Prognostic role of simple inflammatory biomarkers in patients with severe COVID-19: an observational study.

BACKGROUND/AIM: Simple inflammatory biomarkers, such as neutrophil to lymphocyte ratio (NLR), could serve as prognosis indicators in patients with Coronavirus disease 2019 (COVID-19). The utility of on-admission inflammatory biomarkers in predicting outcomes was investigated in patients suffering from severe COVID-19 infection. METHODS: We performed a retrospective study to assess the role of white blood count (WBC), neutrophils (N), lymphocyte (L), platelets (PLTs), C-reactive protein (CRP), reverse transcription polymerase chain reaction (RT-PCR), NLR (N/L), PLR (P/L), dv (derived variation of)-NLR (N/WBC-L), LNR (L/N), dv (derived variation of)-LNR (L/WBC-N), and CLR (CRP/L), in predicting the need for high-flow nasal cannula (HFNC) use, admission to Intensive Care Unit (ICU), and death in adult patients with severe COVID-19 admitted to the Department of Respiratory Medicine from April to September 2021. RESULTS: One hundred and fifteen patients (60 % males) with a mean age of 57.7 ± 16.3 years were included. Thirty-seven patients (32.2 %) required escalation with HFNC, eight patients (7 %) were admitted to the ICU, and nine patients (7.8%) died. Based on univariate analysis, CRP [odds ratio (OR): 1.25, 95 % confidence interval (CI): 1.1-1.42), LNR (OR: 0.015, 95 % CI: 0.00-0.35), dv-NLR (OR: 5*106, 95 % CI: 26.7-9*109), CLR (OR: 7*1058, 95 % CI: 3*1025-2*1092), length of hospitalization (LOH; OR: 1.44, 95 % CI: 1.22-1.63), dyspnea at presentation (OR: 2.83, 95 % CI: 1.23-6.52), and ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) on admission (OR: 0.967, 95 % CI: 0.952-0.983) were independent predictors for oxygen requirements. However, the multivariate analysis showed that LNR (OR: 1.686e0-4, 95 % CI: 6.441e00-8-0.441), PaO2/FiO2 on admission (OR: 0.965, 95 % CI: 0.941-0.989), and LOH (OR: 1.717, 95 % CI: 1.274-2.314) were the most important predictor for HFNC use. Nasal congestion at presentation (OR: 11.5, 95 % CI: 1.61-82.8) was a unique and independent predictor for ICU admission. As far as death is concerned, the univariate analysis identified elevated CRP (OR: 1.11, 95 % CI: 1.0-1.24), low RT-PCR (OR: 0.829, 95 % CI: 0.688-0.999), high CLR (OR: 3.2*1033, 95 % CI: 5.8-1.8*1066), age (OR: 1.08, 95 % CI: 1.02-1.14), body mass index (BMI) over 30 (OR: 5.25, 95 % CI: 1.26-21.96), the chronic use of angiotensin-converting enzyme inhibitors (OR: 5.72, 95 % CI: 1.35-24.09), nitrates (OR: 14.85, 95 % CI: 1.81-121.8), diuretics (OR: 8.21, 95 % CI: 1.97-34.32), PaO2/FiO2 on admission (OR: 0.983, 95 % CI: 0.970-0.998), and nasal congestion at presentation (OR: 9.81, 95 % CI: 1.40-68.68) as independent predictors. However, the multivariate analysis pinpointed that obesity (BMI >30) (OR: 10.498, 95 % CI: 1.107-99.572) remained the most important predictor for death. CONCLUSION: LNR and PaO2/FiO2 on admission could be used to timely identify patients requiring HFNC during hospitalization, while obesity (BMI >30) could be an independent predictor of death. Nasal congestion emerges as a unique predictor for ICU admission. HIPPOKRATIA 2022, 26 (2):70-77.

The characteristics and predictive role of lymphocyte subsets in COVID-19 patients.

