|Year : 2022 | Volume
| Issue : 4 | Page : 113-115
Severe adenoviral pneumonia in children: Much more to learn
Suresh Kumar Angurana1, Renu Suthar1, Maninder Singh Dhaliwal2
1 Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Pediatrics, Pediatric Intensive Care Unit, Medanta The Medicity, Gurugram, Haryana, India
|Date of Submission||03-Jun-2022|
|Date of Acceptance||09-Jun-2022|
|Date of Web Publication||20-Jul-2022|
Dr. Suresh Kumar Angurana
Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Angurana SK, Suthar R, Dhaliwal MS. Severe adenoviral pneumonia in children: Much more to learn. J Pediatr Crit Care 2022;9:113-5
Adenoviruses are DNA viruses classified into seven species (A through G) with more than 100 genotypes and 52 serotypes. Infections due to adenoviruses are more common in younger children due to lack of humoral immunity. Adenovirus infection epidemics may occur among healthy children and adults in closed and crowded settings. The clinical spectrum of infection due to adenoviruses is broad. Adenoviruses typically cause mild self-limiting infections involving upper or lower respiratory tract, conjunctiva, or gastrointestinal tract.,, Respiratory involvement may be in the form of upper respiratory tract infection, bronchitis, bronchiolitis-like illness with predominantly wheezy symptoms, bronchopneumonia, or lobar consolidation, or it may progress to acute respiratory distress syndrome. Patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection) are predisposed to develop severe and disseminated diseases. Mortality rate may exceed 50% among cases with untreated severe adenoviral pneumonia (SAP) or disseminated disease.,, Different adenoviruses have tropism for different tissues leading to several extrapulmonary manifestations in the form of conjunctivitis, hepatitis, gastroenteritis, hemorrhagic cystitis or colitis, myocarditis, cardiomyopathy, nephritis, pancreatitis, or meningoencephalitis. The treatment of adenoviral infections is symptomatic. Cidofovir has been used in cases with severe adenoviral disease. However, there are no randomized trials to support its use.,, After acute phase, adenovirus infections may lead to chronic waxing and waning respiratory symptoms, persistent or recurrent wheezing, need of continuous or intermittent respiratory support and oxygen therapy, and risk of development of postinfection bronchiolitis obliterans (PIBO) and bronchiectasis.,,,,
Several epidemiological studies from India demonstrated that adenovirus is responsible for 8%–20% of severe acute respiratory infections among children.,,, However, the literature on profile of children with SAP admitted to the pediatric intensive care unit (PICU) is limited from India.
In this issue of the Journal of Pediatric Critical Care, authors presented a prospective observational study describing the clinico-epidemiological, biochemical, and radiological profile, as well as long-term follow-up of children aged <10 years with SAP (polymerase chain reaction proven) admitted to the PICU of a tertiary care hospital in Kolkata over a period of 33 months (December 2018 to August 2021). Among 96 children with adenoviral lower respiratory tract infection or pneumonia, 33 (34.4%) had SAP and required PICU care. The mean (standard deviation) age was 9.7 (5.1) months and majority were males (84.8%). All had fever, cough, and respiratory distress; and 96.7% had chest retractions. Among 72.7% of children, SpO2 was <90% at the time of admission. Extrapulmonary manifestations noted were hepatomegaly (33.3%), altered sensorium (27.3%), seizures and diarrhea (in 15.1% each), and both splenomegaly and hepatomegaly (9.1%). Laboratory investigations showed low hemoglobin (50%); elevated leukocyte count (63.6%) and C-reactive protein (66.7%); and deranged sodium (37.5%) and liver enzymes (46%). During the course of illness, 18.2% of children developed hyperferritinemia with multiple organ dysfunction syndrome. Chest radiograph showed bilateral patchy opacities (42.4%), lobar consolidation (9.1%), and hyperaerated lung fields (42.4%). Healthcare-associated infections developed in 21.2% of children. Majority of children (87.9%, n = 29) needed some sort of respiratory support beyond simple oxygen therapy, 75.7% (n = 25) needed invasive mechanical ventilation, 6.1% (n = 2) each required noninvasive ventilation and high-flow nasal cannula oxygen, and 42% required vasoactive drugs. Corticosteroids were used in 72.7% (n = 24) of children, especially among those with hypercytokinemia. Mortality was 27.3% and 66.7% (n = 22) were discharged. Prolonged duration of illness and patchy opacity of chest radiograph were associated with increased risk of mortality. Among discharged children, 91% (n = 20) were followed up till 2.5 years after discharge. During follow-up, majority (90%, n = 18) had recurrent respiratory symptoms needing repeated hospital visits and admissions. Chest imaging (high-resolution computed tomography) was performed among 15 children with recurrent respiratory symptoms which revealed features of PIBO (80%, n = 12) and bronchiectasis (13.3%, n = 2).
