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1.
BMC Pulm Med ; 22(1): 1, 2022 Jan 03.
Article in English | MEDLINE | ID: covidwho-1608729

ABSTRACT

BACKGROUND: Quantitative evaluation of radiographic images has been developed and suggested for the diagnosis of coronavirus disease 2019 (COVID-19). However, there are limited opportunities to use these image-based diagnostic indices in clinical practice. Our aim in this study was to evaluate the utility of a novel visually-based classification of pulmonary findings from computed tomography (CT) images of COVID-19 patients with the following three patterns defined: peripheral, multifocal, and diffuse findings of pneumonia. We also evaluated the prognostic value of this classification to predict the severity of COVID-19. METHODS: This was a single-center retrospective cohort study of patients hospitalized with COVID-19 between January 1st and September 30th, 2020, who presented with suspicious findings on CT lung images at admission (n = 69). We compared the association between the three predefined patterns (peripheral, multifocal, and diffuse), admission to the intensive care unit, tracheal intubation, and death. We tested quantitative CT analysis as an outcome predictor for COVID-19. Quantitative CT analysis was performed using a semi-automated method (Thoracic Volume Computer-Assisted Reading software, GE Health care, United States). Lungs were divided by Hounsfield unit intervals. Compromised lung (%CL) volume was the sum of poorly and non-aerated volumes (- 500, 100 HU). We collected patient clinical data, including demographic and clinical variables at the time of admission. RESULTS: Patients with a diffuse pattern were intubated more frequently and for a longer duration than patients with a peripheral or multifocal pattern. The following clinical variables were significantly different between the diffuse pattern and peripheral and multifocal groups: body temperature (p = 0.04), lymphocyte count (p = 0.01), neutrophil count (p = 0.02), c-reactive protein (p < 0.01), lactate dehydrogenase (p < 0.01), Krebs von den Lungen-6 antigen (p < 0.01), D-dimer (p < 0.01), and steroid (p = 0.01) and favipiravir (p = 0.03) administration. CONCLUSIONS: Our simple visual assessment of CT images can predict the severity of illness, a resulting decrease in respiratory function, and the need for supplemental respiratory ventilation among patients with COVID-19.


Subject(s)
COVID-19/classification , COVID-19/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Amides/therapeutic use , Antiviral Agents/therapeutic use , Body Temperature , C-Reactive Protein/metabolism , COVID-19/drug therapy , COVID-19/physiopathology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , L-Lactate Dehydrogenase/blood , Lung/diagnostic imaging , Lymphocyte Count , Male , Middle Aged , Mucin-1/blood , Neutrophils , Predictive Value of Tests , Prognosis , Pyrazines/therapeutic use , Radiographic Image Interpretation, Computer-Assisted , Retrospective Studies , SARS-CoV-2 , Steroids/therapeutic use
2.
Front Immunol ; 12: 707159, 2021.
Article in English | MEDLINE | ID: covidwho-1581347

ABSTRACT

Coronavirus disease-2019 (COVID-19) was declared as a pandemic by WHO in March 2020. SARS-CoV-2 causes a wide range of illness from asymptomatic to life-threatening. There is an essential need to identify biomarkers to predict disease severity and mortality during the earlier stages of the disease, aiding treatment and allocation of resources to improve survival. The aim of this study was to identify at the time of SARS-COV-2 infection patients at high risk of developing severe disease associated with low survival using blood parameters, including inflammation and coagulation mediators, vital signs, and pre-existing comorbidities. This cohort included 89 multi-ethnic COVID-19 patients recruited between July 14th and October 20th 2020 in Doha, Qatar. According to clinical severity, patients were grouped into severe (n=33), mild (n=33) and asymptomatic (n=23). Common routine tests such as complete blood count (CBC), glucose, electrolytes, liver and kidney function parameters and markers of inflammation, thrombosis and endothelial dysfunction including complement component split product C5a, Interleukin-6, ferritin and C-reactive protein were measured at the time COVID-19 infection was confirmed. Correlation tests suggest that C5a is a predictive marker of disease severity and mortality, in addition to 40 biological and physiological parameters that were found statistically significant between survivors and non-survivors. Survival analysis showed that high C5a levels, hypoalbuminemia, lymphopenia, elevated procalcitonin, neutrophilic leukocytosis, acute anemia along with increased acute kidney and hepatocellular injury markers were associated with a higher risk of death in COVID-19 patients. Altogether, we created a prognostic classification model, the CAL model (C5a, Albumin, and Lymphocyte count) to predict severity with significant accuracy. Stratification of patients using the CAL model could help in the identification of patients likely to develop severe symptoms in advance so that treatments can be targeted accordingly.


