Dexamethasone and tocilizumab treatment considerably reduces the value of C-reactive protein and procalcitonin to detect secondary bacterial infections in COVID-19 patients

Abstract Background Procalcitonin (PCT) and C-reactive protein (CRP) were previously shown to have value for the detection of secondary infections in critically ill COVID-19 patients. However, since the introduction of immunomodulatory therapy, the value of these biomarkers is unclear. We investigated PCT and CRP kinetics in critically ill COVID-19 patients treated with dexamethasone with or without tocilizumab, and assessed the value of these biomarkers to detect secondary bacterial infections. Methods In this prospective study, 190 critically ill COVID-19 patients were divided into three treatment groups: no dexamethasone, no tocilizumab (D−T−), dexamethasone, no tocilizumab (D+T−), and dexamethasone and tocilizumab (D+T+). Serial data of PCT and CRP were aligned on the last day of dexamethasone treatment, and kinetics of these biomarkers were analyzed between 6 days prior to cessation of dexamethasone and 10 days afterwards. Furthermore, the D+T− and D+T+ groups were subdivided into secondary infection and no-secondary infection groups to analyze differences in PCT and CRP kinetics and calculate detection accuracy of these biomarkers for the occurrence of a secondary infection. Results Following cessation of dexamethasone, there was a rebound in PCT and CRP levels, most pronounced in the D+T− group. Upon occurrence of a secondary infection, no significant increase in PCT and CRP levels was observed in the D+T− group (p = 0.052 and p = 0.08, respectively). Although PCT levels increased significantly in patients of the D+T+ group who developed a secondary infection (p = 0.0003), this rise was only apparent from day 2 post-infection onwards. CRP levels remained suppressed in the D+T+ group. Receiver operating curve analysis of PCT and CRP levels yielded area under the curves of 0.52 and 0.55, respectively, which are both markedly lower than those found in the group of COVID-19 patients not treated with immunomodulatory drugs (0.80 and 0.76, respectively, with p values for differences between groups of 0.001 and 0.02, respectively). Conclusions Cessation of dexamethasone in critically ill COVID-19 patients results in a rebound increase in PCT and CRP levels unrelated to the occurrence of secondary bacterial infections. Furthermore, immunomodulatory treatment with dexamethasone and tocilizumab considerably reduces the value of PCT and CRP for detection of secondary infections in COVID-19 patients.

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C-Reactive Protein as A Fungal Infection Marker in Acute Leukemia Patients

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v27i2.1639 ◽

2021 ◽

Vol 27 (2) ◽

pp. 212

Author(s):

Brigitte Rina Aninda Sidharta ◽

JB. Suparyatmo ◽

Avanti Fitri Astuti

Keyword(s):

Acute Leukemia ◽

Predictive Value ◽

Bacterial Infections ◽

Fungal Infections ◽

Lymphoblastic Leukemia ◽

Negative Likelihood Ratio ◽

Receiver Operating Curve ◽

High Morbidity ◽

C Reactive Protein ◽

Reactive Protein

Invasive Fungal Infections (IFIs) can cause serious problems in cancer patients and may result in high morbidity andmortality. C-reactive protein levels increase in response to injury, infection, and inflammation. C-reactive protein increasesin bacterial infections (mean of 32 mg/L) and in fungal infections (mean of 9 mg/L). This study aimed to determineC-Reactive Protein (CRP) as a marker of fungal infections in patients with acute leukemia by establishing cut-off values ofCRP. This study was an observational analytical study with a cross-sectional approach and was carried out at the Departmentof Clinical Pathology and Microbiology of Dr. Moewardi Hospital in Surakarta from May until August 2019. The inclusioncriteria were patients with acute leukemia who were willing to participate in this study, while exclusion criteria were patientswith liver disease. There were 61 samples consisting of 30 male and 31 female patients with ages ranging from 1 to 70 years.Fifty-four patients (88.5%) were diagnosed with Acute Lymphoblastic Leukemia (ALL) and 30 (49.18%) were in themaintenance phase. The risk factors found in those patients were neutropenia 50-1500 μL (23.8%), use of intravenous line(22%), and corticosteroid therapy for more than one week (20.9%). The median of CRP in the group of patients with positiveculture results was 11.20 mg/L (11.20-26.23 mg/L) and negative culture results in 0.38 mg/L (0.01-18.63 mg/L). The cut-offvalue of CRP using the Receiver Operating Curve (ROC) was 9.54 mg/L (area under curve 0.996 and p. 0.026), with a sensitivityof 100%, specificity of 93.2%, Positive Predictive Value (PPV) of 33.3%, Negative Predictive Value (PPV) of 100%, PositiveLikelihood Ratio (PLR) of 1.08, Negative Likelihood Ratio (NLR) of 0 and accuracy of 93.4%. C-reactive protein can be used asa screening marker for fungal infections in patients with acute leukemia.

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C-reactive protein and procalcitonin for antimicrobial stewardship in COVID-19

Infection ◽

10.1007/s15010-021-01615-8 ◽

2021 ◽

Author(s):

Isabell Pink ◽

David Raupach ◽

Jan Fuge ◽

Ralf-Peter Vonberg ◽

Marius M. Hoeper ◽

...

