key: cord-0688517-q1vxu096 authors: Zhan, Canyang; Wang, Weiyan; Chen, Lihua title: Predictive significance of neutrophil‐to‐lymphocyte and platelet‐to‐lymphocyte for cytomegalovirus infection in infants less than 3 months: A retrospective study date: 2021-11-22 journal: J Clin Lab Anal DOI: 10.1002/jcla.24131 sha: f6554c94a156890445337397e2c524c7e77bac62 doc_id: 688517 cord_uid: q1vxu096 BACKGROUND: The aim of this study was to evaluate the predictive value of the hematological parameters in the identification of human cytomegalovirus (CMV) infection in infants less than 3 months. METHODS: A single‐center, observational study of infants with CMV infection was conducted retrospectively. Routine blood parameters were analyzed in CMV‐infected infants and controls with no differences of birthweight, sex, gestational age at birth, and date of admission. Furthermore, receiver‐operating curve was used to assess the predictive value of the hematological parameters for CMV infection. RESULTS: One hundred ninety cases with CMV infection were studied retrospectively. Compared with the control group, there were significant differences in the white blood cell count, neutrophil count, lymphocyte count, platelet count, hemoglobin, neutrophil‐to‐lymphocyte (NLR), platelet‐to‐lymphocyte (PLR), and lymphocyte‐to‐monocyte (LMR) for the patients with CMV infection (all p < 0.001). The best predicted values for CMV infection based on the area under the curve (AUC) were NLR and PLR with the optimal cut‐off value of 0.28 and 65.36. NLR‐PLR score of 0, 1, or 2 based on an elevated NLR (>0.28), an elevated PLR (>65.36), or both. NLR‐PLR score for CMV infection prediction yielded higher AUC values than NLR or PLR alone (0.760 vs. 0.689, 0.689; p < 0.001). CONCLUSIONS: The NLR combined with PLR is potentially useful as a predictor of CMV infection in infants less than 3 months. In China, neonates are not routinely screened for CMV infection. CMV is identified by polymerase chain reaction (PCR) or culture. However, CMV detection is not available for some Chinese hospitals. Therefore, although the CMV infection is common in China, part of infants infected with CMV are missed diagnosis. Routine blood test is the most common test performed in pediatric clinics. Markers of systemic inflammation, such as the neutrophilto-lymphocyte (NLR) and platelet-to-lymphocyte (PLR), are generally appealing to clinicians, as these laboratory data are routinely collected prior to PCR or culture and are therefore readily available. NLR is a novel marker of inflammation, which has been shown to be correlated with thyroid conditions, type 2 diabetes mellitus (DM), irritable bowel syndrome, malignant conditions, ulcerative colitis, and cardiac conditions. [5] [6] [7] [8] [9] [10] On the other hand, platelet-related markers are also considered as a novel inflammatory markers. PLR is one of these novel indices and associated with inflammation in type 2 DM, malignant conditions, and thyroid conditions. 8, 11, 12 Thus, we studied the hematological parameters differences of the patients with CMV infection or without CMV infection, which might provide convenient indicators for CMV infection and then reduce the misdiagnosis of CMV infection. Urine samples were collected for DNA extraction. CMV-DNA was evaluated by RT-PCR according to the instructions. The kit was produced by Da An Gene Co. The Real-Time System was produced by the company ABI 7500 in USA. A routine analyzer (XN-2800, SYSMEX) was used for routine blood tests. The white blood cell (WBC) count, neutrophil (NEU) count, lymphocyte (LYM) count, monocyte (MON) count, platelet (PLT) count, and hemoglobin (HB) were recorded. Additionally, the NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The PLR was calculated by dividing the absolute platelet count by the absolute lymphocyte count, while the lymphocyte-tomonocyte (LMR) was calculated by dividing the absolute lymphocyte count by the absolute monocyte count on routine blood tests. Analysis was performed with SPSS software version 23.0. The Kolmogorov-Smirnov normality test was run for checking the distribution of hematological parameters and the Levene statistic test was used to test the homogeneity of variances. One-way analysis of variance test and t-test were conducted for comparison of normally distributed variables. The results of normally distributed variables are presented as the mean ± standard deviation (SD). was used for comparison of non-normally distrusted hematological parameters. Furthermore, receiver-operating curve (ROC) was used to assess the predictive value of the hematological parameters for CMV infection. Descriptive statistics were performed to determine the patients' features. p-value <0.05 was considered significant. In the present study, 257 infants with CMV infection were admitted at our department in 2019. Sixty-seven infants were excluded, because of the following conditions: older than 3 months, younger than 7 days, repeat hospitalizations, sepsis, urinary tract infection, umbilical abscess, peri-umbilical cellulitis, lacrimal abscess, intracranial infection, necrotic enterocolitis, and fungal pneumonia. Table 1 . There are no statistically significant differences in age, sex, birthweight, and premature/mature distributions between two groups. Compared with the control group, the infants with CMV infection had lower NEU counts, PLT counts and HB values, and higher WBC counts and LYM counts. The NLR and PLR in the CMV infection group were significantly lower than that of control group, while the LMR in the CMV infection group was higher than that of control group (Table 2) . Additionally, no significant difference of MON count was observed between two groups. In the current study, we found that the NEU, NLR, and PLR were sig- affecting tumor metastasis and prognosis. 22 Additionally, a retrospective study of bacteremia found that NLR greater than 7 was an independent risk factor for increased mortality. 23 NLR is also investigated as useful predictors for the viral infection. The NLR is sensitive for the detection of influenza virus infection. 24 Abbreviations: CMV, cytomegalovirus; NLR, neutrophil-to-lymphocyte; PLR, platelet-to-lymphocyte; ROC, receiver-operating characteristic. p-value <0.05 marked in bold font shows statistical significance. Comparison of area under the receiver-operating characteristic curve (AUC) in different inflammation-based scores. NLR-PLR score for CMV infection prediction yielded higher AUC values than NLR or PLR alone COVID-19 cases as compared to healthy controls. 25 Furthermore, CMV-DNA cannot be detected in parts of hospitals, whereas routine blood test is common, convenient, and inexpensive. Compared with simple neutrophils, lymphocytes, and platelets, NLR and PLR are more stable. CMV infection might be considered for the infants with greatly low level of NLR and PLR. Our study had several limitations that must be considered. First, given its retrospective design, the current study was subject to possible selection bias, as well as diagnostic bias. Second, the NLR and PLR, a marker of systemic inflammation, may be affected by many conditions, including chronic inflammatory diseases, granulocyte colony-stimulating factor administration, and other diseases. Therefore, these conditions must be accounted for in clinical practice. Finally, the present study was conducted at a single institution. The performance of multicenter studies of the markers used herein would strengthen our conclusions. A significantly lower NLR and PLR were observed in infants (<3 months) with CMV infection. The NLR/PLR combined is potentially useful as a predictor of CMV infection in infants (<3 months) with an AUC of 0.760, which might provide information for the identification of CMV infection. This work was supported by the National Natural Science Foundation of China (81401235). The authors declare no conflict of interest. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. https://orcid.org/0000-0001-8976-1284 Estimation of the worldwide seroprevalence of cytomegalovirus: a systematic review and metaanalysis Congenital cytomegalovirus infection: clinical outcome Diagnosis and management of infants with congenital cytomegalovirus infection. 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