Cystatin C, COVID-19 severity and mortality: a systematic review and meta-analysis

Zinellu, Angelo; Mangoni, Arduino A.

doi:10.1007/s40620-021-01139-2

Cited by 22 publications

(24 citation statements)

References 55 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[ 21 ] Our study is also in line with a meta-analysis which observed association of higher serum cystatin C concentrations with disease severity and increased mortality in hospitalized COVID-19 patients. [ 22 ] Thus, the results of our study support the possible role of serum cystatin C as an early prognostic marker of COVID-19. This is also supported by the fact that cystatin C is a major secretory product of alveolar macrophages and a potent regulator of inflammation.…”

Section: Discussionsupporting

confidence: 77%

Role of cystatin C and calprotectin as potential early prognostic biomarkers in COVID-19 patients admitted to a dedicated COVID care facility

Jha

Kumar

Bhushan

et al. 2022

Journal of Family Medicine and Primary Care

View full text Add to dashboard Cite

Background: The COVID-19 pandemic has claimed millions of lives. A tool for early prediction of severity and mortality risk is desirable for better utilization of health care facilities. Several biomarkers like D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP) and some recently explored biomarkers like serum cystatin C and serum calprotectin have been proposed as prognostic markers of COVID-19, but their role as prognostic markers is so far undefined. The present work attempted to investigate the possible role of serum cystatin C and serum calprotectin as prognostic tools to predict severity and outcome ahead of time. Material and Methods: This observational cohort study was carried out on 95 COVID-19 patients admitted to a dedicated COVID care facility from mid-October 2020 to January 2021. Serial estimations of serum cystatin C and serum calprotectin levels were done and assessed for significant difference between severe (NEWS 2 score ≥5) and non-severe (NEWS 2 score <5) groups, survivors and deceased and on the basis of comorbidities at each time points. Survival analysis was done based on the optimal thresholds for severity and mortality, calculated from the receiver operating characteristic (ROC). Result: The results showed that median cystatin C levels were significantly higher on the first day in the severe group ( P < 0.001) and in patients with cardiovascular disease ( P < 0.05), chronic lung disease ( P = 0.009) and among patients who died ( P < 0.05). It remained raised on day 3 in severe ( P < 0.05) and deceased ( P < 0.05) group. Serum calprotectin levels were significantly higher in patients with chronic lung disease ( P = 0.008) and in those who died ( P < 0.05). Conclusion: Serum cystatin C could be used as a tool for early prognosis and therapeutic decision-making for COVID-19 patients. Serum calprotectin seems to be a better marker of critical illness.

show abstract

Section: Discussionsupporting

confidence: 77%

Role of cystatin C and calprotectin as potential early prognostic biomarkers in COVID-19 patients admitted to a dedicated COVID care facility

Jha

Kumar

Bhushan

et al. 2022

Journal of Family Medicine and Primary Care

View full text Add to dashboard Cite

show abstract

“…Consistent with our findings, elevated levels of CST3 have been associated with poor prognosis and increased mortality rate in COVID-19. 52 A study has shown that myoglobin level could be contributed by cardiac as well as kidney injury. 53 Consistently, the elevated levels of myoglobin, however, unchanged cTnI levels in our study indicate that increased myoglobin level in severe COVID-19 may be contributed due to kidney injury and injury to other soft organs.…”

Section: Discussionmentioning

confidence: 99%

Lipocalin-2, S100A8/A9, and cystatin C: Potential predictive biomarkers of cardiovascular complications in COVID-19

