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Published in: BMC Infectious Diseases 1/2022

Open Access 01-12-2022 | Septicemia | Research

High prevalence of infections in non-COVID-19 patients admitted to the Emergency Department with severe lymphopenia

Authors: Arthur Baïsse, Thomas Daix, Ana Catalina Hernandez Padilla, Robin Jeannet, Olivier Barraud, François Dalmay, Bruno François, Philippe Vignon, Thomas Lafon

Published in: BMC Infectious Diseases | Issue 1/2022

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Abstract

Background

In the Emergency Department (ED), early and accurate recognition of infection is crucial to prompt antibiotic therapy but the initial presentation of patients is variable and poorly characterized. Lymphopenia is commonly associated with bacteraemia and poor outcome in intensive care unit patients. The objective of this retrospective study was to assess the prevalence of community-acquired infection in a cohort of unselected patients admitted to the ED with undifferentiated symptoms and severe lymphopenia.

Methods

This is a retrospective single-center study conducted over a 1 year-period before the COVID-19 pandemic. Consecutive adult patients admitted to the ED with severe lymphopenia (lymphocyte count < 0.5 G/L) were studied. Patients with hematological or oncological diseases, HIV infection, hepato-cellular deficiency, immunosuppression, or patients over 85 years old were excluded. Diagnoses of infection were validated by an independent adjudication committee. The association between various parameters and infection was assessed using a multivariate logistic regression analysis.

Results

Of 953 patients admitted to the ED with severe lymphopenia, 245 were studied (148 men; mean age: 63 ± 19 years). Infection was confirmed in 159 patients (65%) (bacterial: 60%, viral: 30%, other: 10%). Only 61 patients (25%) were referred to the ED for a suspected infection. In the univariate analysis, SIRS criteria (OR: 5.39; 95%CI: 3.04–9.70; p < 0.001) and temperature ≥ 38.3 °C (OR: 10.95; 95%CI: 5.39–22.26; p < 0.001) were strongly associate with infection. In the multivariate analysis, only SIRS criteria (OR: 2.4; 95%CI: 1.48–3.9; p < 0.01) and fever (OR: 3.35; 95%CI: 1.26–8.93; p = 0.016) were independently associated with infection.

