Prognostic Value of Serum/Plasma Neurofilament Light Chain for COVID-19 Associated Mortality

Given the continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), early predictors of coronavirus disease 19 (COVID-19) mortality might improve patients outcomes. Increased levels of circulating neurofilament light chain (NfL), a biomarker of neuro-axonal injury, have been observed in patients with severe COVID-19. We investigated whether NfL provides non-redundant clinical value to previously identified predictors of COVID-19 mortality. We measured serum or plasma NfL concentrations in a blinded fashion in 3 cohorts totaling 338 COVID-19 patients. In cohort 1, we found significantly elevated NfL levels only in critically ill COVID-19 patients compared to healthy controls. Longitudinal cohort 2 data showed that NfL is elevated late in the course of the disease, following two other prognostic markers of COVID-19: decrease in absolute lymphocyte count (ALC) and increase in lactate dehydrogenase (LDH). Significant correlations between LDH and ALC abnormalities and subsequent rise of NfL implicate multi-organ failure as a likely cause of neuronal injury at the later stages of COVID-19. Addition of NfL to age and gender in cohort 1 significantly improved the accuracy of mortality prediction and these improvements were validated in cohorts 2 and 3. In conclusion, although substantial increase in serum/plasma NfL reproducibly enhances COVID-19 mortality prediction, NfL has clinically meaningful prognostic value only close to death, which may be too late to alter medical management. When combined with other prognostic biomarkers, rising longitudinal NfL measurements triggered by LDH and ALC abnormalities would identify patients at risk of COVID-19 associated mortality who might still benefit from escalated care.

Clinical and laboratory findings of COVID-19 in children younger than six months old; Neutropenia is more common not lymphopenia

Background: Studies on age-related differences in clinical and laboratory features on coronavirus disease 2019 (COVID-19) are limited. We aimed to evaluate the demographic, clinical, and laboratory findings of COVID-19 in children younger than six months old and compare them with older children. Methods: A single-center retrospective study, including 209 confirmed COVID-19 cases, was conducted between March 11, 2020, and September 1, 2021. The case group consisted of 47 patients younger than six months old, and the control group consisted of 162 patients older than six months old. Results: The mean age of the case group was 2.77±1.52 months, and the control group was 101.89±65.77 months. Cough was statistically higher in the control group, poor feeding was higher in the case group (P=.043, .010). The underlying disease ratio was statistically higher in the case group; however, the hospitalization rate was higher in the case group (P=.001, .036). The case group had significantly lower median values of the absolute neutrophil count, hemoglobin, and higher median values of white blood cell, absolute lymphocyte count, platelet than the control group (P<.05). C-reactive protein, fibrinogen values were significantly lower, and procalcitonin, D-dimer, troponin T, N‑terminal pro-B-type natriuretic peptide significantly higher in the case group (P<.05). Lymphopenia was more common in the control group, whereas neutropenia was more common in the case group (P= .001, .011). Conclusions: We showed that most children younger than six months old had mild and asymptomatic COVID-19; however, the hospitalization rate was higher, and neutropenia was more common than older children.

Neurological update: treatment escalation in multiple sclerosis patients refractory to fingolimod—potentials and risks of subsequent highly active agents

A critical issue in the management of relapsing MS (RMS) is the discontinuation of disease-modifying treatments (DMT) due to lack of efficacy, intolerability or impending risks. With new therapeutic agents introduced into the treatment of RMS, immediate- and long-term consequences of sequential drug use, as well as the effect of the sequence in which the drugs are given, are unclear but may affect efficacy, adverse events, and long-term immunocompetence. In the absence of clinical studies specifically addressing these concerns, observations from clinical practice are of particular value in guiding current management algorithms. Prompted by a study published by Ferraro et al. in this journal, we set out to provide an overview of the published real-world evidence on the effectiveness and safety of switching from fingolimod to another DMT in patients with active RMS. Seventeen publications reporting relevant information were identified. The literature suggests that immune cell depletion induced by alemtuzumab or ocrelizumab is associated with an increased risk of relapse and worsening disability in patients switching from fingolimod compared to patients switching from other therapeutic agents. However, the evidence reported for natalizumab and cladribine is inconclusive. While shortening of the washout period may limit early disease reactivation after fingolimod discontinuation, there is no strong evidence that the duration of the washout period or the absolute lymphocyte count at baseline are predictors of attenuated long-term efficacy. Further real-world studies are required to better understand outcomes among patients who are under-represented in controlled trials.

