Lymphocytes, Mean Platelet Volume, and Albumin in Critically Ill COVID-19 Patients with Venous Thromboembolism.

As one of the frequent complications leading to poor prognosis in hospitalized COVID-19 patients, a better understanding of venous thromboembolism (VTE) in COVID-19 patients is needed. We conducted a single-center, retrospective study on 96 COVID-19 patients admitted to the intensive care unit (ICU) from April to June 2022, in Shanghai Renji Hospital. Records of these COVID-19 patients upon admission were reviewed for demographic information, co-morbidities, vaccinations, treatment, and laboratory tests. VTE occurred in 11 (11.5%) cases among 96 COVID-19 patients despite the standard thromboprophylaxis since ICU admission. In COVID-VTE patients, a significant increase in B cells and a decrease in Ts cells were observed and a strong negative correlation (r = -0.9524, P = .0003) was found between these two populations. In COVID-19 patients with VTE, increased MPV and decreased albumin levels were seen in addition to the common VTE indicators of D-dimer abnormalities. The altered lymphocyte composition in COVID-VTE patients is noteworthy. In addition to D-dimer, MPV and albumin levels might be novel indicators for the risk of VTE in COVID-19 patients.

Adjuvant pomegranate juice intake improves the inflammatory status of hospitalized COVID-19 patients: A randomized and placebo-controlled trial.

BACKGROUND: This study aimed to evaluate the effect of pomegranate juice intake on the inflammatory status and complete blood count in hospitalized Covid-19 patients. METHODS: This randomized, double-blinded placebo-controlled trial included 48 patients with two parallel arms. In addition to the standard care provided at the hospital, the patients consumed 500 mL of whole pomegranate juice (PJ) daily or a placebo for 14 days. Inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR)) and complete blood count were determined at baseline and after the 14 days of intervention. RESULTS: At the end of the intervention, a significant decreased was observed in primary outcomes [mean difference (95 %CI)] including IL-6 [5.24(0.87-9.61)], CRP [23.19(11.93-34.44)] and ESR [10.52(1.54-19.50)] in the PJ group vs. before the intervention. In addition, significant changes were also observed in the some of the secondary outcomes, including neutrophils, lymphocytes, platelets, platelets-to-lymphocyte(PLR) and neutrophils-to-lymphocyte (NLR) ratios (p < 0.05) in the PJ group compared to before the intervention. At the end of the intervention period, the mean change of IL-6 [- 7.09(-12.21 to - 1.96)], white blood cells [- 3.09(- 6.14 to - 0.05)], neutrophils [- 9.12(-18.08 to -0.15)], lymphocyte [7.05(0.17-13.92)], platelets [- 94.54(- 139.33 to - 49.75)], PLR [- 15.99(- 29.31 to - 2.67)], blood oxygen saturation [1.75(0.13-3.37)] and MCV [0.31(- 0.25 to 0.88)] levels were significantly different between groups while no difference was observed between the two groups in other blood indices. CONCLUSION: Our results suggest that pomegranate juice intake might slightly improve the inflammatory status and CBC outcomes of COVID-19 patients and it may be beneficial.

Die Kämpfe únd schláchten-the struggles and battles of innate-like effector T lymphocytes with microbes.

The large majority of lymphocytes belong to the adaptive immune system, which are made up of B2 B cells and the αß T cells; these are the effectors in an adaptive immune response. A multitudinous group of lymphoid lineage cells does not fit the conventional lymphocyte paradigm; it is the unconventional lymphocytes. Unconventional lymphocytes-here called innate/innate-like lymphocytes, include those that express rearranged antigen receptor genes and those that do not. Even though the innate/innate-like lymphocytes express rearranged, adaptive antigen-specific receptors, they behave like innate immune cells, which allows them to integrate sensory signals from the innate immune system and relay that umwelt to downstream innate and adaptive effector responses. Here, we review natural killer T cells and mucosal-associated invariant T cells-two prototypic innate-like T lymphocytes, which sense their local environment and relay that umwelt to downstream innate and adaptive effector cells to actuate an appropriate host response that confers immunity to infectious agents.

