COVID-19: presentación clínica en adultos / COVID-19: clinical features in adult patients

Este artículo resume las diferentes formas de presentación clínica de la enfermedad COVID-19 causada por el virus SARS-Co-2 documentadas fundamentalmente en las tres principales revisiones sistemáticas disponibles. Entre las manifestaciones clínicas de frecuente aparición se destacan la fiebre (83 %), la tos (60 %) y la fatiga (38 %), seguidas por las mialgias (29 %), el aumento de la producción del esputo (27 %) y la disnea (25 %). Entre los hallazgos de laboratorio,predominan el aumento de los valores de proteína C reactiva (69 %), la linfopenia (57 %) y el aumento de los niveles de lactato-deshidrogenasa (52 %). Respecto de las manifestaciones radiológicas, tienen especial importancia las opacificaciones en vidrio esmerilado (80 %), la neumonía bilateral (73 %) y la afectación de tres lóbulos pulmonares o más (57 %).Si bien la evidencia sintetizada tiene limitaciones, permite una aproximación actualizada a los conocimientos disponibles sobre la clínica de esta nueva enfermedad en la población adulta. (AU)

This article summarizes the different forms of clinical presentation of COVID-19, caused by the SARS-Co-2 virus, synthesizing the information collected mainly by three published systematic reviews. Frequent clinical manifestations include fever(83 %), cough (60 %), and fatigue (38 %), followed by myalgia (29 %), increased sputum production (27 %) and dyspnea(25 %). Among the laboratory findings, the most common are the increase in C-reactive protein values (69 %), lymphopenia (57 %) and the increase in lactate dehydrogenase levels (52 %).. Most remarkable radiological features include ground glass opacifications (80 %), bilateral pneumonia (73 %) and the involvement of three or more lung lobes (57 %). Although the synthesized evidence has limitations, it allows an updated approach to the available knowledge about the clinical symptoms of this new disease in the adult population. (AU)

Procalcitonin levels among patients with fever secondary to severe intracerebral infection. A cross-sectional study

ABSTRACT BACKGROUND: Making the differential diagnosis between central fever and infectious fever is critically important among intracerebral hemorrhage patients followed up in intensive care units (ICUs). Serum procalcitonin (PCT) has been found to be a promising biomarker for the initial diagnosis of infection, even before culturing results. OBJECTIVES: To investigate the relationship between PCT and both fever etiologies and C-reactive protein (CRP) levels among critically ill patients with suspected intracerebral hemorrhage. DESIGN AND SETTING: Cross-sectional study in a public university hospital in Elazig, Turkey. METHODS: ICU patients diagnosed with intracerebral hemorrhage and normal procalcitonin levels were included in this study. From clinical assessments and cultures, they were classified as presenting either infectious or central fever. The sensitivity and specificity of PCT and CRP for predicting infection were calculated using a receiver operating characteristic (ROC) curve. RESULTS: There were 98 ICU patients with diagnoses of intracerebral hemorrhage. The median (interquartile range) PCT levels of patients with infectious and central fever were 4 (0.9-11) and 0.1 (0.1-0.4) ng/ml, respectively, with a statistically significant intergroup difference (P < 0.001). The areas under the ROC curve for predicting infectious or central fever PCT and CRP were 0.958 (P < 0.001) and 0.816 (P < 0.001), respectively. A statistically significant positive correlation was detected between PCT and CRP levels in patients with infectious fever (rho: 0.461; P = 0.003), but not in patients with central fever. CONCLUSIONS: PCT can possibly be used as a biomarker to differentiate between infectious and central fever among ICU patients.

Serum interleukin -8 is not a reliable marker for prediction of vesicoureteral reflux in children with febrile urinary tract infection

Objective: In view of the side effects of voiding cystourethrography (VCUG), identification of noninvasive markers predicting the presence of vesicoureteral reflux (VUR) is important. This study was conducted to determine the predictive value of serum interleukin-8 (IL-8) in diagnosis of VUR in children with first febrile urinary tract infection (UTI). Materials and Methods: Eighty children with first febrile UTI were divided into two groups, with and without VUR, based on the results of VCUG. The sensitivity, specificity, positive and negative predictive value positive and negative likelihood ratio, and accuracy of IL-8 for prediction of VUR were investigated. Results: Of the 80 children with febrile UTI, 30 (37.5%) had VUR. There was no significant difference between the children with and without VUR and also between low and high-grade VUR groups in terms of serum concentration of IL-8 (P>0.05). Based on ROC curve, the sensitivity, specificity, likelihood ratio positive, and accuracy of serum IL-8 was lower than those of erythrocyte sedimentation rate and C-reactive protein. Multivariate logistic regression analysis showed significant positive correlation only between erythrocyte sedimentation rate and VUR. Conclusions: This study showed no significant difference between the children with and without VUR in terms of the serum concentration of IL-8. Therefore, it seems that serum IL-8 is not a reliable marker for prediction of VUR.

