Characteristics of SARS-CoV-2, COVID-19, and laboratory diagnosis / Características del SARS-CoV-2, COVID-19 y su diagnóstico en el laboratorio

La enfermedad COVID­19 es causada por el virus SARS-CoV-2, descrito por primera vez en diciembre del 2019 en Wuhan, China, y declarada en marzo del 2020 como una pandemia mundial. Actualmente existen diversos métodos diagnósticos para COVID-19, siendo el estándar de oro la detección del material genético mediante la reacción en cadena de la polimerasa (PCR), en su variante, la RT-PCR, que detecta el material genético de tipo ARN presente en el virus. Sin embargo, es necesario disponer de pruebas rápidas con alta sensibilidad y precisión para realizarlas a gran escala y brindar un diagnóstico oportuno. Adicionalmente, se debe disponer de otras herramientas que, si bien no van a establecer un diagnóstico, le van a permitir al profesional brindar un mejor manejo clínico y epidemiológico que ayuden a predecir el agravamiento del paciente y su posible ingreso a UCI, destacando entre estas los niveles de dímero D, linfocitos, ferritina, urea y creatinina, entre otras. En esta revisión se evalúa la utilidad y limitaciones de los diferentes métodos diagnósticos para COVID-19, al igual que las características, fisiopatología y respuesta inmune al SARS-CoV-2, así como algunos aspectos preanalíticos de importancia que ayudan a minimizar errores en el diagnóstico como consecuencia de procedimientos incorrectos en la toma, transporte y conservación de la muestra, y que permiten al profesional emitir resultados veraces y confiables. Lo anterior se realizó basado en artículos originales, revisiones y guías clínicas

COVID­19 is caused by the SARS-CoV-2 virus, first described in December 2019 in Wuhan, China, and declared a global pandemic in March 2020. Currently there are various diagnostic methods for COVID-19, the gold standard is the detection of genetic material through polymerase chain reaction (PCR) in its variant, RT-PCR, which detects RNA-type genetic material present in the virus. However, it is necessary to have rapid tests with high sensitivity and precision to be performed on a large scale and provide timely diagnosis. Furthermore, other tools must be available, and although they will not establish the diagnosis, will allow the professional to provide better clinical and epidemiological management that will help predict the worsening of the patient and possible admission to the ICU. Among these, levels of D-dimer, lymphocytes, ferritin, urea and creatinine. In this review, the usefulness and limitations of the different diagnostic methods for COVID-19 are evaluated, as well as the characteristics, pathophysiology and immune response to SARS-CoV-2, and some important preanalytical aspects that allow minimizing diagnostic errors as a consequence of incorrect procedures in the collection, transport and conservation of the sample, that allow the professional to yield accurate and reliable results. This article was completed based on original articles, reviews and clinical guidelines

Ferritin in pediatric critical illness: a scoping review.

This scoping review aimed to elucidate and summarize the predictive role of serum ferritin in critical pediatric illness. The Preferred Reporting Items for Systematic reviews and Meta-Analyses methodology was employed to conduct a scoping review of five databases (MEDLINE, CENTRAL, ProQuest, ScienceDirect, and Epistemonikos) from the date of inception through January 24, 2022. Primary research studies involving subjects aged <18 years and serum ferritin levels were screened and reviewed independently following an a priori defined protocol. Of the 1,580 retrieved studies, 66 were analyzed. Summary statistics of serum ferritin levels for overall and condition-specific studies were reported in 30 (45.4%) and 47 (71.2%) studies, respectively. The normal range was defined in 16 studies (24.2%), whereas the threshold was determined in 43 studies (65.1%). A value of <500 ng/mL was most often the upper limit of the normal range. Serum ferritin as a numerical variable (78.9%) was usually significantly higher (80.8%) in the predicted condition than in controls, while as a categorical variable with preset thresholds, ferritin was a significant predictor in 84.6% of studies. A total of 22 predictive thresholds predicted mortality (12/46 [26.1%]), morbidity (18/46 [39.1%]), and specific (16/46 [34.8%]) outcomes in 15 unique conditions. Increased precision in serum ferritin measures followed by close attention to the threshold modeling strategy and reporting can accelerate the translation from evidence to clinical practice.

