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1.
J Immunol Methods ; 502: 113230, 2022 03.
Article in English | MEDLINE | ID: covidwho-1720358

ABSTRACT

Innate immune mechanisms are central players in response to the binding of pathogens to pattern-recognition receptors providing a crucial initial block on viral replication. Moreover, innate immune response mobilizes cells of the cellular-mediated immune system, which develop into effector cells that promote viral clearance. Here, we observed circulating leukocyte T cell response in healthy subjects, COVID-19 infected, and in healthy vaccinated subjects. We found a significant CD8+ T cells (p < 0,05) decrease and an augmented CD4+/CD8+ ratio (p < 0,05) in COVID-19 infected group compared with vaccinated subjects. In addition, healthy vaccinated subjects have a significant increased expression of CD8+ T cells, and a reduction of CD4+/CD8+ ratio with respect to subjects previously COVID-19 infected. Central Memory and Terminal Effector Memory cells (TEMRA) increased after vaccine but not among groups.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , /immunology , Adult , Aged , CD4-CD8 Ratio , COVID-19/blood , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Case-Control Studies , Cross-Sectional Studies , Female , Healthy Volunteers , Humans , Immunity, Innate , Immunogenicity, Vaccine , Immunophenotyping , Male , Middle Aged , SARS-CoV-2/immunology , Vaccination
2.
PLoS One ; 16(3): e0248675, 2021.
Article in English | MEDLINE | ID: covidwho-1574573

ABSTRACT

BACKGROUND: In December 2019, a new disease named coronavirus disease 2019 (COVID-19) was occurred. Patients who are critically ill with COVID-19 are more likely to die, especially elderly patients. We aimed to describe the effect of age on the clinical and immune characteristics of critically ill patients with COVID-19. METHODS: We retrospectively included 32 patients with COVID-19 who were confirmed to have COVID-19 by the local health authority and who were admitted to the first affiliated hospital of Zhengzhou University in Zhengzhou, China between January 3 and March 20, 2020. Clinical information and experimental test data were retrospectively collected for the patients. The 32 patients in this study were all in a critical condition and were classified as severe, according to the guidelines of 2019-nCoV infection from the National Health Commission of the People's Republic of China. Data were compared between those <60 years old and ≥60 years old. RESULTS: Of 32 patients, 13 were under 60 years old, and 19 patients were ≥60 years old. The most common symptom among all patients upon admission was fever (93.8%, 30/32). Compared to younger patients, older patients exhibited increased comorbidities. Among patients who were 60 years and older, platelet count, direct bilirubin (DBIL), indirect bilirubin(IBIL), lactate dehydrogenase (LDH), B-type natriuretic peptide (BNP), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-10 (IL-10) were significantly higher than in younger patients who were less than 60 years old. CD4+ T lymphocytes, CD8+ T lymphocytes, and NKT lymphocytes were decreased, CD4+/CD8+ T lymphocytes were significantly increased in all 32 patients, while there were no evident differences between younger and older patients. The CURB-65 (confusion, urea, respiratory, rate, blood pressure plus age ≥65 years), Acute Physiology and Chronic Health Evaluation (APACHE) II and pH value were significantly higher in older patients than in patients who were under 60 years old. However, the PaO2 and PaO2:FiO2 were lower in older patients than the younger. Compared to patients under 60 years old, patients who were 60 years and older tended to develop ARDS (15 [78.9%] vs 5 [38.5%]), septic shock (7 [36.8%] vs 0 [0.0%]) and were more likely to receive mechanical ventilation (13 [68.4%] vs 3[23.1%]). Dynamic trajectories of seven laboratory parameters were tracked on days 1, 3, 5 and 7, and significant differences in lymphocyte count (P = 0.026), D-dimer (P = 0.010), lactate dehydrogenase (P = 0.000) and C-reactive protein (P = 0.000) were observed between the two age groups. CONCLUSIONS: A high proportion of critically ill patients were 60 or older. Furthermore, rapid disease progression was noted in elderly patients. Therefore, close monitoring and timely treatment should be performed in elderly COVID-19 patients.


