Infection

https://doi.org/10.1007/s15010-020-01484-7

REVIEW

Adenovirus diseases: a systematic review and meta‑analysis of 228

case reports
Jie Gu1 · Qing‑qing Su1 · Ting‑ting Zuo1 · Yan‑bin Chen1

Received: 19 April 2020 / Accepted: 19 July 2020

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract
Objective The clinical characteristics of various adenovirus (ADV) infection are underexplored up till now. To investigate
the risk factors, manifestation, current status of ADV species, treatment and prognosis of this disease.
Methods We performed a Pubmed and Embase systematic review for case report reporting the ADV infection to analyze
the clinical characteristics of disease.
Results Initial database searched identified articles of which 168 (228 cases) were included in the final analysis. Previ-
ous solid organ transplantation [odds ratio (OR) = 3.45, 95% CI 1.31–9.08, P = 0.01], hematopoietic stem cell transplant
(OR = 4.24, 95% CI 1.33–13.51, P = 0.01) and hematological malignancy (OR = 4.78, 95% CI 1.70–13.46, P = 0.01) were
associated with increased risk of disseminated ADV infection. Use of corticosteroids (OR = 3.86, 95% CI 1.21–12.24,
P = 0.02) was a significant risk factor for acquiring urinary tract infections. A total of six species (21 types) of ADV infec-
tion have been identified in 100/228 (43.9%) cases. ADV B was the most common species. ADV B species (26/60, 52.0%
or 5/41, 12.2% P = 0.001) were more isolated in patients with ADV pneumonia. ADV C (13/15, 86.7% versus 35/86, 40.7%
P = 0.001) species were more identified in patients with disseminated disease. The species associated with keratoconjuncti-
vitis is only ADV D in our analysis. Urinary tract ADV infections were observed in ADV A/B/D species. Cidofovir (CDV)
(82/228, 36.0%) remained the most commonly antiviral therapy in our cases, followed by ribavirin (15/228, 6.6%), ganciclovir
(18/228, 7.9%), and brincidofovir (12/228, 5.3%). Brincidofovir was administered as salvage therapy in 10 cases. Death
was reported in 81/228 (35.5%) patients. Mortality rate was higher among patients with gastrointestinal (GI) ADV infection
(5/10, 50.0%), ADV pneumonia (20/45, 44.4%) and disseminated ADV infection (53/122, 43.4%).
Conclusion Previous solid organ transplantation, hematopoietic stem cell transplant and hematological malignancy were
risk factors for disseminated ADV infection. Use of corticosteroids was significant for urinary tract ADV infection. Dif-
ferent species correlated with different clinical manifestations of infection. Mortality rate was higher among patients with
GI disease, pneumonia and disseminated disease. Our review clarified the current treatment of ADV infections, and more
treatment required further investigation.

Keywords Adenovirus · Diagnosis · Treatment · Meta-analysis

Background

ADV remains to be an important cause of infection disease

involving tissues ranging from ocular to GI and respiratory
Electronic supplementary material The online version of this
article (https​://doi.org/10.1007/s1501​0-020-01484​-7) contains tissues. It plays an important role in immunocompromised
supplementary material, which is available to authorized users.

* Yan‑bin Chen Ting‑ting Zuo

chen001chen@163.com zuo_tingting@163.com
Jie Gu 1
Department of Pulmonary and Critical Care Medicine,
http://www.gj015@qq.com
The First Affiliated Hospital of Soochow University, 899#
Qing‑qing Su Pinghai Road, Suzhou 215000, China
qingqing_su11@163.com