Subject(s)
Biomarkers/blood , COVID-19/blood , COVID-19/mortality , Complement C5a/analysis , Patient Acuity , Adult , Aged , COVID-19/complications , Cohort Studies , Female , Humans , Hypoalbuminemia/mortality , Hypoalbuminemia/virology , Lymphocyte Count , Lymphopenia/mortality , Lymphopenia/virology , Male , Middle Aged , Prognosis , Prospective Studies , Qatar , SARS-CoV-2
3.
Front Immunol ; 12: 760249, 2021.
Article in English | MEDLINE | ID: covidwho-1581341

ABSTRACT

Background: The humoral and cellular immune responses to SARS-COV-2 vaccination remain to be elucidated in hemodialysis (HD) patients and kidney transplant recipients (KTRs), considering their baseline immunosuppressed status. The aim of our study was to assess the associations of vaccine-induced antibody responses with circulating lymphocytes sub-populations and their respective patterns of alterations in maintenance HD patients and KTRs. Materials and Methods: We included 34 HD patients and 54 KTRs who received two doses of the mRNA-vaccine BNT162b2. Lymphocyte subpopulations were analyzed by flow cytometry before vaccination (T0), before the second vaccine dose (T1) and 2 weeks after the second dose (T2). The anti-SARS-CoV2 antibody response was assessed at T1 and at T2. Results: 31 HD patients (91.8%) and 16 KTRs (29.6%) became seropositive at T2. HD patients who became seropositive following the first dose displayed higher CD19+ B lymphocytes compared to their seronegative HD counterparts. A positive correlation was established between CD19+ B cells counts and antibody titers at all time-points in both groups (p < 0.001). KTRs showed higher naïve CD4+CD45RA+ T helper cells compared to HD patients at baseline and T2 whereas HD patients displayed higher memory CD45RO+ T cells compared to KTRs at T2. The naïve CD4+CD45RA to memory CD4+CD45RO+ T helper cells fraction was negatively associated with antibody production in both groups. Conclusions: Our study provides a potential conceptual framework for monitoring vaccination efficacy in HD patients and KTRs considering the correlation established between CD19+ B cells, generation of memory CD4+ T helper cells and anti SARS-CoV2 antibody response to vaccination.


Subject(s)
Antibody Formation/immunology , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , Immunity, Humoral , Immunocompromised Host , Immunologic Memory , B-Lymphocytes/metabolism , Biomarkers , CD4-Positive T-Lymphocytes/metabolism , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Female , Humans , Immunophenotyping , Kidney Transplantation , Lymphocyte Count , Male , Renal Dialysis , SARS-CoV-2/immunology
4.
Front Immunol ; 12: 789735, 2021.
Article in English | MEDLINE | ID: covidwho-1581322

ABSTRACT

Background: The host immune response has a prominent role in the progression and outcome of SARS-CoV-2 infection. Lymphopenia has been described as an important feature of SARS-CoV-2 infection and has been associated with severe disease manifestation. Lymphocyte dysregulation and hyper-inflammation have been shown to be associated with a more severe clinical course; however, a T cell subpopulation whose dysfunction correlate with disease progression has yet to be identify. Methods: We performed an immuno-phenotypic analysis of T cell sub-populations in peripheral blood from patients affected by different severity of COVID-19 (n=60) and undergoing a different clinical evolution. Clinical severity was established based on a modified WHO score considering both ventilation support and respiratory capacity (PaO2/FiO2 ratio). The ability of circulating cells at baseline to predict the probability of clinical aggravation was explored through multivariate regression analyses. Results: The immuno-phenotypic analysis performed by multi-colour flow cytometry confirmed that patients suffering from severe COVID-19 harboured significantly reduced circulating T cell subsets, especially for CD4+ T, Th1, and regulatory T cells. Peripheral T cells also correlated with parameters associated with disease severity, i.e., PaO2/FiO2 ratio and inflammation markers. CD4+ T cell subsets showed an important significant association with clinical evolution, with patients presenting markedly decreased regulatory T cells at baseline having a significantly higher risk of aggravation. Importantly, the combination of gender and regulatory T cells allowed distinguishing between improved and worsened patients with an area under the ROC curve (AUC) of 82%. Conclusions: The present study demonstrates the association between CD4+ T cell dysregulation and COVID-19 severity and progression. Our results support the importance of analysing baseline regulatory T cell levels, since they were revealed able to predict the clinical worsening during hospitalization. Regulatory T cells assessment soon after hospital admission could thus allow a better clinical stratification and patient management.


