Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 44
Filter
1.
Dis Markers ; 2021: 6304189, 2021.
Article in English | MEDLINE | ID: covidwho-1553755

ABSTRACT

Background: Early identification of patients with severe coronavirus disease (COVID-19) at an increased risk of progression may promote more individualized treatment schemes and optimize the use of medical resources. This study is aimed at investigating the utility of the C-reactive protein to albumin (CRP/Alb) ratio for early risk stratification of patients. Methods: We retrospectively reviewed 557 patients with COVID-19 with confirmed outcomes (discharged or deceased) admitted to the West Court of Union Hospital, Wuhan, China, between January 29, 2020 and April 8, 2020. Patients with severe COVID-19 (n = 465) were divided into stable (n = 409) and progressive (n = 56) groups according to whether they progressed to critical illness or death during hospitalization. To predict disease progression, the CRP/Alb ratio was evaluated on admission. Results: The levels of new biomarkers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, CRP/Alb ratio, and systemic immune-inflammation index, were higher in patients with progressive disease than in those with stable disease. Correlation analysis showed that the CRP/Alb ratio had the strongest positive correlation with the sequential organ failure assessment score and length of hospital stay in survivors. Multivariate logistic regression analysis showed that percutaneous oxygen saturation (SpO2), D-dimer levels, and the CRP/Alb ratio were risk factors for disease progression. To predict clinical progression, the areas under the receiver operating characteristic curves of Alb, CRP, CRP/Alb ratio, SpO2, and D-dimer were 0.769, 0.838, 0.866, 0.107, and 0.748, respectively. Moreover, patients with a high CRP/Alb ratio (≥1.843) had a markedly higher rate of clinical deterioration (log - rank p < 0.001). A higher CRP/Alb ratio (≥1.843) was also closely associated with higher rates of hospital mortality, ICU admission, invasive mechanical ventilation, and a longer hospital stay. Conclusion: The CRP/Alb ratio can predict the risk of progression to critical disease or death early, providing a promising prognostic biomarker for risk stratification and clinical management of patients with severe COVID-19.


Subject(s)
C-Reactive Protein/metabolism , COVID-19/diagnosis , Coronary Disease/diagnosis , Hypertension/diagnosis , Pulmonary Disease, Chronic Obstructive/diagnosis , SARS-CoV-2/pathogenicity , Serum Albumin, Human/metabolism , Aged , Area Under Curve , Biomarkers/blood , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , China/epidemiology , Comorbidity , Coronary Disease/epidemiology , Coronary Disease/mortality , Coronary Disease/virology , Disease Progression , Early Diagnosis , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Hypertension/epidemiology , Hypertension/mortality , Hypertension/virology , Length of Stay/statistics & numerical data , Lymphocytes/pathology , Lymphocytes/virology , Male , Middle Aged , Neutrophils/pathology , Neutrophils/virology , Prognosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Disease, Chronic Obstructive/virology , ROC Curve , Retrospective Studies , SARS-CoV-2/growth & development , Severity of Illness Index , Survival Analysis
2.
Mol Syst Biol ; 17(10): e10387, 2021 10.
Article in English | MEDLINE | ID: covidwho-1478718

ABSTRACT

We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.


Subject(s)
COVID-19/immunology , Computational Biology/methods , Databases, Factual , SARS-CoV-2/immunology , Software , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/genetics , COVID-19/virology , Computer Graphics , Cytokines/genetics , Cytokines/immunology , Data Mining/statistics & numerical data , Gene Expression Regulation , Host Microbial Interactions/genetics , Host Microbial Interactions/immunology , Humans , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Immunity, Innate/drug effects , Lymphocytes/drug effects , Lymphocytes/immunology , Lymphocytes/virology , Metabolic Networks and Pathways/genetics , Metabolic Networks and Pathways/immunology , Myeloid Cells/drug effects , Myeloid Cells/immunology , Myeloid Cells/virology , Protein Interaction Mapping , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Signal Transduction , Transcription Factors/genetics , Transcription Factors/immunology , Viral Proteins/genetics , Viral Proteins/immunology
3.
Clin Microbiol Infect ; 26(10): 1380-1385, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1439953

