Peter J M Openshaw

Imperial College London | Imperial · Faculty of Medicine

Background Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods In t...

Complement, a critical defence against pathogens, has been implicated as a driver of pathology in COVID-19. Complement activation products are detected in plasma and tissues and complement blockade considered for therapy. To delineate roles of complement in immunopathogenesis, we undertook the largest comprehensive study of complement in an COVID-1...

Background: We conducted this study to assess the prevalence of viral coinfection in a well characterized cohort of hospitalized coronavirus disease 2019 (COVID-19) patients and to investigate the impact of coinfection on disease severity. Methods: Multiplex real-time polymerase chain reaction testing for endemic respiratory viruses was performed o...

Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in ba...

Background No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the...

Background Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). This study investigated adults hospitalized with COVID-19 and hypothesized that risk factors for AKI would include comorbidities and non-White race. Methods A prospective multicentre cohort study was performed using patients admitted to 254 UK hospitals with COVI...

Background: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods:...

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene...

Background Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evid...

Background Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital. Methods In this multicentre prospective observational cohort study, the Internation...

Background Predicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length of stay (LoS) in particular bed types. LoS can vary depending on the patient’s “bed pathway” - the sequence of transfers of individual patients between bed types during a hospital stay. In this study, we characterise these pathways, and thei...

Background Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19. Methods The International Severe Ac...

BACKGROUND: Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions. METHODS: We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, o...

ACHOO!-trophils? Why some individuals come down with a cold in any given year, whereas others are spared, is poorly understood. Habibi et al. exposed volunteers to respiratory syncytial virus (RSV), one of the pathogens responsible for the common cold, and then followed them over the ensuing 2 weeks (see the Perspective by Mirchandani and Walmsley)...

Objective: To characterize the clinical features of patients with severe COVID-19 in the UK. Design: Prospective observational cohort study with rapid data gathering and near real-time analysis, using a pre-approved questionnaire adopted by the WHO. Setting: 166 UK hospitals between 6th February and 18th April 2020. Participants: 16,749 people with...

Influenza viruses are highly transmissible, both within and between host species. The severity of the disease they cause is highly variable, from the mild and inapparent through to the devastating and fatal. The unpredictability of epidemic and pandemic outbreaks is accompanied but the predictability of seasonal disease in wide areas of the Globe,...

Background: Influenza A virus (IAV) causes a wide range of extra-respiratory complications. However, the role of host factors in these complications of influenza virus infection remains to be defined. Methods: Here, we sought to use transcriptional profiling, virology, histology and echocardiograms to investigate the role of a high fat diet in I...

Background: . Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in young infants. However, it is also a significant pathogen in older adults. Validated biomarkers of RSV disease severity would benefit diagnostics, treatment decisions, and prophylactic interventions. This review summarizes knowledge of biomarkers for RSV d...

Background: Human respiratory syncytial virus (RSV) is classified into antigenic subgroups A and B. Thirteen genotypes have been defined for RSV-A and 20 for RSV-B, without any consensus on genotype definition. Methods: We evaluated clustering of RSV sequences published in GenBank until February 2018 to define genotypes by using maximum likeliho...

Background: Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary...

BACKGROUND Respiratory syncytial virus (RSV) is an important cause of acute pulmonary disease and one of the last remaining major infections of childhood for which there is no vaccine. CD4+ T cells play a key role in antiviral immunity, but they have been little studied in the human lung.METHODS Healthy adult volunteers were inoculated i.n. with RS...

Background Patients with asthma are at risk of hospitalisation with influenza, but the reasons for this predisposition are unknown. Study setting A prospective observational study of adults with PCR-confirmed influenza in 11 UK hospitals, measuring nasal, nasopharyngeal and systemic immune mediators and whole-blood gene expression. Results Of 133...

Respiratory syncytial virus (RSV) is the most common single cause of respiratory hospitalisation of infants and is the second largest cause of lower respiratory infection mortality worldwide. In adults, RSV is an under-recognised cause of deterioration in health, particularly in frail elderly persons. Infection rates typically rise in late autumn a...

Understanding how immune challenges elicit different responses is critical for diagnosing and deciphering immune regulation. Using a modular strategy to interpret the complex transcriptional host response in mouse models of infection and inflammation, we show a breadth of immune responses in the lung. Lung immune signatures are dominated by either...