OBJECTIVE: To investigate the characteristics and predictive roles of lymphocyte subsets in COVID-19 patients. METHOD: We evaluated lymphocyte subsets and other clinical features of COVID-19 patients, and analyzed their potential impacts on COVID-19 outcomes. RESULTS: 1. Lymphocyte subset counts in the peripheral blood of patients with COVID-19 were significantly reduced, especially in patients with severe disease. 2. In patients with non-severe disease, the time from symptom onset to hospital admission was positively correlated with total T cell counts. 3. Among COVID-19 patients who did not reach the composite endpoint, lymphocyte subset counts were higher than in patients who had reached the composite endpoint. 4. The Kaplan-Meier survival curves showed significant differences in COVID-19 patients, classified by the levels of total, CD8+, and CD4+ T cells at admission. CONCLUSION: Our study showed that total, CD8+, and CD4+ T cell counts in patients with COVID-19 were significantly reduced, especially in patients with severe disease. Lower T lymphocyte subsets were significantly associated with a higher occurrence of composite endpoint events. These subsets may help identify patients with a high risk of composite endpoint events.

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.

The Role of Lymphocyte Subsets, PD-1, and FAS (CD95) in COVID-19 Cancer Patients.

Lymphocytes are the main orchestrators that regulate the immune response in SARS-COV-2 infection. The exhaustion of T lymphocytes is a contributing factor to lymphopenia, which is responsible for the COVID-19 adverse outcome. However, it is still not demonstrated on a large scale, including cancer patients. Peripheral blood samples were obtained from 83 SARS-CoV2 infected cancer patients, and 29 COVID-19 infected noncancer patients compared to 28 age-matched healthy controls. Lymphocyte subsets were assessed for CD3, CD4, CD8, CD56, PD-1, and CD95 using flow cytometry. The data were correlated to the patients' clinical features, COVID-19 severity and outcomes. Lymphopenia, and decreased CD4+ T cells and CD8+ T cells were significantly observed in COVID-19 cancer and noncancer patients compared to the control group (p < 0.001, for all). There was a significantly increased expression of CD95 and PD-1 on the NK cells, CD4+ T cells, and CD8+ T cells in COVID-19 cancer and noncancer patients in comparison to the control group. The increased expression of CD95 on CD8+ T cells, as well as the increased expression of PD-1 on CD8+ T cells and NK cells are significantly associated with the severity of COVID-19 infection in cancer patients. The increased expression of CD95 and PD-1 on the CD4+ T cells, CD8+ T cells, and NK cells was observed significantly in nonsurviving patients and those who were admitted to the intensive care unit in COVID-19 cancer and noncancer patients. The increased expression of PD-1 and CD95 could be possible prognostic factors for COVID-19 severity and adverse outcomes in COVID-19 cancer and noncancer patients.

Evaluation of peripheral lymphocyte subsets' alteration and IL6 serum level correlated with severity and outcome in corona virus disease 2019 (COVID-19)

Background: Coronavirus disease 2019 (COVID-19) has rapid spread worldwide and its pathogenesis is still not well understood. It's critical to identify the key immune inflammatory markers that may be correlated with COVID-19 severity. Objective: This study aimed to study the association of the peripheral lymphocyte subsets' alteration and IL-6 serum level with disease severity and outcome in COVID-19. Methodology: Samples from 30 COVID-19 patients were collected;one is EDTA anticoagulated for flowcytometric analysis of different lymphocyte subsets and the other for Interleukin-6 (IL6) serum level assessed by ELISA technique. Results: Absolute lymphocytic count (0.9 (0.5-1.4)× 103/µL), CD4+ T cells (217 (135.6-445.5) cells/µL), CD8+ T cells (160 (112-338) cells/µL) and natural killer (NK) cells (33.3 (18.2-99.5) cells/µL) were significantly reduced in severe COVID-19 patients with significantly elevated IL-6 serum levels 90 (70-120) (pg/mL) in severe patients. Lower T lymphocytes and NK subset counts with higher IL-6 levels were significantly associated with higher mortality. However, B cell count was not associated with severity or mortality. Il-6 levels, CD4+ and CD8+ T cells counts were considered best predictors of disease severity and mortality according to ROC curve analysis (with AUC 0.842, 0.884 and 0.773 respectively). Conclusion: Peripheral lymphocyte subsets as CD4+ T cells, CD8+ T cells and NK cells were significantly reduced in severe COVID-19 patients. CD4+ T cell count was the most significant biomarker for disease severity.Serum IL-6 levels were higher in severe illness. So, IL-6 can serve as a significant predictor of COVID-19 severity. As regard mortality and relation with lymphocytic count and lymphocytic subsets, total lymphocytic count and all T lymphocyte subsets CD4+, CD8+ and CD56+ cells count can be used as a significant predictor of death in COVID-19 patients. However, CD19+ cells counts had no relation with death. © 2020 The author (s). Published by Zagazig University.

