Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India

Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objective(s): This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Material(s) and Method(s): This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Result(s): A total of 650 tests for COVID-19 were performed for 181 children;22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support;all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusion(s): Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.

Utility of the Brixia CXR score, C-Reactive Protein and Absolute Neutrophil Count in Predicting the Need for Invasive Mechanical Ventilation, Length of Hospital Stay, and Mortality in Moderate to Severe COVID-19 Patients

Background: The Brixia Chest X-ray (CXR) score, C-reactive protein (CRP), and the absolute neutrophil count (ANC) have been useful to predict outcomes in Coronavirus disease 2019 (COVID-19 patients). We studied the utility of the Brixia CXR score, CRP, and ANC in predicting the outcomes in terms of the need for invasive mechanical ventilation, length of stay, and mortality in moderate-severe COVID-19 patients. Material(s) and Method(s): This was a single-centre, retrospective, study on 122 COVID-19 patients. Brixia CXR score, CRP, and ANC on admission to the hospital and the fifth day of hospital stay were noted along with the need for invasive mechanical ventilation (IMV), prolonged length of stay (LOS) >= 14 days, and mortality. Result(s): 122 patients were included for analysis. The median and interquartile range (IQR) for baseline CRP was 81.50 (39-151) mg/L and 11.0 (4-30) mg/L (p < 0.001) on the fifth day. The median and IQR for baseline Brixia score was 10.0 (7-13), and on the fifth day was 7 (4-11) (p <0.001). The receiver operating characteristic curve (ROC) showed that the baseline CRP >= 52.5mg/L predicted both the need for IMV, with an area under the curve (AUC) of 0.628, and prolonged LOS with an AUC of 0.608. The ROC curve depicted that the baseline ANC >8500/muL predicted IMV requirement with an AUC of 0.657. The fifth day CRP >= 32 mg/L, ANC >= 11,000/ muL and Brixia CXR score >= 7 predicted a higher mortality in hospitalized patients. Conclusion(s): Baseline CRP (> 52.5mg/L) predicts the need for IMV and a prolonged LOS, but not mortality. Baseline ANC (> 8500/muL) predicted the need for IMV. CRP, Brixia CXR score, and ANC on the fifth day were not useful to predict LOS or mortality, though there was a significant reduction in CRP and Brixia CXR score on the fifth day compared to baseline after treatment. The fifth day CRP >= 32 mg/L, ANC >= 11,000/ muL and Brixia CXR score >= 7 predicted a higher mortality.Copyright © 2023, College of Anaesthesiologists of Sri Lanka. All rights reserved.

Hematological findings in COVID-19 and their correlation with severity of Disease

Objective: To evaluate the efficacy of hematological parameters to predict severity of COVID-19 patients. Method: This was a cross-sectional comparative study conducted at Central Park Teaching Hospital, Lahore in COVID ward and COVID ICU between April 23, 2021 to June 23, 2021. Patients of all ages and both genders with positive PCR admitted in the COVID ward and ICU during this time span of two months were included in the study. Data was collected retrospectively. Results: This study included 50 patients with male to female ratio of 1.38:1. Though males are more affected by COVID-19 but the difference is not statistically significant. The mean age of the study population was 56.21 and the patients in the severe disease group have higher age. It was observed that in severe/critical group the mean values of total leukocyte count 21.76×103 µI (p-value= 0.002), absolute neutrophil count 71.37% (p-value=0.045), neutrophil lymphocyte ratio (NLR) 12.80 (p-value=0.00) and PT 11.9 seconds (p-value=0.034) and the difference was statistically significant. While in severe/critical group, the mean values of hemoglobin 12.03g/dl (p-value=0.075), lymphocyte count 28.41% (p-value=0.8), platelet count 226×103 µI (p-value=0.67) and APTT 30.7 (p-value=0.081) and the difference was not significantly different between groups. Conclusion: It can be concluded from the study that total leucocyte count, absolute neutrophil count and neutrophil lymphocyte ratio can predict in-hospital mortality and morbidity in COVID-19 patients.

West Nile Meningoencephalitis in a Patient with Leiomyosarcoma Presenting with Neutropenic Fever

