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1.
Front Public Health ; 10: 851295, 2022.
Article in English | MEDLINE | ID: covidwho-1776071

ABSTRACT

Background: Active and severe ulcerative colitis (UC) and non-response to 5-aminosalicylic acid (5-ASA) are related to poor outcomes and should be accurately identified. Several integrated inflammatory indexes are potentially useful to assess the disease severity in patients with acute or critical diseases but are underexplored in patients with UC. Methods: Patients with UC consecutively admitted to our hospital between January 2015 and December 2020 were retrospectively grouped according to the activity and severity of UC and response to 5-ASA. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), neutrophil-to-platelet ratio (NPR), platelet-to-albumin ratio (PAR), C-reactive protein-to-albumin ratio (CAR), and C-reactive protein-to-lymphocyte ratio (CLR) were calculated. The areas under receiver operating characteristic curves (AUC) were calculated. Results: Overall, 187 patients with UC were included, of whom 151 were active, 55 were severe, and 14 were unresponsive to 5-ASA. The active UC group had significantly higher NLR, PLR, SII, and PAR levels. SII had the greatest predictive accuracy for active UC, followed by PLR, PAR, and NLR (AUC = 0.647, 0.641, 0.634, and 0.626). The severe UC group had significantly higher NLR, PLR, SII, PAR, CAR, and CLR levels. CLR had the greatest predictive accuracy for severe UC, followed by CAR, PLR, SII, NLR, and PAR (AUC = 0.732, 0.714, 0.693, 0.669, 0.646, and 0.63). The non-response to the 5-ASA group had significantly higher CAR and CLR levels. CAR had a greater predictive accuracy for non-response to 5-ASA than CLR (AUC = 0.781 and 0.759). Conclusion: SII, CLR, and CAR may be useful for assessing the severity and progression of UC, but remain not optimal.


Subject(s)
Colitis, Ulcerative , Colitis, Ulcerative/diagnosis , Disease Progression , Humans , Lymphocytes , Retrospective Studies
2.
Biomark Med ; 16(7): 559-568, 2022 May.
Article in English | MEDLINE | ID: covidwho-1765636

ABSTRACT

Aim: Our study was designed on the hypothesis that homocysteine levels are a prognostic parameter that can predict the severity of COVID-19 disease. Materials & methods: 117 COVID-19 patients and 34 non COVID-19 individuals were included in the study. Receiver operating characteristic (ROC) analysis was performed for homocysteine, D-dimer and monocyte/lymphocyte ratio (MLR) levels. Results: According to the ROC analysis, in COVID-19 patients group, Area under curve (AUC) values were 0.835 for homocysteine, 0.859 for D-dimer and 0.882 for MLR. According to the ROC analysis, in which homocysteine, MLR and D-dimer parameters were evaluated together, AUC values were 0.951 in the mild disease group, 1000 in severe disease group and 0.967 in COVID-19 patients group. Conclusion: It was concluded that homocysteine level is an important parameter in the follow-up of COVID-19 disease.


Subject(s)
COVID-19 , COVID-19/diagnosis , Homocysteine , Humans , Lymphocytes , Prognosis , ROC Curve , Retrospective Studies , Severity of Illness Index
3.
Crit Rev Immunol ; 41(3): 15-25, 2021.
Article in English | MEDLINE | ID: covidwho-1753246

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus 2019 (COVID-19), which was declared a pandemic in March 2020 by the World Health Organization due the rapid spread representing a global health crisis. The disease is characterized by a wide clinical spectrum ranging from asymptomatic forms until severe viral pneumonia, which can to evolve to severe acute respiratory syndrome, especially in elderly patients and/or with comorbidities. An efficient assembly of the immunological response of the patients becomes fundamental against SARS-CoV-2 infection and it has been demonstrating a significant relationship between the severity of the disease and expression profile of the immune cells and the levels of pro-inflammatory cytokines. This review aims to presents the main immunological mechanisms developed during the infection by SARS-CoV-2 in the evolution of the severe cases of COVID-19. The immune dysregulation of the Th1 cellular response standard, the instability in the production of neutralizing antibodies by plasma B cells, the difference in tropism of CD8+ T cells against virus proteins in early infection, late infection and reinfections, dynamic of alveolar macrophages and pulmonary innate lymphoid cells (TCR γδ) of the natural imune response and the high level of pro-inflammatory cytokines can determine the main cause of breath tissues damages and, consequently, a greater severity of the disease. Therefore, a complete understanding of the main immunological changes involved in SARS-CoV-2 infection can identify possible biomarkers in the evaluation of early prognosis of the severe cases of COVID-19, making possible better therapeutic success to the patients.