Age at SARS-CoV-2 infection and psychological and physical recovery among Chinese health care workers with severe COVID-19 at 28 months after discharge: A cohort study.

Background: No prior study had reported the psychological and physical recovery of patients with COVID-19 2~3 years after discharge from the hospital. Moreover, it is not clear whether there is any difference in the health status of the patients with COVID-19 of different ages after discharge from the hospital. Methods: Embedding in the "Rehabilitation Care Project for Medical Staff Infected with COVID-19" in China, this study included 271 health care workers (HCWs) with severe COVID-19. Their status of health-related quality of life, persistent symptoms, functional fitness and immune function at 28 months after discharge were followed, and compared according to tertiles of age at SARS-CoV-2 infection (group of younger (≤ 33 years); medium (34-42 years); and older (≥43 years)). Multivariate linear regression and multivariable adjusted logistic regression models were applied in investigating the associations of age at SARS-CoV-2 infection and outcomes. Results: At 28 months after discharge, 76% of the HCWs with severe COVID-19 had symptom of fatigue/weakness; 18.7% of the HCWs with severe COVID-19 did not fully recover their functional fitness; the decrease of CD3+ T cells, CD8+ T cells and the increase of natural killer cells accounted for 6.6, 6.6, and 5.5%, respectively. Compared with the HCWs with severe COVID-19 in younger group, HCWs with severe COVID-19 in older group had lower scores regarding physical functioning, role physical, bodily pain and role emotional; HCWs with severe COVID-19 in older group had higher risk of cough, joint pain, hearing loss and sleep disorder; HCWs with severe COVID-19 in older group scored lower on flexibility test. The variance of relative numbers of CD3+ T cells, CD8+ T cells and natural killer cells among HCWs with severe COVID-19 of different age groups were significant. Conclusions: This study demonstrated that older HCWs with severe COVID-19 recovered slower than those with younger age regarding health-related quality of life, persistent symptoms, functional fitness and immune function at 28 months after discharge. Effective exercise interventions regarding flexibility should be performed timely to speed their rehabilitation, especially among those with older age.

Lymphopenia with Altered T Cell Subsets in Hospitalized COVID-19 Patients in Pune, India.

The cellular immune cell subsets affecting COVID-19 disease severity are being studied by researchers from many countries. The current study was carried out to investigate the alteration of peripheral blood mononuclear cells (PBMCs) and their subsets in hospitalized COVID-19 patients in a tertiary care center in Pune, India. The PBMCs were isolated from enrolled study participants, and flow cytometry analysis was done to assess peripheral white blood cell alterations. The lymphocyte subsets of naive, effector, central memory, and effector memory CD4+ or CD8+ T cells were then evaluated in COVID-19 patients with different disease categories and compared to healthy controls. The immunophenotypic characterization of the immune cell subset was done for 139 COVID-19 patients and 21 healthy controls. These data were evaluated based on the disease severity. A total of 139 COVID-19 patients were classified as mild (n = 30), moderate (n = 57), or severe (n = 52) cases. The decreased percentages of total lymphocytes, CD3+ T cells, CD4+ T cells, naive T cells, central memory T cells, and Natural Killer (NK) cytotoxic cells were found, and there was increase in effector T (TEf) cells and effector memory T cells in patients with severe COVID-19 compared to healthy controls. The severity of SARS-CoV-2 infection has an effect on lymphocyte subsets, resulting in reduced T memory cells and NK cells but increased TEf cells in severe cases. Clinical Trial Registration: CTRI ID-CTRI/2021/03/032028.

Immune response to BNT162b2 SARS-CoV-2 vaccine in patients living with HIV: The COVIH-DAPT study.

