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1.
Int J Immunopathol Pharmacol ; 35: 20587384211048567, 2021.
Article in English | MEDLINE | ID: covidwho-1463208

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) had become a worldwide health threat. Early prediction of the severity of COVID-19 patients was important for reducing death rate and controlling this disease. METHODS AND MATERIALS: A total of 301 patients confirmed with COVID-19 in Wuhan from 8 February to 10 April 2020 were included. Clinical data were collected and analyzed. Diagnostic and prognostic utility of blood cell counts and lymphocyte subsets in COVID-19 patients were investigated. The receiver operator characteristic curve (ROC) was used in discriminating the mild and severe/critical cases. RESULTS: There were difference in blood cell counts and lymphocyte subsets among mild, severe and critical patients, which were also influenced by comorbidities and duration of disease. The area under the ROC of lymphocyte, CD3+ T cells, CD4+ T cells, and CD8+ T cells were 0.718, 0.721, 0.718, and 0.670, which were higher than that of other hematological parameters. The optimal threshold was 1205, 691, 402, and 177 per µl, respectively. Patients with higher counts of lymphocyte, CD3+ T cells, CD4+ T cells, or CD8+ T cells were correlated with shorter length of stay in hospital (p < 0.05). Multivariable Cox regression analysis showed disease severity, CD3+ T cells counts and time when the nucleic acid turned negative were independent risk factors for in-hospital death of COVID-19 patients (p < 0.05). CONCLUSION: Blood cell counts and lymphocyte subsets correlated with severity of COVID-19.


Subject(s)
COVID-19/immunology , Lymphocyte Subsets/immunology , Adult , Aged , Aged, 80 and over , CD4 Lymphocyte Count , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , China , Female , Hospital Mortality , Host-Pathogen Interactions , Humans , Lymphocyte Subsets/virology , Male , Middle Aged , Phenotype , Predictive Value of Tests , Prognosis , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index , Time Factors , Young Adult
2.
Eur Rev Med Pharmacol Sci ; 25(15): 5057-5062, 2021 08.
Article in English | MEDLINE | ID: covidwho-1346860

ABSTRACT

OBJECTIVE: Complete blood count parameters are frequently altered in COVID-19 patients. Leucopenia and lymphopenia are the most common findings. This is not specific to COVID-19 as similar alterations are found in various other viral infections. This work is intended to summarize the evidence regarding white blood cell and lymphocyte subset alterations in COVID-19 and their clinical implications. MATERIALS AND METHODS: A PubMed search was conducted to identify relevant original studies. Articles not available in English or referring exclusively to pediatric patients were excluded. The study was designed as a narrative review from its inception. RESULTS: Complete white blood cell number and lymphocytes may be reduced in COVID-19 patients. Circulating CD4+ cells (helper T lymphocytes), CD8+ cells (cytotoxic T lymphocytes), regulatory T cells and natural killer (NK) cells may be reduced, with a greater reduction observed in critically ill patients. CD4+ and regulatory cell deficiencies may contribute to the cytokine storm and subsequent tissue damage observed in severe COVID-19 infection. NK and CD8+ cell deficiency might delay infection clearance. These aberrations of cellular immunity may contribute significantly to the pathogenesis of the disease. Alterations observed in monocyte function can also be implicated as they are effector cells responsible for tissue damage and remodeling. B cell dysfunction and maturation abnormalities have also been reported, suggesting that the virus also impairs humoral immunity. CONCLUSIONS: Lymphocyte subset abnormalities may be useful prognostic biomarkers for COVID-19, with circulating CD8+ cell count being the most promising as a predictor of severe disease requiring mechanical ventilation and mortality.


Subject(s)
COVID-19/immunology , Lymphocyte Subsets/immunology , Lymphocyte Subsets/virology , Monocytes/immunology , Monocytes/virology , B-Lymphocytes/immunology , B-Lymphocytes/virology , COVID-19/virology , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/virology , T-Lymphocytes/immunology , T-Lymphocytes/virology
3.
Nat Cell Biol ; 23(6): 620-630, 2021 06.
Article in English | MEDLINE | ID: covidwho-1263492

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often causes severe complications and even death. However, asymptomatic infection has also been reported, highlighting the difference in immune responses among individuals. Here we performed single-cell chromatin accessibility and T cell-receptor analyses of peripheral blood mononuclear cells collected from individuals convalescing from COVID-19 and healthy donors. Chromatin remodelling was observed in both innate and adaptive immune cells in the individuals convalescing from COVID-19. Compared with healthy donors, recovered individuals contained abundant TBET-enriched CD16+ and IRF1-enriched CD14+ monocytes with sequential trained and activated epigenomic states. The B-cell lineage in recovered individuals exhibited an accelerated developmental programme from immature B cells to antibody-producing plasma cells. Finally, an integrated analysis of single-cell T cell-receptor clonality with the chromatin accessibility landscape revealed the expansion of putative SARS-CoV-2-specific CD8+ T cells with epigenomic profiles that promote the differentiation of effector or memory cells. Overall, our data suggest that immune cells of individuals convalescing from COVID-19 exhibit global remodelling of the chromatin accessibility landscape, indicative of the establishment of immunological memory.