Keyword(s):

Antibiotic Therapy ◽

Bacterial Infection ◽

Bacterial Infections ◽

Roc Analysis ◽

Secondary Infection ◽

C Reactive Protein ◽

Laboratory Findings ◽

Secondary Bacterial Infection ◽

Reactive Protein ◽

Tract Infections

Abstract Purpose Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread around the world. Differentiation between pure viral COVID-19 pneumonia and secondary infection can be challenging. In patients with elevated C-reactive protein (CRP) on admission physicians often decide to prescribe antibiotic therapy. However, overuse of anti-infective therapy in the pandemic should be avoided to prevent increasing antimicrobial resistance. Procalcitonin (PCT) and CRP have proven useful in other lower respiratory tract infections and might help to differentiate between pure viral or secondary infection. Methods We performed a retrospective study of patients admitted with COVID-19 between 6th March and 30th October 2020. Patient background, clinical course, laboratory findings with focus on PCT and CRP levels and microbiology results were evaluated. Patients with and without secondary bacterial infection in relation to PCT and CRP were compared. Using receiver operating characteristic (ROC) analysis, the best discriminating cut-off value of PCT and CRP with the corresponding sensitivity and specificity was calculated. Results Out of 99 inpatients (52 ICU, 47 Non-ICU) with COVID-19, 32 (32%) presented with secondary bacterial infection during hospitalization. Patients with secondary bacterial infection had higher PCT (0.4 versus 0.1 ng/mL; p = 0.016) and CRP (131 versus 73 mg/L; p = 0.001) levels at admission and during the hospital stay (2.9 versus 0.1 ng/mL; p < 0.001 resp. 293 versus 94 mg/L; p < 0.001). The majority of patients on general ward had no secondary bacterial infection (93%). More than half of patients admitted to the ICU developed secondary bacterial infection (56%). ROC analysis of highest PCT resp. CRP and secondary infection yielded AUCs of 0.88 (p < 0.001) resp. 0.86 (p < 0.001) for the entire cohort. With a PCT cut-off value at 0.55 ng/mL, the sensitivity was 91% with a specificity of 81%; a CRP cut-off value at 172 mg/L yielded a sensitivity of 81% with a specificity of 76%. Conclusion PCT and CRP measurement on admission and during the course of the disease in patients with COVID-19 may be helpful in identifying secondary bacterial infections and guiding the use of antibiotic therapy.

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Lymphocyte-to-C-reactive protein ratio may serve as an effective biomarker to determine COVID-19 disease severity

Turkish Journal of Biochemistry ◽

10.1515/tjb-2020-0410 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Tayibe Bal ◽

Serdar Dogan ◽

Mehmet Cabalak ◽

Emre Dirican

Keyword(s):

Critically Ill ◽

Roc Analysis ◽

Receiver Operating Curve ◽

C Reactive Protein ◽

Protein Ratio ◽

Discriminative Performance ◽

Reactive Protein ◽

Single Center Study ◽

Study Population ◽

Better Than

AbstractObjectivesWe aimed to evaluate the ability of lymphocyte-C-reactive protein ratio (LCR) to discriminate between different levels of severity of COVID-19 disease.MethodsThis retrospective observational single-center study was performed on 61 confirmed (PCR positive) COVID-19 patients between March and June 2020. The study population was separated into three groups: mild/moderate (n=24), severe (n=25) and critically ill (n=12). The optimal cut-off values of the LCR and neutrophil-to-lymphocyte ratio (NLR) in discriminating between patients with different severity levels were calculated by applying the receiver operating curve (ROC) analysis.ResultsAt baseline, the LCR decreased significantly across the three severity groups (mild/moderate > severe > critically ill). ROC analysis showed that a mean LCR of 43.21 was the cut-off value which best discriminated patients with the critically ill disease from severe patients (sensitivity: 84% and specificity: 69%). The discriminative performance of LCR (ROC AUC 0.820) was better than that of NLR (0.751) in this regard. LCR, unlike NLR was able to distinguish severe patients from mild/moderate patients, with a cut off value of 458.19 (sensitivity: 80% and specificity: 45%).ConclusionLCR was observed to be able to distinguish COVID-19 infected patients of different severity (mild/moderate, severe and critically ill) and was superior to NLR in this regard.

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A Metabolomics approach for the diagnosis Of SecondAry InfeCtions in COVID-19 (MOSAIC): a study protocol

BMC Infectious Diseases ◽

10.1186/s12879-021-06832-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gordan McCreath ◽

Phillip D. Whitfield ◽

Andrew J. Roe ◽

Malcolm J. Watson ◽

Malcolm A. B. Sim

Keyword(s):

Critically Ill ◽

Antimicrobial Therapy ◽

Critically Ill Patients ◽

Bacterial Infections ◽

Secondary Infection ◽

Data Sets ◽

Critical Care Units ◽

Secondary Infections ◽

Increased Risk ◽

Additional Sample

Abstract Background Critically ill patients with COVID-19 are at an increased risk of developing secondary bacterial infections. These are both difficult to diagnose and are associated with an increased mortality. Metabolomics may aid clinicians in diagnosing secondary bacterial infections in COVID-19 through identification and quantification of disease specific biomarkers, with the aim of identifying underlying causative microorganisms and directing antimicrobial therapy. Methods This is a multi-centre prospective diagnostic observational study. Patients with COVID-19 will be recruited from critical care units in three Scottish hospitals. Three serial blood samples will be taken from patients, and an additional sample taken if a patient shows clinical or microbiological evidence of secondary infection. Samples will be analysed using LC–MS and subjected to bioinformatic processing and statistical analysis to explore the metabolite changes associated with bacterial infections in COVID-19 patients. Comparisons of the data sets will be made with standard microbiological and biochemical methods of diagnosing infection. Discussion Metabolomics analyses may provide additional strategies for identifying secondary infections, which might permit faster initiation of specific tailored antimicrobial therapy to critically ill patients with COVID-19.

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