Risk Of Secondary Bacterial Infections Research Articles

Recent Advances in the Development of Antimicrobial and Antifouling Biocompatible Materials for Dental Applications.

The risk of secondary bacterial infections resulting from dental procedures has driven the design of antimicrobial and antifouling dental materials to curb pathogenic microbial growth, biofilm formation and subsequent oral and dental diseases. Studies have investigated approaches based primarily on contact-killing or release-killing materials. These materials are designed for addition into dental resins, adhesives and fillings or as immobilized coatings on tooth surfaces, titanium implants and dental prosthetics. This review discusses the recent developments in the different classes of biomaterials for antimicrobial and antifouling dental applications: polymeric drug-releasing materials, polymeric and metallic nanoparticles, polymeric biocides and antimicrobial peptides. With modifications to improve cytotoxicity and mechanical properties, contact-killing and anti-adhesion materials show potential for incorporation into dental materials for long-term clinical use as opposed to short-lived antimicrobial release-based coatings. However, extended durations of biocompatibility testing, and adjustment of essential biomaterial features to enhance material longevity in the oral cavity require further investigations to confirm suitability and safety of these materials in the clinical setting. The continuous exposure of dental restorative and regenerative materials to pathogenic microbes necessitates the implementation of antimicrobial and antifouling materials to either replace antibiotics or improve its rational use, especially in the day and age of the ever-increasing problem of antimicrobial resistance.

Impact of tocilizumab on clinical outcomes in severe covid-19 patients and risk of secondary infection: A case-control study

Objective: This study aimed to identify the effect of tocilizumab (TCZ) on clinical outcomes in severe COVID-19 patients. Material and Methods: We included hospitalized COVID-19 patients with an initial WHO scale ≥4. We matched the patients with baseline characteristics by using propensity scores. Then, we selected patients with C-reactive protein levels above 30 and showing an upward trend. We assessed the effect of TCZ in patients on clinical outcomes by using Mann – Whitney U and Chi-square tests. Results: Of 200 patients who had an initial WHO scale ≥ 4, 42 (21%) were given TCZ in addition to standard of care (SOC). Twentyfive patients (50%) needed mechanical ventilation (MV) in the TCZ group, compared with 35 (21%) of 158 patients with SOC (p<0.01). Nineteen (45%) and 37 (23%) patients died in 30 days in these groups, respectively (p <0.01). The secondary infection rate was significantly higher in the TCZ group (p=0.004). However, no difference was observed in all these parameters in the propensity score-matched cohort (14 patients in TCZ and 14 in the SOC group) (p=0.45, 0.45, 1.0 respectively). Conclusions: Tocilizumab does not provide a beneficial effect on MV requirement and mortality in severe COVID-19, and it does not increase the risk of secondary bacterial infection.

Induction of cyclophilin A by influenza A virus infection facilitates group A Streptococcus coinfection.

During influenza A epidemics, bacterial coinfection is a major cause of increased morbidity and mortality. However, the roles of host factors in regulating influenza A virus (IAV)-triggered bacterial coinfection remain elusive. Cyclophilin A (CypA) is an important regulator of infection and immunity. Here, we show that IAV-induced CypA expression facilitates group A Streptococcus (GAS) coinfection both invitro and invivo. Upon IAV infection, CypA interacts with focal adhesion kinase (FAK) and inhibited E3 ligase cCbl-mediated, K48-linked ubiquitination of FAK, which positively regulates integrin α5 expression and actin rearrangement via the FAK/Akt signaling pathway to facilitate GAS colonization and invasion. Notably, CypA deficiency or inhibition by cyclosporine A significantly inhibits IAV-triggered GAS coinfection in mice. Collectively, thesefindings reveal that CypA is critical for GAS infection, and induction of CypA expression is another way for IAV to promote bacterial coinfection, suggesting that CypA is a promising therapeutic target for the secondary bacterial infection.