Introduction: Data on immune response to SARS-CoV-2 vaccine in patients living with HIV (PLWH) over a period longer than 3 months are currently limited. We measured the immune response after BNT162b2 vaccination against SARS-CoV-2 in this population. Methods: We prospectively enrolled PLWH on successful antiretroviral therapy, initiating vaccination with two doses of the BNT162b2 SARS-CoV-2 vaccine administered at six-week interval. SARS-CoV-2 humoral and cellular responses and lymphocyte cell subsets were recorded at inclusion and 6 weeks (W6), 3 months (M3) and 6 months (M6) later. Humoral, humoral strong and cellular responders were defined by IgG titers >10, ≥264BAU/mL and IFN-γ T cell release, respectively. Results: Nineteen subjects without SARS-CoV-2 infection were included (74% men, mean age 51 years, CD4 nadir 399/mm3). All subjects were humoral responders, their antibody titer peak reached at M3. Strong responders' rates were 63% and 21% at M3 and M6, respectively. CD19+CD10+ B cells had increased significantly at W6 then decreased at M3, while CD19+CD27+ B cells remained unchanged. Rates of patients with a cellular response increased from 39% at W6 to 69% at M6. Cellular responders had significantly higher CD3+, CD4+ and CD8+ Effector Memory cells at inclusion (p=0.048, p=0.024, p=0.012, respectively) and CD4+ Terminally Differentiated Effector Memory cells at M3 (p=0.044). Discussion: PLWH have a robust immune response after SARS-CoV-2 vaccination, but a rapid decline in humoral response from 3 months onwards, due to a blunted memory B cell response. Analysis of lymphocyte subsets may help identify optimal times for vaccine boosters.

Immune Response to SARS-CoV-2 Infections in Children with Secondary Immunodeficiencies.

BACKGROUND AND PURPOSE: It is a matter of research, whether children with immunodeficiencies are able to generate an effective immune response to prevent SARS-CoV-2 reinfection. This study aimed to evaluate and compare the seroconversion rates and changes of lymphocyte subsets during COVID-19 in immunocompetent children and those with secondary immunodeficiencies. METHODS: In 55 children - 28 immunocompromised and 27 immunocompetent - hospitalized with confirmed SARS-CoV-2 infection, the level of IgG antibodies against the Spike protein was determined on two to three occasions. In those children from the study group whose immunosuppressive treatment did not alter during the study (n = 13) and in selected children from the control group (n = 11), flow cytometric evaluation of lymphocyte subsets was performed twice - 2 weeks and 3 months post-infection. RESULTS: Seroconversion reached 96.3% in both studied groups; however, the immunocompromised cohort achieved lower titers of detectable anti-S antibodies. There was no correlation between seroconversion or titers of antibodies and the total number of lymphocytes or their subsets. In the immunocompetent cohort, we reported a significant decrease in NK cells during the infection. In this group and the entire study population, a positive correlation was noticed between the CD4 + /CD8 + T cell ratio and the severity of COVID-19 pneumonia. CONCLUSIONS: Children with secondary immunodeficiencies seroconvert in equal percentages but with a significantly lower titer of anti-S antibodies compared to their immunocompetent peers. The lower number of NK cells in the immunocompetent cohort may result from their participation in antiviral immunity, whereas reduced CD4 + /CD8 + T cell ratios among immunocompromised children may be a protective factor against a severe COVID-19.

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.

Thrombosis and lymphocyte subsets of COVID-19 omicron BA.2 variant patients with cancer.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused an ongoing global pandemic of COVID-19. It has been found that COVID-19 has an influence on the changes of blood coagulation parameters and the high incidence of thrombosis. Changchun experienced the epidemic of the Omicron BA.2 variant SARS-CoV-2 in March 2022 in China. Once infected, BA.2 spreads rapidly and most of them are asymptomatic. The purpose of this study is to research venous thrombosis and laboratory changes (including PLT, PT, APTT, DD, FDP, CRP, WBC, IL-6 and lymphocyte subsets) among 92 cancer patients with COVID-19 and 73 COVID-19 patients with non-cancer by Mann-Whitney U and Chi-square test. It was found that the levels of D-dimer, FDP, CRP and IL-6 in cancer patients were significantly higher than those in the COVID-19 cohort. There were 9 (9.8%) cancer patients and 2 (2.7%) non-cancer patients found VTE, with no significant difference. The results showed that WBC, lymphocytes and B cells in cancer patients were significantly lower than those in the other group. Prophylactic anticoagulation was recommended for cancer patients with high risk factors, while paying attention to the occurrence of bleeding events. The detection of leukocyte classification, D-dimer, prothrombin time and fibrinogen at different time points are helpful for the diagnosis and anticoagulation of COVID-19 patients with cancer.

