Serum KL‐6 concentrations as a novel biomarker of severe COVID‐19

d’Alessandro, Miriana; Cameli, Paolo; Refini, Rosa Metella; Bergantini, Laura; Alonzi, Valerio; Lanzarone, Nicola; Bennett, David; Rana, Giuseppe Domenico; Montagnani, Francesca; Scolletta, Sabino; Franchi, Federico; Frediani, Bruno; Valente, Serafina; Mazzei, Maria Antonietta; Bonella, Francesco; Bargagli, Elena

doi:10.1002/jmv.26087

Cited by 78 publications

(75 citation statements)

References 10 publications

(17 reference statements)

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“…Whereas, no difference in the concentration of serum KL-6 was found in non-severe groups and normal control subjects. SARS-CoV-2 is known to have specific tropism for alveolar epithelial cells, which may cause interstitial lung injury and epithelial lung alterations in the acute phase [15] . As a secreted glycoprotein, KL-6 is mainly produced by damaged or regenerating type II alveolar pneumocytes and bronchiolar epithelial cells [29] .…”

Section: Discussionmentioning

confidence: 99%

“…A recent study reported that there is a complexity of interactions between coexisting idiopathic pulmonary fibrosis/ILD and COVID-19 disease [6] . Serum KL-6 has been suggested to be a useful biomarker for evaluating the severity of COVID-19, however, the results from another research did not demonstrate that KL-6 can discriminate different ventilatory phenotypes in COVID-19 patients [14] , [15] , [16] . Moreover, pulmonary fibrosis is identified by excessive deposition of extracellular matrix (ECM) proteins, such as fibronectin (Fn) [17] .…”

Section: Introductionmentioning

confidence: 93%

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Correlation of Krebs von den Lungen-6 and fibronectin with pulmonary fibrosis in coronavirus disease 2019

Peng

Luo

Huang

et al. 2021

Clinica Chimica Acta

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Objective Coronavirus Disease 2019 (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still spreading worldwide, which may progress to pulmonary fibrosis (PF), leading to the worsen outcome. As the markers of lung injury, the correlation of Krebs von den Lungen-6 (KL-6) and fibronectin (Fn) with pulmonary fibrosis in COVID-19 was still unclear. Methods 113 patients diagnosed as COVID-19 were enrolled in this retrospective study, and divided into three categories as mild, moderate and severe cases. The concentrations of serum KL-6 and Fn at hospital admission were tested using the method of latex agglutination assay and immunoturbidimetic assay, respectively. Results Compared with that in the non-severe COVID-19 cases and normal control subjects, serum KL-6 concentrations on admission were significantly higher in the severe group, which was positively correlated with C-reactive protein, and negatively correlated with lymphocytes count. Whereas, no obvious elevation in serum Fn concentration was investigated in COVID-19 patients with the different phenotypes. The severe cases displayed the higher incident rate of pulmonary fibrosis at hospital discharge. Compared with non-PF patients, the COVID-19 cases with PF have the higher serum KL-6 values. Conclusion Serum KL-6 concentration was significantly elevated in severe COVID-19 patients, which may be useful for evaluating the disease severity. For early prevention of the development of pulmonary fibrosis, high concentrations of serum KL-6 in the early stage of COVID-19 should be paid close attention.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Correlation of Krebs von den Lungen-6 and fibronectin with pulmonary fibrosis in coronavirus disease 2019

Peng

Luo

Huang

et al. 2021

Clinica Chimica Acta

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“…Levels of IL-6 at first assessment might predict respiratory failure [ 33 ], other publications with longitudinal analyses demonstrated that IL-6 increases fairly late during the disease’s course, consequently compromising its prognostic value at earlier stages [ 34 ]. Moreover, serum concentrations of KL-6, a molecule elevated in serum of patients with interstitial lung diseases (ILDs), such as idiopathic pulmonary fibrosis and hypersensitivity pneumonitis, was recently proposed to be capable of differentiating between severe and mild COVID-19 patients, being mainly produced by damaged or regenerating alveolar type II pneumocytes [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Persistence of Anti-SARS-CoV-2 Antibodies in Non-Hospitalized COVID-19 Convalescent Health Care Workers

Bruni

Cecatiello

Díaz‐Basabe

et al. 2020

JCM

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Although antibody response to SARS-CoV-2 can be detected early during the infection, several outstanding questions remain to be addressed regarding the magnitude and persistence of antibody titer against different viral proteins and their correlation with the strength of the immune response. An ELISA assay has been developed by expressing and purifying the recombinant SARS-CoV-2 Spike Receptor Binding Domain (RBD), Soluble Ectodomain (Spike), and full length Nucleocapsid protein (N). Sera from healthcare workers affected by non-severe COVID-19 were longitudinally collected over four weeks, and compared to sera from patients hospitalized in Intensive Care Units (ICU) and SARS-CoV-2-negative subjects for the presence of IgM, IgG and IgA antibodies as well as soluble pro-inflammatory mediators in the sera. Non-hospitalized subjects showed lower antibody titers and blood pro-inflammatory cytokine profiles as compared to patients in Intensive Care Units (ICU), irrespective of the antibodies tested. Noteworthy, in non-severe COVID-19 infections, antibody titers against RBD and Spike, but not against the N protein, as well as pro-inflammatory cytokines decreased within a month after viral clearance. Thus, rapid decline in antibody titers and in pro-inflammatory cytokines may be a common feature of non-severe SARS-CoV-2 infection, suggesting that antibody-mediated protection against re-infection with SARS-CoV-2 is of short duration. These results suggest caution in using serological testing to estimate the prevalence of SARS-CoV-2 infection in the general population.

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“…KL‐6 is mainly produced by damaged or regenerating alveolar type II pneumocytes 39 . Both baseline or peak serum KL‐6 levels were higher in critical and severe COVID‐19 cases than in nonsevere cases 225 .…”

Section: Laboratory Indicatorsmentioning

confidence: 96%

“…A good understanding of the possible risk factors in combination to disease immunopathology associated with COVID‐19 severity is helpful for clinicians in identifying patients who are at high risk and require prioritized treatment to prevent disease progression and adverse outcome 4 . Risk factors range from demographic factors, such as age, 3,5–7 sex and ethnicity, 8,9 diet and lifestyle habits 10,11 to underlying diseases 12–22 and complications, 23–26 and laboratory indications 27–39 . Many studies have reported predictive models using various risk factors to identify high‐risk patients that may develop severe and critical illness 40 .…”

Section: Introductionmentioning

confidence: 99%

Risk factors for severe and critically ill COVID‐19 patients: A review

Gao

Ding

Dong

et al. 2020

Allergy

1,007

864

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The pandemic of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID‐19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID‐19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high‐sensitivity C‐reactive protein, proinflammatory cytokines such as interleukin (IL)‐6, IL‐1β, Krebs von den Lungen‐6 (KL‐6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID‐19.

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Serum KL‐6 concentrations as a novel biomarker of severe COVID‐19

Cited by 78 publications

References 10 publications

Correlation of Krebs von den Lungen-6 and fibronectin with pulmonary fibrosis in coronavirus disease 2019

Correlation of Krebs von den Lungen-6 and fibronectin with pulmonary fibrosis in coronavirus disease 2019

Persistence of Anti-SARS-CoV-2 Antibodies in Non-Hospitalized COVID-19 Convalescent Health Care Workers

Risk factors for severe and critically ill COVID‐19 patients: A review

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