Respiratory syncytial virus infections

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

Respiratory syncytial virus infections; RSV infections

Definition
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Common acute infection of the upper and lower respiratory tract in infants and young children. RSV infections lead to clinical symptoms every year (seasonal frequency in late autumn and winter) In the other months only sporadic infections are observed. The RSV virus is highly contagious. > 50% of children (age: <1 year) are exposed. Newborns and young infants are protected from RSV-related disease in the first 4-6 weeks of life by diaplacentally transmitted antibodies. However, premature infants can also become ill with RSV infection in the first weeks of life due to a reduced supply of maternal antibodies. In older infants and toddlers, RSV infection is the most common cause of diseases of the lower respiratory tract. Within the 1st year of life 50-70% and until the end of the 2nd year of life almost all children have undergone at least one infection with RSV.

There is no long-term immunity. Reinfections are frequent, especially in adults with regular contact to small children.

Pathogen
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Worldwide distributed, single-stranded (ss), unsegmented RNA virus of the family Paramyxoviridae (genus Pneumoviridae - pneumoviruses). The incubation period is 2-8 days (average 5 days).

Duration of contagiousness: RSV-infected persons can be infectious already one day after infection and even before the onset of symptoms. The duration of infectiousness is usually 3-8 days and usually subsides within a week in immunocompetent patients. Premature babies, newborns, immunodeficient or immunosuppressed patients can excrete the virus for several weeks, in individual cases for months.

Occurrence/Epidemiology
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The incidence of RSV respiratory diseases is reported worldwide in the first year of life with 48.5 cases and 5.6 severe cases per 1,000 children. On average, 0.2% of cases are fatal in children without known increased risk, 1.2% in premature infants, 4.1% in children with bronchopulmonary dysplasia and 5.2% in children with congenital heart defects.

M:w=1:1; in severe RSV-related diseases in children associated with hospitalisation (nosocomial infections), boys are affected twice as often as girls.

Etiopathogenesis
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The virus infects the cilia-bearing epithelial cells of the upper respiratory tract. This is where viral replication takes place. The formation of syncytia caused by the F protein and the onset of inflammation cause reversible damage to the epithelia. The necrosis of such syncytia as well as the inflammatory exudates lead to an obstruction of the airways. The infection is typically self-limiting. The epithelia regenerate within 4-8 weeks.

Clinical features
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An RSV infection can show a spectrum of symptoms ranging from a simple respiratory tract infection to a severe respiratory disease of the lower respiratory tract requiring ventilation, or it can be asymptomatic. A primary infection with RSV almost always leads to clear clinical symptoms. The disease may be restricted to the upper respiratory tract, but may also manifest itself as bronchiolitis, pneumonia or tracheobronchitis, especially in infants in the first months of life.

A clinical picture similar to pertussis occurs in about 5% of cases involving the lower respiratory tract. Fever is frequent, although the severity of the disease cannot be deduced from its level and duration. In the course of the disease, symptoms of an upper respiratory tract disease (rhinitis, non-productive cough, possibly pharyngitis) are usually first observed, which can progress to symptoms of lower respiratory tract diseases within 1-3 days. Usually the cough becomes more pronounced and productive, the respiratory rate increases and dyspnea may occur. Signs of expiratory obstruction are typical. RSV bronchiolitis is characterised by a reduced general condition, difficulties in food intake (refusal to drink, reflux, vomiting, dehydration), accelerated breathing, coughing and dyspnoea using the respiratory assistance muscles (jugular or intercostal retractions). In severe cases, a "silent obstruction" with tachypnea and poor peripheral circulatory perfusion may also occur, whereas in bronchiolitis expiratory gulling is the main symptom.

Diagnosis
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Auscultation: crackling as well as gushing sounds can be auscultated over the lungs. A narrowing of the airways, poorly ventilated and compensatory over-ventilated lung areas (atelectasis typically affects the right upper lobe of the lung) and a low ventilation-perfusion ratio may lead to hypercapnia, hypoxaemia and also cyanosis.

Pathogen detection should be timely to effectively prevent nosocomial RSV infections. Nasopharyngeal secretion from nasopharyngeal rinsing water, aspiration or swabs is suitable for the detection of RSV.

PCR: Genome detection by PCR is very specific, fast and highly sensitive, even with low virus load in the sample.

Available as antigen detection are the detection methods mostly based on enzyme immunoassays (EIA) rapid tests. They provide a result within 20-75 minutes (sensitivity of EIA is 50-90%; specificity 75-100%). Furthermore, highly specific detection methods based on immunofluorescence techniques (IFT) can be used (sensitivity + specificity > 90%).

Virus culture is possible (formerly the gold standard in laboratory diagnostics), but is practically irrelevant.

Antibody detection is of minor importance compared to direct pathogen detection. In the case of RSV infection, antibodies are only formed in low concentrations. In order to detect an increase in titer, two sera must be tested at least 2-4 weeks apart. Antibody detection is therefore particularly suitable for retrospective confirmation of the diagnosis and for surveillance and research purposes.

Complication(s)
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Secondary infections: Secondary bacterial infections are rather rare in RSV infections, co-infections with other respiratory viruses are frequent.