ABSTRACT

OBJECTIVES: The aim was to determine the clinical characteristics of COVID-19 patients because the SARS-CoV-2 virus continues to circulate in the population. METHODS: This is a retrospective, multicentre, cohort study. Adult COVID-19 cases from four hospitals in Zhejiang were enrolled and clustered into three groups based on epidemiological history. First-generation patients had a travel history to Hubei within 14 days before disease onset; second-generation patients had a contact history with first-generation patients; third-generation patients had a contact history with second-generation patients. Demographic, clinical characteristics, clinical outcomes and duration of viral shedding were analysed. RESULTS: A total of 171 patients were enrolled, with 83, 44 and 44 patients in the first-, second-, and third-generation, respectively. Compared with the first and second generations, third-generation patients were older (61.3 vs. 48.3 and 44.0 years, p < 0.001) and had more coexisting conditions (56.8% vs. 36.1% and 27.3%, p 0.013). At 7 ± 1 days from illness onset, third-generation patients had lower lymphocyte (0.6 vs. 0.8 and 0.8 × 109/L, p 0.007), higher C-reactive protein (29.7 vs. 17.1 and 13.8 mg/L, p 0.018) and D-dimer (1066 vs. 412.5 and 549 µg/L, p 0.002) and more lesions involving the pulmonary lobes (lobes ≥5, 81.8% vs. 53.0% and 34.1%, p < 0.001). The proportions of third-generation patients developing severe illness (72.7% vs. 32.5% and 27.3%, p < 0.001), critical illness (38.6% vs. 10.8% and 6.8%, p < 0.001) and receiving endotracheal intubation (20.5% vs. 3.6% and 2.3%, p 0.002) were higher than in the other two groups. DISCUSSION: Third-generation patients were older, had more underlying comorbidities and had a higher proportion of severe or critical illness than first- and second-generation patients.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Diabetes Mellitus/epidemiology , Hypertension/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Adult , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19 , China/epidemiology , Comorbidity , Contact Tracing , Coronavirus Infections/blood , Coronavirus Infections/physiopathology , Coronavirus Infections/transmission , Diabetes Mellitus/blood , Diabetes Mellitus/physiopathology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Hypertension/blood , Hypertension/physiopathology , Interleukin-6/blood , Intubation, Intratracheal , Lymphocytes/pathology , Lymphocytes/virology , Male , Middle Aged , Pneumonia, Viral/blood , Pneumonia, Viral/physiopathology , Pneumonia, Viral/transmission , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/physiopathology , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Travel/statistics & numerical data , Virus Shedding
4.
J Med Virol ; 93(9): 5438-5445, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363683

ABSTRACT

Adequate maternal selenium level is essential for immune response and healthy pregnancy. This study aimed to shed light on the selenium status of pregnant women with COVID-19 and the effects of potential deficiency in serum selenium levels. Totally 141 pregnant women, 71 of them were COVID-19 patients, in different trimesters were included in the study. Maternal serum selenium levels, demographic and clinical parameters were determined. Serum selenium levels of pregnant women in the second (p: .0003) and third (p: .001) trimesters with COVID-19 were significantly lower than in the healthy group. Maternal selenium level was found to be negatively correlated with gestational week (p < .0001, r: -.541), D-dimer (p: .0002, r: -.363) and interleukin-6 (IL-6) level (p: .02, r: -.243). In the second trimester, serum selenium level positively correlated with white blood cell (p: .002, r: .424), neutrophil (p: .006, r: .39), lymphocyte (p: .004, r: .410) count and hemoglobin (p: .02, r: .323), hematocrit (p: .008, r: .38) status. In the third trimester, it was found that maternal selenium level positively correlated with monocyte (p: .04, r: .353) and negatively correlated with C-reactive protein level (p: .03, r: -.384). Serum selenium level was gradually decreased during the pregnancy period, however, this natural decrease was enhanced together with COVID-19 infection. The reason might be increased selenium needs depended on the immune response against infection. The decrease in maternal selenium level was found to be related to IL-6 and D-dimer levels, which indicate selenium's role in disease progression.