Antibiotic versus no antibiotic approach in the management of lumpy skin disease (LSD) in cattle

Antibiotics do not show effect on infections of solely viral origin. Lumpy Skin Disease is a viral disease where antibiotics are not clinically indicated. Due to monetary worth of high producing animals, Veterinarians are resorting to use antibiotics in LSD as a preventive measure against secondary bacterial infections. Eighteen animals with lumps on the skin were selected and randomly distributed into 3 groups of 6 animals each. Two groups were treated with commonly used broad-spectrum antibiotics and the third group was treated with Neem oil topically over the lesions and were offered fresh Neem leaves smoke. As a result, Lumpy skin disease was treated economically without the inclusion of antibiotics where Neem oil and fresh neem leaves smoke guarded the animals from the risk of secondary bacterial infection. This approach eliminates the risk of antimicrobial resistance, minimises the cost of treatment, and eliminates antibiotic induced undesirable depopulation of rumen microflora.

371. Cluster of carbapenemase-producing Enterobacterales secondary infections during the COVID-19 crisis at a New York City hospital

BackgroundPatients with COVID-19 may be at increased risk for secondary bacterial infections. At our quaternary care hospital in New York City, the rapid escalation of COVID-19 cases was accompanied by a massive surge in the need for hospital and critical care capacity. During this time, we noted a increase in infections caused by carbapenemase-producing Enterobacterales (CPE).MethodsWe retrospectively assessed microbiology data to identify patients with positive testing for SARS-CoV-2 who had clinical cultures with meropenem-resistant and/or carbapenemase gene-positive Enterobacterales. We obtained microbiological and clinical data by manual chart review. Available clinical isolates underwent long-range genomic sequencing using the MinION (Oxford) for rapid genotyping, resistance gene detection, and phylogenetic analysis.ResultsFrom March 1 to May 18, we identified 33 CPE isolates from 13 patients, including 29 Klebsiella pneumonia and four Enterobacter cloacae. Most patients (11/13) had a positive respiratory culture, and 7/13 developed bacteremia. All patients had prolonged, complex hospitalizations with extensive antibiotic exposure. We performed long-range sequencing on 19 isolates from 12 patients. 15/16 K. pneumoniae isolates belonged to sequence type (ST) 258 encoding KPC (14 KPC-2; 1 KPC-3); one ST70 isolate encoded KPC-2. All four E. cloacae isolates belonged to ST270 and encoded NDM-1. Phylogenetic analysis of ST258 isolates including historical isolates from our hospital revealed a distinct lineage of isolates from COVID-19 patients (72% bootstrap support), with expected clustering of isolates from the same patient and patients that were cohorted together.ConclusionWhile CPE have declined substantially in New York City in recent years, increased detection in patients with COVID-19 may signal a reemergence of these highly resistant pathogens in the wake of the global pandemic. System-level factors, such as the rapid scale-up of critical care capacity, while clearly needed to address the unprecedented reach of COVID-19, may have contributed to isolate clustering in these patients. Increased surveillance and antimicrobial stewardship efforts will be needed to mitigate the impact of CPE in the future.Disclosures All Authors: No reported disclosures

Differences in the Clinical and Hematological Characteristics of COVID-19 Patients with and without Type 2 Diabetes.

