AbstractObjective

To compare 30-day mortality in long-term care facility (LTCF) residents with and without COVID-19 and to investigate the impact of 31 potential risk factors for mortality in COVID-19 cases.

Design

Retrospective cohort study.

Setting and Participants

All residents of LTCFs registered in Senior Alert, a Swedish national database of health examinations in older adults, during 2019-2020.

Methods

We selected residents with confirmed COVID-19 until September 15, 2020, along with time-dependent propensity score–matched controls without COVID-19. Exposures were COVID-19, age, sex, comorbidities, medications, and other patient characteristics. The outcome was all-cause 30-day mortality.

Results

A total of 3731 residents (median age 87 years, 64.5% female) with COVID-19 were matched to 3731 controls without COVID-19. Thirty-day mortality was 39.9% in COVID-19 cases and 5.7% in controls [relative risk 7.05, 95% confidence interval (CI) 6.10-8.14]. In COVID-19 cases, the odds ratio (OR) for 30-day mortality was 2.43 (95% CI 1.56-3.79) in cases aged 80-84 years, 2.98 (95% CI 1.92-4.64) in cases aged 85-89 years, and 3.26 (95% CI 2.09-5.06) in cases aged ≥90 years, as compared with cases aged <70 years. Other risk factors for mortality among COVID-19 cases included male sex (OR, 2.56, 95% CI 2.19-3.00), neuropsychological conditions (OR, 2.18; 95% CI 1.75-2.70), impaired walking ability (OR, 1.46, 95% CI 1.19-1.80), urinary and bowel incontinence (OR 1.50, 95% CI 1.22-1.85), diabetes (OR 1.36, 95% CI 1.14-1.62), chronic kidney disease (OR 1.37, 95% CI 1.11-1.69) and previous pneumonia (OR 1.57, 95% CI 1.32-1.85). Nutritional factors, cardiovascular diseases, and antihypertensive medications were not significantly associated with mortality.

Conclusions and Implications

In Swedish LTCFs, COVID-19 was associated with a large excess in mortality after controlling for a large number of risk factors. Beyond older age and male sex, several prevalent clinical risk factors independently contributed to higher mortality. These findings suggest that reducing transmission of COVID-19 in LTCFs will likely prevent a considerable number of deaths.

