Aronen et al.

BMC Geriatrics (2019) 19:111

https://doi.org/10.1186/s12877-019-1125-z

RESEARCH ARTICLE Open Access

Respiratory tract virus infections in the

elderly with pneumonia
Matti Aronen1,6* , Laura Viikari1, Ia Kohonen2, Tytti Vuorinen3, Mira Hämeenaho4, Maarit Wuorela1,
Mohammadreza Sadeghi4, Maria Söderlund-Venermo4, Matti Viitanen1 and Tuomas Jartti5*

Abstract
Background: In children suffering from severe lower airway illnesses, respiratory virus detection has given good
prognostic information, but such reports in the elderly are scarce. Therefore, our aim was to study whether the
detection of nasopharyngeal viral pathogens and conventional inflammatory markers in the frail elderly correlate to
the presence, signs and symptoms or prognosis of radiographically-verified pneumonia.
Methods: Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms (N = 382)
were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory
analyses included PCR diagnostics of nasopharyngeal swab samples for 14 respiratory viruses, C-reactive protein
(CRP) and white blood cell count (WBC). Chest radiographs were systematically analysed by a study radiologist. The
length of hospital stay, hospital revisit and death at ward were used as clinical endpoints.
Results: Median age of the patients was 83 years (range 76–90). Pneumonia was diagnosed in 112/382 (29%) of the
studied episodes. One or more respiratory viruses were detected in 141/382 (37%) episodes and in 34/112 (30%)
episodes also diagnosed with pneumonia. Pneumonia was associated with a WBC over 15 × 109/L (P = .006) and a
CRP value over 80 mg/l (P < .05). A virus was detected in 30% of pneumonia episodes and in 40% of non-
pneumonia episodes, but this difference was not significant (P = 0.09). The presence of a respiratory virus was
associated with fewer revisits to the hospital (P < .05), whereas a CRP value over 100 mg/l was associated with
death during hospital stay (P < .05). Respiratory virus detections did not correlate to WBC or CRP values, signs and
symptoms or prognosis of radiographically-verified pneumonia episodes.
Conclusion: Among the elderly with respiratory symptoms, respiratory virus detection was not associated with an
increased risk of pneumonia or with a more severe clinical course of the illness. CRP and WBC remain important
indicators of pneumonia, and according to our findings, pneumonia should be treated as a bacterial disease
regardless of the virus findings. Our data does not support routine virus diagnostics for the elderly patients with
pneumonia outside the epidemic seasons.
Keywords: Elderly, Etiology, Influenza virus, Parainfluenza virus, Pulmonary disease, Respiratory, Respiratory syncytial
virus, Rhinovirus, Virus

* Correspondence: moaron@utu.fi; ttjartti@utu.fi

1
Department of Geriatrics, Turku City Hospital, Turku, Finland
5
Department of Pediatrics and Adolescent Medicine, University of Turku and
Turku University Hospital, PO Box 52, 20520 Turku, Finland
Full list of author information is available at the end of the article

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Aronen et al. BMC Geriatrics (2019) 19:111 Page 2 of 11

