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Mapping the human genetic architecture of COVID-19The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3-7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Copyright © 2021, The Author(s).
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Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort studyPURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.Copyright © 2020 American Society of Clinical Oncology. All rights reserved.
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Enhancing the experience and outcomes of children with complex care needs in acute paediatric settings: A realist review protocolIntroduction The number of babies, children and young people with complex care needs (henceforth children with complex care needs (CCCN)) in England has increased in recent decades, and this has also been recognised globally. CCCN may have frequent and lengthy hospital admissions, but during these episodes, their needs are not always met, potentially resulting in suboptimal experiences and outcomes. Despite increased numbers of CCCN accessing acute care and displaying greater complexity, much of the contemporary literature has focused on primary care coordination between health, education and social care. Research specifically focused on CCCN in the acute care setting is largely absent. This realist review aims to understand how optimal experience and outcomes are achieved for CCCN during acute care, in different settings, for whom and why. Methods and analysis This realist review will proceed through six steps: (1) clarifying the scope of the review, (2) searching for evidence, (3) data selection and quality appraisal, (4) data extraction, (5) analysis and synthesis and (6) dissemination. We will search Medline, Cumulated Index in Nursing and Allied Health Literature and PsycINFO, alongside grey literature and other sources and will carry out citation tracking. Patient and public involvement and engagement have aided in the development of this protocol and will be maintained through regular consultations with a stakeholder group throughout the review. The review will result in a programme theory which will include context-mechanism-outcome configurations and provide data to support claims of generative causation. Ethics and dissemination Ethical approval is not required for this review as it does not involve primary research. The programme theory developed will be disseminated through peer-reviewed publications and relevant conferences. It will subsequently inform the development of an intervention to improve acute care for CCCN.
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GENESISS 2 - Generating standards for in-situ simulation project: A systematic mapping reviewBACKGROUND: In-situ simulation is increasingly employed in healthcare settings to support learning and improve patient, staff and organisational outcomes. It can help participants to problem solve within real, dynamic and familiar clinical settings, develop effective multidisciplinary team working and facilitates learning into practice. There is nevertheless a reported lack of a standardised and cohesive approach across healthcare organisations. The aim of this systematic mapping review was to explore and map the current evidence base for in-situ interventions, identify gaps in the literature and inform future research and evaluation questions. METHODS: A systematic mapping review of published in-situ simulation literature was conducted. Searches were conducted on MEDLINE, EMBASE, AMED, PsycINFO, CINAHL, MIDIRS and ProQuest databases to identify all relevant literature from inception to October 2020. Relevant papers were retrieved, reviewed and extracted data were organised into broad themes. RESULTS: Sixty-nine papers were included in the mapping review. In-situ simulation is used 1) as an assessment tool; 2) to assess and promote system readiness and safety cultures; 3) to improve clinical skills and patient outcomes; 4) to improve non-technical skills (NTS), knowledge and confidence. Most studies included were observational and assessed individual, team or departmental performance against clinical standards. There was considerable variation in assessment methods, length of study and the frequency of interventions. CONCLUSIONS: This mapping highlights various in-situ simulation approaches designed to address a range of objectives in healthcare settings; most studies report in-situ simulation to be feasible and beneficial in addressing various learning and improvement objectives. There is a lack of consensus for implementing and evaluating in-situ simulation and further studies are required to identify potential benefits and impacts on patient outcomes. In-situ simulation studies need to include detailed demographic and contextual data to consider transferability across care settings and teams and to assess possible confounding factors. Valid and reliable data collection tools should be developed to capture the complexity of team and individual performance in real settings. Research should focus on identifying the optimal frequency and length of in-situ simulations to improve outcomes and maximize participant experience. Copyright © 2022. The Author(s).
