RESEARCH ARTICLE

Predictors of Viral Pneumonia in Patients

with Community-Acquired Pneumonia
Ji Eun Kim, Uh Jin Kim, Hee Kyung Kim, Soo Kyung Cho, Joon Hwan An,
Seung-Ji Kang, Kyung-Hwa Park, Sook-In Jung, Hee-Chang Jang*
Department of Internal Medicine, Chonnam National University Medical School, Gwang-ju, Republic of Korea

*[email protected]

Abstract
Background: Viruses are increasingly recognized as major causes of community-
acquired pneumonia (CAP). Few studies have investigated the clinical predictors of
viral pneumonia, and the results have been inconsistent. In this study, the clinical
predictors of viral pneumonia were investigated in terms of their utility as indicators
for viral pneumonia in patients with CAP.
Methods: Adult patients ($18 years old) with CAP, tested by polymerase chain
reaction (PCR) for respiratory virus, at two teaching hospitals between October
2010 and May 2013, were identified retrospectively. Demographic and clinical data
OPEN ACCESS were collected by reviewing the hospital electronic medical records.
Citation: Kim JE, Kim UJ, Kim HK, Cho SK, An Results: During the study period, 456 patients with CAP were identified who met
JH, et al. (2014) Predictors of Viral Pneumonia in
Patients with Community-Acquired the definition, and 327 (72%) patients were tested using the respiratory virus PCR
Pneumonia. PLoS ONE 9(12): e114710. doi:10.
detection test. Viral pneumonia (n560) was associated with rhinorrhea, a higher
1371/journal.pone.0114710
lymphocyte fraction in the white blood cells, lower serum creatinine and ground-
Editor: James D. Chalmers, University of Dundee,
United Kingdom glass opacity (GGO) in radiology results, compared to non-viral pneumonia
Received: July 20, 2014 (n5250) (p,0.05, each). In a multivariate analysis, rhinorrhea (Odd ratio (OR) 3.52;
Accepted: November 12, 2014 95% Confidence interval (CI), 1.58–7.87) and GGO (OR 4.68; 95% CI, 2.48–8.89)
Published: December 22, 2014 were revealed as independent risk factors for viral pneumonia in patients with CAP.
Copyright: ß 2014 Kim et al. This is an open-
The sensitivity, specificity, positive- and negative-predictive values (PPV and NPV)
access article distributed under the terms of the of rhinorrhea were 22, 91, 36 and 83%: the sensitivity, specificity, PPV and NPV of
Creative Commons Attribution License, which
permits unrestricted use, distribution, and repro- GGO were and 43, 84, 40 and 86%, respectively.
duction in any medium, provided the original author Conclusion: Symptom of rhinorrhea and GGO predicted viral pneumonia in
and source are credited.
patients with CAP. The high specificity of rhinorrhea and GGO suggested that these
Data Availability: The authors confirm that all data
underlying the findings are fully available without could be useful indicators for empirical antiviral therapy.
restriction. All relevant data are within the paper
and its Supporting Information files.
Funding: The authors have no support or funding
to report.
Competing Interests: The authors have declared
that no competing interests exist.

