Clinical presentation, complications, and outcomes of hospitalized COVID‐19 patients in an academic center with a centralized palliative care consult service

Abstract Background and Aims Palliative care is a critical component of the response of a healthcare system to a pandemic. We present risk factors associated with mortality and highlight an operational palliative care consult service in facilitating early identification of risk factors to guide goal‐concordant care and rational utilization of finite healthcare resources during a pandemic. Methods In this case series of 100 consecutive patients hospitalized with COVID‐19, we analyzed clinical data, treatment including palliative care, and outcomes in patients with SARS‐CoV‐2 infection admitted to three hospitals in Seattle, Washington. We compared data between patients who were discharged and non‐survivors. Results Age (OR 4.67 [1.43, 15.32] ages 65‐79; OR 3.96 [1.05, 14.89] ages 80‐97), dementia (OR 5.62 [1.60, 19.74]), and transfer from a congregate living facility (OR 5.40 [2.07, 14.07]), as well hypoxemia and tachypnea (OR 7.00 [2.91, 22.41]; OR 2.78 [1.11, 6.97]) were associated with mortality. Forty‐one (41%) patients required intensive care and 22 (22%) invasive mechanical ventilation. Forty‐six (46%) patients were seen by the palliative care service, resulting in a change of resuscitation status in 54% of admitted patients. Fifty‐eight (58%) patients recovered and were discharged, 34 (34%) died, and eight (8%) remained hospitalized, of which seven ultimately survived and one died. Conclusions Older age, dementia, and congregate living were associated with mortality. Early discussions of goals of care facilitated by an operational palliative care consult service can effectively guide goal‐concordant care in patients at high risk for mortality during a pandemic. Development of a functional palliative care consult service is an important component of pandemic planning.


| INTRODUCTION
Since the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China in early December 2019, a wave of infection has spread across the world. Considerable variability exists among studies evaluating clinical characteristics and risk factors associated with outcomes. [1][2][3][4][5][6] Although some variation may be driven by case ascertainment bias, underlying differences in demographics, socioeconomics, access to care, and clinical characteristics across countries likely drive true differences in prevalence of disease and risk for mortality. With the first case in the United States identified in Washington State, the greater Seattle area was the initial epicenter for transmission in the country. [7][8][9] In this case series, we describe clinical characteristics, interventions including palliative care consultation, and risk factors associated with COVID-19 among the initial hospitalized cases at three major hospitals in Seattle. We focus on palliative care involvement as a crucial component of the pandemic response, including a description of the effect of our system-wide Palliative Care Response Plan in the COVID-19 pandemic, while highlighting the importance of goal-concordant care.

| Patient and public involvement
Patients were not involved in the development of the study design.

| Definitions
Patients admitted from congregate living resided at a skilled nursing facility (SNF), a long-term care facility (LTAC), or an assisted-living facility (ALF). Timing of symptom onset was estimated from chart review. Fever was defined as a core temperature ≥38 C. Hypoxemia was defined as SaO 2 <90% on presentation or <88% in patients with chronic lung disease, or new requirement of supplemental O 2 . Tachycardia was defined as a heart rate of ≥100 beats per minute.
Tachypnea was defined as a respiratory rate of ≥20 respirations per minute. Immunosuppression was defined as a history of solid organ or bone marrow transplant, immunodeficiency, hematologic malignancy, active chemotherapy, neutropenia (absolute neutrophil count <500 Â 10 9 /L), or the use of biologic agents for immunosuppression or corticosteroid equivalent >20 mg/day of prednisone. Malignancy included active cancer, excluding non-melanoma skin cancers. Cardiovascular disease was defined as hypertension, coronary artery disease, congestive heart failure, or a history of cerebrovascular accident.
Dementia was included as a comorbidity in those with a diagnosis of dementia in their medical chart. Leukocytosis was defined as a leukocyte count ≥10.0 Â 10 9 /L; neutrophilia as neutrophil count >7.0 Â 10 9 /L; and lymphopenia as lymphocyte count <1.0 Â 10 9 /L. Acute myocardial injury was defined as troponin-I above the 99th percentile of the institutional upper reference limit for normal, regardless of new onset abnormalities on electrocardiography or echocardiography. Arrhythmias were sub-classified as atrial fibrillation, atrial flutter, bradycardia, ventricular tachycardia, and ventricular fibrillation persisting for more than 30 seconds, as documented in the medical record or a 12-lead electrocardiogram. Cardiomyopathy was defined as newly reduced left ventricular ejection fraction of <50% on transthoracic echocardiography by biplane Simpson's method. The Berlin criteria were used to define acute respiratory distress syndrome (ARDS). 10 Shock was defined by the use of supportive interventions to maintain arterial blood pressure.

| Statistical analysis
Continuous variables were presented as medians and interquartile ranges (IQR), and categorical variables as counts and percentages.
Among patients with known outcomes of death or discharge, we compared between-group differences using Mann-Whitney U tests for continuous variables and Pearson's Chi-squared or Fisher's exact tests for categorical variables. Univariate logistic regression models were used to identify factors associated with intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and death. For risk of ICU admission and IMV, the entire sample was included in these models since these events tended to occur early in the hospital course. For risk of death, the sample was restricted to patients with a definitive outcome of discharge or death. A two-sided P-value ≤.05 was considered to be statistically significant. All statistical analyses were performed using STATA 16.1 (Stata Corp.,Texas).