Objective To examine whether comorbidity with type 2 diabetes (T2D) affects the clinical and hematological parameters of coronavirus disease 2019 (COVID-19) patients. Methods We retrospectively investigated the clinical, imaging, and laboratory characteristics of patients with confirmed COVID-19 who were hospitalized from January 30, 2020 to March 17, 2020, at the Renmin Hospital of Wuhan University. A detailed clinical record was kept for each subject, including the medical history of COVID-19 and physical and laboratory examinations. A total of 164 subjects were eligible for the study, among which 40 patients were comorbid with T2D. Further analysis was conducted in two subcohorts of sex- and age-matched patients with and without T2D to identify hematological and biochemical differences. The laboratory tests, including routine blood tests, serum biochemistry, and coagulation function, were performed upon admission. Results The two groups showed no significant differences in baseline parameters, including age, sex, chest X-ray, or computed tomography (CT) findings, upon admission. However, patients with T2D showed an increased incidence of diarrhea. T2D patients required more recovery time from pneumonia, as shown by follow-up CT findings, which might contribute to the prolonged hospitalization. Comorbidity with T2D also increased risk of secondary bacterial infection during COVID-19. The T2D group had significantly higher white blood cell and neutrophil counts compared with the nondiabetic group, but T2D patients suffered from more severe lymphocytopenia and inflammation (P < 0.05). Most biochemical parameters showed no significant differences between the two groups (P > 0.05). However, patients with T2D seemed to have a significantly higher risk of developing hyperlactatemia, hyponatremia, and hypocalcemia. Conclusions COVID-19 patients comorbid with T2D demonstrated distinguishing clinical features and hematological parameters during the infection. It is necessary to develop a different clinical severity scoring system for COVID-19 patients with T2D. This study may provide helpful clues for the assessment and management of COVID-19 in T2D patients.

Neutropenia resulting from high-dose intravenous immunoglobulin in dermatological patients.

Current guidelines recommend high-dose intravenous immunoglobulin (IVIG) as a rescue therapy to treat severe cutaneous autoimmune disorders. Data on IVIG-induced hematological adverse events are limited in dermatological patients. We assessed the incidence and clinical implications of IVIG-induced neutropenia. Patients who received one or several cycles of IVIG between 2014 and 2019 were retrospectively evaluated. IVIG was given according to standardized infusion protocols. Daily differential blood counts were performed. Information on clinical baseline data, dermatological diagnosis, immunosuppressive pre-treatment, and IVIG-related adverse events was retrieved from patient files. Seventeen patients received 106 IVIG treatment cycles. Neutrophil counts below 1,500/μL were documented during 36 (34.0%) cycles, and neutrophils fell below 1,000/μL in 14 (13.2%) cases. The average drop of neutrophils from day one (pre-dose) to days 2 and 3 of IVIG therapy was statistically significant (p=0.006, and p=0.002, respectively) despite correction for hemodilution, and so was a slight decrease of thrombocytes (p=0.029, and p=0.011, respectively). Four patients developed seven episodes of bacterial infections during or immediately after IVIG therapy. IVIG-induced neutropenia is frequent in dermatological patients. A risk of secondary bacterial infections cannot be excluded.

The Key Roles of Interferon Lambda in Human Molecular Defense against Respiratory Viral Infections.

Interferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of infections, they induce expression of antiviral, interferon-stimulated genes (MX1, OAS, IFITM1), and they have immuno-modulatory activities that shape adaptive immune responses. Unlike other IFN, the type III IFN signal through distinct receptors is limited to a few cell types, primarily mucosal epithelial cells. As a consequence of their greater and more durable production in nasal and respiratory tissues, they can determine the outcome of respiratory infections. This review is focused on the role of IFN-λ in the pathogenesis of respiratory viral infections, with influenza as a prime example. The influenza virus is a major public health problem, causing up to half a million lethal infections annually. Moreover, the virus has been the cause of four pandemics over the last century. Although IFN-λ are increasingly being tested in antiviral therapy, they can have a negative influence on epithelial tissue recovery and increase the risk of secondary bacterial infections. Therefore, IFN-λ expression deserves increased scrutiny as a key factor in the host immune response to infection.

Carbapenemase-producing Enterobacterales causing secondary infections during the COVID-19 crisis at a New York City hospital.

