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Procalcitonin for patient stratification and identification of bacterial co-infection in COVID-19

Authors:
  • Royal Lancaster Infirmary
© Royal College of Physicians 2020. All rights reserved. e47
Letters to the editor
and this led to anticoagulation in nearly double the number of
patients in the intervention group.5
Interestingly, 9% (15/167) of patients had an intracardiac source
of embolus (‘heart failure and thrombus’ and ‘valvular heart
disease’) and 25.1% (42/167) of patients had no underlying cause.
Despite this, only 4.2% (7/167) of patients had transoesophageal
echocardiography (TOE). A thrombus located in the left atrium
or, more precisely, the left atrial appendage (LAA) is the most
prevalent source of intracardiac emboli and is typically associated
with AF. TOE is the imaging modality of choice for the evaluation
of LAA.6 ,7 Furthermore, in the absence of diagnosed AF, left
atrial or L AA abnormalities may be a compelling indication for
prolonged ECG monitoring.
In summary, investigation for aetiology of stroke in young
patients should involve scrupulous cardiac investigations
identifying those patients who would benefit from prolonged
ambulatory ECG monitoring and increased utilisation of TOE. n
Variance in procalcitonin levels have previously been proposed
to differentiate systemic inflammation of bacterial origin from
viral origin in community acquired pneumonia and sepsis, with
a significant rise indicating bacterial infection.5,6 The lack of a
procalcitonin rise in viral infections may be due to virus-stimulated
production of interferon-γ by macrophages, which inhibits TNF-α
in the immune response.5 The presence of lower procalcitonin
levels has been shown to have a 94% negative predictive value
for bacterial co-infection in intensive care unit patients with
confirmed influenza A(H1N1)pdm09.7 Therefore, we suggest that
raised procalcitonin observed in COVID-19 could be due either to
bacterial co-infection, which is itself causing increased severity
and driving systemic sepsis, or as a direct marker of a more severe
or widespread viral infection.
As such, procalcitonin measurement on admission may be a
useful marker to firstly predict patient deterioration in hospital
and secondly, non-elevated procalcitonin on admission may be a
good predictor of the absence of bac terial co-infection and allow
the more targeted use of antimicrobials thus promoting antibiotic
stewardship. Fur ther work is needed to correlate the presence of
raised procalcitonin and the presence of bacterial co-infection in
COVID-19 patients. n
References
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strokes attributable to a cardiac aetiology in an unselected
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2 Kamel H, Okin PM, Elkind MS et al. Atrial fibrillation and mecha-
nisms of stroke: time for a new model. Stroke 2016;47:895–900.
3 Freedman B, Camm J, Calkins H et al. Screening for atrial fibril-
lation: A report of the AF-SCREEN International Collaboration.
Circulation. 2017;135:1851–67.
4 National Institute for Health and Care Excellence. AliveCor Heart
Monitor and AliveECG app (Kardia Mobile) for detecting atrial
fibrillation (MIB35). NICE, 2015. www.nice.org.uk/advice/mib35
5 Gladstone DJ, Spring M, Dorian P et al. Atrial fibrillation in patients
with cryptogenic stroke. N Engl J Med 2014;370:2467–77.
6 Manning EJ, Weintraub RM, Waksmonski CA et al Accuracy of
transesophageal echocardiography for identifying left atrial
thrombi. A prospective, intraoperative study. Ann Intern Med
1995;123:817–22.
7 Veinot JP, Harrity PJ, Gentile F et al. Anatomy of the normal left
atrial appendage. Circulation 1997;96:3112–5.
Procalcitonin for patient stratification and
identification of bacterial co-infection in COVID-19
DOI: 10.7861/clinmed.Let.20.3.3
Editor – an abundance of biomarkers has been measured in
hospitalised patients with COVID-19. Initial reports from China
have shown that most patients with COVID-19 did not have
elevated procalcitonin (>0.5 μg/L).1,2 However, elevated levels were
found more frequently in severe cases and in patients who died.2– 4
EAMON P MCCARRON
Specialty doctor in medicine, Southern Health and Social Care Trust,
Portadown, UK
References
1 Chen N, Zhou M, Dong X et al. Epidemiological and clinical char-
acteristics of 99 cases of 2019 novel coronavirus pneumonia in
Wuhan, China: a descriptive study. Lancet 2020;395:507–13.
2 Guan WJ, Ni ZY, Hu Y et al. Clinical characteristics of coronavirus
disease 2019 in China. N Engl J Med 2020 [Epub ahead of print].