The Predictive Values of Lymphocytopenia in West Darfur Patients with Malaria

Background: In Sudan malaria is most commonly caused by infection with plasmodium falciparum, although by p.vivax. Malaria causes the most dangerous and highest rates of complication and mortality. Most malaria cases in 2018 were reported by the world health organization (WHO) in the African region(213 million cases of malaria or 93% of all malaria cases in the world and 70% is 5 years or younger). Objectives: The aim of this study was to measure and compare the mean of absolute lymphocyte count in malaria patients and control groups, and to determine positive and negative predictive values of lymphocytopenia in malaria patients. Methods: It was conducted on 100 subjects with malaria as cases and 100 subjects without malaria as controls, at EL Genina Hospital after obtaining the ethical approval and the subjects' consent. It was done by testing the CBC, differential counts, and absolute lymphocyte count then determining the means and p-values. The positive and negative predictive values were also determined. Results: It was found that the mean of TWBC count in the case group was(7,13109/l), and (7,84109/l)in the control group, the p-value was (0.150). The mean of lymphocytes differential in the case group was (20.73%)and (33.96%)in the control group, the p-value was (0.000). While the mean of the absolute lymphocytes counts in the case group was (1.39109/l), it was (2.56109/l)in the control group, with a p-value (0.000). This p-value indicated that there was significant lymphocytopenia in malaria patients. The positive predictive value was 83% and the negative predictive value was 69%. Conclusion: This study concluded that there was no significant lymphocytopenia in malaria patients and that lymphocytopenia cannot be used as the key hematological indicator of malaria infection.

Pre-Existing Lymphopenia Increases the Risk of Hospitalization and Death after SARS-CoV-2 Infection

There is limited information regarding the severity of COVID-19 in immunocompromized patients. We conducted a retrospective cohort study considering the period from 1 March 2020 to 31 December 2020 to determine whether previously existing lymphopenia increases the risk of hospitalization and death after SARS-CoV-2 infection in the general population. The laboratory and hospital discharge databases of the Azienda Sanitaria Universitaria Friuli Centrale were used, and 5415 subjects infected with SARS-CoV-2 and with at least one recent absolute lymphocyte count determination before SARS-CoV-2 positivity were included. In total, 817 (15.1%) patients had severe COVID-19. Patients developing severe COVID-19 were more frequently males (44.9% of the severe COVID-19 group vs. 41.5% in the non-severe COVID-19 group; p < 0.0001) and were older (73.2 ± 13.8 vs. 58.4 ± 20.3 years; p < 0.0001). Furthermore, 29.9% of the lymphopenic patients developed severe COVID-19 vs. 14.5% of the non-lymphopenic patients (p < 0.0001). In a logistic regression model, female sex remained a protective factor (OR = 0.514, 95%CI 0.438–0.602, p < 0.0001), while age and lymphopenia remained risk factors for severe COVID-19 (OR = 1.047, 95%CI 1.042–1.053, p < 0.0001 for each additional year of age; OR = 1.715, 95%CI 1.239–2.347, p = 0.0011 for lymphopenia). This provides further information to stratify the risk of COVID-19 severity, which may be an important element in the management of immunosuppressive therapies.

HIV Myelopathy- A cross-sectional study of constellation of bone marrow findings in HIV/AIDS

Introduction and Aim: Haematological manifestations in HIV disease is common and can happen at any phase during the disease course. Anemia and thrombocytopenia are the most frequent hematologic abnormalities and are associated with high morbidity and mortality. The objective of current study was to observe and analyse various spectrum of bone marrow changes and haematological abnormalities in HIV/AIDS and to correlate findings with CD4 count. Material and Methods: A total of 44 patients over a period of 5 years were included. Clinical findings, hematological profile, bone-marrow aspirate, biopsy findings and CD4 count of these patients were documented. The association between absolute lymphocyte count (ALC) and CD4 count were further established. Results: The most common clinical indication for bone-marrow aspiration and trephine biopsy was pancytopenia (47.3%), pyrexia of unknown origin (15.1%), and unresolving hepatosplenomegaly (13.6%). Anemia (72.7%) was commonest haematological abnormality. Bone marrow aspirate was normocellular in majority of patients. Marrow findings were correlated with CD4 count and were found to be statistically significant. Tri-lineage dysplasia was observed in 9.1% of patients, and megakaryocytic dysplasia being the commonest(61.4%). Histiocytic aggregates (27.3%) were noted among which 6.8% showed acid fast bacilli in Ziehl-Neelsen stain. Fungal stains revealed histoplasmosis in 4.5% patients. Conclusion: There was a strong negative association between presence of anemia and dysplasia and CD4 count. When CD4 was <200/µL and ALC<1000/mm3, presence of anemia and dysplasia affecting various cell lines were commonly observed; therefore, can be used as indicators to assess the severity of the disease.

Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets

Cladribine tablets (CladT) preferentially reduce B and T lymphocyte levels. As aging is associated with a decline in immune function, the effect of CladT on lymphocyte levels may differ by age. This post hoc analysis combined data from the Phase 3 CLARITY, CLARITY Extension, and ORACLE-MS studies to examine the effect of age (≤50 or &gt;50 years) on lymphopenia following CladT 3.5 mg/kg (CladT3.5; cumulative dose over 2 years) treatment over 96 weeks. Both CladT3.5 and placebo were given over Weeks 1 and 5 (Year 1 treatment) and Weeks 48 and 52 (Year 2 treatment) from the start of the studies. Absolute lymphocyte count (ALC) and levels of lymphocyte subsets were examined in 1564 patients (Age ≤50 [placebo: N=566; CladT3.5: N=813]; Age &gt;50 [placebo: N=75; CladT3.5: N=110]). In both age groups, following CladT3.5 treatment, nadir for ALC occurred at Week 9 (8 weeks following start of Year 1 treatment) and Week 55 (7 weeks following start of Year 2 treatment) of the 96-week period; for CD19+ B lymphocytes, nadir occurred at Week 9 (Year 1) and Week 52 (Year 2). For CD4+ T lymphocytes, nadir occurred at Week 16 (Year 1) in both age groups, and at Weeks 60 and 72 (Year 2) in the Age ≤50 and &gt;50 groups, respectively. Nadir for CD8+ T lymphocytes occurred at Week 16 (Year 1) and Week 72 (Year 2) in the Age ≤50 group and levels remained in the normal range; nadir occurred at Week 9 (Year 1) and Week 96 (Year 2) in the Age &gt;50 group. Lymphocyte recovery began soon after nadir following CladT3.5 treatment and median levels reached normal range by end of the treatment year in both age groups. By Week 96, ~25% of patients treated with CladT3.5 reported ≥1 episode of Grade ≥3 lymphopenia (Gr≥3L). The rate of certain infections was numerically higher in older versus younger patients who experienced Gr≥3L. In conclusion, CladT3.5 had a similar effect on ALC and lymphocyte subsets in both younger and older patient groups.

Combined Blood Indexes of Systemic Inflammation as a Mirror to Admission to Intensive Care Unit in COVID-19 Patients: A Multicentric Study

Background The Coronavirus 2019 is a pandemic that has spread worldwide, threatening human health. The main cause of death in patients with COVID-19 is a systemic pro-inflammatory mechanism that quickly progresses to acute respiratory distress syndrome. Hematological ratios as affordable indicators of inflammatory response were studied in COVID-19 patients. The study aimed to study the importance of the blood cell indexes of the systemic inflammatory response, as the Aggregate Index of Systemic Inflammation (AISI), neutrophils lymphocyte to platelet ratio (NLPR), systemic immune-inflammation index (SII) and, systemic inflammation response index (SIRI) in predicting intensive care unit (ICU) admission of COVID-19 patients. Methods 495 COVID-19 patients managed in four tertiary centers; divided into non-ICU and ICU groups. Results Total leucocyte count (TLC), AISI, NLPR, SII, and SIRI were more elevated in the ICU group (P < 0.001 for all except AMC P = 0.006), while this group had less absolute lymphocyte count (ALC) (P = 0.047). We estimated the optimal cut-off values of the hematological ratio; AISI (729), NLPR (0.0195), SII (1346), and SIRI (2.5). SII had the highest specificity (95.6%), while NLPR had the highest sensitivity (61.3%). Age, AISI, CRP, D-dimer, and oxygen aid were the independent predictors for ICU admission in COVID-19 in multivariate logistic regression. Conclusion AISI is a predictor for severity and ICU admission in COVID-19 patients, SII is a predictor of survival, while NLPR and SIRI have an additive role that needs further evaluation.