13
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patients including hematopoietic stem cell transplant and
solid organ transplantation, in whom disease is associated
with high mortality [1]. However, clinical studies evaluating
the safety and efficacy of the antiviral therapy are scarce.
Effective treatment of ADV infection remain poses great
challenges. Meanwhile, most of the data investigating the
disease are limited, arising from studies of cases report and
case series. Therefore, we performed a systematic review
of cases of ADV infection published between January 2000
and January 2020 to investigate the clinical manifestations,
current status of ADV types, treatment and prognosis of this
disease.
Methods
Published case reports of proven ADV infection in
patients ≥ 18-years-old were reviewed. To be included in
the review, the published cases must have had description of
following: (1) site(s) of infection, (2) predisposing factors/
underlying medical conditions, (3) method(s) of diagnosis,
(4) use of antiviral and/or other management strategies, and
(5) patient outcomes. Conference abstracts, editorials, poorly
described cases, review articles, or case reports without pri-
mary data or where the analysis was pooled without descrip-
tion of individual patient data were excluded.
Search strategies and information sources
A comprehensive search for studies involving humans
published in English between January 2000 and January
2020 was conducted in PubMed and Embase using various
keywords.
Study selection
Titles and abstracts of references were retrieved from the
databases. After all duplicate studies were excluded, two
independent reviewers (GJ, SQ) analyzed the articles in
terms of title and abstract, valuing which articles have to
be analyzed as full paper. All reviewers agreed to the final
number of studies to be included in the analysis.
Data collection process and data items
The independent reviewers (GJ, SQ) completed the database.
The data extracted included the following: manifestation,
age, gender, publication year, country, underlying condition,
diagnosis, spectrum, treatment and outcomes.
13
J. Gu et al.
Summary measures and statistical analysis
Patient characteristics, disease manifestations, causative
pathogens, treatment and outcomes were summarized
descriptively. Categorical variables were assessed using
χ2 test, whilst continuous variables were compared by
the Wilcoxon–Mann–Whitney or Kruskal–Wallis test. Risk
factors for the different clinical manifestations of ADV
infection were identified using multivariate logistic regres-
sion. A P value ≤ 0.05 was statistically significant. Data
analysis was conducted using SPSS Statistical Software.
Results
The initial database search identified 1384 articles of
which 168 (228 individual patient cases) were included in
the final analysis (Fig. 1). The characteristic of patient’s
cases is summarized in eTable 1 [2–166].
Patient demographics, co‑morbidities
and predisposing factors
Of 228 patients, the median age was 43 ± 15 years and
154 (67.5%) were men. Hematological malignancy was
the most common underlying condition (73/228, 32.0%),
followed by solid organ transplantation (64/228, 28.1%;
53(82.8%) had received a kidney transplant) and hemat-
opoietic stem cell transplant (HSCT) (53/228, 23.2%),
which involved allogeneic HSCT in almost all the cases
(53/56, 94.6%). Acute severe graft-versus-host disease
(aGVHD) occurred in 13/53(24.5%) patients. Human
immunodeficiency virus (HIV) infection was uncommon
(10/228, 4.4%). 7 patients were not on antiretroviral medi-
cation, 1 patient was treated intermittently, 1 patient was
resistant to all antiretroviral drug and 1 patient was in the
terminal phase of HIV (Table 1).
Of the predisposing factors, corticosteroid use was the
most common (76/228, 33.3%), followed by use of bio-
logics (14/228, 6.1%) and use of cancer chemotherapy
(14/228, 6.1%). Of the 14 biologics, 6 (6/14, 42.9%) cases
were caused by infliximab, followed by Rituximab (2/14,
14.3%), basiliximab (2/14, 14.3%), alemtuzumab (2/14,
14.3%), daclizumab (1/14, 7.1%), and etanercept (1/14,
7.1%) (Table 1).
The majority of the cases (100/228, 43.9%) were from
North or South America, followed by Asia (70/228,
30.1%) and Europe (47/228, 20.6%). The remaining cases
were from Africa (2/228, 0.9%), Australia (7/228, 3.1%)
and New Zealand (2/228, 0.9%).
Adenovirus diseases: a systematic review and meta‑analysis of 228 case reports
Fig. 1  Diagram describing the
cases selection process
Clinical manifestations
Disseminated ADV infection was the most commonly
observed manifestation (120/228, 52.6%), followed by
ADV pneumonia (45/228, 19.7%), urinary tract ADV
infection (35/228, 15.4%), keratoconjunctivitis (18/228,
7.9%) and GI ADV infection (10/228, 4.4%). Of 10 cases
of GI ADV infection, infection was mostly involved in the
liver (6/10, 60.0%).
Associations between patient’s underlying conditions/
predisposing factors and ADV infection manifestations
are summarized (Table 2). Previous solid organ trans-
plantation (OR 3.45, 95% CI 1.31–9.08, P = 0.01), HSCT
(OR 4.24 95% CI 1.33–13.51, P = 0.01) and hematologi-
cal malignancy (OR 4.78 95% CI 1.70–13.46, P = 0.01)
were associated with increased risk of disseminated
ADV infection. Use of corticosteroids (OR 3.86 95% CI
1.21–12.24, P = 0.02) was significant for urinary tract
ADV infection (Table 3).
Diagnosis
Diagnosis was largely relied on molecular techniques,
which were employed in 172/228 (75.4%) cases in our
review. Histopathology was performed in 66/228 (28.9%)
cases of which were confirmed by immunohistochemical
staining or in situ hybridization. Culture was employed
in 45/228(19.7%) cases. Other methods include serology
(14/228; 6.1%) and antigen detection.
A total of six species (21 types) of ADV infection have
been identified in 100/228 (43.9%) cases, including ADV
A, ADV B (type 3, 7, 11, 14, 21, 34, 35, 55), ADV C (type
1, 2, 5, 6), ADV D (type 15, 19, 26, 37, 53, 54, 56), ADV
E (type 4), and ADV F (type 41). ADV B species was most
common (59/100, 59.0%), followed by ADV D (16/100,
16.0%), ADV C (15/100, 15.0%), ADV E (8/100, 8.0%),
ADV A (1/100, 1.0%) and ADV F (1/100, 1.0%). We iden-
tified one case complicated with two different species of
13
 J. Gu et al.