Circulating extracellular particles from severe COVID-19 patients show altered profiling and innate lymphoid cell-modulating ability.

Introduction: Extracellular vesicles (EVs) and particles (EPs) represent reliable biomarkers for disease detection. Their role in the inflammatory microenvironment of severe COVID-19 patients is not well determined. Here, we characterized the immunophenotype, the lipidomic cargo and the functional activity of circulating EPs from severe COVID-19 patients (Co-19-EPs) and healthy controls (HC-EPs) correlating the data with the clinical parameters including the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) and the sequential organ failure assessment (SOFA) score. Methods: Peripheral blood (PB) was collected from COVID-19 patients (n=10) and HC (n=10). EPs were purified from platelet-poor plasma by size exclusion chromatography (SEC) and ultrafiltration. Plasma cytokines and EPs were characterized by multiplex bead-based assay. Quantitative lipidomic profiling of EPs was performed by liquid chromatography/mass spectrometry combined with quadrupole time-of-flight (LC/MS Q-TOF). Innate lymphoid cells (ILC) were characterized by flow cytometry after co-cultures with HC-EPs or Co-19-EPs. Results: We observed that EPs from severe COVID-19 patients: 1) display an altered surface signature as assessed by multiplex protein analysis; 2) are characterized by distinct lipidomic profiling; 3) show correlations between lipidomic profiling and disease aggressiveness scores; 4) fail to dampen type 2 innate lymphoid cells (ILC2) cytokine secretion. As a consequence, ILC2 from severe COVID-19 patients show a more activated phenotype due to the presence of Co-19-EPs. Discussion: In summary, these data highlight that abnormal circulating EPs promote ILC2-driven inflammatory signals in severe COVID-19 patients and support further exploration to unravel the role of EPs (and EVs) in COVID-19 pathogenesis.

Hematological characteristics of COVID-19 patients with fever infected by the Omicron variant in Shanghai: A retrospective cohort study in China.

BACKGROUND: A wave of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly spread in Shanghai, China. Hematological abnormalities have been reported in coronavirus disease 2019 (COVID-19) patients; however, the difference in hematological parameters between COVID-19 patients with fever and patients who are febrile from other causes remains unexplored. METHODS: This retrospective cohort study enrolled 663 SARS-CoV-2 positive patients identified by RT-PCR. Clinical parameters, including age, sex, and threshold cycle values of all COVID-19 patients, and hematological parameters of COVID-19 patients in the fever clinic were abstracted for analysis. RESULTS: Overall, 60.8% of COVID-19 patients were male, and the median age was 45 years. Most of COVID-19 patients were asymptomatic, while 25.8% of patients showed fever and 10.9% of patients had other emergencies. COVID-19 patients with fever had significantly lower white blood cells (WBCs), neutrophils, lymphocytes, platelets and C-reactive protein (CRP), and significantly higher monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and mean platelet volume-to-platelet ratio (MPR) levels, compared with those in SARS-CoV-2 negative patients with fever from other causes (p < 0.05). Neutrophil-to-lymphocyte ratio (NLR), PLR, and systemic inflammatory index (SII) levels were significantly higher in COVID-19 patients with emergencies (p < 0.05). WBCs showed the best performance with an area under the curve (0.756), followed by neutrophils (0.730) and lymphocytes (0.694) in the diagnosis of COVID-19 in the fever clinic. CONCLUSION: WBCs, neutrophils, lymphocytes, platelets, CRP and MLR, PLR, and MPR may be useful in early diagnosis of COVID-19 in the fever clinic.

Serial measurements of lymphocytes, D-dimer, LDH, and CRP do not improve the ability to predict COVID-19 adverse outcomes.