Subject(s)
COVID-19 , Pneumonia, Viral , Aged , Humans , Immunity, Innate , Lymphocytes , SARS-CoV-2
4.
Ann Palliat Med ; 11(2): 544-550, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1727123

ABSTRACT

BACKGROUND: Under the current epidemic of the coronavirus disease of 2019 (COVID-19), there is a need to distinguish the differences between the laboratory examinations of COVID-19-infected patients, tumor patients with fever, and those with normal fever patients. We aimed to investigate the temperature of tumor patients with different tumor burdens, stages, and cancer types. METHODS: We recruited 3 groups of patients to this study: fever patients with malignant tumors, ordinary fever patients, and confirmed cases of COVID-19, with 31, 55, and 28 cases in each group, respectively. RESULTS: The levels of leukocytes and neutrophils were the highest among non-tumor patients, and the count of COVID-19 was the lowest, with a P value of 0.000. Among the leukocytosis group, non-tumor patients had the highest proportion (43.6%), while that of COVID-19 was only 3.6% (P=0.000). Similarly, there were significant differences in the grading of neutrophils, where most of the infected patients were in the normal group and the P value was 0.000. The lymphocyte count of the tumor group was significantly reduced, with an average of (0.97±0.66) ×109/L (P=0.004). In the lymphocyte grades, most of the infected patients were the normal group (71.4%), while tumor patients in the lymphocytopenia group accounted for 63.1% (P=0.006). There were also significant differences in the neutrophil to lymphocyte ratio (NLR) (P=0.006). There was a significant difference in temperature between different tumor burden groups (P=0.014). CONCLUSIONS: The normal fever group had the highest count of leukocyte and neutrophils, whereas the infected group had the lowest relative count. The NLR was the lowest in the infected group. The NLR was higher in the bigger tumor load group.


Subject(s)
COVID-19 , Neoplasms , Humans , Lymphocytes , Neoplasms/complications , Prognosis , Retrospective Studies , SARS-CoV-2
5.
Inflammopharmacology ; 30(2): 465-475, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1708824

ABSTRACT

AIMS: COVID-19 is a significant global threat to public health. Despite the availability of vaccines and anti-viral drugs, there is an urgent need for alternative treatments to help prevent and/or manage COVID-19 symptoms and the underlying dysregulated immune response. We hypothesized that administration of Inflawell® syrup, a Boswellia extract formulation enriched for boswellic acids (BAs), can reduce the excessive or persistent inflammation and thereby prevent disease progression. BAs are medicinally activated triterpenoids found in the resins of Boswellia spp., and possess an immense therapeutic potential due to their anti-inflammatory and immunoregulatory activities. We investigated the effect of Inflawell® syrup, on moderate COVID-19 patients along with the current standard of care treatment. METHODS: A randomized placebo-controlled double-blind clinical trial was conducted, following definitive confirmation of COVID-19. Forty-seven hospitalized patients with moderate COVID-19 were enrolled and received either the Inflawell® syrup or placebo. Clinical symptoms and markers of inflammation were evaluated at baseline and completion of the trial. RESULTS: Our clinical trial revealed an increase in the percentage of oxygen saturation level in patients that received the BAs compared to placebo (P < 0.0001). In addition, the average duration of hospitalization was significantly shorter in the BAs group compared with the placebo group (P < 0.04). Concomitantly, some improvement in the clinical symptoms including cough, dyspnea, myalgia, headache, and olfactory and gustatory dysfunction were detected in the BAs group. Hematologic findings showed a significant decrease in the percentage of neutrophils (P < 0.006) and neutrophil-to-lymphocyte ratio (NLR) levels (P < 0.003), associated with a significant increase in the percentage of lymphocytes in the BAs group compared with the placebo (P < 0.002). Additionally, a significant decrease in CRP, LDH, IL - 6 and TNF - α levels was detected in the BAs group. Following the intervention, fewer patients in the BAs group were PCR-positive for COVID-19 compared to placebo, though not statistically significant. CONCLUSION: Overall, the treatment with Inflawell® resulted in shorter hospital stay, alleviation of COVID-19 clinical symptoms and decline in the level of pro-inflammatory cytokines. TRIAL REGISTRATION: The trial has been registered in  https://www.irct.ir  with unique identifier: IRCT20170315033086N10 ( https://en.irct.ir/trial/51631 ). IRCT is a primary registry in the WHO registry network ( https://www.who.int/clinical-trials-registry-platform/network/primary-registries ).


Subject(s)
COVID-19 , Neutrophils , COVID-19/drug therapy , Double-Blind Method , Hospitalization , Humans , Lymphocytes , SARS-CoV-2 , Treatment Outcome
6.
Nutr Hosp ; 39(1): 20-26, 2022 Feb 09.
Article in English | MEDLINE | ID: covidwho-1702346

ABSTRACT

INTRODUCTION: Introduction: patients with COVID-19 undergo changes in leukocyte count, respiratory disorders, and an increase in inflammatory substances. To improve the inflammatory condition, some nutrients can be used, including arginine, omega-3 fatty acids and nucleotides. This study aims to evaluate how oral immunonutrient supplements affects serum C-reactive protein (CRP) levels and lymphocyte count in patients with COVID-19. Methods: in this double-blind clinical trial, we randomized 43 adult patients with COVID-19 to receive a standard high-protein normocaloric supplement (control) or an immunonutrient-enriched supplement (experiment) for 7 days. The primary outcome was to evaluate changes in total lymphocyte count and serum level of CRP. The assessment of risk and nutritional status of these patients was also performed. Results: forty-three patients with mean age of 41.5 (± 1.8) years were followed up, 39.5 % of them women. The mean body mass index was 27.6 (± 0.8) kg/m² and 58.1 % had low nutritional risk. In the experiment group, there was a CRP reduction of 23.6 (± 7.5) mg/L, while in the control branch the decrease was 14.8 (± 12.1) mg/L (p = 0.002). There was an increase in lymphocytes in the experiment group (+367.5 ± 401.8 cells/mm³) and a reduction in the control group (-282.8 ± 327.8 cells/mm³), although there was no statistical significance (p = 0.369). Relative risk (RR) of treatment in reducing CRP by 30 % or more was 4.45 (p < 0.001; 95 % CI, 1.79-11.07). RR in increasing lymphocyte count by 30 % or more was 1.28 (p = 0.327; 95 % CI, 0.67-2.45). Conclusion: we conclude that immunonutrient supplements seem to reduce CRP levels more than standard high-protein normocaloric supplements.