Table 1  Underlying conditions and predisposing factors for 228 cases Table 2  Disease manifestations for 228 cases of adenovirus infection
of adenovirus infection
Disease manifestations Total n (%) Overall mortality n (%)
Underlying conditions/predisposing Total n (%) Mortality n (%)
factors Pneumonia 45 (19.7%) 20 (44.4%)
Keratoconjunctivitis 18 (7.9%) 0
Hematological malignancy 73 (32.0%) 31 (42.5%)
Urinary tract ADV infection 35 (15.4%) 2 (5.7%)
Lymphoma 18 (24.0%) 10 (5.6%)
Cystitis 21 (60.0%) 1 (9.5%)
Multiple myeloma 8 (10.7%) 3 (37.5%)
Nephritis 10 (28.6%) 1 (9.5%)
Acute myeloid leukemia 15 (20.0%) 6 (40.0%)
Urethritis 4 (11.4%) 0
Acute lymphoblastic leukemia 10 (13.3%) 3 (30.0%)
GI ADV infection 10 (4.4%) 5 (50.0%)
Chronic myeloid leukemia 4 (5.3%) 2 (50.0%)
Hepatitis 6 (60.0%) 3 (50.0%)
Chronic lymphocytic leukemia 9 (12.0%) 4 (44.4%)
Colitis 2 (20.0%) 2 (100%)
Othersa 9 (12.0%) 3 (33.3%)
Esophagitis 1 (10.0%) 0
Solid organ transplantation 64 (28.1%) 6 (9.4%)
Stomach 1 (10.0%) 0
Kidney 53 (82.2%) 2 (3.8%)
CNS ADV ­infectiona 3 (1.3%) 1 (33.3%)
Heart 7 (10.9%) 2 (28.6%)
Disseminated ADV i­nfectiona 120 (52.6%) 53 (44.2%)
Liver 3 (4.7%) 1 (33.3%)
Myocarditis 1 (0.4%) 0
Lung 2 (3.1%) 2 (100.0%)
Intestine 2 (3.1%) 0 CNS ADV infection included infections of encephalitis, meningoen-
Pancreas 2 (3.1%) 0 cephalitis, encephalomyeloradiculitis
Hematopoietic stem cell transplant 53 (23.2%) 25 (47.2%) ADV adenovirus, GI gastrointestinal, CNS central nervous system
a
Allogeneic 50 (94.3%) 25 (50.0%) Disseminated ADV infection was defined as infection involving two
or more non-contiguous sites or if ADV were isolated from the blood
Autologous 3 (5.7%) 0
Solid malignant t­umorb 2 (0.9%) 2 (100%)
Human immunodeficiency virus infec- 10 (4.4%) 5 (50%)
tion Treatment and outcomes
Other underlying c­ onditionc 10 (4.4%) 5 (50.0%)
No immunosuppressive conditions 73 (32.0%) 24 (32.9%) CDV was the most commonly administered antiviral treat-
Use of corticosteroids 76 (33.3%) 14 (18.4%) ment (82/228, 36.0%). The remaining cases included ribavi-
Use of cancer chemotherapy 14 (6.1%) 8 (57.1%) rin (15/228, 6.6%), ganciclovir (18/228, 7.9%), brincidofovir
Use of b­ iologicsd 14 (6.1%) 8 (57.1%) (12/228, 5.3%). Of note, 107 cases had no specific antiviral
a
treatment. CDV was primarily initiated as monotherapy
Included T-cell prolymphocytic leukemia (n = 2), waldenstrom
(72/82, 87.8%). Brincidofovir was administered as salvage
macroglobulinemia (n = 1), aplastic anemia (n = 3), myelodysplastic
syndromes(n = 3) therapy in the 10(12.2%) patients in case of renal toxicity
b
Included breast cancer (n = 1), colon cancer (n = 1) of CDV or unsatisfactory clinical response. 4 cases in our
c
Included rheumatoid arthritis (n = 4), crohn’s disease (n = 3), pso- review reported that intravesical administration of CDV in
riasic arthritis (n = 1), systemic lupus erythematosus (n = 1), STAT1- case of non-response to intravenous CDV or renal failure in
deficient (n = 1) patients with urinary tract ADV infection. Adverse event
d
Included infliximab (n = 6), rituximab (n = 2), basiliximab (n = 2), associated with antiviral therapy was renal toxicity, which
alemtuzumab (n = 2), daclizumab (n = 1), etanercept (n = 1) reported in 7(7/82; 8.0%) patients (Table 4).
Death was reported in 81/228 (35.5%) patients, occur-
ring at a median (IQR) of 19(1–91) days. Compared with
ADV infections and four patients infected with urethritis that of other clinical manifestations, mortality (Table 2)
and conjunctivitis. Compared with ADV A, C, D, E and was observed to be the highest among patients with GI
ADV F, ADV B species (24/59, 40.7% or 5/41, 12.2% ADV infection (5/10, 50.0%), followed by ADV pneu-
P = 0.002) were more isolated in patients with ADV pneu- monia (20/45, 44.4%) and disseminated ADV infection
monia. While compared with ADV A, B, D, E and ADV F, (53/120, 44.2%) (Table 2). No deaths were observed among
ADV C (13/15, 86.7% versus 35/85, 41.2% P = 0.001) spe- patients with keratoconjunctivitis. Mortality rate was high
cies were more common in patients with disseminated dis- among patients with HIV (5/10, 50.0%), hematopoietic
ease. The species associated with keratoconjunctivitis is stem cell transplant (25/53, 47.2%) and hematological
only ADV D in our analysis. Urinary tract ADV infections malignancy (31/75, 42.5%), while the mortality rate was
were observed in ADV A/B/D species. GI ADV infection 9.4% in patients with solid organ transplantation. Of note,
was identified in one patient (ADV C) (Fig. 2). the mortality of immunocompetent patients was 32.9%
(Table 1). There is a trend in improvement in the mortality

