Differences in the inflammatory response and outcome among hospitalized patients during different waves of the COVID-19 pandemic

IntroductionThe aim of this study was to evaluate differences in inflammatory biomarkers and their association with outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19) during four pandemic waves determined by different SARSCoV- 2 variants of concern. We explored if laboratory...

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Main Authors: Violeta Briciu, Daniel-Corneliu Leucuta, Monica Muntean, Amanda Radulescu, Cristina Cismaru, Adriana Topan, Lucia Herbel, Melinda Horvat, Mirela Flonta, Mihai Calin, Roxana Dobrota, Mihaela Lupse
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Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1545181/full
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author Violeta Briciu
Violeta Briciu
Daniel-Corneliu Leucuta
Monica Muntean
Monica Muntean
Amanda Radulescu
Amanda Radulescu
Cristina Cismaru
Cristina Cismaru
Adriana Topan
Adriana Topan
Lucia Herbel
Melinda Horvat
Melinda Horvat
Mirela Flonta
Mihai Calin
Roxana Dobrota
Mihaela Lupse
Mihaela Lupse
author_facet Violeta Briciu
Violeta Briciu
Daniel-Corneliu Leucuta
Monica Muntean
Monica Muntean
Amanda Radulescu
Amanda Radulescu
Cristina Cismaru
Cristina Cismaru
Adriana Topan
Adriana Topan
Lucia Herbel
Melinda Horvat
Melinda Horvat
Mirela Flonta
Mihai Calin
Roxana Dobrota
Mihaela Lupse
Mihaela Lupse
author_sort Violeta Briciu
collection DOAJ
description IntroductionThe aim of this study was to evaluate differences in inflammatory biomarkers and their association with outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19) during four pandemic waves determined by different SARSCoV- 2 variants of concern. We explored if laboratory biomarkers of inflammation adjusted to patients’ comorbidities, age, and vaccination status correlated with severity and mortality.MethodsA retrospective study on 8,614 consecutive hospitalized COVID-19 patients was conducted in a Romanian hospital on a 3-year interval (February 2020 to May 2023). Data collected included demographics, duration of hospitalization, comorbidities, vaccination status, COVID-19 severity, outcome, and markers of inflammation from the first blood test performed at admittance [C-reactive protein (CRP), fibrinogen, ferritin, lactate dehydrogenase (LDH), procalcitonin (PCT), IL-6, D-dimer, and complete blood count]. Systemic inflammatory indexes like neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), Systemic Immune-Inflammation Index (SII), and systemic inflammation response index (SIRI) were calculated.ResultsThe Delta wave, characterized by the longest hospitalizations and the highest rates of severe cases and mortality, showed significant elevations in inflammatory biomarkers. CRP, fibrinogen, ferritin, IL-6, D-dimer, and LDH increased in their median values from the Wuhan to Delta wave and decreased in the Omicron wave, except PCT, which increased from the Alpha to Omicron wave. Leukocytes and neutrophils increased in their median values from the Wuhan to Delta wave and decreased in the Omicron wave, while an inverse pattern can be observed for lymphocytes, monocytes, and basophils. The best inflammatory biomarkers for predicting severe/critical COVID-19 were CRP, dNLR, LDH, and NLR (cut-off of 3.41 mg/dL, 3.05, 262 U/L, and 4.5, respectively), while for predicting death outcomes, the best biomarkers were dNLR, NLR, LDH, and NPR (cut-off of 3.6, 4.9, 278 U/L, and 0.02, respectively). For all these biomarkers, the areas under the curve (AUCs) surpassed 0.8. In the multivariate analysis, the highest adjusted OR for death was described for dNLR (8.46), NLR (7.59), LDH (5.99), and NPR (5.5), while increased lymphocytes decreased the highest adjusted OR for death (0.16).ConclusionThe study, underscoring the dynamic nature of COVID-19, brings a detailed analysis of biomarker trends that could provide valuable information for the early identification of patients at risk for severe outcomes, allowing for timely interventions.