3 Chen G, Wu D, Guo W et al. Clinical and immunologic features in
severe and moderate Coronavirus Disease 2019. J Clin Invest 2020
[Epub ahead of print].
4 Chen T, Wu D, Chen H et al. Clinical characteristics of 113
deceased patients with coronavirus disease 2019: retrospective
study. BMJ 2020;368:m1295.
5 Müller B, Becker K, Schächinger H et al. Calcitonin precursors are
reliable markers of sepsis in a medical intensive care unit. Crit Care
Med 2000;28:977–83.
6 Müller B, Harbarth S, Stolz D et al. Diagnostic and prognostic accu-
racy of clinical and laboratory parameters in community-acquired
pneumonia. BMC Infect Dis 2007;7:10.
7 Rodríguez AH, Avilés-Jurado FX, Díaz E et al. Procalcitonin (PCT)
levels for ruling-out bacterial coinfection in ICU patients with
influenza: A CHAID decision-tree analysis. J Infect 2016;72:143–51.
JENNIE HAN
Foundation doctor, Royal Lancaster Infirmary, Ashton Road,
Lancaster, UK
TIMOTHY GATHERAL
Consultant in respiratory medicine, Royal Lancaster Infirmary,
Ashton Road, Lancaster, UK
CRAIG WILLIAMS
Consultant and professor in microbiology, Royal Lancaster Infirmary,
Ashton Road, Lancaster, UK
... 14 Procalcitonin (PCT) as a rapid and feasible laboratory test has been proposed to evaluate the presence of bacterial infection and to differentiate it from other systemic inflammation including viral origin, especially in a resource constraint condition with a shortage of bacteriological culture availability. 15,16 Biomarkers have long been essential in the evaluation of numerous infectious illnesses. In determining disease severity and effectiveness of a management plan, it is crucial to assess the importance of biomarkers and their relationships. ...
... A questionnaire was developed by the authors after reviewing literature related to the study's objectives. 7,[16][17][18][19] The sections of the questionnaire constituted socio-demographic and clinical characteristics. The socio-demographic section included residency and history of smoking in addition to gender and age. ...
... 22 Lack of bacterial culture in certain centers, as that of this study, the measurement of PCT levels might be used as one of the predictor biomarkers for the absence or the presence of bacterial co-infection in COVID-19 patients. 16 Owing to corticosteroid therapy used for COVID-19 or the presence of severe disease, neutrophilia cannot be an applicable laboratory parameter for bacterial infections which might be triggered by such factors. 10,27 Twenty-six (34.7%) of the enrolled patients who had a high PCT level (>0.5 μg/L) showed a non-significant association with the death outcome. ...
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A cross-sectional study was conducted at the Fallujah Teaching Hospital, west of Iraq, which included all admittance with severe COVID-19 between September 20, 2021, and February 30, 2022. A questionnaire was designed to collect socio-clinical characteristics and in-hospital outcomes (recovery/death). Procalcitonin (PCT) and certain biomarkers were analyzed, based on that outcome, and correlations between these markers were assessed. Results: For 75 patients who were enrolled in this study, the mean age was 62.3±14.3 years, of which females constituted 62%. The most preponderance age was ≥60 years with a statistically significant higher rate of death (37.3%) when compared to other ages (P = 0.007), while other socio-clinical characteristics revealed nonsignificant differences. High PCT levels were found in34.7% of the enrolled patients, while neutrophilia, lymphopenia, and elevated levels of troponin, ferritin, and C-reactive protein (CRP) were the prominent abnormal biomarker findings. However, only ferritin and troponin mean levels revealed significant differences in relation to the outcomes(P = 0.019 and 0.010, respectively). A moderate positive correlation was found between PCT andinterleukin-6 (IL-6) (r = 0.586, P = 0.005), and also PCT correlates positively with CRP (r = 0.49, P = 0.005) and troponin (r = 0.41, P = 0.001). Additionally, there were significant positive correlations of troponin with IL-6 (r = 0.41, P = 0.005) and PCT (r = 0.37, P = 0.001). Also, IL-6correlates positively with troponin (r = 0.62, P = 0.005). Conclusions: We found an elevated level of PCT in almost three-quarters of patients with severe COVID-19, with a non-significant difference with the specific recovery/death outcomes. In addition, high troponin levels, neutrophilia, and lymphopenia regardless of the outcome were found. Also, there were valuable correlations between certain biomarkers in patients with COVID-19.