Otitis media: A frequent complication of RSV infection is acute otitis media. In up to ¾ of cases of acute otitis media in children under 3 years of age, RSV is detected alone or as co-infection with other viral or bacterial pathogens.

Hyperreactive bronchial system: Recurrent obstructions and persistent hyperreactivity of the bronchial system as a result of acute RSV-induced bronchiolitis have been described as long-term complications.

Allergic bronchial asthma: Apparently these recurrent infections can lead to induction and exacerbation of allergic bronchial asthma (Nguyen TH et al. 2018).

Risk patients: Risk patients at risk for a severe RSV infection are premature babies, children with previous pulmonary diseases, children with heart defects, adults with previous cardiac or pulmonary diseases. Furthermore immunodeficient and immunosuppressed patients. Nosocomial RSV infections are significant in premature infants, immunodeficient and immunocompromised individuals.

Cave: RSV is one of the most important pathogens of nosocomial infection and pneumonia in infants and young toddlers.

Therapy
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The therapy is symptomatic and consists of sufficient fluid intake to mobilise secretions and keep the nasopharynx free with NaCl nasal rinses or drops. Oxygen administration, respiratory support with CPAP mask or intubation and ventilation may be necessary in individual cases. Inhalation with bronchodilators is helpful. Parallel monitoring of oxygen saturation at the beginning of inhalation treatment should be carried out, as hypoxaemia can be aggravated. Caution: RSV-associated apneas!

Inhaled corticosteroids are neither effective in the acute phase of disease nor in preventing hyperreactivity of the bronchial system. Systemic administration may help to reduce acute symptoms and their duration. Antibiotics do not influence the clinical course of RSV infection or the duration of the ability to infect. They are only indicated in the presence of bacterial coinfection.

Progression/forecast
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98% of RSZ respiratory tract infections in young children are uncomplicated and often go unnoticed. Recurrent apneas are characteristic of premature babies. Overall, the symptoms differ from patient to patient. Some cases are severe in infants, especially in immunological risk patients. Occasionally respirations are necessary. 2% of infections are lethal. In adults, RSV infections are often asymptomatic or uncomplicated upper respiratory tract infections.

RSV reinfections are frequent and occur at any age. Reinfections are possible, but are usually less severe than primary infections. In most cases the disease lasts about 3-12 days, whereas respiratory irritation symptoms, especially coughing, can last for more than 4 weeks.

Prophylaxis
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So far, no vaccine has been approved for active immunization.

Passive immunisation: For this purpose, a monoclonal antibody (palivizumab) directed against the F protein of the RSV virus is available for paediatric risk patients (Meissner HC et al. 1996). The preparation is to be applied monthly during the RSV season. The protective effect begins with the administration of the first dose, but reaches its maximum effect only after the second dose (Resch B 2017).

During the infectiousness period, patients should not visit communal facilities, especially toddler groups, even if there is no explicit ban on visiting communal facilities in accordance with the Infection Protection Act (IfSG) § 34 (1) and (3). If an RSV is detected in a hospitalized patient, the patient should be kept physically separate from others, especially infants and high-risk patients, for the entire duration of the patient's infectiousness. A cohort isolation of several RSV-infected patients is possible.

RSV is sensitive to disinfectants that are effective against enveloped viruses (marked by the manufacturer as "limited virucidal"). For general protection and hygiene measures, please refer to the guideline for hospital hygiene and infection prevention.

Measures in case of outbreaks: In case of an outbreak in hospitals and other health care facilities, protection and hygiene measures apply equally. If an RSV outbreak occurs in high-risk areas, such as a neonatal intensive care unit with critically ill premature babies or long-term ventilated children with bronchopulmonary dysplasia, all high-risk patients in the department should be included in investigations to detect and contain the spread of the pathogen at an early stage.

Note(s)
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Obligation to register according to IfSG: In Germany there is no obligation to register diseases or pathogens according to IfSG.

Literature
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  1. González-Sanz R et al (2016) ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus Growth through Protein ISGylation. J Virol 90:3428-3438.
  2. Kestler M et al (2018) Respiratory syncytial virus burden among adults during flu season: an underestimated pathology. J Hosp Infect 100:463-468.
  3. Meissner HC et al (1996) Prevention of respiratory syncytial virus infection in high risk infants: consensus opinion on the role of immunoprophylaxis with respiratory syncytial virus hyperimmune globulin. Pediatric Infect Dis J 15:1059-1068.
  4. Melero JA et al (2017) Structural, antigenic and immunogenic features of respiratory syncytial virus glycoproteins relevant for vaccine development. Vaccines 35:461-468.
  5. Mesquita FDS et al. (2017) Rapid antigen detection test for respiratory syncytial virus diagnosis as a diagnostic tool. J Pediatr (Rio J) 93:246-252.
  6. Nguyen TH et al. (2018) Identification of IFN-γ and IL-27 as Critical Regulators of Respiratory Syncytial Virus-Induced Exacerbation of Allergic Airways Disease in a Mouse Model. J Immunol 200:237-247.
  7. Resch B (2017) Product review on the monoclonal antibody palivizumab for preventionof respiratory syncytial virus infection. Hum Vaccine Immunother13:2138-2149.
  8. Rossey I et al (w2017) Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state. Nat Commun 8:14158.

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Last updated on: 29.10.2020