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.

Polysaccharide mimicry of the epitope of the broadly neutralizing anti-HIV antibody, 2G12, induces enhanced antibody responses to self oligomannose glycans.

Immunologically, "self" carbohydrates protect the HIV-1 surface glycoprotein, gp120, from antibody recognition. However, one broadly neutralizing antibody, 2G12, neutralizes primary viral isolates by direct recognition of Manalpha1-->2Man motifs formed by the host-derived oligomannose glycans of the viral envelope. Immunogens, capable of eliciting antibodies of similar specificity to 2G12, are therefore candidates for HIV/AIDS vaccine development. In this context, it is known that the yeast mannan polysaccharides exhibit significant antigenic mimicry with the glycans of HIV-1. Here, we report that modulation of yeast polysaccharide biosynthesis directly controls the molecular specificity of cross-reactive antibodies to self oligomannose glycans. Saccharomyces cerevisiae mannans are typically terminated by alpha1-->3-linked mannoses that cap a Manalpha1-->2Man motif that otherwise closely resembles the part of the oligomannose epitope recognized by 2G12. Immunization with S. cerevisiae deficient for the alpha1-->3 mannosyltransferase gene (DeltaMnn1), but not with wild-type S. cerevisiae, reproducibly elicited antibodies to the self oligomannose glycans. Carbohydrate microarray analysis of DeltaMnn1 immune sera revealed fine carbohydrate specificity to Manalpha1-->2Man units, closely matching that of 2G12. These specificities were further corroborated by enzyme-linked immunosorbent assay with chemically defined glycoforms of gp120. These antibodies exhibited remarkable similarity in the carbohydrate specificity to 2G12 and displayed statistically significant, albeit extremely weak, neutralization of HIV-1 compared to control immune sera. These data confirm the Manalpha1-->2Man motif as the primary carbohydrate neutralization determinant of HIV-1 and show that the genetic modulation of microbial polysaccharides is a route towards immunogens capable of eliciting antibody responses to the glycans of HIV-1.