Background hypothesized that virus detection could give clinically

The number of over 80-year-old patients with weaning relevant information in addition to conventional
immune system is rising rapidly in Western societies, inflammatory markers and chest radiograph findings in
but the clinical significance of respiratory virus infec- treating frail elderly patients.
tions among this group remains unclear. The burden of
pneumonia among the elderly is high as it includes sig- Methods
nificant morbidity, mortality and costs around the world Study design
[1]. In the United States alone, about 85% of the deaths This prospective follow-up study investigated the associ-
caused by pneumonia or influenza occur in the age ation between virus detection and predefined clinical
group of 65 years and older, and in 2013, in the health outcomes in elderly hospitalized patients. STROBE cri-
care of patients of all ages, more than 16.1 billion dollars teria were respected.
were spent on pneumonia [2].
As polymerase chain reaction (PCR) and rapid antigen Subjects
detection tests are increasingly available for respiratory The study was carried out in geriatric wards of the
virus detection [3], currently in 13 to 30% of lower re- Turku City Hospital between July 2007 and April 2009
spiratory tract infections among the elderly, a virus has as part of a previously introduced study [20]. Consecu-
been implicated [4, 5]. In the age group of 65 years and tive Turku residing patients of over 65 years of age suf-
older, influenza virus (Flu), respiratory syncytial virus fering from respiratory symptoms requiring hospital
(RSV) and parainfluenza virus (PIV) are the leading viral admission were recruited in this study. Patients were
causes of respiratory morbidity and mortality [6–8], excluded from the study if they were in extremely poor
while other viral causes include rhinovirus (RV) and cor- condition, had severe dementia or had been quarantined.
onaviruses (CoV) [9]. However, in contrast to pediatric The patient or his/her trustee was informed about the
data, there are only a few reports concerning the useful- study both orally and in a written form. Patient’s previ-
ness of respiratory virus diagnostics in the elderly, and ously named trustee was approached if patient’s ability
virus diagnostics have shown only limited value in to independent decision making was deteriorated. A
reducing antibiotic use and the length of hospital stay written consent from the patient or his/her trustee was
[10, 11]. While influenza detection is seen as an import- required to participate in the study. The study protocol
ant diagnostic tool by the physicians, the detection of was approved by the Ethics Committee of the Turku
other viruses is seen less useful [11]. University Hospital and it complies with the ethical rules
Among the elderly, the all-cause mortality rate associ- for human experimentation stated in the Declaration of
ated with respiratory viral infection increases with age Helsinki.
and is approximately 6–7% among the over 85-year-old
subjects [8]. This may, however, be an underestimate Clinical follow-up
due to a general bias towards predominantly recording Patients were considered to have respiratory symptoms
influenza as a death course, while neglecting other virus if they had coryza, cough, sore throat, hoarseness or
infections. Other common risk factors of a severe nasal stuffiness. In pneumonia episodes, the need for
respiratory viral infection among the elderly include oxygen was considered as a sign of dyspnea. At study
underlying medical conditions and poor response to entry patients or their trustees were interviewed using
influenza vaccine [12, 13]. In adults, mixed infections a standardized questionnaire (Additional file 1:
with a respiratory virus and a bacterial pathogen, espe- “Questionnaire”), which included questions concerning
cially rhinovirus with pneumococci, have been shown to the form of living before hospitalization, the hospital
associate with more severe pneumonia and longer unit the patient was coming from, chronic diseases,
hospitalization period [14–17]. C-reactive protein (CRP) influenza vaccination status, height, weight, smoking
value and white blood cell count (WBC) seem to be in- habits and physical activity. Hospital records were
sufficient methods in differentiating sole bacterial, mixed reviewed for the clinical history and gender of the
and sole virus pneumonias, although no unambiguous patient. Having one or more of the following condi-
methods exist [18, 19]. tions was defined as having other diseases: dementia,
All of the aforementioned findings support a clinically depression, diabetes, rheumatic disease or history of
meaningful role of virus diagnosis among the frail cancer.
elderly. Thus, the aim of this study was to investigate The length of the hospital stay, hospital revisit and
how viral pathogens detected in the nasopharynx and death during the hospital stay were used as clinical
conventional inflammatory markers (WBC and CRP) outcomes of this study. Patient was discharged from the
correlate to signs, symptoms and prognosis of pneumo- ward when the illness no longer required hospital treat-
nia among the age group of 65 years and over. We ment. A new episode of hospital care between 2 weeks
Aronen et al. BMC Geriatrics (2019) 19:111 Page 3 of 11