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GENESISS 1- Generating standards for in-situ simulation project: A scoping review and conceptual modelBACKGROUND: In-Situ Simulation (ISS) enables teams to rehearse and review practice in the clinical environment to facilitate knowledge transition, reflection and safe learning. There is increasing use of ISS in healthcare organisations for which patient safety and quality improvement are key drivers. However, the effectiveness of ISS interventions has not yet been fully demonstrated and requires further study to maximise impact. Cohesive programmatic implementation is lacking and efforts to standardise ISS terms and concepts, strengthen the evidence base and develop an integrated model of learning is required. The aim of this study was to explore the current evidence, theories and concepts associated with ISS across all areas of healthcare and develop a conceptual model to inform future ISS research and best practice guidance. METHODS: A scoping review was undertaken with stakeholder feedback to develop a conceptual model for ISS. Medline, OpenGrey and Web of Science were searched in September 2018 and updated in December 2020. Data from the included scoping review studies were analysed descriptively and organised into categories based on the different motivations, concepts and theoretical approaches for ISS. Categories and concepts were further refined through accessing stakeholder feedback. RESULTS: Thirty-eight papers were included in the scoping review. Papers reported the development and evaluation of ISS interventions. Stakeholder groups highlighted situations where ISS could be suitable to improve care and outcomes and identified contextual and practical factors for implementation. A conceptual model of ISS was developed which was organised into four themes: 1. To understand and explore why systematic events occur in complex settings; 2.To design and test new clinical spaces, equipment, information technologies and procedures; 3. To practice and develop capability in individual and team performance; 4. To assess competency in complex clinical settings. CONCLUSIONS: ISS presents a promising approach to improve individual and team capabilities and system performance and address the 'practice-theory gap'. However, there are limitations associated with ISS such as the impact on the clinical setting and service provision, the reliance of having an open learning culture and availability of relevant expertise. ISS should be introduced with due consideration of the specific objectives and learning needs it is proposed to address. Effectiveness of ISS has not yet been established and further research is required to evaluate and disseminate the findings of ISS interventions. Copyright © 2022. The Author(s).
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Pediatric nurse-sensitive outcomes: A systematic review of international literatureBackground: Nurse-sensitive outcomes are measures for improvement and evaluation of the quality of nursing care delivered. The specific outcomes that need to be measured will be determined by the patient population, as well as the field and scope of practice, in which nursing care is being delivered. Currently, there is no internationally agreed upon set of nurse-sensitive outcomes for pediatric nursing, which provides specialist care to infants, children, and young people. Aim(s): To identify and evaluate nurse-sensitive outcomes for pediatric nursing. Method(s): A systematic review was conducted. Five electronic databases (British Nursing Index, CINAHL, EMBASE, MEDLINE, and EMCARE) were searched in the period up to February 2022. Studies were selected for inclusion using title and abstract screening using predetermined criteria. The Critical Appraisal Skills Programme tool was used for quality assessment. A narrative synthesis of the results was performed. Result(s): A total of 633 studies were identified from online searches, with 14 studies meeting the inclusion criteria. All studies had moderate to high methodological strength. A total of 57 nurse-sensitive outcomes were identified from all included studies. Using the nurse-sensitive outcome conceptual analysis framework, 25 (45%) of the items were classified as outcome attributes, 20 (35%) as process attributes, and 13 (23%) as structure attributes. The most frequently reported nurse-sensitive outcomes included pressure ulcers, nosocomial infections, hospital-acquired infections, peripheral intravenous infiltration, failure to rescue, and staffing levels. Conclusion(s): This review provides an up-to-date and comprehensive list of nurse-sensitive outcomes for use in pediatric nursing and describes their frequency of use. However, further work is required to achieve consensus for an international core nurse-sensitive outcome set for pediatric nursing with policy recommendations to ensure agreed-upon minimum standards. Implications for nursing and health policy: Policy initiatives and guideline recommendations on nurse-sensitive outcome frameworks as part of patient safety should be a part of key priorities for policy makers. The commonly reported nurse-sensitive outcomes should be incorporated into daily bedside pediatric clinical nursing practice as a mechanism to evaluate and improve the quality of care, enhancement of patient safety, and better outcomes. Copyright © 2022 International Council of Nurses.
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Priorities for research during the Coronavirus SARS-CoV-2 (COVID-19) pandemic and beyond: A survey of nurses, midwives and health visitors in the United KingdomBackground: The Coronavirus SARS-CoV-2 (COVID-19) pandemic has had a significant burden on global healthcare systems. Nurses, midwives and health visitors remain critical to the rapid responses and innovative solutions required. Their views, however, on priorities for research is mainly muted, necessitating greater clarity to inform research that benefits patients and families across the life course. Aim(s): To identify priorities for research in relation to the COVID-19 pandemic and 'beyond', as recommended by nurses, midwives and health visitors across the four countries of the United Kingdom (UK). Method(s): A cross-sectional, web-based survey design was conducted (5th May-4th June 2020). In addition to the completion of demographic information, respondents identified up to three research areas important to their clinical care/practice in the context of COVID-19 and beyond. Data were imported for analysis into NVivo 12 (QSR International). Descriptive analysis was used to summarise the demographic variables. Free text responses were analysed using a semantic, inductive thematic analysis approach. Result(s): In total 1,296 responses were received from a self-selected sample of predominantly of female, registered nurses of white British ethnicity, located in England and working for acute care providers, providing 3,444 research priority recommendations. Four higher-order themes emerged, (1) New and unknown frontiers; (2) Care and treatment solutions; (3) Healthcare leadership and inclusive workforce; and (4) Emotional and mental health impact. Conclusion(s): At a time of significant global uncertainty, the collective voice of nursing, midwifery and health visiting is never more important to inform clinical research. Whilst generalisability is limited by the homogeneity of the sample, this is the first survey to elicit the priorities for research in relation to the COVID-19 pandemic and beyond from nurses, midwives and health visitors in the UK. Novel findings developed through a rigorous analytical approach illuminate areas that require both urgent and long-term attention and provide a platform to direct priority refinement, future research and the basis for evidence translation. Copyright © The Author(s) 2021.