Subject(s)
COVID-19/epidemiology , Age Factors , Aged , CD4-CD8 Ratio , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Critical Illness , Female , Humans , Immunity , Lymphocyte Count , Male , Middle Aged , Preliminary Data , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index
3.
Scand J Immunol ; 95(3): e13125, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1550854

ABSTRACT

Around half of people with severe COVID-19 requiring intensive care unit (ICU) treatment will survive, but it is unclear how the immune response to SARS-CoV-2 differs between ICU patients that recover and those that do not. We conducted whole-blood immunophenotyping of COVID-19 patients upon admission to ICU and during their treatment and uncovered marked differences in their circulating immune cell subsets. At admission, patients who later succumbed to COVID-19 had significantly lower frequencies of all memory CD8+ T cell subsets, resulting in increased CD4-to-CD8 T cell and neutrophil-to-CD8 T cell ratios. ROC and Kaplan-Meier analyses demonstrated that both CD4-to-CD8 and neutrophil-to-CD8 ratios at admission were strong predictors of in-ICU mortality. Therefore, we propose the use of the CD4-to-CD8 T cell ratio as a marker for the early identification of those individuals likely to require enhanced monitoring and/or pro-active intervention in ICU.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Aged , CD4-CD8 Ratio/methods , Female , Humans , Immunophenotyping/methods , Intensive Care Units , Lymphocyte Count/methods , Male , Middle Aged , Prospective Studies , SARS-CoV-2/immunology
4.
Front Immunol ; 12: 720952, 2021.
Article in English | MEDLINE | ID: covidwho-1417084

ABSTRACT

The ongoing COVID-19 pandemic has increased awareness about sex-specific differences in immunity and outcomes following SARS-CoV-2 infection. Strong evidence of a male bias in COVID-19 disease severity is hypothesized to be mediated by sex differential immune responses against SARS-CoV-2. This hypothesis is based on data from other viral infections, including influenza viruses, HIV, hepatitis viruses, and others that have demonstrated sex-specific immunity to viral infections. Although males are more susceptible to most viral infections, females possess immunological features that render them more vulnerable to distinct immune-related disease outcomes. Both sex chromosome complement and related genes as well as sex steroids play important roles in mediating the development of sex differences in immunity to viral infections.


Subject(s)
COVID-19/pathology , Severity of Illness Index , Sex Characteristics , CD4 Lymphocyte Count , CD4-CD8 Ratio , Cytokines/blood , Female , Humans , Immunity, Innate/genetics , Immunity, Innate/immunology , Male , SARS-CoV-2/immunology , Sex Factors
5.
J Immunol Res ; 2021: 6657894, 2021.
Article in English | MEDLINE | ID: covidwho-1314178

ABSTRACT

BACKGROUND: The 2019 novel coronavirus SARS-CoV-2 caused large outbreaks of COVID-19 worldwide. COVID-19 resembles community-acquired pneumonia (CAP). Our aim was to identify lymphocyte subpopulations to distinguish between COVID-19 and CAP. METHODS: We compared the peripheral blood lymphocytes and their subsets in 296 patients with COVID-19 and 130 patients with CAP. Parameters for independent prediction of COVID-19 were calculated by logistic regression. RESULTS: The main lymphocyte subpopulations (CD3+CD4+, CD16+CD56+, and CD4+/CD8+ ratio) and cytokines (TNF-α and IFN-γ) of COVID-19 patients were significantly different from that of CAP patients. CD16+CD56+%, CD4+/CD8+ratio, CD19+, and CD3+CD4+ were identified as predictors of COVID-19 diagnosis by logistic regression. In addition, the CD3+CD4+counts, CD3+CD8+ counts, andTNF-α are independent predictors of disease severity in patients. CONCLUSIONS: Lymphopenia is an important part of SARS-CoV-2 infection, and lymphocyte subsets and cytokines may be useful to predict the severity and clinical outcomes of the disease.


Subject(s)
CD4-CD8 Ratio , COVID-19/blood , Interferon-gamma/blood , Lymphocyte Subsets/cytology , Pneumonia/blood , Tumor Necrosis Factor-alpha/blood , Adult , Aged , COVID-19/immunology , COVID-19/pathology , COVID-19 Testing , Community-Acquired Infections/microbiology , Female , Humans , Lymphocyte Subsets/immunology , Lymphopenia/blood , Lymphopenia/pathology , Male , Middle Aged , Pneumonia/immunology , Pneumonia/pathology , Prognosis , SARS-CoV-2/immunology , Severity of Illness Index
7.
J Leukoc Biol ; 109(1): 91-97, 2021 01.
Article in English | MEDLINE | ID: covidwho-1188013