PLOS ONE | DOI:10.1371/journal.pone.0114710 December 22, 2014 1 / 13

 Predictors of Viral Pneumonia

Introduction
CAP remains a significant cause of morbidity and mortality [1, 2]. The
development and application of diagnostic tests with improved sensitivity, such as
the polymerase chain reaction (PCR), have led to recognition of the increasing
role of respiratory viruses in CAP in all age groups [3]. These common respiratory
viruses include influenza, parainfluenza viruses, adenoviruses, coronaviruses,
respiratory syncytial viruses (RSV), metapneumoviruses and bocaviruses [4–6].
Evidence of viral infection was detected in 22% of CAP in adults [7]. Moreover,
viruses were frequently found in the airways of patients requiring admission to
intensive care units (ICU) with pneumonia, and patients with viral and bacterial
infections had comparable mortality rates [7–11].
There are a number of studies on the subject of antiviral treatment for viral
infections. Several studies showed the efficacy of antiviral agents including
oseltamivir, zanamivir, amantadine and ribavirin [10, 12–17]. But, the Cochrane
review of randomized controlled trials of antiviral agents does not demonstrate
efficacy in the treatment of influenza [18]. However, the original studies included
in the Cochrane review did not include people with severe underlying disorders or
patients with a severe presentation of influenza. For this reason, no conclusion can
be made on the efficacy of antiviral treatment for viral pneumonia by the
Cochrane review [19]. There is evidence of efficacy in the treatment of influenza
pneumonia [20–22], and early empirical antiviral therapy is still recommended in
critically ill patients in whom viral pneumonia is suspected [7].
Although viral pneumonia is increasingly recognized as a major cause of CAP
and early antiviral therapy can reduce mortality, few studies have investigated the
clinical predictors of viral pneumonia, and the results have been inconsistent [23–
26]. Moreover, evaluations of the diagnostic value of any clinical parameters,
including sensitivity, specificity, and positive and negative predictive values, have
not been performed. Although PCR methods are sensitive and real-time PCR
enables rapid results in a clinically relevant time period, use of PCR is sometimes
limited in CAP patients due to the associated costs [27]. This highlights the need
for clinical predictors of viral infections in patients with CAP.
In this study, we describe the clinical parameters of viral pneumonia that would
be useful in the development of diagnostic tests for respiratory viruses and early
empirical antiviral treatment in patients with CAP.

Patients and Methods

Ethics statement
This study was approved by the Institutional Review Board of Chonnam National
University Hospital. A waiver of the requirement for consent was granted given
the retrospective nature of the project.

PLOS ONE | DOI:10.1371/journal.pone.0114710 December 22, 2014 2 / 13

 Predictors of Viral Pneumonia

Patients
Adult patients ($18 years old) with CAP, who had tested for respiratory viruses
by PCR in hospitalized patients and out-patients at Chonnam National University
Hospital (900 beds, Gwang-ju, Republic of Korea) and Chonnam National
University Hwasun Hospital (600 beds, Hwasun, Republic of Korea) between
October 2010 and May 2013, were retrospectively identified. A case report form
(CRF) was recorded at the time of admission for all pneumonia patients, which
included clinical symptoms, underlying diseases, vital signs, CURB-65 score (the
confusion, urea, respiratory rate, blood pressure, and aged 65 years or over score),
and score on the pneumonia severity index (PSI). We reviewed the CRF which
was stored in the hospital’s electronic medical records.

Definition
Pneumonia was defined as an acute illness with radiographic pulmonary
infiltration, with at least one of the following being present: fever .38 ˚C, WBC
.12,000/mm3 or ,6,000/mm3, and change in the mental status in elderly patients
over the age of 70 years [24]. CAP is defined as pneumonia acquired outside a
hospital or long-term care facility. It occurs within at least 48 hours of hospital
admission or in a patient presenting with pneumonia who does not have any of
the characteristics of health care-associated pneumonia (i.e., hospitalized in an
acute care hospital for two or more days within 90 days of infection; residing in a
nursing home or long-term care facility having received recent intravenous
antibiotic therapy; undergoing chemotherapy; chronic dialysis within the past 30
days; or wound care within the past 30 days of the current infection). The
exclusion criteria were solid organ transplantation and anyone with a diagnosis of
active tuberculosis or a fungal infection [28]. In this study, the viral pneumonia
was confirmed by respiratory viruses multiplex PCR using respiratory specimens
of the patients. Classification of radiologic findings was three types by chest
computerized tomography (CT) confirmed by one clinician and two radiologists;
lobar consolidation, centrilobular nodule, GGO.
Viral pneumonia was diagnosed using the Influenza Antigen Rapid Test kit (SD
BIOLINE, Young-in, Republic of Korea), the Anyplex II RV16 detection kit
(Seegene, Seoul, Republic of Korea), or a multiplex virus RT-PCR. Viruses that
can be diagnosed using the above equipment include influenza viruses A and B;
adenoviruses; RSV A and B; parainfluenza viruses 1, 2, and 3; coronaviruses 229E,
NL63, and OC43; metapneumoviruses; rhinoviruses; enteroviruses; and boca-
viruses. This test is generally done using specimens from nasopharyngeal/
oropharyngeal swabs, sputum, or transtracheal aspirate. The sensitivity and the
specificity of the multiplex PCR kit used in this study are reported to be 95.2%
and 98.6% [29].
Pneumococcal pneumonia was diagnosed when Streptococcus pneumoniae was
isolated from a normally sterile blood or sputum, or the urine antigen assay for S.
pneumoniae (Alere BinaxNOW, Young-in, Korea) was positive. Microbiological

PLOS ONE | DOI:10.1371/journal.pone.0114710 December 22, 2014 3 / 13

 Predictors of Viral Pneumonia

sampling was taken at the time of admission before antimicrobial treatment

commenced.

