Viral Infections of the Respiratory

System

Common cold (rhinitis). Sinusitis & otitis media. Pharyngitis & tonsillitis. Croup (acute laryngotracheobronchitis). Acute bronchitis & acute bronchiolitis. Viral pneumonia.

Respiratory infections caused by viruses:

Name of the virus Disease Rhinoviruses URT infection

Human metapneumovirus LRT infection

Adenoviruses URT and eye infections

Influenza viruses URT & LRT infection

Parainfluenza viruses URT & LRT infection

Respiratory syncytial virus URT & LRT infection

Coronaviruses URT & LRT infection

Common respiratory viruses

URTI: common cold, tonsillitis, pharyngitis. LRTI: croup, bronchitis, bronchiolitis, pneumonia.

Some viruses cause pneumonia as part of a multisystem syndrome, e.g. Measles, Varicella-zoster virus, Epstein - Barr virus, Cytomegalo virus (CMV) and Herpes simplex virus.

RhinovirusesThe most common cause of common cold.• Family: Picornaviridae.• Structural features: Non-enveloped Ss

RNA viruses. more than 100 serotypes.• Transmission: -Inhalation of infectious aerosol droplet -Contaminated fingers or fomites.• Treatment and prevention: self-limiting, no specific treatment & no vaccine available.

Adenovirus Family: Adenoviridae > 50 serotypes. Virology: Non-enveloped, Ds DNA virus. Pathogenesis: Adenoviruses infect the epithelial

cells of respiratory tract, conjunctiva, urogenital tract & GIT.

Clinical syndromes: Pharyngitis and tonsillitis. Epidemic pharyngioconjunctivitis (pink eye). Pneumonia. Gastroenteritis (diarrhoea & vomiting) Acute hemorrhagic cystitis & urethritis.

No specific treatment or vaccine.

Family: Paramyxoviridae. Structural features: Enveloped viruses with

Ss RNA genome. There are 4 types (1-4) Transmission: Inhalation of infected droplets. Clinical syndrome:• Croup (or laryngotracheobronchitis). Fever,

harsh cough, difficult inspiration.• Bronchiolitis (cough, fever & wheeze ≤ 2

years).• Pneumonia.

No specific treatment or vaccine.

Parainfluenza Virus

Respiratory Syncytial Virus (RSV) Family: Paramyxoviridae. Virology: Enveloped, Ss RNA virus. Transmission: Inhalation of infectious aerosols mainly in winter. Clinical syndromes:• Bronchiolitis.• Pneumonia.These conditions can be fatal in neonates, prematures and in infants with congenital defects or who are immunodeficient.

Treatment: Inhaled ribavirin for infants with severe cases.

Vaccine: No vaccine available. Specific immunoglobulin can be given

for high risk infants.

Influenza Viruses

Influenza Virus Family: Orthomyxoviridae Genome: Enveloped Ss RNA with 8 Segments. The envelop contains two glycoproteins:

Haemagglutinin (HA) Neuraminidase (NA)

Three Types (Genera):• Type A: infects Man, and animals (birds, pigs).

Causes epidemics and pandemics.• Type B, C: infects Man only.

Influenza viruses are highly susceptible to mutations and reassortment within the infected hosts.

Haemagglutinin (HA): Attachment to the cell surface receptors. Antibodies to the HA is responsible for immunity. 16 haemagglutinin antigenic type, H1 – H16,

human associated H antigenic type are H1, H2, H3. H5, H7, H9.

Neuraminidase (NA): Responsible for release of the viruses from the

infected cell. 9 neuraminidase antigenic type, N1 – N9 Human associated N antigenic type are N1, N2.

N7.

Genetic variability Antigenic drift: accumulated mutations lead

to chemical changes in HA or NA antigens. Partial protective immunity in population.

Antigenic shift: Genetic re-assortment between two viruses results in production of a new virus with different NA-HA combinations. › Usually in Influenza A virus and lead to

pandemics because there is no previous population immunity.