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Acute paediatric inpatient care of children and young people admitted with self-harm or eating disorders: A single centre evaluationIn the United Kingdom, the prevalence of children and young people (CYP) accessing acute paediatric inpatient care with mental health problems is increasing, with self-harm and eating disorders particularly prevalent. This study evaluated CYP experiences of being in receipt of acute paediatric inpatient care following either self-harm or crisis stemming from an eating disorder to inform domains for a person-centred outcome measure (PCOM). A series of stakeholder engagement events were conducted between April and July 2015 where creative approaches were used to explore stakeholder experiences of care and to identify outcome domains that were subsequently prioritised using a Nominal Group Technique. Data were analysed using inductive thematic approach, with significance scores calculated for domain statements. Ninety-six stakeholders (15 CYP, eight parents and carers, and 73 professionals) participated. Findings showed five priority PCOM domains: privacy and surveillance; holistic care; making choices, appropriate communication; working together to achieve care goals; and respect and empowerment. This single centre evaluation highlights the need for a PCOM to be developed for this patient group that comprehensively reflects stakeholders' expectations in order to inform improvements to quality of acute paediatric care. Copyright © The Author(s) 2022.
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European survey on paediatric early warning systems, and other processes used to aid the recognition and response to children's deterioration on hospital wardsBACKGROUND: Internationally, there is an increasing trend in using Rapid Response Systems (RRS) to stabilize in-patient deterioration. Despite a growing evidence base, there remains limited understanding of the processes in place to aid the early recognition and response to deteriorating children in hospitals across Europe. AIM: To describe the processes in place for early recognition and response to in-patient deterioration in children in European hospitals. STUDY DESIGN: A cross-sectional opportunistic multi-centre European study, of hospitals with paediatric in-patients, using a descriptive self-reported, web-based survey, was conducted between September 2021 and March 2022. The sampling method used chain referral through members of European and national societies, led by country leads. The survey instrument was an adaptation to the survey of Recognition and Response Systems in Australia. The study received ethics approval. Descriptive analysis and Chi-squared tests were performed to compare results in European regions. RESULT(S): A total of 185 questionnaires from 21 European countries were received. The majority of respondents (n=153, 83%) reported having written policies, protocols, or guidelines, regarding the measurement of physiological observations. Over half (n=120, 65%) reported that their hospital uses a Paediatric Early Warning System (PEWS) and 75 (41%) reported having a Rapid Response Team (RRT). Approximately one-third (38%) reported that their hospital collects specific data about the effectiveness of their RRS, while 100 (54%) reported providing regular training and education to support it. European regional differences existed in PEWS utilization (North=98%, Centre=25%, South=44%, pRESULT(S): A total of 185 questionnaires from 21 European countries were received. The majority of respondents (n=153, 83%) reported having written policies, protocols, or guidelines, regarding the measurement of physiological observations. Over half (n=120, 65%) reported that their hospital uses a Paediatric Early Warning System (PEWS) and 75 (41%) reported having a Rapid Response Team (RRT). Approximately one-third (38%) reported that their hospital collects specific data about the effectiveness of their RRS, while 100 (54%) reported providing regular training and education to support it. European regional differences existed in PEWS utilization (North=98%, Centre=25%, South=44%, pRESULT(S): A total of 185 questionnaires from 21 European countries were received. The majority of respondents (n=153, 83%) reported having written policies, protocols, or guidelines, regarding the measurement of physiological observations. Over half (n=120, 65%) reported that their hospital uses a Paediatric Early Warning System (PEWS) and 75 (41%) reported having a Rapid Response Team (RRT). Approximately one-third (38%) reported that their hospital collects specific data about the effectiveness of their RRS, while 100 (54%) reported providing regular training and education to support it. European regional differences existed in PEWS utilization (North=98%, Centre=25%, South=44%, pCONCLUSION(S): RRS practices in European hospitals are heterogeneous. Differences in the uptake of PEWS and RRS process evaluation emerged across Europe. RELEVANCE TO CLINICAL PRACTICE: It is important to scope practices for the safe monitoring and management of deteriorating children in hospital across Europe. To reduce variance in practice, a consensus statement endorsed by paediatric and intensive care societies could provide guidance and resources to support PEWS implementation and for the operational governance required for continuous quality improvement.Copyright © 2024 The Author(s). Nursing in Critical Care published by John Wiley & Sons Ltd on behalf of British Association of Critical Care Nurses.