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spelling doaj-art-62f686a642c6472b8852a4a0e2ca60482025-08-20T03:42:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15451811545181Differences in the inflammatory response and outcome among hospitalized patients during different waves of the COVID-19 pandemicVioleta Briciu0Violeta Briciu1Daniel-Corneliu Leucuta2Monica Muntean3Monica Muntean4Amanda Radulescu5Amanda Radulescu6Cristina Cismaru7Cristina Cismaru8Adriana Topan9Adriana Topan10Lucia Herbel11Melinda Horvat12Melinda Horvat13Mirela Flonta14Mihai Calin15Roxana Dobrota16Mihaela Lupse17Mihaela Lupse18Department of Infectious Diseases and Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, RomaniaThe Clinical Hospital of Infectious Diseases, Cluj-Napoca, RomaniaDepartment of Medical Informatics and Biostatistics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, RomaniaDepartment of Infectious Diseases and Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, RomaniaThe Clinical Hospital of Infectious Diseases, Cluj-Napoca, RomaniaDepartment of Infectious Diseases and Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, RomaniaThe Clinical Hospital of Infectious Diseases, Cluj-Napoca, RomaniaDepartment of Infectious Diseases and Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, RomaniaThe Clinical Hospital of Infectious Diseases, Cluj-Napoca, RomaniaDepartment of Infectious Diseases and Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, RomaniaThe Clinical Hospital of Infectious Diseases, Cluj-Napoca, RomaniaThe Clinical Hospital of Infectious Diseases, Cluj-Napoca, RomaniaDepartment of Infectious Diseases and Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, RomaniaThe Clinical Hospital of Infectious Diseases, Cluj-Napoca, RomaniaThe Clinical Hospital of Infectious Diseases, Cluj-Napoca, RomaniaThe Clinical Hospital of Infectious Diseases, Cluj-Napoca, RomaniaThe Clinical Hospital of Infectious Diseases, Cluj-Napoca, RomaniaDepartment of Infectious Diseases and Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, RomaniaThe Clinical Hospital of Infectious Diseases, Cluj-Napoca, RomaniaIntroductionThe aim of this study was to evaluate differences in inflammatory biomarkers and their association with outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19) during four pandemic waves determined by different SARSCoV- 2 variants of concern. We explored if laboratory biomarkers of inflammation adjusted to patients’ comorbidities, age, and vaccination status correlated with severity and mortality.MethodsA retrospective study on 8,614 consecutive hospitalized COVID-19 patients was conducted in a Romanian hospital on a 3-year interval (February 2020 to May 2023). Data collected included demographics, duration of hospitalization, comorbidities, vaccination status, COVID-19 severity, outcome, and markers of inflammation from the first blood test performed at admittance [C-reactive protein (CRP), fibrinogen, ferritin, lactate dehydrogenase (LDH), procalcitonin (PCT), IL-6, D-dimer, and complete blood count]. Systemic inflammatory indexes like neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), Systemic Immune-Inflammation Index (SII), and systemic inflammation response index (SIRI) were calculated.ResultsThe Delta wave, characterized by the longest hospitalizations and the highest rates of severe cases and mortality, showed significant elevations in inflammatory biomarkers. CRP, fibrinogen, ferritin, IL-6, D-dimer, and LDH increased in their median values from the Wuhan to Delta wave and decreased in the Omicron wave, except PCT, which increased from the Alpha to Omicron wave. Leukocytes and neutrophils increased in their median values from the Wuhan to Delta wave and decreased in the Omicron wave, while an inverse pattern can be observed for lymphocytes, monocytes, and basophils. The best inflammatory biomarkers for predicting severe/critical COVID-19 were CRP, dNLR, LDH, and NLR (cut-off of 3.41 mg/dL, 3.05, 262 U/L, and 4.5, respectively), while for predicting death outcomes, the best biomarkers were dNLR, NLR, LDH, and NPR (cut-off of 3.6, 4.9, 278 U/L, and 0.02, respectively). For all these biomarkers, the areas under the curve (AUCs) surpassed 0.8. In the multivariate analysis, the highest adjusted OR for death was described for dNLR (8.46), NLR (7.59), LDH (5.99), and NPR (5.5), while increased lymphocytes decreased the highest adjusted OR for death (0.16).ConclusionThe study, underscoring the dynamic nature of COVID-19, brings a detailed analysis of biomarker trends that could provide valuable information for the early identification of patients at risk for severe outcomes, allowing for timely interventions.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1545181/fullCOVID-19pandemic wavesinflammatory biomarkerssystemic inflammatory indexesdisease severitymortality
spellingShingle Violeta Briciu
Violeta Briciu
Daniel-Corneliu Leucuta
Monica Muntean
Monica Muntean
Amanda Radulescu
Amanda Radulescu
Cristina Cismaru
Cristina Cismaru
Adriana Topan
Adriana Topan
Lucia Herbel
Melinda Horvat
Melinda Horvat
Mirela Flonta
Mihai Calin
Roxana Dobrota
Mihaela Lupse
Mihaela Lupse
Differences in the inflammatory response and outcome among hospitalized patients during different waves of the COVID-19 pandemic
Frontiers in Immunology
COVID-19
pandemic waves
inflammatory biomarkers
systemic inflammatory indexes
disease severity
mortality
title Differences in the inflammatory response and outcome among hospitalized patients during different waves of the COVID-19 pandemic
title_full Differences in the inflammatory response and outcome among hospitalized patients during different waves of the COVID-19 pandemic
title_fullStr Differences in the inflammatory response and outcome among hospitalized patients during different waves of the COVID-19 pandemic
title_full_unstemmed Differences in the inflammatory response and outcome among hospitalized patients during different waves of the COVID-19 pandemic
title_short Differences in the inflammatory response and outcome among hospitalized patients during different waves of the COVID-19 pandemic
title_sort differences in the inflammatory response and outcome among hospitalized patients during different waves of the covid 19 pandemic
topic COVID-19
pandemic waves
inflammatory biomarkers
systemic inflammatory indexes
disease severity
mortality
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1545181/full
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