... Identifying and resolving pavement distress is an important task in current society [3]. Han et al. [4] noted that pavement distress detection plays an important role in road maintenance [4]. D'Alessandro et al. [5] mentioned that pavement distress recognition technology needs to breakthrough manual operation and relies on scientific and technological means. ...
... Identifying and resolving pavement distress is an important task in current society [3]. Han et al. [4] noted that pavement distress detection plays an important role in road maintenance [4]. D'Alessandro et al. [5] mentioned that pavement distress recognition technology needs to breakthrough manual operation and relies on scientific and technological means. ...
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The current study aims to improve the efficiency of automatic identification of pavement distress and improve the status quo of difficult identification and detection of pavement distress. First, the identification method of pavement distress and the types of pavement distress are analysed. Then, the design concept of deep learning in pavement distress recognition is described. Finally, the mask region-based convolutional neural network (Mask R-CNN) model is designed and applied in the recognition of road crack distress. The results show that in the evaluation of the model's comprehensive recognition performance, the highest accuracy is 99%, and the lowest accuracy is 95% after the test and evaluation of the designed model in different datasets. In the evaluation of different crack identification and detection methods, the highest accuracy of transverse crack detection is 98% and the lowest accuracy is 95%. In longitudinal crack detection, the highest accuracy is 98% and the lowest accuracy is 92%. In mesh crack detection, the highest accuracy is 98% and the lowest accuracy is 92%. This work not only provides an in-depth reference for the application of deep CNNs in pavement distress recognition but also promotes the improvement of road traffic conditions, thus contributing to the progression of smart cities in the future. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.
... Increased PCT values are associated with a nearly 5-fold higher risk of severe SARS-CoV-2 infection (7), and serial procalcitonin measurement may play a role in predicting evolution toward a more severe form of the disease (7,11). Han et al. (12) postulate that raised PCT observed in COVID-19 could be due either to bacterial co-infection, which is itself causing increased severity and driving systemic sepsis or as a direct marker of a more severe or widespread viral infection. Previous studies (13,14) find associations between PCT values, severity, and clinical outcomes, especially for mechanical ventilation and all-cause mortality. ...
... Although PCT is used as a marker for bacterial sepsis, there is still considerable doubt whether the elevated PCT levels observed in some patients with COVID-19 are due to a bacterial infection or are a direct marker for a more severe viral infection (12). ...
Article
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IntroductionA multicenter prospective cohort study studied patients admitted to the intensive care unit (ICU) by coronavirus-19 (COVID-19) with respiratory involvement. We observed the number of occasions in which the value of procalcitonin (PCT) was higher than 0.5 ng/ml.Objective Evaluation of PCT elevation and influence on mortality in patients admitted to the ICU for COVID-19 with respiratory involvement.Measurements and main resultsWe studied 201 patients. On the day of admission, acute physiology and chronic health evaluation (APACHE)-II was 13 (10–16) points. In-hospital mortality was 36.8%. During ICU stay, 104 patients presented 1 or more episodes of PCT elevation and 60 (57.7%) died and 97 patients did not present any episodes of PCT elevation and only 14 (14.4%) died (p < 0.001). Multivariable analysis showed that mortality was associated with APACHE-II: [odds ratio (OR): 1.13 (1.04–1.23)], acute kidney injury [OR: 2.21 (1.1–4.42)] and with the presentation of one or more episodes of escalating PCT: [OR: 5.07 (2.44–10.53)]. Of 71 patients who died, 59.2% had an elevated PCT value on the last day, and of the 124 patients who survived, only 3.2% had an elevated PCT value on the last day (p < 0.001). On the last day of the ICU stay, the sequential organ failure assessment (SOFA) score of those who died was 9 (6–11) and 1 (0–2) points in survivors (p < 0.001). Of the 42 patients who died and in whom PCT was elevated on the last day, 71.4% were considered to have a mainly non-respiratory cause of death.Conclusion In patients admitted to the ICU by COVID-19 with respiratory involvement, numerous episodes of PCT elevation are observed, related to mortality. PCT was elevated on the last day in more than half of the patients who died. Serial assessment of procalcitonin in these patients is useful because it alerts to situations of high risk of death. This may be useful in the future to improve the treatment and prognosis of these patients.
... Además de eso, en pacientes con COVID-19, se observa con cierta frecuencia la neumonía bacteriana [61,62]. La mayoría de los enfermos con infiltrado pulmonar han evidenciado en pruebas de diagnóstico por imagen que deben recibir antibioticoterapia, y esta debe ser discontinuada basándose en la evaluación clínica y en el nivel sérico de biomarcadores como la procalcitonina [63,64]. También en pacientes hospitalizados con COVID-19, el uso del antiviral remdesivir mostró algún beneficio, particularmente cuando se ha iniciado precozmente en el transcurso de la enfermedad [65]. ...
