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Serial KL-6 measurements in COVID-19 patients.

ABSTRACT: SARS-CoV2-induced direct cytopathic effects against type II pneumocytes are suspected to play a role in mediating and perpetuating lung damage. The aim of this study was to evaluate serum KL-6 behavior in COVID-19 patients to investigate its potential role in predicting clinical course. Sixty patients (median age IQR, 65 (52-69), 43 males), hospitalized for COVID-19 at Siena COVID Unit University Hospital, were prospectively enrolled. Twenty-six patients were selected (median age IQR, 63 (55-71), 16 males); all of them underwent follow-up evaluations, including clinical, radiological, functional, and serum KL-6 assessments, after 6 (t1) and 9 (t2) months from hospital discharge. At t0, KL-6 concentrations were significantly higher than those at t1 (760 (311-1218) vs. 309 (210-408) p = 0.0208) and t2 (760 (311-1218) vs 324 (279-458), p = 0.0365). At t0, KL-6 concentrations were increased in patients with fibrotic lung alterations than in non-fibrotic group (755 (370-1023) vs. 305 (225-608), p = 0.0225). Area under the receiver operating curve (AUROC) analysis showed that basal KL-6 levels showed good accuracy in discriminating patients with fibrotic sequelae radiologically documented (AUC 85%, p = 0.0404). KL-6 concentrations in patients with fibrotic involvement were significantly reduced at t1 (755 (370-1023) vs. 290 (197-521), p = 0.0366) and t2 (755 (370-1023) vs. 318 (173-435), p = 0.0490). Serum concentrations of KL-6 in hospitalized COVID-19 patients may contribute to identify severe patients requiring mechanical ventilation and to predict those who will develop pulmonary fibrotic sequelae in the follow-up.

SUBMITTER: d'Alessandro M

PROVIDER: S-EPMC7811154 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The prognostic value of serial troponin measurements in patients admitted for COVID-19.

Project description:AimsMyocardial injury (MI) in coronavirus disease-19 (COVID-19) is quite prevalent at admission and affects prognosis. Little is known about troponin trajectories and their prognostic role. We aimed to describe the early in-hospital evolution of MI and its prognostic impact.Methods and resultsWe performed an analysis from an Italian multicentre study enrolling COVID-19 patients, hospitalized from 1 March to 9 April 2020. MI was defined as increased troponin level. The first troponin was tested within 24 h from admission, the second one between 24 and 48 h. Elevated troponin was defined as values above the 99th percentile of normal values. Patients were divided in four groups: normal, normal then elevated, elevated then normal, and elevated. The outcome was in-hospital death. The study population included 197 patients; 41% had normal troponin at both evaluations, 44% had elevated troponin at both assessments, 8% had normal then elevated troponin, and 7% had elevated then normal troponin. During hospitalization, 49 (25%) patients died. Patients with incident MI, with persistent MI, and with MI only at admission had a higher risk of death compared with those with normal troponin at both evaluations (P < 0.001). At multivariable analysis, patients with normal troponin at admission and MI injury on Day 2 had the highest mortality risk (hazard ratio 3.78, 95% confidence interval 1.10-13.09, P = 0.035).ConclusionsIn patients admitted for COVID-19, re-test MI on Day 2 provides a prognostic value. A non-negligible proportion of patients with incident MI on Day 2 is identified at high risk of death only by the second measurement.

| S-EPMC8426962 | biostudies-literature

Proteomic blood profiling in mild, severe and critical COVID-19 patients

Project description: Not available

| S-BSST416 | biostudies-other

Proximal Tubular Dysfunction as a Predictor of AKI in Hospitalized COVID-19 Patients

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| S-BSST1269 | biostudies-other

Increased KL-6 levels in moderate to severe COVID-19 infection.

