key: cord-298325-2gm4fnqi
authors: Shah, Sonia; Majmudar, Kaushal; Stein, Amy; Gupta, Nita; Suppes, Spencer; Karamanis, Marina; Capannari, Joseph; Sethi, Sanjay; Patte, Christine
title: Novel use of home pulse oximetry monitoring in COVID‐19 patients discharged from the emergency department identifies need for hospitalization
date: 2020-06-17
journal: Acad Emerg Med
DOI: 10.1111/acem.14053
sha: 
doc_id: 298325
cord_uid: 2gm4fnqi

OBJECTIVES: Our objective was to evaluate patient‐reported oxygen saturation (SpO(2)) using pulse oximetry as a home monitoring tool for patients with initially non‐severe COVID‐19 to identify need for hospitalization. METHODS: Patients were enrolled at the emergency department (ED) and outpatient testing centers. Each patient was given a home pulse oximeter and instructed to record their SpO(2) every eight hours. Patients were instructed to return to the ED for sustained home SpO(2) <92% or if they felt they needed emergent medical attention. Relative risk was used to assess the relation between hospitalization and home SpO(2) <92% in COVID‐19 positive patients. RESULTS: We enrolled 209 patients with suspected COVID‐19, of which 77 patients tested positive for COVID‐19 and were included. Subsequent hospitalization occurred in 22/77 (29%) patients. Resting home SpO(2) <92% was associated with an increased likelihood of hospitalization compared to SpO(2) ≥92% [RR 7.0 (95% CI 3.4 – 14.5), p‐value <0.0001]. Home SpO2 <92% was also associated with increased risk of ICU admission, ARDS and septic shock. In our cohort, 50% of patients who ended up hospitalized only returned to the ED for incidental finding of low home SpO(2) without worsening of symptoms. One‐third (33%) of non‐hospitalized patients stated they would have returned to the ED if they did not have a pulse oximeter to reassure them at home. CONCLUSIONS: This study found that home pulse oximetry monitoring identifies need for hospitalization in initially non‐severe COVID‐19 patients when a cut off of SpO(2) 92% is used. Half of patients who ended up hospitalized had SpO(2) <92% without worsening symptoms. Home SpO(2) monitoring also reduces unnecessary ED revisits.

In December 2019, a novel coronavirus called SARS-CoV-2 appeared in Wuhan city, Hubei Province, China and rapidly spread across the rest of the world. This virus causes a disease known as COVID-19. Most patients with this infection recover after experiencing mild flu-like symptoms, but 20% of patients clinically deteriorate, requiring hospitalization and critical care 1 . This deterioration can be quite rapid at times, resulting in patients requiring intubation and other advanced life support measures before or at arrival to the hospital.

One of the challenges of the COVID-19 pandemic in the United States is the strain it is placing on healthcare resources. Drastic measures have been taken to rapidly increase healthcare resources and reallocate healthcare workers to meet the needs during the pandemic. Given the severity of the ongoing global pandemic, the ability to remotely monitor patients who do not require hospitalization is essential for optimal utilization of healthcare resources. Importance A reasonable concern brought forward by emergency medicine physicians discharging initially non-severe patients with COVID-19 is that these patients could potentially decompensate at home after discharge. Home pulse oximetry has been proposed as a way to monitor disease progression in such patients. However, there are currently no data to guide the use of home pulse oximetry in COVID-19 patients or its validity in identifying disease progression.

Additionally, while it is generally known that patients with advanced age, comorbidities or certain laboratory findings are at increased risk for worse clinical outcomes, specific predictors for who will require hospitalization are not known at this time 2, 3 .

Our objective was to evaluate patient-reported oxygen saturation using pulse oximetry as a home monitoring tool for patients with initially non-severe COVID-19 to identify need for hospitalization.

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This prospective, uncontrolled open-label study took place at Swedish Hospital, part of NorthShore University HealthSystem in Chicago, IL between March 20 and April 22, 2020. The institutional review board approved the study and all patients consented to participate in the study. This study was registered with ClinicalTrials.gov (NCT04373161).

