Blood Inflammatory Biomarkers Differentiate Inpatient and Outpatient Coronavirus Disease 2019 From Influenza.

Background: The ongoing circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a diagnostic challenge because symptoms of coronavirus disease 2019 (COVID-19) are difficult to distinguish from other respiratory diseases. Our goal was to use statistical analyses and machine learning to identify biomarkers that distinguish patients with COVID-19 from patients with influenza. Methods: Cytokine levels were analyzed in plasma and serum samples from patients with influenza and COVID-19, which were collected as part of the Centers for Disease Control and Prevention's Hospitalized Adult Influenza Vaccine Effectiveness Network (inpatient network) and the US Flu Vaccine Effectiveness (outpatient network). Results: We determined that interleukin (IL)-10 family cytokines are significantly different between COVID-19 and influenza patients. The results suggest that the IL-10 family cytokines are a potential diagnostic biomarker to distinguish COVID-19 and influenza infection, especially for inpatients. We also demonstrate that cytokine combinations, consisting of up to 3 cytokines, can distinguish SARS-CoV-2 and influenza infection with high accuracy in both inpatient (area under the receiver operating characteristics curve [AUC] = 0.84) and outpatient (AUC = 0.81) groups, revealing another potential screening tool for SARS-CoV-2 infection. Conclusions: This study not only reveals prospective screening tools for COVID-19 infections that are independent of polymerase chain reaction testing or clinical condition, but it also emphasizes potential pathways involved in disease pathogenesis that act as potential targets for future mechanistic studies.

SARS-CoV-2 Antibody Response Is Associated with Age and Body Mass Index in Convalescent Outpatients.

COVID-19 has had an unprecedented global impact on human health. Understanding the Ab memory responses to infection is one tool needed to effectively control the pandemic. Among 173 outpatients who had virologically confirmed SARS-CoV-2 infection, we evaluated serum Ab concentrations, microneutralization activity, and enumerated SARS-CoV-2-specific B cells in convalescent human blood specimens. Serum Ab concentrations were variable, allowing for stratification of the cohort into high and low responders. Neither participant sex, the timing of blood sampling following the onset of illness, nor the number of SARS-CoV-2 spike protein-specific B cells correlated with serum Ab concentration. Serum Ab concentration was positively associated with microneutralization activity and participant age, with participants under the age of 30 showing the lowest Ab level. These data suggest that young adult outpatients did not generate as robust Ab memory, compared with older adults. Body mass index was also positively correlated with serum Ab levels. Multivariate analyses showed that participant age and body mass index were independently associated with Ab levels. These findings have direct implications for public health policy and current vaccine efforts. Knowledge gained regarding Ab memory following infection will inform the need for vaccination in those previously infected and allow for a better approximation of population-wide protective immunity.

SARS-CoV-2 Antibody Response is Associated with Age in Convalescent Outpatients.

COVID-19 has had an unprecedented global impact on human health. Understanding the antibody memory responses to infection is one tool needed to effectively control the pandemic. Among 173 outpatients who had virologically confirmed SARS-CoV-2 infection, we evaluated serum antibody concentrations, microneutralization activity, and enumerated SARS-CoV-2 specific B cells in convalescent blood specimens. Serum antibody concentrations were variable, allowing for stratification of the cohort into high and low responders. Serum antibody concentration was positively associated with microneutralization activity and participant age, with participants under the age of 30 showing the lowest antibody level. Neither participant sex, the timing of blood sampling following the onset of illness, nor the number of SARS-CoV-2 spike protein specific B cells correlated with serum antibody concentration. These data suggest that young adult outpatients did not generate as robust antibody memory, compared with older adults. Further, serum antibody concentration or neutralizing activity trended but did not significantly correlate with the number of SARS-CoV-2 memory B cells. These findings have direct implications for public health policy and current vaccine efforts. Knowledge gained regarding antibody memory following infection will inform the need for vaccination in those previously infected and allow for a better approximation of population-wide protective immunity.

Cost-effectiveness of procalcitonin-guided antibiotic use in community acquired pneumonia.

BACKGROUND: Although prior randomized trials have demonstrated that procalcitonin-guided antibiotic therapy effectively reduces antibiotic use in patients with community-acquired pneumonia (CAP), uncertainties remain regarding use of procalcitonin protocols in practice. OBJECTIVE: To estimate the cost-effectiveness of procalcitonin protocols in CAP. DESIGN: Decision analysis using published observational and clinical trial data, with variation of all parameter values in sensitivity analyses. PATIENTS: Hypothetical patient cohorts who were hospitalized for CAP. INTERVENTIONS: Procalcitonin protocols vs. usual care. MAIN MEASURES: Costs and cost per quality adjusted life year gained. KEY RESULTS: When no differences in clinical outcomes were assumed, consistent with clinical trials and observational data, procalcitonin protocols cost $10-$54 more per patient than usual care in CAP patients. Under these assumptions, results were most sensitive to variations in: antibiotic cost, the likelihood that antibiotic therapy was initiated less frequently or over shorter durations, and the likelihood that physicians were nonadherent to procalcitonin protocols. Probabilistic sensitivity analyses, incorporating procalcitonin protocol-related changes in quality of life, found that protocol use was unlikely to be economically reasonable if physician protocol nonadherence was high, as observational study data suggest. However, procalcitonin protocols were favored if they decreased hospital length of stay. CONCLUSIONS: Procalcitonin protocol use in hospitalized CAP patients, although promising, lacks physician nonadherence and resource use data in routine care settings, which are needed to evaluate its potential role in patient care.

Knowledge and beliefs about influenza, pneumococcal disease, and immunizations among older people.

OBJECTIVES: Despite the burden of disease caused by influenza and pneumococcus, immunization rates are moderate and have not reached national goals set for 2010. This study's objective was to identify patient knowledge, attitudes, and beliefs that serve as facilitators of and barriers to influenza and pneumococcal vaccination. DESIGN: A survey conducted in 2000 by computer-assisted telephone interviewing. SETTING: To encounter a broad spectrum of patients and healthcare systems, we sampled patients at inner-city health centers, Department of Veterans Affairs outpatient clinics, and rural and suburban practices. PARTICIPANTS: Inclusion criteria were patients aged 66 and older and an office visit after September 30, 1998. MEASUREMENTS: Responses to questionnaire. RESULTS: Overall, 1,007 (82%) interviews were completed among 1,234 people contacted by phone. Vaccination against pneumococcal disease was significantly related to being able to accurately describe one or more classic symptoms of pneumonia (P =.05). Vaccination against influenza and pneumococcal disease was significantly related to belief that vaccination was the best way to prevent these diseases (P <.001). The unvaccinated reported that they felt they were not likely to contract influenza and that they did not know they needed the pneumococcal vaccine. Access was not related to vaccination status. CONCLUSIONS: Educational campaigns to increase vaccination rates among older adults should focus on symptoms of, risk for, and severity of influenza and pneumococcal diseases and encouraging physicians to recommend the vaccines to their patients.