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RESUMEN Este artículo de revisión narrativa tiene como objetivo explorar el conocimiento actual disponible basado en datos científicos respeto a la definición, la epidemiología, los criterios diagnósticos, la microbiología, el tratamiento y la prevención de la neumonía grave adquirida en la comunidad) en individuos adultos inmunocompetentes. En la actualidad, pese a los grandes avances científicos obtenidos en la evaluación diagnóstica, el manejo clínico, la terapia antimicrobiana y la prevención, la neumonía grave adquirida en la comunidad sigue siendo una causa importante de morbilidad y mortalidad, además de producir un gran impacto económico con la elevación de los costes sanitarios en todo el mundo. Esta patología es considerada una de las principales causas de sepsis/choque séptico, con una tasa de mortalidad global extremadamente elevada, lo que justifica todo el esfuerzo en el diagnóstico precoz, el manejo en un ambiente adecuado y el inicio temprano y apropiado de la terapia antimicrobiana. La inclusión de biomarcadores (aislados o en combinación) asociada a la aplicación de los criterios diagnósticos y escalas pronósticas de gravedad en la práctica clínica, sirven para identificar a los pacientes con neumonía adquirida en la comunidad grave, definir el ingreso inmediato en la unidad de cuidados intensivos y, de esta forma, minimizar los resultados negativos de esta grave patología. INTRODUCCIÓN La infección de las vías aéreas inferiores es una de las principales causas de morbilidad en todo el mundo. La neumonía adquirida en la comunidad es la segunda causa más frecuente de internación hospitalaria [1,2]. La incidencia de pacientes que necesitan de cuidados intensivos por neumonía grave adquirida en la comunidad viene aumentando globalmente, principalmente en la población de edad avanzada (mayor a 65 años), portadores de enfermedades crónicas (diabetes mellitus, demencia, insuficiencia cardiaca crónica, miocardiopatía isquémica), y en individuos con algún grado de inmunosupresión [3]. Jain et al, en 2015, a través de un amplio estudio pobla-cional en el que se hizo un seguimiento de pacientes hos-pitalizados con diagnóstico de neumonía adquirida en la comunidad, estimaron que el 21% de estos enfermos ingresaron en la unidad de cuidados intensivos y el 26% necesitaron soporte ventilatorio invasivo [4]. La mortalidad hospitalaria por neumonía grave adquirida en la comunidad es elevada, oscilando entre el 25% y más del 50% [5,6]. El retraso en la admisión en la unidad de cuidados intensivos se presenta como uno de los factores de peor pronóstico y mayor mortalidad intrahospitalaria [7]. A lo largo de los años, se han desarrol-lado y validado algunas escalas pronósticas de gravedad en la evaluación clínica de neumonía adquirida en la comunidad, con la finalidad de identificar a los pacientes que deben ser hospitalizados y admitidos inmediatamente en las unidades de cuidados intensivos e iniciarse el tratamiento antimicrobiano apropiado [8]. Aunque no exista un consenso mundial sobre la definición de neumonía grave adquirida en la comunidad, los criterios actualmente aceptados se basan en guías de práctica clínica internacionales. En esta revisión serán utilizadas las de la Sociedad de Enfermedades Infecciosas de América y de la Sociedad Torácica Americana
... In survivors, the median values of procalcitonin remained low while in the mortality group median values were nearly 13-fold higher, meaning an exponential increase of procalcitonin levels as the evolution shifts towards mortality (Table II). In COVID-19 patients increase of procalcitonin levels may act as a bacterial superinfection, as were the majority of cases included in the final analysis (data not shown), or as a direct marker of a more severe or widespread viral infection (42). One of the main problems for the present study was that the cut-off value for procalcitonin (0.28 ng/ml) was within a normal range (0-0.5 ng/ml). ...