BackgroundPatients with COVID-19 may be at increased risk for secondary bacterial infections with MDR pathogens, including carbapenemase-producing Enterobacterales (CPE).ObjectivesWe sought to rapidly investigate the clinical characteristics, population structure and mechanisms of resistance of CPE causing secondary infections in patients with COVID-19.MethodsWe retrospectively identified CPE clinical isolates collected from patients testing positive for SARS-CoV-2 between March and April 2020 at our medical centre in New York City. Available isolates underwent nanopore sequencing for rapid genotyping, antibiotic resistance gene detection and phylogenetic analysis.ResultsWe identified 31 CPE isolates from 13 patients, including 27 Klebsiella pneumoniae and 4 Enterobacter cloacae complex isolates. Most patients (11/13) had a positive respiratory culture and 7/13 developed bacteraemia; treatment failure was common. Twenty isolates were available for WGS. Most K. pneumoniae (16/17) belonged to ST258 and encoded KPC (15 KPC-2; 1 KPC-3); one ST70 isolate encoded KPC-2. E. cloacae isolates belonged to ST270 and encoded NDM-1. Nanopore sequencing enabled identification of at least four distinct ST258 lineages in COVID-19 patients, which were validated by Illumina sequencing data.ConclusionsWhile CPE prevalence has declined substantially in New York City in recent years, increased detection in patients with COVID-19 may signal a re-emergence of these highly resistant pathogens in the wake of the global pandemic. Increased surveillance and antimicrobial stewardship efforts, as well as identification of optimal treatment approaches for CPE, will be needed to mitigate their future impact.

A multi-centre open-label two-arm randomised superiority clinical trial of azithromycin versus usual care in ambulatory COVID-19: study protocol for the ATOMIC2 trial

BackgroundAzithromycin is an orally active synthetic macrolide antibiotic with a wide range of anti-bacterial, anti-inflammatory and antiviral properties. It is a safe, inexpensive, generic licenced drug available worldwide and manufactured to scale and is a potential candidate therapy for pandemic coronavirus disease 2019 (COVID-19). Azithromycin was widely used to treat severe SARS-CoV and MERS-CoV, but to date, no randomised data are available in any coronavirus infections.Other ongoing trials are exploring short courses of azithromycin either in early disease, within the first 7 days of symptoms, when azithromycin’s antiviral properties may be important, or late in disease when anti-bacterial properties may reduce the risk of secondary bacterial infection. However, the molecule’s anti-inflammatory properties, including suppression of pulmonary macrophage-derived pro-inflammatory cytokines such as interleukins-1β, -6, -8, and -18 and cytokines G-CSF and GM-CSF may provide a distinct therapeutic benefit if given in as a prolonged course during the period of progression from moderate to severe disease.MethodsATOMIC2 is a phase II/III, multi-centre, prospective, open-label, two-arm randomised superiority clinical trial of azithromycin versus standard care for adults presenting to hospital with COVID-19 symptoms who are not admitted at initial presentation. We will enrol adults, ≥ 18 years of age assessed in acute hospitals in the UK with clinical diagnosis of COVID-19 infection where management on an ambulatory care pathway is deemed appropriate. Participants will be randomised in a 1:1 ratio to usual care or to azithromycin 500 mg orally daily for 14 days with telephone follow-up at days 14 and 28. The primary objective is to compare the proportion with either death or respiratory failure requiring invasive or non-invasive mechanical ventilation over 28 days from randomisation. Secondary objectives include mortality/respiratory failure in those with a PCR-confirmed diagnosis; all-cause mortality; progression to pneumonia; progression to severe pneumonia; peak severity of illness and mechanistic analysis of blood and nasal biomarkers.DiscussionThis trial will determine the clinical utility of azithromycin in patients with moderately severe, clinically diagnosed COVID-19 and could be rapidly applicable worldwide.Trial registrationClinicalTrials.gov NCT04381962. Registered on 11 May 2020. EudraCT identifier 2020-001740-26. Opened for accrual on 29 May 2020.