Subject(s)
COVID-19/blood , COVID-19/immunology , Pregnancy Trimesters/blood , SARS-CoV-2/pathogenicity , Selenium/blood , Adult , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/virology , Case-Control Studies , Female , Fibrin Fibrinogen Degradation Products/metabolism , Hematocrit , Hemoglobins/metabolism , Humans , Interleukin-6/blood , Lymphocytes/immunology , Lymphocytes/virology , Monocytes/immunology , Monocytes/virology , Neutrophils/immunology , Neutrophils/virology , Pregnancy , Pregnancy Trimesters/immunology , Severity of Illness Index
5.
J Med Virol ; 93(9): 5425-5431, 2021 09.
Article in English | MEDLINE | ID: covidwho-1363680

ABSTRACT

A rapid outbreak of novel coronavirus, coronavirus disease-2019 (COVID-19), has made it a global pandemic. This study focused on the possible association between lymphopenia and computed tomography (CT) scan features and COVID-19 patient mortality. The clinical data of 596 COVID-19 patients were collected from February 2020 to September 2020. The patients' serological survey and CT scan features were retrospectively explored. The median age of the patients was 56.7 ± 16.4 years old. Lung involvement was more than 50% in 214 COVID-19 patients (35.9%). The average blood lymphocyte percentage was 20.35 ± 10.16 (normal range, 20%-50%). Although the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were high in more than 80% of COVID-19 patients; CRP, ESR, and platelet-to-lymphocyte ratio (PLR) may not indicate the in-hospital mortality of COVID-19. Patients with severe lung involvement and lymphopenia were found to be significantly associated with increased odds of death (odds ratio, 9.24; 95% confidence interval, 4.32-19.78). These results indicated that lymphopenia < 20% along with pulmonary involvement >50% impose a multiplicative effect on the risk of mortality. The in-hospital mortality rate of this group was significantly higher than other COVID-19 hospitalized cases. Furthermore, they meaningfully experienced a prolonged stay in the hospital (p = .00). Lymphocyte count less than 20% and chest CT scan findings with more than 50% involvement might be related to the patient's mortality. These could act as laboratory and clinical indicators of disease severity, mortality, and outcome.


Subject(s)
COVID-19/complications , Lung/pathology , Lymphopenia/complications , Pneumonia/complications , SARS-CoV-2/pathogenicity , Adult , Aged , Biomarkers/blood , Blood Platelets/pathology , Blood Platelets/virology , Blood Sedimentation , C-Reactive Protein , COVID-19/diagnostic imaging , COVID-19/mortality , COVID-19/virology , Female , Hospital Mortality , Humans , Iran , Lung/virology , Lymphocytes/pathology , Lymphocytes/virology , Lymphopenia/diagnostic imaging , Lymphopenia/mortality , Lymphopenia/virology , Male , Middle Aged , Pneumonia/diagnostic imaging , Pneumonia/mortality , Pneumonia/virology , Retrospective Studies , Severity of Illness Index , Survival Analysis , Tomography, X-Ray Computed
6.
Immunology ; 164(3): 467-475, 2021 11.
Article in English | MEDLINE | ID: covidwho-1266332

ABSTRACT

A number of mechanisms have been proposed to explain the well-established link between diabetic status and an increased susceptibility to infection. Notably, diabetes has been shown to be one of the strongest factors influencing healthcare outcome in COVID-19 infections. Though it has long been noted that lymphocytes upregulate insulin receptors following immune activation, until recently, this observation has received little attention. Here, we point out key findings implicating dysregulated insulin signalling in immune cells as a possible contributing factor in the immune pathology associated with diabetes. Mechanistically, insulin, by activating the PI3K/Akt/mTOR pathway, regulates various aspects of both myeloid cells and lymphocytes, such as cell survival, metabolic reprogramming and the polarization and differentiation of immune cells. PI3K signalling is also supressed by immune checkpoint proteins, suggesting that insulin signalling may antagonize peripheral tolerance. Remarkably, it has also recently been shown that, following insulin binding, the insulin receptor translocates to the nucleus where it plays a key role in regulating the transcription of various immune-related genes, including pathways involved in viral infections. Taken together, these observations suggest that dysregulated insulin signalling may directly contribute to a defective immune response during COVID-19 infections.


