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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

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Abstract

Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/L (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/L could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

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... Additional factors affecting the severity of the course of SARS-CoV-2 infection are chronic diseases, the prevalence of which increases with age. Although they do not seem to affect the risk of infection with the new coronavirus, diseases such as hypertension, ischaemic heart disease, or diabetes are two (hypertension and diabetes) or even three times (ischaemic disease) more frequent in patients hospitalized in the intensive care unit [21]. Moreover, the risk of death has been demonstrated to be significantly higher in patients with the above-mentioned diseases as well as with chronic obstructive pulmonary disease or chronic kidney disease [22]. ...
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In the wake of the COVID-19 pandemic, international action has been taken to prevent the spread of the disease. The aim of this study is to establish the impact of the COVID-19 pandemic on emergency department utilization patterns in Poland. It was established that age (among COVID-19 positive patients) has a large influence on the occurrence of a mental illness or disorder. It has been proven that the older the person (patients diagnosed with U07.1), the more often mental diseases/disorders are diagnosed (p = 0.009–0.044). Gender decides the course of hospitalization to the disadvantage of men (p = 0.022). Men diagnosed with U07.1 stay much longer in specialized long-term care units. Lower-aged patients have a shorter hospitalization time (up to the age of 29; p = 0.017). The COVID-19 pandemic has placed healthcare systems, their staff, and their patients in an unprecedented situation. Our study showed changes in the number and characteristics of patients visiting the ED during COVID-19. Despite the shift in the center of gravity of health system functioning to the treatment of SARS-CoV-2 infected patients, care must be taken to ensure that uninfected patients have access to treatment for cardiovascular, mental health, oncological, and other diseases.
... Concomitant systemic diseases and the general status of the patients are continuously evaluated to identify predisposing/risk factors that may influence the severity and the mortality of COVID-19. Among these, hypertension, obesity, and diabetes are the three comorbidities with the most unfavorable outcomes, which are hospitalization, intensive care unit (ICU) admission, and eventually death (Richardson et al., 2020;Zhou et al., 2020). ...
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Background: During the pandemic of COVID-19, the scientific community tried to identify the risk factors that aggravate the viral infection. Oral health and specifically periodontitis have been shown to have a significant impact on overall health. Current, yet limited, evidence suggests a link between periodontal status and severity of COVID-19 infection. Objectives: The present pilot study aimed to assess whether younger patients (≤60 years) that have been hospitalized in the intensive care unit (ICU) for severe COVID-19 infection were susceptible to severe periodontitis. Material and methods: All dentate patients ≤60 years of age diagnosed with COVID-19 and surviving hospitalization in the ICU were considered for inclusion. Susceptibility to periodontitis was determined by assessing radiographic bone loss (RBL) in recent dental radiographs (posterior bitewings, periapical, and panoramic X-rays). RBL in % was obtained from the most affected tooth and patients were classified into: Stage I, RBL ≤ 15%; Stage II, RBL = 15%-33% and Stage III/IV, RBL ≥ 33%. The grade was defined using the RBL to age ratio on the most severely affected tooth. Patients were attributed to: Grade A, ratio <0.25; Grade B, ratio 0.25-1 and Grade C, ratio >1. Patients classified into Stage III/IV and Grade C were considered highly susceptible to periodontitis. Results: Of 87 eligible patients, 30 patients were finally assessed radiographically and/or clinically; from the remaining 57 patients, 16 refused participation for various reasons and 41 could not be reached. Based on the radiographic assessment, all patients were periodontally compromised. Half of them were classified with Stage III/IV and Grade B or C; 26.7% were classified with Stage III/IV and Grade C. Conclusions: The present pilot study showed that about half of the patients suffering from severe forms of COVID-19 infection in need of ICU admission suffered also from severe periodontitis, and about one-fourth of them were highly susceptible to it.
... The coronavirus disease pandemic of 2019 (COVID- 19) is still a global concern for human survival. From the first emergence of the COVID-19 infection in Wuhan, China, until now, almost all countries in the world have been affected by COVID-19 (1). Currently, we are witnessing the so-called "fifth wave" of COVID-19 in Iran, which is causing stress among individuals. ...
... Open access associated with adverse outcomes following COVID-19 infection. [8][9][10][11][12] To date, most studies describing incidence or prevalence of COVID-19 among PEH have been cross-sectional in design, many focussing on a convenience sample of shelters during the first or second waves (from March to December 2020). As a result, estimates from these studies vary widely depending on setting, timing and preventive measures in place, [13][14][15][16][17][18][19][20][21][22][23][24][25] with variability primarily determined by whether the settings, in most cases emergency shelters, were experiencing an outbreak. ...
Article
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Introduction: Initial reports suggest people experiencing homelessness (PEH) are at high risk for SARS-CoV-2 infection and associated morbidity and mortality. However, there have been few longitudinal evaluations of the spread and impact of COVID-19 among PEH. This study will estimate the prevalence and incidence of COVID-19 infections in a cohort of PEH followed prospectively in Toronto, Canada. It will also examine associations between individual-level and shelter-level characteristics with COVID-19 infection, adverse health outcomes related to infection and vaccination. Finally, the data will be used to develop and parameterise a mathematical model to characterise SARS-CoV-2 transmission dynamics, and the transmission impact of interventions serving PEH. Design, methods and analysis: Ku-gaa-gii pimitizi-win will follow a random sample of PEH from across Toronto (Canada) for 12 months. 736 participants were enrolled between June and September 2021, and will be followed up at 3-month intervals. At each interval, specimens (saliva, capillary blood) will be collected to determine active SARS-CoV- 2 infection and serologic evidence of past infection and/or vaccination, and a detailed survey will gather self-reported information, including a detailed housing history. To examine the association between individual-level and shelter-level characteristics on COVID-19-related infection, adverse outcomes, and vaccination, shelter and healthcare administrative data will be linked to participant study data. Healthcare administrative data will also be used to examine long-term (up to 5 years) COVID-19-related outcomes among participants.
... A large volume of published literature has reported that various comorbidities may predispose patients with COVID-19 to an unfavorable outcome, and a higher risk of death (44)(45)(46)(47)(48)(49)(50)(51). Hernández-Garduño, after analyzing the data of 32,583 patients, showed that the presence of either obesity, diabetes, or hypertension were strong predictors for both the acquisition of SARS-CoV-2 infection and the development of severe disease (50). ...
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The unprecedented worldwide spread of SARS-CoV-2 has imposed severe challenges on global health care systems. The roll-out and widespread administration of COVID-19 vaccines has been deemed a major milestone in the race to restrict the severity of the infection. Vaccines have as yet not entirely suppressed the relentless progression of the pandemic, due mainly to the emergence of new virus variants, and also secondary to the waning of protective antibody titers over time. Encouragingly, an increasing number of antiviral drugs, such as remdesivir and the newly developed drug combination, Paxlovid® (nirmatrelvir/ritonavir), as well as molnupiravir, have shown significant benefits for COVID-19 patient outcomes. Pre-exposure prophylaxis (PrEP) has been proven to be an effective preventive strategy in high-risk uninfected people exposed to HIV. Building on knowledge from what is already known about the use of PrEP for HIV disease, and from recently gleaned knowledge of antivirals used against COVID-19, we propose that SARS-CoV-2 PrEP, using specific antiviral and adjuvant drugs against SARS-CoV-2, may represent a novel preventive strategy for high-risk populations, including healthcare workers, immunodeficient individuals, and poor vaccine responders. Herein, we critically review the risk factors for severe COVID-19 and discuss PrEP strategies against SARS-CoV-2. In addition, we outline details of candidate anti-SARS-CoV-2 PrEP drugs, thus creating a framework with respect to the development of alternative and/or complementary strategies to prevent COVID-19, and contributing to the global armamentarium that has been developed to limit SARS-CoV-2 infection, severity, and transmission.
... The virus enters the host through inhalation of air contaminated with infected patients' sneezes, coughs, and speech (2). Touching unhygienic surfaces and the eyes, nose, or mouth of infected people could also transmit the virus to a healthy individual (3). ...
Article
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Coronavirus disease 2019 (COVID-19) was found to cause complications in certain groups of people, leading to hospitalization. Several factors have been linked to this, such as gender, age, comorbidity, and race. Understanding the precise reasons for the COVID-19-induced complications might help in designing strategies to minimize hospitalization. A retrospective, cross-sectional observational study was conducted for patients in a COVID-19-designated specialty hospital after obtaining ethical clearance. Patients' demographic and clinical characteristics, such as age, gender, race, vaccinated status, complications, comorbidities, and medications, were retrieved from the hospital medical database. The data were statistically analyzed to determine the association between the predictors and the outcomes of COVID-19. An odds ratio (both unadjusted and adjusted) analysis was carried out to determine the risk factors for hospitalization [non-intensive care (non-ICU) and intensive care (ICU)] due to COVID-19. The data from the study indicated that the majority of patients hospitalized due to COVID-19 were male (>55%), aged > 60 years (>40%), married (>80%), and unvaccinated (>71%). The common symptoms, complications, comorbidities, and medications were fever, pneumonia, hypertension, and prednisolone, respectively. Male gender, patients older than 60 years, unemployed, unvaccinated, complicated, and comorbid patients had an odds ratio of more than 2 and were found to be significantly ( p < 0.05) higher in ICU admission. In addition, administration of prednisolone and remdesivir was found to significantly reduce ( p < 0.05) the odds ratio in ICU patients. The analysis of the data suggested that male gender, age above 60 years, and unvaccinated with comorbidities increased the complications and resulted in hospitalization, including ICU admission. Hypertension and type 2 diabetes associated with obesity as metabolic syndrome could be considered one of the major risk factors. Preventive strategies need to be directed toward these risk factors to reduce the complications, as well as hospitalization to defeat the COVID-19 pandemic.
... Many studies have been conducted to find the causes of differences in the clinical manifestations of COVID-19 and its severity [17][18][19] . Epidemiological studies have identified several risk factors for the severe form of this viral disease 20,21 . ...
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COVID-19 has caused the recent pandemic of respiratory infection, which threatened global health. The severity of the symptoms varies among affected individuals, from asymptotic or mild signs to severe or critical illness. Genetic predisposition explains the variation in disease severity among patients who suffer from severe symptoms without any known background risk factors. The present study was performed to show the association between APOE genotype and the severity of COVID-19 disease. The APOE genotype of 201 COVID-19 patients (101 patients with asymptomatic to mild form of the disease as the control group and 100 patients with severe to critical illness without any known background risk factors as the case group) were detected via multiplex tetra-primer ARMS-PCR method. Results showed that the e4 allele increased the risk of the COVID-19 infection severity more than five times and the e4/e4 genotype showed a 17-fold increase in the risk of severe disease. In conclusion, since our study design was based on the exclusion of patients with underlying diseases predisposing to severe form of COVID-19 and diseases related to the APOE gene in the study population, our results showed that the e4 genotype is independently associated with the severity of COVID-19 disease. However, further studies are needed to confirm these findings in other nations and to demonstrate the mechanisms behind the role of these alleles in disease severity.
... In the context of countries/regions with continuing epidemic, the estimation of CFR remained challenging, which also hindered a rational estimation of the mortality related factors. Although previous efforts have produced consistent results that older age, male sex as well as underlying comorbidities were risk factors for poor outcomes in COVID-19 cases [6][7][8][9][10][11][12], conflicting views remained for many other uncertain factors, such as ethnicity, delayed hospitalization, poverty, obesity, etc. [13][14][15][16][17][18]. Delay between symptom onset to diagnosis was considered as a risk factor for severe or death outcome [19][20][21][22][23][24], however, it remained obscure whether these risky behaviors were independently associated with adverse disease, and whether there is modifying effect on the association between them [25]. ...