Utility of Procalcitonin as an Early Diagnostic Marker of Bacteremia in Patients with Acute Fever

PURPOSE: Procalcitonin (PCT) is a current, frequently used marker for severe bacterial infection. The aim of this study was to assess the ability of PCT levels to differentiate bacteremic from nonbacteremic patients with fever. We assessed whether PCT level could be used to accurately rule out a diagnosis of bacteremia. MATERIALS AND METHODS: Serum samples and blood culture were obtained from patients with fever between August 2008 and April 2009. PCT was analyzed using a VIDAS(R) B.R.A.H.M.S PCT assay. We reviewed the final diagnosis and patient histories, including clinical presentation and antibiotic treatment. RESULTS: A total of 300 patients with fevers were enrolled in this study: 58 with bacteremia (positive blood culture) (group I); 137 with local infection (group II); 90 with other diseases (group III); and 15 with fevers of unknown origin (group IV). PCT levels were significantly higher in patients with bacteremia than in those with non-bacteremia (11.9 +/- 25.1 and 2.5 +/- 14.7 ng/mL, respectively, p < 0.001). The sensitivity and specificity were 74.2% and 70.1%, respectively, at a cut-off value of 0.5 ng/mL. A serum PCT level of < 0.4 ng/mL accurately rules out diagnosis of bacteremia. CONCLUSION: In febrile patients, elevated PCT may help predict bacteremia; furthermore, low PCT levels were helpful for ruling out bacteremia as a diagnosis. Therefore, PCT assessment could help physicians limit the number of prescriptions for antibiotics.

Significance of C-reactive protein during febrile neutropenia in pediatric malignancies.

Fifty episodes of febrile neutropenia (FN) in 33 children with malignancies were studied to evaluate the usefulness of C-reactive protein (CRP) levels as an indicator of infection, and the efficacy of antibiotic therapy. Nineteen FN episodes occurred in children with documented infection whereas, 9 and 22 episodes occurred with probable infection and fever of unknown origin, respectively. CRP positivity during episodes of documented and probable infection was significantly higher than with febrile episodes of unknown origin. Blood culture was positive in 15 episodes; of these, CRP was positive in 11. CRP declined to normal on 7th day of antibiotic therapy. CRP is a useful indicator of infection in neutropenic children and also in determining the efficacy of antibiotic therapy.

Farmacocinética y penetración en líquido tisular de cefepime administrado en conejos hipertérmicos / Pharmacokinetics and penetration into tissue fluid of cefepime administered to hyperthermic rabbits

La farmacocinética sérica y tisular de cefepime administrado por vía endovenosa (20 mg/kg de peso) fue determinada en conejos sanos, con hipertermia producida por lipopolisacáridos de E. coli e implantados en tejido subcutáneo con cajas para recolección de líquido tisular. Diez conejos adultos fueron utilizados en dos experiencias (E1 y E2). Las concentraciones de cefepime en suero (S) y líquido tisular (LT) fueron determinadas por método biológico. Para el análisis cinético se utilizó un modelo no compartimental. Los resultados farmacocinéticos (medias ± error estándar) fueron: tiempo medio de eliminación [t1/2 (E1 S)=1,5±0,2 y (E2 S)=2,0±0,2 h] (p<0,05), área bajo la curva [ABC (E1 S)=181,6±17,5 y (E2 S)=192,3±18,5 (µg/mL/h]; Volumen de distribución en estado estacionario [Vss (E1S)=0,31±0,05 y (E2 S)=0,69±0,28 L/kg] (p<0,05); aclaramiento sérico [CL(E1 S)=118,3±17,7 y (E2 S) =93,1±19,9 (mL/h)kg] (p<0,05); Concentración máxima [Cmax (E1 LT)= 23,5±3,4 y (E2 LT)= 27,6±3,6 (µg/mL]; tiempo en el que se logra la Cmax [t max (E1 LT)=2,3±0,4 y (E2 LT)=1,7±0,4 h)]; t1/2 (E1 LT)= 2,4±0,3 y (E2 LT)=3,4±0,3 h (p<0,05); ABC (E1 LT)=122,0±12,7 y (E2 LT)=156,9±13,6 (µg/mL/h). y penetración [P (E1 LT)=67,3±8,7 y (E2 LT)=88,5±8,7%].