Subject(s)
Blood Glucose/metabolism , COVID-19/metabolism , Diabetes Mellitus, Type 1/metabolism , Insulin/metabolism , Lymphocytes/metabolism , SARS-CoV-2/pathogenicity , Animals , Biomarkers/blood , COVID-19/immunology , COVID-19/physiopathology , COVID-19/virology , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/physiopathology , Host-Pathogen Interactions , Humans , Immune Checkpoint Proteins/metabolism , Insulin Resistance , Lymphocytes/immunology , Lymphocytes/virology , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Receptor, Insulin/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism
7.
J Med Virol ; 93(9): 5438-5445, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1230212

ABSTRACT

Adequate maternal selenium level is essential for immune response and healthy pregnancy. This study aimed to shed light on the selenium status of pregnant women with COVID-19 and the effects of potential deficiency in serum selenium levels. Totally 141 pregnant women, 71 of them were COVID-19 patients, in different trimesters were included in the study. Maternal serum selenium levels, demographic and clinical parameters were determined. Serum selenium levels of pregnant women in the second (p: .0003) and third (p: .001) trimesters with COVID-19 were significantly lower than in the healthy group. Maternal selenium level was found to be negatively correlated with gestational week (p < .0001, r: -.541), D-dimer (p: .0002, r: -.363) and interleukin-6 (IL-6) level (p: .02, r: -.243). In the second trimester, serum selenium level positively correlated with white blood cell (p: .002, r: .424), neutrophil (p: .006, r: .39), lymphocyte (p: .004, r: .410) count and hemoglobin (p: .02, r: .323), hematocrit (p: .008, r: .38) status. In the third trimester, it was found that maternal selenium level positively correlated with monocyte (p: .04, r: .353) and negatively correlated with C-reactive protein level (p: .03, r: -.384). Serum selenium level was gradually decreased during the pregnancy period, however, this natural decrease was enhanced together with COVID-19 infection. The reason might be increased selenium needs depended on the immune response against infection. The decrease in maternal selenium level was found to be related to IL-6 and D-dimer levels, which indicate selenium's role in disease progression.


Subject(s)
COVID-19/blood , COVID-19/immunology , Pregnancy Trimesters/blood , SARS-CoV-2/pathogenicity , Selenium/blood , Adult , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/virology , Case-Control Studies , Female , Fibrin Fibrinogen Degradation Products/metabolism , Hematocrit , Hemoglobins/metabolism , Humans , Interleukin-6/blood , Lymphocytes/immunology , Lymphocytes/virology , Monocytes/immunology , Monocytes/virology , Neutrophils/immunology , Neutrophils/virology , Pregnancy , Pregnancy Trimesters/immunology , Severity of Illness Index
8.
J Med Virol ; 93(9): 5405-5408, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1208994

ABSTRACT

The new type of coronavirus could cause severe acute respiratory syndrome and injuries in other systems as well. Multiple organ damage can occur rapidly in patients infected with coronavirus disease 2019 (COVID-19). Previous studies have shown that many laboratory biomarkers were not within the normal ranges in COVID-19 patients. We aimed to summarize laboratory parameters and the tumor markers in COVID-19 patients. This is a retrospective cohort study conducted on 53 women between the ages of 19-85 years infected with COVID-19 at a training and research hospital between May 2020 and August 2020. Of the 53 women, 16 (30.2%) had leukopenia. The mean C-reactive protein level was 18.42 ± 59.33 mg/L. The mean procalcitonin level was 0.1 ± 0.21 µg/L. The liver function tests were within normal limits. The mean creatinine level was 0.58 ± 0.37 mg/dl. Elevated levels of α-fetoprotein (AFP) in 1 patient, elevated levels of carcinoembryonic antigen (CEA) in 2 patients, elevated levels of cancer antigen 125 (CA125) in 4 patients, elevated levels of CA19-9 in 2 patients, and elevated levels of CA15-3 in 2 patients were detected. One of 4 patients who were taken to the intensive care unit had elevated levels of AFP. In addition, 2 of 4 patients who were taken to the intensive care unit had elevated levels of CA125 and CA15-3. Except for AFP, levels of all tumor markers of the patient who died were high. We found that COVID-19 had no effect on tumor markers (CA125, CA19-9, CA15-3, AFP, and CEA).