Subject(s)
COVID-19/genetics , Epigenesis, Genetic , Epigenomics , Genes, T-Cell Receptor , Immunologic Memory , Lymphocyte Subsets/immunology , Monocytes/immunology , SARS-CoV-2/immunology , Single-Cell Analysis , Adaptive Immunity , Adolescent , Adult , Aged , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , B-Lymphocytes/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/virology , COVID-19/immunology , COVID-19/metabolism , COVID-19/virology , Case-Control Studies , Cell Differentiation , Chromatin Assembly and Disassembly , Female , Gene Expression Profiling , Host-Pathogen Interactions , Humans , Immunity, Innate , Lymphocyte Subsets/metabolism , Lymphocyte Subsets/virology , Male , Middle Aged , Monocytes/metabolism , Monocytes/virology , SARS-CoV-2/pathogenicity , Young Adult
4.
Int Immunopharmacol ; 95: 107586, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1149235

ABSTRACT

The incidence of the novel coronavirus disease (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought daunting complications for people as well as physicians around the world. An ever-increasing number of studies investigating the characteristics of the disease, day by day, is shedding light on a new feature of the virus with the hope that eventually these efforts lead to the proper treatment. SARS-CoV-2 activates antiviral immune responses, but in addition may overproduce pro-inflammatory cytokines, causing uncontrolled inflammatory responses in patients with severe COVID-19. This condition may lead to lymphopenia and lymphocyte dysfunction, which in turn, predispose patients to further infections, septic shock, and severe multiple organ dysfunction. Therefore, accurate knowledge in this issue is important to guide clinical management of the disease and the development of new therapeutic strategies in patients with COVID-19. In this review, we provide a piece of valuable information about the alteration of each subtype of lymphocytes and important prognostic factors associated with these cells. Moreover, through discussing the lymphopenia pathophysiology and debating some of the most recent lymphocyte- or lymphopenia-related treatment strategies in COVID-19 patients, we tried to brightening the foreseeable future for COVID-19 patients, especially those with severe disease.


Subject(s)
COVID-19/drug therapy , COVID-19/immunology , Lymphocyte Subsets/immunology , Lymphocyte Subsets/virology , Lymphopenia/immunology , Lymphopenia/physiopathology , SARS-CoV-2/immunology , COVID-19/complications , Humans , Lymphopenia/etiology , Lymphopenia/virology , Prognosis
5.
Int J Infect Dis ; 104: 315-319, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-988038

ABSTRACT

OBJECTIVES: The immunologic profile and opportunistic viral DNA increase were monitored in Italian patients with COVID-19 in order to identify markers of disease severity. METHODS: A total of 104 patients infected with SARS-CoV-2 were evaluated in the study. Of them, 42/104 (40.4%) were hospitalized in an intensive care unit (ICU) and 62/104(59.6%) in a sub-intensive care unit (SICU). Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), Parvovirus B19 and Human Herpesvirus 6 virus reactivations were determined by real-time PCR, and lymphocyte subpopulation counts were determined by flow cytometry. RESULTS: Among opportunistic viruses, only EBV was consistently detected. EBV DNA was observed in 40/42 (95.2%) of the ICU patients and in 51/61 (83.6%) of the SICU patients. Comparing the two groups of patients, the EBV DNA median level among ICU patients was significantly higher than that observed in SICU patients. In parallel, a significant reduction of CD8 T cell and NK count in ICU patients as compared with SICU patients was observed (p<0.05). In contrast, B cell count was significantly increased in ICU patients (p=0.0172). CONCLUSIONS: A correlation between reduced CD8+ T cells and NK counts, EBV DNA levels and COVID-19 severity was observed. Other opportunistic viral infections were not observed. The relationship between EBV load and COVID-19 severity should be further evaluated in longitudinal studies.