Case Report: West Nile Virus (WNV) was first isolated from the West Nile district of Northern Uganda in 1937, but was first detected in the United States well over half a century later in 1999. The arthropod-borne virus has since persisted, with 2,401 cases reported to the CDC on average annually. The infection typically causes a nonspecific acute systemic febrile illness with occasional gastrointestinal and skin manifestations;however, in less than 1% of infected patients, it can cause severe and potentially fatal neuroinvasive disease, presenting as meningitis, encephalitis or acute flaccid paralysis. Immunosuppression is one of the risk factors associated with the development of neuroinvasive disease, and chemotherapy thus places patients at risk. Uterine leiomyosarcoma is a rare gynecological malignancy. Palliative chemotherapy is common in late stage disease, but may predispose patients to conditions that present as neutropenic fever, leading to a diagnostic conundrum. This is the first case report where patient with neutropenic fever was found to have West Nile neuroinvasive disease, so it is important to include West Nile disease in the differential diagnosis. Case Description: This is a case of a 45-year-old female with history of diabetes, hypothyroidism and recently diagnosed uterine leiomyosarcoma status post tumor debulking with metastasis on palliative chemotherapy with gemcitabine that presented to the Emergency Room for a fever of 103.8 degrees Fahrenheit. Given the history of advanced leiomyosarcoma, the patient was admitted for neutropenic fever with an absolute neutrophil count of 1000. During the hospitalization, the patient became acutely altered and confused. CT head without contrast and lumbar puncture were performed. Due to clinical suspicion of meningitis, she was started on broad spectrum antibiotics. Lumbar puncture revealed leukocytosis of 168 with lymphocytic predominance and elevated protein level in the cerebrospinal fluid, therefore acyclovir was started due to high suspicion of viral meningoencephalitis. An EEG showed severe diffuse encephalopathy as the patient was persistently altered. A broad workup of infectious etiology was considered including HIV, syphilis, hepatitis A, B, C, COVID-19, adenovirus, pertussis, influenza, WNV, HHV6, coccidiomycosis, aspergillus, and tuberculosis. Patient was ultimately found to have elevated IgM and IgG titers for West Nile Virus. Discussion(s): It is important to consider a broad spectrum of diagnosis in patients with metastatic carcinoma presenting with new-onset fever and acute encephalopathy. This includes working up for other causes of altered mental status including cardiac, neurologic, psychiatric, endocrine, metabolic, electrolyte, drug, and infectious etiology. While uncommon in the healthy population, WNV encephalitis should be on the radar for any patient who is immunocompromised or on immunosuppressive therapy, especially those who present with a neutropenic fever.

Evaluation of Neutrophil Percentage to Albumin Ratio as Predictor of Mortality in Patients with Covid-19

Background: Inflammatory acute respiratory syndrome (SARS) is caused by the COV-2 virus. Neutrophils have been implicated in the pathophysiology of the COVID-19 pandemic since its inception, particularly in individuals with advanced disease. This is confirmed by a large number of studies. Method(s): The study included 200 patients, of whom 100 were in the critical group (group 1) and 100 were in the non-critical group (group 2). White blood cell (WBC) percentage, neutrophil count, albumin, and demographic information were recorded. Neutrophil percentage x 100 /Albumin (g/dl) was used to construct the neutrophil count to albumin ratio (NPAR). To determine whether the measure may be utilized as a predictor for mortality, the NPAR is then compared between groups 1 and 2, as well as between discharge and mortality groups. Result(s): Age and gender had no statistically significant differences in either group. There were no significant variations in the median (IQR) values of neutrophil count (89 vs 91.25), WBC (15.65 vs 14.9), and NPAR (41.3 vs 43.7) between the two groups. Significant differences in albumin (3.330.521 vs. 3.10.51) were identified between the critical and non-critical groups. Conclusion(s): According to our research, the COVID-19 patients' NPAR is a poor predictor of mortality. More study is still required to verify and elucidate the clinical implications of these findings.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Optimal approach to T-cell ALL

T-lineage acute lymphoblastic leukemia (T-ALL) is curable for most children and adolescent and young adult patients with contemporary frontline chemotherapy regimens. During the past decade, improved survival rates have resulted from the optimization of frontline chemotherapy regimens, the use of minimal residual disease (MRD) assessment for evaluating a patient's risk for relapse, and the intensification of treatment based on the persistence of MRD. Optimization of initial therapy is critical because relapsed T-ALL after initial intensive chemotherapy is incurable for most adult patients. Current T-ALL salvage chemotherapy regimens are minimally effective, and unlike in B-cell ALL, there are no approved antibody therapies or chimeric antigen receptor T-cell therapies for relapsed disease. Immunotherapy and small-molecule inhibitors are beginning to be tested in relapsed T-ALL and have the potential to advance the treatment. Until effective salvage strategies are discovered, however, intensive frontline therapy is required for cure. In this article I review the current frontline chemotherapy regimens for adult patients with T-ALL, summarize the novel targeted and immune therapeutics currently in early-phase clinical trials, and outline how these therapies are helping to define an optimal approach for T-ALL.Copyright © 2022 by The American Society of Hematology.

SARS-CoV-2 severity prediction in young adults using artificial intelligence.

