Characterization of Post-COVID-19 Definitions and Clinical Coding Practices: Longitudinal Study.

BACKGROUND: Post-COVID-19 condition (colloquially known as "long COVID-19") characterized as postacute sequelae of SARS-CoV-2 has no universal clinical case definition. Recent efforts have focused on understanding long COVID-19 symptoms, and electronic health record (EHR) data provide a unique resource for understanding this condition. The introduction of the International Classification of Diseases, Tenth Revision (ICD-10) code U09.9 for "Post COVID-19 condition, unspecified" to identify patients with long COVID-19 has provided a method of evaluating this condition in EHRs; however, the accuracy of this code is unclear. OBJECTIVE: This study aimed to characterize the utility and accuracy of the U09.9 code across 3 health care systems-the Veterans Health Administration, the Beth Israel Deaconess Medical Center, and the University of Pittsburgh Medical Center-against patients identified with long COVID-19 via a chart review by operationalizing the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) definitions. METHODS: Patients who were COVID-19 positive with either a U07.1 ICD-10 code or positive polymerase chain reaction test within these health care systems were identified for chart review. Among this cohort, we sampled patients based on two approaches: (1) with a U09.9 code and (2) without a U09.9 code but with a new onset long COVID-19-related ICD-10 code, which allows us to assess the sensitivity of the U09.9 code. To operationalize the long COVID-19 definition based on health agency guidelines, symptoms were grouped into a "core" cluster of 11 commonly reported symptoms among patients with long COVID-19 and an extended cluster that captured all other symptoms by disease domain. Patients having ≥2 symptoms persisting for ≥60 days that were new onset after their COVID-19 infection, with ≥1 symptom in the core cluster, were labeled as having long COVID-19 per chart review. The code's performance was compared across 3 health care systems and across different time periods of the pandemic. RESULTS: Overall, 900 patient charts were reviewed across 3 health care systems. The prevalence of long COVID-19 among the cohort with the U09.9 ICD-10 code based on the operationalized WHO definition was between 23.2% and 62.4% across these health care systems. We also evaluated a less stringent version of the WHO definition and the CDC definition and observed an increase in the prevalence of long COVID-19 at all 3 health care systems. CONCLUSIONS: This is one of the first studies to evaluate the U09.9 code against a clinical case definition for long COVID-19, as well as the first to apply this definition to EHR data using a chart review approach on a nationwide cohort across multiple health care systems. This chart review approach can be implemented at other EHR systems to further evaluate the utility and performance of the U09.9 code.

Neurological diagnoses in hospitalized COVID-19 patients associated with adverse outcomes: A multinational cohort study.

Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate the overall risk of adverse outcomes across our geographically diverse populations. For children, we reported descriptive statistics separately due to their low frequency of neurological involvement and poor outcomes. Among the 106,229 hospitalized COVID-19 patients (104,031 patients ≥18 years; 2,198 patients <18 years, January 2020-October 2021), 15,101 (14%) had at least one CNS diagnosis, while 2,788 (3%) had at least one PNS diagnosis. After controlling for demographics and pre-existing conditions, adults with CNS involvement had longer hospital stay (11 versus 6 days) and greater risk of (Hazard Ratio = 1.78) and faster time to death (12 versus 24 days) than patients with no neurological condition (NNC) during acute COVID-19 hospitalization. Adults with PNS involvement also had longer hospital stay but lower risk of mortality than the NNC group. Although children had a low frequency of neurological involvement during COVID-19 hospitalization, a substantially higher proportion of children with CNS involvement died compared to those with NNC (6% vs 1%). Overall, patients with concurrent CNS manifestation during acute COVID-19 hospitalization faced greater risks for adverse clinical outcomes than patients without any neurological diagnosis. Our global informatics framework using a federated approach (versus a centralized data collection approach) has utility for clinical discovery beyond COVID-19.

Characterization of long COVID temporal sub-phenotypes by distributed representation learning from electronic health record data: a cohort study.

Background: Characterizing Post-Acute Sequelae of COVID (SARS-CoV-2 Infection), or PASC has been challenging due to the multitude of sub-phenotypes, temporal attributes, and definitions. Scalable characterization of PASC sub-phenotypes can enhance screening capacities, disease management, and treatment planning. Methods: We conducted a retrospective multi-centre observational cohort study, leveraging longitudinal electronic health record (EHR) data of 30,422 patients from three healthcare systems in the Consortium for the Clinical Characterization of COVID-19 by EHR (4CE). From the total cohort, we applied a deductive approach on 12,424 individuals with follow-up data and developed a distributed representation learning process for providing augmented definitions for PASC sub-phenotypes. Findings: Our framework characterized seven PASC sub-phenotypes. We estimated that on average 15.7% of the hospitalized COVID-19 patients were likely to suffer from at least one PASC symptom and almost 5.98%, on average, had multiple symptoms. Joint pain and dyspnea had the highest prevalence, with an average prevalence of 5.45% and 4.53%, respectively. Interpretation: We provided a scalable framework to every participating healthcare system for estimating PASC sub-phenotypes prevalence and temporal attributes, thus developing a unified model that characterizes augmented sub-phenotypes across the different systems. Funding: Authors are supported by National Institute of Allergy and Infectious Diseases, National Institute on Aging, National Center for Advancing Translational Sciences, National Medical Research Council, National Institute of Neurological Disorders and Stroke, European Union, National Institutes of Health, National Center for Advancing Translational Sciences.