| Hospital admission and length of stay
Fifty-eight percent of patients recovered to discharge, 8% remained hospitalized, and 34% died. Fifty-nine percent were treated in the acute care ward alone and 41% in the intensive care unit (ICU) ( Table 1). Discharged patients had significantly longer time between symptom onset and admission compared to patients who died (7 days vs 3 days, P < .001). The average length of stay was 11 days in discharged patients and 7.5 days in non-survivors. Each patient was followed through his or her admission or at least 22 days if still hospitalized at time of data censoring.

| Comorbidities
Older patients were more likely to die than be discharged, with the

| Vital signs and end-organ dysfunction
Hypoxemia and tachypnea were present in 64% and 59% of patients,  Table 2). Eighty-six percent of patients required oxygen therapy during admission. Most patients (79%) were placed on nasal cannula, 20% received high-flow nasal cannula, and 22% required intermittent mandatory ventilation (IMV) ( Table 1). Abnormal chest image was common (90%) on presentation, with bilateral patchy opacities (73%) being the most common finding (Table S1).
The most common complications were ARDS (26%), shock (19%), and cardiac arrhythmia (18%) ( Table 1). The frequency of complications was significantly higher in patients who died compared to patients discharged. Forty-one percent of deceased patients developed ARDS compared to 13.8% of discharged patients (P = .005). A higher proportion of deceased patients developed shock requiring vasopressor support compared to discharged patients (32.4% vs 8.6%, respectively, P = .008). Cardiac arrhythmia was observed in 18% of all patients and was more commonly seen in patients who died (29.4% vs 10.5%, P = .052). Atrial fibrillation was the most common arrhythmia (58.8%) ( Table 1). Lymphopenia was common on admission (58.6%) but not associated with severe disease or death. Elevated D-dimer and elevated lactate were significantly associated with death (P = .005 and P = .024, respectively). Higher peak troponin-I and brain natriuretic peptide (BNP) levels during hospitalization were significantly associated with death (P < .001 and P = .004, respectively) (Table S1).

| Resuscitation status and palliative care
A formal palliative care consultation was documented in 46% of all patients, 67.6% of those who died, and 31% of those who survived to discharge (   presentation. [9][10][11][12] Gastrointestinal (GI) symptoms such as nausea, vomiting, and diarrhea were reported in <5% of patients. 4 Although fever and cough were common among our patients, nausea or vomiting was present in 24% and diarrhea in 29%. This is consistent with more recent studies suggesting that GI symptoms may be underreported. 14,15 Importantly, under-recognition of GI manifestations of COVID-19 may lead to delayed diagnoses, increasing the spread from undiagnosed individuals.

| Medical therapies
In our study, dementia was the only comorbidity significantly associated with mortality. With regard to other comorbidities, cardiovascular disease, obesity, and diabetes mellitus were the most common in our patients, which is consistent with a recent report of adult patients with COVID-19 in the United States. 15 Obesity was shown to be an independent risk factor for death in H1N1 influenza, and higher BMI has been associated with more severe disease and death in COVID-19. [16][17][18] In our study, obesity was a common comorbidity; 47.9% of patients had a BMI ≥30% and 31% of patients had a BMI ≥35 (Table 1). Importantly, BMI ≥35 was associated with an increased risk of both ICU admission and intubation. This association may be due to a higher prevalence of chronic diseases in this population, decreased respiratory reserve, and increased inflammatory cytokines. 16 Compared to this national cohort, chronic renal disease and immunosuppression were more common among our patients (21% vs 13% and 18% vs 9.6%, respectively). Previous reports from China also reported that hypertension, diabetes, and chronic lung disease were associated with ARDS or death. 11,12,19 In our study, 40.6% of patients had evidence of myocardial injury during admission. Notably, this is even greater than reported in previous studies, which demonstrated substantial rates of acute myocardial injury in COVID-19, ranging from 7.2% to 27.8%. 3,12,[20][21][22] Mechanisms for myocardial injury remain unclear, but proposed pathways include demand ischemia, plaque rupture, cytokine release syndrome (CRS), myocarditis, or stress cardiomyopathy. 23 Regardless of the mechanism, in this study, myocardial injury and elevated BNP were associated with mortality. Arrhythmia during hospitalization was observed in 18% of patients. Of those, 58.8% were atrial fibrillation, 23.5% were bradycardia, and 11.8% were ventricular tachycardia/ Consistent with prior reports, older age was associated with increased risk of severe disease and mortality. Age above 65 years was associated with increasing odds of death. Those with dementia or admitted from congregate living facilities experienced increased mortality.
Importantly, these findings highlight the significant vulnerability of older cohorts to viral pandemics. Following identification of early outbreaks in F I G U R E 1 Relationship between mortality and ICU admission by age group. Older patients were more likely to die but were less likely to be admitted to the ICU. (blue = mortality, red = ICU admission)  of an operational PCR plan will be critical for healthcare systems to respond appropriately and effectively to not only the ongoing COVID-19 pandemic but also other pandemics that will arise inevitably in the future.

FUNDING
None declared.

CONFLICT OF INTEREST
The authors declare no conflicts of interest. The corresponding author had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

TRANSPARENCY STATEMENT
W. Conrad Liles affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.