Respiratory syncytial virus: Infectious substances pathogen safety data sheet

Section I: Infectious agent

Name

Respiratory syncytial virus

Agent type

Virus

Taxonomy

Family

Pneumoviridae

Genus

Orthopneumovirus

Species

Orthopneumovirus hominis

Synonym or cross-reference

Respiratory syncytial virus is also known as human respiratory syncytial virus (hRSV), pneumovirus, and human orthopneumovirus.

Characteristics

Brief description

Respiratory syncytial virus (RSV) is classified as a member of the genus Pneumovirus in the family Pneumoviridae^{Footnote 1},^{Footnote 2},^{Footnote 3},^{Footnote 4}. The viral genome consists of a linear, single-stranded, negative-sense, non-segmented RNA (~15.2 kb). RSV lacks haemagglutinin and neuraminidase activity. Virus particles are enveloped and pleomorphic, occurring as irregular spherical particles that are 100 to 350 nm in diameter, and as long filamentous fibres that are 60 to 200 nm in diameter and 10 µm in length^{Footnote 2}. The virion consists of nine structural proteins^{Footnote 1},^{Footnote 2},^{Footnote 3},^{Footnote 4},^{Footnote 5}. Three proteins are associated with the nucleocapsid and include nucleoprotein (N), phosphoprotein (P), and polymerase or large protein (L). The other six viral proteins are contained within the virus envelope and include nonglycosylated matrix protein (M), M2 (M2-1 and M2-2), fusion protein (F), glycoprotein (G), and short hydrophobic protein (SH)^{Footnote 1},^{Footnote 2},^{Footnote 3},^{Footnote 4},^{Footnote 6},^{Footnote 7}. There are two non-structural proteins, NS-1 and NS-2, which are involved in innate immune response evasion^{Footnote 6},^{Footnote 7}. RSV can be divided into two subtypes, A and B, based on variations in the G protein^{Footnote 8}. The predominance of these subtypes alternates during different epidemic seasons however there is no difference in severity^{Footnote 8}.

Properties

RSV has an RNA genome, thus its replication is RNA-dependent and it lacks proofreading mechanisms^{Footnote 7}. This leads to many single nucleotide polymorphism (SNP) errors and other mutations. The constant change in the genome allows for changes in virulence and makes it difficult to develop vaccines and antiviral agents.

Section II: Hazard identification

Pathogenicity and toxicity

RSV primarily infects human epithelial cells within the nasopharynx; however, it can also infect other types of cells, including cell lines, but with much lower efficacy^{Footnote 1}, ^{Footnote 2}. Infection may lead to the formation of syncytia within the infected cell. Primary infection with RSV is generally exhibited as lower respiratory tract disease, pneumonia, bronchiolitis, tracheobronchitis, or upper respiratory tract illness^{Footnote 1},^{Footnote 2},^{Footnote 3},^{Footnote 4}. In infants, RSV infection causes approximately 70% of viral bronchiolitis cases^{Footnote 6}. Common clinical symptoms include rhinorrhea, sneezing, coughing, pharyngitis, bronchitis, headache, fatigue, chest tightness, wheezing, dyspnea, and fever^{Footnote 1},^{Footnote 2},^{Footnote 3},^{Footnote 4},^{Footnote 5}. In some cases, otitis media may occur^{Footnote 4}. RSV infections usually begin with upper respiratory tract disease, which has the tendency to progress to lower respiratory tract disease (in ~50% cases)^{Footnote 1},^{Footnote 2}. Symptoms begin 3-7 days post infection with RSV^{Footnote 5}. Healthy individuals typically recover in 1-2 weeks, but it can take much longer if serious disease develops^{Footnote 9}. RSV can cause long term-effects ^{Footnote 10},^{Footnote 11}. Approximately half of the infants experience recurrent wheezing following RSV lower respiratory tract infection. Wheezing symptoms can persist for up to 5 years followed by a gradual decrease.