Interleukin-6 versus ferritin and D-Dimer in the cytokine release syndrome in critically ill Covid-19 patients

Introduction: The lack of a clear definition of cytokine release syndrome (CRS) allowed this study to analyze the utility of interleukin-6 (IL-6), ferritin, and D-dimer (DD) with other variables and their clinical evolution. Methods: A prospective, observational, and analytical study was conducted from October 2020 to July 2021 in 125 patients in the intensive care unit (ICU) of Hospital Obrero Nro. 2 of the Caja Nacional de Salud in Cochabamba, Bolivia. The three markers and other exams were requested to determine correlations, survival, and relationship with CRS. Results: The mean ferritin was 1193.7±814.8 ng/ml, D-dimer 1427±1005 ng/ml, and IL-6 58.5±34.1 pg/mL. No statistical association was found between these markers, but a Spearman's Rho of 0.5 between ferritin and DD (p<0.05) was found in patients who died. In addition, there were associations between male gender and ferritin, DD and dyspnea, and IL-6 and tracheostomy. Survival was 9 days 95% CI (8.02-9.98) with similar values of DD and ferritin for both normal and elevated levels. The values of the area under the curve (AUC) did not show prediction of mortality, but a rate of 70%. Survival was better in those who did not suffer from acute respiratory distress syndrome (ARDS), with eight days (p=0.011). Conclusions: It is not possible to relate CRS to IL-6, DD, and ferritin, or to define it with fever, leukocytosis, renal failure, tracheostomy, due to the heterogeneous values of IL-6 in relation to COVID-19 and other inflammatory pathologies. The position of a hypoinflammatory disease rather than a hypercytokinemia remains in doubt. © 2022 The authors.

Analýza pacientů se závažnou zlomeninou s a bez infekce COVID-19

PURPOSE OF THE STUDY As in orthopedic trauma patients, a hyperinflammatory response due to cytokine release occurs in patients with moderate and severe COVID-19 infection. In these patients, untimely surgical intervention can create more destructive situations in the postoperative period. Our aim in this study was to investigate the effect of COVID-19, trauma and surgical intervention on acute phase reactants' levels in patients with and without COVID-19 infection. MATERIAL AND METHODS Twenty-four patients diagnosed with COVID-19 infection and major fractures requiring surgical treatment were evaluated retrospectively (Group 1). Twenty-four COVID-19 negative patients with similar trauma were included in the study as a control group (Group 2). These two groups were compared in terms of demographic data, time to surgery, total hospitalization time, and preoperative and postoperative acute phase reactants' [C-reactive protein (CRP), D-dimer, ferritin, fibrinogen and white blood cell (WBC)] values. RESULTS Time to surgery was 8.3 ± 0.7 days and the total hospital stay was 15.2 ± 0.8 days, in Group 1. These values were determined as 3.3 ± 0.4 and 6.5 ± 0.6 days, respectively for the patients in Group 2 (p < 0.001 and p < 0.001, respectively). When the acute phase reactant values studied during admission were examined, a significant difference was found between the two groups in terms of CRP, D-dimer, ferritin and WBC (p = 0009, p = 0.002, p < 0.001 and p < 0.001, respectively). In the preoperative period, a significant difference was observed between the groups in terms of CRP and ferritin (p = 0.011, p < 0.001, respectively). A significant difference was found only in terms of ferritin from the laboratory values studied in the postoperative period (p < 0.001). DISCUSSION To our knowledge, the present study is the first study which compares and investigates the effects of COVID-19 infection, major fracture and surgical intervention on acute phase reactants' values. Surgical treatment is generally recommended as soon as possible in daily orthopedic practice. However, in patients with asymptomatic or mildly symptomatic COVID-19 infection, it remains unclear how long surgical intervention will be delayed after admission and clinical stabilization of patients with a fracture that requires surgical fixation. In a meta-analysis, patients with COVID-19 infection accompanying hip fracture had a mortality rate of 32.6% in the early postoperative period, and the mortality risk of these patients was found to be 5.66 times higher compared to patients without COVID-19 infection. In our study, one patient (4.2%) with COVID-19 infection who underwent partial hip arthroplasty due to femoral neck fracture. CONCLUSIONS The follow-up and treatment of patients with COVID-19 infection with accompanying a major fracture requiring orthopedic surgery is a complex situation. We recommend that acute phase reactants such as CRP, D-dimer, erythrocyte sedimentation rate (ESR), and ferritin should be closely monitored in these patients during the period from admission to surgery, and surgical intervention should be performed while these values are in remission or decline. Key words: COVID-19, fracture, trauma, acute phase reactants, surgical timing.

