key: cord-0922011-wn0dr50s
authors: Tarteret, Paul; Strazzulla, Alessio; Rouyer, Maxence; Gore, Cecile; Bardin, Guillaume; Noel, Coralie; Benguerdi, Zine-Eddine; Berthaud, Julien; Hommel, Manuel; Aufaure, Sylvie; Jochmans, Sebastien; Diamantis, Sylvain
title: Clinical features and medical care factors associated with mortality in French nursing homes during COVID-19 outbreak
date: 2020-12-07
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.12.004
sha: 4c4204ecf191c739c964c6f17fb10f3e6309a794
doc_id: 922011
cord_uid: wn0dr50s

OBJECTIVES: The aim of this study is to identify demographic, clinical and medical care factors associated with mortality in three nursing homes. METHODS: Two nursing homes were hospital-dependent, had connections with infection prevention and control departments, and had permanent physicians. Third nursing home had no direct connection with general hospital, no infection control practitioner, and no permanent physician. The main outcome was death. RESULTS: During first 3 months of the outbreak, 224/375 (59.7%) residents were classified “COVID-19 cases” and 57/375 (15.2%) died. Hospital dependent nursing homes had lower COVID-19 case fatality rates in comparison to non-hospital dependent nursing home (15 [6.6%] vs 38 [25.8%], OR 0.20 [0.11-0.38], p = 0.001). During first 3 weeks of the outbreak, mortality in COVID-19 patients decreased if they had daily clinical examination (aOR: 0.09 [0.03-0.35], p = 0.01), 3 vital signs measurements per day (OR: 0.06 [0.01-0.30], p = 0.001) and prophylactic anticoagulation (OR: 0 [0.00-0.24], p = 0.001). CONCLUSIONS: This study suggests that high mortality rates in some nursing homes during COVID-19 outbreak might be favoured by a lack of medical care management. Increasing human and material resources, encouraging presence of nursing home physicians and establishing connection with general hospitals should be consider to deal with present and future health disasters in nursing homes.

Coronavirus disease 2019 (COVID-19) pandemic caused 53 million confirmed cases and 1,3 million deaths worldwide by November 15 th , 2020; 1,918,345 cases and 43,913 deaths were reported in France [1] . More specifically, 44% of COVID-19 deaths in France occurred in nursing homes, and among these facilities, mean COVID-19 case fatality rate was 20% [2] . However, many outbreaks in nursing homes resulted in higher case fatality rates, sometimes up to 30% [3] . It underlines the urgent necessity to understand medical care factors associated with mortality and to enforce preventive measures in these facilities [4] .

At the beginning of the pandemic, no validated COVID-19 treatment exists, the World Health Organization therefore proposed standards of care for severe COVID-19 patients including oxygen therapy if required, daily clinical examination for adaptive fluid management and regular monitoring of vital signs [5, 6] . Prophylactic anticoagulation was also necessary in the context of bed rest and prothrombotic infection [7] [8] [9] . French government recommended to increase human and material resources in nursing homes rather than transferring all COVID-19 residents into overcrowded acute care units [10] . Therefore, a high number of physicians, nurses, oxygen tanks and personal protective equipment was required in nursing homes to implement these standards of care.

The aim of this study is to identify demographic, clinical and medical care factors associated with mortality in nursing home residents. This study was conducted according to the Declaration of Helsinki. A written and oral information was given to residents and legal representatives. No patient or legal representative expressed opposition for the inclusion in the study. A declaration of this study has been made to the National health data institute in order to ensure the protection of the computer data used. According with the current French legislation, approval by the local ethic committee was not demanded because a non-interventional research was conducted, meaning that all procedures and drugs administrated did not differed from daily clinical practice.

Two nursing homes (Home A and B) were hospital-dependent, they had connections with infection prevention and control departments, and had permanent physicians. The third nursing home (Home C) had no direct connection with general hospital, no infection control practitioner, and no permanent physician. Clinical data were collected during the first 3 weeks of the epidemic. Outcomes were collected during the first 3 months of the epidemic. Day 0 corresponded to the first day of symptoms of the first confirmed case among residents in each nursing homes. The time frame was: March 18 -April 8, 2020

for home A, March 22 -April 12, 2020 for home B and March 20, 2020 -April 10, 2020 for home C.

Nurses of all nursing homes had been trained to recognize COVID-19 symptoms and alert physicians immediately. Two groups were considered in "COVID-19 cases": i) "confirmed COVID-19 cases" with positive SARS-Cov-2 polymerase chain reaction (PCR) test or positive SARS-Cov2 serology. For the 3week analysis, confirmed cases only having a positive serology have at least one COVID-19 symptom during the first 3 weeks. ii) "presumed COVID-19 cases" who had at least one COVID-19 symptom assessed by a physician and their nursing home presented at least 3 "confirmed cases" in their population. Patients who had a negative serology were not considered as presumed cases.

Nursing home data and prevalence of sick leave among health care personal were collected by interviews with administrators, directors and nursing home physicians. Residents' characteristics were collected retrospectively: age, gender, grade of autonomy, abnormal nutritional status (obesity or underweight), 2019-2020 seasonal flu vaccination, arterial hypertension, heart failure, atrial fibrillation, ischemic heart disease, thromboembolic venous disease, chronic obstructive pulmonary disease, solid or hematologic neoplasia, chronic kidney disease and diabetes. The autonomy, gerontology, isoresources group (autonomie, gerontologie groupe iso resources or AGGIR) panel was used to evaluate the residents' autonomy as it is the scale used in France [11] . According to this panel, grade 1 is given to elderly patients who are confined in bed and require continuous surveillance while grade 6 is given to patients with preserved autonomy. Chronic kidney disease was defined as an estimated glomerular filtration rate below 60 ml/min in at least two blood samples at baseline [12] . Regarding the nutritional status, residents with a body mass index above 30 or below 21 were confirmed obese or malnourished. We performed the following analysis: i) description of the outbreak during the first 3 months, ii) description of nursing home medical care managements during the first 3 weeks, iii) medical care characteristics comparison between high COVID-19 case fatality rate homes and low case fatality rate J o u r n a l P r e -p r o o f homes during the first 3 weeks, iv) analysis of demographic, clinical and medical care characteristics associated with death during the first 3 weeks in COVID-19 residents.

The main outcome was 3-weeks mortality in "COVID-19 cases". Secondary outcomes were 3-weeks "COVID-19 cases", 3-weeks "confirmed COVID-19 cases" in residents, sick leave for health care personnel, 3-months mortality, 3-months "COVID-19 cases", 3-months "confirmed COVID-19 cases".

The following statistic tests were performed: Fisher test test for qualitative variables and Wilcoxon-Mann-Whitney-U-test for quantitative variables. Quantitative variables were presented in the text as median values. Epi-info software (https://www.cdc.gov/epiinfo/index.html) was used to perform univariate analysis. To explore the risk factors associated with death, a multivariate logistic regression model was used. Considering the total number of deaths in our study and to avoid overfitting in the model, three variables were chosen based on previous findings [13] : Age, saturation of peripheral oxygen, daily clinical examination. Multivariate analysis was performed with Spss software (https://www.ibm.com/analytics/spss-statistics-software).

Two-sided α of less than 0.050 was considered statistically significant.

During the first 3 months of the outbreak, among residents, 188/375 (50.1%) were classified "confirmed COVID-19 cases". Overall, 57/375 (15.2%) residents died from all-causes. Only 4/375 (1.1%) residents died without any COVID-19 symptoms. Due to a lack of reagent in France during the first 3 weeks of the study, 31/53 (58.5%) deceased residents had COVID-19 symptoms but couldn't have a SARS-Cov2 PCR and died before having the serology, they were classified as "presumed COVID-19 cases".

Infection control policy and medical care organisation in each nursing home are presented in Table 1 .

Hospital-dependent nursing homes (Home A and B) had the daily presence of a nursing home physician trained in geriatrics. Hospital infection control practitioners had audited those two nursing homes at the onset of the pandemic to train health care personnel and ensure good infection control policy. Hospital dependent nursing homes had expandable health care personnel capacity, oxygen tank and personal protective equipment stock. Nursing home C did not have permanent nursing home physician. In case of a sick resident, its general practitioner located nearby visited the patient. and material resources, a task force intervention took action from April 9 th to April 11 th to implement COVID-19 standards of care in nursing home C. The task force was composed by specialists (infectious diseases, hygiene and geriatrics) of the county general hospital. Most deaths were recorded in non-hospital-dependent home (Home C), where residents received fewer clinical examinations, anticoagulation, fluid therapy, vital signs monitoring and antibiotics. Therefore, residents were more exposed to thromboembolism, hypovolemic shock, hypoxia and bacterial superinfection. In this nursing home, 30.8% of deceased residents had not received oxygen therapy while they had SpO2 < 92%, it can be assumed this was due to limited oxygen tank stock and absence of a permanent physician who could have either demanded oxygen tank supply or transferred the patient to hospital. Moreover, this nursing home had a higher attack rate in residents and had multiple sick leaves in health care personnel which may be the result of an unscrupulous infection control policy, mainly due to a shortage in protective personal equipment and inappropriate surface deterging. This increase in sick leaves might have resulted to inadequate hydration, nutrition and less vital signs monitoring for residents. These deficiencies in medical care and infection control management could be easily avoided in hospital dependent nursing homes due to expandable medical and material resources.

It was interesting to note that these differences in mortality did not occur the previous year, in a normal health context.

Research on the causes of death among COVID-19 patients focused on co-morbidities and direct effects of SARS-Cov2 infection [14] [15] [16] . However, during first 3 weeks of the outbreak, among presumed and confirmed COVID-19 deceased patients, 12/28 (42.6%) had SpO2 > 92% which might suggest that mortality is not always due to severe acute respiratory syndrome. All of these patients were in nursing home C and therefore had less medical care. Reasons of death in these patients are unknown due to J o u r n a l P r e -p r o o f the absence of medical investigations. An hypothesis would be that these deaths may be the consequence of the "confinement disease" defined as all adverse events linked to bed confinement and lack of medical care in confined elderly people [17] . It means increased thrombosis, dehydration, depression, comorbidity decompensations and unknown organ dysfunction. Increased thrombosis is due to bed rest and pro-thrombotic infection [7] [8] [9] . Increased dehydration is due to symptoms like fever, tachypnea and diarrhea but it might also be caused by change in drinking behaviour due to social isolation and lack of care [18, 19] . Depression and comorbidity decompensation are due to social isolation which lead to cachexia and failure to thrive [20] [21] [22] [23] . Unknown organ dysfunction is caused by less vital signs and biological monitoring. The "Confinement disease" can be fatal but could be limited with high standards of care.

Hospital transfer are traumatic for nursing home residents and hospital avoidance programs have proven to be effective [24] [25] [26] [27] [28] [29] . All nursing homes should have an emergency management plan to enhance their infection control and medical response in the event of a local COVID-19 outbreak [30] . It should include an infection control policy, a permanent physician who implement the standards of care guidelines and the reinforcement of material and medical resources with a replacement policy of the sick health care professional [31, 32] . If this policy is implemented, the management of COVID-19 cases in nursing homes might be a safe option.

This study presents several limitations: i) it is retrospective and it include populations of only three nursing homes ii) risk factors of mortality were analyzed with a study period of 21 days and results need to be confirmed over a longer period of time. iii) molecular diagnosis was not available for all deceased patients. However, it is well established that COVID-19 epidemic was ongoing in the three nursing homes during the study period, as confirmed by the extremely high number of SARS-Cov2 positive patients. Misleading with flu was unlikely because influenza season had passed in the Ile-de-France region before the onset of the study [33] . Also, SARS-Cov2 PCR has high false negative rate, even J o u r n a l P r e -p r o o f though it is currently considered the gold standard for the diagnosis of SARS-Cov2 infection [34] . iv) Causes of death remains unclear in presumed and confirmed COVID-19 patients without acute respiratory syndrome and further studies are needed to confirm the hypothesis of the "confinement disease".

In conclusion, this study suggests that high mortality rates in some nursing homes during COVID-19 outbreak might be favoured by a lack of infection control and medical care management. Death may not always be caused by severe acute respiratory syndrome but also by a "confinement disease". Increasing 

We thank health care personal of all nursing homes studied for their work during this outbreak.

We thank Isabelle Merlier (Geriatrics department, Groupe Hospitalier Sud Ile de France, Melun, France) and Raouf Draidi (Geriatrics department, Hopital Leon Binet, Provins, France) who contributed to data collection.

The authors declare that they have no competing interests Alessio Strazzulla declares he has not financial or personal conflict.

Maxence Rouyer declares he has not financial or personal conflict.

Cécile Gore declares she has not financial or personal conflict.

Guillaume Bardin declares he has not financial or personal conflict.

Coralie Noel declares she has not financial or personal conflict.

Zine-Eddine Benguerdi declares he has not financial or personal conflict.

Julien Berthaud declares he has not financial or personal conflict.

Manuel Hommel declares he has not financial or personal conflict.

Sylvie Aufaure declares she has not financial or personal conflict. J o u r n a l P r e -p r o o f Week 

World Health Organisation. Coronavirus disease 2019 (COVID-19)

Ministère de la Santé et de la Solidarité

Epidemiology of Covid-19 in a Long-Term Care Facility in

Preventing the spread of COVID-19 to Nursing Homes: Experience from a Singapore Geriatric Centre

COVID-19 diagnosis and management: A comprehensive review

Clinical management of severe acute respiratory 44 infection (SARI) when COVID-19 disease is suspected: Interim guidance V 1

MD COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

Prophylactic anticoagulation for venous thromboembolic disease in geriatric patients

Stratégie de prise en charge des personnes agées en établissements et à domicile dans le cadre de la gestion de l'épidémie de Covid-10

The assessment of autonomy in elderly people

Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members: guidelines

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Autopsy in suspected COVID-19cases

Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up

SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes

SARS-cov-2 related deaths in French long-term care facilities: the "confinement disease" is probably more deleterious than the COVID-19 itself

Increasing fluid intake and reducing dehydration risk in older people living in long-term care: a systematic review

Water-loss dehydration and aging

Loneliness and Isolation in Long-term Care and the Covid-19 pandemic doi

Loneliness as a public health issue: the impact of loneliness on health care utilization among older adults

Social disconnectedness, perceived isolation, and symptoms of depression and anxiety among older Americans (NSHAP): a longitudinal mediation analysis

Failure to thrive in the elderly : diagnosis and management

A systematic literature review of factors affecting outcome in older medical patients admitted to hospital

Effects of an intervention to reduce hospitalizations from nursing homes: A randomized implementation trial of the INTERACT Program

Emergency commitment from nursing homes

What Are Nursing Facilities Doing to Reduce Potentially Avoid Hospitalizations?

The Interventions to Reduce Acute Care Transfers (INTERACT) quality improvement program: an overview for medical directors and primary care clinicians in long term care

A Hospital Partnership with a Nursing Home Experiencing a COVID-19 Outbreak: Description of a Multi-Phase Emergency Response in Toronto

Nursing home physician specialists: A response to the workforce crisis in long term care

Nursing home medical staff organization: Correlates with quality indicators

False negative: COVID-19 testing's catch-22