We compliment authors for conducting this study which is an important addition to the literature on SAP among children admitted to the PICU from India. We would like to highlight few important points.
It could have been better to include all children with adenoviral pneumonia (n = 96) in the analysis. By comparing children requiring PICU care (n = 33) and those not requiring PICU care (n = 66), the factors associated with PICU admission could have been determined.
The year- and month-wise distribution of cases could have given some information about the season-specific variation of ADVP and rates of ADVP during the coronavirus diseases 2019 (COVID-19) pandemic. It has been demonstrated that during the COVID-19 pandemic, there has been reduction in the incidence, hospitalization, and severity of pediatric infectious respiratory diseases including upper respiratory tract infections, pneumonia, and acute viral bronchiolitis.,,, The infection prevention and control measures (use of face mask, hand hygiene, social distancing, and social isolation), closure of day-care centers and schools leading to limited exposure to other infants and children, restricted transport, and limited accessibility to healthcare settings during the pandemic are the possible reasons.,,
The duration of symptoms was 1 week to 1 month in majority (51.5%) of children (11). Such a long duration of symptoms is not common in pneumonia due to viral etiology. Wei et al. compared children with ADVP and mycoplasma coinfection (n = 125) and those with just ADVP (n = 171) and demonstrated that coinfection group had a significantly longer duration of fever; more severe illness and pulmonary imaging findings (pulmonary consolidation, atelectasis, pleural effusion, and multilobe lesions); significantly longer hospital stay; and higher need of oxygen support, glucocorticoids, and/or immunoglobulin. The coinfection (other viruses or mycoplasma) may be responsible for the longer duration of illness, more severe disease, higher need of mechanical ventilation, longer duration of hospital stay, higher mortality, and higher rates of PIBO in this study. However, the information about coinfection is not available in this study.
The high mortality and PIBO rates in this study could be due to enrolment of cohort with SAP, more sickness level, higher need of mechanical ventilation (75.7%), and higher corticosteroid use (72%). It has been demonstrated that SAP is common among infants and toddlers. The mortality rate varied from 3% to 40%% and 15%–47% of survivors developed PIBO.,, The risk factors associated with the development of PIBO were prolonged duration of fever, male gender, PICU admission, need of invasive mechanical ventilation, and use of intravenous steroids., Similar to index study, corticosteroids are often used in children with severe adenoviral disease, despite lack of randomized trials or guidelines.
Despite several limitations, the study by authors is important to understand the epidemiology, clinical and laboratory profile, and outcome of critically ill children with SAP from India. Further studies are needed to understand the burden of adenovirus among critically ill children presenting with respiratory manifestations, differentiation from other viral etiologies, impact of specific therapies (antiviral agents, steroids), effect on short- and long-term outcomes, and factors associated with mortality and poor long-term respiratory outcome (e.g., PIBO).
| References|| |
Lynch JP 3rd
, Kajon AE. Adenovirus: Epidemiology, global spread of novel types, and approach to treatment. Semin Respir Crit Care Med 2021;42:800-21.
