scholarly journals Inter-individual Variation in Receptor Expression Influences MERS-CoV Infection and Immune Responses in Airway Epithelia

2022 ◽  
Vol 9 ◽  
Author(s):  
Kun Li ◽  
Christine Wohlford-Lenane ◽  
Jennifer A. Bartlett ◽  
Paul B. McCray

Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory infection in humans, with symptom severity that ranges from asymptomatic to severe pneumonia. Known risk factors for severe MERS include male sex, older age, and the presence of various comorbidities. MERS-CoV gains entry into cells by binding its receptor, dipeptidyl peptidase 4 (DPP4), on the surface of airway epithelia. We hypothesized that expression of this receptor might be an additional determinant of outcomes in different individuals during MERS-CoV infection. To learn more about the role of DPP4 in facilitating MERS-CoV infection and spread, we used ELISA and immunofluorescent staining to characterize DPP4 expression in well-differentiated primary human airway epithelia (HAE). We noted wide inter-individual variation in DPP4 abundance, varying by as much as 1000-fold between HAE donors. This variability appears to influence multiple aspects of MERS-CoV infection and pathogenesis, with greater DPP4 abundance correlating with early, robust virus replication and increased cell sloughing. We also observed increased induction of interferon and some interferon-stimulated genes in response to MERS-CoV infection in epithelia with the greatest DPP4 abundance. Overall, our results indicate that inter-individual differences in DPP4 abundance are one host factor contributing to MERS-CoV replication and host defense responses, and highlight how HAE may serve as a useful model for identifying risk factors associated with heightened susceptibility to serious respiratory pathogens.

Author(s):  
Pierre Danneels ◽  
Maria Concetta Postorino ◽  
Alessio Strazzulla ◽  
Nabil Belfeki ◽  
Aurelia Pitch ◽  
...  

Introduction. Treatment of Haemophilus influenzae (Hi) pneumonia is on concern because resistance to amoxicillin is largely diffused. This study describes the evolution of resistance to amoxicillin and amoxicillin/clavulanic acid (AMC) in Hi isolates and characteristics of patients with Hi severe pneumonia. Methods. A monocentric retrospective observational study including patients from 2008 to 2017 with severe pneumonia hospitalized in ICU. Evolution of amoxicillin and AMC susceptibility was showed. Characteristics of patients with Hi pneumonia were compared to characteristics of patients with Streptococcus pneumoniae (Sp) pneumonia, as reference. Risk factors for amoxicillin resistance in Hi were investigated. Results. Overall, 113 patients with Hi and 132 with Sp pneumonia were included. The percentages of AMC resistance among Hi strains decreased over the years (from 10% in 2008-2009 to 0% in 2016-2017) while resistance to amoxicillin remained stable at 20%. Also, percentages of Sp resistant strains for amoxicillin decreased over years (from 25% to 3%). Patients with Hi pneumonia experienced higher prevalence of bronchitis (18% vs. 8%, p=0.02, chronic obstructive pulmonary disease (43% vs. 30% p=0.03), HAP (18% vs. 7%, p=0.01, ventilator-associated pneumonia (27% vs. 17%, p=0.04, and longer duration of mechanical ventilation (8 days vs. 6 days, p=0.04) than patients with Sp pneumonia. Patients with Sp pneumonia had more frequently local complications than patients with Hi pneumonia (17% vs. 7%, p=0.03). De-escalation of antibiotics was more frequent in patients with Sp than in patients with Hi (67% vs. 53%, p=0.03). No risk factors were associated with amoxicillin resistance among patients with Hi pneumonia. Conclusions. Amoxicillin resistance was stable over time, but no risk factors were detected. AMC resistance was extremely low, suggesting that AMC could be used for empiric treatment of Hi pneumonia, as well as other molecules, namely, cephalosporins. Patients with Hi pneumonia had more pulmonary comorbidities and severe diseases than patients with Sp pneumonia.


2002 ◽  
Vol 282 (3) ◽  
pp. L563-L572 ◽  
Author(s):  
Ann Marie LeVine ◽  
Kevan Hartshorn ◽  
James Elliott ◽  
Jeffrey Whitsett ◽  
Thomas Korfhagen

