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COVID-19, which emerged in December 2019 and continues to wreak havoc, has led to the death of many people around the world. In this study, we aimed to uncover the variables underlying the exacerbation of the disease by considering the changes in T cell subsets in adults and juveniles with different disease severity of COVID-19. Peripheral blood samples of 193 patients (128 adults and 65 juveniles) diagnosed with COVID-19 were evaluated in a flow cytometer, and a broad T cell profile was revealed by examining T cell subsets in terms of exhaustion and senescence. We found remarkable differences in the effector memory (EM;CD45RA-CCR7-) cell subsets of severe pneumonia cases. The frequencies of EM2 CD4+ T, EM3 CD4+ T, EM3 CD8+ T, EM2 DN T and EM3 DN T cells were found to increase in severe pneumonia cases. Consistently, these cells were found in juveniles and uncomplicated adults in similar or lower proportions to healthy controls. The findings of our study provide a view of the T cell profile that may underlie differences in the course of COVID-19 cases in juveniles and adults and may provide new insights into the development of effective treatment strategies.
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Objective: In COVID-19 disease, it was observed that T lymphocytes decreased numerically, both CD4+ and CD8+ could decrease, and sometimes the CD8+ level increased significantly. The virus-specific CD8+ T-cells are thought to be TEM or TEMRA cells. However, the characteristics of these cells, particularly their role in the pathogenesis of SARS-CoV-2 infection or COVID-19 disease, are unclear. Therefore, this study aimed to examine the flow cytometric changes observed in T helper, T cytotoxic cells, and subtypes during diagnosis in pediatric patients diagnosed with COVID-19 infection with SARS-CoV-2 PCR positivity. Methods: Twenty-two children aged 0-18, diagnosed with COVID-19, with flow cytometry;T Helper Cell (TH), T Cytotoxic Cell (TC), T Naive Cells (TN), Central Memory (TCM), Effector Memory (TEM), RA + Effector memory (TEMRA) and Recent Thymic Emigrants (RTEs) were studied. Results: T cell counts were found to be expected in all age groups. The CD4/CD8 ratio increased in the under-five and over 16 age group. While TCM among CD4+T cells decreased in the group above 16 years of age, TEM decreased in all age groups. RTEs decreased in all except the age group 16+. Naive CD8+ T cells (TN) were found to be high in all age groups. Conclusion: A low number of CD4+ and CD8+ lymphocytes have been reported as a distinctive laboratory finding in 2019 Coronavirus disease (COVID-19). Having enough naive T cells is essential for the immune system to respond consistently to unknown pathogens. This study found that these cells were higher than expected in children.
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SARS-CoV-2 pandemic is now a global medical and social problem. Little is known about its impact on some vulnerable subgroups, such as immunocompromised patients. Therefore, there is still a strong interest in exploring the impact of SARS- CoV-2 infection among HIV-positive individuals worldwide. Aim of the study: to analyze immunological aspects of the deceased, patients with HIV/COVID-19 coinfection. Materials and. methods. We provided retrospective analysis of 258 patient's electronic medical records. All patients were admitted, to the Infectious diseases hospital N2 with HIV/COVID-19 coinfection and died in May 2020 - February 2022. Standard, immunological parameters were analyzed, like CD4+, CD8+ counts and. immunoregulatory index for different patient's subgroups. Statistical data processing was provided by SPSS 17 version (allowable error E=5%). Results and. discussion. The study demonstrated. CD4+ and CD8+ reduction in HIV-infected with COVID-19. Late HIV-presenters didn't display such phenomenon probably because of immune system, exhaustion. COVID-19 itself in some cases could, lead, to immunodeficiency worsening due to depletion of T cell populations in HIV-patients on effective antiretroviral therapy. Conclusion. Comprehension, of different immunological characteristics in HIV/COVID-19 coinfected patients could, improve therapeutic approaches for this challenging cohort.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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SARS-CoV-2 pandemic is now a global medical and social problem. Little is known about its impact on some vulnerable subgroups, such as immunocompromised patients. Therefore, there is still a strong interest in exploring the impact of SARS- CoV-2 infection among HIV-positive individuals worldwide. Aim of the study: to analyze immunological aspects of the deceased, patients with HIV/COVID-19 coinfection. Materials and. methods. We provided retrospective analysis of 258 patient's electronic medical records. All patients were admitted, to the Infectious diseases hospital N2 with HIV/COVID-19 coinfection and died in May 2020 — February 2022. Standard, immunological parameters were analyzed, like CD4+, CD8+ counts and. immunoregulatory index for different patient's subgroups. Statistical data processing was provided by SPSS 17 version (allowable error E=5%). Results