Subject(s)
COVID-19/epidemiology , COVID-19/immunology , Hospitalization , Lymphocyte Count , SARS-CoV-2/immunology , T-Lymphocytes, Regulatory/immunology , Biomarkers , COVID-19/diagnosis , COVID-19/virology , COVID-19 Serological Testing , Cytokines/blood , Cytokines/metabolism , Disease Progression , Humans , Immunophenotyping , Inflammation Mediators/blood , Inflammation Mediators/metabolism , Prognosis , Public Health Surveillance , ROC Curve , Severity of Illness Index , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , T-Lymphocytes, Regulatory/metabolism
6.
Sci Rep ; 11(1): 24224, 2021 12 20.
Article in English | MEDLINE | ID: covidwho-1585790

ABSTRACT

Since 2019, a large number of people worldwide have been infected with severe acute respiratory syndrome coronavirus 2. Among those infected, a limited number develop severe coronavirus disease 2019 (COVID-19), which generally has an acute onset. The treatment of patients with severe COVID-19 is challenging. To optimize disease prognosis and effectively utilize medical resources, proactive measures must be adopted for patients at risk of developing severe COVID-19. We analyzed the data of COVID-19 patients from seven medical institutions in Tokyo and used mathematical modeling of patient blood test results to quantify and compare the predictive ability of multiple prognostic indicators for the development of severe COVID-19. A machine learning logistic regression model was used to analyze the blood test results of 300 patients. Due to the limited data set, the size of the training group was constantly adjusted to ensure that the results of machine learning were effective (e.g., recognition rate of disease severity > 80%). Lymphocyte count, hemoglobin, and ferritin levels were the best prognostic indicators of severe COVID-19. The mathematical model developed in this study enables prediction and classification of COVID-19 severity.


Subject(s)
COVID-19/pathology , Models, Theoretical , Adolescent , Adult , Aged , C-Reactive Protein/analysis , COVID-19/virology , Female , Ferritins/analysis , Hemoglobins/analysis , Humans , Lymphocyte Count , Machine Learning , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Young Adult
7.
PLoS One ; 16(12): e0261437, 2021.
Article in English | MEDLINE | ID: covidwho-1581743

ABSTRACT

BACKGROUND AND OBJECTIVES: At present, the focus of the fighting against COVID-19 in China is shifting to strictly prevent the entrance of cases from abroad and disease transmission. Therefore, it is extremely urgent to better understand the clinical features of imported cases from overseas countries, which is conductive to formulate the corresponding countermeasures. This study aimed to describe the clinical features of COVID-19 cases imported from Russia through the Suifenhe port, in order to identify baseline and clinical data associated with disease progression and present corresponding countermeasures. METHODS: All COVID-19 cases imported from Russia through the Suifenhe port were included in this retrospective study. According to the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (seventh edition)", imported COVID-19 cases were divided into asymptomatic infection, mild, moderate, severe, and critical groups. Baseline and clinical data, including age, gender, comorbidities, disease severity, symptoms at onset, body temperature, white blood cell (WBC) count, lymphocyte (LYMPH) count, lymphocyte percentage (LYM%), C-reactive protein (CRP), oxygenation index (OI), and the use therapeutic modalities were obtained on admission, and then compared between groups. RESULTS: A total of 375 COVID-19 cases imported from Russia through Suifenhe port were included, of whom the asymptomatic infection, mild, moderate, severe, and critical groups accounted for 4.0%, 13.9%, 75.5%, 5.3%, and 1.3%, respectively. The majority of the imported COVID-19 cases were men (61.9%) with a median age of 38.72 years who had no comorbidity (87.7%). Nearly one-third of them (33.1%) were asymptomatic at onset, and common initial symptoms included fever (36.5%), cough (36.0%), pharyngeal discomfort (12.3%), expectoration (8.0%), and chest tightness (5.3%). In total, 180 (48%) and 4 (1.1%) enrolled imported cases received nasal tube oxygen inhalation therapy and high-flow oxygen absorption, respectively; the remaining patients did not undergo oxygen therapy. The values of age, body temperature, WBC, LYMPH, LYM%, CRP, and OI were 38.72 ± 10.50, 35.10 ± 7.92, 5.59 ± 1.97, 1.67 ± 0.68, 31.05 ± 10.22, 8.00 ± 14.75, and 389.03 ± 74.07, respectively. Gender, age, LYMPH, LYM%, symptoms at onset, cough, fever, other rare symptoms, and oxygen therapy showed significant differences between groups (P = 0.036, < 0.001, < 0.001, < 0.001, < 0.001, < 0.001, < 0.001, = 0.045, < 0.001, respectively). CONCLUSIONS: Compared with domestic confirmed patients, COVID-19 patients who arrived at China from Russia through the Suifenhe port had significantly different clinical features, and the differences in gender, age, LYMPH, LYM%, symptoms at onset, cough, fever, other rare symptoms, and oxygen therapy between groups were statistically significant. Therefore, detailed and comprehensive countermeasures were developed to manage and prevent another outbreak based on these clinical features.