NOX2 decoy peptides disrupt trauma-mediated neutrophil immunosuppression and protect against lethal peritonitis

Trauma and sepsis are frequent causes of immunosuppression and risk of secondary bacterial infections and mortality among critically ill patients. Reduced activity of neutrophil NADPH oxidase 2 (NOX2) and impaired bacterial killing are among the major indices of immunosuppression. We hypothesize that NOX2-decoy peptides disrupt the inhibition of neutrophil NOX2 by plasma of patients with severe trauma and immunosuppression, thereby preserving the neutrophil respiratory burst that is a central antimicrobial mechanism. We demonstrate that plasma from trauma/hemorrhage (T/H) patients, but not healthy donors (HD), significantly reduced the activity of neutrophil NOX2 and impaired bacterial killing. The inhibitory action of plasma was associated with an increase in bacterial infections among trauma survivors. High Mobility Group Box 1 (HMGB1) is a mediator of lethality in trauma and sepsis and our mechanistic studies revealed that disulfide and oxidized forms of HMGB1 bind to the gp91phox subunit of NOX2, and thus decrease the neutrophil respiratory burst and bacterial killing. NOX2 decoy Anti-Immunosuppression (Ai) Peptides 1 and 3 effectively disrupted the immunosuppressive action of T/H plasma. HMGB1 selectively binds to Ai-Peptide 3, supporting the possibility for direct interaction between HMGB1 and the third external loop of gp91phox. In vivo, Ai-Peptides improved survival of mice subjected to lethal peritonitis. Taken together, plasma-dependent inhibition of neutrophil NOX2 appeared to be a suitable indicator of immunosuppression in patients with severe trauma. Given that gp91phox decoys protected the neutrophil respiratory burst, selected Ai-Peptides have therapeutic potential to reduce bacterial infections and end-organ injury associated with sepsis/trauma-induced immunosuppression.

Human Leukocyte Antigen-DR Deficiency and Immunosuppression-Related End-Organ Failure in SARS-CoV2 Infection.

Human Leukocyte Antigen-DR Deficiency and Immunosuppression-Related End-Organ Failure in SARS-CoV2 Infection.

Investigation of occurrence patterns of respiratory syncytial virus A and B in infected-patients from Cheonan, Korea

BackgroundRespiratory infections caused by viruses affect the lower respiratory tract; these infections are severe in patients with underlying diseases and can even lead to death. Respiratory syncytial virus (RSV), one of the causative agents of respiratory viral infections, is the most common cause of pneumonia and bronchiolitis in children and adults.MethodsRespiratory specimens (nasopharyngeal aspirate, nasal swab, throat swab, etc.), which were sent to the Department of laboratory medicine from January 2012 to December 2018 for detection of respiratory viruses via real time reverse transcription PCR (Real time RT-PCR) were used in this study. RSV detected by real-time RT-PCR were analyzed on the basis of co-infection, sex and age of the patients, and year and month of sample collection.ResultsDuring the study period, we observed that the RSV detection rate was 12.8% (n = 1150/9010); the detection rate of RSV-A (7.1%) was higher than that of RSV-B (5.8%). The detection rate of RSV was the highest at 36.5% in December, and RSV-A and RSV-B were in vogue every year. Co-infection rate of RSVs was the highest in the patients over 80 years of age; RSVs showed the highest Co-infection with Rhinoviruses.ConclusionsDuring the study period, prevalence was different among the two subtypes of RSV, and the average age of RSV-B-positive patients was higher than that of RSV-A. Co-infection rate tended to increase every year. RSVs cause mild as well as severe infections. There are reports of serious clinical progress as RSVs cause overlapping infections with other viruses and increase the risk of secondary bacterial infections. Thus, further research on RSV should be done.