Epidemiology

RSV occurs worldwide and is the most common cause of bronchiolitis and pneumonia among infants and young children^{Footnote 1},^{Footnote 2},^{Footnote 3},^{Footnote 4}. Within the United States, hospitalizations due to RSV have increased significantly in 2022 in comparison to previous years^{Footnote 13}. As of November 2022, the overall rate of RSV-associated hospitalizations is 18 per 100,000 people. It is estimated that there are 33 million cases of lower respiratory infections attributed to RSV annually on a global scale^{Footnote 11}. Of those cases, 3 million infections led to hospitalization and approximately 60,000 resulted in death. 99% of RSV-related deaths occur in developing countries^{Footnote 6},^{Footnote 11}. RSV is also a major cause of nosocomial infections. Morbidity and mortality are highest among children with underlying illness and individuals with immunodeficiency or immunosuppression. Virtually all children are infected by age 2 to 3^{Footnote 1},^{Footnote 2},^{Footnote 3}. Repeated infections are common, particularly in young children with up to 5 or 6 infections per year^{Footnote 4}. Although all individuals can be infected with RSV, those at high risk include premature infants, young children, particularly those under age 2 with chronic lung conditions, elderly populations, and immunocompromised individuals^{Footnote 1},^{Footnote 2}, ^{Footnote 3}, ^{Footnote 4}. Other factors that may predispose an individual to RSV infection include: crowding (schools and day care centers), exposure to tobacco and smoke, low socioeconomic status, and family history of atopy and asthma. The presence of older siblings is also a risk factor^{Footnote 6}. Infection among healthy and immunocompetent individuals tends to be less severe. RSV follows a seasonal pattern^{Footnote 1},^{Footnote 2}. Annual outbreaks occur during fall, winter, and early spring among urban centres. In the Northern hemisphere, outbreaks peak in February and March, and may last up to 5 months. In tropical and subtropical regions, most outbreaks occur during the rainy season. RSV outbreaks involving lower respiratory illness have been reported in nursing homes and institutions^{Footnote 1}.

Age is the largest risk factor, with RSV infection being most prominent and severe in young children and elderly persons^{Footnote 6}. Infection is also more prevalent in males. Severe infection (involving pneumonia) may develop among elderly patients with underlying respiratory conditions^{Footnote 1},^{Footnote 2}. Children and immunocompromised individuals are more susceptible to developing severe disease. Comorbidities that increase the risk of RSV infection include low birthweight, immunologic disorders, genetic abnormalities, pulmonary disease, neoplasia, and defects of heart and/or lung structures^{Footnote 7}. Transplant recipients have a higher mortality rate of RSV infection than the general population.

Host range

Natural host(s)

Humans^{Footnote 1},^{Footnote 2}.

Other host(s)

Various animal species have been experimentally infected with RSV, including cotton rats, mice, ferrets, guinea pigs, hamsters, marmosets, lambs, and nonhuman primates ^{Footnote 2}.

Infectious dose

The infectious dose for RSV is > 160 - 640 viral units, administered through intranasal spray, as listed by the National Institutes of Health^{Footnote 14}. An intranasal dose of 10⁶ plaque-forming units (pfu) of RSV type B causes infection in over 50% of participants^{Footnote 15}. After intranasal administration of 5.0 × 10² pfu of RSV A2, 100% of male participants experienced infection without overt disease.

Incubation period

Incubation period for RSV infection ranges from 2 to 8 days^{Footnote 1}. RSV is shed during the period of active disease and can continue for over 20 days after clinical recovery^{Footnote 12}.

Communicability

RSV is most likely transmitted through direct contact with infectious secretions (via fomites) and/or large-particle aerosols^{Footnote 1},^{Footnote 2}; however, close contact with infected individuals, or significant exposure of nasal or conjunctival mucosa with contaminated hands is required for transmission^{Footnote 2}. Transmission via small-particle aerosols is less likely^{Footnote 1}, ^{Footnote 2}.