Mice lacking surfactant protein SP-A [SP-A(−/−)] and wild type SP-A(+/+) mice were infected with influenza A virus (IAV) by intranasal instillation. Decreased clearance of IAV was observed in SP-A(−/−) mice and was associated with increased pulmonary inflammation. Treatment of SP-A(−/−) mice with exogenous SP-A enhanced viral clearance and decreased lung inflammation. Uptake of IAV by alveolar macrophages was similar in SP-A(−/−) and SP-A(+/+) mice. Myeloperoxidase activity was reduced in isolated bronchoalveolar lavage neutrophils from SP-A(−/−) mice. B lymphocytes and activated T lymphocytes were increased in the lung and spleen, whereas T helper (Th) 1 responses were increased [interferon-γ, interleukin (IL)-2, and IgG2a] and Th2 responses were decreased (IL-4, and IL-10, and IgG1) in the lungs of SP-A(−/−) mice 7 days after IAV infection. In the absence of SP-A, impaired viral clearance was associated with increased lung inflammation, decreased neutrophil myeloperoxidase activity, and increased Th1 responses. Because the airway is the usual portal of entry for IAV and other respiratory pathogens, SP-A is likely to play a role in innate defense and adaptive immune responses to IAV.


2020 ◽  
Author(s):  
Li Wang ◽  
Yan Tan ◽  
Jiangnan Zhao ◽  
Lin Gao ◽  
Jing Lei ◽  
...  

Abstract BackgroundPatients with severe pneumonia complicated with hypoxic respiratory failure often associated with increased morbidity and mortality rates. It is critical to discover more sensitive and specific markers for early identification of such high risk patients thus specific and timely treatment can be adjusted.MethodsThis retrospective study was performed in the respiratory intensive care unit (RICU) of Nanjing First Hospital and Jinling Hospital, Nanjing Medical University. Clinical data of patients admitted to the RICU and diagnosed with pneumonia from January 2017 to October 2019 was retrospectively reviewed. The eligible patients were classified into hypoxemia and non hypoxemia groups according to oxygenation index of 250 mmHg. In the meantime, the same cohort was separated into survival and deceased groups after 30 days post hospital admission. The related risk factors in these two classifications were examined separately.ResultsA total of 828 patients were screened for eligibility, and eventually 130 patients with pneumonia were included in our final analysis. Among the patients, 16 passed away despite exhausting standard treatments. The comparison between hypoxemia and non hypoxemia groups suggested that gender, diabetes mellitus status, count of white blood cell(WBC), neutrophils, neutrophils/Lymphocyte, lactic acid, creatinine, D-dimer, procalcitonin (PCT), C-reactive protein (CRP), PH, Lymphocyte, albumin and RAGE were significantly different.ConclusionsPrevious studies have suggested that the APACHE II score, LIS, SOFA, Nutric scores, WBC, neutrophils, lymphocyte counts and albumin levels were independent risk factors for severe pneumonia. Our study indicated that RAGE should be a new biomarker to predict poor prognosis in pneumonia. In addition, we also showed that LIS, SOFA, lactate, lymphocyte, platelet, BUN, total bilirubin, and PCT levels before treatment were independent factors that associated with 30 days survival rate. In addition, we proposed that OSM should be considered as a new prognosis marker for pneumonia patients.


2021 ◽  
Vol 8 ◽  
Author(s):  
Peter Jirak ◽  
Zornitsa Shomanova ◽  
Robert Larbig ◽  
Daniel Dankl ◽  
Nino Frank ◽  
...  

Aims: Thromboembolic events, including stroke, are typical complications of COVID-19. Whether arrhythmias, frequently described in severe COVID-19, are disease-specific and thus promote strokes is unclear. We investigated the occurrence of arrhythmias and stroke during rhythm monitoring in critically ill patients with COVID-19, compared with severe pneumonia of other origins.Methods and Results: This retrospective study included 120 critically ill patients requiring mechanical ventilation in three European tertiary hospitals, including n =60 COVID-19, matched according to risk factors for the occurrence of arrhythmias in n = 60 patients from a retrospective consecutive cohort of severe pneumonia of other origins. Arrhythmias, mainly atrial fibrillation (AF), were frequent in COVID-19. However, when compared with non-COVID-19, no difference was observed with respect to ventricular tachycardias (VT) and relevant bradyarrhythmias (VT 10.0 vs. 8.4 %, p = ns and asystole 5.0 vs. 3.3%, p = ns) with consequent similar rates of cardiopulmonary resuscitation (6.7 vs. 10.0%, p = ns). AF was even more common in non-COVID-19 (AF 18.3 vs. 43.3%, p = 0.003; newly onset AF 10.0 vs. 30.0%, p = 0.006), which resulted in a higher need for electrical cardioversion (6.7 vs. 20.0%, p = 0.029). Despite these findings and comparable rates of therapeutic anticoagulation (TAC), the incidence of stroke was higher in COVID-19 (6.7.% vs. 0.0, p = 0.042). These events also happened in the absence of AF (50%) and with TAC (50%).Conclusions: Arrhythmias were common in severe COVID-19, consisting mainly of AF, yet less frequent than in matched pneumonia of other origins. A contrasting higher incidence of stroke independent of arrhythmias also observed with TAC, seems to be an arrhythmia-unrelated disease-specific feature of COVID-19.