N

Before 1968; H2N2 (Asian flu ; human; killed 1.5 million).

Since 1968; H3N2 (Hong Kong flu; Avian; killed 1 million),

2004- 2009; H5N1 (Hong Kong, Avian); 718 cases and 413 deaths. Rarely spread between humans.

In the last years: › H1N1 (Swine flu; Animal-Human) (five genes

from swine, two from avian, one from human). 12,000 deaths.

› H7N9 (avian, China)no human to human spread

Transmission: Respiratory droplets, aerosols and fomites. Some subtypes can be transmitted from animals

to human e.g. H1N1, H5N1.

Pathogenesis: Tropism: viral hemagglutinin (H) bind to sialic

acid containing glycoproteins on columnar cells of the throat, bronchi and lungs.• Certain subtypes (H5N1, H1N1) bind to lower

cells at a higher rate (sever pneumonia). Up-take of virus into endocytic vesicle.

Uncoating and release of the viral genome segments into the cytoplasm.

Replication of viral RNA in the nucleus & release from the cell by the NA.

N

Tissue Damage: Infected columnar cells produce interferon-α;

monocytic and lymphocytic attraction. Massive inflammation with edema

formation. In sever cases (e.g. H1N1): hemorrhagic and

necrotizing bronchitis and tracheobronchitis and later: bronchopneumonia & alveolar damage with extensive fibrosis can happen.

Symptoms: starts as URTI then LRT: Fever, dry cough, muscle pain, and

generalized pain. In sever cases: bleeding from mouth and

throat with symptoms of acute respiratory distress syndrome (ARDS).

Prognosis: Seasonal influenza is usually a self-limiting

disease but epidemic and pandemic influenza are severe and may be fatal.

Diagnosis: Usually clinical. Specimens: nasopharyngeal swabs, throat

swabs or other respiratory secretions. Laboratory diagnosis: oDirect detection of viral antigens by

rapid test, direct immunofluorescent or ELISA.

oDetection of viral RNA by PCR.

N

Treatment and Prophylaxis:Anti-viral drugs:• Amantadine and rimantadine inhibit viral

uncoating process.• Zanamivir, oseltamivir and peramivir are NA

inhibitors.Vaccines:• Inactivated vaccine: injectable.• Live attenuated vaccine: nasal spray.o Both vaccines contain B virus and two

strains of influenza A virus; It should be given annually for high risk group.

N

CoronavirusesGreek word; crown because of the crown like appearance of the viral surface projections.Virology:• Family: Coronaviridae (Co-Vs).• Helical, enveloped, Ss RNA viruses.• They infect humans and animals and due

to their high mutation rate they can cross species.

Transmission: inhalation of respiratory aerosols.

Clinical manifestations:› Upper respiratory infection: 10-30% of

common cold cases.› Lower respiratory infection: by the new

viruses known as SARS-CoV; and MERS-CoV.

Immunity is short lived and reinfection can happen within few months.

Sever Acute Respiratory Syndrome (SARS- CoV): jumped from bats to civet cats and then to human after mutation.

The virus became able to spread between human in 2003 and caused a large outbreak in china which spread world wide with high mortality. (29 countries, 8273 cases, 775 deaths)

Super spreader: one patient with SARS can transmit the disease to > 10 persons.

Interact with lungs-cellular receptor (angiotensin-converting enzyme 2).

Symptoms: fever, dry cough, myalgia, diarrhea followed by tachypnea and respiratory distress.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Was first identified in Saudi Arabia in 2012 then other cases were discovered inside & outside the Arabian Peninsula.

Symptoms: fever, cough, and shortness of breath, diarrhoea. Severe illness can cause respiratory failure & requires mechanical ventilation.

Mortality rate ≈ 27%. Camels may be the source of infection.

Tell 2nd February 2015 there were 971 laboratory-confirmed cases of MERS-CoV reported to WHO, including at least 356 deaths.

No specific treatment or vaccine is available for coronaviruses.