with an estimated blood loss of 15 (9.9-24) mL/kg. Patients required a median transfusion of 12.63 (7.1-24.5) mL/kg of packed red blood cells and 19.82 (11.1-33) mL/kg of fresh frozen plasma. Intraoperative fluid balance was + 12.5 (0.8-22.8) mL/kg, with a median infusion of 30.4 (23.9-38.7) mL/kg of crystalloids. All patients were transferred to the ICU after surgery to ensure a safe environment for extubation. The median duration of mechanical ventilation in the ICU was 30 (20.25-45) hours, and postoperative ICU length of stay was 2 (2-4) days, and complications were infrequent, with only one extubation failure recorded. CONCLUSION: Le Fort III osteotomy in craniofacial synostosis patients may be characterized by a complex perioperative course. A multidisciplinary approach in the care of these patients allows for minimizing complications in the perioperative phase. Further research is needed to enhance perioperative management in this unique patient population.

Physiologic Effects of Extracorporeal Membrane Oxygenation in Patients with Severe Acute Respiratory Distress Syndrome.

Rationale: Blood flow rate affects mixed venous oxygenation (SvO2) during venovenous extracorporeal membrane oxygenation (ECMO), with possible effects on the pulmonary circulation and the right heart function. Objectives: To describe the physiologic effects of different levels of SvO2 obtained by changing ECMO blood flow in patients with severe acute respiratory distress syndrome receiving ECMO and controlled mechanical ventilation. Methods: Low (SvO2 target, 70-75%), intermediate (SvO2 target, 75-80%), and high (SvO2 target, >80%) ECMO blood flows were applied for 30 minutes in random order in 20 patients. Mechanical ventilation settings were left unchanged. The hemodynamic and pulmonary effects were assessed with pulmonary artery catheter and electrical impedance tomography. Measurements and Main Results: Cardiac output decreased from low to intermediate and to high blood flow/SvO2 (9.2 [6.2-10.9] vs. 8.3 [5.9-9.8] vs. 7.9 [6.5-9.1] L/min; P = 0.014), as well as mean pulmonary artery pressure (34 ± 6 vs. 31 ± 6 vs. 30 ± 5 mm Hg; P < 0.001) and right ventricular stroke work index (14.2 ± 4.4 vs. 12.2 ± 3.6 vs. 11.4 ± 3.2 g × m/beat/m2; P = 0.002). Cardiac output was inversely correlated with mixed venous and arterial Po2 values (R2 = 0.257; P = 0.031; and R2 = 0.324; P = 0.05). Pulmonary artery pressure was correlated with decreasing mixed venous Po2 (R2 = 0.29; P < 0.001) and with increasing cardiac output (R2 = 0.378; P < 0.007). Measures of [Formula: see text]/[Formula: see text] mismatch did not differ between the three steps. Conclusions: In patients with severe acute respiratory distress syndrome, increased ECMO blood flow rate resulting in higher SvO2 decreases pulmonary artery pressure, cardiac output, and right heart workload.

Pulmonary shunt in critical care: a practical approach with clinical scenarios.

BACKGROUND: Pulmonary shunt refers to the passage of venous blood into the arterial blood system bypassing the alveoli-blood gas exchange. Pulmonary shunt is defined by a drop in the physiologic coupling of lung ventilation and lung perfusion. This may consequently lead to respiratory failure. MAIN BODY: The pulmonary shunt assessment is often neglected. From a mathematical point of view, pulmonary shunt can be assessed by estimating the degree of mixing between oxygenated and deoxygenated blood. To compute the shunt, three key components are analyzed: the oxygen (O2) content in the central venous blood before gas exchange, the calculated O2 content in the pulmonary capillaries after gas exchange, and the O2 content in the arterial system, after the mixing of shunted and non-shunted blood. Computing the pulmonary shunt becomes of further importance in patients on extracorporeal membrane oxygenation (ECMO), as arterial oxygen levels may not directly reflect the gas exchange of the native lung. CONCLUSION: In this review, the shunt analysis and its practical clinical applications in different scenarios are discussed by using an online shunt simulator.

The "ZEEP-PEEP test" to evaluate the response to positive end-expiratory pressure delivered by helmet: A prospective physiologic study.