A retrospective cohort analysis leveraging augmented intelligence to characterize long COVID in the electronic health record: A precision medicine framework.

Physical and psychological symptoms lasting months following an acute COVID-19 infection are now recognized as post-acute sequelae of COVID-19 (PASC). Accurate tools for identifying such patients could enhance screening capabilities for the recruitment for clinical trials, improve the reliability of disease estimates, and allow for more accurate downstream cohort analysis. In this retrospective cohort study, we analyzed the EHR of hospitalized COVID-19 patients across three healthcare systems to develop a pipeline for better identifying patients with persistent PASC symptoms (dyspnea, fatigue, or joint pain) after their SARS-CoV-2 infection. We implemented distributed representation learning powered by the Machine Learning for modeling Health Outcomes (MLHO) to identify novel EHR features that could suggest PASC symptoms outside of typical diagnosis codes. MLHO applies an entropy-based feature selection and boosting algorithms for representation mining. These improved definitions were then used for estimating PASC among hospitalized patients. 30,422 hospitalized patients were diagnosed with COVID-19 across three healthcare systems between March 13, 2020 and February 28, 2021. The mean age of the population was 62.3 years (SD, 21.0 years) and 15,124 (49.7%) were female. We implemented the distributed representation learning technique to augment PASC definitions. These definitions were found to have positive predictive values of 0.73, 0.74, and 0.91 for dyspnea, fatigue, and joint pain, respectively. We estimated that 25 percent (CI 95%: 6-48), 11 percent (CI 95%: 6-15), and 13 percent (CI 95%: 8-17) of hospitalized COVID-19 patients will have dyspnea, fatigue, and joint pain, respectively, 3 months or longer after a COVID-19 diagnosis. We present a validated framework for screening and identifying patients with PASC in the EHR and then use the tool to estimate its prevalence among hospitalized COVID-19 patients.

Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study.

Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1-365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings: Advanced age (HR 2.77, 95%CI 2.53-3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03-4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55-5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14-1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37-0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17-1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20-1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45-1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80-13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10-1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32-1.67) and 365 days (RR 1.54, 95%CI 1.21-1.96) compared to COVID-19 patients with no AKI. Interpretation: COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery. Funding: Authors are supported by various funders, with full details stated in the acknowledgement section.

International electronic health record-derived post-acute sequelae profiles of COVID-19 patients.

The risk profiles of post-acute sequelae of COVID-19 (PASC) have not been well characterized in multi-national settings with appropriate controls. We leveraged electronic health record (EHR) data from 277 international hospitals representing 414,602 patients with COVID-19, 2.3 million control patients without COVID-19 in the inpatient and outpatient settings, and over 221 million diagnosis codes to systematically identify new-onset conditions enriched among patients with COVID-19 during the post-acute period. Compared to inpatient controls, inpatient COVID-19 cases were at significant risk for angina pectoris (RR 1.30, 95% CI 1.09-1.55), heart failure (RR 1.22, 95% CI 1.10-1.35), cognitive dysfunctions (RR 1.18, 95% CI 1.07-1.31), and fatigue (RR 1.18, 95% CI 1.07-1.30). Relative to outpatient controls, outpatient COVID-19 cases were at risk for pulmonary embolism (RR 2.10, 95% CI 1.58-2.76), venous embolism (RR 1.34, 95% CI 1.17-1.54), atrial fibrillation (RR 1.30, 95% CI 1.13-1.50), type 2 diabetes (RR 1.26, 95% CI 1.16-1.36) and vitamin D deficiency (RR 1.19, 95% CI 1.09-1.30). Outpatient COVID-19 cases were also at risk for loss of smell and taste (RR 2.42, 95% CI 1.90-3.06), inflammatory neuropathy (RR 1.66, 95% CI 1.21-2.27), and cognitive dysfunction (RR 1.18, 95% CI 1.04-1.33). The incidence of post-acute cardiovascular and pulmonary conditions decreased across time among inpatient cases while the incidence of cardiovascular, digestive, and metabolic conditions increased among outpatient cases. Our study, based on a federated international network, systematically identified robust conditions associated with PASC compared to control groups, underscoring the multifaceted cardiovascular and neurological phenotype profiles of PASC.

Changes in laboratory value improvement and mortality rates over the course of the pandemic: an international retrospective cohort study of hospitalised patients infected with SARS-CoV-2.