Conclusions

The prevalence of underlying infection is high in patients admitted to the ED with lymphopenia, irrespective of the reason for admission. Whether lymphopenia could constitute a valuable marker of underlying infection in this clinical setting remains to be confirmed prospectively in larger cohorts.
Trial registration: No registration required as this is a retrospective study.
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Literature
1.
go back to reference Rhee C, Dantes R, Epstein L, Murphy DJ, Seymour CW, Iwashyna TJ, et al. Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009–2014. JAMA. 2017;318:1241–9.CrossRef Rhee C, Dantes R, Epstein L, Murphy DJ, Seymour CW, Iwashyna TJ, et al. Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009–2014. JAMA. 2017;318:1241–9.CrossRef
2.
go back to reference Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:762–74.CrossRef Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:762–74.CrossRef
3.
go back to reference Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021;49:e1063–143.CrossRef Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021;49:e1063–143.CrossRef
4.
go back to reference Filbin MR, Lynch J, Gillingham TD, Thorsen JE, Pasakarnis CL, Nepal S, et al. Presenting symptoms independently predict mortality in septic shock: importance of a previously unmeasured confounder. Crit Care Med. 2018;46:1592–9.CrossRef Filbin MR, Lynch J, Gillingham TD, Thorsen JE, Pasakarnis CL, Nepal S, et al. Presenting symptoms independently predict mortality in septic shock: importance of a previously unmeasured confounder. Crit Care Med. 2018;46:1592–9.CrossRef
5.
go back to reference Liu VX, Bhimarao M, Greene JD, Manickam RN, Martinez A, Schuler A, et al. The presentation, pace, and profile of infection and sepsis patients hospitalized through the emergency department: an exploratory analysis. Crit Care Explor. 2021;3: e0344.CrossRef Liu VX, Bhimarao M, Greene JD, Manickam RN, Martinez A, Schuler A, et al. The presentation, pace, and profile of infection and sepsis patients hospitalized through the emergency department: an exploratory analysis. Crit Care Explor. 2021;3: e0344.CrossRef
6.
go back to reference Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13:862–74.CrossRef Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13:862–74.CrossRef
7.
go back to reference Delano MJ, Ward PA. The immune system’s role in sepsis progression, resolution, and long-term outcome. Immunol Rev. 2016;274:330–53.CrossRef Delano MJ, Ward PA. The immune system’s role in sepsis progression, resolution, and long-term outcome. Immunol Rev. 2016;274:330–53.CrossRef
8.
go back to reference Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE, Hui JJ, Chang KC, et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol Baltim Md. 1950;2001(166):6952–63. Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE, Hui JJ, Chang KC, et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol Baltim Md. 1950;2001(166):6952–63.
9.
go back to reference Drewry AM, Samra N, Skrupky LP, Fuller BM, Compton SM, Hotchkiss RS. Persistent lymphopenia after diagnosis of sepsis predicts mortality. Shock Augusta Ga. 2014;42:383–91.CrossRef Drewry AM, Samra N, Skrupky LP, Fuller BM, Compton SM, Hotchkiss RS. Persistent lymphopenia after diagnosis of sepsis predicts mortality. Shock Augusta Ga. 2014;42:383–91.CrossRef
10.
go back to reference de Jager CPC, van Wijk PTL, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care Lond Engl. 2010;14:R192.CrossRef de Jager CPC, van Wijk PTL, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care Lond Engl. 2010;14:R192.CrossRef
11.
go back to reference Jiang J, Du H, Su Y, Li X, Zhang J, Chen M, et al. Nonviral infection-related lymphocytopenia for the prediction of adult sepsis and its persistence indicates a higher mortality. Medicine (Baltimore). 2019;98: e16535.CrossRef Jiang J, Du H, Su Y, Li X, Zhang J, Chen M, et al. Nonviral infection-related lymphocytopenia for the prediction of adult sepsis and its persistence indicates a higher mortality. Medicine (Baltimore). 2019;98: e16535.CrossRef
12.
go back to reference Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324:782–93.CrossRef Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324:782–93.CrossRef
13.
go back to reference Lario M, Muñoz L, Ubeda M, Borrero M-J, Martínez J, Monserrat J, et al. Defective thymopoiesis and poor peripheral homeostatic replenishment of T-helper cells cause T-cell lymphopenia in cirrhosis. J Hepatol. 2013;59:723–30.CrossRef Lario M, Muñoz L, Ubeda M, Borrero M-J, Martínez J, Monserrat J, et al. Defective thymopoiesis and poor peripheral homeostatic replenishment of T-helper cells cause T-cell lymphopenia in cirrhosis. J Hepatol. 2013;59:723–30.CrossRef