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Background To quantitatively assess the impact of the onset-to-diagnosis interval (ODI) on severity and death for coronavirus disease 2019 (COVID-19) patients. Methods This retrospective study was conducted based on the data on COVID-19 cases of China over the age of 40 years reported through China’s National Notifiable Infectious Disease Surveillance System from February 5, 2020 to October 8, 2020. The impacts of ODI on severe rate (SR) and case fatality rate (CFR) were evaluated at individual and population levels, which was further disaggregated by sex, age and geographic origin. Results As the rapid decline of ODI from around 40 days in early January to < 3 days in early March, both CFR and SR of COVID-19 largely dropped below 5% in China. After adjusting for age, sex, and region, an effect of ODI on SR was observed with the highest OR of 2.95 (95% CI 2.37‒3.66) at Day 10–11 and attributable fraction (AF) of 29.1% (95% CI 22.2‒36.1%) at Day 8–9. However, little effect of ODI on CFR was observed. Moreover, discrepancy of effect magnitude was found, showing a greater effect from ODI on SR among patients of male sex, younger age, and those cases in Wuhan. Conclusion The ODI was significantly associated with the severity of COVID-19, highlighting the importance of timely diagnosis, especially for patients who were confirmed to gain increased benefit from early diagnosis to some extent.
... Values for aPPT and TT were within the normal range. This is in accordance to results published by several authors [27,[39][40][41]. In addition to the hematological parameters, our results suggested that the oxidative stress parameters of these patients correlate with NLR, PLR, and D-dimer. ...
Article
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Background/aim : Hematological parameters are the starting point in COVID-19 severity classification. The aim of this study was to analyze oxidative stress in hospitalized COVID-19 patients and to determine its association with D-dimer, neutrophil to lymphocyte ratio (NLR), and platelets to lymphocyte ratio (PLR) as markers for disease progression. Materials and method s: 52 patients with moderate and severe forms of COVID-19 were enrolled. A hematological and coagulation profile was performed for each patient. PAT (total antioxidant power, iron-reducing) and d-ROMs (plasma peroxides) were determined in serum at admission and 7 days after hospitalization. Results : The severe group presented parameters that indicated a poor prognosis. Patients that recovered had a significant reduction in d-ROM (t-test, p<0.01) and improvement in oxidative stress index (t-test, p<0.05). Patients that died had significantly decreased PAT (p<0.01) resulting in an increase in oxidative stress. Except for d-ROM vs PLR in both groups and d-ROM vs D-dimer in the severe group, a good correlation between oxidative stress parameters and D-dimer, PLR, and NLR was demonstrated (p<0.01). Conclusion : Our results show that oxidative stress markers can be used as a tool for disease progression in COVID-19. This analysis is easily accessible and affordable in addition to conventional hematological parameters performed for severity classification.
... The common symptoms include fever, dry cough, dyspnea, and sore throat. 6,7 Acute Respiratory Distress Syndrome (ARDS) and shock are the most common complications. 8 Older age, male gender, pre-existing co-morbidities, lower oxygen saturation at admission, lymphopenia, increased C-reactive protein (CRP) and d-dimer levels have been found to be associated with critical illness and death. ...
Article
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Background: Coronavirus disease 2019 (COVID-19) emerged as a challenging pandemic globally. The clinical manifestations range from asymptomatic infection to severe respiratory failure. In-hospital mortality varies from 18.9% to 20.3%. Old age, male gender, co-morbidities, lower oxygen saturation, lymphopenia, raised C-reactive protein, and d-dimer levels increase the risk of critical illness and death. The objective of this study was to compare the clinical characteristics of COVID-19 patients and associated outcomes in a tertiary level hospital in Nepal. Methods: An analytical cross-sectional study was conducted in laboratory-confirmed COVID-19 patients admitted in a tertiary center of Nepal during the peak of the second wave of the pandemic. A non-probabilistic consecutive sampling technique was adopted. Data were analyzed using Statistical Package for the Social Sciences (IBM-SPSS), version-23. Mortality (yes/no) was the primary outcome of interest, and accordingly, the cases were divided into two groups, survivors and non-survivors. Bivariate and multivariate analyses were performed. Results: The overall in-hospital mortality was 84 (19.58%), and Intensive Care Unit (ICU) mortality was 36 (58.06%). The death rate was higher in cases presenting with shortness of breath and anorexia. Hypoxemic respiratory failure (16.08%) and acute respiratory distress syndrome (8.62%) were the most common complications associated with higher mortality. Patients with older age had higher odds of mortality (adjusted OR, 1.077; p<0.001). The risk of mortality was higher in severe to critically ill patients (adjusted OR, 5.861; p=0.001), and those who were under mechanical ventilation (adjusted OR, 39.059; p<0.001). Likewise, the duration of hospital stay was significantly associated with mortality (adjusted OR, 0.795; p<0.001). Conclusions: The non-survivors of COVID-19 tended to be of older age, severe to critically ill at presentation, require mechanical ventilation, and have a shorter duration of hospital stay, compared to survivors. So, these groups of patients need special care and support during hospital admission.
... were diagnosed with non-obstructive coronary artery disease (32, 33). This suggests that COVID-19 itself may be associated with endothelial dysfunction and hypercoagulability (34). Arrhythmias are a common manifestation of COVID-19 cardiovascular complications. ...
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The pandemic respiratory illness SARS-CoV-2 has increasingly been shown to be a systemic disease that can also have profound impacts on the cardiovascular system. Although associated cardiopulmonary sequelae can persist after infection, the link between viral infection and these complications remains unclear. There is now a recognized link between endothelial cell dysfunction and thrombosis. Its role in stimulating platelet activation and thrombotic inflammation has been widely reported. However, the procoagulant role of microparticles (MPs) in COVID-19 seems to have been neglected. As membrane vesicles released after cell injury or apoptosis, MPs exert procoagulant activity mainly by exposing phosphatidylserine (PS) on their lipid membranes. It can provide a catalytic surface for the assembly of the prothrombinase complex. Therefore, inhibiting PS externalization is a potential therapeutic strategy. In this paper, we describe the pathophysiological mechanism by which SARS-CoV-2 induces lung and heart complications through injury of endothelial cells, emphasizing the procoagulant effect of MPs and PS, and demonstrate the importance of early antithrombotic therapy. In addition, we will detail the mechanisms underlying hypoxia, another serious pulmonary complication related to SARS-CoV-2-induced endothelial cells injury and discuss the use of oxygen therapy. In the case of SARS-CoV-2 infection, virus invades endothelial cells through direct infection, hypoxia, imbalance of the RAAS, and cytokine storm. These factors cause endothelial cells to release MPs, form MPs storm, and eventually lead to thrombosis. This, in turn, accelerates hypoxia and cytokine storms, forming a positive feedback loop. Given the important role of thrombosis in the disease, early antithrombotic therapy is an important tool for COVID-19. It may maintain normal blood circulation, accelerating the clearance of viruses, waning the formation of MPs storm, and avoiding disease progression.
... Sepsis is the most frequently observed complication, followed by respiratory failure, acute respiratory distress syndrome (ARDS), heart failure, and septic shock (7). ...
Article
Aim To evaluate clinical and epidemiological characteristics and outcome of patients with COVID-19, and impact of vaccine against COVID-19 on them. Methods This retrospective study included 225 patients treated from COVID-19 in the period from 1 to 30 September 2021 at the Clinic for Infectious Diseases, University Clinical Centre Tuzla (UCC Tuzla). For the diagnosis confirmation of Covid-19, RTPCR was used. Patients were divided in two groups: fully vaccinated with two doses of vaccine, and non-vaccinated or partially vaccinated. Results Of 225 patients, 120 (53.3%) were females, and 105 (46.7%) males. Mean age was 65.6 years. There were 26 (11.6%) fully vaccinated patients. Most common symptoms in unvaccinated patients were fatigue (70.9%), cough (70.4%) and fever (69.8%), and in vaccinated fever (76.9%), fatigue (69.2%) and cough (46.2%). Cough was more common in unvaccinated patients (p=0.013). Fatal outcome happened in 84 (37.3%) patients. Transfer to the Intensive Care Unit (ICU) and older age had a higher risk of death (p<0.001). Older age patients were more likely to have comorbidities like atrial fibrillation (p=0.017), hypertension (p<001) and diabetes mellitus (p=0.002). Atrial fibrillation (p<0.001), hypertension (p<0.001), diabetes mellitus (p=0.009) and history of stroke (p=0.026), were related to fatal outcome in unvaccinated patients, also did a shorter duration of illness prior to hospitalization (p<0.001) and shorter length of hospitalization (p=0.002). Conclusion Older patients with comorbidities, as well as those who were not vaccinated against COVID-19, were at higher risk for severe form of the disease and poor outcome.
... [11][12][13][14] Los factores asociados a una peor evolución de la enfermedad por SARS-CoV-2 son múltiples, entre los que se encuentran: la edad avanzada (mayores de 65 años), trastornos de la hemoglobina, y personas inmunodeprimidas o con enfermedades inflamatorias mediadas por la inmunidad (EIMI), enfermedades crónicas y comorbilidades, influyendo de forma importante en el pronóstico de la enfermedad. [15][16][17] En el caso de los pacientes con EIMI, las recomendaciones incluyen, su monitorización para la detección precoz de la infección por SARS-CoV-2, y fomentar la adherencia al tratamiento y no interrumpirlo y, en el caso de que un paciente desarrolle Covid-19, debe valorarse a nivel individual la supresión del tratamiento. [18][19][20][21] Durante la pandemia, los sistemas de vigilancia epidemiológica han desarrollado estrategias de diagnóstico, vigilancia y control con un doble objetivo: la detección precoz de cualquier caso que pudiese tener infección activa por SARS-CoV-2 y, por otra parte, garantizar la continuidad asistencial de estos pacientes crónicos sin comprometer su salud. ...
Article
bjetivo principal: Describir la incidencia de Covid-19 por sexo y especialidad en pacientes con Enfermedad Inmunomediada Inflamatoria (EIMI). Metodología: Estudio observacional prospectivo de pacientes en seguimiento/tratamiento en un Centro de Enfermedades Inmuno-mediadas Inflamatorias, de marzo a junio de 2020. Resultados: El total de pacientes en seguimiento era de 1672, se realizaron 3480 consultas, siendo telemáticas 2382(68.4 %). Se confirmaron 77(4.60 %) casos de Covid-19, siendo mujeres 40 (51.98 %).Los síntomas prevalentes fueron: tosseca (81.8 %), mialgias/artralgias (77.9 %), cefalea (68.8 %), fiebre (55.8 %) y neumonía (22.4 %). Se encontraron diferencias en los síntomas por especialidad: mial-gias/artralgias (p=0.001), cefalea (p=0.011), fiebre (p=0.012). Necesitaron hospita-lización 17 pacientes (22.10 %) y 3 (17.65 %) en Cuidados Intensivos. Conclusión: La terapia con fármacos biológicos no se asoció con peores resultados de Covid-19. Las consultas telemáticas realizada por Enfermeras de Práctica Avanzada garantiza-ron el seguimiento óptimo, la detección precoz y la continuidad del tratamiento.Palabras clave: Cuidados de Enfermería. Telemedicina. Diagnóstico Precoz. Infecciones por Coronavirus. Reumatología. Enfermedades Inflamatorias del Intestino. Dermatología.
... And the article "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China" conducted by Huang CL et al. was the second most influential by 406 co-citations up to the present (33). In addition, the other three studies were performed by Qin C (270 times of co-citation) (23), Zhou F (264 times of co-citation) (34), and Hoffmann M (259 times of co-citation) (35), respectively. Strikingly, three of the top five influential references regarding times of co-citation were published by scholars in China. ...