Aim: to build, a predictive model for severe COVID-19 prediction in young adults using deep learning methods. Material(s) and Method(s): data from 906 medical records of patients aged. 18 to 44 years with laboratory-confirmed SARS- CoV-2 infection during 2020-2021 period, was analyzed. Evaluation of laboratory and. instrumental data was carried out using the Mann-Whitney U-test. The level of statistical significance was p<0,05. The neural network was trained, using the Pytorch. framework. Result(s): in patients with mild to moderate SARS-CoV-2 infection, peripheral oxygen saturation, erythrocytes, hemoglobin, total protein, albumin, hematocrit, serum, iron, transferrin, and. absolute peripheral blood, eosinophil and. lymphocyte counts were significantly higher than in patients with severe SOVID-19 (p< 0,001). The values of the absolute number of neutrophils, ESR, glucose, ALT, AST, CPK, urea, LDH, ferritin, CRP, fibrinogen, D-dimer, respiration rate, heart rate, blood, pressure in the group of patients with mild and. moderate severity were statistically significantly lower than in the group of severe patients (p < 0.001). Eleven indicators were identified as predictors of severe COVID-19 (peripheral oxygen level, peripheral blood erythrocyte count, hemoglobin level, absolute eosinophil count, absolute lymphocyte count, absolute neutrophil count, LDH, ferritin, C-reactive protein, D-dimer levels) and. their threshold, values. A model intended, to predict COVID-19 severity in young adults was built. Conclusion. The values of laboratory and instrumental indicators obtained in patients with SARS-CoV-2 infection upon admission significantly differ. Among them, eleven indicators were significantly associated with the development of a severe COVID-19. A predictive model based, on artificial intelligence method, with high, accuracy predicts the likelihood, of severe SARS-CoV-2 course development in young adults.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

SARS-CoV-2 severity prediction in young adults using artificial intelligence.

Aim: to build, a predictive model for severe COVID-19 prediction in young adults using deep learning methods. Material(s) and Method(s): data from 906 medical records of patients aged. 18 to 44 years with laboratory-confirmed SARS- CoV-2 infection during 2020-2021 period, was analyzed. Evaluation of laboratory and. instrumental data was carried out using the Mann-Whitney U-test. The level of statistical significance was p<0,05. The neural network was trained, using the Pytorch. framework. Result(s): in patients with mild to moderate SARS-CoV-2 infection, peripheral oxygen saturation, erythrocytes, hemoglobin, total protein, albumin, hematocrit, serum, iron, transferrin, and. absolute peripheral blood, eosinophil and. lymphocyte counts were significantly higher than in patients with severe SOVID-19 (p< 0,001). The values of the absolute number of neutrophils, ESR, glucose, ALT, AST, CPK, urea, LDH, ferritin, CRP, fibrinogen, D-dimer, respiration rate, heart rate, blood, pressure in the group of patients with mild and. moderate severity were statistically significantly lower than in the group of severe patients (p < 0.001). Eleven indicators were identified as predictors of severe COVID-19 (peripheral oxygen level, peripheral blood erythrocyte count, hemoglobin level, absolute eosinophil count, absolute lymphocyte count, absolute neutrophil count, LDH, ferritin, C-reactive protein, D-dimer levels) and. their threshold, values. A model intended, to predict COVID-19 severity in young adults was built. Conclusion. The values of laboratory and instrumental indicators obtained in patients with SARS-CoV-2 infection upon admission significantly differ. Among them, eleven indicators were significantly associated with the development of a severe COVID-19. A predictive model based, on artificial intelligence method, with high, accuracy predicts the likelihood, of severe SARS-CoV-2 course development in young adults.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

A Review: Zinc as an Antivirus Alternative Treatment for Herpes Simplex Virus Infection

This study aimed to review zinc's effectiveness as an antivirus in treating herpes simplex virus infection. The authors use international journals published from 2000-2022, and use search engines such as Google Scholar, PubMed, and Science Direct with the keywords "zinc and herpes simplex virus". The herpes simplex virus that often causes symptoms in humans are HSV type 1 and type 2. The lesions appear as vesicles which then rupture into ulcers. Zinc is one of the most abundant nutrients or metals in the human body besides iron. Studies about the effects of zinc on HSV have shown that it has the function of inhibiting the viral life cycle. HSV attaches to the host cells to replicate and synthesize new viral proteins. Zinc can inhibit this process by depositing on the surface of the virion and inactivating the enzymatic function which is required for the attachment to the host cell, disrupting the surface glycoprotein of the viral membrane so it could not adhere and carry out the next life cycle, it can also inhibit the function of DNA polymerase that works for viral replication in the host cell. This article showed that zinc has effectiveness as an antivirus against the herpes simplex virus, therefore, patients infected with HSV can be treated with zinc as an alternative to an antivirus drug.Copyright © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd.

Hematological findings in COVID-19 and their correlation with severity of Disease.

Objective: To evaluate the efficacy of hematological parameters to predict severity of COVID-19 patients. Method: This was a cross-sectional comparative study conducted at Central Park Teaching Hospital, Lahore in COVID ward and COVID ICU between April 23, 2021 to June 23, 2021. Patients of all ages and both genders with positive PCR admitted in the COVID ward and ICU during this time span of two months were included in the study. Data was collected retrospectively. Results: This study included 50 patients with male to female ratio of 1.38:1. Though males are more affected by COVID-19 but the difference is not statistically significant. The mean age of the study population was 56.21 and the patients in the severe disease group have higher age. It was observed that in severe/critical group the mean values of total leukocyte count 21.76×103 µI (p-value= 0.002), absolute neutrophil count 71.37% (p-value=0.045), neutrophil lymphocyte ratio (NLR) 12.80 (p-value=0.00) and PT 11.9 seconds (p-value=0.034) and the difference was statistically significant. While in severe/critical group, the mean values of hemoglobin 12.03g/dl (p-value=0.075), lymphocyte count 28.41% (p-value=0.8), platelet count 226×103 µI (p-value=0.67) and APTT 30.7 (p-value=0.081) and the difference was not significantly different between groups. Conclusion: It can be concluded from the study that total leucocyte count, absolute neutrophil count and neutrophil lymphocyte ratio can predict in-hospital mortality and morbidity in COVID-19 patients.