PPARα exacerbates necroptosis, leading to increased mortality in postinfluenza bacterial superinfection

Patients infected with influenza are at high risk of secondary bacterial infection, which is a major proximate cause of morbidity and mortality. We have shown that in mice, prior infection with influenza results in increased inflammation and mortality upon Staphylococcus aureus infection, recapitulating the human disease. Lipidomic profiling of the lungs of superinfected mice revealed an increase in CYP450 metabolites during lethal superinfection. These lipids are endogenous ligands for the nuclear receptor PPARα, and we demonstrate that Ppara-/- mice are less susceptible to superinfection than wild-type mice. PPARα is an inhibitor of NFκB activation, and transcriptional profiling of cells isolated by bronchoalveolar lavage confirmed that influenza infection inhibits NFκB, thereby dampening proinflammatory and prosurvival signals. Furthermore, network analysis indicated an increase in necrotic cell death in the lungs of superinfected mice compared to mice infected with S. aureus alone. Consistent with this, we observed reduced NFκB-mediated inflammation and cell survival signaling in cells isolated from the lungs of superinfected mice. The kinase RIPK3 is required to induce necrotic cell death and is strongly induced in cells isolated from the lungs of superinfected mice compared to mice infected with S. aureus alone. Genetic and pharmacological perturbations demonstrated that PPARα mediates RIPK3-dependent necroptosis and that this pathway plays a central role in mortality following superinfection. Thus, we have identified a molecular circuit in which infection with influenza induces CYP450 metabolites that activate PPARα, leading to increased necrotic cell death in the lung which correlates with the excess mortality observed in superinfection.

Asthma, biologics, corticosteroids, and coronavirus disease 2019

Asthma, biologics, corticosteroids, and coronavirus disease 2019

New Corona Virus (COVID-19) Management in Pregnancy and Childbirth

Context: Coronavirus disease 2019 (COVID-19) is an emerging disease that has been associated with a rapid increase in afflicted cases and deaths since its first introduction in Wuhan, China, in December 2019. The emerging infection can have a significant impact on pregnant women and the fetus. The purpose of this study was to review and summarize the latest research on the management and treatment of women in pregnancy and childbirth in the world and management protocols available in Iran and other countries. Evidence Acquisition: In this review study, we examined Persian and English studies by searching the Pubmed, Web of Science, UpToDate, SID, Scopus, Google Scholar, and medRxiv databases with keywords pregnant, pregnancy, gravidity, coronavirus, infection, COVID-19, and their Persian equivalents. Articles and reviews were on humans. After reviewing and removing duplicate and non-eligible articles, 12 articles and 11 guidelines and recommendations were obtained. Results: The results of the review study were categorized as follows: clinical course of COVID-19 in pregnancy, perinatal outcomes, neonatal outcomes, vertical transmission potential, management of COVID-19 in pregnancy, labor, and delivery in women, postpartum stage in women with COVID-19, breastfeeding, and care for a infant born to a mother with COVID-19. The general principles of caring for women in pregnancy and childbirth included early separation, using aggressive infection control methods, non-administration of corticosteroids repeatedly, oxygen therapy, preventing from fluid overload, using empirical antibiotics (due to the risk of secondary bacterial infection), co-infection testing of other infections, avoiding breastfeeding in mothers with definitive positive tests, and being cautious in suspicious cases. Conclusions: Given the limited information on the complications and outcomes of the virus in pregnancy and childbirth and the increasing number of studies, the provision of up-to-date care according to global and regional processes and guidelines is recommended for mothers affected and suspected with COVID-19.