Transient Elastography of Liver and Serum Hyaluronic Acid Levels In Adult Transfusion Dependent Thalassemia Patients

Iron overload occurs as a result of multiple blood transfusions and increased iron absorption in thalassemia patients. Iron deposition in liver results in liver stiffness and fibrosis. Non invasive methods including imaging and serum biomarkers have been introduced for assessment of liver fibrosis. We aimed to study liver stiffness using transient elastography and serum hyaluronic acid levels and correlate them with serum ferritin levels in adult transfusion dependent beta thalassemia patients. MATERIAL: 70 transfusion dependent thalassemia patients of age ≥18 years, registered at Thalassemia Day Care Centre were subjected to investigations like CBC, Liver function tests, viral markers, serum ferritin, serum hyaluronic acid levels and transient elastography. Fibrosis indices like FIB-4, AAR and APRI were also calculated. 45 patients had T2*MRI reports with them;which were also included and analysed. Spearman coefficient r was used to test correlations between TE values and serum HA levels with other variables. OBSERVATION: 70 patients (41 male and 29 female) with mean age of 24.09±5.38 years and BMI 20.51 ±3.47 kg/m², were enrolled. Median values of hemoglobin, AST, ALT, TE, serum HA and serum ferritin were, 9.15 g/dl, 42 IU/L, 47.50 IU/L, 9.1 kPa, 284 ng/dl and 1841 ng/ml, respectively . TE values had significant positive correlation with serum ferritin (r=0.5, p < 0.001), ALT (r=0.59, p < 0.001), AST (r=0.58, p< 0.001), APRI (r=0.5, p<0.001) and FIB-4 (p=0.02), respectively and significant negative correlation with T2* MRI (ms) (r= -0.5, p<0.001). No significant correlation of HA was found with any variable. CONCLUSION: Transient elastography can be used as a non expensive, easily accessible and non invasive marker of liver iron overload. Further detailed studies are required to establish the role of serum Hyaluronic acid in thalassemia patients. © Journal of the Association of Physicians of India 2011.

Comparison of Analytical Values D-Dimer, Glucose, Ferritin and C-Reactive Protein of Symptomatic and Asymptomatic COVID-19 Patients.

Those infected by COVID-19 develop various kinds of complications with varying degrees of severity. For this reason, it is necessary to evaluate its analytical values to predict and reduce the risks and complications derived from this pathology. A cross-sectional study was carried out a population in Almeria (south-eastern Spain) who had a positive Polymerase Chain Reaction test result from 1 March 2020 to 30 November 2020. The study involved 4575 patients, with 1346 who were asymptomatic, 1653 mildly symptomatic (no hospitalisation needed) and 1576 severely symptomatic (symptomatic patients hospitalised). Laboratory values for D-dimer, glucose, serum ferritin, and C-reactive protein were analysed. The mean age of the participants in the study was 53.60 (16.89) years old. A total of 70.6% of the patients were symptomatic, of which 36.1% had mild symptoms. For all of the laboratory predictors analysed (D-dimer, glucose, serum ferritin, and C-reactive protein), it was found that severe alterations in the parameters were more frequent in severely symptomatic patients with statistically significant differences (p < 0.001), although these alterations also occurred in asymptomatic patients. Age correlated with analytical values (D-dimer, glucose, serum ferritin, and C-reactive protein) with statistically significant differences. Patients with severe symptoms presented alterations in the analytical values of D-dimer, glucose, serum ferritin, and C-reactive protein. Asymptomatic patients presented alterations in the analysed parameters, though with less frequency and severity than patients with severe symptoms.