14.
go back to reference Inoue S, Suzuki-Utsunomiya K, Okada Y, Taira T, Iida Y, Miura N, et al. Reduction of immunocompetent T cells followed by prolonged lymphopenia in severe sepsis in the elderly. Crit Care Med. 2013;41:810–9.CrossRef Inoue S, Suzuki-Utsunomiya K, Okada Y, Taira T, Iida Y, Miura N, et al. Reduction of immunocompetent T cells followed by prolonged lymphopenia in severe sepsis in the elderly. Crit Care Med. 2013;41:810–9.CrossRef
15.
go back to reference Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–10.CrossRef Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–10.CrossRef
16.
go back to reference He W, Xiao K, Fang M, Xie L. Immune cell number, phenotype, and function in the elderly with sepsis. Aging Dis. 2021;12:277–96.CrossRef He W, Xiao K, Fang M, Xie L. Immune cell number, phenotype, and function in the elderly with sepsis. Aging Dis. 2021;12:277–96.CrossRef
17.
go back to reference Miller JM, Binnicker MJ, Campbell S, Carroll KC, Chapin KC, Gilligan PH, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2018 update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis. 2018;67:e1–94.CrossRef Miller JM, Binnicker MJ, Campbell S, Carroll KC, Chapin KC, Gilligan PH, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2018 update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis. 2018;67:e1–94.CrossRef
18.
go back to reference Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101:1644–55.CrossRef Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101:1644–55.CrossRef
19.
go back to reference Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801–10.CrossRef Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801–10.CrossRef
20.
go back to reference Minderhoud TC, Spruyt C, Huisman S, Oskam E, Schuit SCE, Levin MD. Microbiological outcomes and antibiotic overuse in Emergency Department patients with suspected sepsis. Neth J Med. 2017;75:196–203.PubMed Minderhoud TC, Spruyt C, Huisman S, Oskam E, Schuit SCE, Levin MD. Microbiological outcomes and antibiotic overuse in Emergency Department patients with suspected sepsis. Neth J Med. 2017;75:196–203.PubMed
21.
go back to reference Heffner AC, Horton JM, Marchick MR, Jones AE. Etiology of illness in patients with severe sepsis admitted to the hospital from the emergency department. Clin Infect Dis. 2010;50:814–20.CrossRef Heffner AC, Horton JM, Marchick MR, Jones AE. Etiology of illness in patients with severe sepsis admitted to the hospital from the emergency department. Clin Infect Dis. 2010;50:814–20.CrossRef
22.
go back to reference Brun-Buisson C, Meshaka P, Pinton P, Vallet B, EPISEPSIS Study Group. EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med. 2004;30:580–8.CrossRef Brun-Buisson C, Meshaka P, Pinton P, Vallet B, EPISEPSIS Study Group. EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med. 2004;30:580–8.CrossRef
23.
go back to reference Shappell CN, Klompas M, Ochoa A, Rhee C, CDC Prevention Epicenters Program. Likelihood of bacterial infection in patients treated with broad-spectrum IV antibiotics in the Emergency Department. Crit Care Med. 2021;49:e1144–50.CrossRef Shappell CN, Klompas M, Ochoa A, Rhee C, CDC Prevention Epicenters Program. Likelihood of bacterial infection in patients treated with broad-spectrum IV antibiotics in the Emergency Department. Crit Care Med. 2021;49:e1144–50.CrossRef
24.
go back to reference Klein Klouwenberg PM, Cremer OL, van Vught LA, Ong DS, Frencken JF, Schultz MJ, et al. Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study. Crit Care. 2015;19:319.CrossRef Klein Klouwenberg PM, Cremer OL, van Vught LA, Ong DS, Frencken JF, Schultz MJ, et al. Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study. Crit Care. 2015;19:319.CrossRef
25.
go back to reference Shapiro NI, Wolfe RE, Moore RB, Smith E, Burdick E, Bates DW. Mortality in Emergency Department Sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule. Crit Care Med. 2003;31:670–5.CrossRef Shapiro NI, Wolfe RE, Moore RB, Smith E, Burdick E, Bates DW. Mortality in Emergency Department Sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule. Crit Care Med. 2003;31:670–5.CrossRef
26.
go back to reference Wyllie DH, Bowler ICJW, Peto TEA. Bacteraemia prediction in emergency medical admissions: role of C reactive protein. J Clin Pathol. 2005;58:352–6.CrossRef Wyllie DH, Bowler ICJW, Peto TEA. Bacteraemia prediction in emergency medical admissions: role of C reactive protein. J Clin Pathol. 2005;58:352–6.CrossRef
27.
