Predictors of critical care, mechanical ventilation, and mortality among hospitalized patients with COVID-19 in an electronic health record database

This was a retrospective cohort study that included patients confirmed with COVID-19 infection between January 2020 and November 2020. Among these patients, a subset of patients hospitalized with COVID-19 was identified from those with an inpatient health care encounter. Confirmation of COVID-19 infection was based on presence of a specific International Classification of Diseases, 10^th Revision, Clinical Modification (ICD-10-CM) diagnosis code (U07.1) and/or a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral test. The date of confirmed infection was the earlier of the date of diagnosis or the date of a positive test. The cohort entry date was the earliest date that the patient met both of the following criteria: confirmed COVID-19 infection and admission to the hospital. For patients who were hospitalized prior to contracting COVID-19, the date of cohort entry was the date of confirmed infection. For patients who were confirmed to have COVID-19 before they were admitted to the hospital, the date of cohort entry was date of hospital admission. This approach for assigning cohort entry date allows for the description of clinical characteristics at the time patients were first hospitalized with COVID-19. For clinical characteristics other than death, patients were followed from cohort entry to discharge or 30 days after cohort entry, whichever came first. Deaths were identified in all follow-up available, including during and after hospitalization.

Patients were identified from Optum’s longitudinal COVID-19 EHR database derived from a network of healthcare provider organizations across the U.S. The COVID-19 EHR database consists of a subset of patients from Optum’s EHR database, which represents a geographically diverse U.S. patient population with more than 85 million patients from 2007 through 2019. Optum’s EHR database includes data collected from tens of thousands of providers and hundreds of hospitals representing more than 60 electronic medical record (EMR)-based provider/hospital networks across the U.S. This database incorporates clinical and medical administrative data from both inpatient and ambulatory EMRs, practice management systems, and numerous other internal systems. Information is processed from across the continuum of care, including acute inpatient stays and outpatient visits. The COVID-19 data captures diagnostics specific to the COVID-19 patient during initial presentation at hospital admission, acute illness, and convalescence with over 500 mapped labs and bedside observations, including COVID-19 specific testing. The data are incorporated into the underlying database on a biweekly basis, allowing for near real-time analysis and assessment of the COVID-19 clinical landscape. The database is certified as de-identified by an independent statistical expert following Health Insurance Portability and Accountability Act statistical de-identification rules.

Demographic characteristics were assessed on the date of cohort entry. Comorbidities and medication use were assessed in the 21 days prior to cohort entry. Comorbidities were identified by ICD-10-CM diagnosis code with a diagnosis status of “history of” and medications were mapped according to the Anatomical Therapeutic Chemical (ATC) classification scheme.

Additionally, vital signs, laboratory results, symptoms, diagnoses, and treatments during hospitalization were assessed. For vital signs and laboratory results, the first measurement on or after the date of cohort entry was selected if the patient had multiple measurements. Symptoms and diagnoses were identified by ICD-10-CM diagnosis codes.

The primary outcomes of interest were receipt of critical care, mechanical ventilation, and death. Patients were classified according to the presence or absence of an outcome, and outcome groups were not mutually exclusive.

Receipt of critical care was identified using Current Procedural Terminology, 4th Edition (CPT-4) codes. Receipt of mechanical ventilation was identified by CPT-4 and International Classification of Diseases, 10th Revision, Procedural Coding System (ICD-10-PCS) codes and included intubation, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO). Receipt of critical care and mechanical ventilation were ascertained during hospitalization.

Death was ascertained via linkage to the Social Security Administration’s Death Master File and/or the presence of a death indicator in the structured EHR data within all data available during and after hospitalization.

All analyses were conducted using SAS version 9.4 (SAS Institute Inc, Cary, NC). Baseline characteristics were examined overall and according to outcome (critical care, mechanical ventilation, and death). Categorical variables were summarized using frequency and percent while continuous variables were summarized using median and interquartile range (IQR).

For the association analyses, vital signs and laboratory values were transformed into categorical variables. Dichotomous variables were created based on clinically-relevant cutpoints. Additionally, categories based on quintiles were generated to examine the shape of the dose–response relationship of vital signs and laboratory values with each outcome. Quintiles were determined based on the distribution of each biomarker among hospitalized patients overall. Tests for linear trend were computed by using the medians of the quintiles modeled as a continuous variable.

