Improving the early identification of COVID-19 pneumonia: a narrative review.

Delayed presentation of COVID-19 pneumonia increases the risk of mortality and need for high-intensity healthcare. Conversely, early identification of COVID-19 pneumonia grants an opportunity to intervene early and thus prevent more complicated, protracted and less successful hospital admissions. To improve the earlier detection of COVID-19 pneumonia in the community we provide a narrative review of current evidence examining the clinical parameters associated with early disease progression. Through an evolving literature review, we examined: the symptoms that may suggest COVID-19 progression; the timing of deterioration; the utility of basic observations, clinical examination and chest X-ray; the value of postexertion oxygen saturations; and the use of CRP to monitor disease progression. We go on to discuss the challenges in monitoring the COVID-19 patient in the community and discuss thresholds for further assessment. Confusion, persistent fever and shortness of breath were identified as worrying symptoms suggestive of COVID-19 disease progression necessitating urgent clinical contact. Importantly, a significant proportion of COVID-19 pneumonia patients appear not to suffer dyspnoea despite severe disease. Patients with this asymptomatic hypoxia seem to have a poorer prognosis. Such patients may present with other signs of hypoxia: severe fatigue, exertional fatigue and/or altered mental status. We found duration of symptoms to be largely unhelpful in determining risk, with evidence of deterioration at any point in the disease. Basic clinical parameters (pulse, respiratory rate, blood pressure, temperature and oxygen saturations (SpO2)) are likely of high value in detecting the deteriorating community COVID-19 patient and/or COVID-19 mimickers/complications (eg, sepsis, bacterial pneumonia and pulmonary embolism). Of these, SpO2 carried the greatest utility in detecting COVID-19 progression. CRP is an early biochemical parameter predictive of disease progression and used appropriately is likely to contribute to the early identification of COVID-19 pneumonia. Identifying progressive COVID-19 in the community is feasible using basic clinical questions and measurements. As such, if we are to limit the mortality, morbidity and the need for complicated, protracted admissions, monitoring community COVID-19 cases for signs of deterioration to facilitate early intervention is a viable strategy.

Reliability of COVID-19 symptom checkers as national triage tools: an international case comparison study.

OBJECTIVES: Triage is a critical component of the pandemic response. It affects morbidity, mortality and how effectively the available healthcare resources are used. In a number of nations the pandemic has sponsored the adoption of novel, online, patient-led triage systems-often referred to as COVID-19 symptom checkers. The current safety and reliability of these new automated triage systems remain unknown. METHODS: We tested six symptom checkers currently in use as triage tools at a national level against 52 cases simulating COVID-19 of various severities to determine if the symptom checkers appropriately triage time-critical cases onward to healthcare contact. We further analysed and compared each symptom checker to determine the discretionary aspects of triage decision-making that govern the automated advice generated. RESULTS: Of the 52 clinical presentations, the absolute rate of onward referral to any form of healthcare contact was: Singapore 100%, the USA 67%, Wales 65%, England 62%, Scotland 54% and Northern Ireland 46%. Triage decisions were broadly based on either estimates of 'risk' or 'disease severity'. Risk-based symptom checkers were more reliable, with severity-based symptom checkers often triaging time-critical cases to stay home without clinical contact or follow-up. CONCLUSION: The COVID-19 symptom checkers analysed here were unable to reliably discriminate between mild and severe COVID-19. Risk-based symptom checkers may hold some promise of contributing to pandemic case management, while severity-based symptom checkers-the CDC and NHS 111 versions-confer too much risk to both public and healthcare services to be deemed a viable option for COVID-19 triage.

Oxygen and Mortality in COVID-19 Pneumonia: A Comparative Analysis of Supplemental Oxygen Policies and Health Outcomes Across 26 Countries.

Introduction: Hypoxia is the main cause of morbidity and mortality in COVID-19. During the COVID-19 pandemic, some countries have reduced access to supplemental oxygen, whereas other nations have maintained and even improved access to supplemental oxygen. We examined whether variation in the nationally determined oxygen guidelines had any association with national mortality rates in COVID-19. Methods: Three independent investigators searched for, identified, and extracted the nationally recommended target oxygen levels for the commencement of oxygen in COVID-19 pneumonia from the 29 worst affected countries. Mortality estimates were calculated from three independent sources. We then applied both parametric (Pearson's R) and non-parametric (Kendall's Tau B) tests of bivariate association to determine the relationship between case fatality rate (CFR) and target SpO2, and also between potential confounders and CFR. Results: Of the 26 nations included, 15 had employed conservative oxygen strategies to manage COVID-19 pneumonia. Of them, Belgium, France, USA, Canada, China, Germany, Mexico, Spain, Sweden, and the UK guidelines advised commencing oxygen when oxygen saturations (SpO2) fell to 91% or less. A statistically significant correlation was found between SpO2 and CFR both parametrically (R = -0.53, P < 0.01) and non-parametrically (-0.474, P < 0.01). Conclusion: Our study highlights the disparity in oxygen provision for COVID-19 patients between the nations analysed. In those nations that pursued a conservative oxygen strategy, there was an association with higher national mortality rates. We discuss the potential reasons for such an association.

