A systematic review and meta-analysis of the relationship between T-lymphocytes and respiratory tract infection in children.

The objective of this paper was to investigate the relationship between T-lymphocytes and respiratory tract infection in children. A meta-analysis was performed of studies related to virus-infected respiratory illnesses in children, and the change in the ratio of their T-lymphocyte subsets CD4+/CD8+. A systematic literature review was performed using MEDLINE (through PubMed), CINAHL (via Ebsco), Scopus, and Web of Science, for studies describing change in T-lymphocyte levels in children suffering from acute respiratory illnesses. Studies were included as per the Population, Intervention, Comparison, Outcomes and Study (PICOS) criteria, and relevant event data were extracted. A risk of publication bias and a risk of bias assessment were performed, and a funnel plot was designed using RevMan software. A column histogram was designed to compare the adverse effects. A total of 12 studies from the years 2000-2022 were included in the meta-analysis, containing information about 1111 patients. The current meta-analysis has a low risk of publication bias with the Egger's test p-value being 0.583 (p > 0.05) and the Begg's test p-value being 0.772 (p > 0.05). The odds ratio (OR) value was 3.66 (95% confidence interval (95% CI): 1.08-12.43), the risk ratio (RR) value was 1.91 (95% CI: 1.07-3.40) and the significance level was p < 0.05, which indicates that an alteration in T-lymphocyte levels occurs in respiratory infections. T-lymphocyte levels are altered during infection, and the association between T-lymphocytes and respiratory diseases in children was investigated in this study. Based on statistically significant data (p < 0.05), we concluded that T-lymphocyte levels are adjusted in the event of viral respiratory sickness in children to alleviate the infection.

Association of Mortality with Lymphocyte Subset in Patients with COVID-19-associated Acute Respiratory Failure: A Subgroup Analysis.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes pneumonia and lymphopenia. We investigated the predictive value of T-lymphocyte subset absolute counts for outcomes following coronavirus disease-2019 (COVID-19)-associated acute respiratory failure (C-ARF). Patients and methods: A retrospective chart review of adult patients with C-ARF was undertaken from 23 March 2020 to 20 November 2021 to obtain relevant data. Patients were divided into two groups based on survival. The T-lymphocyte subsets were determined by flow cytometric analysis. A binomial logistic regression was performed to ascertain factors affecting survival. Cut-off values to differentiate between survivors and non-survivors were identified with the receiver operating characteristic (ROC) analysis. Results: A total of 379 patients were analyzed. Age was negatively correlated with survival. Non-survivors had significantly lower T-lymphocyte subset absolute counts than survivors. Serum ferritin levels were significantly higher in non-survivors. Baseline lymphocyte (%) and a subset were predictive of survival in patients [lymphocyte (%) <5.65%, CD3+ <321 cells/µL, CD4+ <205 cells/µL, CD8+ <103 cells/µL]. Conclusions: Lower T-lymphocyte subsets were associated with higher mortality in patients with C-ARF. Monitoring trends may help in identifying patients at increased risk of poor outcomes. How to cite this article: Vadi S, Pednekar A, Suthar D, Sanwalka N, Rabade N, Ghodke K. Association of Mortality with Lymphocyte Subset in Patients with COVID-19-associated Acute Respiratory Failure: A Subgroup Analysis. Indian J Crit Care Med 2023;27(1):52-56.

A systematic review and meta-analysis of the relationship between T-lymphocytes and respiratory tract infection in children

The objective of this paper was to investigate the relationship between T-lymphocytes and respiratory tract infection in children. A meta-analysis was performed of studies related to virus-infected respiratory illnesses in children, and the change in the ratio of their T-lymphocyte subsets CD4+/CD8+. A systematic literature review was performed using MEDLINE (through PubMed), CINAHL (via Ebsco), Scopus, and Web of Science, for studies describing change in T-lymphocyte levels in children suffering from acute respiratory illnesses. Studies were included as per the Population, Intervention, Comparison, Outcomes and Study (PICOS) criteria, and relevant event data were extracted. A risk of publication bias and a risk of bias assessment were performed, and a funnel plot was designed using RevMan software. A column histogram was designed to compare the adverse effects. A total of 12 studies from the years 2000-2022 were included in the meta-analysis, containing information about 1111 patients. The current meta-analysis has a low risk of publication bias with the Egger's test p-value being 0.583 (p > 0.05) and the Begg's test p-value being 0.772 (p > 0.05). The odds ratio (OR) value was 3.66 (95% confidence interval (95% CI): 1.08-12.43), the risk ratio (RR) value was 1.91 (95% CI: 1.07-3.40) and the significance level was p < 0.05, which indicates that an alteration in T-lymphocyte levels occurs in respiratory infections. T-lymphocyte levels are altered during infection, and the association between T-lymphocytes and respiratory diseases in children was investigated in this study. Based on statistically significant data (p < 0.05), we concluded that T-lymphocyte levels are adjusted in the event of viral respiratory sickness in children to alleviate the infection.