All patients were older than 18 years of age. Patients were enrolled if they had suspected COVID-19 as defined by the World Health Organization (WHO) 1 . Testing for COVID-19 was performed using reverse-transcriptase polymerase-chain-reaction (RT-PCR) of an oropharyngeal or nasopharyngeal swab. Patient testing locations included the emergency department (ED) or Swedish Hospital affiliated testing centers, including outpatient and employee testing sites for symptomatic individuals. For patients seen in the ED, only those being discharged to home were included. All patients had resting SpO 2 >92% on discharge from the ED. Patients being admitted to the hospital or discharged to a nursing facility were excluded. Other exclusion criteria included pregnancy and home oxygen use. Patients were not included if they were unable to be reached after enrollment.

Not all patients with suspected COVID-19 were tested due to ongoing test kit shortages during the time of this study. Only patients with positive COVID-19 testing were included in our outcome measures and analysis. Patients with suspected COVID-19 who did not undergo initial testing were still enrolled in case they were tested at a later time. ED physicians were not blinded to potential patient enrollment, but they were not specifically made aware of which patients were being enrolled into the study, or if patients were already enrolled upon return to the ED.

Upon discharge to home from the ED or testing site, patients were provided with an FDA approved Concord Health Supply EAD Fingertip Pulse Oximeter TM (Skokie, IL, USA) at no

This article is protected by copyright. All rights reserved cost to the patient. Patients had their resting oxygen saturation (SpO 2 ) checked using this pulse oximeter at time of enrollment and this measurement was recorded as Day 0. For seven days, patients checked their SpO 2 using the pulse oximeter at 6:00 AM, 2:00 PM, and 10:00 PM.

Seven day follow up was selected given the duration from symptom onset to hospitalization has been reported as 4, interquartile ratio (IQR) 2-7 days 2 . Investigators on the research study team called patients daily to collect data in real time.

In the study protocol provided to patients, they were instructed to return to the ED if: 1) their resting SpO 2 dropped below 92% and was confirmed with a separate reading ten minutes later or 2) they felt they needed emergent medical attention. During these calls, patients were also surveyed on whether use of home pulse oximetry prevented further ED visits. The standardized script used for patient calls is available as supplemental methods material accompanying the online article. After the home pulse oximeter-monitoring period, patients returned the pulse oximeter along with a standardized form detailing their measurements.

The decision to hospitalize on subsequent return to the ED was left to the discretion of the ED physician evaluating the patient, independent of this study.

Patients' charts were reviewed to identify prior medical problems, laboratory values on preliminary ED visit, laboratory values on subsequent return to the ED or hospitalization and outcomes of hospitalization. Obesity was defined as body mass index (BMI) > 30 kg/m 2 and lymphopenia was defined as lymphocyte count <1,500 cells/μL.

The primary outcome was hospitalization in patients with resting home SpO 2 below 92%. Other outcomes measured included trend in resting home pulse oximetry readings, timing of SpO 2 <92%, if home pulse oximeter use decreased subsequent ED visits, and outcomes of hospitalization such as length of stay and transfer to the intensive care unit (ICU). We also measured time to drop (TTD), defined as time from symptom onset to SpO 2 <92%, to see if this predicted admission to the ICU, development of acute respiratory distress syndrome (ARDS),

This article is protected by copyright. All rights reserved septic shock or mortality. Finally, we collected data on demographics, past medical history and laboratory values.

The relative risk (RR) of hospitalization for COVID-19 positive patients with resting home SpO 2 below 92% was calculated, with p-value and associated 95% confidence interval determined using the Wald method. An a priori power analysis indicated a sample size of 76 to provide 80% power to detect a relative risk of 2.75 between hospitalizations and resting home SpO 2 below 92%. Differences in SpO 2 trends by time of day were compared with a linear mixed effects model with an unstructured covariance matrix. The covariates considered were time of day and hospitalizations with a patient-specific intercept specified as a random effect. Differences between lab values for patients with both initial visit measurements and measurements at hospitalization were analyzed with a Wilcoxon signed rank test. We ran univariate logistic regression to identify predictors of ICU admission, development of ARDS, septic shock or mortality. We considered running multivariate analysis but given the small sample size of our study, this was not considered to be statistically relevant and was not included. Statistical significance was set at the 0.05 level and analysis was performed using R version 3.6.2.