RSV is communicable during the period of active disease, and for as long as a month after^{Footnote 12}. Children especially are known to shed virus for long periods even after clinical recovery^{Footnote 1},^{Footnote 2}. The disease is not readily transmitted from person-to-person, since significant and prolonged contact is required with infected individuals^{Footnote 1}.

Section III: Dissemination

Reservoir

Humans^{Footnote 1},^{Footnote 16}.

Zoonosis

None^{Footnote 16}.

Vectors

None.

Section IV: Stability and viability

Drug susceptibility/resistance

RSV has been shown to be susceptible to ribavirin, which has been used to treat severe RSV infections; however, recent studies suggest that its use produces no significant benefit^{Footnote 1}, ^{Footnote 2}, ^{Footnote 4}. Palivizumab is licensed for RSV prophylaxis and is commonly used to prevent infection for high-risk infants and individuals with cardiopulmonary disorders^{Footnote 5},^{Footnote 6},^{Footnote 7}. It is administered monthly via intramuscular injection^{Footnote 6}. There are several experimental antiviral strategies under development^{Footnote 7}.

RSV strains resistant to palivizumab have been identified in experimental models^{Footnote 7}.

Susceptibility to disinfectants

RSV has been shown to be susceptible to ether, chloroform, and a variety of detergents, including 0.1% sodium deoxycholate, sodium dodecyl sulphate, and Triton X-100^{Footnote 1}. It may also be sensitive to hypochlorites (1% sodium hypochlorite), formaldehyde (18.5 g/L; 5% formalin in water), 2% glutaraldehyde, and iodophores (1% iodine)^{Footnote 17}. Diluted isopropanol (35%) reduces the infectivity of RSV^{Footnote 18}. Other agents effective against RSV include Lysol, povidone-iodine, Amphyl, Hibiclens, O-syl, ethanol, and Listermint^{Footnote 19}.

Physical inactivation

RSV is sensitive to heating above 55°C for 5 minutes (up to 90% decrease in infectivity)^{Footnote 1}. It is also sensitive to freezing and thawing (~90% loss in infectivity following each freeze-thaw cycle). It is also sensitive to acidic media (pH<7).

Survival outside host

RSV is generally very vulnerable to environmental changes, particularly temperature and humidity^{Footnote 1}. It is sensitive to high and low temperatures and to drying (i.e., low humidity levels). It loses up to 90% infectivity at room temperature after 48 hours and up to 99% at 1°C after 7 days^{Footnote 1}. The optimal pH is 7.5. It may survive for about 3 to 30 hours on nonporous surfaces at room temperature. RSV can be recovered from countertops for up to 7 hours, from rubber gloves for 5 hours, from cloth material for 2 hours, and from skin for up to 20 minutes^{Footnote 20}. Survival times decrease slightly in higher temperature environments.

Section V: First aid/medical

Surveillance

RSV can be detected by monitoring for symptoms^{Footnote 4}. There are four main laboratory techniques for diagnosing RSV, including virus cultures, serology, immunofluorescence and/or antigen detection, and nucleic acid-based tests. Being labour-intensive and time consuming, the first two techniques are rarely employed for diagnostic purposes in epidemiological studies. Rapid diagnostic techniques for viral antigen detection, including immunofluorescent-antibody assay, optical immunoassay, enzyme immunoassay, and chromatographic immunoassay are preferred as most are commercially available, easy to perform and produce rapid results^{Footnote 1}. Direct fluorescent antibody testing is useful in high-risk patients and produces a rapid response, however, the sensitivity decreases in adult patients^{Footnote 7}. Nucleic acid tests (such as RT-PCR) are generally more sensitive^{Footnote 4}. A three-tube reverse transcription-PCR (RT-PCR) assay is in development which would enable simultaneous detection of nine respiratory pathogens including RSV^{Footnote 21}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