Project description:BackgroundThe global coronavirus disease 2019 (COVID-19) has presented significant challenges and created concerns worldwide. Besides, patients who have experienced a SARS-CoV-2 infection could present post-viral complications that can ultimately lead to pulmonary fibrosis. Serum levels of Krebs von den Lungen 6 (KL-6), high molecular weight human MUC1 mucin, are increased in the most patients with various interstitial lung damage. Since its production is raised during epithelial damages, KL-6 could be a helpful non-invasive marker to monitor COVID-19 infection and predict post-infection sequelae.MethodsWe retrospectively evaluated KL-6 levels of 222 COVID-19 infected patients and 70 healthy control. Serum KL-6, fibrinogen, lactate dehydrogenase (LDH), platelet-lymphocytes ratio (PLR) levels and other biological parameters were analyzed. This retrospective study also characterized the relationships between serum KL-6 levels and pulmonary function variables.ResultsOur results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects (470 U/ml vs 254 U/ml, P <0.00001). ROC curve analysis enabled us to identify that KL-6 > 453.5 U/ml was associated with COVID-19 (AUC = 0.8415, P < 0.0001). KL-6 level was positively correlated with other indicators of disease severity such as fibrinogen level (r = 0.1475, P = 0.0287), LDH level (r = 0,31, P = 0,004) and PLR level (r = 0.23, P = 0.0005). However, KL-6 levels were not correlated with pulmonary function tests (r = 0.04, P = 0.69).ConclusionsKL-6 expression was correlated with several disease severity indicators. However, the association between mortality and long-term follow-up outcomes needs further investigation. More extensive trials are required to prove that KL-6 could be a marker of disease severity in COVID-19 infection.

| S-EPMC9704627 | biostudies-literature

Serial measurements of KL-6 for monitoring activity and recurrence of interstitial pneumonia with anti-aminoacyl-tRNA synthetase antibody: A retrospective cohort study.

Project description:The aim of this study was to evaluate whether serial measurements of serum Krebs von den Lungen-6 (KL-6) could be used to monitor disease activity and to detect recurrence in patients with interstitial pneumonia (IP) with anti-aminoacyl-tRNA synthetase antibodies (ARS-IP).This retrospective cohort study included 44 patients with ARS-IP. Thirty-six patients had serial data of blood tests and pulmonary function tests. Baseline and longitudinal analyses were performed to investigate whether lung function parameters were associated with serum biomarkers (KL-6, lactate dehydrogenase [LDH], and C-reactive protein [CRP]) using Pearson correlation coefficient. Additionally, the diagnostic accuracy of changes in these biomarkers for detecting ARS-IP recurrence was analyzed by receiver operating characteristic curve analysis.Baseline levels of serum KL-6 were significantly associated with vital capacity (VC) and diffusion capacity for carbon monoxide (DLco) (r?=?-0.40, P?=?.015, and r?=?-0.44, P?=?.010, respectively). Longitudinal changes in KL-6 were inversely correlated with changes in VC and DLco (r?=?-0.57, P?<.001 and r?=?-0.42, P?<.001, respectively), whereas those in LDH and CRP were not. Moreover, longitudinal changes in serum KL-6 were significantly associated with recurrence of ARS-IP and could be used to detect ARS-IP recurrence; the area under the curve was 0.79 (P?=?.002).The present study demonstrated that serial measurement of KL-6 is useful for monitoring disease activity and detecting recurrence of ARS-IP.

| S-EPMC6310603 | biostudies-literature

Krebs von den Lungen 6 (KL-6) levels in COVID-19 ICU patients are associated with mortality.

Project description:BackgroundKrebs von den Lungen 6 (KL-6) is a high-molecular-weight mucin-like glycoprotein, which is also known as MUC1. KL-6 is mainly produced by type 2 pneumocytes and bronchial epithelial cells, and, therefore, elevated circulating KL-6 levels may denote disorders of the alveolar epithelial lining. The objective of this study is to verify if KL-6 serum level might support ICU physicians in predicting mortality, risk stratifying and triaging severe COVID-19 patients.MethodsA retrospective cohort study, including all the COVID-19 patients who measured KL-6 serum values at least once during their ICU stay, was performed. The study sample, 122 patients, was divided in two groups, according to the median KL-6 value at ICU admission (median log-transformed KL-6 value: 6.73 U/ml; group A: KL-6 lower than the median and group B: KL-6 higher than the median).ResultsOne-hundred twenty-two ICU patients were included in this study. Mortality was higher in group B than in group A (80 versus 46%; p < 0.001); both linear and logistic multivariate analyses showed ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (P/F) significantly and inversely related to KL-6 values.ConclusionAt ICU admission, KL-6 serum level was significantly higher in the most hypoxic COVID-19 patients and independently associated with ICU mortality.

| S-EPMC9391655 | biostudies-literature

Serial Measurements of Circulating KL-6, SP-D, MMP-7, CA19-9, CA-125, CCL18, and Periostin in Patients with Idiopathic Pulmonary Fibrosis Receiving Antifibrotic Therapy: An Exploratory Study.