Gupta

Al-Tamimi

Halwani

et al. 2022

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Severe coronavirus (SARS-COV-2) infection often leads to systemic inflammation accompanied by cardiovascular complications including venous thromboembolism (VTE). However, it is largely undefined if inflammatory markers such as lipocalin-2 (LNC2), calprotectin (S100A8/A9), and cystatin C (CST3), previously linked with VTE, play roles in cardiovascular complications and advancement of COVID-19 severity. To investigate the same, hospitalized moderate and severe (presented pneumonia and required intensive care) COVID-19 patients were recruited. The levels of plasma LNC2, S100A8/A9, CST3, myoglobin, and cardiac Troponin I (cTnI) were assessed through enzyme-linked immunosorbent assay (ELISA). The investigation revealed a significantly upregulated level of plasma LNC2 at the moderate stage of SARS-CoV-2 infection. In contrast, the levels of S100A8/A9 and CST3 in moderate patients were comparable to healthy controls; however, a profound induction was observed only in severe COVID-19 patients. The tissue injury marker myoglobin was unchanged in moderate patients; however, a significantly elevated level was observed in the critically ill COVID-19 patients. In contrast, cTnI level was unchanged both in moderate and severe patients. Analysis revealed a positive correlation between the levels of S100A8/A9 and CST3 with myoglobin in COVID-19. In silico analysis predicted interactions of S100A8/A9 with toll-like receptor 4 (TLR-4), MyD88 LY96, and LCN2 with several other inflammatory mediators including MMP2, MMP9, TIMP1, and interleukins (IL-6, IL-17A, and IL-10). In summary, early induction of LCN2 likely plays a role in advancing the COVID-19 severity. A positive correlation of S100A8/A9 and CST3 with myoglobin suggests that these proteins may serve as predictive biomarkers for thromboembolism and tissue injury in COVID-19.

show abstract

“…The systematic review included articles published between 2020 and 2022, comprising a total of 3916 COVID-19 participants ( Table 1 ). The final set considered of 25 eligible studies [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ], including 18 articles conducted in China [ 21 , 22 , 23 , 25 , 26 , 27 , 28 , 31 , 33 , 34 , 36 , 37 , 38 , 39 , 41 , 42 , 43 , 44 ], two articles in Turkey [ 32 , 40 ], and one article each from the following countries: Iraq [ 20 ], India [ 24 ], Mexico [ 29 ], USA [ 30 ] and Egy...…”

Section: Resultsmentioning

confidence: 99%

“…Although some studies have investigated the association between Cystatin C and AKI. Moreover, meta-analysis by Zinellu et al evaluate the relation between Cystatin C and COVID-19, however, contain only 13 articles [ 45 ]. In this meta-analysis, twenty-five studies were included and analyzed which makes it the broadest and most comprehensive meta-analysis available in this area.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Performance of Cystatin C in COVID-19: A Systematic Review and Meta-Analysis

Matuszewski

Reznikov

Pruc³

et al. 2022

IJERPH

View full text Add to dashboard Cite

Cystatin C is a specific biomarker of kidney function. We perform this meta-analysis to determine the association of Cystatin C with the COVID-19 severity. In this systematic review and meta-analysis, we searched PubMed, EMBASE, Cochrane library, and Web of Science for studies published until 2nd September 2022 that reported associations between Cystatin C levels and COVID-19 severity. The analysis was performed using a random-effects model to calculate pooled standard mean difference (SMD). Twenty-five studies were included in the meta-analysis. Pooled analysis showed statistically significant differences of Cystatin C levels among survive vs. decreased patients (0.998 ± 0.225 vs. 1.328 ± 0.475 mg/dL, respectively; SMD = −2.14; 95%CI: −3.28 to −1.01; p < 0.001). Cystatin C levels in COVID-19 severe vs. non-severe groups varied and amounted to 1.485 ± 1.191 vs. 1.014 ± 0.601 mg/dL, respectively (SMD = 1.81; 95%CI: 1.29 to 2.32; p < 0.001). Additionally, pooled analysis showed that Cystatin C levels in patients with acute kidney injury (AKI) was 1.562 ± 0.885 mg/dL, compared to 0.811 ± 0.108 mg/dL for patients without AKI (SMD = 4.56; 95%CI: 0.27 to 8.85; p = 0.04). Summing up, Cystatin C is a potentially very good marker to be used in the context of COVID-19 disease due to the prognosis of patients’ serious condition, risk of AKI and mortality. In addition, Cystatin C could be used as a marker of renal complications in COVID-19 other than AKI due to the need to monitor patients even longer after leaving the hospital.

show abstract

Cystatin C, COVID-19 severity and mortality: a systematic review and meta-analysis

Cited by 22 publications

References 55 publications

Role of cystatin C and calprotectin as potential early prognostic biomarkers in COVID-19 patients admitted to a dedicated COVID care facility

Role of cystatin C and calprotectin as potential early prognostic biomarkers in COVID-19 patients admitted to a dedicated COVID care facility

Lipocalin-2, S100A8/A9, and cystatin C: Potential predictive biomarkers of cardiovascular complications in COVID-19

Prognostic Performance of Cystatin C in COVID-19: A Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About