Direct bilirubin and the neutrophil-to-monocyte ratio timely predict intensive care unit admission in patients with severe acute respiratory syndrome coronavirus-2 infection (COVID-19)

Objective: Intensive care units (ICUs) collapsed under the global wave of coronavirus disease 2019 (COVID-19). Thus, we designed a clinical decision-making model that can help predict at hospital admission what patients with COVID-19 are at higher risk of requiring critical care. Method(s): This was a cross-sectional study in 119 patients that met hospitalization criteria for COVID-19 including less than 30 breaths per minute, peripheral oxygen saturation < 93%, and/or >= 50% lung involvement on imaging. Depending on the need for critical care, patients were retrospectively assigned to ICU and non-ICU groups. Demographic, clinical, and laboratory parameters were collected at admission and analyzed by classification and regression tree (CRT). Result(s): Forty-five patients were admitted to ICU and 80% of them were men older than 57.13 +/- 12.80 years on average. The leading comorbidity in ICU patients was hypertension. The CRT revealed that direct bilirubin (DB) > 0.315 mg/dl together with the neutrophil-to-monocyte ratio (NMR) > 15.90 predicted up to correctly in 92% of the patients the requirement of intensive care management, with sensitivity of 93.2%. Preexisting comorbidities did not influence on the tree growing. Conclusion(s): At hospital admission, DB and NMR can help identify nine in 10 patients with COVID-19 at higher risk of ICU admission.Copyright © 2022 Sociedad Medica del Hospital General de Mexico.

Increased CD14+ monocytes and OPN+ positive airway macrophages in the BAL are associated with Post-COVID19 induced altered respiratory function

The long term consequences of severe COVID-19 in the lungs remain speculative, however interstitial abnormalities in these patients may arise. In this study previously identified fibrotic markers from the BAL were evaluated in PostCOVID-19 patients. 26 patients were referred for evaluation of respiratory symptoms and/or abnormalities on HRCT, on average 5.3 months from the acute disease phase, to the Post COVID-19 clinic. 20 patients showed persistent radiological findings with fibrotic changes and/or altered respiratory function. Bronchoalveolar lavage cellular composition was determined by MGG staining and CD45, CD14, CD11c, CD163 and Osteopontin staining. Airway monocytes were identified by SSClo/CD45+ parameters and surface expression of CD11c, CD14 and CD16 by flow cytometry. FVC% and DLCO% were used as measures of disease severity. Collectively, monocyte percentages in the BAL were associated with lower FVC% (Rs=-0.53,p=0.02). Importantly, patients with DLCO% below 60 showed higher monocyte infiltration (p=0.015). CD14 positivity on monocytes was more pronounced in patients with DLCO% below 60, while CD16 and CD11c were not associated with DLCO. Increased Osteopontin expression in airway macrophages was also linked with lower DLCO% levels (Rs=-0.661, p=0.019), in contrast to CD163 macrophage expression which tended to be higher in patients with higher DLCO%. Neutrophils were negatively associated with DLCO% in Post-COVID-19 patients (Rs=-0.62,p=0.01). Airway immune cell populations from BAL were associated with Post-COVID-19 induced altered respiratory function.

Common Symptom, Rare Etiology: A Case Metastatic Cancers of Unknown Primary Origin Presenting with Epistaxis and Gingival Bleeding

Introduction: Epistaxis and gingival bleeding are among the most common presentation to the emergency department for patients with thrombocytopenia. Here, we present a case who was admitted to the emergency department with thrombocytopenia and was diagnosed with metastatic cancer of unknown primary origin. Case Report: A 26-year-old male patient was admitted to the emergency department with gingival bleeding and epistaxis. The body temperature was 38.3 °C. Petechial rash, ecchymosis or organomegaly was not detected on physical examination. Laboratory results revealed thrombocytopenia as 31 × 103 (159-388 × 103/μL). Although hemoglobin and leukocyte counts were normal, no band or precursor cell was observed in the patient's peripheral blood smear. There was no history of weight loss, night sweats, arthritis, malar rash, photosensitivity, contact with ticks, animals, or a COVID-19 patient. Serological tests performed for infections such as HIV, EBV, HCV, Crimean-Congo hemorrhagic fever were negative. Bone marrow biopsy was performed due to the unexplained cytopenia, reported as "signet ring cell metastatic adenocarcinoma". Gastrointestinal system endoscopy was performed to detect primary cancer. A biopsy was taken from the antrum and corpus revealed gastritis. An FDG PET-CT was revealed heterogeneously pathologically increased FDG attitude in all axial and appendicular bones. Despite all the modalities of diagnosis, the origin was not found and the patient was transferred to the oncology department for treatment with a diagnosis of cancer of unknown origin with bone marrow infiltration. Conclusion: Bone marrow metastases should be kept in mind in patients presenting with thrombocytopenia.