Subject(s)
CA-125 Antigen/blood , CA-19-9 Antigen/blood , COVID-19/blood , Carcinoembryonic Antigen/blood , Leukopenia/blood , Mucin-1/blood , Pandemics , alpha-Fetoproteins/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , C-Reactive Protein/metabolism , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Leukopenia/diagnosis , Leukopenia/virology , Lymphocytes/virology , Middle Aged , Neutrophils/virology , Procalcitonin/blood , Retrospective Studies , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity , Troponin/blood , Turkey/epidemiology
9.
Cell Death Differ ; 28(9): 2765-2777, 2021 09.
Article in English | MEDLINE | ID: covidwho-1195611

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (~45.1 nm/s) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.


Subject(s)
COVID-19/virology , Giant Cells/virology , Lymphocytes/virology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , COVID-19/pathology , Cell Line , Cell Line, Tumor , Giant Cells/pathology , HEK293 Cells , HeLa Cells , Humans , Jurkat Cells , K562 Cells , Lymphocytes/pathology , Virus Internalization , Virus Replication/genetics
10.
Curr Med Sci ; 41(2): 312-317, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1193160

ABSTRACT

We here aimed to investigate the impact of gender on the clinical characteristics and laboratory results of patients with coronavirus disease 2019 (COVID-19) and provide clues to the pathological mechanisms underlying COVID-19. A retrospective study was performed. Clinical characteristics, severity of lung infection, laboratory results, and prognoses of patients of different gender were analyzed. A total of 242 patients were finally included. The median age was 58 years (IQR: 40-68), including 54 (22.3%) hospital staffs. Ninety-four (38.8%) were male and 148 (61.1%) were female. The proportion of patients with diabetes was significantly higher in the male group than in the female group (P=0.034). Male patients had a significantly larger proportion of severe lung infection, higher leukocyte count, neutrophil count, neutrophil-to-lymphocyte ratio, C-reactive protein, and procalcitonin than female. Furthermore, male patients had worse liver, cardiac, and coagulation function than their female counterparts. Male patients with COVID-19 showed more severe inflammation reaction and coagulation dysfunction than female patients. In conclusion, gender is associated with host response to SARS-CoV-2 infection.


Subject(s)
COVID-19/epidemiology , Lung/pathology , SARS-CoV-2/pathogenicity , Sex Characteristics , Adult , Aged , C-Reactive Protein/metabolism , COVID-19/diagnosis , COVID-19/therapy , COVID-19/virology , Hospitalization , Humans , Leukocyte Count , Lung/virology , Lymphocytes/metabolism , Lymphocytes/virology , Male , Middle Aged , Neutrophils/metabolism , Neutrophils/virology , Prognosis
11.
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
12.
Iran J Immunol ; 18(1): 54-64, 2021 03.
Article in English | MEDLINE | ID: covidwho-1160833

ABSTRACT

BACKGROUND: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is recognized for the first time in Wuhan, China. The cytokine storm is a known factor causing major clinical symptoms leading to death in COVID-19 patients. OBJECTIVE: To investigate and compare the serum levels of different cytokines in COVID-19 patients with different clinical severity. METHODS: Concentrations of serum cytokines, including IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, and GM-CSF, were measured in 61 COVID-19 patients and 31 normal controls with ELISA. We investigated the correlation between the levels of these cytokines and clinical severity, CRP level, neutrophil and lymphocyte count in patients with COVID-19. RESULTS: Our data indicated that the levels of IL-1ß, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF, but not IL-10 were significantly increased in COVID-19 patients compared to normal controls. Statistical analysis showed that the level of IL-1ß, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF were higher in severe COVID-19 than those of mild cases. The concentrations of all mentioned cytokines were negatively associated with the absolute count of lymphocytes, and positively correlated with the CRP level and the absolute count of neutrophils. CONCLUSION: The current study suggests that high levels of various cytokines correlate with the disease severity and immunopathogenesis of COVID-19.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Cytokines/blood , SARS-CoV-2/immunology , Aged , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/diagnosis , COVID-19/virology , Case-Control Studies , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/virology , Female , Host-Pathogen Interactions , Humans , Iran , Lymphocytes/immunology , Lymphocytes/metabolism , Lymphocytes/virology , Male , Middle Aged , Neutrophils/immunology , Neutrophils/metabolism , Neutrophils/virology , SARS-CoV-2/pathogenicity , Severity of Illness Index
13.
Platelets ; 32(3): 325-330, 2021 Apr 03.
Article in English | MEDLINE | ID: covidwho-1092288