In the version of this article initially published, a source of funding was not included in the Acknowledgements section. That section should include the following: P.J.M.O. was supported by EU FP7 PREPARE project 602525. The error has been corrected in the HTML and PDF version of the article.

Rationale: Needle-free intranasal vaccines offer major potential advantages, especially against pathogens entering via mucosal surfaces. As yet, there is no effective vaccine against respiratory syncytial virus (RSV), a ubiquitous pathogen of global importance that preferentially infects respiratory epithelial cells; new strategies are urgently req...

Respiratory syncytial virus (RSV) is a common virus that can cause bronchiolitis in infants and pneumonia in immunocompromised and elderly people. RSV belongs to the Pneumoviridae family and consists of a genome of 15 kb. Its genome contains ten genes that code for eleven proteins, with M2 coding for two different proteins in overlapping open readi...

Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and investigational data we...

2018 The Author(s). Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and inv...

Rationale: Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is thought to result from uncontrolled viral replication, an excessive immune response, or both. Objectives: To determine RSV load and immune mediator levels in nasal mucosal lining fluid by serial sampling of nasal f...

Introduction Respiratory viral infections cause significant morbidity and mortality in infants; approximately half of which are associated with respiratory syncytial virus (RSV) infection. Severe bronchiolitis has been associated with an aberrant host response to viral replication. We investigated the patient characteristics, immune response and vi...

Complement, coagulation and fibrinolysis contribute to the pathology of many respiratory diseases. Here we detail the biphasic activation of these pathways following nasal allergen challenge. Understanding these mechanisms may lead to therapeutic insight in common respiratory diseases.

The methods of nasal absorption (NA) and bronchial absorption (BA) use synthetic absorptive matrices (SAM) to absorb the mucosal lining fluid (MLF) of the human respiratory tract. NA is a non-invasive technique which absorbs fluid from the inferior turbinate, and causes minimal discomfort. NA has yielded reproducible results with the ability to fre...

Background RSV is a ubiquitous pathogen causing severe disease in children and the elderly. There is as yet no licensed vaccine. SynGEM, a novel intranasal subunit vaccine based on the RSV F glycoprotein linked to an immunostimulatory bacterium-like-particle carrier, was previously shown in animal models to elicit durable immune responses both loca...

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) annually affecting >2 million children in the US <5 years old. In the elderly (>65 years old), RSV results in ∼175,000 hospitalizations annually in the US with worldwide incidence ∼34 million. There is no approved RSV vaccine and treatments are limited. R...

To address uncertainties in the prevention and management of influenza in people with asthma, we performed a scoping review of the published literature on influenza burden; current vaccine recommendations; vaccination coverage; immunogenicity, efficacy, effectiveness and safety of influenza vaccines; and the benefits of antiviral drugs in people wi...

In each influenza season, a distinct group of young, otherwise healthy individuals with no risk factors succumbs to life-threatening infection. To better understand the cause for this, we analyzed a broad range of immune responses in blood from a unique cohort of patients, comprising previously healthy individuals hospitalized with and without resp...

Background: Existing respiratory mucosal sampling methods are flawed, particularly in a paediatric bronchiolitis setting. Methods: Twenty-four infants with bronchiolitis were recruited: 12 were Respiratory syncytial virus (RSV)+, 12 were RSV-. Infants were sampled by nasosorption (NS) and nasopharyngeal-aspiration (NPA). Results: NS was well t...

Maternal immunisation has the potential to substantially reduce morbidity and mortality from infectious diseases after birth. The success of tetanus, influenza, and pertussis immunisation during pregnancy has led to consideration of additional maternal immunisation strategies to prevent group B streptococcus and respiratory syncytial virus infectio...

Group B streptococcus and respiratory syncytial virus are leading causes of infant morbidity and mortality worldwide. No licensed vaccines are available for either disease, but vaccines for both are under development. Severe respiratory syncytial virus disease can be prevented by passively administered antibody. The presence of maternal IgG antibod...

Respiratory syncytial virus (RSV) is an exceptional mucosal pathogen. It specializes in infection of the ciliated respiratory epithelium, causing disease of variable severity with little or no direct systemic effects. It infects virtually all children by the age of three years and then repeatedly infects throughout life; this it does despite relati...

The viral attachment protein of RSV has many surprising features, especially its mimicry of fractalkine (CX3CL1). Zhivaki et al. (2017) now show that, in addition to using this homology to attach to ciliated cells, it activates human neonatal regulatory B cells, thereby inhibiting immunological responses.