Retrospective Analysis of C - Reactive Protein, Haematological Biomarkers and Coagulation Profile in Patients of SARS-Cov-2 in a Tertiary Care Hospital of Eastern India

Introduction: Blood tests play an important role in the early detection of disease given that they provide doctors with information about inflammatory processes. A complete blood count (CBC) is easy and inexpensive to perform. These parameters can be used alone as markers of inflammation. Their mutual ratio is also an indicator of early inflammation.4 In light of previous studies, the use of circulating biomarkers instead of inflammation and immune system has been considered a prognostic indicator for COVID-19 positive patients. Aims/ objective: To examines the role of biomarkers from peripheral blood samples in the diagnosis of hospitalized COVID-19 patients with a history of fever. Materials and Method: Haematological biomarkers and coagulation profile was compared between RT-PCR positive and negative patients. Systemic inflammatory index (SII) was calculated by multiplying thrombocyte count with neutrophil count and dividing the value by lymphocyte count. Neutrophil lymphocyte ratio (NLR) was calculated by dividing absolute neutrophil count by absolute lymphocyte count. Platelet lymphocyte ratio (PLR) was calculated by dividing absolute platelet by absolute lymphocyte count. Fisher exact test and unpaired t-test were used to compare categorical and continuous data respectively. Results: Analysis was done on 57 retrospective cases of RT-PCR positive patients and 61 RT-PCR negative patients with history of fever. COVID-19 positive patients showed leukopenia, neutropenia, thrombocytopenia, and lymphocytosis. SII and NLR decreased and PLR increased. PT and APTT were generally within normal limits in most of the patients. There was significant difference between two groups with respect to lymphocyte counts and PLR. Conclusion: The most standardized non-invasive and inexpensive tests such as CBC, coagulation and biochemical tests are available to assess disease severity for wise allocation of medical resources in developing countries such as India where resources and care are limited.

Comparison of initial presentations of murine typhus and Multisystem-Inflammatory Syndrome in children in a typhus-endemic area

Purpose of Study: In areas endemic for murine typhus, it can be difficult to distinguish from other febrile syndromes. During COVID-19 surges, we identified several cases of typhus. Presenting symptoms and quantitative lab values at and during admission were compared between patients who were diagnosed with murine typhus or multisystem-inflammatory syndrome in children (MIS-C). Methods Used: Retrospective data was collected at a tertiary care center from July 2020 to March 2022. Inclusion criteria were patients under 21 years of age diagnosed at discharge with murine typhus or MIS-C based on clinical and laboratory evidence, serologic data, and expert consultation. Patients found to have an alternate diagnosis, and those without serologic testing were excluded. Subjects were grouped as either MIS-C or typhus based final diagnosis. Categorical data included headache, fatigue, mucocutaneous changes, rash, con-junctival injection, sore throat, rhinorrhea, palpitations, shortness of breath, chest pain, abdominal pain, nausea/vomiting, diarrhea, myalgia, and appetite change at initial presentation. The categorical data were compared using chi-square test. Quantitative data included age, maximum temperature in first 24 hours of hospitalization, duration of symptoms prior to admission, C-reactive protein, erythrocyte sedimentation rate, platelet count, white blood cell count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count, serum sodium, alanine aminotransferase, hemoglobin (Hgb), and albumin (Alb). Means of the quantitative data were compared with a one-tailed 2- Sample T-Test. The maximum and minimum laboratory values during admission were also compared. Additional demographic data including gender and date of initial presentation was also collected. Summary of Results: There were 7 patients in the MIS-C group and 19 in the typhus group. The average age of MIS-C patients, 6.5 years of age vs. 11.5,was significantly lower (p < 0.5) than the typhus group. Initial mean WBC (cells x 103/mm3) was higher in MIS-C than typhus (12.21, SD = 3.52, vs. 7.85, SD = 3.52, p < 0.05), as was ANC (8.9, SD = 3.7vs. 5.12, SD = 2.05, p < 0.05). During hospitalization, minimum Hgb (g/dL) was 9.3, SD = 2.07, and11.49, SD = 1.67, in MIS-C and typhus respectively (p < 0.05). Minimum albumin (g/dL) was also lower in MIS-C than typhus (2.32, SD = 0.86 vs. 2.8, SD = 0.45, p < 0.05). There were no other statistically significant differences in categorical or quantitative data. Typhus cases typically occurred in the summer and fall months. There was no clear seasonality of MIS-C, but occurred during local COVID-19 surges. Conclusion(s): The initial presenting symptoms of typhus and MIS-C were similar. WBC and ANC were higher in MIS-C, while age, Hgb and Alb were lower. These parameters may aid in distinguishing the diseases. A high clinical suspicion for both typhus and MIS-C in endemic areas for typhus is crucial. A rapid detection for typhus would aid in distinguishing these diseases and allow prompt treatment interventions. Copyright © 2023 Southern Society for Clinical Investigation.