Secondary bacterial infection in dengue fever and associated risk factors – An observational study in children

Background: Dengue fever remains one of the leading causes of hospitalization among children in endemic areas. Clinical manifestations of dengue fever are highly variable. There are only a few pediatric dengue fever cases reported with secondary bacterial infection. Knowledge of prevalence, risk factors, and predictors of bacterial infection among children with dengue fever is essential to initiate antibiotics. Objective: The objective of this study was to assess the prevalence of bacterial infection, analysis of risk factors, and predictors of bacterial infection among dengue fever patients with prolonged or recurrent fever after critical phase of illness. Design: This was a retrospective observational study. Setting: This study was conducted in the pediatric department of a tertiary hospital. Patients: Children with dengue fever who present with persistent or prolonged fever even after critical phase were included in the study. Results: Eighty-three children with dengue fever who had persistent fever for more than 5 days or recurrent fever were included in our study. Twenty-nine patients (34.9%) had definite secondary bacterial infection confirmed by positive culture and seven patients had probable secondary bacterial infection. The risk of secondary bacterial infection was higher in infants (P = 0.054), children who had fever >5 days on admission (P = 0.020), and children who had severe dengue (P = 0.016). The duration of hospital stay increased significantly in those with secondary bacterial infection (P = 0.041). No mortality was reported in culture-positive group. Conclusion: Our study highlights the increased risk of multidrug-resistant secondary bacterial infection among infants and in children who presented with fever >5 days and severe dengue fever. Hence, a low threshold to work up for secondary bacterial infections and early initiation of empirical antibiotics is warranted in these patients.

Lokalni vodič za primenu lekova kod pacijenata obolelih od COVID-19

Objective. Until now, there have been no guidelines for the use of drugs in patients with COVID 19 in the Republic of Serbia that have been authorized and published in the professional or scientific literature, or on the official websites of the Ministry of Health or healthcare institutions. The aim of this paper is to present a local guideline for the use of drugs in patients with COVID 19 and the process of its development and adoption. Methods. The guideline proposal was prepared by a working group based on the results of a systematic research of the medical literature, and quality control of found publications from the category "clinical practice guidelines". The proposal of the working group was considered and adopted at the sessions of the Drug / Therapeutics Committee and the Quality Assurance Committee of the University Clinical Centre Kragujevac. Results. The guideline's recommendations are based on the type of patient, and all have the same degree of recommendation and the same quality of evidence on which they are based. Patient types are formed according to the severity of the disease and the need for respiratory support, as well as according to the risk of secondary bacterial infection. Conclusion. The local guideline to the use of drugs in patients with COVID 19 was developed and adopted in a short period of time, primarily due to the need for its urgent use. A revision of this guide is planned after 6 months from the moment of adoption.

Urgent action on antimicrobial resistance

Urgent action on antimicrobial resistance

Vitamin D attenuates rhinovirus-induced expression of intercellular adhesion molecule-1 (ICAM-1) and platelet-activating factor receptor (PAFR) in respiratory epithelial cells

Human rhinoviruses commonly cause upper respiratory infections, which may be complicated by secondary bacterial infection. Vitamin D replacement reduces risk of acute respiratory infections in vitamin D-deficient individuals, but the mechanisms by which such protection is mediated are incompletely understood. We therefore conducted experiments to characterise the influence of the major circulating metabolite 25-hydroxyvitamin D (25[OH]D) and the active metabolite 1,25-dihydroxyvitamin D (1,25[OH]2D) on responses of a respiratory epithelial cell line (A549 cells) to infection with a major group human rhinovirus (RV-16). Pre-treatment of A549 respiratory epithelial cells with a physiological concentration (10−7M) of 25(OH)D induced transient resistance to infection with RV-16 and attenuated RV-16-induced expression of the genes encoding intercellular adhesion molecule 1 (ICAM-1, a cell surface glycoprotein that acts as the cellular receptor for major group rhinoviruses) and platelet-activating factor receptor (PAFR, a G-protein coupled receptor implicated in adhesion of Streptococcus pneumoniae to respiratory epithelial cells). These effects were associated with enhanced expression of the genes encoding the NF-κB inhibitor IκBα and the antimicrobial peptide cathelicidin LL-37. Our findings suggest possible mechanisms by which vitamin D may enhance resistance to rhinovirus infection and reduce risk of secondary bacterial infection in vitamin D-deficient individuals.