and. discussion. The study demonstrated. CD4+ and CD8+ reduction in HIV-infected with COVID-19. Late HIV-presenters didn't display such phenomenon probably because of immune system, exhaustion. COVID-19 itself in some cases could, lead, to immunodeficiency worsening due to depletion of T cell populations in HIV-patients on effective antiretroviral therapy. Conclusion. Comprehension, of different immunological characteristics in HIV/COVID-19 coinfected patients could, improve therapeutic approaches for this challenging cohort. © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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SARS-CoV-2 pandemic is now a global medical and social problem. Little is known about its impact on some vulnerable subgroups, such as immunocompromised patients. Therefore, there is still a strong interest in exploring the impact of SARS- CoV-2 infection among HIV-positive individuals worldwide. Aim of the study: to analyze immunological aspects of the deceased, patients with HIV/COVID-19 coinfection. Materials and. methods. We provided retrospective analysis of 258 patient's electronic medical records. All patients were admitted, to the Infectious diseases hospital N2 with HIV/COVID-19 coinfection and died in May 2020 - February 2022. Standard, immunological parameters were analyzed, like CD4+, CD8+ counts and. immunoregulatory index for different patient's subgroups. Statistical data processing was provided by SPSS 17 version (allowable error E=5%). Results and. discussion. The study demonstrated. CD4+ and CD8+ reduction in HIV-infected with COVID-19. Late HIV-presenters didn't display such phenomenon probably because of immune system, exhaustion. COVID-19 itself in some cases could, lead, to immunodeficiency worsening due to depletion of T cell populations in HIV-patients on effective antiretroviral therapy. Conclusion. Comprehension, of different immunological characteristics in HIV/COVID-19 coinfected patients could, improve therapeutic approaches for this challenging cohort.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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Objective: To observe early laboratory indicators in peripheral blood of patients infected with SARSCoV- 2 Delta variant and the protective effects of COVID-19 vaccine on patients infected with SARS-CoV-2 Delta variant, in order to provide reference for epidemic prevention and control. Methods: Twenty-five Chengdu local confirmed nonsevere COVID-19 patients over 18 years old who were infected with COVID-19 caused by Delta variant in November 2021 were included as the research group, 22 cases of whom were vaccinated with COVID-19 vaccine before infection, and 3(2 cases over 80 years old)were unvaccinated. In addition, 71 non-severe COVID-19 patients at the age of over 18 years diagnosed in Chengdu from January 2020 to February 2020 were included as the control group. Peripheral blood was collected for laboratory examination in all cases on the first or second days after admission, and peripheral blood was collected for laboratory examination again in patients on day 4 to 8 after admission in the research group. Laboratory indicators included the blood routine, C-reactive protein, procalcitonin, liver function, myocardial enzyme profile, coagulation routine, T lymphocyte subsets, SARS-CoV-2 IgG antibody, and total antibody, etc. The first peripheral blood laboratory test results: of the two groups were compared to observe the protective effect of COVID-19 vaccine on patients infected with SARS-CoV- 2 Delta variant. Results Among the first time of laboratory indicators after admission, the lymphocyte count, lactate dehydrogenase, and D-dimer in the research group were all lower than those in the control group(all P < 0.05), and the procalcitonin and aspartate aminotransferase were higher than those in the control group(all P < 0.05). Among the 22 cases who had gotten vaccine before infection in the research group, there were 5 cases with positive result of SARS-CoV-2 IgG antibody in the first time of peripheral blood, 22 cases with positive result of SARS-CoV-2 IgG antibody in the second time of peripheral blood, and none of them became severe cases. During 3 unvaccinated cases, twice of the SARS-CoV-2 IgG antibody were both negative among the 2 cases over 80 years who had not vaccinated in the research group, then they became severe cases on day 6-8 during hospitalization, and the rest one had negative result of SARS-CoV-2 IgG antibody in the second time of peripheral blood. Among the 22 vaccinated cases in the research group, the lymphocyte count, CD4+T cell count, CD8+T cell count, SARS-CoV-2 specific antibodies in the second time peripheral blood were all higher than those in the first time of peripheral blood(all P < 0.05), and platelet count, hemoglobin, total protein, creatine kinase were all lower than those in the first time of peripheral blood(all P < 0.05). Conclusions: Lymphocyte count at early admission in COVID-19 patients infected with Delta variant may be lower than that infected with wild strain. COVID-19 vaccine can reduce the risk of infection of SARS-CoV-2 Delta variant by preventing the emergence of inflammatory storms and producing a large number of specific antibodies.