A total of 209 patients with suspected COVID-19 were enrolled in our study. Of patients enrolled, 119 (57%) underwent RT-PCR testing and 79 (38%) tested positive for COVID-19.

Patients who tested negative, withdrew consent or were unable to be contacted after enrollment were excluded. A total of 77 COVID-19 positive patients were ultimately included and analyzed in our study ( Figure 1 ). Of these 77 patients, 9 patients were not initially tested on enrollment but tested positive at a subsequent ED visit. Enrollment locations included 61 (79%) patients enrolled from the emergency department, 9 (12%) from employee testing, and 7 (9%) from the outpatient testing center.

Demographic and baseline characteristics in COVID-19 positive patients are summarized in Table 1 . Median age was 44 (IQR 19), 43 (56%) were male and median BMI was 29.7 (IQR 7.9) mg/kg 2 . Patients were Hispanic (57%), Asian (27%), African American (8%), and Caucasian (8%). In our cohort, 20 (26%) were healthcare workers. There were 32 (42%) patients with no medical problems, 20 (25%) with one medical comorbidity, 11 (14%) with two comorbidities, and 14 (18%) with three or more comorbidities. The most common medical comorbidities were obesity (27%), hypertension (26%), diabetes (16%), hyperlipidemia (13%) and asthma (9%).

There were 10 (13%) patients on ACE inhibitor or angiotensin II receptor blockers.

Baseline laboratory values in patients at time of enrollment and subsequent laboratory values for hospitalized patients are summarized in Table 2 . Patients had lymphopenia, elevated lactate dehydrogenase, C-reactive protein, liver enzymes, ferritin and d-dimer on initial visit to the ED and upon hospitalization. Not all patients had laboratory studies drawn on enrollment as the decision to do so was left to the evaluating provider independent of this study. Laboratory values on day of admission to the hospital were not available for six patients as they were hospitalized at other institutions.

This article is protected by copyright. All rights reserved There were 19/77 patients (25%) with home SpO 2 <92%. Of these, 17 came back to the ED and 16 were hospitalized. Remarkably, 8 of these 16 patients (50%) only returned to the ED for incidental finding of low home SpO 2 without worsening symptoms. The single patient with SpO2 <92% who returned to the ED and was not hospitalized had an oxygen saturation of 94% in the ED and was discharged to home. Of the 58 patients who maintained SpO 2 >92%, 11 (19%) returned to the ED, where 5 patients were discharged and 6 patients were hospitalized ( Figure 2 ).

Resting home SpO 2 <92% was strongly associated with hospitalization compared to home SpO 2 >92% [RR 7.0 (95% CI 3.4 -14.5), p-value <0.0001] (Figure 3 ).

Symptoms were present for a median of 5 (IQR 4) days prior to enrollment and 6 (IQR 2) days prior to hospitalization. The median length of stay for hospitalization was 8 (IQR 6) Resting home SpO 2 <92% was not associated with increased mortality (p=0.5). There were 5 (23%) patients still hospitalized at the time of data censoring.

There was no specific time of day that had higher likelihood of SpO 2 <92% (p=0.09). Presented in Figure 4 are longitudinal home pulse oximetry readings in patients who ended up hospitalized and patients who were not hospitalized. All hospitalizations occurred within 5 days of enrollment. The median time to drop (TTD) was 6 (IQR 2) days. TTD was not associated with ICU admission (p=0.3), ARDS (p=0.5), septic shock (p=0.7) or mortality (p=0.7).

Trending laboratory values in patients who ended up hospitalized demonstrated significant increase in lactate dehydrogenase (p=0.03) from initial ED visit to return ED visit for

This article is protected by copyright. All rights reserved hospitalization. See Table 3 . Of COVID-19 positive patients who did not return to the ED, 16 Demographic data and prior medical history in patients with suspected COVID-19 who did not undergo testing are summarized in Supplemental Table S1 . Initial laboratory values on enrollment in this cohort is summarized in Supplemental Table S2 . Longitudinal home pulse oximetry readings in these patients are presented in Supplemental Figure S1 .