Logistic regression models were used to estimate unadjusted and adjusted odds ratios (OR) and corresponding 95% confidence intervals (CI) for associations between the covariates and each outcome. Adjusted models included age, gender, region, race, and week of cohort entry. Week of cohort entry was included as a covariate to adjust for any potential changes in patient characteristics or treatments over time.

A total of 56,996 hospitalized patients with COVID-19 between January 2020 and November 2020 were identified (Fig. 1). Of these, 11,967 (21.0%) received critical care, 9136 (16.0%) received mechanical ventilation, and 8526 (15.0%) died. Table 1 shows the demographics, comorbidities, and patient-reported medications at baseline overall and according to outcome. The majority of hospitalized patients were aged 50 years and older (72.4%), Caucasian (58.8%), and from the Midwest or Northeast (38.0% and 29.0%, respectively); this was also observed for each outcome. Females comprised 50.5% of hospitalized patients, but males comprised the majority of patients experiencing each outcome (58.8% for critical care, 60.4% for mechanical ventilation, and 57.4% for death). Prior to the cohort entry date, 76.7% of patients received care in the emergency department, while fewer patients received care in the outpatient or inpatient settings. Confirmation of COVID-19 infection was based on both a positive SARS-CoV-2 viral test and presence of a U07.1 diagnosis code for 70.2% of hospitalized patients, a U07.1 diagnosis code only for 26.0% of patients, and a positive SARS-CoV-2 viral test only for 3.8% of patients. The largest proportion of patients were admitted to the hospital in April 2020 (18.3%), followed by November 2020 (17.8%).

The most common comorbidities among the patients hospitalized with COVID-19 overall were hypertension (40.8%), kidney disease (31.0%), diabetes (29.5%), and obesity (23.8%) (Table 1). In general, the prevalence of these comorbidities was higher among patients who experienced one of the outcomes of interest, compared to the broader hospitalized population. Among patients who received critical care, 48.9% had hypertension, 51.0% had kidney disease, 40.5% had diabetes, and 32.3% were obese. Among patients who received mechanical ventilation, 49.2% had hypertension, 55.9% had kidney disease, 42.9% had diabetes, and 34.8% were obese. Among patients who died, 47.3% had hypertension, 61.7% had kidney disease, and 39.6% had diabetes; 22.2% were obese, slightly less than hospitalized patients overall. Statins and angiotensin-converting enzyme inhibitors (ACEs)/angiotensin receptor blockers (ARBs) were the most prevalent patient-reported medications (26.2% and 20.2%, respectively, overall).

Table 2 presents the distributions of vital signs, laboratory values, symptoms, diagnoses, and treatments received during hospitalization among COVID-19 patients. The median duration of hospitalization overall was 6 days (IQR: 4, 11). The duration was longer among patients that experienced an outcome: 11 days (IQR: 6, 19) for critical care, 15 days (IQR: 8, 24) for mechanical ventilation, and 10 days (IQR: 5, 17) for death. Among hospitalized patients overall, 6.6% had a temperature > 38 degrees Celsius and 10.1% had an oxygen saturation < 90%. Markers of inflammation and coagulation were elevated for many patients, including 85.7% of patients with C-reactive protein (CRP) > 10 mg/L and 76.8% of patients with D-dimer > 250 ng/mL (DDU).

The most common symptoms during hospitalization among COVID-19 patients were dyspnea (28.0%) and hypoxemia (25.8%) (Table 2). Prevalence of these symptoms was higher among patients who received critical care (37.4% and 33.2%, respectively), those who received ventilation (41.4% and 35.4%, respectively), and those who died (34.8% and 31.9%, respectively). Relatedly, the most prevalent diagnoses during hospitalization among patients overall were pneumonia (59.6%) and acute respiratory failure (44.8%). These diagnoses were even more common among those with an outcome, with the highest prevalence observed among patients that received mechanical ventilation (acute respiratory failure, 85.7%; pneumonia, 84.7%). Anticoagulants were the most prevalent treatment, received by 79.8% of hospitalized patients with COVID-19 overall during their hospitalization. Among other treatments, 15.5% of patients received chloroquine or hydroxychloroquine, 29.3% received dexamethasone, and 22.8% received remdesivir.