Hematologic Outcomes of COVID-19 Patients with and without G6PD Deficiency: A Comparative Study.

INTRODUCTION: Patients with multiple comorbidities who have coronavirus disease 2019 (COVID-19) have high morbidity and mortality. Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to have an enhanced effect on coronavirus in an earlier study. METHODS: We conducted this comparative observational study to evaluate the effects of COVID-19 disease on G6PD deficiency based on the hematologic parameters, COVID-19-related hospitalizations, and mortality in the state of Qatar between January 2020 and May 2020 at four designated COVID-19 facilities. We identified 41 patients with G6PD deficiency who had documented COVID-19 infection. We compared the results with 241 patients with COVID-19 infection who tested negative for G6PD deficiency.: Results: Comparing the COVID-19 positive G6PD deficient with COVID-19 positive G6PD normal activity showed that G6PD normal group had higher white blood cell count (WBC), absolute neutrophil count (ANC), lymphocytes, eosinophils, and monocytes counts versus the G6PD deficient group (p < 0.001). CONCLUSIONS: When compared with COVID-19 patients with normal G6PD, patients with COVID-19 infection and G6PD deficiency had lower total WBC, ANC, lymphocyte, monocyte, and eosinophil counts. However, no evidence of increased hemolysis, thrombosis, morbidity, or mortality was observed in COVID-19 patients with G6PD deficiency.

Severe Covid-19 Associated Hemophagocytic Lymphohistiocytosis : A Comparative Study with Hemophagocytic Lymphohistiocytosis Secondary to Causes Other Than Covid-19

Introduction: Severe COVID-19 infection in a subset of patients is associated with hyperinflammation similar to hemophagocytic lymphohistiocytosis (HLH) however it may not fulfill the required diagnostic criteria (HLH 2004 criteria or H score). We compared clinical, laboratory parameters, bone marrow findings and disease outcome of severe COVID-19 infection related HLH with HLH secondary to causes other than severe COVID-19 to describe features specific to severe COVID-19 associated HLH and limitations of currently available diagnostic criteria of HLH in context to severe COVID -19 infection induced hyperinflammation. Method(s): We analyzed 69 patients diagnosed as HLH of which 47 had severe COVID-19 and 22 had HLH secondary to causes other than COVID-19. Clinical, hematological and biochemical parameters were compared using Mann-Whitney U test. Bone marrow examination (BME) was done in all for presence of hemophagocytosis. Immunohistochemical staining for CD68 and CD163 were done for identification of histiocytes. Occurrence of COVID-19 related HLH was taken as the dependent variable to determine predictors of COVID-19 HLH. Result(s): Organomegaly was seen in only 4.3% (2/47) cases with COVID-19 related HLH as compared to 54.5% (12/22) with non-COVID HLH (p< 0.001). Amongst the quantitative variables, a significant difference in COVID-19 related and non-COVID-19 related HLH was found in the following parameters: Age (p< 0.001), Triglyceride (p=0.009), Fibrinogen (p< 0.001), Ferritin (p< 0.001), Hemoglobin (p< 0.001), Total leukocyte count (p=0.003), Absolute neutrophil count (p< 0.001), Neutrophil lymphocyte ratio (p< 0.001) and H score (p< 0.001). BME of all patients showed presence of hemophagocytes. Only 6.4% (3/47) cases with COVID related HLH had 5/8 HLH 2004 criteria as compared to 63.6% (14/22) cases with non-COVID related HLH (p< 0.001). H-Score >=169 was also significantly less common in COVID HLH as compared to non-COVID HLH (40.42% vs 86.36%, p=0.001). Conclusion(s): Organomegaly, cytopenias, hypofibrinogenemia and hypertriglyceridemia which are part of HLH diagnostic criteria are rare in severe COVID-19 making it difficult to diagnose. Demonstration of hemophagocytes in bone marrow should be recommended in suspicious cases for initiation of early immunosuppressive therapy. (Figure Presented).