Subject(s)
COVID-19/complications , Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/isolation & purification , SARS-CoV-2 , Viral Load , Aged , Aged, 80 and over , CD8-Positive T-Lymphocytes/virology , COVID-19/virology , DNA, Viral/analysis , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnosis , Female , Herpesvirus 4, Human/genetics , Humans , Intensive Care Units , Killer Cells, Natural/virology , Lymphocyte Count , Lymphocyte Subsets/virology , Male , Middle Aged , Opportunistic Infections , Real-Time Polymerase Chain Reaction
6.
Viruses ; 12(11)2020 11 09.
Article in English | MEDLINE | ID: covidwho-918256

ABSTRACT

BACKGROUND: COVID-19 pathophysiology and the predictive factors involved are not fully understood, but lymphocytes dysregulation appears to play a role. This paper aims to evaluate lymphocyte subsets in the pathophysiology of COVID-19 and as predictive factors for severe disease. PATIENT AND METHODS: A prospective cohort study of patients with SARS-CoV-2 bilateral pneumonia recruited at hospital admission. Demographics, medical history, and data regarding SARS-CoV-2 infection were recorded. Patients systematically underwent complete laboratory tests, including parameters related to COVID-19 as well as lymphocyte subsets study at the time of admission. Severe disease criteria were established at admission, and patients were classified on remote follow-up according to disease evolution. Linear regression models were used to assess associations with disease evolution, and Receiver Operating Characteristic (ROC) and the corresponding Area Under the Curve (AUC) were used to evaluate predictive values. RESULTS: Patients with critical COVID-19 showed a decrease in CD3+CD4+ T cells count compared to non-critical (278 (485 IQR) vs. 545 (322 IQR)), a decrease in median CD4+/CD8+ ratio (1.7, (1.7 IQR) vs. 3.1 (2.4 IQR)), and a decrease in median CD4+MFI (21,820 (4491 IQR) vs. 26,259 (3256 IQR)), which persisted after adjustment. CD3+CD8+ T cells count had a high correlation with time to hospital discharge (PC = -0.700 (-0.931, -0.066)). ROC curves for predictive value showed lymphocyte subsets achieving the best performances, specifically CD3+CD4+ T cells (AUC = 0.756), CD4+/CD8+ ratio (AUC = 0.767), and CD4+MFI (AUC = 0.848). CONCLUSIONS: A predictive value and treatment considerations for lymphocyte subsets are suggested, especially for CD3CD4+ T cells. Lymphocyte subsets determination at hospital admission is recommended.


Subject(s)
CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/pathology , COVID-19/diagnosis , Lymphocyte Subsets/pathology , SARS-CoV-2/pathogenicity , Aged , Area Under Curve , Biomarkers/analysis , CD4-CD8 Ratio/statistics & numerical data , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Disease Progression , Female , Humans , Lung , Lymphocyte Count , Lymphocyte Subsets/immunology , Lymphocyte Subsets/virology , Male , Middle Aged , Patient Discharge/statistics & numerical data , Prognosis , Prospective Studies , ROC Curve , SARS-CoV-2/immunology , Severity of Illness Index
7.
Clin Immunol ; 218: 108524, 2020 09.
Article in English | MEDLINE | ID: covidwho-639598

ABSTRACT

The outbreak of SARS-CoV-2-associated pneumonia, a disease called COVID-19, has caused a pandemic worldwide. To investigate the immune responses after infection of SARS-CoV-2 in non-critical patients may help to better understand the disease progression. We collected 334 confirmed COVID-19 cases including 212 still in hospital with nucleic acid test positive on halfway for SARS-CoV-2 and 122 discharged from hospital, compared specific antibodies, immune cells, and cytokine changes between the hospitalized and discharged patients. The hospitalized patients had a longer illness time compared with discharged patients. Analysis of viral loads explained long-term or persistent infection of SARS-CoV-2, which existed with the median time of 18.5 days of the positive nucleic acid test. Serum analysis showed that the specific anti-N IgG antibody was positive in all detected patients after infection of two weeks. Neutrophils, Monocytes, NK cells, and CD4+ T cells significantly increased, while total lymphocytes and CD8+ T cells decreased from non-critical hospitalized patients after longer-term infection. Further analysis of the cytokines showed that IL-6, TNF-α, IFN-γ, IL-2, IL-4, and IL-10 from the hospitalized patients were significantly higher, indicating a potential of the increased CD4+ T cell differentiation.


Subject(s)
Betacoronavirus/pathogenicity , Cardiovascular Diseases/immunology , Coronavirus Infections/immunology , Diabetes Mellitus/immunology , Immunity, Innate , Lung Diseases/immunology , Neoplasms/immunology , Pneumonia, Viral/immunology , Aged , Antibodies, Viral/blood , Betacoronavirus/immunology , COVID-19 , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/pathology , Cardiovascular Diseases/virology , China/epidemiology , Comorbidity , Convalescence , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokines/blood , Diabetes Mellitus/epidemiology , Diabetes Mellitus/pathology , Diabetes Mellitus/virology , Female , Hospitalization , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Killer Cells, Natural/virology , Lung Diseases/epidemiology , Lung Diseases/pathology , Lung Diseases/virology , Lymphocyte Subsets/immunology , Lymphocyte Subsets/pathology , Lymphocyte Subsets/virology , Male , Middle Aged , Monocytes/immunology , Monocytes/pathology , Monocytes/virology , Neoplasms/epidemiology , Neoplasms/pathology , Neoplasms/virology , Neutrophils/immunology , Neutrophils/pathology , Neutrophils/virology , Pandemics , Patient Discharge , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS-CoV-2 , Time Factors , Viral Load/immunology
8.
Stem Cell Res Ther ; 11(1): 207, 2020 05 27.
Article in English | MEDLINE | ID: covidwho-381721