INTRODUCCIÓN: Introducción: los pacientes con COVID-19 sufren cambios en el recuento de leucocitos, trastornos respiratorios y aumento de sustancias inflamatorias. Para mejorar la condición inflamatoria se pueden usar algunos nutrientes, como la arginina, los ácidos grasos omega-3 y los nucleótidos. Este estudio tiene como objetivo evaluar cómo los suplementos de inmunonutrientes orales afectan a los niveles séricos de proteína C-reactiva (PCR) y al recuento de linfocitos en pacientes con COVID-19. Métodos: en este ensayo clínico doble ciego, aleatorizamos a 43 pacientes adultos con COVID-19 para recibir un suplemento normocalórico estándar alto en proteínas (control) o un suplemento enriquecido con inmunonutrientes (experimento) durante 7 días. El resultado primario fue evaluar los cambios en el recuento total de linfocitos y el nivel sérico de PCR. También se realizó la evaluación del riesgo y el estado nutricional de estos pacientes. Resultados: cuarenta y tres pacientes con edad media de 41,5 (± 1,8) años fueron seguidos, el 39,5 % de ellos mujeres. El índice de masa corporal medio fue de 27,6 (± 0,8) kg/m² y el 58,1 % tenían bajo riesgo nutricional. En el grupo experimental hubo una reducción de la PCR de 23,6 (± 7,5) mg/L, mientras que en la rama de control la disminución fue de 14,8 (± 12,1) mg/L (p = 0,002). Hubo un aumento de linfocitos en el grupo experimental (+367,5 ± 401,8 células/mm³) y una reducción en el grupo de control (-282,8 ± 327,8 células/mm³), aunque no hubo significación estadística (p = 0,369). El riesgo relativo (RR) del tratamiento para reducir la PCR en un 30 % o más fue de 4,45 (p < 0,001; IC 95 %: 1,79-11,07). El RR en el aumento del recuento de linfocitos en un 30 % o más fue de 1,28 (p = 0,327; IC 95 %: 0,67-2,45). Conclusión: se concluye que los suplementos de inmunonutrientes parecen reducir los niveles de PCR más que los suplementos normocalóricos estándar altos en proteína.


Subject(s)
C-Reactive Protein , COVID-19 , Adult , Dietary Supplements , Double-Blind Method , Female , Humans , Lymphocytes , SARS-CoV-2
7.
Eur Rev Med Pharmacol Sci ; 26(3): 1056-1064, 2022 02.
Article in English | MEDLINE | ID: covidwho-1704589

ABSTRACT

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has been identified in China as responsible for viral pneumonia, now called COVID-19 (Coronavirus Disease 2019). Patients infected can develop common symptoms like cough and sore throat, and, in severe cases, acute respiratory syndrome and even death. To optimize the available resources, it is necessary to identify in advance the subjects that will develop a more serious illness, therefore requiring intensive care.The neutrophil / lymphocyte ratio (NLR) parameter, resulting from the blood count, could be a significant marker for the diagnosis and management of risk stratification. PATIENTS AND METHODS: A retrospective, single-center case-control observational study was conducted. The differential cell count of leukocytes, the NLR and the clinical course of patients hospitalized in intensive care with COVID-19 were analyzed, comparing them with other patients (COVID-19 and non-COVID-19) and healthy individuals selected among workers of the Teaching Hospital Policlinico Umberto I in Rome. RESULTS: 370 patients (145 cases and 225 controls) were included in the case-control study, 211 males (57%) and 159 females (43%). The average age of the population was 63 years (SD 16.35). In the group of cases, out of 145 patients, 57 deaths and 88 survivors were recorded, with a lethality rate of 39.3%. The group of cases has an NLR of 7.83 (SD = 8.07), a much higher value than the control group where an NLR of 2.58 was recorded (SD = 1.93) (p <0.001). The Neutrophils / Lymphocytes ratio may prove to be a diagnostic factor for COVID-19, an NLR> 3.68 revealed an OR 10.84 (95% CI = 6.47 - 18.13) (p <0.005). CONCLUSIONS: The value of NLR considered together with the age variable allows a risk stratification and allows the development of diagnostic and treatment protocols for patients affected by COVID-19. A high neutrophil to lymphocyte ratio suggests worse survival. Risk stratification and management help alleviate the shortage of medical resources and reduce the mortality of critically ill patients.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Lymphocytes/metabolism , Lymphocytes/virology , Neutrophils/metabolism , Neutrophils/virology , Aged , Biomarkers/blood , Case-Control Studies , Critical Illness , Female , Humans , Intensive Care Units , Italy , Leukocyte Count , Logistic Models , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , Risk Factors , Severity of Illness Index
8.
Diagn Pathol ; 17(1): 31, 2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1690905