13
Adenovirus diseases: a systematic review and meta‑analysis of 228 case reports

Table 3  Multivariate logistic regression analysis of associations between various underlying conditions/predisposing factors and disease mani-
festations
Underlying conditions Pneumonia Conjunctivitis Urinary tract ADV infec- Disseminated ADV infection
tion

Hematological malignan-
cies
Solid organ transplantation
Hematopoietic stem cell
transplantation
Use of corticosteroids
Use of cancer chemo-
therapy
Use of biologics
– 0.17 (0.01–2.50) P = 0.20 2.34 (0.46–12.05) P = 0.31 4.78 (1.70–13.46) P = 0.003*
0.11 (0.02–0.63) P = 0.01* – 2.92 (0.78–10.93 P = 0.11 3.45 (1.31–9.08) P = 0.01*
– 0.56 (0.04–8.43) P = 0.67 0.36 (0.06–2.07) P = 0.25 4.24 (1.33–13.51) P = 0.01*
0.11 (0.01–1.07) P = 0.06 – 3.86 (1.21–12.24) P = 0.02* 0.95 (0.38–2.34) P = 0.91
– – 1.39 (0.21–9.32) P = 0.74 1.41 (0.34–5.91) P = 0.64
– – 0.33 (0.04–2.80) P = 0.31 0.73 (0.21–2.58) P = 0.73

Other underlying conditions were excluded from the model due to the small number of observations
ADV adenovirus
*P < 0.05