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COVID-19 pandemic is a continuing ongoing emergency of public concern. Early identification of markers associated with disease severity and mortality can lead to a prompter therapeutic approach. The present study conducted a multivariate analysis of different markers associated with mortality in order to establish their predictive role. Confirmed cases of 697 patients were examined. Demographic data, clinical symptoms and comorbidities were evaluated. Laboratory and imaging severity scores were reviewed. A total of 133 (19.1%) out of 697 patients succumbed during hospitalization. Obesity was the most common comorbidity, followed by hypertension, diabetes, coronary heart disease and chronic kidney disease. Compared with the survivor patients, non-survivors had a higher prevalence of diabetes, chronic kidney disease and coronary heart disease, as well as higher values of laboratory markers such as neutrophil-lymphocyte ratio (NLR), D-dimer, procalcitonin, IL-6 and C Reactive protein (CRP) and respectively high values of imaging severity scores. Multivariate regression analysis showed that high values of the proposed markers and chest computerized tomography (CT) severity imaging score were predictive for in hospital death: NLR [hazard ratio (HR): 3.127 confidence interval (CI) 95: 2.137-4.576]; D-dimer [HR: 6.223 (CI 95:3.809-10.167)]; procalcitonin [HR: 4.414 (CI 95:2.804-6.948)]; IL-6 [HR: 3.344 (CI 95:1.423-7.855)]; CRP [HR:2.997 (CI 95:1.940-4.630)]; and CT severity score [HR: 3.068 (CI 95:1.777-5.299)]. Laboratory markers and imaging severity scores could be used to stratify mortality risk in COVID-19 patients.
... It is suggested that PCT, HBP, and MMP-9 tests are potentially valuable in the early diagnosis of intracranial infection after brain tumour surgery. PCT is a common biological indicator for the diagnosis of bacterial infections and sepsis and is now recognized to be significantly elevated in bacterial infections combined with a systemic inflammatory response, and its elevation correlates with the severity of the patient's infection, whereas in viral infections or aseptic inflammation, PCT is normal or mildly elevated [14]. Studies [15,16] found that the PCT levels of serum and cerebrospinal fluid in patients with intracranial infection on the first day after craniotomy were significantly higher than those in noninfected patients, and their sensitivity and specificity in the diagnosis of intracranial infection were more than 80%. ...
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Purpose: Analysis of routine biochemical levels of cerebrospinal fluid (CSF), distribution of pathogenic bacteria, and risk factors in patients with intracranial infections secondary to brain tumour surgery. Methods: A total of 208 patients admitted to our hospital for brain tumour surgery from January 2020 to May 2022 were selected. Fully automated biochemical analyzer was employed for CSF routine and for measuring biochemical parameters such as white blood cell (WBC), micrototal protein (M-TP), glucose (GLU), and chlorine (CI). Double antibody sandwich assay for CSF procalcitonin (PCT), heparin-binding protein (HBP), and matrix metalloproteinase-9 (MMP-9) was performed. Fully automated microbiological analyzer for pathogen identification was utilized. Based on the above results, we determined whether the patients had secondary intracranial infections after surgery and analyzed the risk factors for secondary intracranial infections after brain tumour surgery by univariate and multifactorial logistic regression. Results: Among 208 patients with brain tumour surgery, 65 cases (31.25%) had secondary intracranial infection and 143 cases (68.75%) had no secondary intracranial infection. The levels of WBC, M-TP, CI, PCT, HBP, and MMP-9 in the CSF of intracranially infected patients were significantly higher than those of uninfected patients (P < 0.05), and GLU was significantly lower than that of uninfected patients (P < 0.05), and the levels of PCT, HBP, and MMP-9 in infected patients were significantly lower than those before treatment after 3, 7, and 10 d and tended to decrease over time (P < 0.05). A total of 62 pathogenic strains were isolated from 65 intracranial infections, of which 41 (66.13%) were Gram-negative bacteria, mainly resistant to amikacin and ciprofloxacin and sensitive to meropenem and imipenem; 19 (30.65%) were Gram-positive bacteria, mainly highly resistant to penicillin and erythromycin and sensitive to vancomycin. Univariate analysis showed that age, gender, tumour type, history of glucocorticoid application, and prophylactic application of antibiotics were not associated with secondary intracranial infection after brain tumour surgery (P > 0.05); tumour site, operation time, postoperative indwelling drainage time, postoperative cerebrospinal fluid leakage, and history of diabetics were all associated with secondary intracranial infection after brain tumour surgery (P < 0.05). Multivariate logistic regression analysis showed that infratentorial tumour, operation time ≥4 h, postoperative indwelling drainage time ≥24 h, and postoperative cerebrospinal fluid leakage were independent risk factors for secondary intracranial infection after brain tumour surgery (P < 0.05). Conclusion: Patients with intracranial infections secondary to brain tumour surgery have abnormal levels of CSF routine and biochemical parameters, and the detection rate of Gram-negative bacteria is higher than that of Gram-positive bacteria in patients. Treatment should be based on the characteristics of pathogenic bacteria and risk factors with targeted interventions to reduce intracranial infections.