HEMATOBIOCEMICAL AND HISTOPATHOLOGICAL STUDIES ON THE EFFECTS OF RAJ NIRWAN BATI (A NOVEL ALLOVEDIC DRUG) IN WISTAR RATS

Objective: To see the effects of Raj Nirwan Bati (RNB) on the hematobiochemical parameters, coagulation tests, and histopathological changes in the lungs, liver, kidneys and spleen and also to evaluate the immunomodulatory activity of RNBin Wistar rats. Methods: A total of 24 adult albino Wistar rats (of bodyweight 200-250 g) of either sex were divided into 3 groups. In the normal control group (n=8), no drug was administered and in the rest of the groups (A and B), RNB@ 26 mg/kg body weight./day and 260 mg/kg body weight/day respectively were administered orally for a period of 14 d. The blood samples were collected from the jugular vein at zero d (before drug administration) and after the 14th d of drug administration in both groups (A and B). The organ samples (lungs, liver, kidneys, and spleen) were collected after euthanizing the rats using Ketamine anesthesia overdose intraperitoneally (IP) after the 14th d of drug administration. White Blood Cells (WBC), Red Blood Cells (RBC), Hemoglobin (Hb), Hematocrit (HCT), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin(MCH), Mean Corpuscular Hemoglobin Concentration(MCHC), number of platelets, Differential Leucocyte Count(DLC) i.e. the percentage of neutrophils, lymphocytes, eosinophils, monocytes and basophils, neutrophil adhesion percentage, Prothrombin test (PT), Activated Partial Thromboplastin Time (APTT), fibrinogen, D-dimer, Lactate Dehydrogenase (LDH), urea, creatinine, Aspartate Amino Transferase (AST), Alanine amino Transferase (ALT), Alkaline Phosphatase (ALP), C-Reactive Protein (CRP) were evaluated and histological examination of organs were done. Results: After statistical analysis, it was found that the decrease in TLC, RBC, Hb, HCT, and LDH in Wistar rats after RNB intervention in Group A as compared to that of before RNB intervention, was found to be statistically significant (P=0.001, P=0.002, P=0.001, P=0.039, and P=0.008). On the other hand, an increase was observed in MCV, Urea, Creatinine and ALT values in the Wistar rats after RNB intervention in Group ‘A’ as compared to that of before RNB intervention and this increase in values was statistically significant (P=0.007, P=0.001, P<0.001 and P=0.038). After RNB intervention in Group B, the increase in MCH, fibrinogen concentration, and monocytes percentage, was found to be statistically significant (P=0.004, P=0.033, and P=0.001) as well as the decrease in PT and APTT was statistically significant (P=0.007and P=0.002). After comparing the Mean Hematobiochemical and coagulation test parameters in the rats of Group A and Group B, after RNB intervention, it was observed that the concentration of Urea, Creatinine, APTT, and D-dimer were less in Group B as compared to that of Group A and this difference was statistically significant(P<0.001, P<0.001, P<0.001 and P=0.022). Histologically the findings in the lungs of group B were more distortion of lung architecture, most of the alveoli become collapse and make emphysematous changes, more diffuse inflammatory infiltrate within interalveolar septa and around bronchioles as compared to Group A. In the liver of group B rats, the histological findings were mild to moderate distortion of lobular architecture, healthy hepatocytes with more activation of kupffer cells as well as larger and more aggregates of inflammatory cells as compared to group A. Histological findings of kidneys in group A and group B rats were similar to that of control group rats. Conclusion: The results suggest that the RNB is having an immunomodulatory effect. It might be helpful in the restoration of coagulation factors and can help treat the COVID patients. No harmful effects on the lungs, liver, kidney, and spleen were seen. These findings may act as baseline data for planning further clinical trials in human study subjects to evaluate the effects on various comorbidities.