The pharmacokinetic characteristics in serum and tissue of cefepime given intravenously (20 mg/kg body weight) were assessed in healthy rabbits and in rabbits with hyperthermia induced by lipopolysacharide of E. coli, with tissue fluid cages implanted subcutaneously. Ten adult rabbits were used in two trials (E1 and E2). Cefepime concentrations in serum (S) and tissue cage fluid (LT) were determined by biological methods. The kinetic analysis was performed by means of a noncompartmental model. Pharmacokinetic results (means ± standard error): half life of elimination [t1/2 (E1 S)=1.5±0.2 and (E2 S)=2.0±0.2 h] (p<0.05), area under the curve [ABC (E1 S)=181.6±17.5 and (E2 S)= 192.3±18.5 (µg/mL/h]; volume of distribution at steady-state [Vss (E1 S)=0.31±0.05 and (E2 S)=0.69±0.28 L/kg] (p<0.05); total serum clearance [CL (E1 S)=118.3±17.7 and (E2 S)=93.1±19.9 (mL/h)kg] (p<0.05); maximum concentration [Cmax (E1 LT)=23.5±3.4 and (E2 LT)=27.6±3.6 (µg/mL]; time to reach Cmax [t max (E1 LT) =2.3±0.4 and (E2 LT)=1.7±0.4 h)]; t1/2 (E1 LT)=2.4±0.3 and (E2 LT)=3.4±0.3 h (p<0.05); ABC (E1 LT)=122.0±12.7 and (E2 LT)=156.9±13.6 (µg/mL/h); penetration [P (E1 LT)=67.3±8.7 and (E2 LT)=88.5±8.7%]. In conclusion, the pharmacokinetic changes of cefepime observed in rabbits with hyperthermia induced by lipopolysacharide, could be clinically significant if not taken into account when designing the dosing regimens.

Serum complement 3 (C3) and complement 4 (C4) level in febrile neutropenia patients at Dr. Kariadi Hospital, Semarang and Dr. Moewardi Hospital, Surakarta.

AIM: to identify the serum complement 3 (C3) and complement 4 (C4) level in febrile neutropenia and non-febrile neutropenia patients. METHODS: this is a cross-sectional prospective study. Samples were collected from patients with febrile neutropenia as sample group and patients with neutropenia but without fever as control. Both groups were tested for serum complement 3 and complement 4 level, and the data were analyzed using student T-test. RESULTS: from 37 neutropenia patients, 23 were classified as febrile neutropenia group and 14 in non-febrile neutropenia as control group. Total mean neutrophil count was 653.22/ml serum in sample group and 594.36/ml serum in control group (p=0.575). Mean C3 level was 95.74 ug/dl in sample group and 130.00 ug/dl in control group, showing significant difference with p=0.031. The mean serum C4 level was 34.13 ug/ml in sample group and 34.00 ug/dl in control group, the difference is not significant with p=0.98. When sample C3 and C4 data were combined, the total level was 125.61 ug/ml, which was significantly lower than the total C3 and C4 in control group 184.07 ug/dl. (p=0.04). CONCLUSION: in febrile neutropenia there is significant decrease of serum C3 level compared to non-febrile neutropenia. Serum C4 level in febrile neutropenia group is lower than the non-febrile neutropenia group, but the difference is not significant.

Plasma D-dimer levels in patients with typhoid fever.

The plasma levels of D-dimer can be used as a marker of fibrin formation and degradation. Plasma D-dimer levels in the febrile phase of 6 patients with typhoid fever and in the afebrile convalescent phase of 4 of them were measured. D-dimer levels were high in the febrile phase of all 6 patients and within normal range in the afebrile convalescent phase of all 4 patients. Our results indicate that thrombus formation and fibrinolysis may occur in the febrile phase of patients with typhoid fever.