... The clinical features of COVID-19 infection are difficult to distinguish from bacterial pneumonia. Biomarkers, such as procalcitonin (PCT), have been used to determine the likelihood of bacterial infections in patients with COVID-19 infection [18]. However, elevated PCT has not been found to be correlated with the presence of a bacterial infection in COVID-19 patients, but may be an independent predictor of mortality [19]. ...
Article
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Background: At outset of the coronavirus disease 2019 (COVID-19) pandemic, the significance of bacterial and fungal coinfections in individuals with COVID-19 was unknown. Initial reports indicated that the prevalence of coinfection in the general population was low, but there was uncertainty regarding the risk of coinfection in critically ill patients. Methods: Nine hundred critically ill adult patients with COVID-19 infection were enrolled in this observational case-control study. Patients with a coinfection (case) and patients without a coinfection (control) were compared using univariate and multivariable analyses. A subgroup analysis was performed on patients with coinfection, dividing them into early (infection within 7 days) and late (infection after 7 days) infection groups. Results: Two hundred and thirty-three patients (25.9%) had a bacterial or fungal coinfection. Vasopressor use (P<0.001) and severity of illness (higher Acute Physiology and Chronic Health Evaluation III score, P=0.009) were risk factors for the development of a coinfection. Patients with coinfection had higher mortality and length of stay. Vasopressor and corticosteroid use and central line and foley catheter placement were risk factors for late infection (>7 days). There were high rates of drug-resistant infections. Conclusions: Critically ill patients with COVID-19 are at risk for both community-acquired and hospital-acquired infections throughout their hospitalization for COVID-19. It is important to consider the development of a coinfection in clinically worsening critically ill patients with COVID-19 and consider the likelihood of drug-resistance when choosing an empiric regimen.
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В процессе разработки рекомендаций были проанализированы публикации официальных сайтов Российской Федерации, электронных баз данных РИНЦ, PubMed, MEDLINE, EMBASE и Cochrane Central Register of Controlled Trials (CENTRAL) разработчиками независимо друг от друга. Дата последнего поискового запроса — 1 ноября 2021 г. Для разработки положений рекомендаций были использованы документы непосредственно описывающие особенности ведения пациентов с новой коронавирусной инфекцией (НКИ) COVID-19 (руководства и гайдлайны — 35; рандомизированные клинические исследования и Кокрейновские обзоры — 23; наблюдательные и сравнительные исследования — 134; прочие документы, заметки и комментарии — 72). По сравнению с предыдущей, 5-й, версией рекомендаций скорригированы 35 положений в 10 разделах. Положения текущей версии рекомендаций освещают особенности проведения анестезии, интенсивной терапии, реабилитации, реанимационных мероприятий, проведения манипуляций, транспортировки, предупреждения распространения НКИ COVID-19 при осуществлении данных видов деятельности. Рассмотрены методы защиты персонала от заражения НКИ COVID-19 при проведении манипуляций, анестезии и интенсивной терапии. Описаны особенности респираторной поддержки, экстракорпоральной детоксикации, экстракорпоральной мембранной оксигенации, тромбопрофилактики, лекарственных взаимодействий. Рассмотрены особенности ведения беременных, детей разных возрастных групп, пациентов с сопутствующими заболеваниями, принципы формирования запасов лекарственных препаратов и расходных материалов. Применительно к НКИ CОVID-19 уточнены и дополнены: 1) показания и противопоказания к назначению препаратов (ацетоминофена, глюкокортикостероидов, ремдесевира, тоцилизумаба, барицитинаба, статинов, плазмы реконвалесцентов) в зависимости от тяжести течения заболевания; 2) особенности интенсивной терапии при сопутствующих заболеваниях (сердечно-сосудистой системы, воспалительные заболевания кишечника, онкологические заболевания, нарушения ритма сердца); 3) срок проведения плановых операций у пациентов, перенесших НКИ CОVID-19, и после вакцинации; 4) вопросы тромбопрофилактики и лечения расстройств системы гемостаза; 5) нормативно-правовые документы, касающиеся деятельности медработников в связи с распространением НКИ CОVID-19.
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RESUMEN Antecedentes: la infección causada por el virus SARS-CoV-2 es una patología nueva que ha presentado desafíos extremos en la comunidad médica y en investigación, presentado elevadas tasas de mortalidad, ante lo cual los marcadores de la inflamación han sido considerados como valores pronósticos; pues, al elevarse podrían predecir la presencia del síndrome de distrés respiratorio agudo con un porcentaje elevado de ingreso de pacientes a cuidados intensivos. Objetivo: determinar el valor pronóstico de los marcadores de la inflamación en la infección por SARS-CoV-2.