Fig. 2  Species of adenovirus

infection according to clinical
manifestations

over the year: 19/36(52.8%) between 2000 and 2005; 18/55
(32.7%) between 2006 and 2010; 24/61 (39.3%) between
2011 and 2015; and 22/79 (27.8%) between 2016 and 2020
(P = 0.065).
Discussion
To our knowledge, this is the most comprehensive system-
atic review of published cases of ADV infection to investi-
gate clinical characteristics of ADV infection. This review
has provided insights into the risk factors, clinical manifes-
tation and species of ADV. Meanwhile, the prognosis and
treatment were also investigated.
ADV can cause a wide range of diseases including pneu-
monia, keratoconjunctivitis, cystitis, nephritis, urethritis,
hepatitis, colitis, esophagitis, encephalitis and myocardi-
tis that can progress to disseminated ADV infection. Dis-
seminated ADV infection was the most commonly observed
manifestation, followed by ADV pneumonia urinary tract
ADV infection in our review. One major finding in our
study is that previous solid organ transplantation, hemat-
opoietic stem cell transplant and hematological malignancy
were significant risk factors for disseminated ADV infec-
tion. Diagnosis of disseminated ADV infection is made by
PCR in blood or recovery of ADV from more than one site
[167]. Routine monitoring these patients of ADV infection
potentially contributed to the result. More specifically, the
previously identified risk factors of hematopoietic stem cell
transplant in adults with disseminated ADV are allogeneic
HSCT with haplo-SCT, unrelated cord blood graft, severe
(grades II and IV) graft-versus-host disease and receipt of
concurrent immunosuppressive therapy [168–170]. This
review indicates that incidence of ADV infection in patients
with HIV is rare (10/298, 4.4%), and most patients (9/10,
90.0%) in our review were not on antiretroviral medication
regularly, which is consistent with previous conclusion that
ADV does not seem to have any impact on HIV-positive

13
 J. Gu et al.

Table 4  Antiviral treatment in the management of various clinical manifestations

Disease manifestation Treatment (n) Duration of therapy Mortality (n) Adverse event
[median (IOR)]b

Pneumonia (n = 45) CDV (n = 11) 21 (6–42) 6

Ribavirin (n = 4) 11 1
Ganciclovir (n = 1) 14 0
No antiviral therapy (n = 29) N/A 13
Keratoconjunctivitis (n = 18) CDV (n = 1) 28 0
No antiviral therapy (n = 17) N/A 0
Urinary tract ADV infection (n = 33) CDV (n = 3) 11 1 1
Ribavirin (n = 5) 11 (8–19) 1
Ganciclovir (n = 7) 22 (11–64) 0
No antiviral therapy (n = 18) N/A 0
GI ADV infection (n = 10) CDV (n = 2) 21 1
No antiviral therapy (n = 8) N/A 4
CNS ADV infection (n = 3) CDV (n = 1) 56 0
No antiviral therapy (n = 2) N/A 1
Myocarditis (n = 1) No antiviral therapy (n = 1) N/A 1
Disseminated ADV infection (n = 122) CDV (n = 54) 14 (6–16) 20 6
Brincidofovir (n = 2) 40 1
Ribavirin (n = 6) 20 (5–24) 1
Ganciclovir (n = 10) 23 4
Combination therapy (n = 10)a 43 4
No antiviral therapy (n = 40) N/A 23

CDV cidofovir, ADV adenovirus, GI gastrointestinal, CNS central nervous system, IQR inter-quartile range
a
Combination therapy included brincidofovir was subsequently given with cidofovir
b
Other IQR were not given due to the small number of cases

individuals who were received highly active antiretroviral
therapy [171]. We also observed use of corticosteroids to be
a significant risk factor for urinary tract ADV infection. Uri-
nary tract ADV infection was also more common in patients
with solid organ transplantation and hematopoietic stem cell
transplant [172], which did not appear to be an independent
risk factor for urinary tract ADV infection in the current
study, potentially owing to the limitation of the small num-
ber of observations. Of note, the immunocompetent patient
is not rare in our review.
Until now, 103 types have been grouped within seven
species (A–G) [173]. Different species correlate with dif-
ferent clinical manifestations of infection. Consistent with
previous findings, Keratoconjunctivitis is most commonly
caused by representatives of species D. GI manifestation
is mainly associated with ADV F40 and ADV F41(ADV
D) [174]. While in our study, GI ADV infection was only
identified in one patient (ADV C). In the current study, spe-
cies C has been implicated in disseminated ADV infection.
Previous study also reports that species C has an affinity for
immunocompromised patients. It is worth noting that dis-
seminated ADV infection is predominantly seen in immuno-
compromised patients [175]. Respiratory tract involvement
has been associated mainly with ADV B, and rare species
include ADV C, ADV E and ADV F. Most common species
in our study associated with urinary tract ADV infection are
ADV A, ADV B and ADV D. The species associated with
keratoconjunctivitis is only ADV D in our analysis of case
reports, but other species can also cause keratoconjunctivitis
in other retrospective study (ADV B, ADV E) [176, 177].
The knowledge of the tropisms for specific tissues may help
to inform and guide clinical decision. In view of the fact
that HAdV species C is associated with disseminated ADV
infection, typing may permit a better understanding of pro-
gression of the disease and be helpful for epidemiological
studies. However, it is worth noting that the distribution of
ADV infection reported in our study may be biased given
that identification of the species only identified in 43.9% of
the cases.
The main therapeutic strategies include supportive care,
reduction of immunosuppressive agents, and antiviral ther-
apy. Antiviral therapies include CDV, ganciclovir, ribavirin,
and brincidofovir. The primary anti-viral agent for the treat-
ment of ADV infections is CDV. The success rate in patients
with pneumonia (5/10; 50%) and disseminated infection
(27/49; 55.1%) is relatively low in our review. Duration of