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In this study, we assessed the utility of home pulse oximetry monitoring in patients with initially non-severe COVID-19. Our study was designed to be a practical approach to monitor suspected and confirmed COVID-19 patients remotely and reduce in-person healthcare utilization. Our results found that pulse oximetry as a home monitoring tool identifies need for hospitalization in initially non-severe COVID-19 patients when a cut off of SpO 2 92% is used.

We selected SpO 2 <92%, a measure of peripheral oxygen saturation, because this indicates the presence of hypoxemia, a measure of oxygen pressure in arterial blood (PaO 2 ). A recent multicenter, prospective study found SpO 2 <92% had 95% sensitivity and 90% specificity for detecting PaO 2 <60 mmHg 3 . PaO 2 less than 60 mmHg defines hypoxemic respiratory failure 4 .

On the oxygen-dissociation curve, there is a steep drop in oxygen saturation as PaO 2 approaches 60 mmHg known as the "slippery slope". Below this level, small reductions in PaO 2 correlate with disproportionately large reductions in oxygen saturation and thereby oxygen delivery 5 . In a cohort study of 2,923 patients seen in the ED with pneumonia, hospitalizing patients for SpO 2 <92% was associated with improved mortality compared to hospitalizing patients with SpO 2 <90% 6 . This data supports an intervention using SpO 2 <92% as the cutoff to identify patients who may clinically deteriorate.

Over half of hospitalized patients in our cohort presented to the ED due to an incidental finding of low home SpO 2 without change in symptoms. A similar pattern has emerged recently whereby hypoxemia precedes severe symptoms in some patients with COVID-19, termed "silent hypoxemia" 7 . Pathophysiology to explain this phenomenon is still being debated. Histologic evaluation on autopsy in a COVID-19 positive patient demonstrated diffuse alveolar damage, pulmonary edema, lymphocytic inflammatory infiltrate and hyaline membrane formation, consistent with ARDS 8 . A recent publication suggests that while ARDS is present in COVID-19, there appears to be heterogeneity in clinical presentation suggesting two disease phenotypes.

They propose a varying combination of increasing inflammation and edema from patient selfinflicted lung injury related to increased negative intra-thoracic pressure against the otherwise compliant lung 9 . The use of supplemental oxygen improves hypoxemia and decreases work of

This article is protected by copyright. All rights reserved breathing, which may reduce the risk of lung injury. It is plausible that outcomes could be improved with early intervention. Based on our findings, home pulse oximetry may identify these "silent hypoxemia" patients in the outpatient setting prior to onset of severe symptoms and respiratory failure. A randomized controlled trial of pulse oximetry in the patient population that we studied will be required to test that hypothesis.

In our cohort, most patients who had SpO 2 <92% experienced an abrupt drop in SpO 2 rather than a gradual decline. This is consistent with emerging findings of certain patients rapidly deteriorating within a matter of hours 10 . The underlying physiology for this sudden change in clinical status is attributed to a surge in pro-inflammatory molecules including IL-1β, IL-6, CCL-2, CCL-3, CCL-5, TNF, and has been termed the "cytokine storm" phase of COVID-19 11 . It is plausible that "cytokine storm" contributes to this drop in SpO 2 .

Lactate dehydrogenase (LDH) increased in patients who had labs drawn on enrollment and then were subsequently hospitalized after returning to the ED. Our findings are concordant with recent data demonstrating elevated LDH as a predictor of more severe-COVID-19 disease 12 .

This laboratory value could be useful in assessing disease progression in COVID-19 patients who return to the ED. While platelet and albumin were inversely associated with odds of hospitalization, the median levels were within the normal ranges, so these findings may not be clinically relevant.

While recent literature suggests a low prevalence of asthma in patients with severe COVID-19, we found asthma to be associated with ICU admission, ARDS and septic shock in our cohort 12, 13 .

There are proposed mechanisms to account for a potential increased risk of severe disease in some patients with asthma including increased expression of angiotensin converting enzyme 2 and transmembrane protease serine 2. Further investigation into the outcomes of asthma patients with COVID-19 will be needed to better risk stratify these patients.