ABSTRACT

Platelets play an essential role in maintaining vascular integrity after injury. In addition, platelets contribute to the immune response to pathogens. For instance, they express receptors that mediate binding of viruses, and toll-like receptors that activate the cell in response to pathogen-associated molecular patterns. Platelets can be beneficial and/or detrimental during viral infections. They reduce blood-borne viruses by engulfing the free virus and presenting the virus to neutrophils. However, platelets can also enhance inflammation and tissue injury during viral infections. Here, we discuss the roles of platelets in viral infection.


Subject(s)
Blood Platelets/immunology , COVID-19/immunology , Host-Pathogen Interactions/immunology , Neutrophils/immunology , Receptors, Virus/immunology , Viral Proteins/immunology , Viruses/immunology , Animals , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/genetics , COVID-19/pathology , COVID-19/virology , Cell Communication/genetics , Cell Communication/immunology , Dendritic Cells/immunology , Dendritic Cells/pathology , Dendritic Cells/virology , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Humans , Immunity, Innate , Lymphocytes/immunology , Lymphocytes/pathology , Lymphocytes/virology , Neutrophils/pathology , Neutrophils/virology , Platelet Activation/immunology , Protein Binding , Receptors, Virus/genetics , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology , Viral Proteins/genetics , Viruses/pathogenicity
14.
Open Biol ; 11(1): 200347, 2021 01.
Article in English | MEDLINE | ID: covidwho-1066515

ABSTRACT

Coronavirus disease 2019 (COVID-19) has emerged as a new public health crisis, threatening almost all aspects of human life. Originating in bats, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted to humans through unknown intermediate hosts, where it is primarily known to cause pneumonia-like complications in the respiratory system. Organ-to-organ transmission has not been ruled out, thereby raising the possibility of the impact of SARS-CoV-2 infection on multiple organ systems. The male reproductive system has been hypothesized to be a potential target of SARS-CoV-2 infection, which is supported by some preliminary evidence. This may pose a global threat to male fertility potential, as men are more prone to SARS-CoV-2 infection than women, especially those of reproductive age. Preliminary reports have also indicated the possibility of sexual transmission of SARS-CoV-2. It may cause severe complications in infected couples. This review focuses on the pathophysiology of potential SARS-CoV-2 infection in the reproductive organs of males along with their invasion mechanisms. The risks of COVID-19 on male fertility as well as the differences in vulnerability to SARS-CoV-2 infection compared with females have also been highlighted.


Subject(s)
COVID-19/pathology , Reproductive Health , SARS-CoV-2/pathogenicity , COVID-19/immunology , COVID-19/virology , Cytokines/metabolism , DNA Fragmentation , Humans , Lymphocytes/metabolism , Lymphocytes/virology , Male , Oxidative Stress , SARS-CoV-2/isolation & purification , Spermatozoa/physiology , Spermatozoa/virology
15.
Cytometry A ; 99(5): 429-434, 2021 05.
Article in English | MEDLINE | ID: covidwho-1055900

ABSTRACT

Transient lymphocytopenia is frequently observed in acute phase of coronavirus disease 2019 (COVID-19). It remains a concern whether impairment of cellular immunity may be retained after COVID-19. Here, we demonstrate by extensive lymphocyte profiling in 44 adults after mild COVID-19 that cellular immunity is not fundamentally altered in convalescent patients. Except for increased activated CD8+ lymphocytes, total counts of B, T, and NK cells and their subsets did not differ significantly between patients after COVID-19 and healthy controls after a median of 27 days (range 13-45) suggesting no residual cellular immune deficiency after recovery from mild COVID-19.