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Introduction: Although CD4 and CD8 T-cells are the main subset of T-lymphocytes, their roles in COVID-19 infection and severity remain unclear. This study aimed to determine the role of increased CD4/CD8 T-cells ratio as a risk factor for cases of 28-days in-hospital mortality in COVID-19 patients. Materials and Methods: This study employed a prospective cohort design. Inclusion criteria were confirmed COVID-19 cases with a positive polymerase chain reaction report. CD4 and CD8 T-cells absolute counts were measured by flow cytometry. The CD4/CD8 ratio was calculated by dividing the absolute count of CD4 by that of CD8 T-cells. Results: A total of 85 subjects were followed for 28 days. The mean age of the subjects was 52.64 years, and majority of them were females (51.8%). Twenty-eight (32.9%) subjects died within 28 days of follow-up. Receiver operating characteristics analysis obtained an area under curve of 0.68 with the cut-off value 1.26 with p = 0.005. Kaplan-Meier's analysis obtained Hazard Ratio 2.91 (95%CI 1.377-6.161;p = 0.0052). Conclusion: Subjects with an increase in CD4/CD8 T-cells ratio >1.26 had a 2.91-times risk of 28 days in-hospital mortality.
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The SARS-CoV-2 virus caused the COVID-19 pandemic is related to the SARS-CoV-1 and MERS coronaviruses, which were resulted in 2003 and 2012 epidemics. Antibodies in patients with COVID-19 emerge 7-14 days after the onset of symptoms and gradually increase. Because the COVID-19 pandemic is still in progress, it is hard to say how long the immunological memory to the SARS-CoV-2 virus may be retained. The aim of this study was to study a ratio between humoral and cellular immunity against the SARS-CoV-2 S protein in COVID-19 convalescents. There were enrolled 60 adults with mild to moderate COVID-19 2 to 12 months prior to the examination. The control group consisted of 15 adults without COVID-19 or unvaccinated. Specific antibodies to the SARS-CoV-2 virus were determined by ELISA with the SARS-CoV-2-IgG-ELISA-BEST kit. To determine the specific IgG and IgA subclasses, the anti-IgG conjugate from the kit was replaced with a conjugate against the IgG subclasses and IgA. Additional incubation with or without denaturing urea solution was used to determine the avidity of antibodies. Peripheral blood mononuclear cells were isolated by gradient centrifugation, incubated with or without coronavirus S antigen for 20 hours, stained by fluorescently labeled antibodies, and the percentage of CD8(high)CD107a cells was assessed on flow cytometer BD FACSCanto II. In the control group, neither humoral nor cellular immunity against the SARS-CoV-2 S protein was found. In the group of convalescents, the level of IgG antibodies against the SARS-CoV-2 S protein varies greatly not being strictly associated with the disease duration, with 57% and 43% of COVID-19 patients having high vs. low level of humoral response, respectively. A correlation between level of specific IgG and IgA was r = 0.43. The avidity of antibodies increased over time in convalescents comprising 49.9% at 6-12 months afterwards. No virus-specific IgG2 and IgG4 subclasses were detected, and the percentage of IgG1 increased over time comprising 100% 6-12 months after recovery. 50% of the subjects examined had high cellular immunity, no correlations with the level of humoral immunity were found. We identified 4 combinations of humoral and cellular immunity against the SARS- CoV-2 S protein: high humoral and cellular, low humoral and cellular, high humoral and low cellular, and vice versa, low humoral and high cellular immunity.
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Objective:To investigate the changes of Mg2+ levels in serum and peripheral blood mononuclear cells (PB-MCs) of patients with COVID-19 and its effects on the functions of CD8+ T lymphocytes and NK cells.