and six months from the last visit was considered a re- positive [22, 23]. HBoV infections were serologically
visit; earlier visits were considered prolonged illness and confirmed to be acute infections at the Department of
later a separate episode. For this study only hospital Virology, University of Helsinki, Helsinki, Finland.
revisits in which respiratory symptoms were present Blood samples for CRP and WBC analysis were
were recorded. routinely collected from all the patients as part of
hospital treatment. The serum samples were stored at −
Diagnostics 80 °C and analyzed by the hospital laboratory. The high-
Treatment-related chest radiographs taken in the study est values measured during the hospital stay were used
hospital were systematically analysed in a blinded fash- in statistical analysis.
ion by a study radiologist. The presence of interstitial in-
filtrate and/or lobar atelectasis in the chest radiograph
Statistics
was considered pneumonia after congestive heart failure
In basic statistics, two sample t-test, χ2 test and Fischer
as an etiology was excluded.
exact test (when counts < 5) were used when appropri-
From all patients meeting the inclusion criteria, naso-
ate. Logistic regression with full model was used to ana-
pharyngeal swab samples were collected (sterile flocked
lyse the association between clinical outcomes and virus
swab, 520CS01, Copan, Brescia, Italy) by study physi-
etiology, pneumonia, chronic illnesses (cardiovascular
cians within 24 h of admission. The swabs were then
diseases, respiratory diseases, other diseases), age, gender
stored in dry tubes in a refrigerator for a maximum of
and laboratory findings (WBC, CRP). Statistical signifi-
24 h before transportation to the laboratory where they
cance was established at the level of P < .05. For
were stored at − 80 °C. The swab samples were analysed
statistics SAS Enterprise Guide 4.3 (SAS Institute Inc.,
at the Department of Virology, University of Turku,
Cary, NC, USA) was used.
Turku, Finland by a multiplex reverse-transcriptase
(RT-)PCR test (Seeplex RV12 ACE Detection; Seegene,
Seoul, Korea) for adenovirus, coronavirus NL63 and Results
OC43, human bocavirus, human metapneumovirus Study population
(MPV), influenza A and B, and PIV1–3, and by using an A total of 921 episodes of hospital care were screened
‘in-house’ RT-PCR test for RSV, RV - including rhino- (Fig. 1). Of those 921 screened episodes of hospital care
virus type C - and enteroviruses (EVs) [21]. Based on 438 fulfilled the initial study requirements of age 65
our previous experiences in amplicon sequencing, if the years or over, hospitalization-needing disease, respiratory
in-house PCR test could not distinguish enteroviruses symptoms and a signed consent to participate in the
from rhinoviruses, the result was considered rhinovirus study. A swab and serum samples were collected from

Fig. 1 Study flow chart

Aronen et al. BMC Geriatrics (2019) 19:111 Page 4 of 11

the patients of these 438 episodes. Of the 438 episodes, (57%) in the group diagnosed with pneumonia than
a chest radiograph was available for 382 episodes. In 112 in the group not diagnosed with pneumonia (42%)
of the 382 episodes the patient was diagnosed from a (P = .008). The weight of the patients seemed to be lower
chest radiograph finding as having pneumonia. In 55 in the group diagnosed with pneumonia (P = 0.05),
(49%) of these 112 pneumonia episodes the patient had whereas heart dysrhythmia seemed to be more common
pneumonia with dyspnea and in 57 (51%) pneumonia among patients not diagnosed with pneumonia (P = .03).
without dyspnea. The characteristics (age, gender, pres- In connection with the study episodes without pneu-
ence of chronic illnesses, smoking status) of 56 patients monia, in 16% the patient had a history of a stroke
who had respiratory symptoms but no chest radiograph or transient ischemic attack (TIA) and in 16% the
available, were not different from the included subjects patient smoked, compared to 9.2 and 25% of the
(P > .08, data not shown). study episodes diagnosed with pneumonia, respect-
ively. These differences were, however, not statistically
Patient characteristics significant (P = .08 and P = .1, in the same order).
Mean age of the patients in the study was 82.9 (sd Otherwise cardiovascular, respiratory and other
7.2) years (Table 1). A diagnosis of cardiovascular diseases were equally common in the study episodes
disease was present in 74% and respiratory disease in diagnosed with pneumonia and the study episodes
34% of the study episodes. There were more men not diagnosed with pneumonia (all P > .1).