Systemic Immune Inflammation Index & Sysmex Xn-1000 Research White Blood Cell Parameters in Covid-19 Patients

Introduction: Inflammation mechanisms play a critical role in Coronavirus disease 2019 (COVID-19) severity Systemic immune inflammation (SII) index is reported to have a diagnostic value in COVID-19 diagnosis Sysmex XN-1000 analyzer provides during routine full blood count two parameters for neutrophil activation measurement;NE-SSC, which represents the inner complexity of neutrophils and is strongly related to granularity and NE-SFL, which reveals the neutrophil nucleic acid/protein content and is related to production or release of proteins and reactive oxygen intermediates and one parameter for lymphocytes;the high- fluorescent lymphocyte count (HFLC) as antibody-producing plasma cells. The aim of our retrospective study is the evaluation of SSI index and NE-SSC, NE-SFL & HFLC parameters in COVID-19 patients treated with the relevant medical intervention as outpatients or inpatients. Method(s): Patients admitted to our hospital with COVID-19 diagnosed through real-time reverse transcription polymerase chain reaction, and had a complete blood count (on Sysmex XN-1000 hematology analyzer) within 24 hours of diagnosis were included. We retrospectively recorded the demographic data, the laboratory findings upon admission (NE-SSC, NE-SFL & HFLC) retrieved from the hospital electronic database system and calculated the SII index as followed: platelet count x absolute neutrophil count / absolute lymphocyte count Patients were divided in two groups: patients discharged and treated as outpatients (N = 105) and patients hospitalized in COVID-19 inpatient wards (N = 174) Statistical analysis: Mann-Whitney U test was applied P value of < 0.05 was considered significant. Result(s): The two groups do not differ in genders (P = 0.183) but inpatients are older [70 (58-79) vs 60 (39-71) years, P = 0.000]. Results are summarized in Table 1. SII index values are higher in inpatients in a statistically significant degree (P = 0.000). There is no statistically significant difference in NE-SSC, NE-SFL & HFLC values between the two groups (all P >0.05). Table 1. Results (Table Presented) hospitalization present systemic inflammation in a higher degree as compared to outpatients without any differentiation in neutrophil activation or lymphocyte morphology as indicated by morphology - associated white blood cells studied parameters.

Role of Inflammatory Markers and Clinical Correlate in Children Infected with the Novel SARS-CoV-2: A Prospective Observational Study

Introduction: Inflammatory markers have been used as predictors of adverse outcomes in adults with Coronavirus Disease-2019 (COVID-19) infection. Children mostly have mild infections and raised inflammatory markers have been reported only with severe COVID-19 or Multisystem Inflammatory Disorder (MIS-C). Studies in children showing the role of inflammatory markers in disease prognosis are few, and findings are not conclusive. Aim(s): To find out correlation, if any, between the inflammatory markers {Interleukin-6 (IL-6), C-reactive Protein (CRP), procalcitonin, Pro-B-type natriuretic Peptide (Pro-BNP), ferritin, D-dimer} with clinical presentation, prognosis, and outcome in children with acute COVID-19. Material(s) and Method(s): The prospective, observational study was conducted at a tertiary care COVID-19 Paediatric Intensive Care Unit {PICU (Vardhaman Medical College and Hospital, New Delhi)}, Northern India, between September 2020 and December 2020. All children aged less than 12 years, with a positive COVID-19 report were enrolled and investigated. Data was collected for clinical presentation, severity, treatment and outcome. The following variables were recorded: Complete Blood Count (CBC), Kidney Function Test (KFT) and Liver function Test (LFT), Absolute Lymphocyte Count (ALC), Absolute Neutrophil Count (ANC), Neutrophil-lymphocyte Ratio (NLR), Platelet Count (PLT), C-reactive Protein (CRP), Procalcitonin (PCT), serum ferritin, Lactate Dehydrogenase (LDH), fibrinogen, and Erythrocyte Sedimentation Rate (ESR) and ProBNP. Coagulation parameters like Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), International Normalised Ration (INR), D-dimer were taken. Data was analysed using Statistical Package for the Social Sciences (SPSS) software version 21.0. Result(s): A total of 35 children were admitted during the study period. Seventeen children met the criteria for severe disease. Seven children met the criteria for MIS-C. Children presenting with conjunctivitis (n=3) were more likely to have signs of peripheral inflammation hypotension (n=4), tachycardia (n=6), and raised IL-6 levels (pg/mL) as well as the need for inotropic support. IL-6 values were higher in children (Mean+/-SD= 182.47+/-149.83). Median IL-6 value 199.8 (96.17-275.24) was highest in children with CRP <10 mg/dL (p-value<0.01). Children with raised D-dimer (Mean+/-SD=1881.94+/-1265.66 mg/dL) had a longer duration of stay (p-value=0.031). conclusion: The study didn't find any correlation between inflammatory markers with clinical presentation and the outcome of COVID-19 infection in children. Copyright © 2023 Journal of Clinical and Diagnostic Research. All rights reserved.