ABSTRACT

Regulatory T cell can protect against severe forms of coronaviral infections attributable to host inflammatory responses. But its role in the pathogenesis of COVID-19 is still unclear. In this study, frequencies of total and multiple subsets of lymphocytes in peripheral blood of COVID-19 patients and discharged individuals were analyzed using a multicolor flow cytometry assay. Plasma concentration of IL-10 was measured using a microsphere-based immunoassay kit. Comparing to healthy controls, the frequencies of total lymphocytes and T cells decreased significantly in both acutely infected COVID-19 patients and discharged individuals. The frequencies of total lymphocytes correlated negatively with the frequencies of CD3- CD56+ NK cells. The frequencies of regulatory CD8+ CD25+ T cells correlated with CD4+ /CD8+ T cell ratios positively, while the frequencies of regulatory CD4+ CD25+ CD127- T cells correlated negatively with CD4+ /CD8+ T cell ratios. Ratios of CD4+ /CD8+ T cells increased significantly in patients beyond age of 45 years. And accordingly, the frequencies of regulatory CD8+ CD25+ T cells were also found significantly increased in these patients. Collectively, the results suggest that regulatory CD4+ and CD8+ T cells may play distinct roles in the pathogenesis of COVID-19. Moreover, the data indicate that NK cells might contribute to the COVID-19 associated lymphopenia.


Subject(s)
CD8-Positive T-Lymphocytes , COVID-19 , SARS-CoV-2 , T-Lymphocytes, Regulatory , Adult , Aged , Antigens, CD/blood , Antigens, CD/immunology , CD4-CD8 Ratio , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , COVID-19/blood , COVID-19/immunology , COVID-19/pathology , Female , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/pathology
8.
Biosci Rep ; 41(1)2021 01 29.
Article in English | MEDLINE | ID: covidwho-1174708

ABSTRACT

Millions of people infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been diagnosed with coronavirus infectious disease 2019 (COVID-19). The prevalence and severity of COVID-19 differ between sexes. To explain these differences, we analyzed clinical features and laboratory values in male and female COVID-19 patients. The present study included a cohort of 111 people, i.e. 36 COVID-19 patients, 54 sex- and age-matched common viral community-acquired pneumonia (CAP) patients, and 21 healthy controls. Monocyte counts, lymphocyte subset counts, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels in the peripheral blood were analyzed. Higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, monocyte counts, and CRP and ALT levels were found in male COVID-19 patients. Decreased lymphocyte subset counts and proportions were observed in COVID-19 patients, except for the CD3+ and CD8+ T cell proportions. The lower CD4+ T cell proportions and higher CD8+ T cell proportions were observed in male and severe COVID-19 patients and the differences were independent of estrogen level. The CD4+ T cell proportion was negatively associated with the CD8+ T cell proportion in male COVID-19 patients; this correlation was non-significant in females. Our work demonstrates differences between sexes in circulating monocyte counts and CD4+ T cell and CD8+ T cell proportions in COVID-19 patients, independent of estrogen levels, are associated with the clinical manifestations in COVID-19 patients with high specificity.


Subject(s)
COVID-19/immunology , Immunity, Innate , Lymphocytes/virology , Monocytes/virology , Pneumonia, Viral/immunology , SARS-CoV-2/pathogenicity , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , C-Reactive Protein/metabolism , CD4-CD8 Ratio , COVID-19/pathology , COVID-19/virology , Case-Control Studies , Community-Acquired Infections , Estradiol/blood , Female , Humans , Leukocyte Count , Lymphocytes/immunology , Male , Middle Aged , Monocytes/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Severity of Illness Index , Sex Factors
9.
Int Immunopharmacol ; 95: 107531, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1122564