Table 1 Patient Characteristics

Respiratory Symptoms (n = 382)
Pneumonia (n = 112) No Pneumonia (n = 270) P-value
Gender (male/female) 64/48 (57%/43%) 114/156 (42%/58%) 0.008
Age 83 (7) 83 (7) 0.8
Weight 65 (15) 69 (17) 0.05
Respiratory diseases 41/109 (38%) 90/262 (34%) 0.5
- Asthma/COPD 32/109 (30%) 76/262 (29%) 0.9
- Other lung disease 11/109 (10%) 29/262 (11%) 0.9
Cardiovascular diseases 80/109 (73%) 202/262 (77%) 0.4
- Stroke/TIA 10/109 (9.2%) 42/262 (16%) 0.08
- Heart dysrythmia 23/109 (21%) 84/262 (32%) 0.03
- Myocardial infarction 18/109 (17%) 38/262 (15%) 0.6
- Heart failure 24/109 (22%) 69/262 (26%) 0.4
- Hypertension 52/109 (48%) 120/262 (46%) 0.7
- MCC 34/108 (31%) 87/261 (33%) 0.7
Other diseases 65/105 (62%) 183/256 (71%) 0.07
- Dementia 22/105 (21%) 55/256 (21%) 0.9
- Depression 5/105 (4.8%) 20/256 (7.8%) 0.3
- Rheumatic disease 25/105 (24%) 72/256 (28%) 0.4
- Diapetes mellitus 0.4
- Type 1 0/105 (0%) 2/256 (0.8%)
- Type 2 19/105 (23%) 58/256 (18%)
- Cancer status 0.2
- Terminal 2/105 (1.9%) 9/256 (3.5%)
- Have been treated 7/105 (6.7%) 32/256 (13%)
- Under treatment 6/105 (5.7%) 20/256 (7.8%)
Smoking 20/81 (25%) 31/192 (16%) 0.1
Data expressed as n (%) or mean (standard deviation)
Two sample t-test, χ2 test and Fischer exact test (when counts < 5) were used
Significant values are shown bold and italic
COPD, chronic obstructive pulmonary disease, TIA Transient ischemic attack, MCC Morbus coronarius cordis
Aronen et al. BMC Geriatrics (2019) 19:111 Page 5 of 11

Virus detection study episodes diagnosed with pneumonia but without

A respiratory virus was detected in 141/382 (37%) respiratory viruses, no differences between WBC or CRP
nasopharyngeal swabs of the study episodes (Table 2). values were found (P > .2, Table 4). Corresponding ef-
Overall, rhinovirus and influenza virus were the two fects of the most common viruses (rhinovirus, influenza
most common viruses detected, both present in 35 (9%) virus, coronavirus, RSV and parainfluenza virus) were
study episodes, followed by parainfluenza in 28 (7%), also tested separately, and no differences were found
coronavirus in 24 (6%), RSV in 22 (6%), MPV in 8 (2%) (P > .1).
and adenovirus in 2 (1%) cases. During one study
episode, prolonged bocavirus shedding was found in the
nasopharynx of the patient, but serology did not confirm Clinical outcomes
an acute infection. In 30% of the study episodes A clinical outcome was available for 357 of the 382 study
diagnosed with pneumonia a respiratory virus was also episodes. Of the 357 study episodes with clinical out-
detected, whereas the same was true for 40% of the come available, in 108, the patient stayed in the hospital
study episodes not diagnosed with pneumonia. This for more than 13 nights, in 127, the patient had a revisit
association was, however, not statistically significant and in 29, the patient died during the hospital stay
(P = 0.09). Virus detection was also found not to be asso- (Table 5).
ciated with dyspnea (P > .5), nor were there virus-specific In study episodes diagnosed with pneumonia, the
differences found between study episodes diagnosed with presence of a respiratory virus was neither associated
pneumonia and with dyspnea, and study episodes diag- with clinical outcomes (i.e. over 13-night hospital stay,
nosed with pneumonia but without dyspnea (P > .1). number of revisits or death at ward) nor with WBC
values over 15 × 109/L or CRP values over 100 mg/l
White blood cell count and CRP-reactive protein level (all P > .1, Table 4). Similar results were also seen with
The mean WBC value was 13.8 × 109/L in study episodes lower WBC and CRP cutoff values of 10 × 109/L and
with pneumonia and 11.1 × 109/L in study episodes with- 80 mg/l, respectively (data not shown). Also in con-
out pneumonia, but this difference was not statistically nection with study episodes diagnosed with pneumo-
significant (P = 0.07, Table 3). As a categorical variable, nia, there was no association between the above
WBC over 15 × 109/L was associated with study episodes mentioned clinical outcomes and laboratory findings
diagnosed with pneumonia (P < .006, Table 3). (WBC over 15 × 109/L/l or CRP over 100 mg/l)
The mean CRP value was 146 mg/l in study episodes (P > .2). In study episodes diagnosed with pneumonia
with pneumonia and 105 mg/l in study episodes without and with dyspnea, death at ward was seen in 15% of
pneumonia (P < 0.001). As a categorical variable, a CRP the study episodes, whereas in connection to study
value over 100 mg/l, or even over 80 mg/l, was associated episodes diagnosed with pneumonia but without
with a pneumonia finding in the chest radiograph (P < .05 dyspnea, the same was true in 5.3% of the study epi-
for both, Table 3). sodes, although this difference was not statistically
When comparing study episodes diagnosed with pneu- significant (P = 0.07). However, study episodes diag-
monia and with one or more respiratory viruses, and nosed with pneumonia and with dyspnea lasted longer