Statistical analyses
Categorical variables were compared using Fisher’s exact test or the Pearson x2
test, and continuous variables were compared using Student’s t-test or Mann-
Whitney U-test, as appropriate. Multivariate analyses were performed using the
logistic regression model in the backward stepwise conditional manner.
All significance tests were two-tailed, and p-values #0.05 were deemed to
indicate statistical significance. Statistical analyses were performed using the SPSS
software version 21.0 (IBM Corporation, Armonk, NY, USA).

Results
Etiology of CAP
During the study period, 456 patients with CAP were identified who met the
definition, and 327 (72%) patients were tested with the respiratory virus PCR.
Among the 327 patients, an etiologic diagnosis could be established in 204 cases
(62%). In this study, 317 patients were tested using specimens from
nasopharyngeal swabs or sputum, with the exception of 10 patients who were
intubated at admission using specimens from transtracheal aspirate.
Among 327 patients, respiratory viruses were detected in 60 (18%) patients,
while 250 (76%) patients were diagnosed with non-viral pneumonia with negative
PCR results, and 17 (5%) patients were diagnosed as being co-infected with a
virus and bacteria. Co-infected patients (n517, 5%) were excluded from the
study.
Among the 60 patients with respiratory viruses, influenza viruses was most
common (n523, 38%). Other etiological agents included RSV (n59, 15%),
rhinoviruses (n57, 12%), coronaviruses (n56, 10%), adenoviruses (n55, 8%),
metapneumoviruses (n55, 8%), parainfluenza viruses (n53. 5%) and bocaviruses
(n52, 3%).
Among 250 cases of non-viral pneumonia, Streptococcus pneumoniae pathogen
was most common (n588, 35%). Other etiological pathogen included
Mycoplasma pneumoniae (n510, 4%), Klebsiella pneumoniae (n57, 3%),
Staphylococcus aureus (n55, 2%), Haemophilus influenza (n55, 2%), Escherichia
coli (n53, 1%), Pseudomonas aeruginosa (n52, 1%), Moraxella catarrhalis (n51,
,1%), Proteus mirabilis (n51, ,1%) and Peptostreptococcus spp. (n55, 2%).

Clinical features and outcomes of viral pneumonia compared to

non-viral CAP
The clinical features and the outcomes of CAP are shown in Table 1. No
differences were found in terms of age and gender ratio in a comparison of viral
and non-viral pneumonia. No significant difference was found in co-morbidity

PLOS ONE | DOI:10.1371/journal.pone.0114710 December 22, 2014 4 / 13

 Predictors of Viral Pneumonia

Table 1. Clinical features and outcomes of 310 patients with viral or non-viral community-acquired pneumonia.

No. (%) of patients

P
Characteristics Viral Pneumonia (N560) Non-viral Pneumonia (N5250) value
Demographic data
Male sex 43 (72) 194 (78) 0.397
Agea 67 (¡14) 70 (¡11) 0.106
Underlying diseases
Diabetes mellitus 12 (20) 50 (20) .0.999
Hypertension 15 (25) 77 (31) 0.433
Cancer 14 (23) 45 (18) 0.362
Chronic obstructive lung disease 12 (20) 79 (32) 0.084
Ischemic heart disease 7 (12) 21 (8) 0.452
Cerebral vascular accident 2 (3) 14 (6) 0.746
Chronic kidney disease 1 (2) 13 (5) 0.319
Symptoms
Fever 41 (68) 152 (61) 0.373
Cough 43 (72) 149 (60) 0.103
Sputum 31 (52) 134 (54) 0.886
Rhinorrhea 13 (22) 23 (9) 0.012
Dyspnea 22 (37) 112 (45) 0.310
Chest pain 3 (5) 26 (10) 0.228
Diarrhea 4 (7) 12 (5) 0.523
Severity and Outcomes
CURB-65b 1.3 (1, 2) 1.4 (1, 2) 0.094
PSIb 97 (68, 116) 102 (73, 126) 0.188
ICU admission 8 (13) 44 (18) 0.564
Mechanical ventilation 10 (17) 30 (12) 0.390
30-day mortality 10/58 (17) 38/249 (15) 0.843
30-day attributable mortality 9/58 (16) 38/249 (15) .0.999