OBJECTIVE: We evaluated the discriminatory ability of variations in lymphocyte, D-dimer, C-reactive protein (CRP), and lactate dehydrogenase (LDH) serum levels at 48 to 72 hours of hospitalization compared with baseline measurements to predict unfavorable clinical outcomes in patients with COVID-19. METHODS: We analyzed diagnostic test results based on a retrospective cohort to determine the ability of variations (gradients or ratios) in patients' lymphocyte, D-dimer, CRP, and LDH serum levels taken 48 to 72 hours after hospital admission to predict adverse outcomes such as death, mechanical ventilation, or intensive care unit (ICU) admission developing. RESULTS: Among 810 patients (56.1% men, age 61.6 ± 16.2 years), 37.5% had at least one adverse outcome; 28.2% required ICU admission, 26.5% required mechanical ventilation, and 19.4% died during hospitalization. In comparing baseline measurements with measurements at 48 to 72 hours, D-dimer, lymphocyte delta, LDH, and CRP had similar discriminatory ability (area under the receiver operating characteristic curve [AUC] 0.57 vs. 0.56, 0.53 vs. 0.57, 0.64 vs. 0.66, and 0.62 vs. 0.65, respectively). CONCLUSIONS: Measuring serum risk markers upon hospital admission can be used to evaluate risk of adverse outcomes in hospitalized patients with COVID-19. Repeating these measurements at 48 to 72 hours does not improve discriminatory ability.

Fasting Plasma Glucose Increase and Neutrophil-to-Lymphocyte Ratio as Risk Predictors of Clinical Outcome of COVID-19 Pneumonia in Type 2 Diabetes Mellitus.

AIM OF THE STUDY: To evaluate fasting plasma glucose (FPG) increase and neutrophil-to-lymphocyte ratio (NLR) as risk predictors of severe clinical outcome of COVID-19 pneumonia in type 2 diabetes mellitus (T2DM) hospitalised patients. PATIENTS AND METHODS: Type 2 diabetes mellitus (T2DM) patients hospitalised between March 2020 and February 2021 were studied retrospectively. The NLR ratio at admission and FPG increase (day 7, day with maximal FPG) were evaluated in association with the clinical progression of SARS-CoV-2 infection. RESULTS: Three hundred patients (165 men, 135 women) were included in the study. The mean age was 67.17±8.65 years. Severe COVID-19 pneumonia was diagnosed in 170 patients (56.7%). Fifty-four patients (18%) were intubated and 49 (16.3%) died. Greater increase in FPG (79.5 vs. 44.5 mg/dL for day 1-7, p<0.001; and 113.5 vs. 75 mg/dL for day 1-day with maximum glucose value, p<0.001) and higher NLR at admission (10.65 vs. 6.85) were seen in patients with need of high-flow oxygen compared to those without need, and they were associated with a higher probability of intubation and death. CONCLUSION: FPG increase and NLR could be significant risk predictors of severe COVID-19 pneumonia in T2DM hospitalised patients.

A Cross-Sectional Comparative Characterization of Hematological Changes in Patients with COVID-19 Infection, Non-COVID Influenza-like Illnesses and Healthy Controls.