Pneumonia is of great global public health importance. Viral infections play both direct and indirect parts in its cause across the globe. Influenza is a leading cause of viral pneumonia in both children and adults, and respiratory syncytial virus is increasingly recognized as causing disease at both extremes of age. Vaccination offers the best pro...

Background: Asthmatic persons tend to suffer from severe influenza, but the reasons for enhanced severity are unknown. Objectives: To determine the clinicopathological correlates of this susceptibility, we examined nasal and systemic immune responses in adults admitted to hospital with influenza-like illnesses. Methods: We studied 210 patients a...

Background: Asthmatic persons tend to suffer from severe influenza, but the reasons for enhanced severity are unknown. Objectives: To determine the clinicopathological correlates of this susceptibility, we examined nasal and systemic immune responses in adults admitted to hospital with influenza-like illnesses. Methods: We studied 210 patients ad...

Background: Recent advances in systems medicine allow detailed reconstruction of molecular interactions in particular diseases e.g. Parkinson's disease map (Fujita et al. , Molecular Neurobiology, 2013) and Atlas of Cancer Signalling Networks (Kuperstein et al. , Oncogenesis, 2015). Objectives: 1. Integration of current knowledge on asthma into a...

Respiratory Syncytial Virus (RSV) is a major pathogen causing low respiratory tract disease (bronchiolitis), primarily in infants. Helminthic infections may alter host immune responses to both helminths and to unrelated immune triggers. For example, we have previously shown that filarial cystatin (AvCystatin/Av17) ameliorates allergic airway inflam...

Reduced RSV-induced immunopathology by AvCystatin treatment in a model of FI-RSV of viral lung eosinophilia. A) Schematic of the FI RSV model: i.m. intramuscular; i.p. intraperitoneal; i.n. intranasal application. B) Weight loss in the FI-RSV model. Total cell number of eosinophil (C) and macrophages in the BAL (D). Viral load in the lungs measured...

Frequency of IL-10 producing T-cells in the lungs and airways after AvCystatin treatment. Flowcytometric analysis of IL-10 intracellular cytokine content in RSV challenged or AvCystatin/RSV challenged mice is shown (A). Graphical visualization of IFNγ and IL-10 production by CD4+ T cells in the BAL (D and E) and lungs (B and C). Representative data...

AvCystatin induced FoxP3+ T cell induction in the mediastinal lymph node. Total number of FoxP3+ CD4+ T cells (A) and the number of IL-10+ CD4+ T cells in the mLN (B) after AvCystatin treatment and RSV challenge. Representative data of 2 experiments, 5 mice per group. Error bars indicate SEM. P values reflect Mann-Whitney t-test: * p<0.05, **p<0.01...

AvCystatin treatment reduces Muc5a production in lung. Relative expression of MUC5a in mice lungs after the vvG RSV model (A) or primary RSV model (B). Error bars indicate SEM. P values reflect Mann-Whitney t-test: * p<0.05. (TIF)

Introduction: There are few reliable ways to study respiratory mucosal immune responses to viruses, viral-type toll-like receptor (TLR) agonists and vaccines. To investigate innate immune responses to TLR agonists (TLR3: poly IC/ poly ICLC; TLR7/8: resiquimod), we compared the effects on human nasal mucosa and zebrafish gills in vivo. Methods: Na...

Respiratory syncytial virus (RSV) infection has an estimated global incidence of 33 million cases in children younger than 5 years, with 10% requiring hospital admission and up to 199,000 dying of the disease. There is growing evidence that severe infantile RSV bronchiolitis, a condition characterised by an inflammatory reaction to the virus, is as...

In animal models, resident memory CD8 + T (Trm) cells assist in respiratory virus elimination but their importance in man has not been determined. Here, using experimental human respiratory syncytial virus (RSV) infection, we investigate systemic and local virus-specific CD8 + T-cell responses in adult volunteers. Having defined the immunodominance...

Supplementary Figures 1-7 and Supplementary Tables 1-8

Background Practical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide (LPS) is a component of the cell wall of Gram negative bacteria and a potent activator of Toll-like receptor (TLR)-4. To measure LPS responsiveness of the nasal mucosa, we administered LPS as a nasal spray and quantified chemokine and cyt...

CONSORT Checklist. (DOC)

Data Files. (XLS)

Study Protocol. (DOC)