Characteristics and Predictive Value of T-lymphocyte Subset Absolute Counts in Patients with COVID-19-associated Acute Respiratory Failure: A Retrospective Study.

Background: Of the factors influencing severity and outcomes following coronavirus disease-2019 (COVID-19), cellular immune response has a strong impact. The spectrum of response varies from over-activation to hypo-functioning. The severe infection leads to reduction in numbers and dysfunction of T-lymphocytes/subsets. Patients and methods: This retrospective, single-center study aimed to analyze the expression of T-lymphocyte/subsets by flow cytometry and inflammation-related biomarker, serum ferritin in real-time polymerase chain reaction (RT-PCR) positive patients. According to oxygen requirements, patients were stratified into nonsevere (room air, nasal prongs, and face mask) and severe [nonrebreather mask (NRBM), noninvasive ventilation (NIV), high-flow nasal oxygen (HFNO), and invasive mechanical ventilation (IMV)] subgroups for analysis. Patients were classified into survivors and nonsurvivors. Mann-Whitney U test was used to analyze differences in T-lymphocyte and subset values when classified according to gender, the severity of COVID, outcome, and prevalence of diabetes mellitus (DM). Cross tabulations were computed for categorical data and compared using Fisher's exact test. Spearman correlation was used to analyze the correlation of T-lymphocyte and subset values with age or serum ferritin levels. p <0.05 values were considered to be statistically significant. Results: A total of 379 patients were analyzed. Significantly higher percentage of patients with DM were aged ≥61 years in both nonsevere and severe COVID groups. A significant negative correlation of CD3+, CD4+, and CD8+ was found with age. CD3+ and CD4+ absolute counts were significantly higher in females as compared to males. Patients with severe COVID had significantly lesser total lymphocyte (%), CD3+, CD4+, and CD8+ counts as compared to those with nonsevere COVID (p <0.05). T-lymphocyte subsets were reduced in patients with severe disease. A significant negative correlation of total lymphocyte (%), CD3+, CD4+, and CD8+ counts was found with serum ferritin levels. Conclusions: T-lymphocyte/subset trends are an independent risk factor for clinical prognosis. Monitoring may help in intervening in patients with disease progression. How to cite this article: Vadi S, Pednekar A, Suthar D, Sanwalka N, Ghodke K, Rabade N. Characteristics and Predictive Value of T-lymphocyte Subset Absolute Counts in Patients with COVID-19-associated Acute Respiratory Failure: A Retrospective Study. Indian J Crit Care Med 2022;26(11):1198-1203.

Evaluation the Role of CD4 and CD8 Reducing the Deterioration of COVID-19 Iraqi Patients

Since its start spreed "Severe acute respiratory syndrome coronavirus 2" was discovered in Wuhan, China.that is chargeable COVID-19, a pandemic virus, has end up a widespread fitness hassle everywhere in the global Over 2.1 million people have been affected. We analyze serum concentration of CD4 marker and CD8 marker depend in COVID-19 sufferers, and to make clear a relationship between these variables and disorder Progression and severity For those purpose, (158) sufferers with COVID-19 (showed with the aid of using polymerase chain reaction) and (22) seemingly wholesome human beings have been protected withinside the present day examine and taken into consideration as a manipulate group. All examine population (sufferers and manipulate) have been subjected to the assessment of serum awareness of CD4 marker and CD8 marker. COVID-19 sufferers displayed a huge elevation withinside the tiers of parameters protected on this examine while in comparison with wholesome controls. We additionally observed that concentration of CD4 and CD8 high in sever (CD4 5.68 +/- 0.16-CD8 961.74149.48 ) than critical (CD4 4.7610.14- CD8 880.19 +/- 52.03 )and moderate (CD43.83 +/- 0.09 - CD8 647.52 +/- 44.54) groups with high significant different (P <= 0.01(.