Subject(s)
COVID-19/epidemiology , COVID-19/etiology , Adolescent , Adult , Aged , COVID-19/therapy , China/epidemiology , Comorbidity , Cough/virology , Female , Humans , Lymphocyte Count , Male , Middle Aged , Retrospective Studies , Russia , Severity of Illness Index , Young Adult
8.
Ann Med ; 53(1): 181-188, 2021 12.
Article in English | MEDLINE | ID: covidwho-1575964

ABSTRACT

OBJECTIVE: To illustrate the effect of corticosteroids and heparin, respectively, on coronavirus disease 2019 (COVID-19) patients' CD8+ T cells and D-dimer. METHODS: In this retrospective cohort study involving 866 participants diagnosed with COVID-19, patients were grouped by severity. Generalized additive models were established to explore the time-course association of representative parameters of coagulation, inflammation and immunity. Segmented regression was performed to examine the influence of corticosteroids and heparin upon CD8+ T cell and D-dimer, respectively. RESULTS: There were 541 moderate, 169 severe and 156 critically ill patients involved in the study. Synchronous changes of levels of NLR, D-dimer and CD8+ T cell in critically ill patients were observed. Administration of methylprednisolone before 14 DFS compared with those after 14 DFS (ß = 0.154%, 95% CI=(0, 0.302), p=.048) or a dose lower than 40 mg per day compared with those equals to 40 mg per day (ß = 0.163%, 95% CI=(0.027, 0.295), p=.020) significantly increased the rising rate of CD8+ T cell in 14-56 DFS. CONCLUSIONS: The parameters of coagulation, inflammation and immunity were longitudinally correlated, and an early low-dose corticosteroid treatment accelerated the regaining of CD8+ T cell to help battle against SARS-Cov-2 in critical cases of COVID-19.


Subject(s)
CD8-Positive T-Lymphocytes/drug effects , COVID-19/drug therapy , Glucocorticoids/administration & dosage , Inflammation/drug therapy , Adult , Aged , Aged, 80 and over , Blood Coagulation/drug effects , Blood Coagulation/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Dose-Response Relationship, Drug , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/immunology , Heparin/administration & dosage , Humans , Inflammation/blood , Inflammation/diagnosis , Inflammation/immunology , Linear Models , Longitudinal Studies , Lymphocyte Count , Male , Methylprednisolone/administration & dosage , Middle Aged , Models, Biological , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Time Factors , Time-to-Treatment , Young Adult
9.
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
10.
J Med Virol ; 94(1): 272-278, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544342

ABSTRACT

Data pertaining to risk factor analysis in coronavirus disease 2019 (COVID-19) is confounded by the lack of data from an ethnically diverse population. In addition, there is a lack of data for young adults. This study was conducted to assess risk factors predicting COVID-19 severity and mortality in hospitalized young adults. A retrospective observational study was conducted at two centers from China and India on COVID-19 patients aged 20-50 years. Regression analysis to predict adverse outcomes was performed using parameters including age, sex, country of origin, hospitalization duration, comorbidities, lymphocyte count, and National Early Warning Score 2 (NEWS2) score at admission. A total of 420 patients (172 East Asians and 248 South Asians) were included. The predictive model for intensive care unit (ICU) admission with variables NEWS2 Category II and higher, diabetes mellitus, liver dysfunction, and low lymphocyte counts had an area under the curve (AUC) value of 0.930 with a sensitivity of 0.931 and a specificity of 0.784. The predictive model for mortality with NEWS2 Category III, cancer, and decreasing lymphocyte count had an AUC value of 0.883 with a sensitivity of 0.903 and a specificity of 0.701. A combined predictive model with bronchial asthma and low lymphocyte count, in contrast, had an AUC value of 0.768 with a sensitivity of 0.828 and a specificity of 0.719 for NEWS2 score (5 or above) at presentation. NEWS2 supplemented with comorbidity profile and lymphocyte count could help identify hospitalized young adults at risk of adverse COVID-19 outcomes.


Subject(s)
COVID-19/diagnosis , COVID-19/ethnology , Adult , COVID-19/mortality , COVID-19/physiopathology , China , Comorbidity , Disease Progression , Early Warning Score , Female , Hospitalization , Humans , India , Intensive Care Units , Lymphocyte Count , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Severity of Illness Index , Young Adult
11.
J Med Virol ; 94(1): 211-221, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544338