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Introduction: As the first bibliometric analysis of COVID-19 and immune responses, this study will provide a comprehensive overview of the latest research advances. We attempt to summarize the scientific productivity and cooperation across countries and institutions using the bibliometric methodology. Meanwhile, using clustering analysis of keywords, we revealed the evolution of research hotspots and predicted future research focuses, thereby providing valuable information for the follow-up studies. Methods: We selected publications on COVID-19 and immune response using our pre designed search strategy. Web of Science was applied to screen the eligible publications for subsequent bibliometric analyses. GraphPad Prism8.0, VOSviewer, and CiteSpace were applied to analyze the research trends and compared the contributions of countries, authors, institutions, and journals to the global publications in this field. Results: We identified 2,200 publications on COVID-19 and immune response published between December 1, 2019, and April 25, 2022, with a total of 3,154 citations. The United States (611), China (353), and Germany (209) ranked the top three in terms of the number of publications, accounting for 53.3% of the total articles. Among the top 15 institutions publishing articles in this area, four were from France, four were from the United States, and three were from China. The journal Frontiers in Immunology published the most articles (178) related to COVID-19 and immune response. Alessandro Sette (31 publications) from the United States were the most productive and influential scholar in this field, whose publications with the most citation frequency (3,633). Furthermore, the development and evaluation of vaccines might become a hotspot in relevant scope. Conclusions: The United States makes the most indispensable contribution in this field in terms of publication numbers, total citations, and H-index. Although publications from China also take the lead regarding quality and quantity, their international cooperation and preclinical research need to be further strengthened. Regarding the citation frequency and the total numberof published articles, the latest research progress might be tracked in the top-ranking journals in this field. By analyzing the chronological order of the appearance of retrieved keywords, we speculated that vaccine-related research might be the novel focus in this field.
... 3 Aged patients and those with preexisting medical conditions, such as pulmonary disease or immunodeficiency, are at greater risk of developing this life-threatening respiratory condition that requires supplemental oxygen support. 4 The coronavirus that caused the severe acute respiratory syndrome pandemic of 2002-2003 has 70% of its genome resemblance to this new virus (SARS-CoV-2). 5 Chronic inflammation, oxidative stress, and endothelial dysfunction are the key possible pathophysiological pathways of COVID-19 that may cause multiple organ failures and mortality. ...
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Vitamin C has been predicted to be effective as an antioxidant in treating various ailments, including viral infections such as pervasive coronavirus disease (COVID‐19). With this meta‐analysis, we looked to ascertain the relationship between high‐dose vitamin C administration and mortality, severity, and length of hospitalization of COVID‐19 patients. We collected articles from PubMed, Google Scholar, ScienceDirect, SAGE, and Cochrane databases between January 1, 2020, and May 30, 2022. Odds ratio (ORs) with corresponding 95% confidence interval (CI) and p value were calculated to assess the connection of high‐dose vitamin C in COVID‐19 patients' mortality and severity. The length of hospitalization was calculated and pooled with the mean difference (MD), 95% CI, and p value. Review manager 5.3 was used to carry out this meta‐analysis. This meta‐analysis included 15 complete studies involving 2125 COVID‐19 patients. Our study demonstrated a significant correlation between vitamin C consumption and death. Vitamin C consumption significantly reduces mortality risk with COVID‐19 patients (OR = 0.54, 95% CI = 0.42–0.69, p < 0.00001). Furthermore, there was a link between the severity of COVID‐19 and the intake of vitamin C. Patients who consumed vitamin C showed 0.63 times less severity than those who did not take vitamin C (OR = 0.63, 95% CI = 0.43–0.94, p = 0.02). Patients taking vitamin C spent slightly more time in hospital than those who did not take vitamin C (MD = 0.19, 95% CI = −1.57 to 1.96, p = 0.83). During COVID‐19, there was a substantial advantage in taking supplementary vitamin C, at least in terms of severity and mortality.
... As clinical manifestations of COVID-19 range from mild to moderate, more systematic symptoms and severe radiological abnormalities are seen in older patients [37]. Children and younger adults can remain as asymptomatic carriers [38][39][40]. The possibility for gastrointestinal involvement in SARS-CoV-2 infection and feco-oral transmission has been suggested [41]. ...
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Your article is protected by copyright and all rights are held exclusively by Springer Nature Switzerland AG. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com". Abstract Coronavirus disease 2019 (COVID-19), an ongoing global health emergency, is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging in Wuhan, China, in December 2019, it spread widely across the world causing panic-worst ever economic depression is visibly predictable. Coronaviruses (CoVs) have emerged as a major public health concern having caused three zoonotic outbreaks; severe acute respiratory syndrome-CoV (SARS-CoV) in 2002-2003, Middle East respiratory syndrome-CoV (MERS-CoV) in 2012, and currently this devastating COVID-19. Research strategies focused on understanding the evolutionary origin, transmission, and molecular basis of SARS-CoV-2 and its pathogenesis need to be urgently formulated to manage the current and possible future coronaviral outbreaks. Current response to the COVID-19 outbreak has been largely limited to monitoring/containment. Although frantic global efforts for developing safe and effective prophylactic and therapeutic agents are on, no licensed antiviral treatment or vaccine exists till date. In this review, research strategies for coping with COVID-19 based on evolutionary and molecular aspects of coronaviruses have been proposed.
... No proven effective treatment is currently found against the virus, and its effect on other diseases such as inherited syndromes is unknown [3]. Studies have indicated that while most patients are asymptomatic or have minor symptoms [4], those with underlying diseases, especially cardiovascular disease or the elderly may have a worse prognosis than others. In addition, understanding that most clinical manifestations are related to the respiratory system is essential, however, the disease may also affect the cardiovascular system [5,6]. ...
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Electrocardiographic (ECG) changes have been investigated in the condition of coronavirus disease (COVID-19) indicating that COVID-19 infection exacerbates arrhythmias and triggers conduction abnormalities. However, the specific type of ECG abnormalities in COVID-19 and their impact on mortality fail to have been fully elucidated. The present retrospective, tertiary care hospital-based cross-sectional study was conducted by reviewing the medical records of all patients diagnosed with COVID-19 infection who were admitted to Booali Sina Hospital in Qazvin, Iran from March to July 2020. Demographic information, length of hospital stay, treatment outcome, and electrocardiographic information (heart rate, QTc interval, arrhythmias, and blocks) were extracted from the medical records of the patients. Finally, a total of 231 patients were enrolled in the study. Atrial fibrillation was a common arrhythmia, and the left anterior fascicular block was a common cardiac conduction defect other than sinus arrhythmia. The deceased patients were significantly older than the recovered ones (71 ± 14 vs. 57 ± 16 years, p < 0.001). Longer hospital stay (p = 0.036), non-sinus rhythm (p < 0.001), bundle and node blocks (p = 0.002), ST-T waves changes (p = 0.003), and Tachycardia (p = 0.024) were significantly prevalent in the deceased group. In baseline ECGs, no significant difference was observed in terms of the absolute size of QT; however, a prolonged QTc in the deceased was about twice of the recovered patients (using Bazett, Sagie, and Fridericia’s formula). Serial ECGs are recommended to be taken from all hospitalized patients with COVID-19 due to increased in-hospital mortality in patients with prolonged QTc interval, non-sinus rhythms, ST-T changes, tachycardia, and bundle, and node blocks.
... Our results highlight the effect of age on mortality in COVID-19 infection, which is consistent with other studies worldwide. [30][31][32][33][34][35] A meta-analysis of 611,583 COVID-19 patients by Bonanad et al. 3 reported that mortality increased exponentially in those aged > 60 years, and that the mortality rate was < 1% in those aged < 50 years and highest (29.6%) in those aged > 80 years. In our elderly group, the median age was 72.5 years with an in-hospital mortality rate of 7.1%, which is much lower compared to previous results, ranging from 7.94% to 20.99%. 3 A possible reason for the difference may be due to the delayed pandemic in Taiwan. ...
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Background: Geriatric patients with COVID-19 have had poor clinical outcomes globally, especially during the first wave of the pandemic. In Taiwan, the first wave of the COVID-19 pandemic occurred from May to July 2021. This retrospective study aimed to compare the characteristics and outcomes between geriatric and younger patients with COVID-19 infection. Methods: A total of 257 confirmed COVID-19 cases who were hospitalized from May to June 2021 were included. Their characteristics and outcomes, including in-hospital mortality, use of mechanical ventilation, and hospital stay, were collected for analysis. Results: There were 98 elderly patients (aged < 65 years, median, 72.5 (interquartile range, 69.0–78.0) years) and 159 younger patients (aged < 65 years, median 55.0 (46.0–60.0) years). The elderly patients had a significantly higher Charlson comorbidity score (4.0 (3.0–5.0) vs. 1.0 (1.0–2.0), p < 0.001), and significantly higher D-dimer, procalcitonin, ferritin, and creatinine levels, but lower albumin level than the younger patients. The elderly group also had higher in-hospital mortality (7.1% vs. 1.9%, p < 0.05), were more likely to develop severe disease (83.7% vs. 67.9%, p < 0.01), and had a longer hospital stay (15.0 (11.0–23.0) vs. 12.0 (9.0–16.5) days, p < 0.001). Nevertheless, the elderly patients did not have a higher risk of using high-flow nasal cannulas (17.3% vs. 15.1%, p = 0.63) or mechanic ventilation (23.5% vs. 17.0%, p = 0.20). Conclusion: Elderly COVID-19 patients had significant higher risks of severe disease, mortality, and longer duration of hospitalization, possible due higher rates of comorbidities and pro-inflammatory status.
Article
Objectives: COVID-19 may predispose to thromboembolism due to excessive inflammation, hypoxia, and immobilization. We investigated whether these antithrombotic drugs are useful or harmful to tackle COVID-19 and which laboratory parameters are more usable for this purpose. Methods: In our study, patients diagnosed with COVID-19 while using antithrombotic drugs and COVID-19 patients who did not use antithrombotic drugs were compared. Demographic data, laboratory values, clinical results, duration of hospital stay, and mortality were noted and compared. Results: The study was conducted on 236 patients admitted to the emergency department. The mean value of creatine, LDH, PT, NLR, troponin, and ferritin were higher in the drug-using group. Home quarantine and hospitalization rate was 68.8% (n = 33) in antiplatelet users, and 46.2% (n = 6) in the anticoagulant group. Conclusion: The difference between the groups may have been caused by the number of chronic diseases and polypharmacy. The interaction of drugs used for the treatment of COVID-19 with antithrombotic agents is unknown. In addition, as the correlation between COVID-19 and thrombosis is not exactly known, adding antithrombotic drugs to the treatment of the disease is controversial. In our study, the biomarkers used to predict prognosis were worse in COVID-19 patients who continued antithrombotic therapy at the therapeutic dose. In the case of antithrombotic agents, the risks that may arise should always be considered. We recommend monitoring routine blood parameters, especially NLR, LDH, PT, APTT, troponin, and ferritin levels, for the prognosis monitoring of COVID-19 patients who will continue their current antithrombotic therapy
Article
With the rapid increase in the number of COVID-19 patients in Japan, the number of patients receiving oxygen at home has also increased rapidly, and some of these patients have died. An efficient approach to identify high-risk patients with slowly progressing and rapidly worsening COVID-19, and to avoid missing the timing of therapeutic intervention will improve patient prognosis and prevent medical complications. Patients admitted to medical institutions in Japan from November 14, 2020 to April 11, 2021 and registered in the COVID-19 Registry Japan were included. Risk factors for patients with High Flow Nasal Cannula invasive respiratory management or higher were comprehensively explored using machine learning. Age-specific cohorts were created, and severity prediction was performed for the patient surge period and normal times, respectively. We were able to obtain a model that was able to predict severe disease with a sensitivity of 57% when the specificity was set at 90% for those aged 40–59 years, and with a specificity of 50% and 43% when the sensitivity was set at 90% for those aged 60–79 years and 80 years and older, respectively. We were able to identify lactate dehydrogenase level (LDH) as an important factor in predicting the severity of illness in all age groups. Using machine learning, we were able to identify risk factors with high accuracy, and predict the severity of the disease. We plan to develop a tool that will be useful in determining the indications for hospitalisation for patients undergoing home care and early hospitalisation.