ABSTRACT

BACKGROUND: Despite a reported cardiac injury in patients with new coronavirus infection, the possibility and specifics of genuine viral myocarditis in COVID-19 remains not fully clear. PURPOSE: To study the presence of SARS-CoV-2 in the myocardium and the morphological properties of myocarditis in patients with severe coronavirus infection (COVID-19). METHODS: Autopsy data of eight elderly patients (75.6 ± 7.4 years), four male and four female, with severe new coronavirus infection were studied. The lifetime diagnosis of COVID-19 is based on a positive result of the PCR study. The inclusion criterion was the presence of morphological signs of myocarditis according to the Dallas criteria. A standard histological examination included staining by hematoxylin and eosin, toluidin blue and Van Gieson. An immunohistochemical study was performed using antibodies to CD3, CD 68, CD20, perforin, toll-like receptor (TLR) types 4 and 9. PCR in real-time was performed to determine the viral RNA in the myocardium. RESULTS: All patients had severe bilateral viral pneumonia. In all cases, myocarditis was not clinically diagnosed. Morphological examination of the heart found signs of active lymphocytic myocarditis. PCR identified the SARS-Cov2 RNA in all cases. There were also signs of destructive coronaritis in all cases, thrombovasculitis, lymphocytic pericarditis (in 3 cases) and endocarditis (in 2 cases). The absence of neutrophils confirms the aseptic nature of inflammation. An immunohistochemical study showed the CD3-positive T lymphocytes in the infiltrates. Increased expression of TLR type 4 and less 9 was also detected. CONCLUSION: Morphological and immunohistochemical evidence of myocarditis in COVID-19 was presented. Lymphocytic infiltrations and positive PCR confirm the viral nature of inflammation. Myocarditis in COVID-19 is also characterized by coronaritis with microvascular thrombosis and associated with lymphocytic endo- and pericarditis.


Subject(s)
COVID-19/pathology , Myocarditis/pathology , Pneumonia, Viral/pathology , SARS-CoV-2/isolation & purification , Aged , Aged, 80 and over , Autopsy , COVID-19/complications , COVID-19/diagnosis , COVID-19/virology , Female , Heart/virology , Humans , Immunohistochemistry , Inflammation , Lymphocytes/pathology , Male , Middle Aged , Myocarditis/complications , Myocarditis/diagnosis , Myocarditis/virology , Myocardium/pathology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2/genetics
9.
Nutr Hosp ; 39(1): 20-26, 2022 Feb 09.
Article in English | MEDLINE | ID: covidwho-1689650

ABSTRACT

INTRODUCTION: Introduction: patients with COVID-19 undergo changes in leukocyte count, respiratory disorders, and an increase in inflammatory substances. To improve the inflammatory condition, some nutrients can be used, including arginine, omega-3 fatty acids and nucleotides. This study aims to evaluate how oral immunonutrient supplements affects serum C-reactive protein (CRP) levels and lymphocyte count in patients with COVID-19. Methods: in this double-blind clinical trial, we randomized 43 adult patients with COVID-19 to receive a standard high-protein normocaloric supplement (control) or an immunonutrient-enriched supplement (experiment) for 7 days. The primary outcome was to evaluate changes in total lymphocyte count and serum level of CRP. The assessment of risk and nutritional status of these patients was also performed. Results: forty-three patients with mean age of 41.5 (± 1.8) years were followed up, 39.5 % of them women. The mean body mass index was 27.6 (± 0.8) kg/m² and 58.1 % had low nutritional risk. In the experiment group, there was a CRP reduction of 23.6 (± 7.5) mg/L, while in the control branch the decrease was 14.8 (± 12.1) mg/L (p = 0.002). There was an increase in lymphocytes in the experiment group (+367.5 ± 401.8 cells/mm³) and a reduction in the control group (-282.8 ± 327.8 cells/mm³), although there was no statistical significance (p = 0.369). Relative risk (RR) of treatment in reducing CRP by 30 % or more was 4.45 (p < 0.001; 95 % CI, 1.79-11.07). RR in increasing lymphocyte count by 30 % or more was 1.28 (p = 0.327; 95 % CI, 0.67-2.45). Conclusion: we conclude that immunonutrient supplements seem to reduce CRP levels more than standard high-protein normocaloric supplements.