Early in the coronavirus disease 2019 (COVID-19) pandemic, long-term care facilities (LTCFs) were pointed out as high-risk environments, requiring high priority for prevention and precaution.1World Health Organization
Infection prevention and control guidance for long-term care facilities in the context of COVID-19: Interim guidance, 21 March 2020. In spite of this, many countries have reported a considerable proportion of COVID-19–related deaths in LTCFs.2Danis K. Fonteneau L. Georges S. et al.ECDC Public Health Emergency Team
High impact of COVID-19 in long-term care facilities, suggestion for monitoring in the EU/EEA, May 2020., 3Thompson D.C. Barbu M.G. Beiu C. et al.The impact of COVID-19 pandemic on long-term care facilities worldwide: An overview on international issues., 4Sepulveda E.R. Stall N.M. Sinha S.K. A comparison of COVID-19 mortality rates among long-term care residents in 12 OECD countries., 5Lau-Ng R. Caruso L.B. Perls T.T. COVID-19 deaths in long-term care facilities: A critical piece of the pandemic puzzle. In Sweden, 50% of all deaths have occurred in LTCFs.6Socialstyrelsen
Statistik om smittade och avlidna med covid-19 bland äldre efter boendeform. Sweden has also had a much higher rate of COVID-19 mortality in LTCFs than neighboring countries, being 5-fold higher than in Denmark and 11-fold higher than in Norway and Finland.7Coronakommissionen
Internationella erfarenheter av covid-19 i äldreboenden. Underlagsrapport till SOU 2020:80 Äldreomsorgen under pandemin. In line with this observation, an independent committee of inquiry appointed by the Swedish government concluded that Sweden’s strategy to protect older adults living in LTCFs has failed.8Coronakommissionen
Äldreomsorgen under pandemin (SOU 2020:80). 2020. Thus, as the world continues to battle new waves of the pandemic, it is imperative to identify the most important risk factors for COVID-19 mortality in countries where mortality has been high in LTCFs, such as in Sweden, so that premature deaths can be prevented.Although previous research has identified male sex, older age, and comorbidity as risk factors for severe COVID-19 in the general population,9Docherty A.B. Harrison E.M. Green C.A. et al.Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study., 10Kim L. Garg S. O'Halloran A. et al.Risk factors for intensive care unit admission and in-hospital mortality among hospitalized adults identified through the U.S. Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET)., 11Petrilli C.M. Jones S.A. Yang J. et al.Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: Prospective cohort study., 12Williamson E.J. Walker A.J. Bhaskaran K. et al.Factors associated with COVID-19-related death using OpenSAFELY., 13Reilev M. Kristensen K.B. Pottegard A. et al.Characteristics and predictors of hospitalization and death in the first 11 122 cases with a positive RT-PCR test for SARS-CoV-2 in Denmark: A nationwide cohort., 14Huang Y. Lu Y. Huang Y.M. et al.Obesity in patients with COVID-19: A systematic review and meta-analysis. data from LTCF residents are lacking. Other than a few small studies,15Bielza R. Sanz J. Zambrana F. et al.Clinical characteristics, frailty, and mortality of residents with COVID-19 in nursing homes of a region of Madrid., 16Graham N.S.N. Junghans C. Downes R. et al.SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes., 17Shi S.M. Bakaev I. Chen H. et al.Risk factors, presentation, and course of coronavirus disease 2019 in a large, academic long-term care facility., 18Tarteret P. Strazzulla A. Rouyer M. et al.Clinical features and medical care factors associated with mortality in French nursing homes during the COVID-19 outbreak. only 1 large study has investigated risk factors for 30-day mortality following COVID-19 in LTCF residents.19Panagiotou O.A. Kosar C.M. White E.M. et al.Risk factors associated with all-cause 30-day mortality in nursing home residents with COVID-19. Strong risk factors in this study, apart from older age and male sex, were diabetes, chronic kidney disease, and impaired physical and cognitive function.19Panagiotou O.A. Kosar C.M. White E.M. et al.Risk factors associated with all-cause 30-day mortality in nursing home residents with COVID-19. Yet, the median age was only 79 years, and the study did not include a control group, highlighting that more studies in large, representative populations of LTCF residents are warranted. The aim of the present cohort study was to compare all-cause, 30-day mortality in COVID-19 cases and matched controls living in Swedish LTCFs. An additional aim was to also investigate the impact of 31 potential risk factors for all-cause 30-day mortality in COVID-19 cases.Discussion

This study showed that 30-day mortality was 40% in Swedish LTCF residents with COVID-19, which was 7 times higher than in matched controls without COVID-19. Beyond older age and male sex, independent risk factors for higher mortality were neuropsychological conditions, impaired walking ability, incontinence, diabetes, chronic kidney disease, and previous pneumonia. These risk factors, most of which are not modifiable, were highly prevalent, and associated with a high absolute risk of death, altogether emphasizing the importance of preventing COVID-19 transmission to LTCFs.

The 40% mortality rate in our study is almost twice as high as in a US study of more than 5000 nursing home residents.19Panagiotou O.A. Kosar C.M. White E.M. et al.Risk factors associated with all-cause 30-day mortality in nursing home residents with COVID-19. This difference likely reflects that our study cohort was older. Smaller studies, conducted in age groups similar to ours, showed more comparable mortality rates.15Bielza R. Sanz J. Zambrana F. et al.Clinical characteristics, frailty, and mortality of residents with COVID-19 in nursing homes of a region of Madrid.,28Atalla E. Zhang R. Shehadeh F. et al.Clinical presentation, course, and risk factors associated with mortality in a severe outbreak of COVID-19 in Rhode Island, USA, April-June 2020.,29Brouns S.H. Bruggemann R. Linkens A. et al.Mortality and the use of antithrombotic therapies among nursing home residents with COVID-19. A limitation of all these studies is that they lacked a control group, impeding assessment of excess mortality. In this sense, our results add important evidence regarding the profound dangers of COVID-19 in LTCFs, as illustrated by the 7-fold higher mortality. Although the reason for the high mortality is likely multifactorial and complex, the disease indisputably has a tremendous significance from a public health perspective, affecting older adults, especially those living in LTCFs, disproportionally. In support, a recent study showed that LTCF residents had 4 times higher risk of COVID-19 mortality, compared with community-dwelling older adults.30Brandén M. Aradhya S. Kolk M. et al.Residential context and COVID-19 mortality among adults aged 70 years and older in Stockholm: A population-based, observational study using individual-level data. Further, another study showed that COVID-19 is more dangerous for older adults compared to seasonal influenza, especially for older adults with certain comorbidities, being associated with a 5-fold higher risk of death.31Xie Y. Bowe B. Maddukuri G. Al-Aly Z. Comparative evaluation of clinical manifestations and risk of death in patients admitted to hospital with COVID-19 and seasonal influenza: Cohort study. Our study provides additional evidence that COVID-19 mortality is high also in older adults without other risk factors. Altogether, the findings from our study suggest that COVID-19 has caused a large number of premature deaths in Swedish LTCFs.In our study, older age, male sex, and neuropsychological conditions were among the most important risk factors for 30-day mortality in LTCF residents with COVID-19. Although these risk factors are known from previous studies,15Bielza R. Sanz J. Zambrana F. et al.Clinical characteristics, frailty, and mortality of residents with COVID-19 in nursing homes of a region of Madrid.,16Graham N.S.N. Junghans C. Downes R. et al.SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes.,19Panagiotou O.A. Kosar C.M. White E.M. et al.Risk factors associated with all-cause 30-day mortality in nursing home residents with COVID-19.,29Brouns S.H. Bruggemann R. Linkens A. et al.Mortality and the use of antithrombotic therapies among nursing home residents with COVID-19. less is known about their additive effects. Therefore, we also examined how the absolute risk of death varied depending on these 3 risk factors. For example, a 90-year-old male resident with severe neuropsychological conditions had a 30-day mortality risk of around 50%, which would have been 30% if he had not had neuropsychological conditions. In women, the corresponding difference was around 25% vs 15%. These large absolute differences strengthen the clinical importance of these 3 risk factors, and pinpoints groups that are especially critical to protect against being infected in LTCFs.Two other common patient characteristics that were associated with higher mortality were impaired walking ability and urine and bowel incontinence. Previous studies found physical function and frailty to be risk factors for 30-day mortality after COVID-19 in LTCFs15Bielza R. Sanz J. Zambrana F. et al.Clinical characteristics, frailty, and mortality of residents with COVID-19 in nursing homes of a region of Madrid.,19Panagiotou O.A. Kosar C.M. White E.M. et al.Risk factors associated with all-cause 30-day mortality in nursing home residents with COVID-19. and in-hospital mortality in older adults.32Hagg S. Jylhava J. Wang Y. et al.Age, frailty, and comorbidity as prognostic factors for short-term outcomes in patients with coronavirus disease 2019 in geriatric care. In one study, bowel incontinence was a risk factor for COVID-19 diagnosis.17Shi S.M. Bakaev I. Chen H. et al.Risk factors, presentation, and course of coronavirus disease 2019 in a large, academic long-term care facility. Thus, our study shows that in a large cohort of LTCF residents, easy-to-assess characteristics such as walking ability and incontinence are prevalent and independent risk factors for mortality after COVID-19.In contrast, no association was found between obesity and mortality. Although obesity is a well-known risk factor for developing severe COVID-19 in the general population,14Huang Y. Lu Y. Huang Y.M. et al.Obesity in patients with COVID-19: A systematic review and meta-analysis. studies in older people have shown conflicting results.33Sattar N. Ho F.K. Gill J.M. et al.BMI and future risk for COVID-19 infection and death across sex, age and ethnicity: Preliminary findings from UK biobank.,34Tobolowsky F.A. Bardossy A.C. Currie D.W. et al.Signs, symptoms, and comorbidities associated with poor outcomes among residents of a skilled nursing facility with SARS-CoV-2 infection—King County, Washington. The lack of association in our study may be related to the well-known obesity paradox in very old people,35Obesity paradox in aging: From prevalence to pathophysiology. for whom body-mass-index is a poor indicator of body composition and body fat distribution.36Kuk J.L. Saunders T.J. Davidson L.E. Ross R. Age-related changes in total and regional fat distribution. It has also been hypothesized that malnutrition could be an important risk factor,37Lidoriki I. Frountzas M. Schizas D. Could nutritional and functional status serve as prognostic factors for COVID-19 in the elderly?.,38Li T. Zhang Y. Gong C. et al.Prevalence of malnutrition and analysis of related factors in elderly patients with COVID-19 in Wuhan, China. but we did not find an association between food intake and mortality after adjustment for other risk factors, as in a previous study.18Tarteret P. Strazzulla A. Rouyer M. et al.Clinical features and medical care factors associated with mortality in French nursing homes during the COVID-19 outbreak. However, there was a trend toward an increased risk of mortality in those with the lowest BMI. Although this did not reach statistical significance, likely because of the small number of people in that BMI category, it cannot be ruled out that underweight is a risk factor for COVID-19 mortality in LTCF residents.Having diabetes or renal failure or chronic kidney disease was both common and associated with increased risk of 30-day mortality. Both these conditions have previously been identified as risk factors for mortality following COVID-19 in LTCF residents.19Panagiotou O.A. Kosar C.M. White E.M. et al.Risk factors associated with all-cause 30-day mortality in nursing home residents with COVID-19. Also, history of pneumonia was common and a strong risk factor for 30-day mortality. Although we are not aware of any other studies that have investigated pneumonia as a risk factor in LTCF residents, it was recently shown that previous pneumonia is a risk factor for COVID-19 diagnosis, hospitalization, and subsequent all-cause mortality in the general Swedish population.39Bergman J. Ballin M. Nordström A. Nordström P. Risk factors for COVID-19 diagnosis, hospitalization and subsequent all-cause mortality in Sweden: A nationwide study. Hypothetically, previous pneumonia could be a marker of impaired immune function that increases one’s susceptibility for severe COVID-19 infection.In our study, antihypertensives were not associated with mortality after COVID-19. This extends the results of observational studies showing that hypertension is not a risk factor in LTCF residents19Panagiotou O.A. Kosar C.M. White E.M. et al.Risk factors associated with all-cause 30-day mortality in nursing home residents with COVID-19.,29Brouns S.H. Bruggemann R. Linkens A. et al.Mortality and the use of antithrombotic therapies among nursing home residents with COVID-19. and is supported by randomized studies showing that continuation of antihypertensive treatment did not increase the risk of severe outcomes, as compared to discontinuation, in patients hospitalized with COVID-19.40Lopes R.D. Macedo A.V.S. de Barros E. et al.Effect of discontinuing vs continuing angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on days alive and out of the hospital in patients admitted with COVID-19: A randomized clinical trial.,41Cohen J.B. Hanff T.C. William P. et al.Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: A prospective, randomised, open-label trial. Similarly, many other common diseases or medications were not associated with mortality in this study, including cardiovascular disease, antithrombotics, pulmonary disease, and cancer. An explanation for these findings could be that many prevalent diagnoses have little impact on mortality risk in very frail older people who have lived to an old age. It should also be noted that because different conditions are likely less often diagnosed in LTCFs, and primary care diagnoses care are not captured in the NPR, the sensitivity to capture different diagnoses is likely lower than in community-dwelling individuals. Regardless, our results are similar to previous studies of nursing home residents,15Bielza R. Sanz J. Zambrana F. et al.Clinical characteristics, frailty, and mortality of residents with COVID-19 in nursing homes of a region of Madrid.,19Panagiotou O.A. Kosar C.M. White E.M. et al.Risk factors associated with all-cause 30-day mortality in nursing home residents with COVID-19.,29Brouns S.H. Bruggemann R. Linkens A. et al.Mortality and the use of antithrombotic therapies among nursing home residents with COVID-19. geriatric patients,32Hagg S. Jylhava J. Wang Y. et al.Age, frailty, and comorbidity as prognostic factors for short-term outcomes in patients with coronavirus disease 2019 in geriatric care. and veterans.42Ioannou G.N. Locke E. Green P. et al.Risk factors for hospitalization, mechanical ventilation, or death among 10131 US Veterans with SARS-CoV-2 infection.This study has several important strengths. To our knowledge, this is the first study to evaluate 30-day mortality following COVID-19 in LTCFs using a control group. The study cohort included a large representative population of LTCF residents from the whole of Sweden, who are of particular importance to study given that they have experienced the highest mortality rates from COVID-19. Moreover, more than 30 potential risk factors and clinical patient characteristics were available, and these were investigated through a comprehensive set of analyses, increasing the credibility of our findings. Some limitations of this study should also be considered. First, the data obtained from Senior Alert may not be completely accurate for the time of COVID-19 infection owing to the lag time between assessment in Senior Alert and baseline (COVID-19), although a sensitivity analysis suggested that this did not bias associations. Second, because the study cohort was restricted to residents in LTCFs with a record in Senior Alert in the past year, generalizability to all LTCF residents in Sweden may in theory be limited. However, our data captured 5409 cases compared to the 7143 cases confirmed in LTCFs in Sweden until mid-September according to official data,43Folkhälsomyndigheten
Veckorapport om covid-19, vecka 37. meaning that the coverage in our study was high. Third, the accuracy regarding identification of certain risk factors may be limited. For example, neuropsychological conditions comprised both dementia and depression, although these are clearly different conditions. Yet, using this item, we observed an OR of similar magnitude to that shown in a previous study where cognitive function was assessed using the Minimum Data Set.19Panagiotou O.A. Kosar C.M. White E.M. et al.Risk factors associated with all-cause 30-day mortality in nursing home residents with COVID-19. Moreover, although we had access to a wide array of potential risk factors, we lacked data on symptoms at COVID-19 presentation, which have previously been associated with mortality following COVID-19 in LTCF residents.19Panagiotou O.A. Kosar C.M. White E.M. et al.Risk factors associated with all-cause 30-day mortality in nursing home residents with COVID-19. Fifth, data on LTCF characteristics were lacking, for example data on staffing and structure, which could have influenced the transmission and mortality of COVID-19. Sixth, the results are not necessarily generalizable to other countries. Finally, although COVID-19 cases and controls were matched, there may be unmeasured differences between the groups that may partly have contributed to the higher mortality in cases.Article InfoPublication History

Published online: June 23, 2021

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The authors received funding used for salaries from Foundation Stockholms Sjukhem (MK), Academy of Finland (MK), Läkarsällskapet (MK), and the Swedish Research Council (MK, AN, PN). The funders had no role in any part of this manuscript or the decision to publish.

The authors declare no conflicts of interest.

Identification

DOI: https://doi.org/10.1016/j.jamda.2021.06.010

Copyright

© 2021 The Authors. Published by Elsevier Inc. on behalf of AMDA - The Society for Post-Acute and Long-Term Care Medicine.

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