SARS-CoV-2 Antibody Levels Associate with Neutrophil Activation

Background. COVID-19 disease severity and outcomes have been linked to high antibody titers and a dysregulated neutrophil immune response. Here we query associations and connections between the endogenous SARS-CoV-2 antibody response and neutrophil activation in COVID-19. Methods. Baseline serum or plasma samples from 57 patients hospitalized on oxygen with COVID-19 were used to perform;1) quantitative measurements of SARS-CoV-2 specific antibodies using a luciferase-based immunoprecipitation system assay, 2) quantitative measurements of neutrophil specific biomarkers using Luminex technology, and 3) neutrophil extracellular traps (NETs) as measured by myeloperoxidase-DNA (MPO-DNA) complexes by ELISA. Absolute neutrophil count (ANC) and immature granulocyte count (IGC) were measured from complete blood counts (CBC). Antibody levels were compared by disease severity using Wilcoxon rank-sum test and correlations were generated between antibody levels and neutrophil activation markers using Spearman's correlation (SC). Results. In a cohort of hospitalized patients, severe/critical COVID-19 was associated with higher levels of nucleocapsid-IgA (p=0.011) as well as spike-IgG (p= 0.0007) compared tomoderate disease,while spike-IgA and nucleocapsid-IgG showed similar associations, trending towards significance (Figure 1A). Levels of IgG-spike and IgG-nucleocapsid both had significant correlations with the ANC (SC 0.33, p = 0.029;SC 0.38 p = 0.012). All four antibody titers showed strong correlations with IGC, lactoferrin and lipocalin-2, evidence of emergency granulopoiesis. Further, S100A9, a component calprotectin correlated with spike-IgG and nucleocapsid-IgA levels (SC 0.29, p = 0.030, SC 0.29 p = 0.029). Lastly, we found circulating NETs correlated with spike IgA levels (SC 0.38 p = 0.006), and its correlations with IgG-spike and IgA-nucleocapsid additionally approached significance with NETs levels as well (Figure 1B). Antibody Levels Correlate with Disease Severity and Neutrophil Activation Markers Figure 1: A) Levels of anti-Spike and anti-Nucleocapsid IgA and IgG levels measured in the serum of 57 unvaccinated hospitalized COVID-19 patients. Moderate illness represents ordinal scale 5 requiring low flow oxygen, while severe/critical patients represent ordinal scale 6 and 7, requiring high flow oxygen, non-invasive or mechanical ventilation, respectively. P values are compared by a Wilcoxon ranked sum test. B) Heatmap showing Spearman correlations between levels of anti-Spike and anti-Nucleocapsid IgA and IgG and markers of neutrophil activation. P values for individual correlations are represented in parentheses. MPO (myeloperoxidase), ANC (absolute neutrophil count), S100A9 (S100 calcium binding protein A9). Conclusion. Higher anti-spike and anti-nucleocapsid IgG and IgA levels associate with more severe COVID-19 illness. Further, endogenous SARS-CoV-2 specific antibody levels associate with markers of emergency granulopoiesis and neutrophil activation. Inhibiting antibody mediated neutrophil activation may improve outcomes in COVID-19.

Teleconsultation: An importatnt tool leading to a paradigm shift in the management of maintenance phase chemotherapy of acute lymphoblastic leukemia

Background: The COVID-19 pandemic severely impacted patients with acute lymphoblastic leukemia(ALL) in maintenance phase of chemotherapy. Teleconsultation was introduced to ensure continuity of care for these patients during the lock-down phase of the pandemic and was continued well after its end. Hence, we decided to analyze the impact of teleconsultation in a cohort of ALL patients. Method(s): Our study was a single-centre retrospective analysis of patients with ALL on maintenance chemotherapy. Thirty-five patients records were analyzed, comparison was made between absolute neutrophil counts (ANC) and frequency of consultations before and after the start of teleconsultation, which included 2-weekly phone calls, necessitating visit only once in 3 months as opposed to a monthly visit as required before. Hemograms were done twice a month and sent on WhatsApp. Consultations were done via phone calls and prescriptions sent via WhatsApp. Result(s): The median [IQR] age of our cohort was 7.5 [4.2;9.3] years and age at diagnosis was 5.4 [2.3;7.5] years;23/35 (66%) were male and 30/35 (88%) were phenotypically B-ALL;rest T-ALL/Lymphoma. All patients received chemotherapy as per the ICiCLE (Indian Collaborative Childhood Leukaemia group) protocol. A total of 437 teleconsultations were done (73/month). Before teleconsultation, the mean (SD) ANC was 2272 (644)//microL, and after teleconsultation it was 1754 (461)/microL (p value=0.0001). Teleconsultation improved target ANC (<2000/microL) attainment in our cohort of patients (31% vs 80%, p value=0.0002). Prior to teleconsultation, majority (27/35, 77%) visited the hospital once a month which reduced to once in 3 months, after teleconsultation. Conclusion(s): Teleconsultation is time saving, economical and reduces the gap in schooling in a child with ALL. It also helps optimize compliance during this maintenance phase of chemotherapy, a key in management of leukemia patients, contributing to the continuum of care and improvement in overall survival of these patients. Copyright © 2022

Neutrophil Counts Related to Presentation of Covid in Autoimmune Neutropenia?