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Engaging nurses to achieve a culture of excellence: A children's hospital journey towards Pathway to Excellence accreditationHigh-quality nursing care is linked to improved patient experience and patient outcomes, so having work environments that nurture a culture of nursing excellence is fundamental to delivering high-quality patient care. The American Nurses Credentialing Center (ANCC) runs the Pathway to Excellence programme, an international accreditation recognising healthcare organisations that provide nurses with a positive and safe practice environment in which they can excel. In 2020, Nottingham Children's Hospital became the first children's hospital in Europe to gain Pathway to Excellence accreditation, demonstrating that it has developed a culture of nursing excellence and a positive environment for nurses to work in. This article describes the hospital's journey towards accreditation. Crucial to its success were strategic planning, transformational leadership and using a change management approach, as well as effective staff engagement guided by the ADKAR model for change, an acronym representing five individual outcomes in terms of awareness, desire, knowledge, ability and reinforcement. Copyright © 2021 RCN Publishing Company Ltd.. All rights reserved.
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A non-randomised feasibility study of the Rehabilitation Potential Assessment Tool (RePAT) in frail older people in the acute healthcare settingBackground: Rehabilitation potential involves predicting who will benefit from rehabilitation. Decisions about rehabilitation potential must take into account personal, clinical and contextual factors, a process which is complicated in the presence of acute ill-health and frailty. This study aimed to evaluate the feasibility and acceptability of the Rehabilitation Potential Assessment Tool (RePAT) - a 15 item holistic, person-centred assessment tool and training package - in the acute hospital setting. Method(s): A non-randomised feasibility study with nested semi-structured interviews explored whether RePAT was feasible and acceptable. Feasibility was tested by recruiting physiotherapy and occupational therapy participants delivering the RePAT intervention to patients alongside usual clinical care. Acceptability was tested by conducting semi-structured interviews with staff, patient and carer participants. Staff and patient characteristics were analysed using descriptive statistics. Interview data were analysed thematically. Fidelity of completed RePAT items was assessed against a priori criteria on how closely they matched tool guidance by two researchers. Mean values of the two scores were calculated. RePAT content was analysed and supported with verbatim quotes. Result(s): Six staff participants were recruited and trained. They assessed 26 patient participants using RePAT. Mean (SD) patient age was 86.16 (+/-6.39) years. 32% were vulnerable or mildly frail, 42% moderately frail and 26% severely or very severely frail using the Clinical Frailty Scale. Mean (SD) time to complete RePAT was 32.7 (+/-9.6) minutes. RePAT fidelity was good where 13 out of 15 items achieved a priori fidelity. RePAT was acceptable and tolerated by staff and patients. Staff participants reported RePAT enabled them to consider rehabilitation decisions in a more structured and consistent way. Patients and carer participants, although unable to comment directly on RePAT, reported being satisfied with their rehabilitation assessments which were found to embrace a person-centred approach. Conclusion(s): RePAT was found to be acceptable and feasible by staff, carers and patients. It allowed clinicians to make explicit their reasoning behind rehabilitation assessments and encouraged them to become more cognisant of factors which affected their clinical decision-making. Trial registration: ID ISRCTN31938453. Registered 05/10/2021. Copyright © 2022, The Author(s).