Introduction: The improvement in oxygenation after helmet application in hypoxemic patients may be explained by the alveolar recruitment obtained with positive end expiratory pressure (PEEP) or by the administration of a more accurate inspiratory fraction of oxygen (FiO2). We have designed the "ZEEP-PEEP test", capable to distinguish between the FiO2-related or PEEP-related oxygenation improvement. Our primary aim was to describe the use of this test during helmet CPAP to assess the oxygenation improvement attributable to PEEP application. Material and methods: We performed a prospective physiological study including adult critically ill patients. Respiratory and hemodynamic parameters were recorded before helmet application (PRE step), after helmet application without PEEP (ZEEP step) and after the application of the PEEP valve (PEEP step), while maintaining a constant FiO2. We defined as "PEEP responders" patients showing a PaO2/FiO2 ratio improvement ≥10% after PEEP application. Results: 93 patients were enrolled. Compared to the PRE step, PaO2/FiO2 ratio was significantly improved during helmet CPAP both at ZEEP and PEEP step (189 ± 55, 219 ± 74 and 241 ± 82 mmHg, respectively, p < 0.01). Both PEEP responders (41%) and non-responders showed a significant improvement of PaO2/FiO2 ratio after the application of helmet at ZEEP, PEEP responders also showed a significant improvement of oxygenation after PEEP application (208 ± 70 vs 267 ± 85, p < 0.01). Conclusions: Helmet CPAP improved oxygenation. This improvement was not only due to the PEEP effect, but also to the increase of the effective inspired FiO2. Performing the ZEEP-PEEP test may help to identify patients who benefit from PEEP.

Extracorporeal cardio-pulmonary resuscitation in a patient with missed diagnosis of sodium nitrite intoxication.

INTRODUCTION: Critical poisoning with sodium nitrite (NaNO2) can present challenges in promptly identifying and managing acute methemoglobinemia. CASE REPORT: We report the case of an overt self-intoxication by an initially unknown agent, leading to cardiac arrest. Despite prodromal signs of cyanosis, coma, desaturation, and hypotension, methemoglobinemia went unrecognized during extracorporeal cardiopulmonary resuscitation (ECPR) as the point-of-care test failed to provide methemoglobin levels, leading to untreated methemoglobinemia. The blood flowing through the oxygenator notably maintained the same brown colour. Return of spontaneous circulation was never achieved, and the patient was declared dead after 60 min of unsuccessful resuscitation. Cause of death by means of NaNO2 voluntary ingestion was later clarified and confirmed by postmortem finding of elevated nitrite and nitrate concentration. CONCLUSIONS: This case highlights the risk of failure of ECPR in the context of cardiac arrest due to methemoglobinemia, emphasizing the critical need for prompt recognition of the causative agent and early administration of antidotes.

The occurrence of pressure injuries and related risk factors in patients undergoing extracorporeal membrane oxygenation for respiratory failure: A retrospective single centre study.

INTRODUCTION: Limited data is available regarding the incidence of pressure injuries in patients who have undergone Extracorporeal Membrane Oxygenation (ECMO), a life-saving technique that provides respiratory support for hypoxemia that does not respond to conventional treatment. AIM: To assess the incidence of pressure injuries and identify the risk factors in Acute Respiratory Distress Syndrome patients receiving ECMO. METHODS: A retrospective observational study utilizing prospectively collected data was performed in an Italian intensive care unit, between 1 January 2012 and 30 April 2022 enrolling all consecutive patients with Acute Respiratory Distress Syndrome who underwent ECMO. RESULTS: One hundred patients were included in this study. 67 patients (67%) developed pressure injuries during their intensive care unit stay, with a median of 2 (1-3) sites affected. The subgroup of patients with pressure injuries was more hypoxic before ECMO implementation, received more frequent continuous renal replacement therapy and prone positioning, and showed prolonged ECMO duration, intensive care unit and hospital length of stay compared to patients without pressure injuries. The logistic model demonstrated an independent association between the pO2/FiO2 ratio prior to ECMO initiation, the utilization of the prone positioning during ECMO, and the occurrence of pressure injuries. CONCLUSIONS: The incidence of pressure injuries was elevated in patients with Adult Respiratory Distress Syndrome who received ECMO. The development of pressure injuries was found to be independently associated with hypoxemia before ECMO initiation and the utilization of prone positioning during ECMO. IMPLICATIONS FOR CLINICAL PRACTICE: Patients who require ECMO for respiratory failure are at a high risk of developing pressure injuries. To ensure optimal outcomes during ECMO implementation and treatment, it is vital to implement preventive measures and to closely monitor skin health in at-risk areas.

Long term outcome in patients treated with veno-venous extracorporeal membrane oxygenation: A prospective observational study.