ABSTRACT

Prognostic predictors are of paramount interest for prompt intervention and optimal utilization of the healthcare system in the ongoing context of the COVID-19 pandemic. The platelet-to-lymphocyte count ratio (PLR), has emerged as a potential tool for risk stratification of critically ill patients with sepsis. The current systematic review explores the utility of PLR as a prognostic predictor of COVID-19 patients. We screened the electronic databases until May 15, 2021 after enrolling in PROSPERO (CRD42021220269). Studies evaluating the association between PLR on admission and outcomes in terms of mortality and severity among COVID-19 patients were included. We retrieved 32 studies, with a total of 2768 and 3262 COVID-19 patients for mortality and disease severity outcomes. Deceased and critically ill patients had higher PLR levels on admission in comparison to survivors and non-severe patients (mean differences [MD] = 66.10; 95% confidence interval [CI]: 47.75-84.44; p < 0.00001 and MD = 86.74; 95% CI: 67.7-105.7; p < 0.00001, respectively). A higher level of PLR on admission in COVID-19 patients is associated with increased morbidity and mortality. However, the evidence is of low quality and further studies regarding the cut-off value of PLR are the need of the hour.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Lymphocyte Count , Platelet Count , COVID-19/mortality , COVID-19/physiopathology , Humans , Prognosis , Severity of Illness Index
12.
Eur Rev Med Pharmacol Sci ; 25(21): 6767-6774, 2021 11.
Article in English | MEDLINE | ID: covidwho-1524864

ABSTRACT

OBJECTIVE: We aimed to test the efficiency of CHA2DS2-VASc, CHA2DS2-VASc-HS, R2CHA2DS2-VASc score systems on the prediction of mortality in the patients with COVID-19. PATIENTS AND METHODS: The data were collected from 508 hospitalized patients with COVID-19. Comorbidity features including coronary artery disease, peripheral arterial disease, congestive heart failure, hypertension, atrial fibrillation, diabetes mellitus, hyperlipidemia, smoking, chronic obstructive pulmonary disease, cerebrovascular event, cancer status, and renal disease were recorded. The patients were divided as surviving group (n=440) and non-survivors (n=68). RESULTS: The in-hospital mortality rate of the patients with COVID-19 was 13.4%. Factors found to be associated with mortality in univariate analysis were CHA2DS2-VASc, CHA2DS2-VASc-HS, R2CHA2DS2-VASc, cancer state, atrial fibrillation, hemoglobin, lymphocyte count, CRP, albumin and ferritin. Model 1 multivariate cox regression analysis revealed CHA2DS2-VASc, hemoglobin, CRP and ferritin levels to be independently associated with mortality. Factors that were found to be independently associated with in-hospital mortality in Model 2 analysis were CHA2DS2-VASc-HS, R2CHA2DS2-VASc, hemoglobin, CRP and ferritin whereas except hemoglobin in Model 3 analysis, the other variables had been the same. Predictive power of R2CHA2DS2-VASc was better than of both CHA2DS2-VASc (p=0.002) and CHA2DS2-VASc-HS (p=0.034) in determining the in-hospital mortality. Patients with higher R2CHA2DS2-VASc (> 3 points), CHA2DS2-VASc-HS (> 3 points) and CHA2DS2-VASc (> 2 points) scores exhibited the highest mortality rate in survival analysis by using Kaplan-Meier and long-rank tests. CONCLUSIONS: CHA2DS2-VASc, CHA2DS2-VASc-HS, and R2CHA2DS2-VASc were found to be independent predictors of mortality in hospitalized COVID-19 patients. The current study revealed that the predictive ability of R2CHA2DS2-VASc was better than the both of CHA2DS2-VASc and CHA2DS2-VASc-HS score.


Subject(s)
COVID-19/mortality , Comorbidity , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Area Under Curve , COVID-19/pathology , COVID-19/virology , Female , Hemoglobins/analysis , Hospital Mortality , Hospitalization , Humans , Kaplan-Meier Estimate , Lymphocyte Count , Male , Middle Aged , Proportional Hazards Models , ROC Curve , SARS-CoV-2/isolation & purification
13.
Am J Perinatol ; 38(12): 1236-1243, 2021 10.
Article in English | MEDLINE | ID: covidwho-1521902