Angiotensin-Converting Enzyme Receptor Genotype and its Activity Level as Potential Predictors of the Severity COVID-19 among Iraqi Patients

Objectives: The purpose of this study is to determine whether the angiotensin-converting enzyme activity and various biomarkers are used to investigate the severity of Covid-19 and to study the genetic variation occurs in angiotensin-converting enzyme-2 (ACE-2) receptor in severe Covid-19-related genes in the Iraqi population of Kerbala Province. Methods: This case-control study was conducted on 176 subjects who survived hospitalization and diagnosed by physician. Various biomarkers including ferritin, C-reactive protein, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, angiotensin-converting enzyme-2 activity levels were determined. Accordingly, they were divided into three groups: 59 of them were infected with severe Covid-19, 54 of them were infected with moderate Covid-19 and 63 of them were checked and obtained as apparently healthy control. Severe and moderate patients were collected from Al-Hayat tertiary center at AI-Hussein Medical City, Kerbala Health Directorates, Kerbala - Iraq during Oct., 2020-July, 2021 with matched age ranged between (23-88) years. Blood samples of apparently healthy and Covid-19 samples were subjected to genomic DNA extraction within 24-48 hours of aspi ration. The genomic DNA extracted was subjected to electrophoresis through 1.5% of agarose gels which was detected by staining with the fluorescent dye ethidium bromide and then visualized by illumination with UV light to confirm the presence and integrity of the extracted DNA. Results: Genotyping of ACE-2 (I/D) polymorphism (rs4646994), which has a high prevalence, was performed by polymerase chain reaction assay. The amplification of an Alu repetitive element in an intron of the ACE-2 has shown three potential genotypes of I/I and D/D as homozygous, and l/D as heterozygous. Individuals with normal homozygous (DD) revealed band of (190 bp), while individuals with normal (II) revealed band of (490 bp), and the individuals with heterozygous (ID) revealed two bands (190, 490 bp) respectively. Every severe Covid-19 group carried (DD) allele genotype, moderate group carried (ID and II) alleles and finally the control group carried (DD, ID, II) alleles genotype. Conclusion: In the ACE-2 polymorphism, the D/D genotype allele is implicated as a risk factor for severe Covid-19 patients, in Iraqi population.

Systemic inflammatory markers and psychophysical olfactory scores in coronavirus disease 2019 patients: is there any correlation?

OBJECTIVE: To analyse the correlations between olfactory psychophysical scores and the serum levels of D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio in coronavirus disease 2019 patients. METHODS: Patients underwent psychophysical olfactory assessment with the Connecticut Chemosensory Clinical Research Center test, and determination of blood serum levels of the inflammatory markers D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio within 10 days of the clinical onset of coronavirus disease 2019 and 60 days after. RESULTS: Seventy-seven patients were included in this study. D-dimer, procalcitonin, ferritin and neutrophil-to-lymphocyte ratio correlated significantly with severe coronavirus disease 2019. No significant correlations were found between baseline and 60-day Connecticut Chemosensory Clinical Research Center test scores and the inflammatory markers assessed. CONCLUSION: Olfactory disturbances appear to have little prognostic value in predicting the severity of coronavirus disease 2019 compared to D-dimer, ferritin, procalcitonin and neutrophil-to-lymphocyte ratio. The lack of correlation between the severity and duration of olfactory disturbances and serum levels of inflammatory markers seems to further suggest that the pathogenetic mechanisms underlying the loss of smell in coronavirus disease 2019 patients are related to local rather than systemic inflammatory factors.

Gender-based disparities in COVID-19 patient outcomes.