13
Adenovirus diseases: a systematic review and meta‑analysis of 228 case reports
therapy depends upon clinical response and persistence or
eradication of ADV [178]. Cidofovir can display a dose-
limiting nephrotoxicity, and the incidence in our review
is relatively low (5/72; 6.9%). Intravesical administration
of cidofovir in our 4 cases achieved favorable outcomes in
case of non-response to intravenous CDV or renal failure.
The findings also suggested that this method could be an
alternative to intravenous administration of cidofovir to
reduce nephrotoxicity. Owing to less nephrotoxicity and
high potency against all clinically significant ADV sub-
types, brincidofovir is an attractive antiviral therapy for
the management of ADV disease [179]. In our review that
includes 12 patients with disseminated infection, treatment
with brincidofovir was associated with favorable outcome.
Of the 12 cases, 10 cases also showed that brincidofovir may
be a promising salvage therapy for the treatment in case of
renal toxicity of cidofovir or unsatisfactory clinical response
to cidofovir. However, given the small sample size, more
studies are expected to provide important evidence for the
efficacy of brincidofovir [180]. The clinical effect of ribavi-
rin in our review appeared to be associated with an appreci-
able benefit among patients with various manifestations of
ADV disease. However, the small number of cases in ours
study limits the interpretation of this conclusion. Based on
current data, there is no recommendation of the use of gan-
ciclovir for ADV treatment [181]. In the current review, a
possible benefit of ganciclovir against urinary tract infection
has been suggested. The prognosis is poor in the absence of
antiviral therapy except in patients with urinary tract ADV
infection and keratoconjunctivitis. Previous study observed
that hemorrhagic cystitis and nephritis probably can gener-
ally be treated only with reduction in immunosuppression
without specific antiviral therapy, as also demonstrated in
our review [182]. However, for patients with early ADV
disease, especially for patients with pneumonia, hepatitis or
enteritis, antiviral treatment may be beneficial, while treat-
ment for ADV keratoconjunctivitis is primarily supportive
includes article tears and cool compresses [183].
The severity of ADV infections varies widely from self-
limited to fatal. The mortality rate of ADV infection in our
study is 35.5%, while in GI ADV infection, ADV pneumo-
nia and disseminated disease tend to show a worse outcome
with rates ranging from 44.2% to 50%. Severe HAdV infec-
tion have mostly been recognized in immunocompromised
patients. However, ADV infection in the context of immu-
nocompetent patients is associated with a mortality of up to
32.9% in our analysis, which is contrary to previous study
[184]. In the further analysis, we found that the adenovirus
pneumonia and disseminated infection displayed the greatest
risk of lethal outcome in immunocompetent adult patients
(etable 2). Fatality rates for severe HAdV pneumonia or
disseminated disease may exceed 50% in previous report
[185]. Recent study also found that there is no significant
difference between immunocompetent and immunocompro-
mised patients with HAdV pneumonia in severity of infec-
tion [186]. On the other hand, we also thought the high mor-
tality could be partially explained by the publication bias, in
other words, more severe adenovirus pneumonia tended to
be reported. However, this review indicated that there is a
trend in improvement in ADV infection-associated mortal-
ity in recent years, potentially owing to the advent of newer
antiviral therapy and understanding of the disease.
There were limitations in this meta-analysis as well. The
potential influence of published bias could impact the out-
comes because the case reports of unique condition are more
likely to be published. Meanwhile, not all species and details
of treatment were described. However, this review helped to
investigate the association between risk factors and various
manifestation of ADV infection. We also ascertain the asso-
ciation between different species and various manifestation.
Mortality rate remained high, especially among patients with
pneumonia and disseminated disease. Our review clarifies
the current treatment of ADV infections, and more treatment
requires further investigation.
Compliance with ethical standards
Conflicts of interest All authors declare that they have no conflicts of
interest in relation to the present manuscript.
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