INTRODUCCIÓN: Introducción: los pacientes con COVID-19 sufren cambios en el recuento de leucocitos, trastornos respiratorios y aumento de sustancias inflamatorias. Para mejorar la condición inflamatoria se pueden usar algunos nutrientes, como la arginina, los ácidos grasos omega-3 y los nucleótidos. Este estudio tiene como objetivo evaluar cómo los suplementos de inmunonutrientes orales afectan a los niveles séricos de proteína C-reactiva (PCR) y al recuento de linfocitos en pacientes con COVID-19. Métodos: en este ensayo clínico doble ciego, aleatorizamos a 43 pacientes adultos con COVID-19 para recibir un suplemento normocalórico estándar alto en proteínas (control) o un suplemento enriquecido con inmunonutrientes (experimento) durante 7 días. El resultado primario fue evaluar los cambios en el recuento total de linfocitos y el nivel sérico de PCR. También se realizó la evaluación del riesgo y el estado nutricional de estos pacientes. Resultados: cuarenta y tres pacientes con edad media de 41,5 (± 1,8) años fueron seguidos, el 39,5 % de ellos mujeres. El índice de masa corporal medio fue de 27,6 (± 0,8) kg/m² y el 58,1 % tenían bajo riesgo nutricional. En el grupo experimental hubo una reducción de la PCR de 23,6 (± 7,5) mg/L, mientras que en la rama de control la disminución fue de 14,8 (± 12,1) mg/L (p = 0,002). Hubo un aumento de linfocitos en el grupo experimental (+367,5 ± 401,8 células/mm³) y una reducción en el grupo de control (-282,8 ± 327,8 células/mm³), aunque no hubo significación estadística (p = 0,369). El riesgo relativo (RR) del tratamiento para reducir la PCR en un 30 % o más fue de 4,45 (p < 0,001; IC 95 %: 1,79-11,07). El RR en el aumento del recuento de linfocitos en un 30 % o más fue de 1,28 (p = 0,327; IC 95 %: 0,67-2,45). Conclusión: se concluye que los suplementos de inmunonutrientes parecen reducir los niveles de PCR más que los suplementos normocalóricos estándar altos en proteína.


Subject(s)
C-Reactive Protein , COVID-19 , Adult , Dietary Supplements , Double-Blind Method , Female , Humans , Lymphocytes , SARS-CoV-2
10.
J Nepal Health Res Counc ; 19(3): 536-542, 2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1687864

ABSTRACT

BACKGROUND: Several laboratory parameters have been linked to Corona Virus Disease 2019 (COVID-19), with lymphocytes being one of the most important. Lymphopenia is frequently linked to a worsening of clinical symptoms and an increased risk of death in COVID-19. This study aimed to determine the role of lymphocyte levels in predicting COVID-19 patient mortality. METHODS: This is a prognostic study that is conducted from March 1 to August 31, 2020. Data from medical records and laboratory findings of COVID-19 patients were used in the study. Patient distribution and complete blood count were among the information gathered. ROC curve analysis, bivariate analysis (Chi-Square and Mann Whitney), in addition to survival analysis (Kaplan-Meier) were used to analyze the data. RESULTS: In a total of 318 patients, 59 were non-survivors and 259 were survivors. Besides, a cut-off value of ?1460 cells/µL (P<0.05) was used for lymphocyte levels. Lymphopenia also has a 4.35-fold increase in the risk of mortality. Furthermore, the survival analysis revealed differences in the probability of survival within 30 days between COVID-19 patients with lymphopenia and those without (HR: 5.5722 (3.2509-9.5510), 95% CI; p<0.0001). A lymphocyte count of ?1460 cell/µL can increase the risk of death by fourfold. CONCLUSIONS: The findings of this study indicated a significant difference in outcome between lymphopenia and non-lymphopenia patients. Lymphopenia plays an important role in estimating COVID-19 patient mortality.


Subject(s)
COVID-19 , Humans , Indonesia/epidemiology , Lymphocyte Count , Lymphocytes , Nepal , Prognosis , Retrospective Studies , SARS-CoV-2
11.
Clin Lab ; 68(3)2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1675214

ABSTRACT

BACKGROUND: Covid-19 is a pandemic viral infection with high pathogenicity and contagiousness. Our aim is to evaluate the preliminary hematological findings analyzed during admission in order to determine the diagnostic value of hematological parameters in Covid-19 patients and to reveal their relationship with the severity of the disease. METHODS: Our study includes a total of 169 patients, whose diagnosis was confirmed and 93 of whom were treated in the ward, 76 of whom were treated in the Intensive Care Unit (ICU), and 67 control patients. Neutrophil-to-lymphocyte ratio (NLR), monocyte-lymphocyte (MLR) ratio, platelet-lymphocyte ratio (PLR), mean platelet volume/platelet count ratio (MPV/PLT) data on admission were analyzed retrospectively and compared. RESULTS: ICU patients had significantly higher values of NLR, MLR, PLR, and MPV/PLT (p < 0.001 for each) but had lower values of lymphocyte count and hemoglobin (p < 0.001 for each) compared to that of ward patients. According to the results of ROC analysis, the diagnostic values of NLR, MLR, PLR, and MPV/PLT parameters were statistically significant (p < 0.05). CONCLUSIONS: According to the results of our study, abnormal routine peripheral blood examination results were detected in Covid-19 patients. NLR, MLR, and PLR can be considered as independent, reliable biomarkers for assessing disease severity, hospitalization, and clinical classification in Covid-19. Therefore, it was concluded that fast, cost-effective, easily accessible admission hemogram parameters are reasonably important to predict the prognosis of Covid-19 patients.


