Human adenovirus respiratory infections in the pediatric population – Why it's so special?

The last few months were really bad for children with many suffering from recurrent episodes of upper respiratory infections, which was at times getting severe requiring hospitalization in some. Even some children were developing recurrent fever up to 3–4 episodes per month causing panic among the parents. This was because of the circulation of Omicron strains of COVID-19 along with human adenoviruses (HAdVs) and influenza strains. Of these, adenovirus was causing much fear among the health-care providers as some children needed intensive care with a fatality.[1] That’s why, everyone was curious to know more about these HAdVs and the spectrum of respiratory diseases caused by them. HAdVs are naturally found in the upper respiratory and gastrointestinal tracts of humans and mammals.[2] The viruses derived their name from adenoids, from which they were isolated first in 1953.[3] Till date, 104 different HAdV types are known. HAdVs have a predilection for children younger than 5 years as they spend maximum time in closed environments (e.g., schools and orphanages). Of children <5 years of age, infants are more commonly and severely affected. HAdVs commonly affect the respiratory system, and the disease spectrum varies from upper (common cold features) to lower respiratory symptoms (bronchiolitis, bronchitis, and pneumonia).[2] Bronchiolitis can sometimes be severe, leading to the development of postinfectious bronchiolitis obliterans (PIBO) as is severe adenoviral pneumonia, both of them causing high morbidity and mortality.[2] “Acute febrile pharyngitis” is the most common HAdV infection in children, and the manifestations include high-grade fever, exudative tonsillitis, and cervical lymphadenopathy mimicking bacterial tonsillitis.[2] In infants and young children, nasal symptoms (congestion or rhinorrhea) are more common along with the occurrence of pain abdomen. When this is associated with conjunctivitis, the condition is known as “pharyngoconjunctival fever.” HAdVs are responsible for 5%–18% of bronchiolitis cases in infants. Bronchiolitis obliterans (BO) is a rare complication of HAdV lower respiratory tract infection (LRTI) that typically occurs in preschool children after a severe episode. In fact, HAdVs are a major cause of PIBO and bronchiectasis in childhood.[4] Children with severe LRTI who have prolonged fever (>10-day duration), develop progressive breathing difficulty with hypoxemia, or require invasive ventilation during acute phase, are more likely to develop BO.[5] The clinical features of BO include persistent wheezing, often refractory to standard treatments, crackles, and persistent hypoxemia, with chest imaging showing hyperinflation. Early administration of pulse steroid may hasten recovery in some cases, and a poor response indicates a higher risk of persistent symptoms. Irrespective of the initial response, typically a monthly pulse steroid dose for 6 months is given before drawing any conclusion. Other treatment modalities in children with persistent symptoms include low-dose daily oral steroid, inhaled steroids, inhaled salbutamol during acute exacerbation, inhaled tiotropium, oral montelukast, and immunomodulatory drugs. Pneumonia caused by HAdVs though less common than that of respiratory syncitial virus (RSV) and Parainfluenza type 3, the severity is more with a high case fatality rate.[1] HAdV accounts for 10% of cases of childhood pneumonia that can occur in a sporadic or epidemic manner. HAdV types 3, 7, and 21 are the most common. In the recent epidemic in Kolkata, nearly 30% of childhood pneumonia requiring hospitalizations were due to HAdVs, and type 7 was found to be the most dangerous, followed by type 3.[1] The combination of these two led to fatal diseases in some children. There is no definitive treatment for HAdV infection. Like any other virus, supportive treatment is the mainstay of management. Severe cases of BO or pneumonia requiring intensive care unit admissions might show some response to steroid treatment.