Different humoral but similar cellular responses of patients with autoimmune inflammatory rheumatic diseases under disease-modifying antirheumatic drugs after COVID-19 vaccination.

OBJECTIVES: The effect of different modes of immunosuppressive therapy in autoimmune inflammatory rheumatic diseases (AIRDs) remains unclear. We investigated the impact of immunosuppressive therapies on humoral and cellular responses after two-dose vaccination. METHODS: Patients with rheumatoid arthritis, axial spondyloarthritis or psoriatic arthritis treated with TNFi, IL-17i (biological disease-modifying antirheumatic drugs, b-DMARDs), Janus-kinase inhibitors (JAKi) (targeted synthetic, ts-DMARD) or methotrexate (MTX) (conventional synthetic DMARD, csDMARD) alone or in combination were included. Almost all patients received mRNA-based vaccine, four patients had a heterologous scheme. Neutralising capacity and levels of IgG against SARS-CoV-2 spike-protein were evaluated together with quantification of activation markers on T-cells and their production of key cytokines 4 weeks after first and second vaccination. RESULTS: 92 patients were included, median age 50 years, 50% female, 33.7% receiving TNFi, 26.1% IL-17i, 26.1% JAKi (all alone or in combination with MTX), 14.1% received MTX only. Although after first vaccination only 37.8% patients presented neutralising antibodies, the majority (94.5%) developed these after the second vaccination. Patients on IL17i developed the highest titres compared with the other modes of action. Co-administration of MTX led to lower, even if not significant, titres compared with b/tsDMARD monotherapy. Neutralising antibodies correlated well with IgG titres against SARS-CoV-2 spike-protein. T-cell immunity revealed similar frequencies of activated T-cells and cytokine profiles across therapies. CONCLUSIONS: Even after insufficient seroconversion for neutralising antibodies and IgG against SARS-CoV-2 spike-protein in patients with AIRDs on different medications, a second vaccination covered almost all patients regardless of DMARDs therapy, with better outcomes in those on IL-17i. However, no difference of bDMARD/tsDMARD or csDMARD therapy was found on the cellular immune response.

Reduced Counts of Various Subsets of Peripheral Blood T Lymphocytes in Patients with Severe Course of COVID-19.

This study was intended to define T lymphocyte subsets in different clinical groups of COVID-19-infected patients to explore the interaction between T cell-mediated immune response and the severity of COVID-19 course. Lymphopenia in patients with severe COVID-19 was found. In patients with severe COVID-19 course, the absolute counts of CD3+, CD4+, and CD8+ T lymphocytes at admission were lower than on day 14 after discharge. Further analysis showed that the older were the patients with COVID-19, the more likely they developed severe infection. The results confirmed the significance of T lymphocytes in the clearance of the COVID-19.

Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases.

BACKGROUND: Patients with immune-mediated rheumatic diseases (IMRDs) are commonly treated with immunosuppressors and prone to infections. Recently introduced mRNA SARS-CoV-2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-CoV-2 mRNA vaccines. AIMS: To fully characterise B-cell and T-cell immune responses elicited by mRNA SARS-CoV-2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine's immunogenicity. METHODS: Humoral, CD4 and CD8 immune responses were investigated in 100 naïve patients with SARS-CoV-2 with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-CoV-2 mRNA vaccine. Responses were compared with age, gender and disease-matched patients with IMRD not receiving immunosuppressors and with healthy controls. RESULTS: Patients with IMRD showed decreased seroconversion rates (80% vs 100%, p=0.03) and cellular immune responses (75% vs 100%, p=0.02). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept decreased humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed impaired humoral responses, but cellular responses were often preserved. Antibody titres were reduced with mycophenolate and azathioprine but preserved with leflunomide and anticytokines. CONCLUSIONS: Patients with IMRD exhibit impaired SARS-CoV-2 vaccine immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine's immunogenicity.

B cell depletion impairs vaccination-induced CD8+ T cell responses in a type I interferon-dependent manner.