Table 2 Presence of respiratory viruses in episodes with pneumonia and dyspnea

Respiratory symptoms (n = 382) P- Pneumonia (n = 112) P-
value value
Pneumonia (n = 112) No pneumonia (n = 270) Dyspnea (n = 57) No dyspnea (n = 55)
Rhinovirus 12 (11%) 23 (8.5%) 0.5 8 (15%) 4 (7.0%) 0.2
Influenza virus 7 (6.3%) 28 (10.4%) 0.2 2 (3.6%) 5 (8.8%) 0.4
Parainfluenza virus 5 (4.5%) 23 (8.5%) 0.2 2 (3.6%) 3 (5.3%) 1.0
Coronavirus 7 (6.3%) 17 (6.3%) 1.0 4 (7.3%) 3 (5.3%) 0.7
Respiratory syncytial virus 3 (2.7%) 19 (7.0%) 0.1 3 (5.5%) 0 (0%) 0.1
Human metapneumovirus 3 (2.7%) 5 (1.9%) 0.7 2 (3.6%) 1 (1.8%) 0.6
Adenovirus 1 (0.89%) 1 (0.37%) 0.5 1 (1.8%) 0 (0%) 0.5
Bocavirus 1 (0.89%) 0 (0%) Na 1 (1.8%) 0 (0%) 0.5
1 or more viruses 34 (30%) 107 (40%) 0.09 18 (33%) 16 (28%) 0.6
2 or more viruses 7 (6.3%) 13 (4.8%) 0.6 4 (7.3%) 3 (5.3%) 0.7
χ < 2 test and Fischer exact test (when counts < 5) were used
Data expressed as n (%)
Aronen et al. BMC Geriatrics (2019) 19:111 Page 6 of 11

Table 3 White blood cell count and C-reactive protein values in episodes with pneumonia and dyspnea
Respiratorys symptoms (382) P-value Pneumonia (112) P-
value
Pneumonia (112) No pneumonia (270) Dyspnea (57) No dyspnea (55)
WBC 13.8 (sd 14) 11.1 (sd 9.3) 0.07 12.4 (sd 5.7) 15.1 (sd 19) 0.3
WBC over 10 57 (51%) 111 (42%) 0.08 27 (47%) 30 (56%) 0.4
WBC over 15 29 (26%) 38 (14%) 0.006 14 (26%) 15 (26%) 1.0
CRP 146 (sd 92) 105 (sd 79) < 0.0001 158 (sd 95) 134 (sd 88) 0.2
CRP over 80 81 (72%) 151 (56%) 0.003 43 (78%) 38 (67%) 0.2
CRP over 100 71 (63%) 120 (44%) 0.0007 38 (69%) 33 (58%) 0.2
Data expressed as mean (standard deviation) or n (%)
Two sample t-test, χ2 test were used
Significant values are shown bold and italic
WBC White blood cell count (×109/L), CRP C-reactive protein (mg/l)