Subject(s)
COVID-19 , Neutrophils , Blood Platelets , COVID-19/diagnosis , Humans , Lymphocytes , Monocytes , Retrospective Studies , SARS-CoV-2
12.
Cells ; 11(3)2022 02 04.
Article in English | MEDLINE | ID: covidwho-1674518

ABSTRACT

This review is a comprehensive analysis of the effects of SARS-CoV-2 infection on Unconventional T cells and innate lymphoid cells (ILCs). COVID-19 affected patients show dysregulation of their adaptive immune systems, but many questions remain unsolved on the behavior of Unconventional cells and ILCs during infection, considering their role in maintaining homeostasis in tissue. Therefore, we highlight the differences that exist among the studies in cohorts of patients who in general were categorized considering symptoms and hospitalization. Moreover, we make a critical analysis of the presence of particular clusters of cells that express activation and exhausted markers for each group in order to bring out potential diagnostic factors unconsidered before now. We also focus our attention on studies that take into consideration recovered patients. Indeed, it could be useful to determine Unconventional T cells' and ILCs' frequencies and functions in longitudinal studies because it could represent a way to monitor the immune status of SARS-CoV-2-infected subjects. Possible changes in cell frequencies or activation profiles could be potentially useful as prognostic biomarkers and for future therapy. Currently, there are no efficacious therapies for SARS-CoV-2 infection, but deep studies on involvement of Unconventional T cells and ILCs in the pathogenesis of COVID-19 could be promising for targeted therapies.


Subject(s)
Adaptive Immunity/immunology , COVID-19/immunology , Immunity, Innate/immunology , Lymphocytes/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , COVID-19/epidemiology , COVID-19/virology , Homeostasis/immunology , Humans , Lymphocyte Activation/immunology , Lymphocyte Count , Pandemics/prevention & control , SARS-CoV-2/physiology
13.
Sci Rep ; 12(1): 1727, 2022 02 02.
Article in English | MEDLINE | ID: covidwho-1671625

ABSTRACT

As the first dose of Gam-COVID-Vac, is currently used as a single dose vaccine in some countries, we investigated the immunogenicity of this at 4 weeks (327 naïve individuals). 88.7% seroconverted, with significantly lower seroconversion rates in those over 60 years (p = 0.004) and significantly lower than previously seen with AZD1222 (p = 0.018). 82.6% developed ACE2 receptor blocking antibodies, although levels were significantly lower than following natural infection (p = 0.0009) and a single dose of AZD1222 (p < 0.0001). Similar titres of antibodies were observed to the receptor binding domain of WT, B.1.1.7 and B.1.617.2 compared to AZD1222, while the levels for B.1.351 were significantly higher (p = 0.006) for Gam-COVID-Vac. 30% developed ex vivo IFNγ ELISpot responses (significantly lower than AZD1222), and high frequency of CD107a expressing T cells along with memory B cell responses. Although single dose of Gam-COVID-Vac was highly immunogenic, administration of a second dose is likely to be beneficial.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunization , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Vaccines, Synthetic/administration & dosage , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/immunology , Biomarkers/blood , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Female , Humans , Interferon-gamma/metabolism , Lymphocytes/immunology , Lymphocytes/metabolism , Lymphocytes/virology , Male , Middle Aged , Seroconversion , Time Factors , Treatment Outcome , Vaccines, Synthetic/immunology , Young Adult
14.
Front Endocrinol (Lausanne) ; 12: 774346, 2021.
Article in English | MEDLINE | ID: covidwho-1662575

ABSTRACT

Background: Both lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated. Methods: We included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to April 2021 who had thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and LYM measured on admission. Results: A total of 541 patients were included. Median LYM was 1.22 x 109/L, with 36.0% of the cohort lymphopenic. 83 patients (15.4%) had abnormal thyroid function tests (TFTs), mostly non-thyroidal illness syndrome (NTIS). Patients with lymphopenia had lower TSH, fT4 and fT3 levels than those without. Multivariable stepwise linear regression analysis revealed that both TSH (standardized beta 0.160, p<0.001) and fT3 (standardized beta 0.094, p=0.023), but not fT4, remained independently correlated with LYM, in addition to age, SARS-CoV-2 viral load, C-reactive protein levels, coagulation profile, sodium levels and more severe clinical presentations. Among the 40 patients who had reassessment of TFTs and LYM after discharge, at a median of 9 days from admission, there were significant increases in TSH (p=0.031), fT3 (p<0.001) and LYM (p<0.001). Furthermore, patients who had both lymphopenia and NTIS were more likely to deteriorate compared to those who only had either one alone, and those without lymphopenia or NTIS (p for trend <0.001). Conclusion: TSH and fT3 levels showed independent positive correlations with LYM among COVID-19 patients, supporting the interaction between the hypothalamic-pituitary-thyroid axis and immune system in COVID-19.


Subject(s)
COVID-19/complications , Lymphocytes/pathology , Lymphopenia/epidemiology , SARS-CoV-2/isolation & purification , Thyroid Diseases/epidemiology , Thyrotropin/blood , Triiodothyronine/blood , Adult , Aged , COVID-19/virology , China/epidemiology , Female , Hospitalization , Humans , Lymphocyte Count , Lymphopenia/blood , Lymphopenia/immunology , Lymphopenia/virology , Male , Middle Aged , Thyroid Diseases/blood , Thyroid Diseases/immunology , Thyroid Diseases/virology , Thyroid Function Tests , Thyroid Hormones/blood
15.
Cell ; 185(5): 916-938.e58, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1654147

ABSTRACT

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19.


