Risk Factors Associated with Post-Acute Sequelae of SARS-CoV-2 in an EHR Cohort: A National COVID Cohort Collaborative (N3C) Analysis as part of the NIH RECOVER program (preprint)

BackgroundMore than one-third of individuals experience post-acute sequelae of SARS-CoV-2 infection (PASC, which includes long-COVID). ObjectiveTo identify risk factors associated with PASC/long-COVID. DesignRetrospective case-control study. Setting31 health systems in the United States from the National COVID Cohort Collaborative (N3C). Patients8,325 individuals with PASC (defined by the presence of the International Classification of Diseases, version 10 code U09.9 or a long-COVID clinic visit) matched to 41,625 controls within the same health system. MeasurementsRisk factors included demographics, comorbidities, and treatment and acute characteristics related to COVID-19. Multivariable logistic regression, random forest, and XGBoost were used to determine the associations between risk factors and PASC. ResultsAmong 8,325 individuals with PASC, the majority were >50 years of age (56.6%), female (62.8%), and non-Hispanic White (68.6%). In logistic regression, middle-age categories (40 to 69 years; OR ranging from 2.32 to 2.58), female sex (OR 1.4, 95% CI 1.33-1.48), hospitalization associated with COVID-19 (OR 3.8, 95% CI 3.05-4.73), long (8-30 days, OR 1.69, 95% CI 1.31-2.17) or extended hospital stay (30+ days, OR 3.38, 95% CI 2.45-4.67), receipt of mechanical ventilation (OR 1.44, 95% CI 1.18-1.74), and several comorbidities including depression (OR 1.50, 95% CI 1.40-1.60), chronic lung disease (OR 1.63, 95% CI 1.53-1.74), and obesity (OR 1.23, 95% CI 1.16-1.3) were associated with increased likelihood of PASC diagnosis or care at a long-COVID clinic. Characteristics associated with a lower likelihood of PASC diagnosis or care at a long-COVID clinic included younger age (18 to 29 years), male sex, non-Hispanic Black race, and comorbidities such as substance abuse, cardiomyopathy, psychosis, and dementia. More doctors per capita in the county of residence was associated with an increased likelihood of PASC diagnosis or care at a long-COVID clinic. Our findings were consistent in sensitivity analyses using a variety of analytic techniques and approaches to select controls. ConclusionsThis national study identified important risk factors for PASC such as middle age, severe COVID-19 disease, and specific comorbidities. Further clinical and epidemiological research is needed to better understand underlying mechanisms and the potential role of vaccines and therapeutics in altering PASC course. KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat risk factors are associated with post-acute sequelae of SARS-CoV-2 (PASC) in the National COVID Cohort Collaborative (N3C) EHR Cohort? FindingsThis national study identified important risk factors for PASC such as middle age, severe COVID-19 disease, specific comorbidities, and the number of physicians per capita. MeaningClinicians can use these risk factors to identify patients at high risk for PASC while they are still in the acute phase of their infection and also to support targeted enrollment in clinical trials for preventing or treating PASC.

Generalizable Long COVID Subtypes: Findings from the NIH N3C and RECOVER Programs (preprint)

Accurate stratification of patients with Post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) would allow precision clinical management strategies and could enable more focussed investigation of the molecular pathogenetic mechanisms of this disease. However, the natural history of long COVID is incompletely understood and characterized by an extremely wide range of manifestations that are difficult to analyze computationally. In addition, the generalizability of machine learning classification of COVID-19 clinical outcomes has rarely been tested. We present a method for computationally modeling long COVID phenotype data based on electronic healthcare records (EHRs) and for assessing pairwise phenotypic similarity between patients using semantic similarity. Using unsupervised machine learning (k-means clustering), we found six distinct clusters of long COVID patients, each with distinct profiles of phenotypic abnormalities with enrichments in pulmonary, cardiovascular, neuropsychiatric, and constitutional symptoms such as fatigue and fever. There was a highly significant association of cluster membership with a range of pre-existing conditions and with measures of severity during acute COVID-19. We show that the clusters we identified in one hospital system were generalizable across different hospital systems. Semantic phenotypic clustering can provide a foundation for assigning patients to stratified subgroups for natural history or therapy studies on long COVID.

Public sentiment analysis and topic modeling regarding COVID-19 vaccines on the Reddit social media platform: A call to action for strengthening vaccine confidence (preprint)

The COVID-19 pandemic fueled one of the most rapid vaccine developments in history. However, misinformation spread through online social media often leads to negative vaccine sentiment and hesitancy. To investigate COVID-19 vaccine-related discussion in social media, we conducted a sentiment analysis and Latent Dirichlet Allocation topic modeling on textual data collected from 13 Reddit communities focusing on the COVID-19 vaccine from Dec 1, 2020, to May 15, 2021. Data were aggregated and analyzed by month to detect changes in any sentiment and latent topics. ty analysis suggested these communities expressed more positive sentiment than negative regarding the vaccine-related discussions and has remained static over time. Topic modeling revealed community members mainly focused on side effects rather than outlandish conspiracy theories. Covid-19 vaccine-related content from 13 subreddits show that the sentiments expressed in these communities are overall more positive than negative and have not meaningfully changed since December 2020. Keywords indicating vaccine hesitancy were detected throughout the LDA topic modeling. Public sentiment and topic modeling analysis regarding vaccines could facilitate the implementation of appropriate messaging, digital interventions, and new policies to promote vaccine confidence.

An Urban Population Health Observatory System to Support COVID-19 Pandemic Preparedness, Response, and Management: Design and Development Study (preprint)

Background: COVID-19 is impacting people worldwide and is currently a leading cause of death in many countries. This study sought to redefine the Healthy People 2030 SDoH taxonomy to accommodate the COVID-19 pandemic. Furthermore, we aim to provide a blueprint and implement a prototype for the Urban Population Health Observatory (UPHO), a web-based platform that integrates classified group-level SDoH indicators to individual- and aggregate-level population health data. The process of building the UPHO involves collecting and integrating data from several sources, classifying the collected data into drivers and outcomes, incorporating data science techniques for calculating measurable indicators from the raw variables, and studying the extent to which interventions are identified or developed to mitigate drivers that lead to the undesired outcomes. We generated and classified the indicators of social determinants of health, which are linked to COVID-19. To display the functionalities of the UPHO platform, we presented a prototype design to demonstrate its features. We provided a use case scenario for 4 different users. UPHO serves as an apparatus for implementing effective interventions and can be adopted as a global platform for chronic and infectious diseases. The UPHO surveillance platform provides a novel approach and novel insights into immediate and long-term health policy responses to the COVID-19 pandemic and other future public health crises. The UPHO assists public health organizations and policymakers in their efforts in reducing health disparities, achieving health equity, and improving urban population health.