INTRODUCTION: Over the last few decades, the use of veno-venous extracorporeal membrane oxygenation (VV-ECMO) support for severe respiratory failure has increased. AIM: This study aimed to assess the long-term outcomes of patients treated with VV-ECMO for respiratory failure. METHODS: We performed a single-centre prospective evaluation of patients on VV-ECMO who were successfully discharged from the intensive care unit of an Italian University Hospital between January 2018 and May 2021. The enrolled patients underwent follow-up evaluations at 6 and 12 months after ICU discharge. The follow-up team performed psychological and functional assessments using the following instruments: Hospital Anxiety and Depression Scale (HADS), Post-traumatic Stress Disorder Symptom Severity Scale (PTSS-10), Euro Quality Five Domains Five Levels (EQ-5L-5D), and 6-minute walk test. RESULTS: We enrolled 33 patients who were evaluated at a follow-up clinic. The median patient age was 51 years (range: 45-58 years). The median duration of VV-ECMO support was 12 (9-19) days and the length of ICU stay was 23 (18-42) days. A HADS score higher than 14 was reported in 8 (24 %) and 7 (21 %) patients at the six- and twelve-month visit, respectively. PTSS-10 total score ≥ 35 points was present in three (9 %) and two (6 %) patients at the six- and twelve-month examination. The median EQ-5L-5D-VAS was respectively 80 (80-90) and 87.5 (70-95). The PTSS-10 score significantly decreased from six to 12 months in COVID-19 survivors (p = 0.024). CONCLUSIONS: In this cohort of patients treated with VV-ECMO, cognitive and psychological outcomes were good and comparable to those of patients with Adult Respiratory Distress Syndrome (ARDS) managed without ECMO. IMPLICATIONS FOR CLINICAL PRACTICE: The findings of this study confirm the need for long-term follow-up and rehabilitation programs for every ICU survivor after discharge. COVID-19 survivors treated with VV-ECMO had outcomes comparable to those reported in non-COVID patients.

Noninvasive Ventilation Before Intubation and Mortality in Patients Receiving Extracorporeal Membrane Oxygenation for COVID-19: An Analysis of the Extracorporeal Life Support Organization Registry.

Bilevel-positive airway pressure (BiPAP) is a noninvasive respiratory support modality which reduces effort in patients with respiratory failure. However, it may increase tidal ventilation and transpulmonary pressure, potentially aggravating lung injury. We aimed to assess if the use of BiPAP before intubation was associated with increased mortality in adult patients with coronavirus disease 2019 (COVID-19) who received venovenous extracorporeal membrane oxygenation (ECMO). We used the Extracorporeal Life Support Organization Registry to analyze adult patients with COVID-19 supported with venovenous ECMO from January 1, 2020, to December 31, 2021. Patients treated with BiPAP were compared with patients who received other modalities of respiratory support or no respiratory support. A total of 9,819 patients from 421 centers were included. A total of 3,882 of them (39.5%) were treated with BiPAP before endotracheal intubation. Patients supported with BiPAP were intubated later (4.3 vs . 3.3 days, p < 0.001) and showed higher unadjusted hospital mortality (51.7% vs. 44.9%, p < 0.001). The use of BiPAP before intubation and time from hospital admission to intubation resulted as independently associated with increased hospital mortality (odds ratio [OR], 1.32 [95% confidence interval {CI}, 1.08-1.61] and 1.03 [1-1.06] per day increase). In ECMO patients with severe acute respiratory failure due to COVID-19, the extended use of BiPAP before intubation should be regarded as a risk factor for mortality.

High-sensitivity analysis of clonal hematopoiesis reveals increased clonal complexity of potential-driver mutations in severe COVID-19 patients.

Whether Clonal Hematopoiesis (CH) represents a risk factor for severity of the COVID-19 disease remains a controversial issue. We report the first high- sensitivity analysis of CH in COVID-19 patients (threshold of detection at 0.5% vs 1 or 2% in previous studies). We analyzed 24 patients admitted to ICU for COVID-19 (COV-ICU) and 19 controls, including healthy subjects and asymptomatic SARS-CoV2-positive individuals. Despite the significantly higher numbers of CH mutations identified (80% mutations with <2% variant allele frequency, VAF), we did not find significant differences between COV-ICU patients and controls in the prevalence of CH or in the numbers, VAF or functional categories of the mutated genes, suggesting that CH is not overrepresented in patients with COVID-19. However, when considering potential drivers CH mutations (CH-PD), COV-ICU patients showed higher clonal complexity, in terms of both mutation numbers and VAF, and enrichment of variants reported in myeloid neoplasms. However, we did not score an impact of increased CH-PD on patient survival or clinical parameters associated with inflammation. These data suggest that COVID-19 influence the clonal composition of the peripheral blood and call for further investigations addressing the potential long-term clinical impact of CH on people experiencing severe COVID-19. We acknowledge that it will indispensable to perform further studies on larger patient cohorts in order to validate and generalize our conclusions. Moreover, we performed CH analysis at a single time point. It will be necessary to consider longitudinal approaches with long periods of follow-up in order to assess if the COVID-19 disease could have an impact on the evolution of CH and long-term consequences in patients that experienced severe COVID-19.