2017 ◽  
Vol 5 (1) ◽  
pp. 61
Author(s):  
Dewa Ayu Ketut Sri Abadi ◽  
Dewa Nyoman Wirawan ◽  
Anak Agung Sagung Sawitri ◽  
I Gusti Ayu Trisna Windiani

Background and purpose: Period prevalence of pneumonia among children in Indonesia increased from 2.1 in 2007 to 2.7 per 1000 children in 2013. The highest incidence was found among children aged 12-23 months. This study aims to examine association between delayed access to health care facilities and severity of children pneumonia.Methods: A case control study was conducted in Denpasar City. A total of 132 children were recruited to participate in this study, consisted of 44 cases and 88 controls. Cases were selected from 161 children with severe pneumonia who registered at Pulmonology Department of Sanglah General Hospital between January 2015 to April 2016. Controls were selected from 261 children aged 12-59 months with mild pneumonia who visited out-patient service at all community health centres in Denpasar City between January 2015 and April 2016. Cases and controls were matched by sex. Data were collected by interview with the parents in their houses. Data were analysed using multivariate analysis with logistic regression.Results: Risk factors associated to severity of pneumonia among children aged 12-59 months were delayed access to treatment for more than three days (AOR=2.15;95%CI: 1.39-3.32), non-health care facilities at first episode of illness (AOR=4.02; 95%CI: 1.53-10.61) and frequent episodes of respiratory infections (>4 times) over the last 6 months (AOR=5.45; 95%CI: 2.13-13.96).Conclusion: Delayed access to treatment, did not access healthcare facilities at first episode of illness, and high frequency of acute respiratory infections are risk factors of severe pneumonia among children.


2022 ◽  
Vol 9 ◽  
Author(s):  
Karine Vidal ◽  
Shamima Sultana ◽  
Alberto Prieto Patron ◽  
Irene Salvi ◽  
Maya Shevlyakova ◽  
...  

Objectives: Risk factors for acute respiratory infections (ARIs) in community settings are not fully understood, especially in low-income countries. We examined the incidence and risk factors associated with ARIs in under-two children from the Microbiota and Health study.Methods: Children from a peri-urban area of Dhaka (Bangladesh) were followed from birth to 2 years of age by both active surveillance of ARIs and regular scheduled visits. Nasopharyngeal samples were collected during scheduled visits for detection of bacterial facultative respiratory pathogens. Information on socioeconomic, environmental, and household conditions, and mother and child characteristics were collected. A hierarchical modeling approach was used to identify proximate determinants of ARIs.Results: Of 267 infants, 87.3% experienced at least one ARI episode during the first 2 years of life. The peak incidence of ARIs was 330 infections per 100 infant-years and occurred between 2 and 4 months of age. Season was the main risk factor (rainy monsoon season, incidence rate ratio [IRR] 2.43 [1.92–3.07]; cool dry winter, IRR 2.10 [1.65–2.67] compared with hot dry summer) in the first 2 years of life. In addition, during the first 6 months of life, young maternal age (<22 years; IRR 1.34 [1.01–1.77]) and low birth weight (<2,500 g; IRR 1.39 [1.03–1.89]) were associated with higher ARI incidence.Conclusions: Reminiscent of industrialized settings, cool rainy season rather than socioeconomic and hygiene conditions was a major risk factor for ARIs in peri-urban Bangladesh. Understanding the causal links between seasonally variable factors such as temperature, humidity, crowding, diet, and ARIs will inform prevention measures.


Animals ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2828
Author(s):  
Lorcan O’Neill ◽  
Julia Adriana Calderón Díaz ◽  
Maria Rodrigues da Costa ◽  
Sinnead Oakes ◽  
Finola C. Leonard ◽  
...  

The threat to public health posed by antimicrobial resistance in livestock production means that the pig sector is a particular focus for efforts to reduce antimicrobial use (AMU). This study sought to investigate the risk factors for AMU in Irish pig production. Antimicrobial use data were collected from 52 farrow-to-finish farms. The risk factors investigated were farm characteristics and performance, biosecurity practices, prevalence of pluck lesions at slaughter and serological status for four common respiratory pathogens and vaccination and prophylactic AMU practices. Linear regression models were used for quantitative AMU analysis and risk factors for specific AMU practices were investigated using logistic regression. Farms that milled their own feed had lower total AMU (p < 0.001), whereas higher finisher mortality (p = 0.043) and vaccinating for swine influenza (p < 0.001) increased AMU. Farms with higher prevalence of pericarditis (p = 0.037) and lung abscesses (p = 0.046) used more group treatments. Farms with higher prevalence of liver milk spot lesions (p = 0.018) and farms practising prophylactic AMU in piglets (p = 0.03) had higher numbers of individual treatments. Farms practising prophylactic AMU in piglets (p = 0.002) or sows (p = 0.062) had higher use of cephalosporins and fluoroquinolones. This study identified prophylactic use and respiratory disease as the main drivers for AMU in Irish pig production. These findings highlight areas of farm management where interventions may aid in reducing AMU on Irish pig farms.