Continuous variables were expressed as means ¡ SDsa or medians (IQRs)b and were compared by the Student’s t testa or Mann-Whitney U testb.
CURB-65: Confusion-Urea-Respiratory-Blood pressure-65 score, PSI: Pneumonia severity index, ICU: Intensive care unit.

doi:10.1371/journal.pone.0114710.t001

between viral and non-viral pneumonia. Viral pneumonia was characterized by a

higher frequency of rhinorrhea, compared to non-viral pneumonia (p50.012).
There was no significant difference in other symptoms between viral and non-viral
pneumonia.
In terms of severity, CURB-65, PSI, ICU admission, mechanical ventilation and
30-day mortality were not significantly different between the two groups.
All of the patients with CAP were treated with empirical antibiotics at
admission. After they tested positive for viral PCR, the influenza virus was
detected in 23 patients who were given the antiviral agent; oseltamivir (n517) or
peramivir (n56).

PLOS ONE | DOI:10.1371/journal.pone.0114710 December 22, 2014 5 / 13

 Predictors of Viral Pneumonia

Laboratory and radiological findings of viral pneumonia compared

to non-viral community-acquired pneumonia
The laboratory and radiological findings of CAP resulting from viruses or bacteria
are shown in Table 2. Viral pneumonia was associated with a significantly higher
lymphocyte fraction in the white blood cells, and significantly lower serum
creatinine levels than non-viral pneumonia (p,0.05, each). However, no
significant differences were found in the total white blood cell counts (WBC) and
C-reactive protein (CRP).
All of the patients underwent a chest CT. The GGO radiology pattern on chest
CT was more frequently observed in viral than non-viral pneumonia (p,0.01).

Clinical features and outcomes, laboratory and radiological

findings of influenza pneumonia compared to pneumococcal
pneumonia
No differences were found in terms of age and gender ratio between influenza and
pneumococcal pneumonia (Table 3). In terms of severity, the CURB-65 score,
PSI, mechanical ventilation and 30-day mortality were not significantly different
between the two groups (Table 3). However, influenza pneumonia was associated
with significantly higher rates of rhinorrhea, and GGO on radiological findings
than pneumococcal pneumonia (p,0.05, each).

Independently associated factors and predictors of viral

pneumonia in patients with CAP
Independently associated factors of viral pneumonia in patients with CAP are
shown in Table 4. Rhinorrhea (OR 3.52; 95% CI, 1.58–7.87) and GGO (OR 4.68;
95% CI, 2.48–8.89) were seen as independent risk factors for viral pneumonia in
patients with CAP.
The sensitivity, specificity, PPV and NPV of rhinorrhea were 22%, 91%, 36%
and 83%, respectively. The sensitivity, specificity, PPV and NPV of GGO were and
43%, 84%, 40% and 86%, respectively. Fig. 1 shows the Receiver operating
characteristics (ROC) curves for rhinorrhea, GGO and rhinorrhea or GGO for
predicting viral pneumonia CAP. The resulting of Area under the curves (AUCs)
were 0.562 (95% CI, 0.477–0.647) for rhinorrhea, 0.639 (95% CI, 0.555–0.723) for
GGO, and 0.672 (95% CI, 0.592–0.751) for GGO or rhinorrhea.
Because the etiologic role of rhinoviruses, coronaviruses, and bocaviruses in
patients with CAP is still in debate [30, 31], we analyzed the data after excluding
patients who were tested using a PCR and shown to have rhinoviruses,
coronaviruses, and bocaviruses, and it was found that the results were the same
(S1 Table, S2 Table and S3 Table).