INTRODUCTION: Studies have documented the role of the "neutrophil-to-lymphocyte ratio" (NLR) in influenza virus infection. In addition, morphometric parameters derived from automated analyzers on the volume, scatter and conductivity of monocytes, neutrophils and lymphocytes in many viral etiologies have helped with their early differentiation. With this background, we aimed to characterize the hematological changes of coronavirus-positive cases and also compare them with the healthy controls and patients affected by non-COVID Influenza-like illnesses so that early isolation could be considered. MATERIAL AND METHODS: This was a cross-sectional analytical study carried out in the years 2020-2022. All cases with COVID-19 and non-COVID-19 Influenza-like illnesses and healthy controls above 18 years were included. Cases were diagnosed according to the WHO guidelines. All samples were processed on a Unicel DxH 800 (Beckman Coulter, California, USA) automated hematology analyzer. The demographic, clinical and regular hematological parameters along with additional parameters such as volume, conductivity and scatter (VCS) of the three groups were compared. RESULTS: The 169 COVID-19 cases were in the moderate to severe category. Compared with 140 healthy controls, the majority of the routine hematological values including the NLR (neutrophil-to-lymphocyte ratio) and PLR (platelet-to-lymphocyte ratio) showed statistically significant differences. A cutoff of an absolute neutrophil count of 4350 cell/cumm was found to have a sensitivity of 76% and specificity of 70% in differentiating moderate and severe COVID-19 cases from healthy controls. COVID-19 and the non-COVID-19 Influenza-like illnesses were similar statistically in all parameters except the PLR, mean neutrophilic and monocytic volume, scatter parameters in neutrophils, axial light loss in monocytes and NLR. Interestingly, there was a trend of higher mean volumes and scatter in neutrophils and monocytes in COVID-19 cases as compared to non-COVID-19 Influenza-like illnesses. CONCLUSION: We demonstrated morphological changes in neutrophils, monocytes and lymphocytes in COVID-19 infection and also non-COVID-19 Influenza-like illnesses with the help of VCS parameters. A cutoff for the absolute neutrophils count was able to differentiate COVID-19 infection requiring hospitalization from healthy controls and eosinopenia was a characteristic finding in cases with COVID-19 infection.

C-reactive protein to lymphocyte ratio is a significant predictive factor for poor short-term clinical outcomes of SARS-CoV-2 BA.2.2 patients.

Objective: The aim of the present study is to assess the utility of C-reactive protein to Lymphocyte Ratio (CLR) in predicting short-term clinical outcomes of patients infected by SARS-CoV-2 BA.2.2. Methods: This retrospective study was performed on 1,219 patients with laboratory-confirmed SARS-CoV-2 BA.2.2 to determine the association of CLR with short-term clinical outcomes. Independent Chi square test, Rank sum test, and binary logistic regression analysis were performed to calculate mean differences and adjusted odds ratios (aORs) with their 95% CI, respectively. Results: Over 8% of patients admitted due to SARS-CoV-2 BA.2.2. were critically ill. The best cut-off value of CLR was 21.25 in the ROC with a sensitivity of 72.3% and a specificity of 86%. After adjusting age, gender, and comorbidities, binary logistic regression analysis showed that elevated CLR was an independent risk factor for poor short-term clinical outcomes of COVID-19 patients. Conclusion: C-reactive protein to Lymphocyte Ratio is a significant predictive factor for poor short-term clinical outcomes of SARS-CoV-2 BA.2.2 inflicted patients.

Clinical relevance and therapeutic potential of IL-38 in immune and non-immune-related disorders

Interleukin-38 (IL-38) is the most recent member of the IL-1 family that acts as a natural inflammatory inhibitor by binding to cognate receptors, particularly the IL-36 receptor. In vitro, animal and human studies on autoimmune, metabolic, cardiovascular and allergic diseases, as well sepsis and respiratory viral infections, have shown that IL-38 exerts an anti-inflammatory activity by modulating the generation and function of inflammatory cytokines (e.g. IL-6, IL-8, IL-17 and IL-36) and regulating dendritic cells, M2 macrophages and regulatory T cells (Tregs). Accordingly, IL-38 may possess therapeutic potential for these types of diseases. IL-38 down-regulates CCR3+ eosinophil cells, CRTH2+ Th2 cells, Th17 cells, and innate lymphoid type 2 cells (ILC2), but up-regulates Tregs, and this has influenced the design of immunotherapeutic strategies based on regulatory cells/cytokines for allergic asthma in future studies. In auto-inflammatory diseases, IL-38 alleviates skin inflammation by regulating γδ T cells and limiting the production of IL-17. Due to its ability to suppress IL-1ß, IL-6 and IL-36, this cytokine could reduce COVID-19 severity, and might be employed as a therapeutic tool. IL-38 may also influence host immunity and/or the components of the cancer microenvironment, and has been shown to improve the outcome of colorectal cancer, and may participate in tumour progression in lung cancer possibly by modulating CD8 tumour infiltrating T cells and PD-L1 expression. In this review, we first briefly present the biological and immunological functions of IL-38, and then discuss the important roles of IL-38 in various types of diseases, and finally highlight its use in therapeutic strategies.

sCXCL16 as a prognostic biomarker for COVID-19 outcome.