Lynch JP 3rd
, Kajon AE. Adenovirus: Epidemiology, global spread of novel serotypes, and advances in treatment and prevention. Semin Respir Crit Care Med 2016;37:586-602.
Shieh WJ. Human adenovirus infections in pediatric population – An update on clinico-pathologic correlation. Biomed J 2022;45:38-49.
Siew JX, Seah XFV, Chew YR, Thoon KC, Chong CY, Yung CF, et al
. Epidemiology of adenovirus infections and outcomes of cidofovir treatment in severely ill children. Pediatr Infect Dis J 2020;39:907-13.
Li L, Woo YY, de Bruyne JA, Nathan AM, Kee SY, Chan YF, et al
. Epidemiology, clinical presentation and respiratory sequelae of adenovirus pneumonia in children in Kuala Lumpur, Malaysia. PLoS One 2018;13:e0205795.
Castro-Rodriguez JA, Daszenies C, Garcia M, Meyer R, Gonzales R. Adenovirus pneumonia in infants and factors for developing bronchiolitis obliterans: A 5-year follow-up. Pediatr Pulmonol 2006;41:947-53.
Malhotra B, Swamy MA, Janardhan Reddy PV, Gupta ML. Viruses causing severe acute respiratory infections (SARI) in children s obliterans:.g., PIBO) comesm outcomeserm outcomesy manifestati Indian J Med Res 2016;144:877-85.
Sabharwal S, Datta S, Wattal C, Sachdeva A. A prospective study of prevalence of respiratory viruses causing acute respiratory infection in pediatric in-patients during pre- COVID times. Indian J Med Microbiol 2021;39:429-33.
Gaur B, Saha S, Iuliano AD, Rai SK, Krishnan A, Jain S, et al
. Use of TaqMan Array card for the detection of respiratory viral pathogens in children under 5 years old hospitalised with acute medical illness in Ballabgarh, Haryana, India. Indian J Med Microbiol 2019;37:105-8.
] [Full text]
Mishra P, Nayak L, Das RR, Dwibedi B, Singh A. Viral agents causing acute respiratory infections in children under five: A study from eastern India. Int J Pediatr 2016;2016:7235482.
Rajbanshi A, Giri PP, Laha S, Poddar S. Epidemiology, clinical presentation and respiratory sequelae of severe Adenoviral Pneumonia (ADVP) in children admitted in a tertiary care pediatric Intensive Care Unit (PICU) in Kolkata, India. J Pediatr Crit Care 2022;9:20. [Full text]
Friedrich F, Ongaratto R, Scotta MC, Veras TN, Stein RT, Lumertz MS, et al
. Early impact of social distancing in response to coronavirus disease 2019 on hospitalizations for acute bronchiolitis in infants in Brazil. Clin Infect Dis 2021;72:2071-5.
Van Brusselen D, De Troeyer K, Ter Haar E, Vander Auwera A, Poschet K, Van Nuijs S, et al
. Bronchiolitis in COVID-19 times: A nearly absent disease? Eur J Pediatr 2021;180:1969-73.
Takia L, Awasthi P, Angurana SK. Impact of COVID-19 on acute viral bronchiolitis hospitalization among infants in North India. Indian J Pediatr 2021;88:1154.
Angurana SK, Takia L, Awasthi P. Impact of COVID-19 on acute viral bronchiolitis hospitalization among infants in North India: Authors' reply. Indian J Pediatr 2022;89:423.
Wei J, Wu S, Jin X, Zhang J, Pan S. Association of Mycoplasma pneumoniae
coinfection with adenovirus pneumonia severity in children. Allergol Immunopathol (Madr) 2022;50:31-6.
Wang X, Tan X, Li Q. The difference in clinical features and prognosis of severe adenoviral pneumonia in children of different ages. J Med Virol 2022;94:3303-11.
Gu J, Su QQ, Zuo TT, Chen YB. Adenovirus diseases: A systematic review and meta-analysis of 228 case reports. Infection 2021;49:1-13.