2020 ◽  
Vol 13 ◽  
pp. 175628482097491
Author(s):  
Jonathan P. Segal ◽  
Joyce W. Y. Mak ◽  
Benjamin H. Mullish ◽  
James L. Alexander ◽  
Siew C. Ng ◽  
...  

The novel coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus has spread rapidly across the globe, culminating in major global morbidity and mortality. As such, there has been a rapid escalation in scientific and clinical activity aimed at increasing our comprehension of this virus. This volume of work has led to early insights into risk factors associated with severity of disease, and mechanisms that underpin the virulence and dynamics involved in viral transmission. These insights ultimately may help guide potential therapeutics to reduce the human, economic and social impact of this pandemic. Importantly, the gastrointestinal (GI) tract has emerged as an important organ influencing propensity to, and potentially severity of, COVID-19 infection. Furthermore, the gut microbiome has been linked to a variety of risk factors for COVID-19 infection, and manipulation of the gut microbiome is an attractive potential therapeutic target for a number of diseases. While data profiling the gut microbiome in COVID-19 infection to date are limited, they support the possibility of several routes of interaction between COVID-19, the gut microbiome, angiotensin converting enzyme 2 (ACE-2) expression in the small bowel and colon and gut inflammation. This article will explore the evidence that implicates the gut microbiome as a contributing factor to the pathogenesis, severity and disease course of COVID-19, and speculate about the gut microbiome’s capability as a therapeutic avenue against COVID-19. Lay summary It has been noted that certain baseline gut profiles of COVID-19 patients are associated with a more severe disease course, and the gut microbiome impacts the disease course of several contributory risk factors to the severity of COVID-19. A protein called ACE-2, which is found in the small intestine among other sites, is a key receptor for COVID-19 virus entry; there is evidence that the gut microbiome influences ACE-2 receptor expression, and hence may play a role in influencing COVID-19 infectivity and disease severity. Furthermore, the gut microbiome plays a significant role in immune regulation, and hence may be pivotal in influencing the immune response to COVID-19. In terms of understanding COVID-19 treatments, the gut microbiome is known to interact with several drug classes being used to target COVID-19 and should be factored into our understanding of how patients respond to treatment. Importantly, our understanding of the role of the gut microbiome in COVID-19 infection remains in its infancy, but future research may potentially aid our mechanistic understanding of viral infection, and new ways in which we might approach treating it.


Author(s):  
Sunil Kumar Kasundriya ◽  
Mamta Dhaneria ◽  
Aditya Mathur ◽  
Ashish Pathak

Childhood pneumonia is a major public health problem. The aim of this prospective hospital-based study is to determine the incidence and risk factors for community-acquired severe pneumonia in children in Ujjain, India. The study includes 270 children, 161 (60%) boys and 109 (40%) girls, aged between 2 months and 5 years with World Health Organization defined and radiologically confirmed severe pneumonia. Considering the 270 children, 64% (95% confidence interval (CI) 57.9–69.4) have severe pneumonia. The following are identified as risk factors for severe pneumonia from the generalized logistic regression model: Born premature (adjusted odds ratio (AOR) 7.50; 95% CI 2.22–25.31; p = 0.001); history of measles (AOR 6.35; 95% CI 1.73–23.30; p = 0.005); incomplete vaccination (AOR 2.66; 95% CI 1.09–6.48; p = 0.031); acyanotic congenital heart disease (AOR 9.21; 95% CI 2.29–36.99; p = 0.002); home treatment tried (AOR 3.84; 95% CI 1.42–10.39; p = 0.008); living in a kuchha house (AOR 3.89; 95% CI 1.51–10.01; p = 0.027); overcrowding (AOR 4.50; 95% CI 1.75–11.51; p = 0.002);poor ventilation in living area (AOR 16.37; 95% CI 4.67–57.38; p < 0.001); and practicing open defecation (AOR 16.92; 95% CI 4.95–57.85; p < 0.001). Awareness of these risk factors can reduce mortality due to severe pneumonia.


Sign in / Sign up

Export Citation Format

Share Document