Prioritization of COVID-19 risk factors in July 2020 and February 2021 in the UK.

BACKGROUND: Risk for COVID-19 positivity and hospitalization due to diverse environmental and sociodemographic factors may change as the pandemic progresses. METHODS: We investigated the association of 360 exposures sampled before COVID-19 outcomes for participants in the UK Biobank, including 9268 and 38,837 non-overlapping participants, sampled at July 17, 2020 and February 2, 2021, respectively. The 360 exposures included clinical biomarkers (e.g., BMI), health indicators (e.g., doctor-diagnosed diabetes), and environmental/behavioral variables (e.g., air pollution) measured 10-14 years before the COVID-19 time periods. RESULTS: Here we show, for example, "participant having son and/or daughter in household" was associated with an increase in incidence from 20% to 32% (risk difference of 12%) between timepoints. Furthermore, we find age to be increasingly associated with COVID-19 positivity over time from Risk Ratio [RR] (per 10-year age increase) of 0.81 to 0.6 (hospitalization RR from 1.18 to 2.63, respectively). CONCLUSIONS: Our data-driven approach demonstrates that time of pandemic plays a role in identifying risk factors associated with positivity and hospitalization.

Social, demographic, and environmental factors have been shown to impact whether a person becomes infected following SARS-CoV-2 exposure. However, it is unclear whether the impact of different factors has changed as the pandemic has progressed. Here we analyze 360 factors and whether they are associated with the proportion of people being found to be infected with SARS-CoV-2 across two periods of time in the UK. Overall, we found that different risk factors were associated with testing positive for SARS-CoV-2 infection early in the pandemic compared to later in the pandemic. These results highlight that public health priorities should be adjusted as a consequence of changing risk and susceptibility to infection as the pandemic progresses.

Evolving phenotypes of non-hospitalized patients that indicate long COVID.

BACKGROUND: For some SARS-CoV-2 survivors, recovery from the acute phase of the infection has been grueling with lingering effects. Many of the symptoms characterized as the post-acute sequelae of COVID-19 (PASC) could have multiple causes or are similarly seen in non-COVID patients. Accurate identification of PASC phenotypes will be important to guide future research and help the healthcare system focus its efforts and resources on adequately controlled age- and gender-specific sequelae of a COVID-19 infection. METHODS: In this retrospective electronic health record (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3-6 and 6-9 months after the test and by age and gender. Data from longitudinal diagnosis records stored in EHRs from Mass General Brigham in the Boston Metropolitan Area was used for the analyses. Statistical analyses were performed on data from March 2020 to June 2021. Study participants included over 96 thousand patients who had tested positive or negative for COVID-19 and were not hospitalized. RESULTS: We identified 33 phenotypes among different age/gender cohorts or time windows that were positively associated with past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients' medical records 2 months or longer after a COVID-19 RT-PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR 2.60, 95% CI [1.94-3.46]), alopecia (OR 3.09, 95% CI [2.53-3.76]), chest pain (OR 1.27, 95% CI [1.09-1.48]), chronic fatigue syndrome (OR 2.60, 95% CI [1.22-2.10]), shortness of breath (OR 1.41, 95% CI [1.22-1.64]), pneumonia (OR 1.66, 95% CI [1.28-2.16]), and type 2 diabetes mellitus (OR 1.41, 95% CI [1.22-1.64]) is one of the most significant indicators of a past COVID-19 infection. Additionally, more new phenotypes were found with increased confidence among the cohorts who were younger than 65. CONCLUSIONS: The findings of this study confirm many of the post-COVID-19 symptoms and suggest that a variety of new diagnoses, including new diabetes mellitus and neurological disorder diagnoses, are more common among those with a history of COVID-19 than those without the infection. Additionally, more than 63% of PASC phenotypes were observed in patients under 65 years of age, pointing out the importance of vaccination to minimize the risk of debilitating post-acute sequelae of COVID-19 among younger adults.

Leveraging vibration of effects analysis for robust discovery in observational biomedical data science.

Hypothesis generation in observational, biomedical data science often starts with computing an association or identifying the statistical relationship between a dependent and an independent variable. However, the outcome of this process depends fundamentally on modeling strategy, with differing strategies generating what can be called "vibration of effects" (VoE). VoE is defined by variation in associations that often lead to contradictory results. Here, we present a computational tool capable of modeling VoE in biomedical data by fitting millions of different models and comparing their output. We execute a VoE analysis on a series of widely reported associations (e.g., carrot intake associated with eyesight) with an extended additional focus on lifestyle exposures (e.g., physical activity) and components of the Framingham Risk Score for cardiovascular health (e.g., blood pressure). We leveraged our tool for potential confounder identification, investigating what adjusting variables are responsible for conflicting models. We propose modeling VoE as a critical step in navigating discovery in observational data, discerning robust associations, and cataloging adjusting variables that impact model output.

Geospatial Analysis of Individual and Community-Level Socioeconomic Factors Impacting SARS-CoV-2 Prevalence and Outcomes.

BACKGROUND: The SARS-CoV-2 pandemic has disproportionately affected racial and ethnic minority communities across the United States. We sought to disentangle individual and census tract-level sociodemographic and economic factors associated with these disparities. METHODS AND FINDINGS: All adults tested for SARS-CoV-2 between February 1 and June 21, 2020 were geocoded to a census tract based on their address; hospital employees and individuals with invalid addresses were excluded. Individual (age, sex, race/ethnicity, preferred language, insurance) and census tract-level (demographics, insurance, income, education, employment, occupation, household crowding and occupancy, built home environment, and transportation) variables were analyzed using linear mixed models predicting infection, hospitalization, and death from SARS-CoV-2. Among 57,865 individuals, per capita testing rates, individual (older age, male sex, non-White race, non-English preferred language, and non-private insurance), and census tract-level (increased population density, higher household occupancy, and lower education) measures were associated with likelihood of infection. Among those infected, individual age, sex, race, language, and insurance, and census tract-level measures of lower education, more multi-family homes, and extreme household crowding were associated with increased likelihood of hospitalization, while higher per capita testing rates were associated with decreased likelihood. Only individual-level variables (older age, male sex, Medicare insurance) were associated with increased mortality among those hospitalized. CONCLUSIONS: This study of the first wave of the SARS-CoV-2 pandemic in a major U.S. city presents the cascade of outcomes following SARS-CoV-2 infection within a large, multi-ethnic cohort. SARS-CoV-2 infection and hospitalization rates, but not death rates among those hospitalized, are related to census tract-level socioeconomic characteristics including lower educational attainment and higher household crowding and occupancy, but not neighborhood measures of race, independent of individual factors.