ABSTRACT

OBJECTIVE: This study aimed to determine if laboratory inflammatory markers can predict critical disease in symptomatic COVID-19 pregnant women. STUDY DESIGN: Multicenter, retrospective cohort study of all pregnant women presenting to New York City Health + Hospitals emergency departments from March 1 to May 30, 2020. We assessed all symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive pregnant women with room air oxygen saturation <95% on presentation. Logistic regression modeled the relationship of inflammatory markers to outcomes. Area under receiver operating characteristic (ROC) curve and maximum Youden index determined prognostic ability and optimal predictive cut-off values. RESULTS: A total of 498 of 5,002 pregnant women were SARS-CoV-2 RT-PCR positive of which 77 presented with hypoxemia. The absolute lymphocyte count (ALC) and neutrophil to lymphocyte ratio (NLR) were highly sensitive for progression to severe illness. ROC curve analysis identified predictive cutoffs: ALC < 1.49 × 109/L (96% sensitivity, 52% specificity, area under the receiver operating characteristic curve [AUC] = 0.80 (95% confidence interval [CI]: 0.70-0.90) and NLR >8.1 (100% sensitivity, 70% specificity, AUC = 0.86 (95% CI: [0.76-0.96]). CONCLUSION: ALC and NLR on presentation are sensitive markers of progression to critical COVID-19 disease in symptomatic pregnant women. This finding provides a practical, rapid method for assessment and can assist clinicians with decision-making regarding triage, level of care, and patient management. KEY POINTS: · Few tools exist to gauge risk of severe COVID-19 disease in pregnancy.. · ALC and NLR are sensitive predictive markers of disease progression in symptomatic women.. · Cut-off values for ALC and NLR will help direct patient triage and management..


Subject(s)
COVID-19/complications , Lymphocyte Count , Lymphopenia/virology , Neutrophils/metabolism , Pregnancy Complications, Infectious/virology , Severity of Illness Index , Adult , Cohort Studies , Disease Progression , Female , Humans , Pregnancy , Retrospective Studies , Sensitivity and Specificity
14.
Clin Transl Sci ; 14(6): 2556-2565, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526359

ABSTRACT

Nezulcitinib (TD-0903), a lung-selective pan-Janus-associated kinase (JAK) inhibitor designed for inhaled delivery, is under development for treatment of acute lung injury associated with coronavirus disease 2019 (COVID-19). This two-part, double-blind, randomized, placebo-controlled, single ascending dose (part A) and multiple ascending dose (part B) phase I study evaluated the safety, tolerability, and pharmacokinetics (PK) of nezulcitinib in healthy participants. Part A included three cohorts randomized 6:2 to receive a single inhaled dose of nezulcitinib (1, 3, or 10 mg) or matching placebo. Part B included three cohorts randomized 8:2 to receive inhaled nezulcitinib (1, 3, or 10 mg) or matching placebo for 7 days. The primary outcome was nezulcitinib safety and tolerability assessed from treatment-emergent adverse events (TEAEs). The secondary outcome was nezulcitinib PK. All participants completed the study. All TEAEs were mild or moderate in severity, and none led to treatment discontinuation. Overall (area under the plasma concentration-time curve) and peak (maximal plasma concentration) plasma exposures of nezulcitinib were low and increased in a dose-proportional manner from 1 to 10 mg in both parts, with no suggestion of clinically meaningful drug accumulation. Maximal plasma exposures were below levels expected to result in systemic target engagement, consistent with a lung-selective profile. No reductions in natural killer cell counts were observed, consistent with the lack of a systemic pharmacological effect and the observed PK. In summary, single and multiple doses of inhaled nezulcitinib at 1, 3, and 10 mg were well-tolerated in healthy participants, with dose-proportional PK supporting once-daily administration.


Subject(s)
Azetidines/adverse effects , COVID-19/drug therapy , Imidazoles/adverse effects , Indazoles/adverse effects , Piperidines/adverse effects , Administration, Inhalation , Adult , Area Under Curve , Azetidines/administration & dosage , Azetidines/pharmacokinetics , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Healthy Volunteers , Humans , Imidazoles/administration & dosage , Imidazoles/pharmacokinetics , Indazoles/administration & dosage , Indazoles/pharmacokinetics , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Lymphocyte Count , Male , Middle Aged , Piperidines/administration & dosage , Piperidines/pharmacokinetics , Young Adult
15.
Front Immunol ; 12: 697622, 2021.
Article in English | MEDLINE | ID: covidwho-1518482

ABSTRACT

Objectives: The longitudinal and systematic evaluation of immunity in coronavirus disease 2019 (COVID-19) patients is rarely reported. Methods: Parameters involved in innate, adaptive, and humoral immunity were continuously monitored in COVID-19 patients from onset of illness until 45 days after symptom onset. Results: This study enrolled 27 mild, 47 severe, and 46 deceased COVID-19 patients. Generally, deceased patients demonstrated a gradual increase of neutrophils and IL-6 but a decrease of lymphocytes and platelets after the onset of illness. Specifically, sustained low numbers of CD8+ T cells, NK cells, and dendritic cells were noted in deceased patients, while these cells gradually restored in mild and severe patients. Furthermore, deceased patients displayed a rapid increase of HLA-DR expression on CD4+ T cells in the early phase, but with a low level of overall CD45RO and HLA-DR expressions on CD4+ and CD8+ T cells, respectively. Notably, in the early phase, deceased patients showed a lower level of plasma cells and antigen-specific IgG, but higher expansion of CD16+CD14+ proinflammatory monocytes and HLA-DR-CD14+ monocytic-myeloid-derived suppressor cells (M-MDSCs) than mild or severe patients. Among these immunological parameters, M-MDSCs showed the best performance in predicting COVID-19 mortality, when using a cutoff value of ≥10%. Cluster analysis found a typical immunological pattern in deceased patients on day 9 after onset, which was characterized as the increase of inflammatory markers (M-MDSCs, neutrophils, CD16+CD14+ monocytes, and IL-6) but a decrease of host immunity markers. Conclusions: This study systemically characterizes the kinetics of immunity of COVID-19, highlighting the importance of immunity in patient prognosis.


