key: cord-277278-lg38l5gh
authors: Tang, Olive; Bigelow, Benjamin F.; Sheikh, Fatima; Peters, Matthew; Zenilman, Jonathan M.; Bennett, Richard; Katz, Morgan J.
title: Outcomes of nursing home COVID-19 patients by initial symptoms and comorbidity: Results of universal testing of 1,970 residents
date: 2020-10-14
journal: J Am Med Dir Assoc
DOI: 10.1016/j.jamda.2020.10.011
sha: 
doc_id: 277278
cord_uid: lg38l5gh

Objective Clinical implications of asymptomatic cases of the novel coronavirus disease 2019 (COVID-19) in nursing homes remain poorly understood. We assessed the association of symptom status and medical comorbidities on mortality and hospitalization risk associated with COVID-19 in residents of a large nursing home system. Design Retrospective cohort study. Setting and Participants 1,970 residents from 15 nursing home facilities with universal COVID-19 testing in Maryland. Methods We used descriptive statistics to compare baseline characteristics, logistic regression to assess the association of comorbidities with COVID-19, and Cox regression to assess the association of asymptomatic and symptomatic COVID-19 with mortality and hospitalization. We assessed the association of comorbidities with mortality and hospitalization risk. Symptom status was assessed at the time of the first test. Maximum follow-up was 94 days. Results Among the 1,970 residents (mean age 73.8, 57% female, 68% Black), 752 (38.2%) were positive on their first test. Residents who were positive for COVID-19 and had multiple symptoms at the time of testing had the highest risk of mortality (HR 4.44; 95% CI: 2.97, 6.65) and hospitalization (SHR 2.38; 95% CI: 1.70, 3.33), even after accounting for comorbidity burden. Cases who were asymptomatic at testing had a higher risk of mortality (HR 2.92; 95% CI: 1.95, 4.35), but not hospitalization (HR 1.06; 95% CI: 0.82, 1.38) compared to those who were negative for COVID-19. Of 52 SARS-CoV-2 positive residents who were asymptomatic at the time of testing and were closely monitored for 14 days at one facility, only 6 (11.6%) developed symptoms. Conclusions and Implications Asymptomatic infection with SARS-CoV-2 in the nursing home setting was associated with increased risk of death suggesting a need for closer monitoring of these residents, particularly those with underlying cardiovascular and respiratory comorbidities.

setting was associated with increased risk of death suggesting a need for closer monitoring of 24 these residents, particularly those with underlying cardiovascular and respiratory comorbidities. Based on case reports of COVID-19 submitted to the CDC surveillance network, adults with 56 comorbidities such as diabetes, lung disease, or heart disease had a higher prevalence of COVID-57 19 and may develop more severe illness 9-12 . However, comorbidity data was missing for over 58 half of the reported cases. Another study looking at hospitalized patients with COVID-19 59 showed a relationship between increasing age and number of comorbidities with in-hospital 60 mortality 13 . In particular, a history of chronic kidney disease, lung disease, or cardiovascular 61 disease was associated with higher mortality 13 . Literature examining the effect of comorbidities 62 on outcomes has predominantly focused on hospitalized cohorts, or those in middle-age without 63 testing of all individuals regardless of symptoms 5, 14, 15 . 64

On April 29, 2020, the Maryland Governor mandated that all residents of nursing homes in the 66

State of Maryland must undergo testing for SARS-CoV-2. We assessed outcomes associated 67 with SARS-CoV-2 infection among residents who were tested for SARS-CoV-2 RNA across one 68 nursing home system with both long-term and post-acute rehabilitation services. Signs and 69 symptoms of illness were obtained at the time of testing, and risk of infection, hospitalization, 70 and death was analyzed based on symptoms and underlying comorbidities. 71