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Severe acute respiratory coronavirus 2 (SARS-CoV-2) interacts with the host cells through its spike protein by binding to the membrane enzyme angiotensin-converting enzyme 2 (ACE2) and it can have a direct effect on endocrine function as ACE2 is expressed in many glands and organs with endocrine function. Furthermore, several endocrine conditions have features that might increase the risk of SARS-CoV-2 infection and the severity and course of the infection, as obesity for the underlying chronic increased inflammatory status and metabolic derangement, and for the possible changes in thyroid function. Vitamin D has immunomodulatory effects, and its deficiency has negative effects. Adrenal insufficiency and excess glucocorticoids affect immune conditions also besides metabolism. This review aims to analyze the rationale for the fear of direct effects of SARS-Cov-2 on endocrinological disorders, to study the influence of pre-existing endocrine disorders on the course of the infection, and the actual data in childhood. Currently, data concerning endocrine function during the pandemic are scarce in childhood and for many aspects definite conclusions cannot be drawn, however, data on properly managed patients with adrenal insufficiency at present are re-assuring. Too little attention has been paid to thyroid function and further studies may be helpful. The available data support a need for adequate vitamin D supplementation, caution in obese patients, monitoring of thyroid function in hospitalized patients, and confirm the need for an awareness campaign for the increased frequency of precocious puberty, rapidly progressive puberty and precocious menarche. The changes in lifestyle, the increased incidence of overweight and the change in the timing of puberty lead also to hypothesize that there might be an increase in ovarian dysfunction, as for example polycystic ovarian disease, and metabolic derangements in the next years, and in the future we might be facing fertility problems. This prompts to be cautious and maintain further surveillance.
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It is widely known that blood stream infections (BSIs) in critically ill patients may affect mortality, length of stay, or the duration of mechanical ventilation. There is scarce data regarding blood stream infections in mechanically ventilated COVID-19 patients. Preliminary studies report that the number of secondary infections in COVID-9 patients may be higher. This retrospective analysis was conducted to determine the incidence of BSI. Furthermore, risk factors, mortality, and other outcomes were analyzed. The setting was an Intensive Care Unit (ICU) at a University Hospital. Patients suffering from SARS-CoV-2 infection and requiring mechanical ventilation (MV) for >48 h were eligible. The characteristics of patients who presented BSI were compared with those of patients who did not present BSI. Eighty-four patients were included. The incidence of BSI was 57%. In most cases, multidrug-resistant pathogens were isolated. Dyslipidemia was more frequent in the BSI group (p < 0.05). Moreover, BSI-group patients had a longer ICU stay and a longer duration of both mechanical ventilation and sedation (p < 0.05). Deaths were not statistically different between the two groups (73% for BSI and 56% for the non-BSI group, p > 0.05). Compared with non-survivors, survivors had lower baseline APACHE II and SOFA scores, lower D-dimers levels, a higher baseline compliance of the respiratory system, and less frequent heart failure. They received anakinra less frequently and appropriate therapy more often (p < 0.05). The independent risk factor for mortality was the APACHE II score [1.232 (1.017 to 1.493), p = 0.033].
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The COVID-19 pandemic spread all over the world, starting in China in late 2019, and significantly affected life in all aspects. As seen in SARS, MERS, COVID-19 outbreaks, coronaviruses pose a great threat to world health. The COVID-19 epidemic, which caused pandemics all over the world, continues to seriously threaten people's lives. Due to the rapid spread of COVID-19, many countries' healthcare sectors were caught off guard. This situation put a burden on doctors and healthcare professionals that they could not handle. All of the studies on COVID-19 in the literature have been done to help experts to recognize COVID-19 more accurately, to use more accurate diagnosis and appropriate treatment methods. The alleviation of this workload will be possible by developing computer aided early and accurate diagnosis systems with machine learning. Diagnosis and evaluation of pneumonia on computed tomography images provide significant benefits in investigating possible complications and in case follow-up. Pneumonia and lesions occurring in the lungs should be carefully examined as it helps in the diagnostic process during the pandemic period. For this reason, the first diagnosis and medications are very important to prevent the disease from progressing. In this study, a dataset consisting of Pneumonia and Normal images was used by proposing a new image preprocessing process. These preprocessed images were reduced to 15x15 unit size and their features were extracted according to their RGB values. Experimental studies were carried out by performing both normal values and feature reduction among these features. RGB values of the images were used in train and test processes for MLAs. In experimental studies, 5 different Machine Learning Algorithms (MLAs) (Multi Class Support Vector Machine (MC-SVM), k Nearest Neighbor (k-NN), Decision Tree (DT), Multinominal Logistic Regression (MLR), Naive Bayes (NB)). The following accuracy rates were obtained in train operations for MLAs, respectively; 1, 1, 1, 0.746377, 0.963768. Accuracy results in test operations were obtained as follows; 0.87755, 0.857143, 0.857143, 0.877551, 0.938776.
Chapter
The novel coronavirus, Severe Acute Respiratory Syndrome (SARS)-CoV-2 originating in the City of Wuhan, China in December 2019 and spread rapidly throughout China (an epidemic). Within 2 months, it had spread throughout the entire world becoming the pandemic labeled COVID-19. As this chapter is being written (early 2021), this devastating disease remains uncontrolled, causing countless and tragic death worldwide. The life cycle of the virus including its spike protein and affinity to ACE-2 receptors is well understood, but notwithstanding vaccines (Pfizer and Moderna mRNA), antiviral drugs, and monoclonal antibodies just being FDA approved (emergency use authorization—EAU), this highly contagious agent continues to spread. Only classic public health preventive measures like isolation, social distancing, masks, and copious handwashing are effective, yet difficult to enforce with people and politics in open societies. As with any pandemic, unless herd immunity is achieved through an effective immunization program, identifying infected individuals is critical. Antigen tests (polymerase chain reaction) detect active viral infection while antibody tests identify previously infected people who might be considered henceforth immune (though inconclusive with SARS-CoV2). Perhaps the most valuable information on the disease is coming from the enormous body of AI assisted research of which this chapter addresses.
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High levels of inflammatory cytokines in serum have been reported in patients with severe SARS-CoV-2 infection. There is growing interest in recognizing the role of inflammatory biomarkers in saliva in diagnosing systemic diseases. This study assumed that estimating biomarkers in saliva samples from patients infected with SARS-CoV-2 would distinguish between mild and severe cases. Saliva was collected from 142 controls and 158 SARS-CoV-2 patients (mild 72 and severe 86) to measure interleukin-6 (IL-6), C-reactive protein (CRP), and C-X-C motif chemokine ligand-10 (CXCL-10). IL-6 and CXCL-10 were significantly increased in patients with mild and severe SARS-CoV-2 infections. CRP was significantly increased only in severe SARS-CoV-2 cases. All biomarkers were significantly higher in severe cases than in mild cases ( p < 0.001 ). Among patients with SARS-CoV-2 infection, men showed significantly higher CRP and CXCL-10 levels than females ( p < 0.01 and 0.05, respectively). In addition, elderly patients (40–80 years) had significantly higher IL-6, CRP, and CXCL-10 ( p < 0.001 ). Patients with diabetes and hypertension showed elevated IL-6, CRP, and CXCL-10 ( p < 0.001 ). There was a significant positive correlation between IL-6, CRP, CXCL-10, and between age, IL-6, CRP, and CXCL-10. Saliva may have a future value in measuring the inflammatory biomarkers associated with the severity of SARS-CoV2 infection and therapeutic monitoring.
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In the struggle against COVID-19 pandemic, chloroquine (CQ) (a 4-aminoquinoline) and its derivative hydroxychloroquine (HCQ) have both been used as a potential form of treatment among infected patients. Originally known as an antimalarial quinolone, many countries have adopted their use as an option to treat COVID-19 patients. In humans, dose-dependent chloroquine induces QT interval prolongation. It also blocks the human ether-a-go-go-related gene (hERG), which encodes the rapidly activating delayed rectifier K+ channel. The action potential duration is then prolonged, as the eventual QTc interval of the electrocardiogram (ECG), resulting in torsade de pointes and cardiac arrhythmias that could lead to sudden death. It is yet unknown whether COVID-19 itself has any effect on the QTc interval. The current review established what is new and different from other studies involving the use of chloroquine and hydroxychloroquine among COVID-19 patients plus the corresponding QT interval prolongation in affected individuals.
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Interferons (IFNs) were first discovered over 60 years ago in a classic experiment by Isaacs and Lindenman showing that type I IFNs have antiviral activity. IFNs are widely used in the treatment of multiple sclerosis, viral hepatitis B and C, and some forms of cancer. Preliminary clinical data support the efficacy of type I IFN against potential pandemic viruses such as Ebola and SARS. Nevertheless, more effective and specific drugs have found their place in the treatment of such diseases. As the COVID-19 (SARS-CoV-2) pandemic is evolving, type I IFN is being re-discussed as one of the main pathogenic drugs, and initial clinical trials have shown promising results in reducing the severity and duration of COVID-19. Although SARS-CoV-2 inhibits the production of IFN-β and prevents a full innate immune response to this virus, it is sensitive to the antiviral activity of externally administered type I IFN. The review presents current data on the classification and mechanisms of action of IFN. Possible options for the optimal use of IFN in the fight against COVID-19 are discussed.
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RESEARCH APPROACHES IN MULTIDISCIPLINARY SUBJECTS, VOLUME – 4 Edited by: Crispin J Fernandez, Dr. Mohd. Shaikhul Ashraf, Prof. (Dr.) Arunaanchal, Dr. Surapati Pramanik, Lt. (Dr.) Seema Singh Pundir, Dr. Priya Soni, Prof. Amar Vinod Chavan, Dr. P. Suriya, Dr. G. Vedanthadesikan
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COVID-19 disease is caused by SARS-CoV-2. Hyper-inflammation mediated by proinflammatory cytokines is humans’ primary etiology of SARS-CoV-2 infection. Kochiae Fructus is widely used in China as traditional Chinese medicine (TCM) to treat inflammatory diseases. Due to its anti-inflammatory properties, we hypothesized that Kochiae Fructus would be a promising therapeutic agent for COVID-19. The active phytomolecules, targets, and molecular pathways of Kochiae Fructus in treating COVID-19 have not been explored yet. Network pharmacology analysis was performed to determine the active phytomolecules, molecular targets, and pathways of Kochiae Fructus. The phytomolecules in Kochiae Fructus were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and their potential targets were predicted with the SwissTargetPrediction webserver. COVID-19-related targets were recovered from the GeneCards database. Intersecting targets were determined with the VENNY tool. The Protein-protein interaction (PPI) and Molecular Complex Detection (MCODE) network analyses were constructed using the Cytoscape software. Using the DAVID tool, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the intersecting targets. AutoDock Vina (version 1.2.0.) was used for molecular docking analysis. Six active phytomolecules and 165 their potential targets, 1,745 COVID-19-related targets, and 34 intersecting targets were identified. Network analysis determined 13 anti-COVID-19 core targets and three key active phytomolecules (Oleanolic acid, 9E,12Z-octadecadienoic acid, and 11,14-eicosadienoic acid). Three key pathways (pathways in cancer, the TNF signaling pathway, and lipid and atherosclerosis) and the top six anti-COVID-19 core targets (IL-6, PPARG, MAPK3, PTGS2, ICAM1, and MAPK1) were determined to be involved in the treatment of COVID-19 with active phytomolecules of Kochiae Fructus. Molecular docking analysis revealed that three key active phytomolecules of Kochiae Fructus had a regulatory effect on the identified anti-COVID-19 core targets. Hence, these findings offer a foundation for developing anti-COVID-19 drugs based on phytomolecules of Kochiae Fructus.