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To determine the clinical value of diammonium glycyrrhizinate (DG) in treatment of patients with novel coronavirus pneumonia (NCP). According to the random-number method, 104 NCP patients were divided equally into control group and observation group in our hospital. In the control group, patients were treated according to the Pneumonia diagnosis and treatment scheme for new coronavirus infection (trial version 5). In the observation group, patients were administered DG enteric capsules (150 mg, t.d.s.). All patients were treated continuously for 2 weeks. The clinical effects in both groups were observed. Levels of inflammation indicators [C-reactive protein (CRP), interleukin (IL) -4, tumor necrosis factor (TNF) -a] and immune-function indicators [cluster of differentiation (CD)3+, CD4+, CD8+, CD4+/CD8+] were compared between the two groups. Adverse reactions were documented. The prevalence of cure [19.23% (10/52) vs. 7.69% (4/ 52)], significant efficacy [28.85% (15/52) vs. 17.31% (9/52)] and total efficacy [61.54% (32/52) vs. 40.38% (20/52)] of the observation group was significantly higher than that of the control group (P < 0.05 for all). After treatment, the serum levels of CRP [(1.90 +or- 085) vs. (3.26 +or- 1.63) mg/L], IL-4 [(21.35 +or- 8.90) vs. (26.24 +or- 9.16) pg/mL], and TNF-a [(4.85 +or- 2.15) vs. (7.97 +or- 3.36) pg/mL] of the observation group were significantly lower than those of the control group (P < 0.05 for all). The levels of CD3+ [(6630 +or- 8.83)% vs. (54.19 +or- 7.79)%], CD4+ [(39.42 +or- 4.72)% vs, (33.18 +or- 4.10)%], CD8+ [(28.14 +or- 4.22)% vs. (23.39 +or- 3.88)%], and CD4+/CD8+ [(1.62+or- 043) vs. (1.21 +or- 0.29)] of the observation group were significantly higher than those of the control group (P < 0.05 for all). The prevalence of adverse reactions [15.38% (8/52) vs. 28.85% (15/52)] of the observation group was significantly lower than that of the control group (P < 0.05). DG has a significant clinical effect and a good safety profile for NCP treatment.
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Objective: To investigate the effect and mechanism of high-dose clodronate liposomes (CL) treatment on the growth of Plasmodium yoelii 17XL (Py17XL) in mice.
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Objective: To retrospectively evaluate the clinical efficacy of Qingfei Paidu decoction in the treatment of coronavirus disease 2019 (COVID-19)and to explore the possible mechanism.
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Background/aim: This study was to describe the clinical characteristics, chest CT image findings, and potential role of T cells immunity in adenovirus positive pneumonia. Materials/methods: In this retrospective study, medical records of 53 adult Adv+ patients who were admitted to the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from May 2015 to August 2019 were included. The presence of adenovirus and other respiratory viruses was detected using polymerase chain reaction of throat swabs samples. Clinical features and chest computed tomography (CT) findings were compared between patients with Adv+ pneumonia and Adv+ non-pneumonia.
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Objective: Deficiencies in immune-regulatory mechanisms such as immune activation and T-regulatory cells are classically referred to as cytokine storms. Mesenchymal stem cells (MSCs) act as living anti-inflammatory cells that can rebalance cytokine/immune responses to restore balance in patients with coronavirus disease-2019 (COVID-19) acute respiratory distress syndrome by reducing the activation of T and B cells, and dendritic and natural killer cells. The aim of this study is to provide immune modulation with stem cell transplantation by reducing the damage caused and COVID-19 infection to tissues and organs. Material and Methods: In this prospective randomized single-center clinical trial, patients were divided into 3 groups: intubated without comorbidity (n = 7);intubated with comorbidity (n = 7);not intubated (n = 7). Dosage of MSCs transplantation for each group was 1 million cell/kg intravenous at days 0, 2, and 4. age, gender, APACHE II scores, procalcitonin, C-reactive protein (CRP) and leukocyte values, and cluster of difference 4 (CD4), CD8, interleukin 2 (IL-2), and IL-6 levels, morbidities, number of days in intensive care unit, mortality were recorded. Clinical results, changes in inflammatory and immune function levels, and side effects were evaluated. Each patient's improvement in oxygenation and symptoms were recorded in the days after MSC transplantation. After treatment, lymphocyte, CRP, tumor necrosis factor-a level, and IL-6 levels were recorded.
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Objective: To retrospectively analyze the follow-up data of 134 patients diagnosed with COVID-19 in Guangzhou one year after they were discharged from the hospital and summarize their characteristics, and we provide a basis for further evaluation of long-term efficacy of COVID-19 patients.
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Infection by novel coronavirus SARS-CoV-2 causes different presentations of COVID-19 and some patients may progress to a critical, fatal form of the disease that requires their admission to ICU and invasive mechanical ventilation. In order to predict in advance which patients could be more susceptible to develop a critical form of COVID-19, it is essential to define the most adequate biomarkers. In this study, we analyzed several parameters related to the cellular immune response in blood samples from 109 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centers in Madrid, Spain, during the first pandemic peak between April and June 2020. Hospitalized patients with the most severe forms of COVID-19 showed a potent inflammatory response that was not translated into an efficient immune response. Despite the high levels of effector cytotoxic cell populations such as NK, NKT and CD8+ T cells, they displayed immune exhaustion markers and poor cytotoxic functionality against target cells infected with pseudotyped SARS-CoV-2 or cells lacking MHC class I molecules. Moreover, patients with critical COVID-19 showed low levels of the highly cytotoxic TCRγδ+ CD8+ T cell subpopulation. Conversely, CD4 count was greatly reduced in association to high levels of Tregs, low plasma IL-2 and impaired Th1 differentiation. The relative importance of these immunological parameters to predict COVID-19 severity was analyzed by Random Forest algorithm and we concluded that the most important features were related to an efficient cytotoxic response. Therefore, efforts to fight against SARS-CoV-2 infection should be focused not only to decrease the disproportionate inflammatory response, but also to elicit an efficient cytotoxic response against the infected cells and to reduce viral replication.