ABSTRACT

PURPOSE: Researches revealed that probiotics maybe a potential strategy for COVID-19, whereas there is a lack of related evidence. This study aims to analyze the role of probiotics on severe COVID-19 patients. METHODS: In the current retrospective single-center study, we collected data of 311 consecutive severe patients with confirmed COVID-19 in Wuhan Union Hospital from Feb 3rd to Feb 20th, 2020. Epidemiological, clinical and medication characteristics were compared and analyzed between patients with or without probiotics. RESULTS: In total, 93 of the 123 patients (75.61%) who were treated with probiotics survived to hospital discharge with the median inpatient day of 32 days and mean virus clearance time of 23 days, which were significantly longer than those of patients without probiotics. There were no bias in laboratory parameters, except for IL-6 and ESR, which were significantly higher in patients treated probiotics. We tracked the dynamic changes of 8 selected laboratory parameters (IL-6, CRP, total T lymphocytes, NK cells, B lymphocyte, CD4 + T cells, CD8 + T cells and CD4/CD8 ratio) and found that probiotics could not reduce the increased IL-6 levels but possessed the ability to moderate the immunity and decreased the incidence of secondary infection in COVID-19 patients. CONCLUSIONS: Probiotics could be an effective strategy for the treatment of COVID-19 patients to reduce the secondary infection and moderated the immunity.


Subject(s)
COVID-19/therapy , Probiotics/therapeutic use , Aged , B-Lymphocytes/immunology , CD4-CD8 Ratio , COVID-19/blood , COVID-19/immunology , Female , Humans , Inflammation/therapy , Interleukin-6/blood , Killer Cells, Natural/immunology , Male , Middle Aged , Receptors, Immunologic/blood , Retrospective Studies , Severity of Illness Index , T-Lymphocytes/immunology , Treatment Outcome
10.
Sci Rep ; 10(1): 22369, 2020 12 22.
Article in English | MEDLINE | ID: covidwho-997944

ABSTRACT

We aimed to analyse clinical characteristics and identify risk factors predicting all-cause mortality in older patients with severe coronavirus disease 2019 (COVID-19). A total of 281 older patients with severe COVID-19 were categorized into two age groups (60-79 years and ≥ 80 years). Epidemiological, clinical, and laboratory data, and outcome were obtained. Patients aged ≥ 80 years had higher mortality (63.6%) than those aged 60-79 years (33.5%). Anorexia and comorbidities including hypertension, diabetes and COPD, higher levels of lactate dehydrogenase (LDH), osmotic pressure, C-reactive protein, D-dimer, high-sensitivity troponin I and procalcitonin, and higher SOFA scores were more common in patients aged > 80 years than those aged 60-79 years and also more common and higher in non-survivors than survivors. LDH, osmotic pressure, C-reactive protein, D-dimer, high-sensitivity troponin I, and procalcitonin were positively correlated with age and sequential organ failure assessment (SOFA), whereas CD8+ and lymphocyte counts were negatively correlated with age and SOFA. Anorexia, comorbidities including hypertension, diabetes, and chronic obstructive pulmonary disease (COPD), LDH, osmotic pressure, and SOFA were significantly associated with 28-day all-cause mortality. LDH, osmotic pressure and SOFA were valuable for predicting 28-day all-cause mortality, whereas the area under the receiver operating characteristic curve of LDH was the largest, with sensitivity of 86.0% and specificity of 80.8%. Therefore, patients with severe COVID-19 aged ≥ 80 years had worse condition and higher mortality than did those aged 60-79 years, and anorexia and comorbidities including hypertension, diabetes, COPD, elevated plasma osmotic pressure, LDH, and high SOFA were independent risk factors associated with 28-day all-cause mortality in older patients with severe COVID-19. LDH may have the highest predictive value for 28-day all-cause mortality in all examined factors.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Organ Dysfunction Scores , SARS-CoV-2/genetics , Age Factors , Aged , Aged, 80 and over , Anorexia , CD4-CD8 Ratio , COVID-19/blood , COVID-19/virology , China/epidemiology , Comorbidity , Female , Humans , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Prognosis , Real-Time Polymerase Chain Reaction , Retrospective Studies , Risk Factors
11.
Biosci Rep ; 41(1)2021 01 29.
Article in English | MEDLINE | ID: covidwho-989978