High Number and Specific Comorbidities Could Impact the Immune Response in COVID-19 Patients.

Background: Cellular immunodeficiency and comorbidities are common in COVID-19 patients. Aim: The purpose of this study was to investigate comorbidities impacting on the cellular immunity in COVID-19 patients. Methods: The research objects included 55 healthy controls and 718 COVID-19 patients who divided into the control group and the COVID-19 group, respectively. Those in the COVID-19 group were divided into subgroups on the basis of the number and types of comorbidities present. Lymphocyte itself and its subsets were compared between the control group and the COVID-19 group, the groups with comorbidities based on the different number and types of comorbidities, and the relationship between the lymphocyte counts and subsets with the number and types of comorbidities was investigated. Results: Compared with the control group, the lymphocyte counts and T cell subsets were significantly increased in the groups with comorbidities, but both B and NK cell subsets were significantly decreased in the no comorbidity group and in most of the groups with comorbidities (all P<0.05). In the three comorbidities group, the lymphocyte counts and T cell subsets were all significantly decreased, but the CD56+ percentage was obviously increased (all P<0.05). The number of comorbidities was negatively correlated with the lymphocyte counts and the T and NK cell subsets. A negative correlation also existed between cancer and both the lymphocyte counts and the T cell subsets, between chronic hepatitis B and the lymphocyte counts, and between chronic kidney disease and the CD3+ counts. A positive correlation existed between nonalcoholic fatty liver disease (NAFLD) disease and both lymphocyte and CD3+ counts. The risk factors were number of comorbidities for the lymphocyte count, CD3+CD4+ and CD3+CD8+ percentages, NAFLD for the lymphocyte and CD3+ counts, cardiovascular diseases for CD3+CD4+ and CD3+CD8+ percentages, diabetes mellitus for the CD3+CD8+ percentage, and cancer for the CD3+ percentage, respectively. Conclusions: High numbers of comorbidities and specific comorbidities could impact the immune response of COVID-19 patients. This study provides a reference for clinicians in the identification of suitable and timely immunotherapy for COVID-19 patients. Clinical Trial Registry: https://www.chictr.org.cn/enindex.aspx, identifier ChiCTR2000034563.

Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which had rapidly spread all over the world and caused public health emergencies in the past two years. Although the diagnosis and treatment for COVID-19 have been well defined, the immune cell characteristics and the key lymphocytes subset alterations in COVID-19 patients have not been thoroughly investigated. METHODS: The levels of immune cells including T cells, B cells, and natural killer (NK) cells in 548 hospitalized COVID-19 patients, and 30 types of lymphocyte subsets in 125 hospitalized COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China were measured using flow cytometry. The relationship between lymphocytes subsets with the cytokine interleukin-6 (IL-6) and the characteristics of lymphocyte subsets in single-cell RNA sequencing (scRNA-seq) data obtained from peripheral blood mononuclear cells (PBMCs) were also analysed in COVID-19 patients. RESULTS: In this study, we found that patients with critical COVID-19 infection exhibited an overall decline in lymphocytes including CD4+ T cells, CD8+ T cells, total T cells, B cells, and NK cells compared to mild and severe patients. However, the number of lymphocyte subsets, such as CD21low CD38low B cells, effector T4 cells, and PD1+ depleted T8 cells, was moderately increased in critical COVID-19 patients compared to mild cases. Notably, except for effector memory T4 cells, plasma blasts and Tregs, the number of all lymphocyte subsets was markedly decreased in COVID-19 patients with IL-6 levels over 30-fold higher than those in healthy cases. Moreover, scRNA-seq data showed obvious differences in the distribution and numbers of lymphocyte subsets between COVID-19 patients and healthy persons, and subsets-specific marker genes of lymphocyte subsets including CD4, CD19, CCR7, and IL7R, were markedly decreased in COVID-19 patients compared with those in healthy cases. CONCLUSION: A comprehensive decrease in immune cell and lymphocyte subsets in critical COVID-19 patients, and peripheral lymphocyte subset alterations showed a clear association with clinical characteristics.

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.

D-dimer levels and characteristics of lymphocyte subsets, cytokine profiles in peripheral blood of patients with severe COVID-19: A systematic review and meta-analysis.