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COVID‐19 remains a major cause of respiratory failure, and means to identify future deterioration is needed. We recently developed a prediction score based on breath‐holding manoeuvres (desaturation and maximal duration) to predict incident adverse COVID‐19 outcomes. Here we prospectively validated our breath‐holding prediction score in COVID‐19 patients, and assessed associations with radiological scores of pulmonary involvement. Hospitalized COVID‐19 patients (N = 110, three recruitment centres) performed breath‐holds at admission to provide a prediction score (Messineo et al.) based on mean desaturation (20‐s breath‐holds) and maximal breath‐hold duration, plus baseline saturation, body mass index and cardiovascular disease. Odds ratios for incident adverse outcomes (composite of bi‐level ventilatory support, ICU admission and death) were described for patients with versus without elevated scores (>0). Regression examined associations with chest x‐ray (Brixia score) and computed tomography (CT; 3D‐software quantification). Additional comparisons were made with the previously‐validated ‘4C‐score’. Elevated prediction score was associated with adverse COVID‐19 outcomes (N = 12/110), OR[95%CI] = 4.54[1.17–17.83], p = 0.030 (positive predictive value = 9/48, negative predictive value = 59/62). Results were diminished with removal of mean desaturation from the prediction score (OR = 3.30[0.93–11.72]). The prediction score rose linearly with Brixia score (β[95%CI] = 0.13[0.02–0.23], p = 0.026, N = 103) and CT‐based quantification (β = 1.02[0.39–1.65], p = 0.002, N = 45). Mean desaturation was also associated with both radiological assessment. Elevated 4C‐scores (≥high‐risk category) had a weaker association with adverse outcomes (OR = 2.44[0.62–9.56]). An elevated breath‐holding prediction score is associated with almost five‐fold increased adverse COVID‐19 outcome risk, and with pulmonary deficits observed in chest imaging. Breath‐holding may identify COVID‐19 patients at risk of future respiratory failure. An elevated breath‐holding‐based prediction score was associated with increased COVID‐19 incident adverse outcome risk in a validation cohort of 110 hospitalized COVID‐19 patients. The prediction score was also positively associated with increasing radiological severity, per chest x‐ray and computed tomography (CT) assessment. Our prediction score performed better than the previously‐validated, biomarker‐based 4C‐score.
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Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated, which results in a cytokine storm at the late stage of COVID-19. Autophagy regulation is involved in the infection and replication of SARS-CoV-2 at the early stage and the inhibition of NLRP3 inflammasome-mediated lung inflammation at the late stage of COVID-19. Here, we discuss the autophagy regulation at different stages of COVID-19. Specifically, we highlighted the therapeutic potential of autophagy activators in COVID-19 by inhibiting the NLRP3 inflammasome, thereby avoiding the cytokine storm. We hope this review provides enlightenment for the use of autophagy activators targeting the inhibition of the NLRP3 inflammasome, specifically the combinational therapy of autophagy modulators with the inhibitors of the NLRP3 inflammasome, antiviral drugs, or anti-inflammatory drugs in the fight against COVID-19.
Article
Introduction The COVID-19 pandemic has emerged as a global health problem, associated with high morbidity and mortality rates. The aim of this study was to compare the outcomes of hospitalized patients with COVID-19 or with seasonal influenza in a teaching hospital in Belgium. Methods In this retrospective, single-center cohort study, 1384 patients with COVID-19 and 226 patients with influenza were matched using a propensity score with a ratio of 3:1. Primary outcomes included admission to intensive care unit (ICU), intubation rates, hospital length of stay, readmissions within 30 days and in-hospital mortality. Secondary outcomes included pulmonary bacterial superinfection, cardiovascular complications and ECMO. Results Based on the analysis of the matched sample, patients with influenza had an increased risk of readmission within 30 days (Risk Difference (RD): 0.07, 95% CI: 0.03 to 0.11) and admission to intensive care unit (RD: 0.09, 95% CI: 0.03 to 0.15) compared with those with COVID-19. Patients with influenza had also more pulmonary bacterial superinfections (46.2% vs 7.4%) and more cardiovascular complications (32% vs 3.9%) than patients with COVID-19.However, a two-fold increased risk of mortality (RD: −0.10, 95% CI: 0.15 to −0.05) was observed in COVID-19 compared to influenza. ECMO was also more required among the COVID-19 patients who died than among influenza patients (5% vs 0%). Conclusions COVID-19 is associated with a higher in-hospital mortality compared to influenza infection, despite a high rate of ICU admission in the influenza group. These findings highlighted that the severity of hospitalized patients with influenza should not be underestimated.
Article
Severe COVID-19 is associated with the dynamic changes in coagulation parameters. Coagulopathy is considered as a major extra-pulmonary risk factor for severity and mortality of COVID-19; patients with elevated levels of coagulation biomarkers have poorer in-hospital outcomes. Oxidative stress, alterations in the activity of cytochrome P450 enzymes, development of the cytokine storm and inflammation, endothelial dysfunction, angiotensin-converting enzyme 2 (ACE2) enzyme malfunction and renin–angiotensin system (RAS) imbalance are among other mechanisms suggested to be involved in the coagulopathy induced by severe acute respiratory syndrome coronavirus (SARS-CoV-2). The activity and function of coagulation factors are reported to have a circadian component. Melatonin, a multipotential neurohormone secreted by the pineal gland exclusively at night, regulates the cytokine system and the coagulation cascade in infections such as those caused by coronaviruses. Herein, we review the mechanisms and beneficial effects of melatonin against coagulopathy induced by SARS-CoV-2 infection.
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The COVID-19 pandemic ushered in a bereavement crisis unparalleled in a generation, with devastating consequences for the mental health of those who lost a loved one to the virus. Using national survey data ( n = 2,000) containing detailed information about people’s experiences of pandemic-related stressors, coping resources, and mental health, in this study we examine whether and how three psychosocial coping resources—mastery, self-esteem, and social support—moderate the association between COVID-19 bereavement and psychological distress. We find that coping resources have both expected and unanticipated effects on the relationship between bereavement and mental health. Consistent with the stress process model, higher levels of mastery uniformly reduce the damaging effects of bereavement on depressive symptoms and anger, whereas self-esteem mitigates the positive association between losing a close tie to the virus and reports of anger. Contrary to the stress-buffering hypothesis, however, higher levels of perceived support exacerbate the positive associations between bereavement and each indicator of psychological distress. Our findings suggest that the putatively advantageous aspects of social support may be compromised, or even reversed, in the context of constrained social engagement. We discuss the theoretical implications of these findings for sociological research on the stress process.
Article
While coronavirus disease 2019 (COVID-19) begins as a respiratory infection, it progresses as a systemic disease involving multiorgan microthromboses that underly the pathology. SARS-CoV-2 enters host cells via attachment to the angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is widely expressed in a multitude of tissues, including the lung (alveolar cells), heart, intestine, kidney, testis, gallbladder, vasculature (endothelial cells), and immune cells. Interference in ACE2 signaling could drive the aforementioned systemic pathologies, such as endothelial dysfunction, microthromboses, and systemic inflammation, that are typically seen in patients with severe COVID-19. ACE2 is a component of the renin-angiotensin system (RAS) and is intimately associated with the plasma kallikrein-kinin system (KKS). As many papers are published on the role of ACE and ACE2 in COVID-19, we will review the role of bradykinin, and more broadly the KSS, in SARS-CoV-2-induced vascular dysfunction. Furthermore, we will discuss the possible therapeutic interventions that are approved and in development for the following targets: coagulation factor XII (FXII), tissue kallikrein (KLK1), plasma kallikrein (KLKB1), bradykinin (BK), plasminogen activator inhibitor (PAI-1), bradykinin B1 receptor (BKB1R), bradykinin B2 receptor (BKB2R), ACE, furin, and the NLRP3 inflammasome. Understanding these targets may prove of value in the treatment of COVID-19 as well as in other virus-induced coagulopathies in the future.
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Abstract: It is need to understand and manage the the Workforce Diversity of Gender professionals The issue women gender diversity is common in most parts of the Hospitality Industry. This regularly comes when women are employee part of today’s workforce.As they are the backbone of country economy. A total 38 men and women food production professional participated in this exploratory research. There are several hypothesis related to age, gender, profession tested with ANNOVA and Z test by using SPPS. Result of the study indicates that gender pay and gender bias is a big issue for many people in the workplace. Regardless of similar issue laws and other laws that have been created to address these issues, Women are still far behind men in pay. Although not all causes of gender pay gaps can be changed, resolutions should be evaluated.
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This study investigates how ageism is displayed among Japanese women in their mid-twenties when they talk about their experiences with COVID-19. Ageism, which is discrimination, stereotypes and prejudice based on people’s age, was reinforced by the outbreak of the disease. This study gathered data through virtual conversations recorded during the second wave of COVID-19 cases that hit Japan in August 2020. The conversation is examined using discourse analysis, focusing on how the participants position themselves and others through the narration of their personal experience. The analysis shows how participants co-construct the image of elderly people as others who are vulnerable to the virus but ignorant of their own risks. This image is created as the participants establish rapport-oriented interactions with friends that they align with as young and healthy citizens who are responsible for preventing the spread of the virus.
Article
Background: Enlargement of the pulmonary artery (PA) could be helpful in risk stratification by the chest CT on the admission of COVID-19 patients. Methods: This study aimed to associate PA diameter and overall mortality in COVID-19 pneumonia. We designed a retrospective study between January 2021 and May 2021 in tertiary-level hospitals in Gebze, Turkey. Subjects were evaluated in two groups according to their survivor status (survivors and non-survivors). Then biochemical, demographic, and clinical values were compared via the groups to define the predictive value of PA diameter on chest CT images. Results: In the enrolled 594 COVID-19 in-hospital patients (median age was 45 (34-58) years, 263patients (44.3%) were female. 44 patients (7.4%) died during hospitalization. Multivariate Cox-proportion regression model yielded main PA ≥ 29 mm on admission showed that as independent predictors of death (long rank <0.001, median survival time 28 days). Cumulative survival rates were MPAD ≥ 29 mm 45% and < 29 mm 90% yielded (p < 0.001) Conclusions: PA dilatation is strongly linked with in-hospital mortality in hospitalized patients with COVID-19 infection. Thus increased PA diameter on chest CT at admission may guide rapid and early diagnosis of high-risk patients.
Article
Background Pneumothorax has been increasingly observed among patients with coronavirus disease-2019 (COVID-19) pneumonia, specifically in those patients who develop acute respiratory distress syndrome (ARDS). In this study, we sought to determine the incidence and potential risk factors of pneumothorax in critically ill adults with COVID-19. Method This retrospective cohort study included adult patients with laboratory-confirmed SARS-CoV-2 infection admitted to one of the adult intensive care units of a tertiary, academic teaching hospital from May 2020 through May 2021. Results Among 334 COVID-19 cases requiring ICU admission, the incidence of pneumothorax was 10% (33 patients). Patients who experienced pneumothorax more frequently required vasopressor support (28/33 [84%] vs. 191/301 [63%] P = 0.04), were more likely to be proned (25/33 [75%] vs. 111/301 [36%], P<0.001), and the presence of pneumothorax was associated with prolonged duration of mechanical ventilation; 21 (1–97) versus 7 (1–79) days, p<0.001 as well as prolonged hospital length of stay (29 [9–133] vs. 15 [1–90] days, P<0.001), but mortality was not significantly different between groups. Importantly, when we performed a Cox proportional hazard ratio (HR) model of multivariate parameters, we found that administration of tocilizumab significantly increased the risk of developing pneumothorax (HR = 10.7; CI [3.6–32], P<0.001). Conclusion Among 334 critically ill patients with COVID-19, the incidence of pneumothorax was 10%. Presence of pneumothorax was associated with prolonged duration of mechanical ventilation and length of hospital stay. Strikingly, receipt of tocilizumab was associated with an increased risk of developing pneumothorax.
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COVID-19-associated coagulopathy (CAC) is a life-threatening complication of SARS-CoV-2 infection. However, the underlying cellular and molecular mechanisms driving this condition are unclear. Evidence supports the concept that CAC involves complex interactions between the innate immune response, the coagulation and fibrinolytic pathways, and the vascular endothelium, resulting in a procoagulant condition. Understanding of the pathogenesis of this condition at the genomic, molecular and cellular levels is needed in order to mitigate thrombosis formation in at-risk patients. In this Perspective, we categorize our current understanding of CAC into three main pathological mechanisms: first, vascular endothelial cell dysfunction; second, a hyper-inflammatory immune response; and last, hypercoagulability. Furthermore, we pose key questions and identify research gaps that need to be addressed to better understand CAC, facilitate improved diagnostics and aid in therapeutic development. Finally, we consider the suitability of different animal models to study CAC. Here, the authors consider our emerging understanding of COVID-19-associated coagulopathy. They focus on the complex interactions between innate immune, coagulation and fibrinolytic pathways that can lead to potentially life-threatening thrombosis following SARS-CoV-2 infection.