PLOS ONE | DOI:10.1371/journal.pone.0114710 December 22, 2014 6 / 13

 Predictors of Viral Pneumonia

Table 2. Laboratory and radiological findings of 310 cases of viral or non-viral community-acquired pneumonia.

No. (%) of patients

P
Characteristics Viral Pneumonia (N560) Non-viral Pneumonia (N5250) value
Laboratory findings
White blood cell counts (/mm3)a 12985 (7925, 12550) 13946 (9950, 17120) 0.300
Neuotrophil %a 77 (71, 86) 78 (76, 89) 0.239
a
Lymphocyte % 13 (7, 18) 11 (5, 14) 0.032
C-reactive protein (mg/dL)a 14 (7, 20) 14 (5, 13) 0.764
Serum creatinine (mg/dL)a 1.1 (0.6, 1.3 ) 1.4 (0.8, 1.5) 0.025
Radiologic findings
Lobar consolidation 17 (28) 111 (44) 0.028
GGO 26 (43) 39 (16) ,0.001
Centrilobular 17 (28) 100 (40) 0.104

Continuous variables were expressed as medians (IQRs)a and were compared by Mann-Whitney U testa. GGO: Ground-glass opacity.

doi:10.1371/journal.pone.0114710.t002

Discussion
In this study, rhinorrhea and the GGO radiologic pattern were independently
associated with viral pneumonia, and were specific predictors of viral pneumonia
in patients with CAP.
The use of highly sensitive diagnostic tests in CAP patients increased the
number of microbiological diagnoses and enabled identification of viral infection,
despite an unknown etiology in ,50% of cases [32]. It is estimated that 100
million cases of viral pneumonia occur each year [30]. The prevalence of viral
infection was 22–33% in CAP, and influenza viruses accounted for most cases of
viral pneumonia (6–8% of CAP) [7, 25, 32]. In this study, viral infection was
detected in 18% of CAP, slightly lower than reported previously, but influenza
pneumonia accounted for 7% of CAP, which is similar to previous reports. The
slightly lower value for viral pneumonia is possibly due to a delay in applying the
diagnostic tests for the virus because this study was performed across two referral
centers, not primary care clinics.
Previous studies have demonstrated that the PSI score, ICU admission, need of
mechanical ventilation and mortality rate were not different between bacterial and
viral pneumonia [26]. Our results were consistent with previous findings, and no
differences in severity of disease and mortality were observed between viral and
bacterial CAP.
Previous studies showed some clinical parameters associated with viral
pneumonia in patients with CAP, however, the results were inconsistent; age and
an immunocompetent host were associated with viral pneumonia in some studies
[33, 34], but not in others [25]. The presence of a cough was associated with a
higher incidence of viral pneumonia in one study [25], but in another study, it
was associated with a lower frequency of a dry cough [26]. Several studies showed
that purulent sputum, high fever, chest pain, an altered mental state, and dyspnea

PLOS ONE | DOI:10.1371/journal.pone.0114710 December 22, 2014 7 / 13

 Predictors of Viral Pneumonia

Table 3. Clinical features, outcomes, laboratory and radiological findings of influenza pneumonia, compared to pneumococcal pneumonia.

No. (%) of patients

P
Characteristics Viral Pneumonia (Influenza) (N523) Pneumococcal Pneumonia (N588) value
Demographic data
Male sex 19 (83) 73 (83) .0.99-
9
Agea 71 (¡10) 69 (¡11) 0.342
Underlying diseases
Diabetes mellitus 8 (35) 18 (20) 0.161
Hypertension 7 (30) 24 (27) 0.793
Chronic obstructive lung disease 6 (26) 31 (35) 0.463
Cancer 7 (30) 14 (16) 0.140
Ischemic heart disease 3 (13) 12 (14) .0.99-
9
Symptoms
Fever 17 (74) 46 (52) 0.097
Cough 17 (74) 51 (58) 0.231
Sputum 11 (48) 52 (59) 0.348
Rhinorrhea 6 (26) 6 (7) 0.017
Dyspnea 8 (35) 46 (52) 0.161
Severity and Outcomes
CURB-65b 1.7 (1, 2) 1.5 (1, 2) 0.981
PSIb 117 (78, 136) 104 (75, 122) 0.286
Mechanical ventilation 6 (26) 13 (15) 0.526
30-day mortality 6 (26) 15 (17) 0.375
Laboratory findings
White blood cell counts (/mm3)b 13070 (7800, 18400) 14410 (9425, 17275) 0.382
b
Neuotrophil % 76 (70, 87) 78 (76, 90) 0.240
b
Lymphocyte % 15 (7, 21) 11 (6, 15) 0.081
C-reactive protein (mg/dL)b 17 (8, 26) 13 (4, 18) 0.056
Serum creatinine (mg/dL)b 1.3 (0.7, 1.5) 1.6 (0.8, 1.7) 0.868
Radiologic findings
Lobar consolidation 6 (26) 42 (48) 0.091
Centrilobular nodule 8 (35) 34 (39) .0.99-
9
GGO 8 (35) 12 (14) 0.030