A Comparative Study of Hematological Parametersin COVID-19 Positive Cases, Influenza like Illness Patients, and Healthy Subjects

Introduction: Since its origin in December 2019, Novel Corona virusinfection has behaved in an unprecedented manner. Viral infectionsare characterized by atypical and reactive lymphocytosis as is seen ininfectious mononucleosis and dengue viral infection respectively.Previous studies on influenza like illnesses have demonstrated the roleof Neutrophil-to-lymphocyte as a preferable diagnostic tool to screeninfluenza virus-infected patients. In addition to these, volume conductivity and scatter has revealed significant findings in volumescatter and conductivity of monocytes and neutrophils in the past ininfluenza and influenza like illnesses.Aims &Objectives: To study the hematological parameters ofCOVID-19 positive cases and to compare the hematological parameters in COVID-19 positive cases, patients with influenza andinfluenza like illness.Materials &Methods: 169 Covid positive cases, 113 influenza andinfluenza like illnesses and 140 healthy controls were included in thestudy. All samples were processed on DXH 800 and all parameterswere recorded.Result: There was significant difference between Covid 19 and influenza and influenza like illness in terms of age, percentage ofneutrophils, percentage of lymphocyte, percentage of monocyte, percentage of eosinophil and basophil. Significant difference was alsofound between mean neutrophilic and mean monocytic volume, and inall the scatter parameters of neutrophils. Neutrophil-to-lymphocyteratio (NLR) and platelet-to-lymphocyte ratio (PLR) also showed significant difference in both the conditions. Multivariate analysis wasperformed and a joint probability was calculated which showed a cutoffin differentiating Covid 19 from influenza and influenza like illnesses.Conclusions: Covid 19 and Influenza can cause different changes inperipheral blood parameters and the diagnostic formula developed inthis study will enable the clinicians to differentiate Covid 19 frominfluenza during the early stages.

Dynamic alterations of immunophenotype, C reactive protein and interleukine-6 levels in peripheral blood of severe COVID-19 patients

Introduction. Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) causes a coronavirus disease 2019 (COVID-19) characterized by a "cytokine storm"-increased activity of immune cells with the elevated production of inflammatory cytokines leading to respiratory failure. Additionally, the course of pneumonia is characterized by an increased content of C reactive protein. Leukocytosis, leukopenia and lymphopenia are also commonly present in COVID-19 patients. Fine alterations of the immune cells subpopulations and cytokines level in COVID-19 patients are little known. This work aimed to determine the immunophenotype of peripheral blood cells subpopulations and to study the mentioned underlying changes in IL-6 and CRP levels in patients with COVID-19 pneumonia. Methods. Blood count with Erythrocyte Sedimentation Rate (ESR) was completed by routine blood assay. CRP and IL-6 levels were measured by ELISA. Immunophenotype of subpopulations of peripheral blood cells was acquired by multiparametric fluorescence flow cytometry. Results. Blood parameters comparison in 14 hospitalized severe COVID-19 patients showed that WBC count increased on day 7 and steadily decreased by day 28, while the percentage of neutrophils decreased gradually from the time of admission to full-recovery state. The percentage and count of lymphocytes regularly increased. The percentage of monocytes had a trend to rising but not statistically significant. The red blood cells count, ESR, and platelet count were not altered during COVID-19 progression. On initial admission, 35.7 % of COVID-19 patients had leucopenia, while 14.3 % of patients had leukocytosis on day 7. Lymphopenia occurred in 76.9 % of patients on day 0 and was not present on day 28. Changes in CRP levels were statistically significant over the duration of COVID-19 progression and recovery (p=0.003;n=15). The maximum CRP value was at day 0 but reached a normal range on day 28. The Il-6 level did not change significantly over 28 days of observation demonstrating a steady twice higher level in COVID-19 patients compared to healthy donors (p=0.934;n=8). The population of CD45+ cells was significantly lower in COVID-19 patients than in the healthy donors group (p=0.009;n=12). Despite it grew gradually from day 0 to 28, it did not reach the normal value at full-recovery state. The population of CD3+ cells was higher than the normal ranges at the first assessment, then dropped on day 7 but return to elevated levels on days 14 and 28 (p=0.008;n=12). Changes in the CD19+ cells count were significantly lower than those of the healthy volunteers during the period of observations (p=0.007;n=12). There were decreases in CD16+CD56+ cells counts over each time of assessment compared to healthy donors, but not statistically significant. Conclusion. The understanding of the dynamic changes of lymphocyte populations, cytokines production in COVID-19 patients will provide an in-depth knowledge of the COVID-19 pneumonia progression.