Rapid detection of methicillin resistant staphylococcus aureus bacteraemia in bactec blood culture bottles of ICU patients

Methicillin resistance and infections caused by methicillin-resistant Staphylococcus aureus [MRSA] represent a growing problem and a challenge for health-care institutions. Resistance to methicillin is primarily associated with acquisition of mecA gene. The aim of the current study was to find out the incidence of MRSA bacteraemia among ICU bacteraemic patients and evaluate direct mecA gene detection from blood culture bottles and the oxacillin [methicillin] disk diffusion method commonly used in hospitals to identify MRSA using PCR for mecA detection in isolates as the golden. The study was conducted on 300 ICU patients with pyrexia of unknown origin. Blood samples were collected under complete aseptic precautions for blood culture onto BACTEC blood culture bottles. Detection of mecA gene by Polymerase Chain Reaction [PCR] was carried directly on any bottle showing Gram-positive cocci in clusters in film. Isolates of all positive blood culture bottles were identified. For Staph aureus isolates oxacillin disk diffusion and mecA gene detection was carried. Out of 300 samples included in the study, 190 [63.3%] yielded growth. Methicillin resistant Staph aureus was isolated from 88/190 patients [46.3%]. The agreement between the results of mecA gene detection among isolates and those among blood culture bottles was found to be 100% [Kappa = 1] and the sensitivity 100%. Disk diffusion method detected 79 cases out of the 88 MRSA strains The agreement between the results of oxacillin disk diffusion sensitivity method and mecA detection either in isolates or blood culture bottles was found to be 94% [Kappa= 0.87] and the sensitivity was 89. 8%.Methicillin resistant Staph. aureus bacteraemia is a major problem in ICU. Detection of mecA gene by PCR from blood culture bottles is a good tool for rapid detection of methicillin resistance in staph aureus bacteremia. To confirm the specificity of this test, more samples from patients with Enterococcus and Streptococcus species bacteraemias need to be studied

Inflammatory Processes in Kawasaki Disease Reach their Peak at the Sixth Day of Fever Onset: Laboratory Profiles According to Duration of Fever

We evaluated the inflammatory indices according to the fever duration in children with Kawasaki disease (KD), and determined duration when the inflammatory processes in KD reach their peak. Children with KD (n=152) were classified into 7 groups according to fever duration: at the third day or earlier (n=20), fourth (n=33), fifth (n=46), sixth (n=15), seventh (n=15), eighth (n=9), and at the ninth day or later after fever onset (n= 14). The levels of various laboratory indices were determined 3 times: before, 24 hr and 7 days after intravenous immunoglobulin administration (2 g/kg). WBC and neutrophil counts, and C-reactive protein level were the highest at the sixth day. Levels of hemoglobin, albumin, and high density lipoprotein cholestrol were the lowest at the sixth day. Although these indices were not significant statistically between groups, the indices showed either bell-shaped or U-shaped distribution of which peak or trench were at the sixth day. These findiugs showed that the inflammatory processes in KD reach peak on the sixth day of fever onset. This finding is important because a higher single-dose intravenous immunoglobulin treatment before the peak day may help reduce the coronary artery lesions in KD.

Production of Chemokines in Kawasaki Disease, Henoch-Schonlein Purpura and Acute Febrile Illness

We compared the production of three chemokines; interferon-gamma-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and growth-related onco-gene-alpha(Gro-alpha) that attracts monocytes or neutrophils, or both, in peripheral blood at acute stage of Kawasaki disease (n=29), Henoch-Schonlein purpura (n=15) and acute febrile illnesses (n=12). The production of the chemokines was assayed by ELISA. The plasma levels of IP-10 were markedly elevated in Kawasaki disease (538.6 +/-336.4 pg/mL) and acute febrile illnesses (417.1 +/-262.2 pg/mL) compared with in Henoch-Schonlein purpura (58.7 +/-95.7 pg/mL) (p<0.05). The MCP-1 levels were elevated in Kawasaki disease (443.0 +/-473.1 pg/mL) and acute febrile illnesses (328.6 +/-261.1 pg/mL) compared with in Henoch-Schonlein purpura (82.9 +/-79.0 pg/mL) (p<0.05). The Gro- levels were elevated only in acute febrile illnesses (134.3 +/-153.6 pg/mL) compared with in Kawasaki disease (31.8 +/-22.1 pg/mL) or Henoch-Schonlein purpura (29.4 +/-53.3 pg/mL) (p<0.05). According to these results, monocytes may play an important role in Kawasaki disease. In acute febrile illness-es, both monocytes and neutrophils may play an important role. By contrast, Henoch-Schonlein purpura may not be associated with the role of monocytes and neutrophils. Further studies using a larger number of cases are needed.

Predictors of bacteraemia among febrile infants in Ibadan, Nigeria.

