Mapping each pre-existing conditions association to short-term and long-term COVID-19 complications

Understanding the relationships between pre-existing conditions and complications of COVID-19 infection is critical to identifying which patients will develop severe disease. Here, we leverage 1.1 million clinical notes from 1,903 hospitalized COVID-19 patients and deep neural network models to characterize associations between 21 pre-existing conditions and the development of 20 complications (e.g. respiratory, cardiovascular, renal, and hematologic) of COVID-19 infection throughout the course of infection (i.e. 0-30 days, 31-60 days, and 61-90 days). Pleural effusion was the most frequent complication of early COVID-19 infection (23% of 383 complications) followed by cardiac arrhythmia (12% of 383 complications). Notably, hypertension was the most significant risk factor associated with 10 different complications including acute respiratory distress syndrome, cardiac arrhythmia and anemia. Furthermore, novel associations between cancer (risk ratio: 3, p=0.02) or immunosuppression (risk ratio: 4.3, p=0.04) with early-onset heart failure have also been identified. Onset of new complications after 30 days is rare and most commonly involves pleural effusion (31-60 days: 24% of 45 patients, 61-90 days: 25% of 36 patients). Overall, the associations between pre-COVID conditions and COVID-associated complications presented here may form the basis for the development of risk assessment scores to guide clinical care pathways.

Longitudinal lab test analysis confirms pre-existing anemia as a severe risk factor for post-viral clearance hospitalization in COVID-19 patients

BackgroundAs the number of new and recovering COVID-19 cases continues to rise, it has become evident that patients can experience symptoms and complications after viral clearance. Clinical biomarkers characterizing patients who are likely to experience these prolonged effects are unknown. MethodsWe conducted a retrospective study to compare longitudinal lab test measurements (hemoglobin, hematocrit, estimated glomerular filtration rate, serum creatinine, and blood urea nitrogen) in patients rehospitalized after PCR-confirmed SARS-CoV-2 clearance (n=104) versus patients not rehospitalized after viral clearance (n=278). FindingsCompared to patients who were not rehospitalized after PCR-confirmed viral clearance, those who were rehospitalized had lower median hemoglobin levels in the year prior to COVID-19 diagnosis (cohens D = -0.50; p=1.2x10-3) and during the active infection window (cohens D = -0.71; p=4.6x10-8). Patients hospitalized after viral clearance were also more likely to be diagnosed with moderate or severe anemia during the active infection window (OR = 2.18; p = 4.99x10-9). ConclusionsThe occurrence of moderate or severe anemia in hospitalized COVID-19 patients is strongly associated with rehospitalization after viral clearance. Whether interventions to mitigate anemia can improve long term outcomes of COVID-19 patients should be further investigated. FundingThis study was funded by nference.

Pre-existing conditions are associated with long-COVID patients hospitalization, despite confirmed clearance of SARS-CoV-2 virus

The current diagnostic gold-standard for SARS-CoV-2 clearance from infected patients is two consecutive negative PCR test results. However, there are anecdotal reports of hospitalization from protracted COVID complications despite such confirmed viral clearance, presenting a clinical conundrum. We conducted a retrospective analysis of 266 COVID patients to compare those that were admitted/re-admitted post-viral clearance (hospitalized post-clearance cohort, n=93) with those that were hospitalized pre-clearance but were not re-admitted post-viral clearance (non-hospitalized post-clearance cohort, n=173). In order to differentiate these two cohorts, we used neural network models for the augmented curation of comorbidities and complications with positive sentiment in the EHR physician notes. In the year preceding COVID onset, acute kidney injury (n=15 (16.1%), p-value: 0.03), anemia (n=20 (21.5%), p-value: 0.02), and cardiac arrhythmia (n=21 (22.6%), p-value: 0.05) were significantly enriched in the physician notes of the hospitalized post-clearance cohort. This study highlights that these specific pre-existing conditions are associated with amplified hospitalization risk in COVID patients, despite their successful SARS-CoV-2 viral clearance. Our finding that pre-COVID anemia amplifies risk of post-COVID hospitalization is particularly concerning given the high prevalence and endemic nature of anemia in many low- and middle-income countries (per the World Bank definition; e.g. India, Brazil), which are unfortunately also seeing high rates of SARS-CoV-2 infection and COVID-induced mortality. This study motivates follow-up prospective research into the specific risk factors we have identified that appear to predispose some patients towards the after effects of COVID-19. Article summary - Strengths and limitations of this studyO_LIThis is the first study at a major healthcare center analyzing risk factors for post-viral clearance hospitalization of COVID-19 patients. C_LIO_LIThis analysis uses augmented curation methods to identify complications and comorbidities from the physician notes, rather than relying upon ICD codes. C_LIO_LIThe statistical analysis identifies specific comorbidities in the year preceding PCR diagnosis of SARS-CoV-2 which are associated with increased rates of post-viral clearance hospitalization. C_LIO_LIThe dataset used for this study is limited to a single healthcare system, so the underlying clinical characteristics of the study population are biased to reflect the clinical characteristics of individuals that receive medical treatment in certain regions of the United States (Arizona, Florida, Minnesota). C_LIO_LIIn this study, we use the first of two consecutive negative PCR tests to estimate the viral clearance date for each patient, however the true viral clearance date for each patient is unknown. C_LI

Enoxaparin is associated with lower rates of thrombosis, kidney injury, and mortality than Unfractionated Heparin in hospitalized COVID patients

Although anticoagulants such as unfractionated heparin and low molecular weight heparin (LMWH, e.g. enoxaparin) are both being used for therapeutic mitigation of COVID associated coagulopathy (CAC), differences in their clinical outcomes remain to be investigated. Here, we employ automated neural networks supplemented with expert curation ( augmented curation) for retrospectively analyzing the complete electronic health records (EHRs) of 671 hospitalized COVID-19 patients administered either enoxaparin or unfractionated heparin, but not both. We find that COVID-19 patients administered unfractionated heparin but not enoxaparin have higher rates of mortality (risk ratio: 2.6; 95% C.I.: [1.2-5.4]; p-value: 0.02; BH adjusted p-value: 0.09), thrombotic events (risk ratio: 5.7, 95% C.I.: [2.1, 33.9], p-value: 0.024), acute kidney injury (risk ratio: 5.5; 95% C.I.: [1.2-17.7]; p-value: 0.02; BH adjusted p-value: 0.10), and bacterial pneumonia (risk ratio undefined; 95% C.I.: [1.0, 292]; p-value:0.02; BH adjusted p-value:0.10), compared to patients administered enoxaparin but not unfractionated heparin. Notably, even after controlling for potential confounding factors such as demographics, comorbidities, admission diagnosis, initial ICU status, and initial level of oxygen support, the above differences between the enoxaparin and unfractionated heparin patient cohorts remain statistically significant. This study emphasizes the need for mechanistically investigating differential modulation of the COVID-associated coagulation cascades by enoxaparin versus unfractionated heparin.