YKL-40 as a new promising prognostic marker of severity in COVID infection

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a disease named COVID-19, which may be associated with common symptoms or lead patients to intensive care unit (ICU) or death. The severity of the disease is mainly driven by diffuse interstitial lung diseases (ILD). YKL-40 has a promitogenic action on pulmonary fibroblasts, increases the activity of macrophages and is associated with inflammatory disorders, arteriosclerosis and endothelial dysfunction. In ILD, YKL-40 has been described to be associated with the severity of lung diseases and with the risk of death [1–6]. Yet, in COVID-19 infection, YKL-40 serum levels could therefore be of interest for diagnosis and prognosis since it is at the cross-link between vascular and epithelial lung damage, which are typical characteristics of COVID-19 infection. By closing the gap between those two pathological characteristics, we thought that YKL-40 could be of interest a specific biomarker of severe COVID-19 infection. We thus retrospectively compared serum levels of YKL40 in a cohort of 103 patients infected by SARS-CoV-2 hospitalized between March 1 and April 29, 2020, with a group of 58 appariated healthy subjects (HS), 26 patients suffering from chronic obstructive pulmonary disease (COPD) and 53 from non-COVID ILD. Measurement of YKL-40 was taken with the MicroVueTM YKL-40 enzyme immunoassay kit during the 3 first days of admission and retrospectively analyzed and correlated the results with clinical data [ICU admission, acute renal failure (ARF) or multiple organ failure (MOF)]. Median age of COVID-19 positive patients was 69 yo with a male predominancy (67%). A significant proportion of the cohort (n = 103) experienced ICU admission (30%), ARF (32%) and MOF (28%). COVID-19 patients who were admitted in ICU had statistically higher CRP, creatinine, LDH and YKL-40 (p < 0.05) (Table 1). The lymphocyte count was not statistically lower (p = 0.059) and D-dimers were not higher (p = 0.1297) compared to the other group. COVID-19 patients exhibited higher serum levels of YKL-40 than HS, COPD and ILD (p < 0.0001 for all groups) (Fig. 1). Median serum level of YKL-40 was 206 ng/ml (95–431) in the COVID-19 group, 46 ng/ml (34–67) in the HS subgroup, whereas they were of 60 ng/ ml (41–73) in the COPD and 73 ng/ml (42–91) in the ILD groups, respectively. Patients suffering from more severe diseases had significantly higher YKL-40 values than those who did not experience ICU admission, MOF or ARF (p < 0.05, p < 0.05, p < 0.001, respectively). Patients infected by COVID-19 suffering from prior chronic renal failure and chronic cardiopathy were exhibiting an increased serum level of YKL-40 (p < 0.0001 and p < 0.001, respectively). Death was not statistically correlated to levels of YKL-40 within the COVID-19 patient group (p = 0.12). The area under the ROC curve (AUC) for the discrimination of patients admitted or not to the ICU in association with the levels of YKL-40, the age and the percentage of lesions visible on the thoracic scanner Open Access

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a disease named COVID-19, which may be associated with common symptoms or lead patients to intensive care unit (ICU) or death. The severity of the disease is mainly driven by diffuse interstitial lung diseases (ILD). YKL-40 has a promitogenic action on pulmonary fibroblasts, increases the activity of macrophages and is associated with inflammatory disorders, arteriosclerosis and endothelial dysfunction. In ILD, YKL-40 has been described to be associated with the severity of lung diseases and with the risk of death [1][2][3][4][5][6]. Yet, in COVID-19 infection, YKL-40 serum levels could therefore be of interest for diagnosis and prognosis since it is at the cross-link between vascular and epithelial lung damage, which are typical characteristics of COVID-19 infection. By closing the gap between those two pathological characteristics, we thought that YKL-40 could be of interest a specific biomarker of severe COVID-19 infection.
We thus retrospectively compared serum levels of YKL-40 in a cohort of 103 patients infected by SARS-CoV-2 hospitalized between March 1 and April 29, 2020, with a group of 58 appariated healthy subjects (HS), 26 patients suffering from chronic obstructive pulmonary disease (COPD) and 53 from non-COVID ILD. Measurement of YKL-40 was taken with the MicroVue ™ YKL-40 enzyme immunoassay kit during the 3 first days of admission and retrospectively analyzed and correlated the results with clinical data [ICU admission, acute renal failure (ARF) or multiple organ failure (MOF)].
COVID-19 patients who were admitted in ICU had statistically higher CRP, creatinine, LDH and YKL-40 (p < 0.05) ( Table 1). The lymphocyte count was not statistically lower (p = 0.059) and D-dimers were not higher (p = 0.1297) compared to the other group.
Patients suffering from more severe diseases had significantly higher YKL-40 values than those who did not experience ICU admission, MOF or ARF (p < 0.05, p < 0.05, p < 0.001, respectively). Patients infected by COVID-19 suffering from prior chronic renal failure and chronic cardiopathy were exhibiting an increased serum level of YKL-40 (p < 0.0001 and p < 0.001, respectively). Death was not statistically correlated to levels of YKL-40 within the COVID-19 patient group (p = 0.12).
The area under the ROC curve (AUC) for the discrimination of patients admitted or not to the ICU in association with the levels of YKL-40, the age and the percentage of lesions visible on the thoracic scanner Open Access  In conclusion, this study showed that firstly the COVID-19 patients had higher levels of YKL-40 compared to a control population (HS, COPD and ILD) and secondly that within the COVID-19 population YKL-40 was an indicator of the seriousness of infection since it is linked to complications such as admission to ICU, ARF or MOF. This marker could also be a predictive marker to anticipate management at the ICU and is useful for the prognosis of the onset of an ILD later. Future studies are also needed to assess the correlation between the levels of YKL-40 and pulmonary sequelae that patients with COVID-19 would develop.