Overview

Following the devastating effects of the COVID-19 pandemic in 2020, viral infections have become a dreaded topic for discussion. This is because, when it comes to viruses, the unknown variables are largely unpredictable, and the virus can undergo mutation and become extremely contagious. However, when it comes to newborns or neonates, viral infections pose an even greater risk due to their fragile immune systems.  

Respiratory Syncytial Virus (RSV) causes a lower respiratory tract infection that preys on newborns and immunocompromised adults, especially the elderly. Considering its unusual timing, precise persistence, and alarming increase in the number of cases in children’s hospitals, we deem it fit to identify the risk factors for severe RSV infection in newborns in this article.

What is respiratory syncytial virus (RSV)?

RSV is an enveloped, single-stranded RNA virus belonging to the Paramyxoviridae family (same family as parainfluenza and measles virus) and the genus Pneumovirus.¹ This virus causes infection in the lungs and airways. RSV was first discovered in chimpanzees in 1956 and subsequently confirmed to be a human pathogen after that.²

The colony of chimpanzees used for research developed a runny nose due to inflammation, and the causative agent was called chimpanzee coryza agent (CCA) then.² However, in 1957, a virus was discovered in Baltimore to be identical to CCA and caused severe respiratory illness in infants.³ The pathogen was renamed Respiratory Syncytial Virus (as the virus caused neighbouring cells to fuse together).³ 

Due to the absence of long-term immunity, frequent reinfection occurs with RSV, especially in older children and adults.RSV infection comes with seasonal variation.¹ In temperate climates, RSV epidemics occur every winter for 4-5 months. During the remainder of the year, infections are less frequent. RSV causes approximately 33 million lower respiratory tract infections, 3 million hospitalizations, and about 199,000 childhood deaths; the majority of deaths are in developing countries.

How does RSV cause infection in neonates?

Infection of RSV occurs when newborns come in contact with respiratory droplets and oral secretion from an infected person. A child can either inhale the droplets directly or come in contact with contaminated surfaces or objects such as pacifiers, toys, etc.⁴ The virus can survive for six hours on counters, 45 minutes on paper, and 25 minutes on dirty skin surfaces such as the hands.⁴

On entry into the body, RSV rapidly spreads into the respiratory tract, where it targets a group of cells called apical ciliated epithelial cells.¹ There it binds to cellular receptors, fuses with host cell membranes, and inserts its nucleocapsid into the host cell to initiate its intracellular replication.¹ This triggers the host's inflammatory immune response, leading to a combination of viral cytotoxicity and the host's cytotoxic response⁵. This causes necrosis of respiratory epithelial cells, shedding of necrotic cells, excessive mucus production, and airway edema.⁵

Viral spread lasts usually for 3–8 days but can extend for weeks in immunocompromised patients.⁵ RSV can lead to lower respiratory tract infection (LRTI) in 25-40% of patients.⁵ 

What are the symptoms of an RSV infection?

The incubation period of RSV is estimated to be within 2–5 days before the onset of symptoms.⁶ These symptoms include; 

• Cough and fever
• Rhinitis and pharyngitis
• Congestion of conjunctiva and tympanic membranes
• Tachypnea
• Wheezing
• Flaring of the nostrils 
• Bluish colouration around the fingertips and lips⁷
• Apnea⁸
• Breathing difficulty and runny nose

What are the risk factors that cause a severe form of RSV?

The risk factors that have been identified to lead to severe cases of RSV in neonates include;

Being a premature infant

Premature babies usually have an immature immune system, vulnerable airways, incomplete transfer of maternal antibodies, and underdeveloped cellular immunity needed for viral clearance. 

Prematurity also exacerbates RSV infection. Prematurely born infants have more cases of apnoea, a higher incidence of atelectasis, extended hospital stays, and were more likely to receive supplemental oxygen, mechanical ventilation, and parenteral fluid therapy.¹⁰

Low birth weight

Babies born with low birth weight, particularly < 1000g, have an increased risk of developing bronchopulmonary dysplasia (BPD), i.e., poorly developed lungs. These infants need to be given oxygen therapy for support. Consequently, high amounts of inhaled oxygen and pressure can overload the alveoli. This can lead to inflammation and damage to the inside lining of the airways, the alveoli, and the blood vessels around them and increase susceptibility to viral respiratory infections like RSV.¹¹  

Siblings

Having siblings was previously studied to be a common indicator of the severity of RSV infection ¹². Older siblings who attend daycare can be a source of RSV transmission in the household. This might be characterized by a higher viral load on exposure. Alternatively, parents with several children may seek healthcare for younger children at a later stage, as they feel confident handling the infection at home without going to a hospital.