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Abstract Introduction COVID-19 is a global pandemic caused by the SARS-CoV-2 virus. Although most COVID-19 cases are asymptomatic or mild, a significant number of patients experienced adverse outcomes. In addition, studies have shown that cardiac abnormalities are associated with increased mortality in hospitalised patients with COVID-19. This finding sets a precedent for the potential use of ECG tracing as an indicator of patient mortality and morbidity. This study aims to determine associations between the 12-lead ECG findings and various clinical outcomes of hospitalised patients with COVID-19, measured as incidence of endotracheal intubation, intensive care unit (ICU) admission and mortality rate. Methods and analysis An electronic literature search will identify all potentially relevant articles using specific databases and websites. The search will be limited to studies published from December 2019 to May 2021. In addition, studies will include hospitalised patients with COVID-19 with normal and abnormal 12-lead ECG findings assessed for clinical outcomes, including the incidence of endotracheal intubation, ICU admission and mortality rate. The risk of bias in individual studies will be evaluated using the Quality in Prognostic Studies tool or the Cochrane risk of bias tool. A meta-analysis will be conducted if at least two studies indicate a prognostic factor’s effect. Moreover, subgroup and sensitivity analyses will be performed accordingly to address heterogeneity. Reporting the review results will comply with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. The quality of evidence generated will be assessed using the Grades of Recommendation, Assessment, Development and Evaluation system. Ethics and dissemination This study has been exempted from ethics review. There will be no patient or public involvement in this study. Furthermore, the findings will be disseminated via conferences, seminars, symposia and congresses on top of peer-reviewed journals. PROSPERO registration number CRD42021257155.
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The influenza vaccine is less effective in older adults compared to their younger counterparts. At the same time, this population is more susceptible to contracting influenza, with more severe consequences, including higher rates of complications, hospitalisations, and deaths. There is an abundance of evidence demonstrating how psychological factors, such as stress, can influence and modulate immune function, including response to vaccinations. Recent work has extended this to other psychological factors, suggesting that mood, or affect, may also be linked to vaccine response, however the evidence here is much more limited. This thesis presents three inter-related pieces of research, which sought to build on this evidence base and contribute to our current understanding of the influence of mood on vaccinations. The ultimate aim of this research was to develop an intervention to enhance positive mood, with a view to enhancing the effectiveness of the influenza vaccination in the older adult population. First, the evidence surrounding the effectiveness of using participant-driven choice in interventions compared to ‘no-choice’ interventions was systematically reviewed. This review sought to investigate whether the integration of participant choice within an existing, previously trialled, positive mood intervention would maximise mood enhancement and thus the potential to enhance vaccine-specific antibody levels. The review found that whilst choice-interventions led to less drop-out and greater adherence, evidence for mood-related outcomes was unclear and warranted further investigation. Second, a randomised controlled clinical study (n=654) was conducted to investigate the effectiveness of the previously trialled fixed-content positive mood intervention, a new choice-based intervention, and usual care, in terms of enhancing positive mood. Vaccine response at four-weeks post-vaccination was assessed as a secondary outcome. Results showed that both the fixed-content and choice-based interventions significantly improved mood compared to usual care, however there were no significant differences between the two interventions. There were no significant differences between groups in terms of antibody levels at four weeks post-vaccination. Finally, a qualitative study using a thematic-content hybrid analysis approach was carried out with a selection of participants from the randomised trial, to assess participants’ perceptions of how the intervention may or may not have worked, and to identify ways in which both the intervention and study experience as a whole could be improved for a future trial implementing the optimised intervention. Analysis revealed that both interventions, as well as the overall study experience, were liked by participants, indicating that further optimisation may not be necessary. Additionally, several potential mechanisms underlying the relationship between the interventions and mood were identified. The research presented in this thesis has several important implications. Firstly, that the use of choice should be considered where there is concern regarding drop-out or adherence, but may not be more effective than no-choice interventions in enhancing mood. Secondly, that brief positive mood interventions are effective in enhancing positive mood in older adults in a primary care setting. Future work is required to evaluate their impact on immune outcomes including mechanistic work to understand the relationship between mood and immunity, and a large scale trial, with immune response as the primary outcome.
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Background Widespread respiratory infections with high morbidity rates caused by respiratory viruses represent a significant global public health problem. Our objective was to describe cases and deaths from severe acute respiratory infection (SARI) in Brazil over the past 8 y as well as changes in the distribution and risk of illness and death from SARI before and in the first year of the coronavirus disease 2019 (COVID-19) pandemic (FYP). Methods We performed a descriptive epidemiological study of hospitalized SARI cases and deaths between 2013 and 2020 in Brazil, separated into pre-pandemic (2013 to 2019) and FYP (2020). We estimate the increase in SARI cases and deaths in the FYP as well as the mortality and infection risks attributable to the FYP (MRAP and IRAP, respectively). Results In 2020, an excess of 425 054 cases and 109 682 deaths was observed, with a significant increase in the risk of falling ill and dying from SARI, with an IRAP of 200.06 and an MRAP of 51.68 cases per 100 000 inhabitants. The increase in SARI cases and deaths was particularly prominent among patients with COVID-19, the elderly, males, those self-identifying as mixed race and patients with heart disease and diabetes. We conclude that an important increase in morbidity and mortality due to SARI was observed in the FYP. More vulnerable groups and those living in the Southeast, North and Center-West regions of the country suffered the most.
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The present outbreak of lower respiratory tract infections, including respiratory distress syndrome, is the third spillover, in only two decades, of an animal coronavirus to humans resulting in a major epidemic. Here, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the official classification of viruses and taxa naming (taxonomy) of the Coronaviridae family, assessed the novelty of the human pathogen tentatively named 2019-nCoV. Based on phylogeny, taxonomy and established practice, the CSG formally recognizes this virus as a sister to severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus and designates it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate communication, the CSG further proposes to use the following naming convention for individual isolates: SARS-CoV-2/Isolate/Host/Date/Location. The spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined. The independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying the entire (virus) species to complement research focused on individual pathogenic viruses of immediate significance. This research will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.
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Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 10⁹/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
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Background: The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.).
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Background: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods: All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation: The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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Background: Acute respiratory infections are associated with increased risk of myocardial infarction (MI) and stroke, however, the role of different organisms is poorly characterised. Methods: We undertook a time-series analysis of English hospital admissions for MI and stroke (age-stratified: 45-64, 65-74, 75+ years), laboratory-confirmed viral respiratory infections and environmental data for 2004-2015. Weekly counts of admissions were modelled using multivariable Poisson regression with weekly counts of respiratory viruses (influenza, parainfluenza, rhinovirus, respiratory syncytial virus (RSV), adenovirus or human meta-pneumovirus (HMPV)) investigated as predictors. We controlled for seasonality, long-term trends and environmental factors. Results: Weekly hospital admissions in adults aged 45+ years averaged 1347 (IQR 1217-1541) for MI and 1175 (IQR 1023-1395) for stroke. Median numbers of respiratory infections ranged from 11 cases per week (IQR 5-53) for influenza to 55 (IQR 7-127) for rhinovirus. In the adjusted models, all viruses except parainfluenza were significantly associated with MI and ischaemic stroke admissions in those aged 75+. Among 65-74 year olds, adenovirus, rhinovirus and RSV were associated with MI but not ischaemic stroke admissions. Respiratory infections were not associated with MI or ischaemic stroke in people aged 45-64, nor with haemorrhagic stroke in any age group. An estimated 0.4-5.7% of MI and ischaemic stroke admissions may be attributable to respiratory infection, with greater excess burden during weeks with high circulating virus levels. Conclusions: We identified small but strongly significant associations in the timing of respiratory infection (with HMPV, RSV, influenza, rhinovirus and adenovirus) and MI or ischaemic stroke hospitalisations in the elderly. Registered at clinicaltrials.gov: NCT02984280.
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Middle East respiratory syndrome coronavirus continues to circulate in the Middle East. During a recent outbreak in Korea, changes in MERS coronavirus viral load were determined during the course of illness in 17 patients.
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It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.
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Background: The MERS coronavirus causes isolated cases and outbreaks of severe respiratory disease. Essential features of the natural history of disease are poorly understood. Methods: We studied 37 adult patients infected with MERS-CoV for viral load in the lower and upper respiratory tract (LRT and URT), blood, stool, and urine. Antibodies and serum neutralizing activities were determined over the course of disease. Results: 199 LRT samples collected during the 3 weeks following diagnosis yielded virus RNA in 93% of tests. Average (maximum) viral loads were 5x10(6) (6x10(10)) copies per mL. Viral loads (positive detection frequencies) in 84 URT samples were 1.9x10(4) cop/mL (47.6%). 33% of all 108 sera tested yielded viral RNA. Only 14.6% of stool and 2.4% of urine samples yielded viral RNA. All seroconversions occurred during the first 2 weeks after diagnosis, which corresponds to the 2nd and 3rd week after symptoms onset. IgM detection provided no advantage in sensitivity over IgG detection. All surviving patients, but only slightly more than half of all fatal cases, produced IgG and neutralizing antibodies. The levels of IgG and neutralizing antibodies were weakly and inversely correlated with LRT viral loads. Presence of antibodies did not lead to the elimination of virus from LRT. Conclusions: The timing and intensity of respiratory viral shedding in MERS patients closely matches that of Severe Acute Respiratory Syndrome (SARS) patients. Blood viral RNA does not seem to be infectious. Extra-pulmonary loci of virus replication seem possible. Neutralizing antibodies do not suffice to clear the infection.
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The renin-angiotensin system (RAS) is a key component of cardiovascular physiology and homeostasis due to its influence on the regulation of electrolyte balance, blood pressure, vascular tone and cardiovascular remodeling. Deregulation of this system contributes significantly to the pathophysiology of cardiovascular and renal diseases. Numerous studies have generated new perspectives about a noncanonical and protective RAS pathway that counteracts the proliferative and hypertensive effects of the classical angiotensin-converting enzyme (ACE)/angiotensin (Ang) II/angiotensin type 1 receptor (AT1R) axis. The key components of this pathway are ACE2 and its products, Ang-(1-7) and Ang-(1-9). These two vasoactive peptides act through the Mas receptor (MasR) and AT2R, respectively. The ACE2/Ang-(1-7)/MasR and ACE2/Ang-(1-9)/AT2R axes have opposite effects to those of the ACE/Ang II/AT1R axis, such as decreased proliferation and cardiovascular remodeling, increased production of nitric oxide and vasodilation. A novel peptide from the noncanonical pathway, alamandine, was recently identified in rats, mice and humans. This heptapeptide is generated by catalytic action of ACE2 on Ang A or through a decarboxylation reaction on Ang-(1-7). Alamandine produces the same effects as Ang-(1-7), such as vasodilation and prevention of fibrosis, by interacting with Mas-related GPCR, member D (MrgD). In this article, we review the key roles of ACE2 and the vasoactive peptides Ang-(1-7), Ang-(1-9) and alamandine as counter-regulators of the ACE-Ang II axis as well as the biological properties that allow them to regulate blood pressure and cardiovascular and renal remodeling. © The Author(s), 2015.