Study Population. All residents (N=1,970) from a large system of skilled nursing facilities who 75 were universally tested for SARS-CoV-2 and had recorded test results between March 1, 2020 76

and June 12, 2020, were included in our study. Data was obtained from respiratory surveillance 77 line list and manual chart review of the skilled nursing facility Electronic Health Record. A 78 cohort of all residents at one facility who were asymptomatic at the time of testing were closely 79 monitored by nursing home staff for development of symptoms over a 14 day period; this was 80 documented in a dedicated line list and included as a sub-analysis. This study protocol was 81 approved by the Institutional Review Board with a waiver of written consent. 82 83 Exposure. Nasopharyngeal samples were collected at the nursing homes for reverse transcription 84 polymerase chain reaction testing for SARS-CoV-2 RNA. When nasopharyngeal swabs were not 85 available or if the resident would only consent to oropharyngeal swabs, an oropharyngeal sample 86 was collected instead. All residents who consented to testing were tested. Residents who did not 87 consent to testing were considered positive and isolated accordingly. Symptom status at the time 88 of testing was determined based on review of respiratory surveillance line list documentation 89 maintained by nursing facility in the health system. The respiratory surveillance line list is used 90 to monitor staff and resident symptoms during a respiratory disease outbreak or cluster. 68% Black) who were tested at least once for SARS-CoV-2 RNA; of these 752 (38.2%) initially 131 tested positive between March 1, 2020 and June 12, 2020. Of the 1,218 residents who initially 132 tested negative, 558 (45.8%) had at least 1 additional test, and 169 (13.9%) eventually tested 133 positive at some point before the end of follow-up. Residents who were positive for SARS-CoV-134

2 on their first test were significantly more likely to be hospitalized and die during follow-up 135 than residents who tested negative (Table 1, p<0.001). 136 not at a higher risk of testing positive for SARS-CoV-2 (OR 1.07, 95% CI: 0.80, 1.42). 143

Peripheral vascular disease, diabetes, chronic kidney disease, and depression remained 144 significantly associated with increased risk for infection after accounting for age, sex, and 145 facility ( Table 2) . 146

After accounting for age, sex, race, and facility (model 1) among those who tested 147 positive for SARS-CoV-2, coronary artery disease, heart failure, peripheral vascular disease, 148 anemia, diabetes, end-stage kidney disease, and depression were at increased risk of 149 hospitalization ( Table 2) . Only a history of COPD/emphysema was significantly associated with 150 higher mortality from COVID-19 after accounting for age, sex, and facility ( Table 2) . 151 152

Of the 752 residents who tested positive, 56.4% (n=424) had no documented signs or 154 symptoms at the time of testing. Of the cases with documented signs or symptoms (n=328), the 155 most common were fever 49.1 % (n=161) and cough 59.5% (n=195 , Table 1 ), and 56.4% of 156 residents (n=185) had only 1 documented sign or symptom. Among residents with COVID-19, 157 those with anemia, cancer, or end-stage renal disease were more likely to have signs and 158 symptoms of illness at the time of testing and those with dementia and peripheral vascular 159 disease were more likely to be asymptomatic ( Table 1) . 160

Over a maximum of 94 days of follow-up, there were 475 incident hospitalizations 161 observed among the 1,845 residents who consented to hospital transfer from the nursing home 162 system. The 30-day cumulative hospitalization rate was 45% among cases with multiple 163 symptoms at testing, 35% among cases with 1 symptom at testing, 22% among cases 164 asymptomatic at testing, and 21% among those who were negative. After accounting for all 165 confounders, cases who were symptomatic at testing remained at significantly higher risk of 166 hospitalization than those who were asymptomatic or negative (Figure 1a) . 167

