Pre-Existing and Pragmatically-Derived Immunohematologic Phenotypes Predict All-Cause and COVID-19-Specific Mortality: A 'Population Immunology' Approach (preprint)

Background: Dysregulation of immunohematologic function (IHF) promotes cardiovascular disease and impairs protective responses to cancer and infection. A pragmatic method to identify those as risk due to IHF could improve the precision of preventive interventions and provide insight into the heterogeneity of immunologic capacity. We developed and validated a method to distill complete blood cell count data into distinct IHF profiles of prognostic relevance. Methods: We adapted latent profile analysis methods to simultaneously identify distinct groups of patients with respect to 10 immunohematologic indicators and regress time to all-cause mortality on this latent IHF profile. The model was developed using data from 30274 National Health and Nutrition Examination Survey participants and externally validated in 49851 outpatients in the Veterans Heath Administration (VHA) system and 44142 SARS-CoV-2 positive VHA patients.Findings: Ten distinct IHF profiles were identified. Profile 1, with relative mild pan-leukopenia in absence of red cell abnormalities, was associated with the best long term survival in each setting. Profiles 8-10, featuring anemia/anisocytosis especially in the setting of lymphopenia (Profiles 9-10) were associated with adjusted hazard ratio (HR) estimates of 1.76-2.62 for mortality across the three cohorts, compared to Profile 1. Profiles 6-7, featuring relative neutrophilia, were less common but also independently associated with mortality risk, especially after COVID-19 infection (Profile 7 HR [95% CI]: 2.51 [1.63 – 3.86]). The magnitude of adjusted risk conveyed by IHF profiles was greater than individual clinical risk factors (i.e., smoking, diabetes) or prevalent co-morbidities.Interpretation: Distinct immunohematologic endotypes can be identified during routine blood panels which project to mortality risk on par with a decade of life, additive to demographic and clinical factors. Applications that consider immunohematologic dysfunction may improve prevention of common fatal diseases, including COVID-19.Funding Information:This study was funded in part by The National Institute on Aging (R01AG055480; Dalton and Perzynski), the National Cancer Institute (U01CA260513; Zidar and Chan), and the United States Veteran Administration (COVID19-8900-05; Zidar). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veteran Affairs or the National Institutes of Health.Declaration of Interests: No conflict of interest exists between any of the authors and the contents of this paper.Ethics Approval Statement: The study was approved by the Institutional Review Board of the Louis Stokes Cleveland VAMC.

On the Front (Phone) Lines: Results of a COVID-19 Hotline in Northeast Ohio (preprint)

ImportanceSevere acute respiratory syndrome coronavirus (SARS-CoV-2) and the associated coronavirus disease of 2019 (COVID-19) have presented immense challenges for health care systems. Many regions have struggled to adapt to disruptions to health care practice and employ systems that effectively manage the demand for services. ObjectiveTo examine the effectiveness of the first five weeks of a 24/7 physician-staffed COVID-19 hotline. DesignCohort study using electronic health records. SettingA single large health care system in Northeast Ohio. ParticipantsDuring 5 weeks of operation, 10,112 patients called the hotline (callers) and were evaluated by a registered nurse (RN) using standardized protocols. Of these, 4,213 (42%) were referred for a physician telehealth visit (telehealth patients). The mean age of callers was 42 years. 67% were female, 51% white, and 46% were on Medicaid or uninsured. InterventionPhysician telehealth visits for COVID-19. Main Outcomes and MeasuresWe describe clinical diagnosis, patient characteristics (age, sex race/ethnicity, smoking status, insurance status), and visit disposition. We use logistic regression to evaluate associations between patient characteristics, visit disposition and subsequent emergency department use, hospitalization, and SARS-Cov-2 PCR testing. ResultsCommon caller concerns included cough, fever, and shortness of breath. Most telehealth patients (79%) were advised to self-isolate at home, 14% were determined to be unlikely to have COVID-19, 3% were advised to seek emergency care, and 4% had miscellaneous other dispositions. A total of 287 (7%) patients had a subsequent ED visit, and 44 (1%) were hospitalized with a COVID-19 diagnosis. Of the callers, 482 (5%) had a COVID-19 test reported with 69 (14%) testing positive. Among patients advised to stay at home, 83% had no further face-to-face visits. In multivariable results, only a physician recommendation to seek emergency care was associated with emergency room use (OR=4.73, 95%CI 1.37-16.39, p=.014). Only older age was associated with having a positive test result. Conclusions and RelevanceRobust, physician-directed telehealth services can meet a wide range of needs during the acute phase of a pandemic, conserving scarce resources such as personal protective equipment and testing supplies and preventing the spread of infections to patients and health care workers. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the feasibility and effectiveness of physician telehealth services during a pandemic? FindingsIn this cohort study of a COVID-19 telehealth hotline that included 10,112 callers and 4,213 physician telehealth visits, most patients (79%) were advised to self-isolate at home, 14% were found unlikely to have COVID-19, 4% dispositions (e.g. testing or office visit) and 3% were advised to immediately seek care emergency department. 83% of patients who were advised to stay home did not require in-person visits. MeaningPhysician-directed telehealth services conserve scarce resources and provide effective, equitable care during a pandemic without compromising patient safety.

Time-Varying COVID-19 Reproduction Number in the United States (preprint)

The basic reproduction number is the average number of people to whom an infected person transmits the infection when virtually all individuals in a population are susceptible. We sought to calculate the current reproduction number for COVID-19 for each state in the United States. For the entire United States, the reproduction number declined from 4.02 to 1.51 between March 17 and April 1, 2020. We also found that the reproduction number for COVID-19 has declined in most states over the past two weeks which suggests that social isolation measures may be having a beneficial effect.