Subject(s)
COVID-19/immunology , Immunity, Cellular , Lymphocytes/immunology , SARS-CoV-2/immunology , Adolescent , Adult , COVID-19/diagnosis , COVID-19/virology , Female , Host-Pathogen Interactions , Humans , Lymphocyte Count , Lymphocytes/virology , Male , Middle Aged , Phenotype , Retrospective Studies , SARS-CoV-2/pathogenicity , Time Factors , Young Adult
17.
Stem Cell Rev Rep ; 17(1): 296-299, 2021 02.
Article in English | MEDLINE | ID: covidwho-1009200

ABSTRACT

We report the case of an HIV-1-infected patient, treated with anti-CD20 monoclonal antibody for a B-cell lymphoma previously treated by autologous stem cell transplant. He suffered from chronic COVID19 and we monitored by plasma SARS-CoV-2 RNA by highly sensitive droplet-based digital PCR technology (ddPCR). Under tocilizumab therapy and despite a first clinical improvement biologically associated with decreasing inflammatory markers, a slight increase of SARS-CoV-2 RNAaemia quantified by ddPCR was highlighted, confirming the absence of viral efficacy of this treatment and predicting the subsequent observed deterioration. As expected, his complete recovery, finally achieved after COVID-19 convalescent plasmatherapy, strictly paralleled plasma SARS-CoV-2 RNA clearance. With these results, we confirmed the interest of SARS-CoV-2 RNAaemia monitoring by ddPCR in COVID-19 patients, particularly during treatment, and firstly showed that this new and specific biomarker could be helpful to select eligible patient for anti-IL6 receptors therapy considering the variable levels of efficacy recently observed with such therapy.


Subject(s)
COVID-19/blood , HIV Infections/blood , Lymphoma, B-Cell/drug therapy , RNA, Viral/blood , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , COVID-19/genetics , COVID-19/virology , HIV Infections/genetics , HIV Infections/therapy , HIV Infections/virology , HIV-1/pathogenicity , Humans , Lymphocytes/virology , Lymphoma, B-Cell/complications , Lymphoma, B-Cell/genetics , Lymphoma, B-Cell/virology , RNA, Viral/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Viral Load/drug effects
18.
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
19.
J Med Virol ; 92(10): 2055-2066, 2020 10.
Article in English | MEDLINE | ID: covidwho-969528

ABSTRACT

Clinical and laboratory data on patients with coronavirus disease 2019 (COVID-19) in Beijing, China, remain extremely limited. In this study, we summarized the clinical characteristics of patients with COVID-19 from a designated hospital in Beijing. In total, 55 patients with laboratory-confirmed SARS-CoV-2 infection in Beijing 302 Hospital were enrolled in this study. Demographic data, symptoms, comorbidities, laboratory values, treatments, and clinical outcomes were all collected and retrospectively analyzed. A total of 15 (27.3%) patients had severe symptoms, the mean age was 44.0 years (interquartile range [IQR], 34.0-56.0), and the median incubation period was 7.5 days (IQR, 5.0-11.8). A total of 26 (47.3%) patients had exposure history in Wuhan of less than 2 weeks, whereas 20 (36.4%) patients were associated with familial clusters. Also, eighteen (32.7%) patients had underlying comorbidities including hypertension. The most common symptom of illness was fever (45; 81.8%); 51 (92.7%) patients had abnormal findings on chest computed tomography. Laboratory findings showed that neutrophil count, percentage of lymphocyte, percentage of eosinophil, eosinophil count, erythrocyte sedimentation rate, albumin, and serum ferritin are potential risk factors for patients with a poor prognosis. A total of 26 patients (47.3%) were still hospitalized, whereas 29 (52.7%) patients had been discharged. Compared with patients in Wuhan, China, the symptoms of patients in Beijing are relatively mild. Older age, more comorbidities, and more abnormal prominent laboratory markers were associated with a severe condition. On the basis of antiviral drugs, it is observed that antibiotics treatment, appropriate dosage of corticosteroid, and gamma globulin therapy significantly improve patients' outcomes. Early identification and timely medical treatment are important to reduce the severity of patients with COVID-19.