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Among nontraditional cardiovascular risk factors, recent influenzalike infection is associated with fatal and nonfatal atherothrombotic events. To determine if influenza vaccination is associated with prevention of cardiovascular events. A systematic review and meta-analysis of MEDLINE (1946-August 2013), EMBASE (1947-August 2013), and the Cochrane Library Central Register of Controlled Trials (inception-August 2013) for randomized clinical trials (RCTs) comparing influenza vaccine vs placebo or control in patients at high risk of cardiovascular disease, reporting cardiovascular outcomes either as efficacy or safety events. Two investigators extracted data independently on trial design, baseline characteristics, outcomes, and safety events from published manuscripts and unpublished supplemental data. High-quality studies were considered those that described an appropriate method of randomization, allocation concealment, blinding, and completeness of follow-up. Random-effects Mantel-Haenszel risk ratios (RRs) and 95% CIs were derived for composite cardiovascular events, cardiovascular mortality, all-cause mortality, and individual cardiovascular events. Analyses were stratified by subgroups of patients with and without a history of acute coronary syndrome (ACS) within 1 year of randomization. Five published and 1 unpublished randomized clinical trials of 6735 patients (mean age, 67 years; 51.3% women; 36.2% with a cardiac history; mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%; RR, 0.64 [95% CI, 0.48-0.86], P = .003) in published trials. A treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32-0.63]) and without (RR, 0.94 [95% CI, 0.55-1.61]) recent ACS (P for interaction = .02). Results were similar with the addition of unpublished data. In a meta-analysis of RCTs, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events. The greatest treatment effect was seen among the highest-risk patients with more active coronary disease. A large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular end points.
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The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-kappaB as central player, whereas expression of type I interferon (IFN)-beta is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.
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Coagulation abnormalities are common in severe pneumonia and sepsis, yet little is known about the presence of coagulopathy or its significance in patients with lesser illness severity. We examined coagulation abnormalities in 939 subjects hospitalized with community-acquired pneumonia (CAP) in 28 US hospitals, hypothesizing that abnormalities would increase with illness severity and poor outcomes. We measured plasma coagulation markers (D-dimer, plasminogen activator inhibitor [PAI], antithrombin, factor IX, and thrombin-antithrombin complex [TAT]) at the time of patient presentation to the emergency department and daily during the first wk of hospitalization. Day-1 clinical laboratory test results for international normalized ratio, activated partial thromboplastin time, and platelet count were recorded from the medical record. In our cohort, 32.5% of patients developed severe sepsis and 11.1% died by d 90. Day-1 coagulation abnormalities were common, especially for D-dimer (80.6%) and TAT (36.0%), and increased with illness severity and poor outcomes. However, abnormalities also occurred in those patients who never developed organ dysfunction and differences between groups were modest. The proportion of patients with abnormalities changed over time, yet the magnitude of change was small and not always in the direction of normality. Many patients remaining in the hospital continued to manifest coagulation abnormalities on d 7, especially for D-dimer (86.5%) and TAT (36.9%). In conclusion, coagulation abnormalities were common and persistent in CAP patients, even among the least ill. These findings underscore the complexity of the coagulation response to infection and may offer insights into coagulation-based therapeutics in clinical sepsis trials.
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Severe acute respiratory syndrome (SARS) was diagnosed in Hong Kong in over 1700 patients between March and early June 2003. 115 patients diagnosed with SARS were admitted to Queen Elizabeth Hospital, a large regional hospital in Hong Kong, from March 2003, of whom 100 were either discharged or were dead at 31 May. The patients were prospectively studied after admission to assess their short term outcomes and the risk factors associated with adverse outcomes, defined as death or the need for mechanical ventilation At the time of writing 18 patients had died, with a crude mortality rate of 15.7% and a 21 day mortality of 10% (standard error 3%). Thirty nine patients (34%) were admitted to the intensive care unit, 30 of whom (26%) required mechanical ventilation. Multivariate analysis showed that age above 60 (hazards ratio (HR) 3.5, 95% CI 1.2 to 10.2; p=0.02), presence of diabetes mellitus or heart disease (HR 9.1, 95% CI 2.8 to 29.1; p<0.001), and the presence of other comorbid conditions (HR 5.2, 95% CI 1.4 to 19.7; p=0.01) were independently associated with mortality. However, only the presence of diabetes mellitus and/or cardiac disease (HR 7.3, 95% CI 3.1 to 17.4; p<0.001) was associated with adverse outcomes as a whole. SARS is a new disease entity that carries significant morbidity and mortality. Specific clinical and laboratory parameters predicting unfavourable outcomes have been identified.
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Prominent among the numerous events that contribute to the enhanced susceptibility of elderly patients to infection is the decline of immune function that accompanies aging. Elderly patients experience a marked decline in cell-mediated immune function and reduced humoral immune function. Age-dependent defects in T and B cell function are readily demonstrable in elderly patients, yet the essential elements of innate immunity are remarkably well preserved. The cytokine and chemokine signaling networks are altered in elderly patients and tends to favor a type 2 cytokine response over type 1 cytokine responses. The induction of proinflammatory cytokines after septic stimuli is not adequately controlled by anti-inflammatory mechanisms in elderly persons. This immune dysregulation is accompanied by a more pronounced procoagulant state in older patients. These molecular events function in concert to render elderly patients at excess risk for mortality from severe sepsis and septic shock.
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Background: An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings: Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3-11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation: The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1-2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding: None.
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
Although broad knowledge of influenza viral pneumonia has been established, the significance of non-influenza respiratory viruses in community-acquired pneumonia (CAP) and their impact on clinical outcomes remains unclear, especially in the non-immunocompromised adult population. Hospitalised immunocompetent patients with CAP were prospectively recruited from 34 hospitals in mainland China. Respiratory viruses were detected by molecular methods. Comparisons were conducted between influenza and non-influenza viral infection groups. In total, 915 out of 2336 adult patients with viral infection were enrolled in the analysis, with influenza virus (28.4%) the most frequently detected virus, followed by respiratory syncytial virus (3.6%), adenovirus (3.3%), human coronavirus (3.0%), parainfluenza virus (2.2%), human rhinovirus (1.8%) and human metapneumovirus (1.5%). Non-influenza viral infections accounted for 27.4% of viral pneumonia. Consolidation was more frequently observed in patients with adenovirus infection. The occurrence of complications such as sepsis (40.1% versus 39.6%; p=0.890) and hypoxaemia (40.1% versus 37.2%; p=0.449) during hospitalisation in the influenza viral infection group did not differ from that of the non-influenza viral infection group. Compared with influenza virus infection, the multivariable adjusted odds ratios of CURB-65 (confusion, urea >7 mmol·L ⁻¹ , respiratory rate ≥30 breaths·min ⁻¹ , blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years) ≥3, arterial oxygen tension/inspiratory oxygen fraction <200 mmHg, and occurrence of sepsis and hypoxaemia for non-influenza respiratory virus infection were 0.87 (95% CI 0.26–2.84), 0.72 (95% CI 0.26–1.98), 1.00 (95% CI 0.63–1.58) and 1.05 (95% CI 0.66–1.65), respectively. The hazard ratio of 90-day mortality was 0.51 (95% CI 0.13–1.91). The high incidence of complications in non-influenza viral pneumonia and similar impact of non-influenza respiratory viruses relative to influenza virus on disease severity and outcomes suggest more attention should be given to CAP caused by non-influenza respiratory viruses.
Article
Background: Data are limited on the impact of neuraminidase inhibitor (NAI) treatment on avian influenza A(H7N9) virus RNA shedding. Methods: In this multicenter, retrospective study, data were collected from adults hospitalized with A(H7N9) infection during 2013-2017 in China. We compared clinical features and A(H7N9) shedding among patients with different NAI doses and combination therapies and evaluated factors associated with A(H7N9) shedding, using Cox proportional hazards regression. Results: Among 478 patients, the median age was 56 years, 71% were male, and 37% died. The median time from illness onset to NAI treatment initiation was 8 days (interquartile range [IQR], 6-10 days), and the median duration of A(H7N9) RNA detection from onset was 15.5 days (IQR, 12-20 days). A(H7N9) RNA shedding was shorter in survivors than in patients who died (P < .001). Corticosteroid administration (hazard ratio [HR], 0.62 [95% confidence interval {CI}, .50-.77]) and delayed NAI treatment (HR, 0.90 [95% CI, .91-.96]) were independent risk factors for prolonged A(H7N9) shedding. There was no significant difference in A(H7N9) shedding duration between NAI combination treatment and monotherapy (P = .65) or between standard-dose and double-dose oseltamivir treatment (P = .70). Conclusions: Corticosteroid therapy and delayed NAI treatment were associated with prolonged A(H7N9) RNA shedding. NAI combination therapy and double-dose oseltamivir treatment were not associated with a reduced A(H7N9) shedding duration as compared to standard-dose oseltamivir.
Article
We evaluated the clinical characteristics, cytokine/chemokine concentrations, viral shedding and antibody kinetics in 30 patients with Middle East respiratory syndrome (MERS), including 6 non-survivors admitted to 3 MERS-designated hospitals. Old age, low albumin, altered mentality and high pneumonia severity index score at admission were risk factors for mortality. In addition, severe signs of inflammation at initial presentation (at hospital days 1-4), such as high inducible protein-10 (p=0.0013), monocyte chemoattractant protein-1 (p=0.0007) and interleukin 6 (p=0.0007) concentrations, and poor viral control (high viral load at hospital days 5–10, p<0.001) without adequate antibody titres (low antibody titre at hospital days 11–16, p=0.07) during the course of disease, were associated with mortality.
Article
The Middle East respiratory syndrome is caused by a coronavirus that was first identified in Saudi Arabia in 2012. Periodic outbreaks continue to occur in the Middle East and elsewhere. This report provides the latest information on MERS.
Article
Importance Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.Objective To evaluate and, as needed, update definitions for sepsis and septic shock.Process A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment).Key Findings From Evidence Synthesis Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant.Recommendations Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.Conclusions and Relevance These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.
Article
Context Evaluation of trends in organ dysfunction in critically ill patients may help predict outcome.Objective To determine the usefulness of repeated measurement the Sequential Organ Failure Assessment (SOFA) score for prediction of mortality in intensive care unit (ICU) patients.Design Prospective, observational cohort study conducted from April 1 to July 31, 1999.Setting A 31-bed medicosurgical ICU at a university hospital in Belgium.Patients Three hundred fifty-two consecutive patients (mean age, 59 years) admitted to the ICU for more than 24 hours for whom the SOFA score was calculated on admission and every 48 hours until discharge.Main Outcome Measures Initial SOFA score (0-24), Δ-SOFA scores (differences between subsequent scores), and the highest and mean SOFA scores obtained during the ICU stay and their correlations with mortality.Results The initial, highest, and mean SOFA scores correlated well with mortality. Initial and highest scores of more than 11 or mean scores of more than 5 corresponded to mortality of more than 80%. The predictive value of the mean score was independent of the length of ICU stay. In univariate analysis, mean and highest SOFA scores had the strongest correlation with mortality, followed by Δ-SOFA and initial SOFA scores. The area under the receiver operating characteristic curve was largest for highest scores (0.90; SE, 0.02; P<.001 vs initial score). When analyzing trends in the SOFA score during the first 96 hours, regardless of the initial score, the mortality rate was at least 50% when the score increased, 27% to 35% when it remained unchanged, and less than 27% when it decreased. Differences in mortality were better predicted in the first 48 hours than in the subsequent 48 hours. There was no significant difference in the length of stay among these groups. Except for initial scores of more than 11 (mortality rate >90%), a decreasing score during the first 48 hours was associated with a mortality rate of less than 6%, while an unchanged or increasing score was associated with a mortality rate of 37% when the initial score was 2 to 7 and 60% when the initial score was 8 to 11.Conclusions Sequential assessment of organ dysfunction during the first few days of ICU admission is a good indicator of prognosis. Both the mean and highest SOFA scores are particularly useful predictors of outcome. Independent of the initial score, an increase in SOFA score during the first 48 hours in the ICU predicts a mortality rate of at least 50%.