As elevated levels of the soluble CXCL16 (sCXCL16) chemokine have been reported in severe coronavirus disease 2019 (COVID-19) patients, this study examined whether sCXCL16 concentration on the first day of hospitalization predicted death in COVID-19 patients. A total of 76 patients with COVID-19 were admitted to the Military Hospital of Tunis, Tunisia, between October 2020 and April 2021, and later classified as survivors or nonsurvivors based on their outcomes. At admission, the groups were matched by age, gender, comorbidities, and the percentage of patients with moderate conditions. On the first day of admission, serum's sCXCL16 concentrations were measured using a magnetic-bead assay. There was an eightfold increase in serum sCXCL16 levels in the nonsurvivors' group (3661.51 ± 2464.87 pg/mL vs. 454.3 ± 338.07 pg/mL, p < 0.0001). For the optimal cutoff value of sCXCL16 at 2095 pg/mL, we found a 94.6% sensitivity and a 97.4% specificity, with an area under curve of 0.981 (p = 5.03E-08; 95% confidence interval [95% CI]: 0.951-1.0114). Considering the risk of death at a concentration above the threshold, the unadjusted odds ratio was 36 (p < 0.0001). The adjusted odd ratio was estimated at 1.003 (p < 0.0001; 95% CI: 1.002-1.004). Finally, there was a significant difference between survival and nonsurvival groups in leukocyte numbers (p = 0.006), lymphocytes (p = 0.001), polymorphonuclear neutrophils (p = 0.001), and C-reactive protein levels (p = 0.007), except for monocytes (p = 0.881). Based on these results, sCXCL16 level could be used for detecting nonsurvival COVID-19 patients. Therefore, we recommend assessing this marker in hospitalized COVID-19 patients.

How to diagnose COVID-19 in family practice? Usability of complete blood count as a COVID-19 diagnostic tool: a cross-sectional study in Turkey.

OBJECTIVE: COVID-19 is currently diagnosed in hospital settings. An easy and practical diagnosis of COVID-19 is needed in primary care. For this purpose, the usability of complete blood count in the diagnosis of COVID-19 was investigated. DESIGN: Retrospective, cross-sectional study. SETTING: Single-centre study in a tertiary university hospital in Erzurum, Turkey. PARTICIPANTS: Between March 2020 and February 2021, patients aged 18-70 years who applied to the hospital and underwent both complete blood count and reverse-transcription-PCR tests for COVID-19 were included and compared. Conditions affecting the test parameters (oncological-haematological conditions, chronic diseases, drug usage) were excluded. OUTCOME MEASURE: The complete blood count and COVID-19 results of eligible patients identified using diagnostic codes [U07.3 (COVID-19) or Z03.8 (observation for other suspected diseases and conditions)] were investigated. RESULTS: Of the 978 patients included, 39.4% (n=385) were positive for COVID-19 and 60.6% (n=593) were negative. The mean age was 41.5±14.5 years, and 53.9% (n=527) were male. COVID-19-positive patients were found to have significantly lower leucocyte, neutrophil, lymphocyte, monocyte, basophil, platelet and immature granulocyte (IG) values (p<0.001). Neutrophil/lymphocyte, neutrophil/monocyte and IG/lymphocyte ratios were also found to be significantly decreased (p<0.001). With logistic regression analysis, low lymphocyte count (OR 0.695; 95% CI 0.597 to 0.809) and low red cell distribution width-coefficient of variation (RDW-CV) (OR 0.887; 95% CI 0.818 to 0.962) were significantly associated with COVID-19 positivity. In receiver operating characteristic analysis, the cut-off values of lymphocyte and RDW-CV were 0.745 and 12.35, respectively. CONCLUSION: Although our study was designed retrospectively and reflects regional data, it is important to determine that low lymphocyte count and RDW-CV can be used in the diagnosis of COVID-19 in primary care.