Our patient cohort differs in several characteristics compared to other published studies. Most studies evaluate the hospitalized COVID-19 population, which is comprised of patients who are more likely to be older and have more comorbid disease 14, 15 . In contrast, our patient population

This article is protected by copyright. All rights reserved was younger and almost half had no chronic medical problems. Additionally, while our hospital serves a community that is 72% non-Hispanic, our hospitalized cohort was predominantly Hispanic. Despite this, Hispanic ethnicity did not emerge as a factor associated with hospitalization in our univariate analysis. It is unknown if our findings will translate similarly to other patient populations.

This intervention was also successful in reassuring patients who may not require hospitalization, which in turn reduces ED utilization. This finding has two important benefits. Reducing ED utilization may reduce the risk of exposure to COVID-19 in healthcare workers in the emergency department. Additionally, this intervention may reduce unnecessary personal protective equipment (PPE) use. Globally, there is a PPE shortage including medical masks, respirators, gloves, gowns and eye protection. The WHO has released guidelines that call for minimizing the need for PPE in healthcare settings given the global shortage 16 . Our study found that providing home pulse oximeters to those with suspected or confirmed COVID-19 made patients feel more comfortable not returning to the ED as long as their oxygen saturation remained appropriate.

Home pulse oximetry is made less accurate by nail polish, severe anemia, hyperbilirubinemia, hemoglobinopathies, or poor peripheral perfusion from severe vasoconstriction or poor cardiac output 17 . While none of these conditions were present in our patients, it is important to note if applying to a larger patient population.

Given that one-quarter of our COVID-19 positive patients were healthcare workers, it is possible our cohort was easier to train in using the home pulse oximeter and had better follow up than the general population. Two patients withdrew from the study due to difficulty understanding how to use the pulse oximeter. Some patients could not be reached after enrollment. These occurrences emphasize the importance of patient selection and patient education when utilizing this intervention.

We standardized the home pulse oximeter used in our study to avoid variability between different brands. If multiple brands of pulse oximeters are used, the findings could be more

This article is protected by copyright. All rights reserved heterogeneous with variability between home pulse oximeter readings. In a study of three different commercially available pulse oximeters, good correlation was observed for each of the finger pulse oximeters when compared to arterial blood gas samples in 94 patients 18 . However, agreement may vary from device to device.

Patients were called once per day to collect data in real time. It is possible these patient callbacks highlighted the importance of SpO 2 below 92%, which may have increased likelihood of patients returning to the ED. The use of home pulse oximetry monitoring may perform better when paired with some form of telemedicine.

Given the need to censor data in order to be shared, outcomes of patients may underrepresent ICU status, ARDS, septic shock or mortality. Hospital length of stay is likely skewed lower as five patients remained hospitalized at time of data censoring. Additionally, our study is a small sample size, and larger scale studies need to be conducted to further investigate the utilization of home pulse oximetry monitoring to identify robust predictors of hospitalization. Such future studies should consider using known risk factors for poor outcomes in COVID-19 including age, gender, pre-existing hypertension, diabetes, chronic lung disease, cardiovascular disease, low albumin, elevated CRP and lymphopenia [19] [20] [21] [22] . Finally, we opted to exclude patients who tested negative for COVID-19, however it should be noted that there is a significant false negative rate with the current iteration of the RT-PCR test 23 . There may be some utility to providing pulse oximeters to patients with high index of suspicion for COVID-19 who test negative, however we did not investigate this.

This study found that home pulse oximetry monitoring identifies need for hospitalization in initially non-severe COVID-19 patients when resting home oxygen saturation drops below 92%.

Half of patients who ended up hospitalized had SpO 2 <92% without worsening symptoms. Home pulse oximetry monitoring reduces ED utilization, which in turn reduces exposure risk to frontline healthcare workers and conserves PPE. 

This article is protected by copyright. All rights reserved 

This article is protected by copyright. All rights reserved 

This article is protected by copyright. All rights reserved 

In accordance with our institutional review board, patients who withdrew consent or met exclusion criteria were not included. 209 were enrolled, 77 were ultimately included in our study. * RT-PCR = reverse-transcriptase polymerase-chain-reaction This article is protected by copyright. All rights reserved Accepted Article

Global Surveillance for human infection with coronavirus disease (COVID-19)

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