Fever is a common complaint in infancy, and bacteraemia is one of the more serious causes of such fever. However, there exists scanty data on risk of bacteraemia among febrile infants of developing countries and what clinical predictors, if any, could identify those febrile infants with bacteraemia. To address this issue, 102 infants aged 1-12 month(s) attending the Children's Emergency Ward of University College Hospital, Ibadan, Nigeria, with rectal temperatures of > or = 38 degrees C and with a negative history of antimicrobial use for at least one week prior to presentation, were studied to identify clinical predictors of bacteraemia. Infants, meeting the eligibility criteria of the study, underwent a full clinical evaluation and had blood cultures done for aerobic organisms by standard methods. Over 38% of the infants had bacteraemia. Escherichia coli (35.9%), Staphylococcus aureus (33.3%), and Klebsiella spp. (10.3%) of positive cultures were commonly isolated. Three variables, age of < or = 6 months, restlessness, and a white cell count of >15,000/mm3, were significant independent predictors of bacteraemia. Each of these variables was associated with a 3-6-fold increase in risk of bacteraemia (age of < or = 6 months: odds ratio 3.2, p = 0.017; restlessness: odds ratio 6.3, p = 0.019; and white cell count of >15,000/mm3: odds ratio 5.4, p = 0.024). The variables, in combination, correctly classified 70% of the infants into 'bacteraemia' or 'no bacteraemia'. It is concluded that; in the setting of the study, about 4 in 10 febrile infants would have a positive blood culture for aerobic organisms and that age of < or = 6 months, restlessness, and a white cell count of > or = 15,000/mm3 are associated with a significantly increased risk of bacteraemia. Clinicians practising in such a setting need to be aware of the increased risk of bacteraemia in infants with these clinical features.

Circulating interleukin (IL)-1 beta, IL-6 and tumor necrosis factor-alpha in children with febrile infection--a comparison with C-reactive protein.

Circulating interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were examined in 42 febrile children with fever lasting more than 4 days. Their diagnosis were probable viral syndrome in 22, urinary tract infection (UTI) in 10, and probable bacterial pneumonia in 10. None of our study patients had detectable serum IL-1 beta. TNF-alpha levels were significantly higher in children with pneumonia than in those with viral syndrome (p < 0.01). Children with UTI and pneumonia had significantly higher IL-6 and CRP, compared to those with probable viral syndrome (p < 0.01 for both IL-6 and CRP). When appropriate cutoff values are chosen, IL-6 had greatly improved specificity (86.4%, > 20 pg/ml) to demonstrate UTI and pneumonia, as compared to that using CRP (48%, > 40 mg/l). After three days' antibiotic treatment, IL-6 fell to control levels in children with UTI and pneumonia, while CRP remained elevated. There was no difference in TNF-alpha values before and after treatment. Thus, IL-6, rather than IL-1 beta and TNF-alpha, may be a helpful diagnostic tool for evaluation of pediatric febrile infection. Sequential studies involving more patients are needed to determine whether IL-6 is better than CRP in this clinical setting.

Leukocyte and neutrophil counts in differential diagnosis of acute febrile conditions.

Leukocyte and neutrophil counts are two of the commonest laboratory tests used in clinical medicine. The usefulness of the tests is still controversial. It has been found that the tests were useful to a limited extent. We performed leukocyte and neutrophil counts in patients manifesting acute febrile illness, to identify the best cut-off point in differential diagnosis of underlying disorders causing such conditions. Patients were enrolled randomly on the basis of acute febrile illness. Those who suffered from diseases affecting myeloproliferative system were excluded. Leukocyte and neutrophil counts were performed by the standard method. Diagnosis of target organ disorder was obtained from the house staff's final diagnosis. Both laboratory and clinical performance were assessed in double blind fashion. Patients were divided into 2 groups. Group 1 consisted of 47 patients with acute bacterial infections and group 2 consisted of 53 cases with acute febrile conditions caused by diverse, non-bacterial disease. Various cut off points ranging from 5,000-25,000/mm3 and 10-100 per cent were used for leukocyte and neutrophil counts. Sensitivity, specificity and Youden index for each cut off point were determined. Receiver operating characteristic (ROC) curves were constructed. It was found that sensitivity and specificity for each cut off point for both leukocyte and neutrophil counts displayed perfect trade-offs and the Youden indices were similar. The ROC curves for both counts were depicted as a 45-degree lines of non-discrimination. Leukocyte and neutrophil counts were proved to be non-discriminate of acute febrile conditions.(ABSTRACT TRUNCATED AT 250 WORDS)