Objective: To describe 2 cases of autoimmune neutropenia (AIN) patients infected with Sars-Cov-2. Design/Method: Two subjects case report. Result(s): Case report 1: A girl with primary AIN since 1 year and 10 months old, maintaining severe neutropenia and mild recurrent infections. Presented to the emergency department in June/2020, at 3 years and 8 months old, with flu-like symptoms, afebrile, in good general condition. Physical examination was normal. The absolute neutrophil count (ANC) was 0.279 x 109/L. At hospital admission, Sars-Cov-2 (RT-PCR) tested positive and filgrastim (G-CSF) 5 mug/kg/day was initiated. Chest X-ray was also normal and blood culture resulted negative. She remained in great general condition, afebrile, and was discharged on the 2nd day of hospitalization, with clarithromycin (15 mg/kg/day). After G-CSF, ANC: 0.494 x 109/L (1st dose), 1.431 x 109/L (2nd dose). On outpatient follow-up, she had no long-term complications from Covid-19. Case Report 2: A man with chronic immune thrombocytopenia purpura (ITP) since 2008, autoimmune hemolytic anemia since 2013, evolved with AIN on May/2020, at 42 years old, with ANC lower than 0.5 x 109/L. On 6/1/2020, he had ANC 0.170 x 109/L. On 6/25/2020, he started flu-like symptoms, had ANC of 5.118 x 109/L, and tested positive for Sars-Cov-2 (RT-PCR). He kept high fever (102,2degreeF) and was hospitalized for 10 days without use of G-CSF. After discharge, on outpatient follow-up, he had no long-term complications from Covid-19, and presented ANC 0.338 x 109/L (Aug/2020). Discussion(s): At beginning of Covid-19 pandemic, severity infection in children was unknown. Today is known that most of them have milder clinical course, regardless of chronic diseases. In adults, in contrast, the inflammatory response tends to exacerbation, with more severe clinical conditions. Furthermore, many case reports of patients infected by SARS-CoV-2 with comorbidities literature are published. However, to date there are no reports on the impact of COVID-19 in AIN patients. Increased neutrophil counts during infectious episodes are common in AIN, which appears to be related to the benign course of most infections. We reported 2 cases of AIN patients diagnosed with Covid-19, both with favorable clinical outcomes despite heterogenic clinical course. On the first case, she presented few symptoms and ANC increased only after using G-CSF. On the second reported patient, there was a spontaneous increase of ANC and greater inflammatory response than the first case. It could suggest a correlation between inflammatory response to COVID-19 and ANC in cases of autoimmune neutropenia. Conclusion(s): In the reported cases, clinical course of disease and neutrophil count were different between adult and pediatric patients. It is not possible to state whether this difference is due to age group, individual response to infection or other variables. It is important to assess other cases of AIN infected by COVID 19 to better understand correlation between severity of infection and neutrophil count response. Copyright © 2022

Role of copper levels in patients with myelodysplastic syndromes

Background: Patients with inadequate amounts of copper often present with cytopenias and exhibit dysplasia on bone marrow, mimicking myelodysplastic syndrome (MDS) and pose diagnostic difficulties. Method(s): This cross-sectional observational study was performed from January 2020 to June 2021. Patients diagnosed with MDS were included in the study and serum copper levels were measured by the Inductively Coupled Plasma Mass Spectrometry (ICPMS) method. Copper supplementation with intravenous copper chloride 2.5mg daily for the first two weeks, followed by oral 3mg copper sulfate thrice daily for the next three months, was given for copper-deficient patients. Response assessment was performed with repeat hemogram and serum copper levels. Result(s): A total of 57 patients were diagnosed with MDS, of these, 33 (57.89%) were males and 24 (42.10%) were females. The mean age was 54.3+/-14.6 years (13-81). The distribution of patients in different types of MDS was MDS-SLD in 15, MDS-MLD in 18, MDS-EB1 in 7, MDS-EB2 in 8, and MDS-U in 9 patients. Anemia was seen in (87.71%) of patients, with mean hemoglobin 7.6+/-2.1g/dL (4.6-14.5g/dL). Neutropenia was seen in 31 (54.38%) with a mean absolute neutrophil count(ANC) of 2073+/-2139/muL (211-10,952/muL). Thirty seven (64.91%) patients had thrombocytopenia with a mean platelet count of 1,05,298+/-1,21,769/muL (9,000-6,74,000/muL). The mean serum copper levels were 146.69+/-42.36mug/dL (54.2-254.0mug/dL). Only three (5.26%) patients out of 57 were found to have copper deficiency. All three patients with low copper levels were found to have anemia, thrombocytopenia, and mildly raised serum erythropoietin levels. All three patients had dyserythropoiesis on bone marrow examination, and only one patient each had cytoplasmic vacuolations in erythroid precursors and dysmegakaryopoiesis. Among the three patients with copper deficiency, two patients had significant improvement in cytopenias after copper supplementation, and one had lost follow-up due to COVID-19. Conclusion(s): This study is the first from India to evaluate the role of copper in patients presenting with predominantly hematological manifestations. For patients presenting with cytopenias or marrow dysplasia resembling MDS, copper deficiency should be considered in the differential diagnosis. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Copyright © 2022