Performance of national COVID-19 'symptom checkers': a comparative case simulation study.

OBJECTIVES: Identifying those individuals requiring medical care is a basic tenet of the pandemic response. Here, we examine the COVID-19 community triage pathways employed by four nations, specifically comparing the safety and efficacy of national online 'symptom checkers' used within the triage pathway. METHODS: A simulation study was conducted on current, nationwide, patient-led symptom checkers from four countries (Singapore, Japan, USA and UK). 52 cases were simulated to approximate typical COVID-19 presentations (mild, moderate, severe and critical) and COVID-19 mimickers (eg, sepsis and bacterial pneumonia). The same simulations were applied to each of the four country's symptom checkers, and the recommendations to refer on for medical care or to stay home were recorded and compared. RESULTS: The symptom checkers from Singapore and Japan advised onward healthcare contact for the majority of simulations (88% and 77%, respectively). The USA and UK symptom checkers triaged 38% and 44% of cases to healthcare contact, respectively. Both the US and UK symptom checkers consistently failed to identify severe COVID-19, bacterial pneumonia and sepsis, triaging such cases to stay home. CONCLUSION: Our results suggest that whilst 'symptom checkers' may be of use to the healthcare COVID-19 response, there is the potential for such patient-led assessment tools to worsen outcomes by delaying appropriate clinical assessment. The key features of the well-performing symptom checkers are discussed.

The CHIR Score for Evaluating the Hyperimmune Response in COVID-19: A Preliminary Concept.

Similar to SARS and MERS, the host immune response to COVID-19 is implicated in the severity of the disease itself. Here, we investigate the possible use of scoring systems to help guide clinicians in their determination as to when to commence immunosuppressive treatment in COVID-19. We utilized the relatively established clinical and biochemical severity indicators from large cohort studies to develop a potential scoring system for the hyperimmune response in COVID-19.

Early intervention likely improves mortality in COVID-19 infection.

While some risk factors have been identified, the reasons for the disparities in disease progression with COVID-19 are unclear, with some patients developing progressive and severe disease while in others the course is benign. Given this sense of randomness, and in the absence of a definitive treatment, medical professionals can feel helpless. It is useful to remember how much can be done to affect the trajectory of illness, even without a 'magic bullet'. With evidence emerging that late presentation is directly associated with increased mortality, we make the case for increased vigilance in the community and earlier intervention.

Room to Breathe: The Impact of Oxygen Rationing on Health Outcomes in SARS-CoV2.

As the primary surge of coronavirus disease 2019 (COVID-19) wanes in many countries, it is important to reconsider best practice. More cases, probably the majority of cases, are yet to come. Hopefully, during this next phase, we will have more time, more resources, and more experience from which to affect better outcomes. Here, we examine the compromised oxygen strategy that many nations followed. We explore the evidence related to such strategies and discuss the potential mortality impact of delaying oxygen treatment in COVID-19 pneumonia.

Neuro-immune abnormalities in autism and their relationship with the environment: a variable insult model for autism.

Autism spectrum disorder (ASD) is a heterogeneous condition affecting an individual's ability to communicate and socialize and often presents with repetitive movements or behaviors. It tends to be severe with less than 10% achieving independent living with a marked variation in the progression of the condition. To date, the literature supports a multifactorial model with the largest, most detailed twin study demonstrating strong environmental contribution to the development of the condition. Here, we present a brief review of the neurological, immunological, and autonomic abnormalities in ASD focusing on the causative roles of environmental agents and abnormal gut microbiota. We present a working hypothesis attempting to bring together the influence of environment on the abnormal neurological, immunological, and neuroimmunological functions and we explain in brief how such pathophysiology can lead to, and/or exacerbate ASD symptomatology. At present, there is a lack of consistent findings relating to the neurobiology of autism. Whilst we postulate such variable findings may reflect the marked heterogeneity in clinical presentation and as such the variable findings may be of pathophysiological relevance, more research into the neurobiology of autism is necessary before establishing a working hypothesis. Both the literature review and hypothesis presented here explore possible neurobiological explanations with an emphasis of environmental etiologies and are presented with this bias.