Subject(s)
Biomarkers/blood , COVID-19/pathology , Proteome/analysis , Adult , Blood Proteins/metabolism , COVID-19/blood , COVID-19/virology , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Female , Humans , Influenza, Human/blood , Influenza, Human/pathology , Lymphocytes/immunology , Lymphocytes/metabolism , Machine Learning , Male , Middle Aged , Mitogen-Activated Protein Kinase 14/genetics , Mitogen-Activated Protein Kinase 14/metabolism , Monocytes/immunology , Monocytes/metabolism , Principal Component Analysis , SARS-CoV-2/isolation & purification , Sepsis/blood , Sepsis/pathology , Severity of Illness Index , Transcription Factor AP-1/genetics , Transcription Factor AP-1/metabolism
16.
Cytokine ; 151: 155804, 2022 03.
Article in English | MEDLINE | ID: covidwho-1630370

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disorder caused by a new coronavirus called SARS-CoV-2. The pathophysiology of severe COVID-19 is associated with a "cytokine storm". IL-32 is a key modulator in the pathogenesis of various clinical conditions and is mostly induced by IL-8. IL-32 modulates important inflammatory pathways (including TNF-α, IL-6 and IL-1b), contributing to the pathogenesis of inflammatory diseases. Il-32 was never evaluated before in COVID-19 patients stratifying as mild-moderate and severe patients. A total of 64 COVID-19 patients, 27 healthy controls were consecutively enrolled in the study. Serum concentrations of biomarkers including IL-1ß, IL-10, IFN-γ, TNF-α and IL-6 were quantified by bead-based multiplex analysis and Serum concentration of IL-8 and IL-32 were determined by enzyme-linked immunosorbent assay (ELISA) kits. Interestingly, among the blood parameters, neutrophil and lymphocyte counts were significantly lower in severe COVID-19 patients than in the other, on the contrary, CRP was significantly higher in severe patients than in other groups. The cytokines that best distinguished controls from COVID-19 patients were IL-8 and IL-32, while IL-6 resulted the better variables for discriminate severe group. The best model performance for severe group was obtained by the combination of IL-32, IL-6, IFN-γ, and CRP serum concentration showing an AUC = 0.83. A cut off of 15 pg/ml of IL-6 greatly discriminate survivor from death patients. New insights related to the cytokine storm in COVID-19 patients, highlighting different severity of disease infection.


Subject(s)
COVID-19/blood , Cytokines/blood , Interleukin-8/blood , Interleukins/blood , Lung/immunology , Aged , Biomarkers/blood , COVID-19/immunology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/immunology , Cytokines/immunology , Female , Humans , Interleukin-10/blood , Interleukin-10/immunology , Interleukin-8/immunology , Interleukins/immunology , Lymphocyte Count/methods , Lymphocytes/immunology , Male , Middle Aged , Neutrophils/immunology , Prospective Studies , SARS-CoV-2/immunology
17.
Viruses ; 14(1)2022 01 14.
Article in English | MEDLINE | ID: covidwho-1625756

ABSTRACT

Bats are reservoirs of a large number of viruses of global public health significance, including the ancestral virus for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the causative agent of coronavirus disease 2019 (COVID-19). Although bats are natural carriers of multiple pathogenic viruses, they rarely display signs of disease. Recent insights suggest that bats have a more balanced host defense and tolerance system to viral infections that may be linked to the evolutionary adaptation to powered flight. Therefore, a deeper understanding of bat immune system may provide intervention strategies to prevent zoonotic disease transmission and to identify new therapeutic targets. Similar to other eutherian mammals, bats have both innate and adaptive immune systems that have evolved to detect and respond to invading pathogens. Bridging these two systems are innate lymphocytes, which are highly abundant within circulation and barrier tissues. These cells share the characteristics of both innate and adaptive immune cells and are poised to mount rapid effector responses. They are ideally suited as the first line of defense against early stages of viral infections. Here, we will focus on the current knowledge of innate lymphocytes in bats, their function, and their potential role in host-pathogen interactions. Moreover, given that studies into bat immune systems are often hindered by a lack of bat-specific research tools, we will discuss strategies that may aid future research in bat immunity, including the potential use of organoid models to delineate the interplay between innate lymphocytes, bat viruses, and host tolerance.


Subject(s)
Chiroptera/immunology , Host-Pathogen Interactions/immunology , Immunity, Innate/immunology , Lymphocytes/immunology , Animals , Chiroptera/virology , Disease Reservoirs/virology , Humans , Immune Tolerance , Virus Diseases/immunology , Virus Diseases/transmission , Viruses/pathogenicity
18.
Nat Commun ; 13(1): 269, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1621240

ABSTRACT

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.