than study episodes diagnosed with pneumonia but of hospital revisits. Secondly, radiologically confirmed
without dyspnea (P = .02). pneumonia was associated with the indicators of a se-
No difference in the number of deaths at ward was vere bacterial infection, WBC over 15 × 109/L and CRP
seen between study episodes diagnosed with pneumonia over 100 mg/l. Thirdly, a CRP value over 100 mg/l was
and study episodes not diagnosed with pneumonia. A associated with death at ward.
negative association was found between hospital revisit Our finding, namely that 30% of the study patients
and virus detection; a revisit was less probable when a diagnosed with pneumonia also had a respiratory
virus was present than when a virus was not present; 43 virus present in nasopharynx, is in line with recent
(31%) revisits occurred among the virus-positive study studies executed on adults that suggest that even one
episodes and 93 (39%) revisits among the virus-negative third of pneumonia cases are associated with a re-
study episodes (P < .05, Table 6). Finally, a CRP value spiratory virus [4, 5, 9]. In our study, rhinovirus was
over 100 mg/l was associated with death at ward; 21 of the most common virus present in the study episodes
the 29 (72%) deceased patients had CRP values over 100 diagnosed with pneumonia, followed by coronavirus
mg/l (P = .04. Table 6). and influenza virus. Treanor et al. anticipated in their
study that the role of these common cold viruses,
Discussion coronavirus and rhinovirus, among the elderly will
The study shows three main findings. Firstly, radiologic- rise in the future, although PIV, RSV and influenza
ally confirmed pneumonia was not associated with are still considered the most harmful viruses among
respiratory virus detection. Moreover, in the studied the elderly [6–8]. Our findings also support this idea
episodes of hospital care diagnosed with pneumonia, the of a rising clinical significance of common cold vi-
presence of a respiratory virus was associated neither ruses, especially rhinovirus, among the elderly [6, 24,
with clinical outcomes, nor with WBC or CRP values. 25]. An association between elevated disease severity
Against our study hypothesis, all the studied episodes of and dual infection, especially rhinovirus/pneumococcal
hospital care in which the patient was diagnosed with infection, in the adult population have been reported
one or more respiratory viruses were, in fact, associated previously [14, 17]. Our analyses, however, showed no dif-
with a less severe clinical course in terms of the number ferences in the severity of the study episodes diagnosed

Table 4 Associations between laboratory findings, clinical outcomes, pneumonia and presence of a virus in hospital episodes with
respiratory symptoms
Pneumonia+/virus+ Pneumonia+/virus- Pneumonia−/virus+ Pneumonia−/virus- P (1vs2) P (1vs3) P (3vs4) P (1vs4)
(1) (2) (3) (4)
WBC over 15 7 (21%) 22 (29%) 8 (7.5%) 30 (19%) 0.4 0.03 0.01 0.8
CRP over 100 24 (71%) 47 (60%) 40 (37%) 80 (49%) 0.3 0.001 0.06 0.02
Had a revisit 11 (32%) 26 (33%) 32 (30%) 67 (41%) 0.9 0.8 0.06 0.3
Over 13 nights at ward 11 (32%) 23 (29%) 28 (26%) 59 (36%) 0.8 0.5 0.08 0.7
Death at ward 1 (2.9%) 10 (13%) 7 (6.5%) 11 (6.8%) 0.1 0.4 0.9 0.4
χ2 test and Fischer exact test (when counts < 5)
Significant values are shown bold and italic
Pneumonia + Episodes with pneumonia, Pneumonia- Episodes without pneumonia, Virus + Episodes with a virus detected, Virus- Episodes without a virus detected,
CRP C-reactive protein (mg/l), WBC White blood cell count (×109/L)
Table 5 Patient characteristics of those who died at ward
Case number Age range Gender Pneumonia Dyspnea Respiratory disease Cardiovascular disease Other disease A respiratory virus Over 13 nights at ward WBC over 15
1 70–80 M 0 1 0 1 1 1 1 0
2 90–100 M 0 1 1 1 1 1 1 0
3 80–90 F 0 1 1 0 1 1 1 1
4 90–100 F 0 1 0 1 1 1 1 0
5 90–100 F 0 1 0 1 1 1 0 0
Aronen et al. BMC Geriatrics

6 90–100 F 1 0 0 1 Na 1 1 0
7 90–100 M 0 1 0 1 1 1 1 0
8 80–90 M 0 0 0 0 1 1 1 0
9 80–90 F 1 0 0 0 Na 0 1 1
(2019) 19:111