There were 242 total deaths among the 1,970 residents over the 94 day follow up period; 168 155 (64%) were in those who tested positive for SARS-CoV-2. Mortality rates were highest 169 among residents who tested positive for SARS-CoV-2 and had COVID-19 signs or symptoms 170 (Figure 1b) . The 30-day cumulative mortality was 39% among cases with 2 or more signs or 171 symptoms at testing, 27% among cases with 1 sign or symptom at testing, 14% among cases who 172 were asymptomatic at testing, and 7% among those who were negative for SARS-CoV-2. After 173 accounting for demographics, comorbidities, and resuscitation preference (model 2), cases who 174 were symptomatic at testing remained at highest risk of mortality, and cases asymptomatic at 175 testing were at intermediate risk (HR 2.92; 95% CI: 1.95, 4.35) compared to those who were 176 negative (Table 3) . Those with multiple signs or symptoms also had a higher risk of mortality 177 compared to those with a single sign or symptom (Model 1 HR 1.52, 95% CI: 1.01, 2.99; Model 178 2 HR 1.52, 95% CI: 0.99, 2.35). 179

One facility had 52 cases who were asymptomatic at the time of testing and were closely 180 monitored for 14 days for development of signs or symptoms. Of these, only 6 (11.5%) 181 developed any documented symptoms over the 14 day follow up from point prevalence testing. 182

Of the 6 residents that became symptomatic, one developed a non-productive cough at day 9 post 183 diagnosis and remained stable in the facility. Three residents were hospitalized: one developed 184 malaise and shortness of breath at day 12 and was transferred to the hospital, then returned 5 185 days later; one developed an elevated temperature (99 o F) on day 10-he was transferred to the 186 hospital on day 12 when his oxygen saturation reached 91% and expired the next day. One 187 resident developed chills, shortness of breath, and diminished lung sounds on day 12 and expired during transfer to the hospital. The remaining two residents passed away abruptly in the facility-189 both were noted to rapidly develop restlessness and shortness of breath and expired shortly 190 thereafter (one on day 6 post diagnosis and one on day 11). state reporting data have all demonstrated that mortality from COVID-19 is higher in 206 underrepresented minority groups. Our findings suggest that this mortality differential among 207

Blacks is predominantly due to increased prevalence, and possibly severity of underlying 208 diseases, rather than a COVID-19-specific cause. 209

The clinical implications of COVID-19 detection among asymptomatic people remains 210 poorly understood 17 . The published prevalence of asymptomatic cases varies greatly from 211 population to population, ranging from 1.6% in China 18 to 88% in a Boston homeless shelter 19 . 212

In our study population of residents of long-term care facilities undergoing point prevalence 213

testing, over half of the cases detected were asymptomatic at testing, which is consistent with 214 other early reports in this setting 10,20,21 . 215

Despite a lack of documented symptoms at the time of testing, our data shows that 216 residents who are asymptomatic at testing have up to two times the mortality risk of residents 217 who test negative for SARS-CoV-2. However, there was no difference in risk of hospitalization 218 between residents who tested negative and asymptomatic residents who tested positive. This may 219

suggest that staff are unable to accurately elicit symptoms, or that infected individuals are 220 decompensating so rapidly that nursing home staff are not able to identify a clinical decline and 221 transfer them to a higher level of care prior to death. Indeed, residents with dementia or 222 cerebrovascular disease or history of stroke were more likely to be deemed asymptomatic than 223 others, suggesting that assessing symptom status in this population is particularly challenging 

Infections with SARS-CoV-2 detected on asymptomatic screening in the nursing home 273 setting are not benign, underscoring the importance of universal testing, especially in high-risk 274 subgroups. Reliance on signs and symptoms for SARS-CoV-2 risk assessment alone may not be 275 sufficient, as residents living with dementia may be at a higher risk of infection but less likely to 276 report or exhibit signs and symptoms, and the natural history of this disease remains to be fully 277 established, particularly in the setting of hypoxia without dyspnea. In addition to the obvious 278 benefits of case identification to assist with infection control practices, our data suggest that 279 asymptomatic residents are at higher risk of death than residents who tested negative and may 280 benefit from close monitoring, such as regular pulse oximetry, as well as any future treatments. 

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