Purpose: A series of complications caused by severe COVID-19 can significantly affect short-term results. Therefore, early diagnosis is essential for critically COVID-19 patients. we aimed to investigate the correlation among D-dimer levels, lymphocyte subsets, cytokines, and disease severity in COVID-19 patients. Methods: Systematic review and meta- analysis of PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, Embase, clinical trials, and China National Knowledge Infrastructure (CNKI) until 1 August 2022. We considered case-control, and cohort studies that compared laboratory parameters between patients with severe or non-serious diseases or between survivors and non-survivors. Pooled data was assessed by use of a random-effects model and used I 2 to test heterogeneity. We assessed the risk of bias using the Newcastle- Ottawa Scale. Results: Of the 5,561 identified studies, 32 were eligible and included in our analysis (N = 3,337 participants). Random-effect results indicated that patients with COVID-19 in severe group had higher levels for D-dimer (WMD = 1.217 mg/L, 95%CI=[0.788, 1.646], P < 0.001), neutrophil-to-lymphocyte ratio (NLR) (WMD = 6.939, 95%CI = [4.581, 9.297], P < 0.001), IL-2 (WMD = 0.371 pg/ml, 95%CI = [-0.190, 0.932], P = 0.004), IL-4 (WMD = 0.139 pg/ml, 95%CI = [0.060, 0.219], P = 0.717), IL-6 (WMD = 44.251 pg/ml, 95%CI = [27.010, 61.493], P < 0.001), IL-10 (WMD = 3.718 pg/ml, 95%CI = [2.648, 4.788], P < 0.001) as well as lower levels of lymphocytes (WMD = -0.468( × 109/L), 95%CI = [-0.543, -0.394], P < 0.001), T cells (WMD = -446.746(/µL), 95%CI = [-619.607, -273.885], P < 0.001), B cells (WMD = -60.616(/µL), 95%CI = [-96.452, -24.780], P < 0.001), NK cells (WMD = -68.297(/µL), 95%CI = [-90.600, -45.994], P < 0.001), CD3+T cells (WMD = -487.870(/µL), 95%CI = [-627.248, -348.492], P < 0.001), CD4+T cells (WMD = -290.134(/µL), 95%CI = [-370.834, -209.435], P < 0.001), CD8+T cells (WMD = -188.781(/µL), 95%CI = [-227.806, -149.757], P < 0.001). Conclusions: There is a correlation among higher levels of D-dimer, cytokines, lower levels of lymphocyte subsets, and disease severity in COVID-19 patients. These effective biomarkers may help clinicians to evaluate the severity and prognosis of COVID-19. This study is registered with PROSPERO, number CRD42020196659. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=196659; PROSPERO registration number: CRD42020196659.

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.

Recovery of functional fitness, lung function, and immune function in healthcare workers with nonsevere and severe COVID-19 at 13 months after discharge from the hospital: a prospective cohort study.

OBJECTIVES: This study aimed to evaluate the recovery of functional fitness, lung function, and immune function in healthcare workers (HCWs) with nonsevere and severe COVID-19 at 13 months after discharge from the hospital. METHODS: The participants of "Rehabilitation Care Project for Medical Staff Infected with COVID-19" underwent a functional fitness test (muscle strength, flexibility, and agility/dynamic balance), lung function test, and immune function test (including cytokines and lymphocyte subsets) at 13 months after discharge. RESULTS: The project included 779 HCWs (316 nonsevere COVID-19 and 463 severe COVID-19). This study found that 29.1% (130/446) of the HCWs have not yet recovered their functional fitness. The most affected lung function indicator was lung perfusion capacity (34% with diffusion capacity for carbon monoxide-single breath <80%). The increase of interleukin-6 (64/534, 12.0%) and natural killer cells (44/534, 8.2%) and the decrease of CD3+ T cells (58/534, 10.9%) and CD4+ T cells (26/534, 4.9%) still existed at 13 months after discharge. No significant difference was found in the HCWs with nonsevere and severe COVID-19 regarding recovery of functional fitness, lung function, and immune function at 13 months after discharge. CONCLUSION: The majority of Chinese HCWs with COVID-19 had recovered their functional fitness, lung function, and immune function, and the recovery status in HCWs with severe COVID-19 is no worse than that in HCWs with nonsevere COVID-19 at 13 months after discharge from the hospital.