Subject(s)
COVID-19/immunology , SARS-CoV-2 , Adaptive Immunity , Aged , Aged, 80 and over , Antibodies, Viral/blood , B-Lymphocytes/immunology , COVID-19/blood , COVID-19/classification , COVID-19/physiopathology , Cytokines/blood , Dendritic Cells/immunology , Female , Humans , Immunity, Innate , Immunoglobulin G/blood , Killer Cells, Natural/immunology , Lymphocyte Count , Male , Middle Aged , SARS-CoV-2/immunology , Severity of Illness Index , T-Lymphocytes/immunology
16.
Viral Immunol ; 34(9): 639-645, 2021 11.
Article in English | MEDLINE | ID: covidwho-1517820

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may produce a systemic disease, the coronavirus disease-19 (COVID-19), with high morbidity and mortality. Even though we do not fully understand the interaction of innate and adaptive immunity in the control and complications of the viral infection, it is well recognized that SARS-CoV-2 induces an immunodepression that impairs the elimination of the virus and favors its rapid dissemination in the organism. Even less is known about the possible participation of inhibitory cells of the innate immune system, such as the myeloid-derived suppressor cells (MDSCs), or the adaptive immune system, such as the T regulatory cells (Tregs). That is why we aimed to study blood levels of MDSCs, as well as lymphocyte subpopulations, including Tregs, and activated (OX-40+) and inhibited (PD-1) T lymphocytes in patients with mild COVID-19 in comparison with data obtained from control donors. We have found that 20 hospitalized patients with COVID-19 and no health history of immunosuppression had a significant increase in the number of peripheral monocytic MDSCs (M-MDSC), but a decrease in Tregs, as well as an increase in the number of inhibited or exhausted T cells, whereas the number of activated T cells was significantly decreased compared with that from 20 healthy controls. Moreover, there was a significant negative correlation (r = 0.496) between the number of M-MDSC and the number of activated T cells. Therefore, M-MDSC rather than Tregs may contribute to the immunosuppression observed in patients with COVID-19.


Subject(s)
COVID-19/immunology , Myeloid-Derived Suppressor Cells/immunology , SARS-CoV-2/immunology , T-Lymphocytes, Regulatory/immunology , Aged , COVID-19/blood , COVID-19/classification , Female , Humans , Lymphocyte Activation , Lymphocyte Count/methods , Lymphocyte Subsets , Male , Middle Aged , SARS-CoV-2/pathogenicity
17.
Saudi Med J ; 42(4): 370-376, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1513257

ABSTRACT

OBJECTIVES: To assess the neutrophil-to-lymphocyte ratio (NLR) diagnostic and prognostic value in the context of Coronavirus disease-2019 (COVID-19) infection in Saudi Arabia. METHODS: A case-control study in which 701 confirmed COVID-19 patients (of which 41 were intensive care unit [ICU]-admitted) and 250 control subjects were enrolled. The study was conducted retrospectively in October on patients admitted to 3 separate hospitals in Saudi Arabia namely: King Abdullah Bin Abdulaziz University Hospital (Riyadh), Ohud Hospital (Madinah), and Nojood Medical Center (Madinah) between May and September 2020. Neutrophil-to-lymphocyte ratio was calculated based on absolute neutrophil and lymphocyte count. Institutional ethical approval was obtained prior to the study. RESULTS: Patients (median age 35 years), of which 54.8% were females, were younger than the control cohort (median age 48 years). Patients had significantly higher NLR compared to the control group. Intensive care unit admitted patients had significantly higher platelet, WBC and neutrophil counts. The ICU patients' NLR was almost twice as of the non-intensive patients. The NLR value of 5.5 was found to be of high specificity (96.4%) and positive predictive value (91.4%) in diagnosing COVID-19. Furthermore, it had a very good sensitivity (86.4%) in predicting severe forms of disease, such as, ICU admission. CONCLUSION: Neutrophil-to-lymphocyte ratio is an important tool in determining the COVID-19 clinical status. This study further confirms the prognostic value of NLR in detecting severe infection, and those patients with high NLR should be closely monitored and managed.