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) has grown to be a global public health emergency since patients were first detected in Wuhan, China. Thus far, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. The immune system and inflammation are proposed to play a central role in COVID-19 pathogenesis. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. Intravenous infusion of MSCs has shown promising results in COVID-19 treatment. Here, we report a case of a severe COVID-19 patient treated with human umbilical cord Wharton's jelly-derived MSCs (hWJCs) from a healthy donor in Liaocheng People's Hospital, China, from February 24, 2020. The pulmonary function and symptoms of the patient with COVID-19 pneumonia was significantly improved in 2 days after hWJC transplantation, and recovered and discharged in 7 days after treatment. After treatment, the percentage and counts of lymphocyte subsets (CD3+, CD4+, and CD8+ T cell) were increased, and the level of IL-6, TNF-α, and C-reactive protein is significantly decreased after hWJC treatment. Thus, the intravenous transplantation of hWJCs was safe and effective for the treatment of patients with COVID-19 pneumonia, especially for the patients in a critically severe condition. This report highlights the potential of hWJC infusions as an effective treatment for COVID-19 pneumonia.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Pneumonia, Viral/therapy , Betacoronavirus/genetics , C-Reactive Protein/immunology , C-Reactive Protein/metabolism , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Humans , Immunomodulation , Infusions, Intravenous , Interleukin-6/blood , Interleukin-6/immunology , Lymphocyte Subsets/immunology , Lymphocyte Subsets/virology , Male , Mesenchymal Stem Cells/immunology , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , SARS-CoV-2 , Treatment Outcome , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/immunology , Umbilical Cord/cytology , Umbilical Cord/immunology , Wharton Jelly/cytology , Wharton Jelly/immunology
9.
Clin Chim Acta ; 508: 122-129, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-260025

ABSTRACT

BACKGROUND: The underlying changes of peripheral blood inflammatory cells (PBICs) in COVID-19 patients are little known. Moreover, the risk factors for the underlying changes of PBICs and their predicting role in severe COVID-19 patients remain uncertain. MATERIAL AND METHODS: This retrospective study including two cohorts: the main cohort enrolling 45 patients of severe type serving as study group, and the secondary cohort enrolling 12 patients of no-severe type serving as control group. The PBICs analysis was based on blood routine and lymphocyte subsets. The inflammatory cell levels were compared among patients according to clinical classifications, disease-associated phases, as well as one-month outcomes. RESULTS: Compared with patients of non-severe type, the patients of severe type suffered from significantly decreased counts of lymphocytes, eosinophils, basophils, but increased counts of neutrophils. These PBICs alterations got improved in recovery phase, but persisted or got worse in aggravated phase. Compared with patients in discharged group, the patients in un-discharged/died group suffered from decreased counts of total T lymphocytes, CD4 + T lymphocytes, CD8 + T lymphocytes, as well as NK cells at 2 weeks after treatment. Clinical classification-critically severe was the independently risk factor for lymphopenia (OR = 7.701, 95%CI:1.265-46.893, P = 0.027), eosinopenia (OR = 5.595, 95%CI:1.008-31.054, P = 0.049), and worse one-month outcome (OR = 8.984; 95%CI:1.021-79.061, P = 0.048). CONCLUSION: Lymphopenia and eosinopenia may serve as predictors of disease severity and disease progression in COVID-19 patients, and enhancing the cellular immunity may contribute to COVID-19 treatment. Thus, PBICs might become a sentinel of COVID-19, and it deserves attention during COVID-19 treatment.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/diagnosis , Eosinophils/pathology , Lymphocyte Subsets/pathology , Lymphopenia/diagnosis , Pneumonia, Viral/diagnosis , Aged , Biomarkers/blood , COVID-19 , Cell Count , Coronavirus Infections/blood , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Disease Progression , Eosinophils/virology , Female , Humans , Killer Cells, Natural/pathology , Killer Cells, Natural/virology , Lymphocyte Subsets/virology , Lymphopenia/blood , Lymphopenia/physiopathology , Lymphopenia/virology , Male , Middle Aged , Monocytes/pathology , Monocytes/virology , Neutrophils/pathology , Neutrophils/virology , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Prognosis , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
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