Continuous variables were expressed as means ¡ SDsa or medians (IQRs)b and were compared by the Student’s t test a or Mann-Whitney U testb
CURB-65: Confusion-Urea-Respiratory-Blood pressure-65 score, PSI: Pneumonia severity index, GGO: Ground-glass opacity.

doi:10.1371/journal.pone.0114710.t003

were present in similar proportions to non-viral pneumonia [24–26]. In this

study, none of the above parameters were associated with, or were predictive of,
viral pneumonia. Only rhinorrhea was associated with a viral etiology.
Some studies showed that WBC and CRP were increased significantly in
individuals with bacterial pneumonia, compared with viral pneumonia [4, 7, 35];
however, in another study, WBC count and CRP levels were not different between

PLOS ONE | DOI:10.1371/journal.pone.0114710 December 22, 2014 8 / 13

 Predictors of Viral Pneumonia

Table 4. Independently associated factors for viral pneumonia in patients with community-acquired pneumonia.

Logistic regression analysis without variable Logistic regression analysis with backward conditional variable
Risk Factor selection selection
OR 95% CI P value OR 95% CI P value
Lower Upper Lower Upper
Rhinorrhea 3.59 1.59 8.10 0.002 3.52 1.58 7.87 0.002
Lymphocyte % 1.01 0.98 1.04 0.436
Creatinine 0.63 0.39 1.02 0.629
GGO 4.35 2.27 8.34 ,0.001 4.68 2.46 8.89 ,0.001

GGO: ground glass opacity.

doi:10.1371/journal.pone.0114710.t004

viral and non-viral CAP [26]. We found no differences in WBC count and CRP
levels between viral and non-viral CAP, and these parameters were not helpful in
differentiating the two. Univariate analysis showed that viral pneumonia was
associated only with a significantly lower concentration of serum creatinine and a

Fig. 1. Receiver operating characteristics (ROC) curves of rhinorrhea and ground glass opacity in chest imaging as a predictor of viral pneumonia
in 310 patients with community-acquired pneumonia. GGO: ground glass opacity. Area under the curve: (a) rhinorrhea, 0.562 (95% CI, 0.477–0.647); (b)
GGO, 0.639 (95% CI, 0.555–0.723); (c) GGO or rhinorrhea, 0.672 (95% CI, 0.592–0.751).

doi:10.1371/journal.pone.0114710.g001

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 Predictors of Viral Pneumonia