ABSTRACT

Millions of people infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been diagnosed with coronavirus infectious disease 2019 (COVID-19). The prevalence and severity of COVID-19 differ between sexes. To explain these differences, we analyzed clinical features and laboratory values in male and female COVID-19 patients. The present study included a cohort of 111 people, i.e. 36 COVID-19 patients, 54 sex- and age-matched common viral community-acquired pneumonia (CAP) patients, and 21 healthy controls. Monocyte counts, lymphocyte subset counts, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels in the peripheral blood were analyzed. Higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, monocyte counts, and CRP and ALT levels were found in male COVID-19 patients. Decreased lymphocyte subset counts and proportions were observed in COVID-19 patients, except for the CD3+ and CD8+ T cell proportions. The lower CD4+ T cell proportions and higher CD8+ T cell proportions were observed in male and severe COVID-19 patients and the differences were independent of estrogen level. The CD4+ T cell proportion was negatively associated with the CD8+ T cell proportion in male COVID-19 patients; this correlation was non-significant in females. Our work demonstrates differences between sexes in circulating monocyte counts and CD4+ T cell and CD8+ T cell proportions in COVID-19 patients, independent of estrogen levels, are associated with the clinical manifestations in COVID-19 patients with high specificity.


Subject(s)
COVID-19/immunology , Immunity, Innate , Lymphocytes/virology , Monocytes/virology , Pneumonia, Viral/immunology , SARS-CoV-2/pathogenicity , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , C-Reactive Protein/metabolism , CD4-CD8 Ratio , COVID-19/pathology , COVID-19/virology , Case-Control Studies , Community-Acquired Infections , Estradiol/blood , Female , Humans , Leukocyte Count , Lymphocytes/immunology , Male , Middle Aged , Monocytes/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Severity of Illness Index , Sex Factors
12.
Transpl Infect Dis ; 23(2): e13500, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-916948

ABSTRACT

There is still no consensus on the optimal management of COVID-19 within the general population due to the emerging evidence base. High-risk groups, including kidney transplant recipients living with HIV present unique additional challenges. Here we discuss two kidney transplant recipients living with HIV with SARS-CoV-2 infection and their clinical course, and review the existing literature for this subset of challenging patients.


Subject(s)
Anti-HIV Agents/therapeutic use , COVID-19/therapy , Glucocorticoids/therapeutic use , Graft Rejection/prevention & control , HIV Infections/drug therapy , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Adult , Anti-Bacterial Agents/therapeutic use , Atovaquone/therapeutic use , CD4 Lymphocyte Count , CD4-CD8 Ratio , COVID-19/complications , COVID-19/immunology , Dideoxynucleosides/therapeutic use , Female , HIV Infections/complications , HIV Infections/immunology , HIV-1/genetics , Humans , Immunocompromised Host/immunology , Lamivudine/therapeutic use , Male , Middle Aged , Mycophenolic Acid/therapeutic use , Pneumonia, Pneumocystis/prevention & control , Prednisolone/therapeutic use , RNA, Viral , Raltegravir Potassium/therapeutic use , SARS-CoV-2 , Tacrolimus/therapeutic use , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use
13.
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
14.
Pediatr Pulmonol ; 55(12): 3602-3609, 2020 12.
Article in English | MEDLINE | ID: covidwho-915178

ABSTRACT

OBJECTIVE: To identify the risk factors for redetectable positivity (RP), and to provide a basis for prevention and control of coronavirus disease-2019 (COVID-19) in children. METHODS: A retrospective study was performed on all pediatric patients diagnosed with COVID-19. RP was defined as the positive result of real-time reverse transcriptase polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after symptom resolution and discharge. Children were defined as being less than 18 years old. RESULTS: Fourteen out of 38 (36.8%) pediatric patients exhibited RP. Compared with the non-RP group (n = 24), the RP group (n = 14) had more family cluster infections, relatively higher white blood cell (WBC) count and longer plasma prothrombin time (PT), while age and gender were insignificant. T lymphocyte subclassification was observed at five-time points: the first test after admission, 2 weeks, and 1, 2, and 3 months after discharge. The RP group had a higher percentage and count of CD8+ T lymphocytes and lower CD4+/CD8+ ratio at 2 weeks, while a lower percentage and count of CD4+ T lymphocytes and lower CD4+/CD8+ ratio at 2 months. The positive rate of nasopharyngeal swabs by RT-PCR was higher during the onset, while that of anal swabs was higher during the recovery of COVID-19. CONCLUSIONS: Family cluster infection, higher WBC count, and longer PT are the early risk factors for RP in recovered COVID-19 children. The dynamic changes in number and ratio of CD4+ and CD8+ T lymphocytes may be involved in prolonged SARS-CoV-2 clearance. Nasopharyngeal swabs sampling during the onset and anal swabs sampling during the recovery may improve the positivity rate of RT-PCR.