Subject(s)
COVID-19/diagnosis , Lymphocyte Count , Neutrophils , Adult , Blood Cell Count , COVID-19/blood , Case-Control Studies , Female , Hospitalization , Humans , Intensive Care Units , Leukocyte Count , Male , Middle Aged , Platelet Count , Predictive Value of Tests , Prognosis , Retrospective Studies , SARS-CoV-2 , Saudi Arabia , Sensitivity and Specificity , Severity of Illness Index
18.
Saudi Med J ; 42(11): 1223-1228, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1502888

ABSTRACT

OBJECTIVES: To investigate the relationship of the neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) with lung involvement and total lung severity score (TLSS) in computed tomography (CT) of patients with coronavirus disease -19 (COVID-19) and to evaluate their clinical usability. METHODS: Basic laboratory, clinical features and imaging data of patients was obtained by examining the file and archive records of our hospital. According to the findings of lung CT scan at the time of diagnosis among COVID-19 patients, 2 groups were formed. RESULTS: The NLR was 2.22±11.15 and the PLR was 142.77±387.10 in patients with COVID-19 pneumonia. The NLR was 1.88±7.47 and the PLR was 130.65±203.6 8 in patients without COVID-19 pneumonia. The differences in the NLR and the PLR were determined to be statistically significant between the 2 groups. A positive correlation was observed between NLR and PLR (r=0.225, p=0.010) and TLSS (r=0.244, p=0.005). CONCLUSION: This study showed that the NLR and PLR values can be 2 inflammatory markers that can be used to evaluate lung involvement and disease severity in COVID-19 patients. At the time of initial diagnosis and during follow-up, these markers can give an idea in terms of prognosis, together with other clinical findings and markers.


Subject(s)
COVID-19 , Neutrophils , Blood Platelets , Humans , Lung , Lymphocyte Count , Lymphocytes , Platelet Count , Prognosis , Retrospective Studies , SARS-CoV-2
19.
Medicine (Baltimore) ; 100(28): e26503, 2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1494082

ABSTRACT

ABSTRACT: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading on a global scale and poses a great threat to human health. However, efficient indicators for disease severity have not been fully investigated. Here, we aim to investigate whether dynamic changes of lymphocyte counts can predict the deterioration of patients with COVID-19.We collected data from 2923 patients with laboratory-confirmed COVID-19. Patients were then screened, and we focused on 145 severe cases and 60 critical cases (29 recovered cases, 31 deaths). The length of hospitalization was divided into five time points, namely admission, 25%, 50%, 75% and discharge or death, according to the principle of interquartile distance. A series of laboratory findings and clinical data were collected and analyzed during hospitalization. The results showed that there were differences in levels of leukocytes, neutrophils and lymphocytes at almost every time point in the severe cases and 60 critical cases (29 recovered cases, 31 deaths). Further analysis showed that 70.2% of the COVID-19 cases had low circulating lymphocyte count, of which 64.1% were severe cases and 85.0% were critical cases (75.9% recovered cases and 93.5% died). Moreover, the lymphocyte count in dead cases was significantly lower than that of critical cases who recovered, at almost every time point in the critical groups. We also divided critical patients into group A (<1.1 × 109/L) and group B (>1.1 × 109/L) according to number of lymphocytes. Through survival analysis, we found that there was no significant difference in survival between group A and group B at admission (P = .3065). However, the survival rate according to lymphocyte levels in group A was significantly lower than that of group B at 25% hospital stay (on average day 6.5), 50% and 75% time points (P < .001).Lymphocyte counts that remain lower after the first week following symptom onset are highly predictive of in-hospital death of adults with COVID-19. This predictor may help clinicians identify patients with a poor prognosis and may be useful for guiding clinical decision-making at an early stage.


Subject(s)
COVID-19/blood , COVID-19/mortality , Lymphocyte Count/statistics & numerical data , Lymphocytes/metabolism , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/virology , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Severity of Illness Index , Time Factors , Young Adult
20.
Eur Rev Med Pharmacol Sci ; 25(19): 5889-5903, 2021 10.
Article in English | MEDLINE | ID: covidwho-1478931

ABSTRACT

OBJECTIVE: Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19. PATIENTS AND METHODS: We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020. RESULTS: Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality. CONCLUSIONS: Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.


Subject(s)
COVID-19/blood , COVID-19/mortality , Estradiol/blood , Inflammation/blood , Inflammation/etiology , Testosterone/blood , Vitamin D/analogs & derivatives , Adult , Aged , Aged, 80 and over , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Hospitalization , Humans , Leukocyte Count , Lymphocyte Count , Male , Middle Aged , Procalcitonin/blood , Retrospective Studies , Risk Factors , Severity of Illness Index , Survival Analysis , Vitamin D/blood
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