Platelet-albumin-bilirubin score and neutrophil-to-lymphocyte ratio predict intensive care unit admission in patients with end-stage kidney disease infected with the Omicron variant of COVID-19: a single-center prospective cohort study.

OBJECTIVES: The objective of this study was to develop clinical scores to predict the risk of intensive care unit (ICU) admission in patients with COVID-19 and end stage kidney disease (ESKD). METHODS: This was a prospective study in which 100 patients with ESKD were enrolled and divided into two groups: the ICU group and the non-ICU group. We utilized univariate logistic regression and nonparametric statistics to analyze the clinical characteristics and liver function changes of both groups. By plotting receiver operating characteristic curves, we identified clinical scores that could predict the risk of ICU admission. RESULTS: Out of the 100 patients with Omicron infection, 12 patients were transferred to the ICU due to disease aggravation, with an average of 9.08 days from hospitalization to ICU transfer. Patients transferred to the ICU more commonly experienced shortness of breath, orthopnea, and gastrointestinal bleeding. The peak liver function and changes from baseline in the ICU group were significantly higher, with p values <.05. We found that the baseline platelet-albumin-bilirubin score (PALBI) and neutrophil-to-lymphocyte ratio (NLR) were good predictors of ICU admission risk, with area under curve values of 0.713 and 0.770, respectively. These scores were comparable to the classic Acute Physiology and Chronic Health Evaluation II (APACHE-II) score (p > .05). CONCLUSION: Patients with ESKD and Omicron infection who are transferred to the ICU are more likely to have abnormal liver function. The baseline PALBI and NLR scores can better predict the risk of clinical deterioration and early transfer to the ICU for treatment.

Complete blood count derived inflammation indexes predict outcome in COVID-19 patients: a study in Indonesia.

INTRODUCTION: Inflammation plays a vital role in the pathophysiology of COVID-19. Complete blood count (CBC) is a routine test performed on patients. It provides information regarding the inflammatory process and can be used as a predictor of outcome. This study aimed to explore the correlation between different complete blood count (CBC)-derived inflammation indexes at hospital admission, such as neutrophil to lymphocyte ratio (NLR), derived NLR (dNLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte × platelet ratio (NLPR), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII), to in-hospital mortality in confirmed COVID-19 patients. METHODOLOGY: A retrospective observational study was performed at Ulin Referral Hospital of South Kalimantan with 445 COVID-19 patients from April to November 2020. The patients were divided into two groups, non-survivor and survivor. A receiver operating characteristic (ROC) curve was used to determine the cut-off values. Bivariate analysis was performed using the Chi Square test, the risk ratio was calculated, and logistics regression was determined. RESULTS: Increase of NLR, dNLR, PLR, MLR, NLPR, MLR, AISI, SIRI, and SII from cut-off values were significantly correlated with patient survival outcome. The cut off values were 6.90, 4.10, 295, 0.42, 0.037, 1,422, 1.80, and 2,504 respectively. NLPR was dominant in predicting in-hospital mortality (OR: 6.668, p = 0.000) with a 28.1% sensitivity and 95.9% specificity. CONCLUSIONS: CBC-derived inflammation indexes were associated with the survival outcome of confirmed COVID-19 patients and NLPR was a dominant variable.

Changes in PD-1- and CTLA-4-bearing blood lymphocytes in ICU COVID-19 patients treated with Favipiravir/Kaletra or Dexamethasone/Remdesivir: a pilot study.

COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.e., severe) or infection ward (i.e., moderate) and after 7 days of antiviral therapy. COVID-19 patients were treated with either favipiravir or Kaletra (FK group, 11 severe and 11 moderate) or dexamethasone plus remdesivir (DR group, 7 severe and 10 moderate) for 7 days in a pilot study. Eight healthy control subjects were also enrolled. The frequency of PD-1+ and CTLA-4+ lymphocytes in whole blood was evaluated by flow cytometry. Patients on DR therapy had shorter hospital stays than those on FK therapy. The frequency of PD-1+ lymphocytes in the FK group at baseline differed between COVID-19 patients and healthy controls, while the frequency of both PD-1+ and CTLA-4+ cells increased significantly 7 days of FK therapy. The response was similar in both moderate and severe patients. In contrast, the frequency of PD-1+ and CTLA-4+ lymphocytes varied significantly between patients and healthy controls before DR treatment. DR therapy enhanced PD-1+ but not the CTLA-4+ frequency of these cells after 7 days. We show that the frequency of PD-1 and CTAL-4-bearing lymphocytes during hospitalization was increased in Iranian ICU COVID-19 patients who received FK treatment, but that the frequency of CTLA-4+ cells was higher at baseline and did not increase in patients who received DR. The effectiveness of DR treatment may reflect differences in T-cell activation or exhaustion status, particularly in CTLA-4-expressing cells.

Thymosin alpha 1 restores the immune homeostasis in lymphocytes during Post-Acute sequelae of SARS-CoV-2 infection.

The complex alterations of the immune system and the immune-mediated multiorgan injury plays a key role in host response to SARS-CoV-2 infection and in the pathogenesis of COVID-19, being also associated with adverse outcomes. Thymosin alpha 1 (Tα1) is one of the molecules used in the treatment of COVID-19, as it is known to restore the homeostasis of the immune system during infections and cancer. The use of Tα1 in COVID-19 patients had been widely used in China and in COVID-19 patients, it has been shown to decrease hospitalization rate, especially in those with greater disease severity, and reduce mortality by restoring lymphocytopenia and more specifically, depleted T cells. Persistent dysregulation with depletion of naive B and T cell subpopulations and expansion of memory T cells suggest a chronic stimulation of the immune response in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Our data obtained from an ex vivo study, showed that in PASC individuals with a chronically altered immune response, Tα1 improve the restoration of an appropriate response, most evident in those with more severe illness and who need respiratory support during acute phase, and in those with specific systemic and psychiatric symptoms of PASC, confirming Tα1 treatment being more effective in compromised patients. The results obtained, along with promising reports on recent trials on Tα1 administration in patients with COVID-19, offer new insights into intervention also for those patients with long-lasting inflammation with post-infectious symptoms, some of which have a delayed onset.

A retrospective study of age-defined hematologic inflammatory markers related to pediatric COVID-19 diagnosis.

BACKGROUND: The aim of this study was to examine age-related differences in hemogram parameters and hematologic inflammatory markers in pediatric patients with COVID-19. METHODS: This retrospective study included children aged 2 months to 18 years (n = 208) who have a confirmed diagnosis of COVID-19 and a control group comprising 117 healthy children between February 2021 and July 2021. The analysis of subgroup hematological values were performed according to the children's age cutoffs. RESULTS: The most significant difference between pediatric patients with COVID-19 and controls were peripheral blood eosinophil counts and eosinophil-to-monocyte ratio (EMR) levels on admission. The levels of monocyte-to-lymphocyte ratio, aggeregate index of systemic inflammation (neutrophil × platelet × monocyte/lymphocyte), neutrophil-to- lymphocyte × platelet ratio, and systemic inflammation response index (neutrophil × monocyte/ lymphocyte) were higher in patients than in controls. EMR had the highest area under the curve (AUC) value of 0.777, with a cutoff value of 0.26. The sensitivity for EMR was 75% under 2 years of age, and between 78.6-87.5% in the other age groups. CONCLUSION: In children younger than 6 months, the discriminative power of hematological indices is low, while the discriminative power of EMR is high at all ages when age appropriate cutoffs are used. Hematological inflammatory parameters may be particularly practical in pediatric clinics to help identify COVID-19 infection.