Subject(s)
COVID-19/epidemiology , COVID-19/immunology , Cytotoxicity, Immunologic , Intensive Care Units , Leukocytes, Mononuclear/immunology , Patient Admission/statistics & numerical data , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , Biomarkers , COVID-19/diagnosis , COVID-19/virology , Comorbidity , Cytokines/metabolism , Female , Humans , Immunophenotyping , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Severity of Illness Index , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolismABSTRACT
Introduction: While pathogenesis in COVID-19 is not fully known and the effects between SARS-CoV-2 and the immune system are complicated, it is known that lymphopenia, hyper-inflammatory responses, and cytokines play an important role in the pathology of COVID-19. While some hematological abnormalities have been described among the laboratory features of COVID-19, there have not been studies reported on lymphocyte subset analyses in children. The aim of this study was to describe lymphocyte subsets in pediatric patients with mild/moderate or severe COVID-19. Methods: The subjects in the study were children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia confirmed with the real-time RT-PCR. The subjects were admitted to the Children's Medical Center, affiliated with the Tehran University of Medical Sciences, between March 7th and June 10th of 2020. The complete blood counts and lymphocyte subpopulations were analyzed for each patient. Results: The study included 55 hospitalized patients with confirmed SARS-CoV-2 infection (34 patients (62%) with an observed mild/moderate case of the disease and 21 patients (38%) with severedisease). Lymphocyte counts were found to be lower in patients with a severe case (mean ± SD 1.6 ± 0.9 in the severe group vs. 2.3 ± 2.2 in the mild group). Compared to the group with mild/moderate pneumonia, children with severe pneumonia had an increased count of CD8+ T cell and a lower percentage of CD4+ T cell. However, the differences between the groups were negligible. Interestingly, the severe group had a lower CD4+/CD8+ T cell ratio compared to the mild group (1.1 ± 0.47 vs. 1.4 ± 0.8, p-value: 0.063). CD4+/CD8+ T cell ratio <2, 1.5, and 1 was found in 48 (87%), 40 (73%), and 19 cases (35%). All of the seven cases in which the subject passed (13%) had CD4+/CD8+ T cell ratio of <2, 86% had CD4+/CD8+ T cell ratio of <1.5, and 29% had CD4+/CD8+ T cell ratio of <1. Conclusion: The CD4+/CD8+ T cell ratio was lower in patients with severe COVID-19 compared to those with mild/moderate form of disease. However, although a decline in CD4+/CD8+ ratio may serve as a useful metric in analyzing of the derangement in immune responses in patients with severe COVID-19, further study with larger sample sizes is highly recommended.
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The severity of SARS-CoV-2 infection has been related to uncontrolled inflammatory innate responses and impaired adaptive immune responses mostly due to exhausted T lymphocytes and lymphopenia. In this work we have characterized the nature of the lymphopenia and demonstrate a set of factors that hinder the effective control of virus infection and the activation and arming of effector cytotoxic T CD8 cells and showing signatures defining a high-risk population. We performed immune profiling of the T helper (Th) CD4+ and T CD8+ cell compartments in peripheral blood of 144 COVID-19 patients using multiparametric flow cytometry analysis. On the one hand, there was a consistent lymphopenia with an overrepresentation of non-functional T cells, with an increased percentage of naive Th cells (CD45RA+, CXCR3-, CCR4-, CCR6-, CCR10-) and persistently low frequency of markers associated with Th1, Th17, and Th1/Th17 memory-effector T cells compared to healthy donors. On the other hand, the most profound alteration affected the Th1 subset, which may explain the poor T cells responses and the persistent blood virus load. Finally, the decrease in Th1 cells may also explain the low frequency of CD4+ and CD8+ T cells that express the HLA-DR and CD38 activation markers observed in numerous patients who showed minimal or no lymphocyte activation response. We also identified the percentage of HLA-DR+CD4+ T cells, PD-1+CD+4/CD8+ T cells in blood, and the neutrophil/lymphocyte ratio as useful factors for predicting critical illness and fatal outcome in patients with confirmed COVID-19.