Persistent lymphopenia is a risk factor for ICU-acquired infections and for death in ICU patients with sustained hypotension at admission

Adrie, Christophe; Lugosi, M.; Sonneville, Romain; Souweine, Bertrand; Ruckly, Stéphane; Cartier, Jean-Charles; Garrouste-Orgeas, Maïté; Schwebel, Carole; Timsit, Jean‐François

doi:10.1186/s13613-017-0242-0

Cited by 79 publications

(86 citation statements)

References 39 publications

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“…Whether there is viremia of SARS-CoV-2 causing septic shock is difficult to determine. But the bottom line is that lymphocytopenia was associated with an increased risk of acquired infection in ICU [22]. And lymphocytopenia was proved to be associated with the probability of 28-day septic shock and 28-day mortality [23].…”

Section: Discussionmentioning

confidence: 99%

Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study

et al. 2020

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Background: A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. Methods: A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied.Results: A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57-70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5-17) days, and the duration from onset of symptoms to the study date was 31 (24-36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2-8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital.(Continued on next page)

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Section: Discussionmentioning

confidence: 99%

Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study

et al. 2020

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“…These were compared against simple enumeration of leucocyte populations and lymphocyte to neutrophil ratios which have previously been reported to be predictive of subsequent infection [21, 22]. …”

Section: Methodsmentioning

confidence: 99%

Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study

et al. 2018

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PurposeCellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients.MethodsMulti-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (Tregs)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections.ResultsA total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of Tregs were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00–4.74), 3.44 (1.58–7.47) and 2.41 (1.14–5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9.ConclusionsThis study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies.Trial registrationThe study was registered with clinicaltrials.gov (NCT02186522).Electronic supplementary materialThe online version of this article (10.1007/s00134-018-5247-0) contains supplementary material, which is available to authorized users.

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“…However, the extent of this lymphopenia is variable depending on cell subpopulations, with some subpopulations such as regulatory T cells (Tregs) being less affected (see below). Because ALC is part of the complete blood cell count on hematology analyzers and is thus available 24/7 in every hospital, the association of this cellular alteration and poor outcomes in septic patients is now easily evaluated in large prospective clinical studies and can be retrospectively assessed in various sepsis cohorts . Overall, results homogenously show that decreased ALC is associated with initial severity upon ICU admission while persistent lymphopenia is associated with increased mortality and occurrence of nosocomial infections after sepsis.…”

Section: Landmarks Of Flow Cytometry In Sepsismentioning

confidence: 99%

How Clinical Flow Cytometry Rebooted Sepsis Immunology

et al. 2019

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On May 2017, the World Health Organization (WHO) recognized sepsis as a global health priority by adopting a resolution to improve the prevention, diagnosis, and management of this deadly disease. While it has long been known that sepsis deeply perturbs immune homeostasis by inducing a tremendous systemic inflammatory response, pivotal observations based on clinical flow cytometry indicate that sepsis indeed initiates a more complex immune response that varies over time, with the concomitant occurrence of both pro-and anti-inflammatory mechanisms. As a resultant, some septic patients enter a stage of protracted immunosuppression. This paved the way for immunostimulation approaches in sepsis. Clinical flow cytometry permitted this evolution by drawing a new picture of pathophysiology and reshaping immune trajectories in patients. Additional information from cytometry by time of flight mass cytometry and other highdimensional flow cytometry platform should rapidly enrich our understanding of this complex disease. This review reports on landmarks of clinical flow cytometry in sepsis and how this single-cell analysis technique permitted to breach the wall of decades of unfruitful anti-inflammatory-based clinical trials in sepsis.On May 2017, the World Health Organization (WHO) recognized sepsis as a global health priority by adopting a resolution to improve the prevention, diagnosis, and management of this deadly disease (1). Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection (2). Septic shock is the most severe form of sepsis in which hypotension persists despite adequate volume resuscitation thus requiring the use of vasopressors. According to recent definitions, in response to an infectious trigger, the unbalanced host (immune) response is at the center of sepsis pathophysiology (2).Sepsis represents a major healthcare problem worldwide. As an example, in the US, sepsis is more frequent than myocardial infarction, breast, or colon cancers (3-6). Recent modeling of available data determined the number of cases of sepsis in the entire world to over 20-25 million corresponding to >6 million deaths per annum (7,8). Over the years, 28-day mortality has remained high, ranging from 20% for sepsis to over 40% for septic shock despite improvement in patients' care (fluid resuscitation, source control, antimicrobial therapy). Whereas few therapeutic options evaluated in phase II clinical trials have demonstrated the potential efficacy of immunostimulation in sepsis, to date, no therapeutic intervention targeting host response has specifically been approved and sepsis remains the leading cause of mortality in intensive care units (ICU)(9,10). In addition, sepsis incidence has dramatically increased over the past decade and is expected to further augment. This rising

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Persistent lymphopenia is a risk factor for ICU-acquired infections and for death in ICU patients with sustained hypotension at admission

Cited by 79 publications

References 39 publications

Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study

Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study

Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study

How Clinical Flow Cytometry Rebooted Sepsis Immunology

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