To the best of our knowledge this is the first study in the literature on diagnostic value of DNI in MIS-C. Early diagnosis and treatment of MIS-C is very important in reducing mortality and morbidity. A specific inflammatory marker that can be used in the diagnosis of MIS-C has not been reported yet. In this current study, the importance of DNI in the early diagnosis of MIS-C was evaluated and it was shown that DNI is an effective marker in the diagnosis and determination of the severity of MIS-C.
The diagnostic value of inflammatory markers that can be used in the diagnosis of MIS-C has been previously evaluated in many studies. Increased ANC, decreased ALC, decreased platelet count, hyponatremia and hypoalbuminemia that may accompany with increased CRP and, erythrocyte sedimentation rate were determined as the first step tests in the diagnosis of MIS-C by the American College of Rheumatology . These tests are easily accessible and affordable tests that pediatricians often prefer in their daily practice. Zhao et al. showed that ALC, ANC, platelet count and CRP changes in 787 MIS-C patients compared to active COVID-19 patients, as a result of increased inflammatory response, excessive release of inflammatory mediators and cytokine storm . Similarly, in our study, increased CRP, decreased ALC, increased ANC and decreased platelet count were found to be significant in the MIS-C group compared to the COVID-19 and control groups. In addition, the DNI level was 4.60 ± 5.70 in the MIS-C group, 0.30 ± 0.99 in the COVID-19 group and 0.20 ± 0.56 in the control group. Early release of immature neutrophils from bone marrow into peripheral blood in correlation with inflammation has been reported, especially in many infectious diseases. Similarly, in COVID-19 patients, it has been reported that immature neutrophils increase in the circulation and are associated with increased inflammation and disease severity .
DNI is a simple test that can be quantitatively measured in routine complete blood counts. It has a diagnostic value in diseases such as pediatric sepsis, meningitis, appendicitis, urinary tract infection, and KD; it has even been also reported to be an important marker in determining prognosis [13–16]. Park et al. emphasized that DNI is a potentially useful diagnostic tool in infected patients and should be used more widely in clinical practice to predict mortality . However, studies of DNI in COVID-19 patients are limited in the literature. Birben et al. showed that DNI is an effective predictor of the intensive care unit mortality in 388 COVID-19 adult patients . In our study, prognosis of MIS-C was not evaluated, but DNI levels were found to be correlated with disease severity. DNI cut-off levels were 0.45% for MIS-C. It is important to pay attention to both this cut-off value and to be aware that the increase in DNI level is related to the MIS-C severity. Prediction of the MIS-C severity by the DNI level at the time of diagnosis may affect the management of the patient and the choice of treatment.
MIS-C is a new phenomenon that causes multiorgan involvement with cardiac involvement and hemodynamic instability. Monitoring of inflammatory markers in patients diagnosed with MIS-C is important in determining early diagnosis and treatment of patients who may require critical care . The majority of children affected are RT-PCR negative for SARS-CoV-2 virus, but are antibody positive, indicating a post-infectious inflammatory response following SARS-CoV-2 infection. However, in some of the patients, both RT-PCR and serology tests are positive. Although it is known that there are clinical and laboratory findings specific to MIS-C, if RT-PCR is found positive for SARS-CoV-2 in MIS-C patients, differentiating COVID-19 from MIS-C may be challenging for the clinician. The optimal inflammatory markers to demonstrate the difference in these diseases are still unclear. Some laboratory findings of active COVID-19 and MIS-C are similar (eg lymphopenia, increased CRP). In our study, it was shown that the DNI at the time of diagnosis was significantly higher in MIS-C compared to COVID-19. Moreover, the simple scoring system we created in our study, which can only be calculated with basal laboratory tests and DNI, may contribute to the diagnosis of MIS-C.
Our study has several limitations, first of all, it was designed as a retrospective study. In addition, a limited number of inflammatory markers such as ANC, ALC, PLT and CRP have been evaluated in our study. Finally, the high DNI levels in the cases were not confirmed by flow cytometry or peripheral smear. However, our study is the first study in the literature evaluating DNI in MIS-C patients and contributed to the literature with its significant results.
In conclusion, early diagnosis and management are important for optimal outcomes in children affected with MIS-C. DNI is an easily accessible, inexpensive and dynamic marker that can be used in the diagnosis of MIS-C such as ANC, ALC, platelet count and CRP. Diagnostic tests have not been clearly established in MIS-C, DNI levels in simple hemogram analysis will guide pediatricians in determining the diagnosis and severity. However, randomized, long-follow-up studies with larger patient groups are required to demonstrate the role of DNI.