Subject(s)
Anal Canal/virology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Coronavirus Infections/diagnosis , Nasopharynx/virology , Pneumonia, Viral/diagnosis , Betacoronavirus , CD4 Lymphocyte Count , CD4-CD8 Ratio , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Child , Child, Preschool , Clinical Laboratory Techniques , Coronavirus , Coronavirus Infections/blood , Coronavirus Infections/immunology , Coronavirus Infections/transmission , Female , Hospitalization , Humans , Length of Stay , Leukocyte Count , Male , Pandemics , Patient Discharge , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/transmission , Prothrombin Time , Real-Time Polymerase Chain Reaction , Recurrence , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , SARS-CoV-2 , Virus Shedding
15.
J Clin Virol ; 133: 104661, 2020 12.
Article in English | MEDLINE | ID: covidwho-856844

ABSTRACT

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is threatening billions of people. We described the clinical characteristics and explore virological and immunological factors associated with clinical outcomes. METHODS: 297 COVID-19 patients hospitalized in Guangzhou Eighth People's Hospital between January 20 and February 20, 2020 were included. Epidemiological, clinical and laboratory data were collected and analyzed. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA in respiratory tract, blood samples and digestive tract was detected and lymphocyte subsets were tested periodically. RESULT: Among the 297 patients (median age of 48 years), 154 (51.9 %) were female, 245 (82.5 %) mild/moderate cases, and 52 (17.5 %) severe/critical cases. 270 patients were detected for SARS-CoV-2 RNA in anal swabs and/or blood samples, and the overall positive rate was 23.0 % (62/270), higher in severe/critical cases than in mild/moderate cases (52.0 % vs. 16.4 %, P < 0.001). The CD4/CD8 ratio on admission was significantly higher in severe/critical cases than in mild/moderate cases (1.84 vs. 1.50, P = 0.022). During a median follow-up period of 17 days, 36 (12.1 %) patients were admitted to intensive care unit (ICU), 16 (5.4 %) patients developed respiratory failure and underwent mechanical ventilation, four (1.3 %) patients needed extracorporeal membrane oxygenation (ECMO), only one (0.34 %) patients died of multiple organ failure. Detectable SARS-CoV-2 RNA in anal swabs and/or blood samples, as well as higher CD4/CD8 ratio were independent risk factors of respiratory failure and ICU admission. CONCLUSIONS: Most of COVID-19 patients in Guangzhou are mild/moderate, and presence of extrapulmonary virus and higher CD4/CD8 ratio are associated with higher risk of worse outcomes.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Adult , CD4-CD8 Ratio , COVID-19/mortality , COVID-19/therapy , China , Female , Humans , Intensive Care Units , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Factors
16.
PLoS One ; 15(9): e0239532, 2020.
Article in English | MEDLINE | ID: covidwho-798278

ABSTRACT

To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease.


Subject(s)
CD4-Positive T-Lymphocytes/pathology , Coronavirus Infections/blood , Coronavirus Infections/immunology , Cytokines/blood , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Adolescent , Adult , Aged , Betacoronavirus , CD4 Lymphocyte Count , CD4-CD8 Ratio , COVID-19 , Child , Coronavirus Infections/diagnosis , Female , Humans , Interleukin-6/blood , Lymphopenia/blood , Lymphopenia/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , SARS-CoV-2 , Severity of Illness Index , Tumor Necrosis Factor-alpha/blood
17.
Mult Scler ; 26(10): 1261-1264, 2020 09.
Article in English | MEDLINE | ID: covidwho-696957

ABSTRACT

Approximately 200,000 multiple sclerosis (MS) patients worldwide receive B-cell-depleting immunotherapy with rituximab (anti-CD20), which eliminates the ability to generate an antibody response to new infections. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies might help viral clearance, these patients could be at risk of severe complications if infected. Here, we report on an MS patient who had received rituximab for ~3 years. The patient was examined 5 days before the onset of coronavirus disease 2019 (COVID-19) symptoms and was admitted to the hospital 2 days after. She recovered 14 days after symptom onset despite having a 0% B lymphocyte count and not developing SARS-CoV-2 immunoglobulin G (IgG) antibodies.