Treatment is mainly supportive for infants with mild disease; however, children with severe disease, people with underlying illness, and/or immunocompromised individuals may require hospitalization^{Footnote 1},^{Footnote 2},^{Footnote 4}. There are currently two antivirals for RSV available, ribavirin for treatment and palivizumab for prevention^{Footnote 7}. Aerosolized ribavirin may be administered to immunocompromised patients with severe illness; however, recent studies suggest that its use produces no significant benefit^{Footnote 1},^{Footnote 2}. Palivizumab prophylactic treatment, in combination with aerosolized ribavirin, may also be considered for high-risk children. Inhaled nanobodies are being studied in clinical trials for RSV treatment^{Footnote 7}. There are several other antiviral strategies in experimental stages. Another approach is to consider the use of anti-inflammatory drugs; however, their overall efficacy is yet to be determined^{Footnote 4}. Berberine, an anti-inflammatory drug, has been shown to have potential as a therapeutic drug for RSV induced respiratory infection, although its underlying mechanisms are unclear^{Footnote 22}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

No vaccine is currently available; however, there are several vaccines being developed^{Footnote 7}. The Novavax vaccine has completed Phase II clinical trial^{Footnote 7}. There are five subunit vaccines in Phase I trials and one in a Phase II trial^{Footnote 6}.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

Palivizumab prophylactic treatment has been shown to reduce the rate of hospitalization in children by up to 55%; however, convincing results on its therapeutic efficacy following an infection have not been observed^{Footnote 1},^{Footnote 2},^{Footnote 4}. Palivizumab is a humanized monoclonal antibody that is administered intramuscularly as prophylaxis to high-risk infants for RSV infection^{Footnote 7}. Other monoclonal antibodies are in preclinical development and preclinical trials^{Footnote 5}. Aerosolized ribavirin may be administered to immunocompromised patients with severe illness and can be used in combination with palivizumab prophylactic treatment^{Footnote 1},^{Footnote 2}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI: Laboratory hazard

Laboratory-acquired infections

One case of laboratory-acquired infection with RSV was reported before 1976^{Footnote 23}. In a review of laboratory-acquired infections in Canada from 2016 to 2021, RSV was not identified^{Footnote 24}.

Note: Please consult the (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

The main sources for RSV include saliva, mucous droplets, nasal secretions, nasal swabs, nasopharyngeal swabs, and nasopharyngeal aspirates^{Footnote 1},^{Footnote 4},^{Footnote 5}.

Primary hazards

Droplet or aerosol exposure of mucous membranes and accidental inoculation are the primary hazards associated with exposure to RSV^{Footnote 2}.

Special hazards

None.

Section VII: Exposure controls/personal protection

Risk group classification

RSV is a Risk Group 2 Human Pathogen and Risk Group 1 Animal Pathogen^{Footnote 25}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment (PPE) and clothing outlined in the CBS are to be followed. At minimum, use of a lab coat and closed-toe cleanable shoes, gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.

Other precautions

A biological safety cabinet (BSC) or other primary containment devices to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.

Use of needles and syringes is to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes is to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large-scale activities.

For diagnostic laboratories handling primary specimens that may contain RSV, the following resources may be consulted:

• Human Diagnostic Activities Biosafety Guideline
• Local Risk Assessment Biosafety Guideline

Section VIII: Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time with the disinfectant before clean up (CBH).

Disposal

All materials/substances that have come in contact with the regulated material should be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area / third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

Containment Level 2: The applicable Containment Level 2 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX: Regulatory and other information

Canadian regulatory information

Controlled activities with respiratory syncytial virus require a Human Pathogens and Toxins Licence issued by the Public Health Agency of Canada. Respiratory syncytial virus is a non-indigenous animal pathogen in Canada; therefore, its importation requires an import permit, issued by the Canadian Food Inspection Agency.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Transportation of Dangerous Goods Regulations
• Domestic Substances List

Last file update

November, 2022

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright^© Public Health Agency of Canada, 2023, Canada

References