OBJECTIVE: To assess changes in international mortality rates and laboratory recovery rates during hospitalisation for patients hospitalised with SARS-CoV-2 between the first wave (1 March to 30 June 2020) and the second wave (1 July 2020 to 31 January 2021) of the COVID-19 pandemic. DESIGN, SETTING AND PARTICIPANTS: This is a retrospective cohort study of 83 178 hospitalised patients admitted between 7 days before or 14 days after PCR-confirmed SARS-CoV-2 infection within the Consortium for Clinical Characterization of COVID-19 by Electronic Health Record, an international multihealthcare system collaborative of 288 hospitals in the USA and Europe. The laboratory recovery rates and mortality rates over time were compared between the two waves of the pandemic. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was all-cause mortality rate within 28 days after hospitalisation stratified by predicted low, medium and high mortality risk at baseline. The secondary outcome was the average rate of change in laboratory values during the first week of hospitalisation. RESULTS: Baseline Charlson Comorbidity Index and laboratory values at admission were not significantly different between the first and second waves. The improvement in laboratory values over time was faster in the second wave compared with the first. The average C reactive protein rate of change was -4.72 mg/dL vs -4.14 mg/dL per day (p=0.05). The mortality rates within each risk category significantly decreased over time, with the most substantial decrease in the high-risk group (42.3% in March-April 2020 vs 30.8% in November 2020 to January 2021, p<0.001) and a moderate decrease in the intermediate-risk group (21.5% in March-April 2020 vs 14.3% in November 2020 to January 2021, p<0.001). CONCLUSIONS: Admission profiles of patients hospitalised with SARS-CoV-2 infection did not differ greatly between the first and second waves of the pandemic, but there were notable differences in laboratory improvement rates during hospitalisation. Mortality risks among patients with similar risk profiles decreased over the course of the pandemic. The improvement in laboratory values and mortality risk was consistent across multiple countries.

Distinguishing Admissions Specifically for COVID-19 From Incidental SARS-CoV-2 Admissions: National Retrospective Electronic Health Record Study.

BACKGROUND: Admissions are generally classified as COVID-19 hospitalizations if the patient has a positive SARS-CoV-2 polymerase chain reaction (PCR) test. However, because 35% of SARS-CoV-2 infections are asymptomatic, patients admitted for unrelated indications with an incidentally positive test could be misclassified as a COVID-19 hospitalization. Electronic health record (EHR)-based studies have been unable to distinguish between a hospitalization specifically for COVID-19 versus an incidental SARS-CoV-2 hospitalization. Although the need to improve classification of COVID-19 versus incidental SARS-CoV-2 is well understood, the magnitude of the problems has only been characterized in small, single-center studies. Furthermore, there have been no peer-reviewed studies evaluating methods for improving classification. OBJECTIVE: The aims of this study are to, first, quantify the frequency of incidental hospitalizations over the first 15 months of the pandemic in multiple hospital systems in the United States and, second, to apply electronic phenotyping techniques to automatically improve COVID-19 hospitalization classification. METHODS: From a retrospective EHR-based cohort in 4 US health care systems in Massachusetts, Pennsylvania, and Illinois, a random sample of 1123 SARS-CoV-2 PCR-positive patients hospitalized from March 2020 to August 2021 was manually chart-reviewed and classified as "admitted with COVID-19" (incidental) versus specifically admitted for COVID-19 ("for COVID-19"). EHR-based phenotyping was used to find feature sets to filter out incidental admissions. RESULTS: EHR-based phenotyped feature sets filtered out incidental admissions, which occurred in an average of 26% of hospitalizations (although this varied widely over time, from 0% to 75%). The top site-specific feature sets had 79%-99% specificity with 62%-75% sensitivity, while the best-performing across-site feature sets had 71%-94% specificity with 69%-81% sensitivity. CONCLUSIONS: A large proportion of SARS-CoV-2 PCR-positive admissions were incidental. Straightforward EHR-based phenotypes differentiated admissions, which is important to assure accurate public health reporting and research.

Distinguishing Admissions Specifically for COVID-19 from Incidental SARS-CoV-2 Admissions: A National EHR Research Consortium Study.

Admissions are generally classified as COVID-19 hospitalizations if the patient has a positive SARS-CoV-2 polymerase chain reaction (PCR) test. However, because 35% of SARS-CoV-2 infections are asymptomatic, patients admitted for unrelated indications with an incidentally positive test could be misclassified as a COVID-19 hospitalization. EHR-based studies have been unable to distinguish between a hospitalization specifically for COVID-19 versus an incidental SARS-CoV-2 hospitalization. From a retrospective EHR-based cohort in four US healthcare systems, a random sample of 1,123 SARS-CoV-2 PCR-positive patients hospitalized between 3/2020â€"8/2021 was manually chart-reviewed and classified as admitted-with-COVID-19 (incidental) vs. specifically admitted for COVID-19 (for-COVID-19). EHR-based phenotyped feature sets filtered out incidental admissions, which occurred in 26%. The top site-specific feature sets had 79-99% specificity with 62-75% sensitivity, while the best performing across-site feature set had 71-94% specificity with 69-81% sensitivity. A large proportion of SARS-CoV-2 PCR-positive admissions were incidental. Straightforward EHR-based phenotypes differentiated admissions, which is important to assure accurate public health reporting and research.