Subject(s)
B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , Coronavirus Infections/immunology , Immunity, Cellular/immunology , Killer Cells, Natural/immunology , Multiple Sclerosis, Chronic Progressive/drug therapy , Pneumonia, Viral/immunology , Rituximab/therapeutic use , Betacoronavirus , CD4-CD8 Ratio , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Disease Progression , Female , Humans , Lymphocyte Count , Middle Aged , Multiple Sclerosis, Chronic Progressive/complications , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , SARS-CoV-2
18.
Front Immunol ; 11: 1648, 2020.
Article in English | MEDLINE | ID: covidwho-685338

ABSTRACT

Cytokine storm is an acute hyperinflammatory response that may be responsible for critical illness in many conditions including viral infections, cancer, sepsis, and multi-organ failure. The phenomenon has been implicated in critically ill patients infected with SARS-CoV-2, the novel coronavirus implicated in COVID-19. Critically ill COVID-19 patients experiencing cytokine storm are believed to have a worse prognosis and increased fatality rate. In SARS-CoV-2 infected patients, cytokine storm appears important to the pathogenesis of several severe manifestations of COVID-19: acute respiratory distress syndrome, thromboembolic diseases such as acute ischemic strokes caused by large vessel occlusion and myocardial infarction, encephalitis, acute kidney injury, and vasculitis (Kawasaki-like syndrome in children and renal vasculitis in adult). Understanding the pathogenesis of cytokine storm will help unravel not only risk factors for the condition but also therapeutic strategies to modulate the immune response and deliver improved outcomes in COVID-19 patients at high risk for severe disease. In this article, we present an overview of the cytokine storm and its implications in COVID-19 settings and identify potential pathways or biomarkers that could be targeted for therapy. Leveraging expert opinion, emerging evidence, and a case-based approach, this position paper provides critical insights on cytokine storm from both a prognostic and therapeutic standpoint.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Critical Care/methods , Cytokines/blood , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Adrenal Cortex Hormones/therapeutic use , Angiotensin-Converting Enzyme 2 , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , CD4-CD8 Ratio , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 , Clinical Decision-Making/methods , Coronavirus Infections/blood , Coronavirus Infections/mortality , Critical Illness , Endothelial Cells/metabolism , Female , Humans , Immunocompromised Host , Interleukin-6/antagonists & inhibitors , Janus Kinase Inhibitors/therapeutic use , Male , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/blood , Pneumonia, Viral/mortality , SARS-CoV-2 , Sex Factors , Thrombosis
19.
Life Sci ; 258: 118167, 2020 Oct 01.
Article in English | MEDLINE | ID: covidwho-684176

ABSTRACT

AIMS: This study aimed to make a comparison between the clinical laboratory-related factors, complete blood count (CBC) indices, cytokines, and lymphocyte subsets in order to distinguish severe coronavirus disease 2019 (COVID-19) cases from the non-severe ones. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, Scopus, and Web of Science databases until March 31, 2020. Cochrane's Q test and the I2 statistic were used to determine heterogeneity. We used the random-effect models to pool the weighted mean differences (WMDs) and 95% confidence intervals (CIs). KEY FINDINGS: Out of a total of 8557 initial records, 44 articles (50 studies) with 7865 patients (ranging from 13 to 1582), were included. Our meta-analyses with random-effect models showed a significant decrease in lymphocytes, monocyte, CD4+ T cells, CD8+ T cells, CD3 cells, CD19 cells, and natural killer (NK) cells and an increase in the white blood cell (WBC), neutrophils, neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP)/hs-CRP, erythrocyte sedimentation rate (ESR), ferritin, procalcitonin (PCT), and serum amyloid A (SAA), interleukin-2 (IL-2), IL-2R, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (INF-γ) in the severe group compared to the non-severe group. However, no significant differences were found in IL-1ß, IL-17, and CD4/CD8 T cell ratio between the two groups. SIGNIFICANCE: Decrease in total lymphocytes and lymphocyte subsets as well as the elevation of CRP, ESR, SAA, PCT, ferritin, and cytokines, but not IL-1ß and IL-17, were closely associated with COVID-19 severity, implying reliable indicators of severe COVID-19.


Subject(s)
Coronavirus Infections/blood , Cytokines/blood , Lymphocytes/immunology , Pneumonia, Viral/blood , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , CD4-CD8 Ratio , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Cytokines/immunology , Humans , Lymphocyte Count , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Prognosis , SARS-CoV-2
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