10 70–80 M 1 1 0 0 0 0 1 1
11 70–80 M 0 1 0 1 Na 0 1 1
12 80–90 M 0 0 Na Na Na 0 1 1
13 80–90 F 0 1 1 1 1 0 1 1
14 80–90 M 0 1 0 0 0 0 0 1
15 90–100 F 0 1 0 1 0 0 0 1
16 70–80 M 1 1 1 1 0 0 1 0
17 90–100 M 1 1 0 1 0 0 1 0
18 80–90 F 0 0 Na Na Na 0 1 0
19 70–80 M 0 1 1 0 1 0 1 0
20 80–90 F 1 1 0 1 1 0 0 0
21 80–90 F 1 0 0 1 1 0 0 0
22 70–80 M 1 1 0 0 0 0 0 0
23 70–80 M 0 1 1 0 1 0 0 0
24 80–90 M 0 1 0 0 1 0 0 0
25 80–90 M 0 1 1 1 1 0 0 0
26 80–90 M 1 1 1 1 1 0 1 0
27 80–90 F 0 0 0 1 1 0 1 0
28 80–90 F 1 1 Na Na Na 0 0 0
29 90–100 M 1 0 1 1 1 0 1 1
Σ 11 9 17 17 8 19 9
% 42 35 65 74 31 73 31
Significant values are shown bold and italicΣ Sum of a column, % Column sum percentage, WBC White blood cell count (×109/L), CRP C-reactive protein (mg/l), M Male, F Female, 1 Present, 0 Not present, Na Data not
available
Page 7 of 11
Table 5 Patient characteristics of those who died at ward (Continued)
Case number CRP over 100 Human metapneumovirus Adenovirus Rhinovirus Influenza virus Respiratory syncytial virus Parainfluenza virus Coronavirus
1 1 0 0 0 0 0 0 1
2 1 0 0 0 0 0 1 0
3 0 0 0 0 0 0 1 0
4 0 0 0 0 0 0 1 0
5 0 0 0 0 0 0 1 0
Aronen et al. BMC Geriatrics

6 1 0 0 1 0 0 0 0
7 1 0 0 1 0 0 0 0
8 0 1 0 0 0 0 0 0
9 1 0 0 0 0 0 0 0
(2019) 19:111

10 1 0 0 0 0 0 0 0
11 1 0 0 0 0 0 0 0
12 1 0 0 0 0 0 0 0
13 1 0 0 0 0 0 0 0
14 1 0 0 0 0 0 0 0
15 1 0 0 0 0 0 0 0
16 1 0 0 0 0 0 0 0
17 1 0 0 0 0 0 0 0
18 1 0 0 0 0 0 0 0
19 1 0 0 0 0 0 0 0
20 1 0 0 0 0 0 0 0
21 1 0 0 0 0 0 0 0
22 1 0 0 0 0 0 0 0
23 1 0 0 0 0 0 0 0
24 1 0 0 0 0 0 0 0
25 1 0 0 0 0 0 0 0
26 0 0 0 0 0 0 0 0
27 0 0 0 0 0 0 0 0
28 0 0 0 0 0 0 0 0
29 0 0 0 0 0 0 0 0
21 1 0 2 0 0 4 1
81 4 0 8 0 0 15 4
Page 8 of 11
Aronen et al. BMC Geriatrics (2019) 19:111 Page 9 of 11

Table 6 Association between CRP and leukocyte values and main viral findings and clinical outcomes
Variable Over 13 nights at ward Had a revisit Exitus at ward
OR 95% limits OR 95% limits OR 95% limits
Pneumonia 0.767 0.449 1.309 0.818 0.491 1.360 0.886 0.336 2.337
Leuk >15 1.303 0.690 2.460 1.336 0.726 2.461 1.158 0.376 3.565
CRP > 100 1.279 0.785 2.084 1.104 0.691 1.764 2.845 1.021 7.933
Virus 0.736 0.450 1.203 0.620 0.385 0.998 0.836 0.318 2.199
Influenza virus 0.480 0.188 1.221 0.441 0.181 1.071 – – –
Rhinovirus 1.508 0.685 3.320 1.153 0.525 2.530 0.421 0.052 3.378
Coronavirus 0.744 0.278 1.988 0.785 0.309 1.995 0.981 0.118 8.146
Multivariable logistic regression analysis was used
CRP C-reactive protein (mg/l), WBC White blood cell count (× 109/L)