Article
Although traditionally regarded as a disease confined to the lungs, acute pneumonia has important effects on the cardiovascular system at all severities of infection. Pneumonia tends to affect individuals who are also at high cardiovascular risk. Results of recent studies show that about a quarter of adults admitted to hospital with pneumonia develop a major acute cardiac complication during their hospital stay, which is associated with a 60% increase in short-term mortality. These findings suggest that outcomes of patients with pneumonia can be improved by prevention of the development and progression of associated cardiac complications. Before this hypothesis can be tested, however, an adequate mechanistic understanding of the cardiovascular changes that occur during pneumonia, and their role in the trigger of various cardiac complications, is needed. In this Review, we summarise knowledge about the burden of cardiac complications in adults with acute pneumonia, the cardiovascular response to this infection, the potential effects of commonly used cardiovascular and anti-infective drugs on these associations, and possible directions for future research.
Article
The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg), moderate (100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm H2O), positive end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P < .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P < .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P < .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning.
Article
Purpose: The aim of the study was to determine whether C-reactive protein (CRP), procalcitonin (PCT), and d-dimer (DD) are markers of mortality in patients admitted to the emergency department (ED) with suspected infection and sepsis. Basic procedures: We conducted a prospective cohort in a university hospital in Medellín, Colombia. Patients were admitted between August 1, 2007, and January 30, 2009. Clinical and demographic data and Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment scores as well as blood samples for CRP, PCT, and DD were collected within the first 24 hours of admission. Survival was determined on day 28 to establish its association with the proposed biomarkers using logistic regression and receiver operating characteristic curves. Main findings: We analyzed 684 patients. The median Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment scores were 10 (interquartile range [IQR], 6-15) and 2 (IQR, 1-4), respectively. The median CRP was 9.6 mg/dL (IQR, 3.5-20.4 mg/dL); PCT, 0.36 ng/mL (IQR, 0.1-3.7 ng/mL); and DD, 1612 ng/mL (IQR, 986-2801 ng/mL). The median DD in survivors was 1475 ng/mL (IQR, 955-2627 ng/mL) vs 2489 ng/mL (IQR, 1698-4573 ng/mL) in nonsurvivors (P=.0001). The discriminatory ability showed area under the curve-receiver operating characteristic for DD, 0.68; CRP, 0.55; and PCT, 0.59. After multivariate analysis, the only biomarker with a linear relation with mortality was DD, with an odds ratio of 2.07 (95% confidence interval, 0.93-4.62) for values more than 1180 and less than 2409 ng/mL and an odds ratio of 3.03 (95% confidence interval, 1.38-6.62) for values more than 2409 ng/mL. Principal conclusions: Our results suggest that high levels of DD are associated with 28-day mortality in patients with infection or sepsis identified in the emergency department.
Article
Community-acquired pneumonia (CAP) affects >5 million adults each year in the United States. Although incident cardiac complications occur in patients with community-acquired pneumonia, their incidence, timing, risk factors, and associations with short-term mortality are not well understood. A total of 1343 inpatients and 944 outpatients with community-acquired pneumonia were followed up prospectively for 30 days after presentation. Incident cardiac complications (new or worsening heart failure, new or worsening arrhythmias, or myocardial infarction) were diagnosed in 358 inpatients (26.7%) and 20 outpatients (2.1%). Although most events (89.1% in inpatients, 75% in outpatients) were diagnosed within the first week, more than half of them were recognized in the first 24 hours. Factors associated with their diagnosis included older age (odds ratio [OR]=1.03; 95% confidence interval [CI], 1.02-1.04), nursing home residence (OR, 1.8; 95% CI, 1.2-2.9), history of heart failure (OR, 4.3; 95% CI, 3.0-6.3), prior cardiac arrhythmias (OR, 1.8; 95% CI, 1.2-2.7), previously diagnosed coronary artery disease (OR, 1.5; 95% CI, 1.04-2.0), arterial hypertension (OR, 1.5; 95% CI, 1.1-2.1), respiratory rate ≥30 breaths per minute (OR, 1.6; 95% CI, 1.1-2.3), blood pH <7.35 (OR, 3.2; 95% CI, 1.8-5.7), blood urea nitrogen ≥30 mg/dL (OR, 1.5; 95% CI, 1.1-2.2), serum sodium <130 mmol/L (OR, 1.8; 95% CI, 1.02-3.1), hematocrit <30% (OR, 2.0; 95% CI, 1.3-3.2), pleural effusion on presenting chest x-ray (OR, 1.6; 95% CI, 1.1-2.4), and inpatient care (OR, 4.8; 95% CI, 2.8-8.3). Incident cardiac complications were associated with increased risk of death at 30 days after adjustment for baseline Pneumonia Severity Index score (OR, 1.6; 95% CI, 1.04-2.5). Incident cardiac complications are common in patients with community-acquired pneumonia and are associated with increased short-term mortality. Older age, nursing home residence, preexisting cardiovascular disease, and pneumonia severity are associated with their occurrence. Further studies are required to test risk stratification and prevention and treatment strategies for cardiac complications in this population.
Article
Angiotensin-converting enzyme 2 (ACE2) preferentially forms angiotensin-(1-7) [ANG-(1-7)] from ANG II. We showed that cardiac ACE2 is elevated following treatment of coronary artery-ligated rats with AT1 receptor blockers (ARBs). Cardiac myocytes and fibroblasts were isolated from neonatal rats to determine the molecular mechanisms for the ACE2 upregulation by ARB treatment. ANG II significantly reduced ACE2 activity and downregulated ACE2 mRNA in cardiac myocytes, effects blocked by the ARB losartan, indicating that ANG II regulates ACE2. ANG II also reduced ACE2 mRNA in cardiac fibroblasts; however, no enzyme activity was detected, reflecting the limited expression of ACE2 in these cells. Endothelin-1 (ET-1) also significantly reduced myocyte ACE2 mRNA. The reduction in ACE2 mRNA by ANG II or ET-1 was blocked by inhibitors of mitogen-activated protein kinase kinase 1, suggesting that ANG II or ET-1 activates extracellular signal-regulated kinase (ERK) 1/ERK2 to reduce ACE2. Although ACE2 mRNA was not affected by ANG-(1-7), both the ANG II- and ET-1-mediated reductions in ACE2 mRNA were blocked by the heptapeptide. The ANG-(1-7) modulatory effect was prevented by the ANG-(1-7) receptor antagonist [D-Ala7]-ANG-(1-7), indicating that the ANG-(1-7) response was mediated by a specific AT(1-7) receptor. Myocyte treatment with atrial natriuretic peptide (ANP) also reversed the ACE2 mRNA downregulation by ANG II or ET-1, whereas treatment with ANP alone was ineffective. These results indicate that multiple hypertrophic and anti-hypertropic peptides regulate ACE2 production in myocytes, suggesting that ACE2 expression in the heart is dependent upon the compliment and concentration of regulatory molecules.
Article
Severe acute respiratory syndrome (SARS) has become a global public health emergency. To evaluate the characteristics and outcomes of patients with SARS in Hong Kong and to identify predictors of mortality. Retrospective cohort study. Quarantine hospital for patients with SARS in Hong Kong. 267 consecutive patients hospitalized from 26 February to 31 March 2003 for probable or confirmed SARS. Clinical, laboratory, and radiographic measures; 3-month mortality rate. According to our case definition, there were 227 cases of confirmed SARS and 40 cases of probable SARS. Common presenting symptoms were fever (99% of patients), chills (74%), malaise (63%), and myalgia (50%). Laboratory findings included lymphopenia (73%), thrombocytopenia (50%), hyponatremia (60%), and elevated levels of lactate dehydrogenase (47%) and C-reactive protein (75%). During hospitalization, incidence of diarrhea (53%), anemia (53%), and acute renal failure (6%) increased. Sixty-nine patients (26%) required intensive care because of respiratory failure. The 3-month mortality rate was 12% (95% CI, 8% to 16%). Factors contributing to mortality were respiratory failure, acute renal failure, and nosocomial sepsis. On multivariate Cox regression, age older than 60 years (relative risk, 5.10 [CI, 2.30 to 11.31]; P < 0.001) and lactate dehydrogenase level greater than 3.8 micro kat/L at presentation (relative risk, 2.20 [CI, 1.03 to 4.71]; P = 0.04) were independent predictors of mortality. Because of the longer follow-up period in our cohort, the mortality rate in these patients is higher than rates reported in previous studies. Advanced age and high lactate dehydrogenase level at presentation predict mortality. *For members of the Princess Margaret Hospital SARS Study Group, see the Appendix.
Article
There is evidence that chronic inflammation may promote atherosclerotic disease. We tested the hypothesis that acute infection and vaccination increase the short-term risk of vascular events. We undertook within-person comparisons, using the case-series method, to study the risks of myocardial infarction and stroke after common vaccinations and naturally occurring infections. The study was based on the United Kingdom General Practice Research Database, which contains computerized medical records of more than 5 million patients. A total of 20,486 persons with a first myocardial infarction and 19,063 persons with a first stroke who received influenza vaccine were included in the analysis. There was no increase in the risk of myocardial infarction or stroke in the period after influenza, tetanus, or pneumococcal vaccination. However, the risks of both events were substantially higher after a diagnosis of systemic respiratory tract infection and were highest during the first three days (incidence ratio for myocardial infarction, 4.95; 95 percent confidence interval, 4.43 to 5.53; incidence ratio for stroke, 3.19; 95 percent confidence interval, 2.81 to 3.62). The risks then gradually fell during the following weeks. The risks were raised significantly but to a lesser degree after a diagnosis of urinary tract infection. The findings for recurrent myocardial infarctions and stroke were similar to those for first events. Our findings provide support for the concept that acute infections are associated with a transient increase in the risk of vascular events. By contrast, influenza, tetanus, and pneumococcal vaccinations do not produce a detectable increase in the risk of vascular events.
Article
In order to further the present knowledge of the emerging severe acute respiratory syndrome-associated coronavirus (SARS-CoV), 486 different specimens from 54 patients with a clinical diagnosis of SARS were investigated for the presence of viral RNA, and 314 plasma specimens of 73 patients were examined for IgM and IgG antibodies specific against SARS-CoV using an indirect ELISA. Viral RNA was detectable in 28 of the 54 patients tested. Cumulative data showed that 67 of the 73 SARS patients demonstrated seroconversion by week 5 of illness. In contrast, only 1 of 278 healthy subjects enrolled in the study was found to be positive for the IgG antibody. Coexistence of viral RNA in plasma and specific antibodies was simultaneously observed over three consecutive weeks in two critical cases. In three convalescent patients in particular, cultivable SARS-CoV was detected in stool or urine specimens for longer than 4 weeks (29-36 days). These findings suggest that SARS-CoV may remain viable in the excretions of convalescent patients.
Article
Severe community-acquired pneumonia (CAP) requiring admission to an intensive care unit (ICU) has been inadequately studied. We compared characteristics and outcomes of patients with CAP who were admitted to the ICU with those of patients managed on the ward. Of the 3675 patients hospitalized with CAP, 374 (10%) were admitted to the ICU. The main reason for ICU admission was respiratory failure requiring intubation and ventilation (n = 303, 81%), although this indication decreased with increasing age (p < 0.05 for trend). Most patients (62%) required mechanical ventilation for 3 days or less. The following factors were predictive of ICU admission on multivariable analysis: younger age, smoker, limitation of functional status, absence of cough or pleurisy, presence of chronic obstructive pulmonary disease, substance abuse, elevated serum creatinine, abnormal serum glucose concentration, and a respiratory rate of <16 or >24 breaths per minute. Patients with low Pneumonia Severity Index scores and low CURB-65 scores were admitted to the ICU based on clinical judgment that appeared to supersede objective scoring. Severe CAP requiring admission to the ICU is common, and the decision about which patients to admit often requires clinical judgment that in many cases appears at odds with various validated pneumonia severity scoring systems.
Pathological findings of COVID-19 associated with acute respiratory distress syndrome
  • Z Xu
  • L Shi
  • Y Wang
Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; published online Feb 18. https://doi.org/10.1016/ S2213-2600(20)30076-X.