go back to reference Su C-P, Chen TH-H, Chen S-Y, Ghiang W-C, Wu GH-M, Sun H-Y, et al. Predictive model for bacteremia in adult patients with blood cultures performed at the emergency department: a preliminary report. J Microbiol Immunol Infect Wei Mian Yu Gan Ran Za Zhi. 2011;44:449–55.CrossRef Su C-P, Chen TH-H, Chen S-Y, Ghiang W-C, Wu GH-M, Sun H-Y, et al. Predictive model for bacteremia in adult patients with blood cultures performed at the emergency department: a preliminary report. J Microbiol Immunol Infect Wei Mian Yu Gan Ran Za Zhi. 2011;44:449–55.CrossRef
28.
go back to reference Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, et al. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med. 1999;27:1230–51.CrossRef Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, et al. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med. 1999;27:1230–51.CrossRef
29.
go back to reference Hotchkiss RS, Swanson PE, Cobb JP, Jacobson A, Buchman TG, Karl IE. Apoptosis in lymphoid and parenchymal cells during sepsis: findings in normal and T- and B-cell-deficient mice. Crit Care Med. 1997;25:1298–307.CrossRef Hotchkiss RS, Swanson PE, Cobb JP, Jacobson A, Buchman TG, Karl IE. Apoptosis in lymphoid and parenchymal cells during sepsis: findings in normal and T- and B-cell-deficient mice. Crit Care Med. 1997;25:1298–307.CrossRef
30.
go back to reference Krabbe KS, Bruunsgaard H, Qvist J, Fonsmark L, Møller K, Hansen CM, et al. Activated T lymphocytes disappear from circulation during endotoxemia in humans. Clin Diagn Lab Immunol. 2002;9:731–5.PubMedPubMedCentral Krabbe KS, Bruunsgaard H, Qvist J, Fonsmark L, Møller K, Hansen CM, et al. Activated T lymphocytes disappear from circulation during endotoxemia in humans. Clin Diagn Lab Immunol. 2002;9:731–5.PubMedPubMedCentral
31.
go back to reference Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306:2594–605.CrossRef Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306:2594–605.CrossRef
32.
go back to reference Warny M, Helby J, Nordestgaard BG, Birgens H, Bojesen SE. Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study. PLoS Med. 2018;15: e1002685.CrossRef Warny M, Helby J, Nordestgaard BG, Birgens H, Bojesen SE. Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study. PLoS Med. 2018;15: e1002685.CrossRef
33.
go back to reference Serafim R, Gomes JA, Salluh J, Póvoa P. A Comparison of the Quick-SOFA and systemic inflammatory response syndrome criteria for the diagnosis of sepsis and prediction of mortality: a systematic review and meta-analysis. Chest. 2018;153:646–55.CrossRef Serafim R, Gomes JA, Salluh J, Póvoa P. A Comparison of the Quick-SOFA and systemic inflammatory response syndrome criteria for the diagnosis of sepsis and prediction of mortality: a systematic review and meta-analysis. Chest. 2018;153:646–55.CrossRef
34.
go back to reference Shaaban H, Daniel S, Sison R, Slim J, Perez G. Eosinopenia: is it a good marker of sepsis in comparison to procalcitonin and C-reactive protein levels for patients admitted to a critical care unit in an urban hospital? J Crit Care. 2010;25:570–5.CrossRef Shaaban H, Daniel S, Sison R, Slim J, Perez G. Eosinopenia: is it a good marker of sepsis in comparison to procalcitonin and C-reactive protein levels for patients admitted to a critical care unit in an urban hospital? J Crit Care. 2010;25:570–5.CrossRef
35.
go back to reference Sinistro A, Almerighi C, Ciaprini C, Natoli S, Sussarello E, Di Fino S, et al. Downregulation of CD40 ligand response in monocytes from sepsis patients. Clin Vaccine Immunol CVI. 2008;15:1851–8.CrossRef Sinistro A, Almerighi C, Ciaprini C, Natoli S, Sussarello E, Di Fino S, et al. Downregulation of CD40 ligand response in monocytes from sepsis patients. Clin Vaccine Immunol CVI. 2008;15:1851–8.CrossRef
36.
go back to reference Chalupa P, Beran O, Herwald H, Kaspříková N, Holub M. Evaluation of potential biomarkers for the discrimination of bacterial and viral infections. Infection. 2011;39:411–7.CrossRef Chalupa P, Beran O, Herwald H, Kaspříková N, Holub M. Evaluation of potential biomarkers for the discrimination of bacterial and viral infections. Infection. 2011;39:411–7.CrossRef
37.
go back to reference Tan L, Wang Q, Zhang D, Ding J, Huang Q, Tang Y-Q, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct Target Ther. 2020;5:33.CrossRef Tan L, Wang Q, Zhang D, Ding J, Huang Q, Tang Y-Q, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct Target Ther. 2020;5:33.CrossRef
Metadata
Title
High prevalence of infections in non-COVID-19 patients admitted to the Emergency Department with severe lymphopenia
Authors
Arthur Baïsse
Thomas Daix
Ana Catalina Hernandez Padilla
Robin Jeannet
Olivier Barraud
François Dalmay
Bruno François
Philippe Vignon
Thomas Lafon
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2022
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-022-07295-5

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