with pneumonia regardless of whether there was a respira- contrast to CRP increased with the severity of a
tory virus present or not. community-acquired pneumonia [30, 33].
Frailty, immunologic weakening and cardiopulmonary The strengths of our study include prospective design,
diseases are understood to predispose to pneumonia large sample size and sensitive virus-detection methods.
when a viral infection occurs [26]. In our study, a re- Also, pneumonia was radiologically confirmed. However,
spiratory virus was found in no less than 40% of the eld- there are some limitations to our study as well. As the
erly patients who suffered from respiratory symptoms study observed hospitalization-requiring episodes among
but were not diagnosed with pneumonia. At the same frail geriatric patients, the results cannot be generalized
time, the risk of a hospital revisit in all the studied epi- as such to treating outpatients. Also, the swab samples
sodes of hospital care seemed to be lower when a virus were collected from the upper airways and thus infec-
was present than when no virus was fund. These find- tions solely in the lower airways may have been missed.
ings support the idea that respiratory viruses are merely Further, as the virus samples were collected in 2007–
innocent bystanders in patients with pneumonia [27]. 2009, they naturally give specific information concerning
Our study strengthens the idea that high CRP and WBC those years only. The study was carried out ten years
values are associated with pneumonia in patients with re- ago and in one center which limits the generalizability of
spiratory symptoms but have limited value as independent the results. Many respiratory viruses exhibit a seasonal
predictors [28]. In adult populations, only relatively high variation in temperate climates. However, at species level
CRP values have been shown useful in predicting the pres- annual virus epidemics are relatively stable in climates
ence of pneumonia, and a cut-off value of 100 mg/l is with defined winter seasons like in Finland [34]. We
mentioned in some studies [29]. Krueger et al. concluded used modern PCR diagnostics that have been in routine
in their CAPNETZ-study with 1337 patients aged 62 ± 18 use ever since. We believe that nearly a 2-year recruit-
years that WBC and CRP are higher in typical bacterial ment period with 438 samples gives a relatively good
than in atypical or viral etiology community-acquired picture of virus epidemics at species levels in our area.
pneumonias [30]. Gao et al. showed in their study that This study has prospective design and gives information
high levels of CRP were induced as well as correlated with about the effect of common respiratory virus infections,
the complement activation in patients infected with severe even though there is some annual variation in circulating
influenza A [31]. In our study, we saw no difference in in- viruses. Due to many chronic diseases in the elderly,
flammatory markers according to virus etiology. virus-induced respiratory symptoms may be difficult to
According to our data, among the elderly, a respiratory distinguish from other symptoms. However, for dyspnea,
disease that elevates CRP to over 100 mg/l could be we used an objective criterion based on oxygen
linked to death on the count of that in such cases pneu- saturation.
monia is probable. Lee et al. showed similar results in This study gives valuable information about the signifi-
their study with 424 patients aged 70.4 +/− 15.6 years cance of virus findings in nasopharynx and inflammatory
[32]. Interestingly, they also showed that in addition to markers among frail elderly patients with respiratory
CRP the albumin level was associated with a 28-day symptoms.
mortality in hospitalized patients with a community-ac-
quired pneumonia. On the other hand, Ortqvist et al. Conclusions
saw no association between high CRP and mortality In elderly patients, the presence of respiratory viruses in
in hospital-treated pneumonia patients and Krueger et the nasopharynx seems to have limited value in assessing
al. stated in the CAPNETZ-study that WBC in the severity and the short-time prognosis of the disease.
Aronen et al. BMC Geriatrics (2019) 19:111 Page 10 of 11

If a virus is found, it may in fact indicate a clinical situ- Competing interests

ation with a better prognosis. In this study, not one The authors declare that they have no competing interests.

respiratory virus correlated with the presence, signs and

symptoms or prognosis of radiographically-verified Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in
pneumonia among the elderly. However, this study did published maps and institutional affiliations.
find that a CRP over 80 mg/l and a WBC over 15 ×
109/L were linked to pneumonia and a CRP over 100 Author details
1
Department of Geriatrics, Turku City Hospital, Turku, Finland. 2Department of
mg/l to elevated mortality during hospital stay. All in Radiology, Turku University Hospital, Turku, Finland. 3Department of Medical
all, this study shows that pneumonia should be Microbiology, Turku University Hospital and Institute of Biomedicine,
treated in elderly people as a bacterial disease regard- University of Turku, Turku, Finland. 4Department of Virology, University of
Helsinki, Helsinki, Finland. 5Department of Pediatrics and Adolescent
less of virus findings. Medicine, University of Turku and Turku University Hospital, PO Box 52,
20520 Turku, Finland. 6Pori, Finland.
Additional file Received: 6 August 2018 Accepted: 28 March 2019

Additional file 1: Standard clinical questionnaire. A written form to

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