Subject(s)
COVID-19/immunology , SARS-CoV-2/physiology , Aged , Autopsy , COVID-19/diagnosis , COVID-19/genetics , COVID-19/virology , China , Diagnosis , Female , Hepatitis A Virus Cellular Receptor 2/genetics , Hepatitis A Virus Cellular Receptor 2/immunology , Humans , Lymphocyte Activation , Lymphocytes/immunology , Male , Middle Aged , Myeloid Cells/immunology , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2/immunology , Viral Load
19.
Biometals ; 35(1): 125-145, 2022 02.
Article in English | MEDLINE | ID: covidwho-1611429

ABSTRACT

The role of micronutrient deficiency in the pathogenesis of COVID-19 has been reviewed in the literature; however, the data are limited and conflicting. This study investigated the association between the status of essential metals, vitamins, and antioxidant enzyme activities in COVID-19 patients and disease severity. We recruited 155 patients, who were grouped into four classes based on the Adults guideline for the Management of Coronavirus Disease 2019 at King Faisal Specialist & Research Centre (KFSH&RC): asymptomatic (N = 16), mild (N = 49), moderate (N = 68), and severe (N = 22). We measured serum levels of copper (Cu), zinc (Zn), selenium (Se), vitamin D3, vitamin A, vitamin E, total antioxidant capacity, and superoxide dismutase (SOD). Among the patients, 30%, 25%, 37%, and 68% were deficient in Se (< 70.08 µg/L), Zn (< 0.693 µg/mL), vitamin A (< 0.343 µg/mL), and vitamin D3 (< 20.05 µg/L), respectively, and SOD activity was low. Among the patients, 28% had elevated Cu levels (> 1.401 µg/mL, KFSH&RC upper reference limit). Multiple regression analysis revealed an 18% decrease in Se levels in patients with severe symptoms, which increased to 30% after adjusting the model for inflammatory markers. Regardless of inflammation, Se was independently associated with COVID-19 severity. In contrast, a 50% increase in Cu levels was associated with disease severity only after adjusting for C-reactive protein, reflecting its possible inflammatory and pro-oxidant role in COVID-19 pathogenesis. We noted an imbalance in the ratio between Cu and Zn, with ~ 83% of patients having a Cu/Zn ratio > 1, which is an indicator of inflammation. Cu-to-Zn ratio increased to 45% in patients with mild symptoms and 34%-36% in patients with moderate symptoms compared to asymptomatic patients. These relationships were only obtained when one of the laboratory parameters (lymphocyte or monocyte) or inflammatory markers (neutrophil-to-lymphocyte ratio) was included in the regression model. These findings suggest that Cu/Zn might further exacerbate inflammation in COVID-19 patients and might be synergistically associated with disease severity. A 23% decrease in vitamin A was seen in patients with severe symptoms, which disappeared after adjusting for inflammatory markers. This finding may highlight the potential role of inflammation in mediating the relationship between COVID-19 severity and vitamin A levels. Despite our patients' low status of Zn, vitamin D3, and antioxidant enzyme (SOD), there is no evidence of their role in COVID-19 progression. Our findings reinforce that deficiency or excess of certain micronutrients plays a role in the pathogenesis of COVID-19. More studies are required to support our results.


Subject(s)
COVID-19/blood , Copper/blood , SARS-CoV-2/pathogenicity , Selenium/blood , Zinc/blood , Adolescent , Adult , Aged , Aged, 80 and over , Asymptomatic Diseases , C-Reactive Protein/metabolism , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Cell Count , Cholecalciferol/blood , Humans , Lymphocytes/immunology , Lymphocytes/virology , Middle Aged , Monocytes/immunology , Monocytes/virology , Neutrophils/immunology , Neutrophils/virology , Regression Analysis , SARS-CoV-2/growth & development , Severity of Illness Index , Superoxide Dismutase/blood , Vitamin A/blood , Vitamin E/blood
20.
Int Immunopharmacol ; 102: 108392, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1608746

ABSTRACT

The outbreak of novel coronavirus disease 2019 (COVID-19) poses a great stress to frontline medical workers. Our previous study indicated that immune cells in the peripheral blood of frontline medical workers changed significantly. However, the dynamic changes of immune cells of frontline medical workers remain unclear. Here, we reported the dynamic changes of lymphocyte subsets in the peripheral blood of 51 frontline medical worker. The frontline medical workers struggling with COVID-19 from February 8 to March 31, 2020. Demographic and clinical data, including routine blood test data were extracted from the electronic health examination record and retrospectively analyzed. The lymphocyte (LYM) count and LYM ratio increased while the monocyte (MONO) ratio, neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and neutrophil (NEUT) ratio in the peripheral blood of frontline medical workers decreased 10 days after struggling with COVID-19. Interestingly, the differences of LYM count, LYM ratio, MONO ratio, NLR, NEUT ratio were more significantly in nurse than doctor. The differences of LYM ratio, NLR and NEUT ratio were more significantly in female than male. However, the changes of LYM count, LYM ratio, MONO ratio, NLR, MLR, NEUT ratio returned to the baseline 10 months after struggling with COVID-19. Together, these data indicated that immune cells in the peripheral blood changed significantly 10 days after struggling with COVID-19, but returned to normal after 10 months. Those maybe caused by psychological stress and we recommend to pay more attention to mental health and immune response of frontline medical workers.


Subject(s)
COVID-19/therapy , Health Personnel/statistics & numerical data , Immunity, Cellular , Stress, Psychological/immunology , Workload/psychology , Adult , COVID-19/epidemiology , COVID-19/virology , Female , Humans , Lymphocyte Count , Lymphocytes , Male , Monocytes , Neutrophils , Occupational Exposure , Retrospective Studies , SARS-CoV-2/pathogenicity , Sex Factors , Stress, Psychological/blood , Workload/statistics & numerical data
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