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Introduction Despite the advance in vaccination, the SARS-CoV-2 infection remains a challenge for the medical community. Outpatient and hospital therapy for COVID-19 are still improving. Our study aimed to report the results of a series of patients with COVID-19 who participated in an outpatient treatment protocol since the first clinical manifestation. Methods A case series report of individuals aged ≥ 18 years with clinical symptoms and a confirmed test for COVID-19 submitted to a treatment protocol. Patients were enrolled between May and September 2020 and followed for at least 15 days. The assessed clinical outcomes were the need for hospitalization, admission to the intensive care unit, orotracheal intubation, and death. Results We studied a hundred and sixteen patients. The mean age was 48 ± 14 years. Females formed 53%. The main comorbidities were type II diabetes (6%), systemic arterial hypertension (10.3%), obesity (15.5%), and lung diseases (6.0%). Temperature > 37.7°C (51.7%), cough (55.2%), myalgia (37.1%), headache (37.9%) and fatigue (34.5%) were the most frequent signs and symptoms. According to different disease staging, the most administered drugs were: azithromycin, ivermectin, corticosteroid, antibiotics, and anticoagulants. There was no death, and hospitalization accounted for only 8.6% of the patients (one in ICU); none required orotracheal intubation. The mean length of hospital stay was 5.8 days.
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Objective To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. Design Retrospective case series. Setting Tongji Hospital in Wuhan, China. Participants Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. Main outcome measures Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. Results The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. Conclusion Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.
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The incidence of acute ischaemic stroke in young patients is increasing and identifying the underlying cause is critically important with regards to their optimal management. The true proportion of cardiac causes of stroke in young patients is poorly defined. We aimed to determine the proportion of strokes attributable to cardiac causes in an unselected, consecutive cohort of young patients. We used the database of a large stroke service to identify patients aged ≤55 years presenting with stroke between 01 January 2015 and 31 December 2017. We reviewed their clinical notes and investigations and then categorised patients by the cause of their stroke.We screened 202 cases, and excluded 35, resulting in a study population of 167 patients; 24.0% (40/167) had a cardiac cause of stroke including 9.6% (16/167) had patent foramen ovale, 9.0% (15/167) had intracardiac source of embolus and 5.4% (9/167) had atrial fibrillation; 50.8% (85/167) had other more likely causes; and 25.1% (42/167) had no clear underlying cause.A high proportion (24%) of strokes in young patients are secondary to a cardiac cause. Thorough investigation in these patients is warranted and requires close interdisciplinary links between cardiologists and stroke physicians to ensure optimal management.
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Background: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).
Article
Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
Article
Background: Since December 2019, an outbreak of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunologic features of severe and moderate COVID-19. Methods: In this retrospective study, the clinical and immunologic characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the Guidelines released by the National Health Commission of China. Results: The median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough and fatigue. Compared to moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute number of T lymphocytes, CD4+T and CD8+T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5 and 89.0 × 106/L) than moderate cases (640.5, 381.5 and 254.0 × 106/L). The expressions of IFN-γ by CD4+T cells tended to be lower in severe cases (14.1%) than moderate cases (22.8%). Conclusion: The SARS-CoV-2 infection may affect primarily T lymphocytes particularly CD4+T and CD8+ T cells, resulting in decrease in numbers as well as IFN-γ production. These potential immunological markers may be of importance due to their correlation with disease severity in COVID-19.