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Effect of implementing the NEWS2 escalation protocol in a large acute NHS trust: A retrospective cohort analysis of mortality, workload and ability of early warning score to predict death within 24 hoursObjectives To describe the inpatient population, establish patterns in admission and mortality over a 4-year period in different cohorts and assess the prognostic ability and workload implications of introducing the National Early Warning Score 2 (NEWS2) and associated escalation protocol. Design Retrospective cohort analyses of medical and surgical inpatient admissions. Setting Large teaching hospital with tertiary inpatient care and a major trauma centre employing an electronic observations platform, initially with a local early warning score, followed by NEWS2 introduction in June 2019. Participants 332 682 adult patients were admitted between 1 January 2016 and 31 December 2019. Outcome measures Mortality, workload and ability of early warning score to predict death within 24 hours. Results Admissions rose by 19% from 76 055 in 2016 to 90 587 in 2019. Total bed days rose by 10% from 433 382 to 477 485. Mortality fell from 3.7% to 3.1% and was significantly lower in patients discharged from a surgical specialty, 1.0%–1.2% (p<0.001). Total observations recorded increased by 14% from 1 976 872 in 2016 to 2 249 118 in 2019. 65% of observations were attributable to patients under medical specialties, 34% to patients under surgical specialties. Recorded escalations to the registrar were stable from January 2016 to May 2019 but trebled following the introduction of NEWS2 in June 2019. Conclusions There was an increase in hospital inpatient activity between 2016 and 2019, associated with a reduction in mortality and percentage of observations calculated as reaching threshold NEWS2 score of 7 for escalation to the registrar. The introduction of the NEWS2, with a higher sensitivity and lower specificity, when allied to its escalation protocol, was associated with a significant increase in actual recorded escalations to the registrar. This was more marked in the surgical population and would support refining threshold scores based on admission characteristics when developing the next iteration of NEWS.
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'It is designed for everybody to find their own level and to improve themselves'; views of older people and instructors of the Falls Management Exercise (FaME) programmeBackground Older adults are at increased risk of falls due to ageing, decreased muscle strength and impaired balance. Clinical trials have demonstrated the efficacy and effectiveness of the Falls Management Exercise (FaME) programme in improving functioning and preventing falls. However, programme completion is often low, impacting the potential benefits of FaME. Objective To explore the barriers and facilitators for participation and completion of the FaME programme from an instructor and participant perspective. Methods Semi-structured interviews were conducted with 20 FaME users and seven Postural Stability Instructors from the East Midlands region of England, UK. Interviews were conducted using a topic guide and explored their views of the programme, intended benefits, reasons for participating, instructor’s approach and venue facilities. Data were transcribed verbatim and analysed using thematic analysis. Written informed consent was obtained from all participants and instructors. Results Common themes identified by participants and instructors for adherence related to perceived health benefits, psychological well-being, intervention characteristics, cost, instructors’ qualities, opportunity to socialise, venue accessibility and facilities. Further factors such as maintaining independence, discipline, relationship with peers and caring responsibilities influenced participants’ engagement with the programme. Instructor factors such as progression were also reported as important predictors. Conclusions Instructor and participant factors influence uptake, attendance and adherence of FaME. The findings from this study can inform the development and improvement of additional falls-prevention programmes. It can also guide marketing strategies to promote uptake of exercise-based falls-prevention programmes among older adults.
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RCN Gastroenterology Committee team member spotlight: Amanda Cetroni, gastroenterology research nurseSenior research nurse and RCN Gastroenterology Committee team member, Amanda Cetroni, highlights the diverse skills required for her role and emphasises the importance of clinical research for improving healthcare outcomes.
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Reply to: Inaccuracy of pulse oximetry in darker-skinned patients is unchanged across 32 yearsWe thank M.J. Tobin and A. Jubran for their interest in our data [1]. As they state, it is an extension of a body of work that they helped establish over 30 years ago.
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Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infectionsAlthough the antimicrobial potential of nitric oxide (NO) is widely published, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses. Endogenous antimicrobial activity is largely mediated by high local NO concentrations produced by cellular inducible nitric oxide synthase, and by derivative reactive nitrogen oxide species including peroxynitrite and S-nitrosothiols. NO may be taken as dietary substrate (inorganic nitrate, L-arginine), and therapeutically as gaseous NO, and transdermal, sublingual, oral, intranasal and intravenous nitrite or nitrate. Numerous preclinical studies have demonstrated that NO has generic static and cidal activities against viruses (including beta-coronaviruses such as SARS-CoV-2), bacteria, protozoa and fungi/yeasts in vitro. Therapeutic effects have been seen in animal models in vivo, and phase II trials have demonstrated that NO donors can reduce microbial infection. Nevertheless, excess NO, as occurs in septic shock, is associated with increased morbidity and mortality. In view of the dose-dependent positive and negative effects of NO, safety and efficacy trials of NO and its donors are needed for assessing their role in the prevention and treatment of infections. Trials should test dietary inorganic nitrate for pre- or post-exposure prophylaxis and gaseous NO or oral, topical or intravenous nitrite and nitrate for treatment of mild-to-severe infections, including due to SARS-CoV-2 (COVID-19). This review summarises the evidence base from in vitro, in vivo and early phase clinical studies of NO activity in viral, bacterial, protozoal and fungal infections. Copyright: © 2021 Bath PM et al.