Project description:Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal disease with a heterogeneous clinical course. This study aimed to evaluate the usefulness of circulating biomarkers in routine IPF clinical practice. We conducted an exploratory study in a cohort of 28 IPF subjects qualified for anti-fibrotic therapy with up to 24 months serial measurements of seven IPF biomarkers, including those that are well-established, Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), matrix metalloproteinase 7 (MMP-7), and more recently introduced ones, cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA-125), chemokine (C-C motif) ligand 18 (CCL18), and periostin. Among studied biomarkers, SP-D had the highest diagnostic accuracy to differentiate IPF subjects from controls, followed by MMP-7 and KL-6. At each study timepoint, KL-6 levels correlated inversely with forced vital capacity % predicted (FVC% pred.), and transfer factor of the lung for carbon monoxide % predicted (TL,CO% pred.), while SP-D levels correlated inversely with FVC% pred. and TL,CO% pred. at 24 months of anti-fibrotic therapy. Baseline KL-6 and CA19-9 concentrations were significantly elevated in patients with progressive disease in comparison to patients with stable disease. In addition, in the progressors subgroup CA19-9 concentrations significantly increased over the second year of study follow-up. In patients with progressive disease, we observed a significant inverse correlation between a change in SP-D levels and a change in FVC% pred. in the first year of treatment, whereas in the second year a significant inverse correlation between a change in KL-6 levels and a change in FVC% pred. was noted. Our study findings support the view that both well-established IPF biomarkers, including KL-6, SP-D, and MMP-7, and more recently introduced ones, like CA19-9, have the potential to support clinical practice in IPF.

| S-EPMC8432145 | biostudies-literature

Next generation plasma proteome profiling of COVID-19 patients with mild to moderate symptoms

Project description: Not available

| S-BSST719 | biostudies-other

A novel assessment method for COVID-19 humoral immunity duration using serial measurements in naturally infected and vaccinated subjects.

Project description:BackgroundCollecting information on sustainability of immune responses after infection or vaccination is crucial to inform medical decision-making and vaccination strategies. Data on how long-lasting antibodies against SARS-COV-2 could provide a humoral and protective immunity and prevent reinfection with SARS-CoV-2 or its variants is particularly valuable. This study presents a novel method to quantitatively measure and monitor the diversity of SARS-CoV-2 specific antibody profiles over time.MethodsSerum samples from two groups were used in this study: Samples from 20 naturally infected subjects (followed for up to 1 year) and samples from 83 subjects vaccinated with one or two doses of the Pfizer BioNtech vaccine (BNT162b2/BNT162b2) (followed for up to 6 months). The Multi-SARS-CoV-2 assay, a multiparameter serology test developed for the serological confirmation of past-infections, was used to determine the reactivity of six different SARS-CoV-2 antigens. For each subject sample, 3 dilutions (1/50, 1/400 and 1/3200) were defined as an optimal set over the six antigens and their respective linear ranges. This allowed accurate quantification of the corresponding six antibodies. Nonlinear mixed-effects modelling was applied to convert intensity readings from 3 determined dilutions to a single quantification value for each antibody.ResultsMedian half-life for the 20 naturally infected vs 74 vaccinated subjects (two doses) was 120 vs 50 days for RBD, 127 vs 53 days for S1 and 187 vs 86 days for S2 antibodies respectively.ConclusionThe newly proposed method, based on a series of a limited number of dilutions, can convert a conventional qualitative assay into a quantitative assay. This conversion helps define the sustainability of specific immune responses against each relevant viral antigen and can help in defining the protection characteristics after an infection or a vaccination.

| S-EPMC9521896 | biostudies-literature

Antiviral use in liver function abnormalities and Covid-19 patients: Serial cases.

Project description:IntroductionSome SARS-CoV-2 patients have liver function abnormalities due to anti-viral drug effects.MethodsThe design of this study was a case series reported using retrospectives. Data collection was carried out from December 2020 to February 2021. All participants were diagnosed with SAR-CoV-2 and received an anti-viral drug which identified liver function abnormalities.ResultsThe patients' average age was 54.56 ± 14.46 years old. Most patients experienced shortness of breath and cough, with hypertension as the accompanying comorbid. Increased AST and ALT were found in one patient who used Lopinavir-Ritonavir. The increase was 1.0 times to 2.0 times the expected value. Increased CRP, D-dimer and procalcitonin were also found, with a mean of 12.27 ± 15,34, 1861.29 ± 1828.85 and 1.54 ± 2.84, respectively. One of the patients in the Lopinavir-Ritonavir group died while receiving treatment.ConclusionSAR-CoV-2 is one of the risk factors that cause liver function abnormalities supported by anti-viral drugs that cause liver work to increase.

| S-EPMC9652095 | biostudies-literature

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