Subject(s)
COVID-19/physiopathology , Coronary Disease/physiopathology , Diabetes Mellitus/physiopathology , Hypertension/physiopathology , Kidney Failure, Chronic/physiopathology , Adrenal Cortex Hormones/therapeutic use , Adult , Age Factors , Antiviral Agents/therapeutic use , COVID-19/diagnostic imaging , COVID-19/therapy , COVID-19/virology , China , Comorbidity , Coronary Disease/diagnostic imaging , Coronary Disease/therapy , Coronary Disease/virology , Diabetes Mellitus/diagnostic imaging , Diabetes Mellitus/therapy , Diabetes Mellitus/virology , Eosinophils/pathology , Eosinophils/virology , Female , Ferritins/blood , Fever/physiopathology , Hospitalization , Hospitals , Humans , Hypertension/diagnostic imaging , Hypertension/therapy , Hypertension/virology , Immunoglobulins, Intravenous/therapeutic use , Infectious Disease Incubation Period , Kidney Failure, Chronic/diagnostic imaging , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/virology , Leukocyte Count , Lymphocytes/pathology , Lymphocytes/virology , Male , Middle Aged , Neutrophils/pathology , Neutrophils/virology , Retrospective Studies , Risk Factors , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Severity of Illness Index , Tomography, X-Ray Computed
20.
J Immunother Cancer ; 8(2)2020 11.
Article in English | MEDLINE | ID: covidwho-939903

ABSTRACT

BACKGROUND: The risk-benefit calculation for corticosteroid administration in the management of COVID-19 is complex and urgently requires data to inform the decision. The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation associated with poor prognosis in both COVID-19 and cancer. Investigating NLR as an inflammatory marker and lymphocyte levels as a critical component of antiviral immunity may inform the dilemma of reducing toxic hyperinflammation while still maintaining effective antiviral responses. METHODS: We performed a retrospective analysis of NLR, absolute neutrophil counts (ANCs) and absolute lymphocyte counts (ALCs) in patients with cancer enrolled in immunotherapy trials who received moderate-dose to high-dose corticosteroids. We compared paired presteroid and available poststeroid initiation values daily during week 1 and again on day 14 using the Wilcoxon signed-rank test. Associated immune subsets by flow cytometry were included where available. RESULTS: Patients (n=48) with a variety of solid tumors received prednisone, methylprednisolone, or dexamethasone alone or in combination in doses ranging from 20 to 190 mg/24 hours (prednisone equivalent). The median NLR prior to steroid administration was elevated at 5.0 (range: 0.9-61.2). The corresponding median ANC was 5.1 K/µL (range: 2.03-22.31 K/µL) and ALC was 1.03 K/µL (0.15-2.57 K/µL). One day after steroid administration, there was a significant transient drop in median ALC to 0.54 K/µL (p=0.0243), driving an increase in NLR (median 10.8, p=0.0306). Relative lymphopenia persisted through day 14 but was no longer statistically significant. ANC increased steadily over time, becoming significant at day 4 (median: 7.31 K/µL, p=0.0171) and remaining significantly elevated through day 14. NLR was consistently elevated after steroid initiation, significantly at days 1, 7 (median: 8.2, p=0.0272), and 14 (median: 15.0, p=0.0018). Flow cytometry data from 11 patients showed significant decreases in activated CD4 cells and effector memory CD8 cells. CONCLUSIONS: The early drop in ALC with persistent lymphopenia as well as the prolonged ANC elevation seen in response to corticosteroid administration are similar to trends associated with increased mortality in several coronavirus studies to include the current SARS-CoV-2 pandemic. The affected subsets are essential for effective antiviral immunity. This may have implications for glucocorticoid therapy for COVID-19.


Subject(s)
COVID-19/drug therapy , Inflammation/drug therapy , Neoplasms/therapy , Neutrophils/immunology , Pandemics , Adrenal Cortex Hormones/administration & dosage , Adult , Aged , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/virology , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Female , Humans , Immunotherapy/adverse effects , Inflammation/immunology , Inflammation/pathology , Inflammation/virology , Lymphocyte Count , Lymphocytes/immunology , Lymphocytes/virology , Male , Middle Aged , Neoplasms/blood , Neoplasms/complications , Neoplasms/pathology , Neutrophils/virology , Risk Assessment , SARS-CoV-2/pathogenicity
SELECTION OF CITATIONS
SEARCH DETAIL
...