OBJECTIVES: The monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses. METHODS: CD8+ T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens. RESULTS: Rituximab-treated RA patients vaccinated with Influvac showed reduced expansion of influenza-specific CD8+ T cells when compared with healthy controls. Moreover, B cell-deficient JHT mice infected with mouse-adapted Influenza or modified vaccinia virus Ankara showed less vigorous expansion of virus-specific CD8+ T cells than wild type mice. Of note, JHT mice do not have an intrinsic impairment of CD8+ T cell expansion, since infection with vaccinia virus induced similar T cell expansion in JHT and wild type mice. Direct type I interferon receptor signalling of B cells was necessary to induce several chemokines in B cells and to support T cell help by enhancing the expression of MHC-I. CONCLUSIONS: Depending on the stimulus, B cells can modulate CD8+ T cell responses. Thus, B cell depletion causes a deficiency of de novo antibody responses and affects the efficacy of cellular response including cytotoxic T cells. The choice of the appropriate vaccine to vaccinate B cell-depleted patients has to be re-evaluated in order to efficiently induce protective CD8+ T cell responses.

Pathophysiology of acute respiratory syndrome coronavirus 2 infection: a systematic literature review to inform EULAR points to consider.

BACKGROUND: The SARS-CoV-2 pandemic is a global health problem. Beside the specific pathogenic effect of SARS-CoV-2, incompletely understood deleterious and aberrant host immune responses play critical roles in severe disease. Our objective was to summarise the available information on the pathophysiology of COVID-19. METHODS: Two reviewers independently identified eligible studies according to the following PICO framework: P (population): patients with SARS-CoV-2 infection; I (intervention): any intervention/no intervention; C (comparator): any comparator; O (outcome) any clinical or serological outcome including but not limited to immune cell phenotype and function and serum cytokine concentration. RESULTS: Of the 55 496 records yielded, 84 articles were eligible for inclusion according to question-specific research criteria. Proinflammatory cytokine expression, including interleukin-6 (IL-6), was increased, especially in severe COVID-19, although not as high as other states with severe systemic inflammation. The myeloid and lymphoid compartments were differentially affected by SARS-CoV-2 infection depending on disease phenotype. Failure to maintain high interferon (IFN) levels was characteristic of severe forms of COVID-19 and could be related to loss-of-function mutations in the IFN pathway and/or the presence of anti-IFN antibodies. Antibody response to SARS-CoV-2 infection showed a high variability across individuals and disease spectrum. Multiparametric algorithms showed variable diagnostic performances in predicting survival, hospitalisation, disease progression or severity, and mortality. CONCLUSIONS: SARS-CoV-2 infection affects both humoral and cellular immunity depending on both disease severity and individual parameters. This systematic literature review informed the EULAR 'points to consider' on COVID-19 pathophysiology and immunomodulatory therapies.

GSK-3 Inhibition as a Therapeutic Approach Against SARs CoV2: Dual Benefit of Inhibiting Viral Replication While Potentiating the Immune Response.

The SARS-CoV2 (COVID-19) pandemic and uncertainties in developing a vaccine have created an urgent need for new therapeutic approaches. A key question is whether it is possible to make rational predictions of new therapies based on the presently available scientific and medical information. In this regard, I have noticed an omission in the present analysis in the literature related to the exploitation of glycogen synthase kinase 3 (GSK-3) as a therapeutic approach. This is based on two key observations, that GSK-3 inhibitors can simultaneously block SARs viral replication, while boosting CD8+ adaptive T-cell and innate natural killer (NK) responses. Firstly, it is already clear that GSK-3 phosphorylation of SARs CoV1 N protein on key serine residues is needed for viral replication such that small molecule inhibitors (SMIs) of GSK-3 can inhibit viral replication. In comparing protein sequences, I show here that the key sites in the N protein of SARs CoV1 N for replication are conserved in SARs CoV2. This strongly suggests that GSK-3 SMIs will also inhibit SARs Cov2 replication. Secondly, we and others have previously documented that GSK-3 SMIs markedly enhance CD8+ cytolytic T-cell (CTL) and NK cell anti-viral effector functions leading to a reduction in both acute and chronic viral infections in mice. My hypothesis is that the repurposing of low-cost inhibitors of GSK-3 such as lithium will limit SARS-CoV2 infections by both reducing viral replication and potentiating the immune response against the virus. To date, there has been no mention of this dual connection between GSK-3 and SARs CoV2 in the literature. To my knowledge, no other drugs exist with the potential to simultaneously target both viral replication and immune response against SARs CoV2.