Preprint
Background Since late December, 2019, an outbreak of pneumonia cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and continued to spread throughout China and across the globe. To date, few data on immunologic features of Coronavirus Disease 2019 (COVID-19) have been reported. Methods In this single-centre retrospective study, a total of 21 patients with pneumonia who were laboratory-confirmed to be infected with SARS-CoV-2 in Wuhan Tongji hospital were included from Dec 19, 2019 to Jan 27, 2020. The immunologic characteristics as well as their clinical, laboratory, radiological features were compared between 11 severe cases and 10 moderate cases. Results Of the 21 patients with COVID-19, only 4 (19%) had a history of exposure to the Huanan seafood market. 7 (33.3%) patients had underlying conditions. The average age of severe and moderate cases was 63.9 and 51.4 years, 10 (90.9%) severe cases and 7 (70.0%) moderate cases were male. Common clinical manifestations including fever (100%, 100%), cough (70%, 90%), fatigue (100%, 70%) and myalgia (50%, 30%) in severe cases and moderate cases. PaO2/FiO2 ratio was significantly lower in severe cases (122.9) than moderate cases (366.2). Lymphocyte counts were significantly lower in severe cases (7000 million/L) than moderate cases (11000 million/L). Alanine aminotransferase, lactate dehydrogenase levels, high-sensitivity C-reactive protein and ferritin were significantly higher in severe cases (41.4 U/L, 567.2 U/L, 135.2 mg/L and 1734.4 ug/L) than moderate cases (17.6 U/L, 234.4 U/L, 51.4 mg/L and 880.2 ug /L). IL-2R, TNF-α and IL-10 concentrations on admission were significantly higher in severe cases (1202.4 pg/mL, 10.9 pg/mL and 10.9 pg/mL) than moderate cases (441.7 pg/mL, 7.5 pg/mL and 6.6 pg/mL). Absolute number of total T lymphocytes, CD4+T cells and CD8+T cells decreased in nearly all the patients, and were significantly lower in severe cases (332.5, 185.6 and 124.3 million/L) than moderate cases (676.5, 359.2 and 272.0 million/L). The expressions of IFN-γ by CD4+T cells tended to be lower in severe cases (14.6%) than moderate cases (23.6%). Conclusion The SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+T cells, resulting in significant decrease in number as well as IFN-γ production, which may be associated with disease severity. Together with clinical characteristics, early immunologic indicators including diminished T lymphocytes and elevated cytokines may serve as potential markers for prognosis in COVID-19.
Article
Background: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding: National Key R&D Program of China.
Article
Thirty-three million people have atrial fibrillation (AF), a disorder of heart rhythm.1 Over the past several decades, we have learned that this dysrhythmia originates in the interplay between genetic predisposition, ectopic electrical activity, and abnormal atrial tissue substrate and then feeds back to remodel and worsen tissue substrate and, thereby, propagates itself.2 Although the importance of AF partly derives from its strong association with ischemic stroke, there have not been as many advances in our understanding of the mechanisms of stroke in AF. Current views rest on a century old hypothesis that fibrillation of the atrium produces stasis of blood, which causes thrombus formation and embolism to the brain. When other abnormalities are acknowledged to play a role, the dysrhythmia is still considered the primary cause of thromboembolism.3 Although this formulation is intuitively appealing, recent work suggests that the pathogenesis of stroke in AF is more complicated and involves factors in addition to the dysrhythmia. AF and stroke have been associated in rigorous studies,4 indicating a true association rather than a spurious finding. Epidemiological logic suggests 3 explanations: (1) AF causes stroke, (2) stroke causes AF, and (3) AF is associated with other factors that cause stroke. To help judge whether one factor causes another or whether the 2 are simply correlated, the epidemiologist Bradford Hill proposed the following widely accepted criteria: (1) strength of association, (2) consistency, (3) specificity, (4) temporality, (5) biological gradient, (6) plausibility, (7) coherence, (8) accordance with experimental results, and (9) analogy.5 The relationship between AF and stroke fulfills several of these criteria. Patients with AF face a strongly elevated risk of stroke—about 3- to 5-fold higher after adjustment for risk factors.4 AF has been consistently associated with stroke in different cohorts.6 And a causal association is biologically …
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Objectives: To define which variables upon ICU admission could be related to the presence of coinfection using CHAID (Chi-squared Automatic Interaction Detection) analysis. Methods: A secondary analysis from a prospective, multicentre, observational study (2009-2014) in ICU patients with confirmed A(H1N1)pdm09 infection. We assessed the potential of biomarkers and clinical variables upon admission to the ICU for coinfection diagnosis using CHAID analysis. Performance of cut-off points obtained was determined on the basis of the binominal distributions of the true (+) and true(-) results. Results: Of the 972 patients included, 196 (20.3%) had coinfection. Procalcitonin (PCT;ng/mL 2.4 vs. 0.5, p<0.001), but not C-reactive protein (CRP;mg/dL 25 vs. 38.5; p=0.62) was higher in patients with coinfection. In CHAID analyses, PCT was the most important variable for coinfection. PCT<0.29ng/mL showed high sensitivity (Se=88.2%), low Sp(33.2%) and high negative predictive value (NPV= 91.9%). The absence of shock improved classification capacity. Thus, for PCT <0.29ng/mL, the Se was 84%, the Sp 43% and an NPV of 94% with a post-test probability of coinfection of only 6%. Conclusion: PCT has a high negative predictive value (94%) and lower PCT levels seems to be a good tool for excluding coinfection, particularly for patients without shock.