Maternal smoking

Maternal prenatal smoking can damage fetal lung development and, in the future, lead to a risk of developing RSV infection, bronchiolitis, and asthma.¹⁵ This is because exposure to tobacco smoke impairs the protective channels of the airways, such as mucociliary clearance, and weakens cell-mediated and humoral immunity in infants.¹⁶

History of atopy: 

A family history of atopy has been studied to increase the risk of RSV infection.¹²  The risk of severe RSV infection requiring hospitalization may be increased in infants that have genetically determined airway hypersensitivity and/or atopic disposition.¹² Also, there is a strong association between maternal asthma and RSV hospitalization due to RSV infection in offspring.¹²

Infants with congenital heart disease

Infants with congenital heart disease are known to be at increased risk of severe illness from RSV infection with a high morbidity and mortality rate.⁹ These children require oxygen therapy for a significantly long time.⁹ This is accompanied by a higher risk of developing severe RSV infection in these infants compared to children without cardiac disease.⁹

Lack of breastfeeding and crowded living conditions

Absence of breastfeeding in combination with crowded living conditions notably increases the risk of chronic RSV infection.⁹ The reason for the protective effect of breastmilk is attributed to the presence of RSV- IgA and lactoferrin.⁹ Additionally, breast milk promotes maturation probably through the influence of prolactin.⁹

Infants aged below 6 months at the beginning of RSV season

A study according to the Journal of Pediatrics for the hospitalization rates of RSV infection revealed that approximately 10% to 28% of infants hospitalized with RSV are aged < 6 weeks, 49% to 70% < 6 months, and 66% to 100% < 1 year. The greatest risk factor for hospitalization due to RSV infection appears to be the first few months of life and this coincides with the first half of the RSV season.

How to prevent RSV infection in neonates

In hospitals, the most vital preventive measure is to avoid nosocomial spread to other infants. However, to prevent RSV infection in neonates, the following are recommended: 

• Getting an RSV vaccine if you are 32-36 weeks pregnant, especially during RSV season (winter months).⁷
• Getting an RSV antibody immunization called Nirsevimab for your baby if they are younger than 8 months and born during or within the first RSV season.⁷
• Basic hygiene, breastfeeding, and contact isolation should be followed for newborns infected with RSV.
• Palivizumab prophylaxis: This is an RSV-specific monoclonal antibody licensed in 1998 for the prevention of severe RSV infection in high-risk children.¹⁷
• Healthcare professionals should also comply with appropriate use of gloves, surgical masks, disposable gowns and should have continued education about the symptoms, epidemiology and transmission of RSV infection.⁷

Summary 

RSV infection poses great risk to newborns, and measures to prevent the spread of this infection are paramount to avoid disease progression. Risks associated with RSV infection, such as maternal smoking, breastfeeding, crowded living conditions, prematurity, low birth weight, etc., place infants in jeopardy with a potential for long-term morbidity and an increased mortality rate. Therefore, preventive measures are critical to improve overall survival rates of this highly insidious infection. 

FAQs

Who is at most risk of developing severe RSV infection?

People at highest risk of RSV infection include infants and children under 6 months of age with chronic lung disease, infants exposed to second-hand smoke, infants with Down syndrome, and preterm infants less than 35 weeks gestational age, HIV-exposed but uninfected infants, and older immunocompromised adults.⁷

What other complications are associated with RSV infection?

The complications associated with RSV infection include pneumonia, middle ear infections, asthma, bronchiolitis, etc. In older adults and infants less than 6 months of age, hospitalization may be required if they have trouble breathing or feel dehydrated. 

What are the treatment options available? 

Antiviral therapy with aerosolized ribavirin and symptomatic therapy using bronchodilators and corticosteroids are the available treatment options for infection caused by RSV.¹⁸ however, close monitoring of the patient, administration of intravenous fluid, and oxygen treatment could also be required.