Studies reported to date suggest that men with COVID-19 have more severe disease and worse outcomes when compared with women. The explanation for this finding is not entirely clear. The goal of this study was to compare clinical characteristics, inflammatory biomarkers and clinical outcome between men and women. This retrospective study included patients with COVID-19 admitted to 10 Virginia hospitals from January 1, 2020, to June 15, 2020. Demographic data, comorbidities, and inflammatory markers, including C reactive protein (CRP), D-dimer, ferritin, and the neutrophil:lymphocyte ratio, as well as patient outcomes, were compared between men and women. During the study period, 701 patients with PCR-confirmed COVID-19 infection were admitted. The patient's mean age was 61±17 years. There were 370 men (52.8%). There was no difference in age, racial distribution, and comorbidities in the male patients compared with the female patients. However, both the baseline and peak levels of CRP and ferritin were significantly higher in men as compared with women. While the baseline D-dimer was similar between the sexes, men had a significantly higher maximal D-dimer. Men had evidence of greater disease severity, with a significantly greater admission to the intensive care unit and borderline higher hospital mortality. Our study supports the observation that COVID-19 causes more severe disease in men. The greater disease severity in men was not due to the effect of age or comorbidities; however, in keeping with experimental studies, men had evidence of a heightened inflammatory response, likely contributing to disease severity.

A Review of Clinical and Laboratory Predictors of Severe COVID-19 Disease.

INTRODUCTION: In late December 2019, the coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. It quickly spread and emerged as a global pandemic with far-reaching impacts on society. As clinical research on this novel virus emerges, there is a limited amount of data that review clinical and laboratory predictors of severe disease. We present a case of a patient with severely elevated inflammatory markers who remained clinically stable during his hospital course. CASE DISCUSSION: A 53-year-old male presented to the emergency room with 11 days of persistent fevers and new-onset anterior chest tightness. He was admitted to the hospital due to a reported oxygen desaturation at home to 87% (taken by his spouse, a healthcare professional) and ambulatory oxygen desaturation down to 87%. He was noted to have severely elevated inflammatory markers, lymphopenia, and computed tomography pulmonary angiograph findings consistent with COVID-19. He remained on room air and clinically stable throughout his 3-day hospital course. While his C-reactive protein levels improved, his ferritin and erythrocyte sedimentation rate continued to elevate. He was discharged home and was symptom-free within 4 days of hospital discharge. DISCUSSION: COVID-19 has proven to be a viral disease with a high transmission rate, that has caused over 100,000 deaths in the United States, thus far. The decision to admit a patient must balance the risks of transmission with the benefit of being readily available to provide urgent supportive care should the patient develop complications. Thus, there is a significant benefit to being able to predict poor outcomes. We performed a targeted review of the literature, focusing on clinical and laboratory predictors of poor outcomes in COVID-19. Our case report and narrative review outline these findings within the context of our case.

Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study.

BACKGROUND: Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis. METHODS: We performed an observational study during the peak of pandemic in our intensive care unit, dosing D-dimer, C-reactive protein, troponin T, lactate dehydrogenase, ferritin, serum iron, transferrin, transferrin saturation, transferrin soluble receptor, lymphocyte count and NK, CD3, CD4, CD8 and B subgroups of 31 patients during the first 2 weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with the Spearman coefficient and Mann-Whitney test. Trends over time were tested with the Kruskal-Wallis analysis. RESULTS: Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 109/L; interquartile range (IQR) 0.450 109/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither ferritin nor lymphocyte count follows significant trends in ICU patients. Transferrin saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at days 3 to 6 (median 33%, IQR 26.5%, p value 0.026). The same trend is observed with serum iron levels (median 25.5 µg/L, IQR 69 µg/L at admission; median 73 µg/L, IQR 56 µg/L on days 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing haemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 µg/L; IQR 1285 µg/L) to days 3 to 6 (median 6820 µg/L; IQR 6619 µg/L), despite not reaching significant results. We describe trends of all the abovementioned parameters during ICU stay. CONCLUSIONS: The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the intensive care unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology.