DOI: 10.1111/ggi.

13960

ORIGINAL ARTICLE
EPIDEMIOLOGY, CLINICAL PRACTICE AND HEALTH

Clinical characteristics and prognostic factors in COVID-19

patients aged ≥80 years
Marcello Covino,1 Giuseppe De Matteis,2 Michele Santoro,1 Luca Sabia,1 Benedetta Simeoni,1
Marcello Candelli,1 Veronica Ojetti1,3 and Francesco Franceschi1,3
1 Aim: The aim of the present study was to describe the clinical presentation of patients aged
Emergency Department,
Fondazione Policlinico ≥80 years with coronavirus disease 2019 (COVID-19), and provide insights regarding the
prognostic factors and the risk stratification in this population.
Universitario A. Gemelli, IRCCS ,
Rome, Italy Methods: This was a single-center, retrospective, observational study, carried out in a refer-
2 ral center for COVID-19 in central Italy. We reviewed the clinical records of patients consecu-
Department of Internal Medicine,
Fondazione Policlinico tively admitted for confirmed COVID-19 over a 1-month period (1–31 March 2020). We
excluded asymptomatic discharged patients. We identified risk factors for death, by a uni- and
Universitario A. Gemelli IRCCS ,
multivariate Cox regression analysis. To improve model fitting and hazard estimation, contin-
Rome, Italy
3
uous parameters where dichotomized by using Youden’s index.
Catholic University of the Sacred
Heart, Rome, Italy Results: Overall, 69 patients, aged 80–98 years, met the inclusion criteria and were included
in the study cohort. The median age was 84 years (82–89 years is interquartile range);
37 patients (53.6%) were men. Globally, 14 patients (20.3%) presented a mild, 30 (43.5%) a
Correspondence
severe and 25 (36.2%) a critical COVID-19 disease. A total of 23 (33.3%) patients had died at
Dr. Marcello Covino, Emergency 30 days’ follow up. Multivariate Cox regression analysis showed that severe dementia, pO2
Department, Fondazione ≤90 at admission and lactate dehydrogenase >464 U/L were independent risk factors for
Policlinico Universitario death.
A. Gemelli, IRCCS, Università
Conclusions: The present data suggest that risk of death could be not age dependent in
Cattolica del Sacro Cuore – Roma, patients aged ≥80 years, whereas severe dementia emerged is a relevant risk factor in this pop-
Largo A. Gemelli 1, 00168 – Roma, ulation. Severe COVID-19, as expressed by elevated lactate dehydrogenase and low oxygen
Italy. saturation at emergency department admission, is associated with a rapid progression to death
Email: marcello. in these patients. Geriatr Gerontol Int 2020; ••: ••–••.
covino@policlinicogemelli.it
Keywords: COVID-19, dementia, older adults, prognostic factors.
Received: 12 May 2020
Accepted: 18 May 2020

Introduction The overall estimated case fatality rate of COVID-19 in Italy is

7.2%; however, the median age for all COVID-19 related death is
Since the first case was identified in Wuhan city (China) in 81 years (73–86 years), and the case fatality rate in patients aged
December 2019, the novel coronavirus designated SARS-CoV-2, ≥80 years is >20%.8 Nevertheless, up to now, limited data are
has caused an international outbreak of respiratory illness named available for COVID-19 in older patients, and no reports have
coronavirus disease 2019 (COVID-19). The spectrum of COVID- focused on patients aged ≥80 years.9–11
19 is various, ranging from possible asymptomatic patients to The aim of the present study was to describe the clinical pre-
sentation of patients aged ≥80 years with COVID-19, and provide
severe progressive pneumonia and acute respiratory distress syn-
insights regarding the prognostic factors and the risk stratification
drome leading to death.1–5
in this distinctive population.
After the first case of COVID-19 was diagnosed in the Lom-
bardy region of Italy, in February, one of the largest and most seri-
ous clusters of COVID-19 in the world struck the Italian nation.
Methods
Despite an aggressive effort of containment put in place, the dis-
ease continues to spread and the number of affected patients is Study design
still rising; furthermore, the case fatality rate has been very high This was a single-center, retrospective, observational study carried
and dominated by older patients.6 out in an urban teaching hospital, which is a referral center for
Italy presents one of the highest life expectancies in the world, COVID-19, in central Italy. We reviewed the clinical records of all
which is at birth 80.3 years for men and 84.9 years for women.7 In the patients aged ≥80 years consecutively admitted to our emer-
Italy, people aged >65 years now represent approximately 22.6% gency department (ED) for suspected COVID-19 over a 1-month
of the population, and older adults aged ≥80 years represent 6.5% period (1–31 March 2020). COVID-19 was diagnosed based on
of the total population.7 the World Health Organization interim guidance.12 We included

© 2020 Japan Geriatrics Society | 1

 M Covino et al.

Table 1 Clinical and demographic characteristics of patients aged ≥80 years included in the study cohort

Variable All population (n = 69) Survived (n = 46) Died (n = 23) P

Age (years) 84 (82–89) 84 (81–89) 85 (83–86) 0.858
Sex (male) 37 (53.6%) 25 (54.3%) 12 (52.2%) 0.864
Ed presentation
• Heart rate (min−1) 85 (75–95) 83 (75–92) 87 (73–107) 0.404
• Systolic BP (mmHg) 127 (111–140) 130 (112–140) 122 (100–137) 0.132
• Diastolic BP (mmHg) 75 (65–89) 78 (65–90) 68 (60–86) 0.183
• pO2 (%) 94 (90–96) 95 (93–96) 89 (82–94) 0.001
• Temperature ( C) 36 (35.5–36.5) 36 (35.5–36.5) 36.2 (35.7–36.8) 0.596
• GCS 15 (15–15) 15 (15–15) 15 (15–15) 0.202
• NEWS ≥3 41 (59.4%) 24 (52.2%) 17 (73.9%) 0.083
Symptoms
• Fever 56 (81.2%) 56 (81.2%) 56 (81.2%) 0.663
• Dyspnea 32 (46.4%) 13 (28.3%) 19 (82.6%) <0.001
• Cough 29 (42.0%) 22 (47.8%) 7 (30.4%) 0.168
• Fatigue 8 (11.6%) 6 (13.0%) 2 (8.7) 0.595
• Other 11 (15.9%) 7 (15.2%) 5 (21.7%) 0.500
Clinical history
• CHF/CAD 21 (30.4%) 14 (30.4%) 7 (30.4%) 1.000
• Hypertension 41 (59.4%) 31 (67.4%) 10 (43.5%) 0.057
• Cerebrovascular disease 20 (29.0%) 11 (23.9%) 9 (39.1%) 0.189
• Diabetes 9 (13.0%) 7 (15.2%) 2 (8.7%) 0.448
• COPD 7 (10.1%) 3 (6.5%) 4 (17.4%) 0.159
• Severe dementia 8 (11.6%) 2 (4.3%) 6 (26.1%) 0.014
• Malignancy 3 (4.3%) 2 (4.3%) 1 (4.3%) 1.000
• Living in institution 17 (24.6%) 11 (23.9%) 6 (26.1%) 0.843
Radiology
• Negative 8 (11.6%) 7 (15.2%) 1 (4.3%)
• Monolateral pneumonia 29 (42.0%) 20 (43.5%) 9 (39.1%) 0.302
• Bilateral pneumonia 32 (46.4%) 19 (41.3%) 13 (56.5%)
Severity classification
• Mild 14 (20.3%) 13 (28.3%) 1 (4.3%)
• Severe 30 (43.5%) 22 (47.8%) 8 (34.8%) 0.005
• Critical 25 (36.2%) 11 (23.9%) 14 (60.9%)
Outcome
• ICU admission 11 (15.9%) 4 (8.7%) 7 (30.4%) 0.034
• Survival time (days) 26 (11–35) 35 (32–39) 5 (2–13) –
• Deaths 23 (33.3%) –
P-values are shown with regard to comparison between patients who survived and died. Survival follow up was assessed at 30 days from emergency
department admission. BP, blood pressure; CAD, coronary artery disease; CHF, congestive heart failure; COPD, chronic obstructive pulmonary dis-
ease; GCS, Glasgow Coma Scale; ICU, intensive care unit; NEWS, National Early Warning Score; pO2, peripheral oxygen saturation.

in the analysis only patients with a positive result on real-time • Symptoms at admission: fever (core temperature >37.5 C), dys-
reverse transcription polymerase chain reaction assay of nasal and pnea, cough, fatigue or other (including sore throat, headache,
pharyngeal swab specimens. diarrhea, abdominal pain, dysgeusia).
We excluded from the study cohort patients discharged from • Radiographic findings: based on chest X-ray or CT scan
ED, and patients already on orotracheal intubation at ED arrival. obtained in ED, patients were categorized as normal, mono-
For patients with more than one admission, only the latest access lateral ground-glass opacity or interstitial involvement and bilat-
was included in the analysis. eral pneumonia.
• Laboratory findings: hemoglobin, total white cell blood
Study variables count, serum creatinine, blood urea nitrogen, alanine amino-
transferase, lactate dehydrogenase, fibrinogen, prothrombin
We extracted from computerized clinical records clinical, labora- time, D-dimer, ferritin, C-reactive protein (CRP) and
tory and radiological findings at admission. We included in the procalcitonin.
analysis the following: • Patient disease presentation in ED: categorized as mild for nor-
mal X-ray findings, severe for positive S-ray and pO2 ≥92%,
• Physiological parameters: age, sex, temperature, heart rate, and critical for positive X-ray and pO2 <92%.
respiratory rate, blood pressure, Glasgow Coma Scale score, • Clinical history: coronary artery disease or congestive heart
oxygen supplementation and peripheral oxygen saturation failure, hypertension, diabetes, chronic obstructive pulmo-
(pO2). Based on physiological parameters, we calculated the nary disease, severe dementia, malignancy and institution
National Early Warning Score for all patients. residency.

2 | © 2020 Japan Geriatrics Society

 Covid-19 in older adults

Table 2 Laboratory values of patients aged ≥80 years in the study cohort

Laboratory Reference value Entire population (n = 69) Survived (n = 46) Died (n = 23) P
Haematology
Hemoglobin (g/dL) 13.0–16.0 13.2 (11.9–14.5) 13.2 (11.9–14.3) 13.2 (11.7–14.7) 0.784
White cell blood count (x109/L) 3.5–9.5 5.78 (4.55–7.67) 5.78 (4.83–7.50) 5.93 (3.94–8.27) 0.636
Biochemistry
Creatinine (mg/dL) 0.67–1.17 1.05 (0.88–1.52) 1.03 (0.88–1.32) 1.45 (0.88–2.05) 0.068
Blood urea nitrogen (mg/dL) 10–23 22 (17–38) 20 (16–31) 39 (20–58) 0.006
Alanine aminotransferase (U/L) 7–45 19 (14–32) 18 (13–27) 21 (15–53) 0.175
Lactate dehydrogenase (U/L) <250 322 (269–480) 305 (239–409) 511 (297–724) 0.005
Blood coagulation
Prothrombin time (s) 11–13 11.3 (18.8–11.9) 11.2 (10.9–11.9) 11.4 (10.8–12.6) 0.678
Fibrinogen (mg/dL) 200–400 478 (375–551) 475 (372–530) 497 (394–649) 0.225
D-dimer (ng/mL) <500 1446 (916–4729) 1374 (946–4824) 1875 (834–5090) 0.962
Inflammatory markers
C-reactive protein (mg/dL) <5 88.1 (33.2–156.7) 62.4 (28.1–102.6) 145.7 (77.9–210.5) 0.002
Procalcitonin (ng/mL) <0.5 0.11 (0.00–0.35)† 0.06 (0.00–0.18)† 0.29 (0.11–0.55)† 0.001
Ferritin (ng/mL) 12–240 732 (493–1267) 721 (413–1302) 806 (566–1381) 0.888
The P-value comparison is shown for differences between patients who survived and patients who died.
†
A total of 14 procalcitonin values are missing: nine among patients who survived and five among patients who died.

Figure 1 Multivariate Cox regression for prognostic factors. The forest plot graphically represents hazard ratios (95% confidence
interval) for peripheral oxygen saturation (pO2), blood urea nitrogen (BUN), lactate dehydrogenase (LDH), C-reactive protein
(CRP) and dementia. All parameters were assessed at emergency department admission.

Study end-points (percentage), and are compared by the χ2-test (with Fisher’s test if
appropriate).
The primary study end-point was the patient’s death. Survival fol- We compared the clinical and laboratory variables by a univari-
low up was assessed at 30 days from admission. ate Cox analysis (proportional hazards regression) for their associ-
ation with survival. The post-hoc analysis was made by log–rank
test. We entered significant parameters at univariate analysis into a
multivariate Cox regression model to identify independent predic-
Statistical analysis
tors of death. For a better model fitting and hazard estimation, we
Continuous variables are reported as the median (interquartile categorized the continuous variables into dichotomous parameters
range), and are compared at univariate analysis by Mann–Whitney (i.e. low/high). For each variable, we obtained the optimal dividing
U-test. Categorical variables are reported as the absolute number cut-off by Youden’s index, carrying out a receiver operating

© 2020 Japan Geriatrics Society | 3

 M Covino et al.

characteristic (ROC) curve analysis with respect to association CoV, the SARS-CoV-2 binds to human angiotensin-converting
with death. Survival curves were estimated by the Kaplan–Meier enzyme 2 (ACE2) for cell entry.15,16 Angiotensin-converting
method. We regarded a two-sided P-value ≤0.05 as significant. enzyme 2 is a membrane protein expressed in the lung, heart, kid-
Data were analyzed by SPSS v25 (IBM, Chicago, IL, USA) and ney and intestine. Angiotensin-converting enzyme 2 is largely
Medcalc 18.2 (MedCalc Software, Ostend, Belgium). expressed in the upper and lower respiratory tract, and this could
explain both the infectivity and lethality of Sars-Cov2.15
There is clear evidence that older patients are at higher risk of
Statement of ethics
death from COVID-19.1–5,17–20 Italian national data show an over-
The study was carried out in accordance with the Declaration of all mortality rate of 12.6%.21 However, mortality steeply increases
Helsinki, and was approved by the local ethics committee. with age; for patients aged <50 years it is <1%, in the fifth decade
it is 2.6%, in the sixth decade it is 9.8%, in the seventh decade it
Results rises to 24.2% and in the eighth decade it rises to 29.0%. Interest-
ingly, the mortality rate decreases to 24.7% in people aged
≥90 years.20 The present data, although in a limited sample,
A total of 69 patients, aged 80–98 years, met the inclusion criteria
appear to confirm this tendency. We found, in the present cohort
and were included in the study cohort. The median age was
of people aged ≥80 years, that increasing age does not represent a
84 years (82–89 years is interquartile range); 37 patients (53.6%)
risk factor for death. Whether this is due to a minor susceptibility
were men. Globally, 14 patients (20.3%) presented a mild,
of patients aged >90 years to Sars-CoV-2 infection damage, or
30 (43.5%) a severe and 25 (36.2%) a critical COVID-19 disease
possibly to a reduced secondary lung inflammation, should be fur-
(Table 1). Overall, 23 patients died. Interestingly, the age and sex
ther investigated.
distribution were similar between the patients who survived and
As the Sars-Cov2 cell entry receptor is located mainly in the
died (Table 1).
lungs, more than half of patients might develop dyspnea, and
Clinical history was quite homogeneous among the patients,
>10% might require ventilatory support.1–5,17–20 With acute hyp-
and the patients who survived did not present relevant differences
oxia being the main determinant of disease progression and sever-
compared with those who died. However, the patients who died
ity, the pO2 at admission is crucial for death risk stratification.
presented more frequently a history of severe dementia (Table 1).
The present data confirm that patients aged ≥80 years who are
As expected, the disease severity classification in ED was associ-
severely hypoxic at ED admission (pO2 <90%) have an increased
ated with outcome: among the patients who died, 14 (60.9%) had
risk of death. However, a pO2 ≤90% was not associated with death
a critical, eight (34.8%) a severe and just one patient had a mild
in the present cohort at multivariate analysis. Certainly, the
presentation. Disease progression was quite fast in the patients
reduced sample and the subsequent wide confidence interval of
who died. The median survival time for non-survivors was 5 days
our hazard estimation could not provide final clues on this point.
(2–13 days is interquartile range).
Indeed, the present patients were mainly severe and critical at
Among physiological parameters at admission, pO2 was the
admission, thus reducing the relative influence of hypoxia on our
only parameter significantly associated with death in the present
final hazard estimation.
cohort. For as laboratory values, patients who died had higher
An elevation of lactate dehydrogenase in COVID-19 patients
blood urea nitrogen, lactate dehydrogenase, CRP and pro-
who died was found in most of the studies currently available.22
calcitonin levels (Table 2). By using the ROC analysis with regard
These observations appear to be consistent with SARS, where
to these continuous variables, we found the best cut-off values
multivariate analysis identified elevated lactate dehydrogenase as a
discriminating death occurrence. Values were pO2 ≤90% (AUC
marker associated with worse outcomes.23 However, lactate dehy-
0.748 [0.608–0.889], P = 0.001), blood urea nitrogen >37 mg/dL
drogenase is a non-specific marker, which is commonly found in
(AUC 0.680 [0.526–0.835], P = 0.023), CRP >112 mg/dL (AUC
critically ill patients. Nevertheless, the present data confirm that
0.717 [0.577–0.857], P = 0.006) and lactate dehydrogenase
>464 U/L could be a relevant prognostic factor in patients aged
>464 U/L (AUC 0.708 [0.561–0.855]). The best discriminating
≥80 years affected by COVID-19.
value for procalcitonin was >0.19 ng/mL; however, we did not
The CRP level correlates to inflammation, and its concentra-
include it in the multivariate model, as we had 14 missing values.
tion is not affected by age, sex and physical condition.24 CRP is a
Multivariate Cox regression analysis showed that severe
well-known index of severe pulmonary infections, and CRP levels
dementia, pO2 ≤90 at admission and lactate dehydrogenase
were shown to positively correlate with lung lesions and disease
>464 U/L were independent risk factors for survival in these
severity in COVID-19.1–5,25 The present data suggest that elevated
patients (Fig. 1).
CRP could have a predictive role in oldest-old patients with
COVID-19; however, because of the small sample size in the pre-
Discussion sent study, an association between elevated CRP and an increased
risk of death cannot be established with certainty.
The present study evaluated the clinical course and risk factors for A distinct aspect of the present study is the association
patients aged >80 years affected by COVID-19. Our data suggest between dementia and poor outcome. Indeed, medical assistance
that for patients aged ≥80 years, further increasing age is not a risk to COVID-19 patients could be extremely difficult for patients
factor for survival, whereas a history of severe dementia, low pO2 with dementia.26 First, the new hospital environment can lead to
at admission, high CRP and lactate dehydrogenase >464 U/L are increased stress and behavioral problems in these patients.27 Sec-
risk factors for death. ond, hypoxia, which is a prominent clinical feature of COVID-19,
Until 2002, four coronavirus were known to infect humans, could complicate the presentation of dementia and induce delir-
and they globally accounted for 10–30% of upper respiratory tract ium, increasing the need for medical care, and the need for
infections in adults, with mild clinical consequences.5,13 The out- dementia support.28
break of SARS-CoV and MERS-CoV caused international alarm, The outbreak of the COVID-19 pandemic has raised great
whereas the factors associated with transmission of these human concerns for the >50 million people living with dementia world-
coronaviruses remain poorly understood.14,15 Similar to SARS- wide.26 These people might have difficulties in remembering

4 | © 2020 Japan Geriatrics Society

 Covid-19 in older adults

safeguard procedures, such as wearing masks, and self-quarantine 11 Wang L, He W, Yu X et al. Coronavirus disease 2019 in elderly patients:
measures could not apply to patients who are not self-sufficient. characteristics and prognostic factors based on 4-week follow-up.
J Infect 2020 (Mar 30); 80 6: 639–645.
Finally, long-term care facilities for dementia patients are at 12 World Health Organization. Clinical management of severe acute respi-
extreme risk for COVID-19 infection.29 The present data suggest ratory infection when novel coronavirus (2019-nCoV) infection is
that severe dementia itself is an independent risk factor for survival suspected: interim guidance. January 28, 2020 https://www.who.int/
in COVID-19 patients aged ≥80 years. Thus, as recommended by docs/default-source/coronaviruse/clinical-management-of-novel-cov.
pdf Accessed on April 1 2020.
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