Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019

Yamaya, Takafumi; Hagiwara, Eri; Baba, Tomohisa; Kitayama, Takaaki; Murohashi, Kota; Higa, Katsuyuki; Sato, Yozo; Otoshi, Ryota; Tabata, Erina; Shintani, Ryota; Okabayashi, Hiroko; Ikeda, Satoshi; Niwa, Takashi; Nakazawa, Atsuhito; Oda, Toshiatsu; Okuda, Ryo; Sekine, Akimasa; Kitamura, Hideya; Komatsu, Shigeru; Ogura, Takashi

doi:10.1016/j.resinv.2021.04.002

Cited by 17 publications

(24 citation statements)

References 25 publications

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“…According to our data, a significantly greater risk for worse outcomes should be considered for patients having a serum KL-6 value of 968 U/mL or more, with a sensitivity and specificity of 79.2% and 87.1%, respectively, and a positive predictive value of 70.4%. These findings fully match data obtained from previous studies in which elevated levels of serum KL-6 are a significant predictor of poor outcomes in patients with COVID-19 [ 23 , 24 , 25 , 26 , 27 ].…”

Section: Discussionsupporting

confidence: 90%

Exploring the Role of Krebs von den Lungen-6 in Severe to Critical COVID-19 Patients

D’Agnano

Scialò

Perna

et al. 2022

Life

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COVID-19 encompasses a broad spectrum of clinical conditions caused by SARS-CoV-2 infection. More severe cases experience acute respiratory and/or multiorgan failure. KL-6 is a glycoprotein expressed mainly from type II alveolar cells with pro-fibrotic properties. Serum KL-6 concentrations have been found in patients with COVID-19. However, the relevance of KL-6 in patients with severe and critical COVID-19 has not been fully elucidated. Methods: Retrospective data from consecutive severe to critical COVID-19 patients were collected at UOC Clinica Pnuemologica “Vanvitelli”, A.O. dei Colli, Naples, Italy. The study included patients with a positive rhinopharyngeal swab for SARS-CoV-2 RNA with severe or critical COVID-19. Results: Among 87 patients, 24 had poor outcomes. The median KL-6 value in survivors was significantly lower when compared with dead or intubated patients (530 U/mL versus 1069 U/mL p < 0.001). KL-6 was correlated with body mass index (BMI) (r: 0.279, p: 0.009), lung ultrasound score (LUS) (r: 0.429, p < 0.001), Chung Score (r: 0.390, p < 0.001). KL-6 was associated with the risk of death or oro-tracheal intubation (IOT) after adjusting for gender, BMI, Charlson Index, Chung Score, and PaO2/FIO2 (OR 1.003 95% CI 1.001–1.004, p < 0.001). Serum KL-6 value of 968 has a sensitivity of 79.2%, specificity of 87.1%, PPV 70.4%, NPV 91.5%, AUC: O.85 for risk of death or IOT. Conclusions: The presented research highlights the relevance of serum KL-6 in severe to critical COVID-19 patients in predicting the risk of death or IOT.

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Section: Discussionsupporting

confidence: 90%

Exploring the Role of Krebs von den Lungen-6 in Severe to Critical COVID-19 Patients

D’Agnano

Scialò

Perna

et al. 2022

Life

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“…The clinical implications of serum KL‐6 and SP‐D levels have been investigated in the above‐stated context. As per reports, both serum KL‐6 and SP‐D levels are elevated in patients with severe COVID‐19 and, therefore, these constituents are useful biomarkers of disease severity 9,11,13,20,21 . In addition to disease severity, serum KL‐6 was reported to predict pulmonary fibrosis followed by infection with SARS‐CoV‐2 10,22 and serum SP‐D was reported to be useful for distinguishing pandemic influenza A (H1N1) from COVID‐19 in patients who required mechanical ventilation 23 .…”

Section: Discussionmentioning

confidence: 79%

Surfactant protein D: A useful biomarker for distinguishing COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases

Togashi

Kono

Okuma

et al. 2022

Health Science Reports

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Introduction: Computed tomography is useful for the diagnosis of coronavirus disease (COVID-19) pneumonia. However, many types of interstitial lung diseases and even bacterial pneumonia can show abnormal chest shadows that are indistinguishable from those observed in COVID-19 pneumonia. Thus, it is necessary to identify useful biomarkers that can efficiently distinguish COVID-19 pneumonia from COVID-19 pneumonia-like diseases. Herein, we investigated the usefulness of serum Krebs von den Lungen 6 (KL-6) and surfactant protein D (SP-D) for identifying patients with COVID-19 pneumonia among patients with abnormal chest shadows consistent with COVID-19 pneumonia. Method: This was a retrospective cohort study of consecutive patients who underwent evaluation of serum KL-6 and SP-D at a single center from February 2019 to December 2020. A total of 54 patients with COVID-19 pneumonia and 65 patients with COVID-19 pneumonia-like diseases were enrolled in this study from the source population. Serum KL-6 and SP-D levels in both groups were analyzed. Result: The serum levels of KL-6 and SP-D in patients with COVID-19 pneumonia were significantly lower than those in patients with COVID-19 pneumonia-like disease (median [interquartile range]: 208.

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“…A few studies have looked at the sensitivity, specificity, and predictive values of sKL-6 in COVID-19. Yamaya et al found a sensitivity of 83.3% and a specificity of 90.5 (AUC 0.89) to predict respiratory worsening with a sKL-6 cutoff point of 684 U/ml in 356 patients with sKL-6 determinations ( 26 ). Interestingly, they found a statistical association between baseline, peak, and Δ sKL-6 levels with severe illness and survival.…”

Section: Discussionmentioning

confidence: 99%

Krebs von den Lungen-6 glycoprotein circulating levels are not useful as prognostic marker in COVID-19 pneumonia: A large prospective cohort study

et al. 2022

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Coronavirus disease 2019 (COVID-19) has rapidly expanded worldwide. Currently, there are no biomarkers to predict respiratory worsening in patients with mild to moderate COVID-19 pneumonia. Small studies explored the use of Krebs von de Lungen-6 circulating serum levels (sKL-6) as a prognostic biomarker of the worsening of COVID-19 pneumonia. We aimed at a large study to determine the prognostic value of sKL-6 in predicting evolving trends in COVID-19. We prospectively analyzed the characteristics of 836 patients with COVID-19 with mild lung disease on admission. sKL-6 was obtained in all patients at least at baseline and compared among patients with or without respiratory worsening. The receiver operating characteristic curve was used to find the optimal cutoff level. A total of 159 (19%) patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were not higher in patients who had respiratory worsening (median {IQR} 315.5 {209–469} vs. 306 {214–423} U/ml p = 0.38). The last sKL-6 and the change between baseline and last sKL-6 were higher in the respiratory worsening group (p = 0.02 and p < 0.0001, respectively). The best sKL-6 cutoff point for respiratory worsening was 497 U/ml (area under the curve 0.52; 23% sensitivity and 85% specificity). sKL-6 was not found to be an independent predictor of respiratory worsening. A conditional inference tree (CTREE) was not useful to discriminate patients at risk of worsening. We found that sKL-6 had a low sensibility to predict respiratory worsening in patients with mild-moderate COVID-19 pneumonia and may not be of use to assess the risk of present respiratory worsening in inpatients with COVID-19 pneumonia.

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Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019

Cited by 17 publications

References 25 publications

Exploring the Role of Krebs von den Lungen-6 in Severe to Critical COVID-19 Patients

Exploring the Role of Krebs von den Lungen-6 in Severe to Critical COVID-19 Patients

Surfactant protein D: A useful biomarker for distinguishing COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases

Krebs von den Lungen-6 glycoprotein circulating levels are not useful as prognostic marker in COVID-19 pneumonia: A large prospective cohort study

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