higher lymphocyte fraction than non-viral pneumonia; however, multivariate

analysis revealed no differences in these parameters between viral and non-viral
CAP. Serum creatinine level was also not associated with viral pneumonia.
Previous studies suggested that radiology imaging of viral pneumonia was not
predictive of its origin, because both bacteria and viruses could induce a broad
range of changes on radiographic images of the chest [7, 36, 37]. However, it was
suggested that viral pneumonia should be considered when multifocal GGO
findings are observed [38]. Previous studies did not evaluate the sensitivity,
specificity, PPV and NPV of the radiology findings for viral pneumonia in
patients with CAP, in terms of which parameters were of help in the clinical
decision to commence antiviral treatment. In our study, GGO was not sufficiently
sensitive to detect viral pneumonia (indicating that other radiology findings are
also commonly present in viral pneumonia) but was highly specific for viral
pneumonia in patients with CAP. In our study, an AUC of 0.672 may not be
sufficient for a clinical decision. However, there are no other clinical parameters
that are preferable or useful for making decisions concerning empirical antiviral
agents in clinical practice, although such parameters are badly needed. In our
study, 73 patients had rhinorrhea or GGO, but only 10 (14%) of those patients
were treated with antiviral drugs empirically, while 25 (40%) of the remaining 63
patients with rhinorrhea or GGO were diagnosed with viral pneumonia and were
not treated with empirical antiviral agents.
This study had several limitations. First, the etiologic microorganism was
heterogeneous and not identified in 50% of patients with non-viral CAP. For this
reason, Influenza pneumonia was compared, additionally, with only pneumo-
coccal pneumonia which mostly accounts for CAP and similar results. Second,
although this study was undertaken at two hospitals, they were referral centers,
not primary health-care clinics. There is the possibility that patients with less
severe CAP could have been included if data from a primary healthcare clinic had
been available. Third, because of the retrospective study design, 28% of the CAP
patients were not tested using the respiratory virus PCR test and were excluded
from the study, although the medical doctors were educated and were in
consensus regarding the routine prescription of the respiratory virus PCR for
correct etiologic diagnosis of CAP patients at our hospital. Because the factors
influencing the physicians’ decision to prescribe respiratory virus PCR were not
determined, they may have influenced our results as unmeasured confounding
factors in the analysis. Fourth, we did not perform bronchoalveolar lavage for the
diagnosis of viral pneumonia because its diagnostic role in viral pneumonia is still
not well defined and review articles still recommend upper respiratory specimens
for the diagnosis of viral pneumonia [7, 10, 32]. Fifth, serum procalcitonin levels,
which indicate the acute phase of bacterial CAP, were not reviewed and analyzed
in this study, because procalcitonin was not checked routinely in all patients.
Further study is needed to evaluate the usefulness of novel biomarkers for
predicting viral pneumonia in CAP, including procalcitonin. Sixth, there is a
possibility of co-infection in patients with a positive viral PCR and no positive
bacteriology because of the limited sensitivity of current diagnostic methods.

PLOS ONE | DOI:10.1371/journal.pone.0114710 December 22, 2014 10 / 13

 Predictors of Viral Pneumonia

In conclusion, symptom of rhinorrhea and GGO on radiology findings were

independently associated with viral pneumonia. The sensitivity of these
parameters was low, which suggests that all patients with CAP should be tested for
viral pneumonia. However, the high specificity of rhinorrhea and GGO suggests
that these could be useful clinical indicators for empirical antiviral therapy such as
oseltamivir, zanamivir, peramivir, and/or ribavirin for the patients with CAP [7],
especially in severe or rapidly progressing cases.

Supporting Information
S1 Table. Clinical features and outcomes of 295 patients with viral or non-viral
community-acquired pneumonia. Continuous variables were expressed as means
¡ SDsa or medians (IQRs)b and were compared by the Student’s t testa or Mann-
Whitney U testb. CURB-65: Confusion-Urea-Respiratory-Blood pressure-65
score, PSI: Pneumonia severity index, ICU: Intensive care unit.
doi:10.1371/journal.pone.0114710.s001 (DOCX)
S2 Table. Laboratory and radiological findings of 295 cases of viral or non-viral
community-acquired pneumonia. Continuous variables were expressed as
medians (IQRs)a and were compared by Mann-Whitney U testa. GGO: Ground-
glass opacity.
doi:10.1371/journal.pone.0114710.s002 (DOCX)
S3 Table. Independently associated factors for viral pneumonia in patients
with community-acquired pneumonia. GGO: ground glass opacity.
doi:10.1371/journal.pone.0114710.s003 (DOCX)

Acknowledgments
Disclaimer: There were no conflicts of interest, and no financial support was
received for this study.
Presented in part: ID Week 2014, Philadelphia, October 8–12, 2014 (abstract
no. 792).

Author Contributions
Conceived and designed the experiments: HCJ. Performed the experiments: JEK.
Analyzed the data: JEK HCJ. Contributed reagents/materials/analysis tools: UJK
HKK SKC JHA SJK KHP. Wrote the paper: JEK SIJ HCJ.

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