Coronaviruses, SARS, RSV:

Respiratory Viruses
 Influenza
 Parainfluenza viruses
 Respiratory syncytial virus (RSV)
 Rhinovirus
 Adenovirus
 Coronavirus – SARS .

Clinical:
 Bronchiolitis
 Croup
 Upper respiratory tract
 Influenza
 Pneumonia
 Infectious mononucleosis

CORONAVIRUS
- Diseases
Coronaviruses are an important cause of the common cold, probably second only to
rhinoviruses in frequency. Coronaviruses also cause a range of diseases in farm animals and
domesticated pets, some of which can be serious

- The viruses:
Coronaviruses (CoV), including SARS CoV, are enveloped + RNA viruses. Their outer surface
has club shaped spikes that gives the virus a crown like appearance (corona = crown)

Pathogenesis & Immunity:

- Coronavirus infection is typically limited to the mucosal cells of the respiratory tract.
- Approximately 50% of infections are asymptomatic.
Immunity following infection appears to be brief, and reinfection can occur.
- The viruses spread by respiratory droplets. Infection usually occur in winter and early
spring. Incubation period is short 2 –4 days.
-The severity of illness is similar to that of rhinovirus infection, but less severe than
infection with respiratory syncitial virus or influenza viruses.
-At present, six CoVs have been identified that infect humans.
- Pneumonia caused by SARS coronavirus is characterized by diffuse edema resulting in
hypoxia.
- The binding of the virus to angiotensin-converting enzyme-2 (ACE-2) on the surface of
respiratory tract epithelium may contribute to the dysregulation of fluid balance that
causes the edema in the alveolar space.
- SARS CoV causes high fever (>38C), dry cough, shortness of breath, myalgia, headache .
- Chest X-rays show pneumonia.
- SARS may have originated in wild bats in China .
- SARS-CoV is predominantly spread in droplets shed from respiratory secretions of patients

Laboratory Diagnosis:
 Antigen and Nucleic Acid Detection: ELISA,PCR .
 Isolation and Identification of Virus:
 Serology.

Middle East respiratory syndrome coronavirus (MERS):

- MERS-CoV seems to be widely present in camels in the Middle East and some parts of
Africa. DPP4 has been identified as the receptor for MERS-CoV.
- When MERS is compared with SARS, many similarities in the clinical symptoms and
respiratory disease are noted.
- The high mortality rate may be due to delayed diagnosis and the lack of effective
therapies. Associated comorbidities, including end-stage renal disease on hemodialysis,
diabetes, and chronic cardiopulmonary disease, have been associated with increased
mortality rates.
-Human to human spread of MERS-CoV is reported in hospital outbreaks and travelers
returning from the Middle East and their close contacts. MERS affect people of all age
groups

Respiratory Syncytial Virus (RSV)

- Respiratory syncytial virus is a ss RNA virus belonging to the family Paramyxoviridae
- RSV most serious cause of bronchiolitis & pneumonia in infants < 6 months of age.

Epidemiology & Pathogenesis

- RSV spreads in infants & young children during winter months. Highly contagious &
spreads by respiratory route with progressive involvement of the middle and lower airways.
Short incubation period (1-4) days . Viral shedding may persist for 1–3 weeks from infants
and young children, but adults shed virus for only 1–2 days. .
Symptoms of fever, lethargy & apnea results as sloughing of epithelium & exudate occlude
the lumen of airways.
 Clinical diseases:
(1) Lower respiratory tract infections (bronchiolitis, pneumonia, tracheobronchitis) (major
cause of brochiolitis in infant under 6 month of age)
(2) Upper respiratory tract infections : manifested as common cold.
(3) Complication of RSV: occur in infants includes otitis media (common), myocarditis (rare).

Immunity:
High levels of neutralizing antibody that is maternally transmitted and present during
the first several months of life are believed to be critical in protective immunity against
lower respiratory tract illness.
Severe respiratory syncytial disease begins to occur in infants at 2–4 months of age
when maternal antibody levels are falling.
-Immunity to reinfection is brief.
-Multiple bouts of infection in the same season

Diagnosis
1-Clinical.
2-RSV isolated using nasal swabs, inoculated at different human cell culture, give
characteristics CPE in form of syncytial effect, & presence of cytoplasmic inclusion bodies in
infected cells.
3-Rapid diagnostic technique by indirect immunofluorecent test ELISA to detect RSV Ag in
exfoliated cells of nasal washes.
4-Serology: to detect increased in the titer in RSV Abs detected by CF, ELISA.

 Respiratory disease accounts for an estimated 75% to 80% of all acute morbidity, and most of
these illnesses (approximately 80%) are viral infections.
 The viruses that are major causes of acute respiratory disease (ARD) include influenza viruses,
parainfluenza viruses, respiratory syncytial virus (RSV), adenoviruses, rhinoviruses, respiratory
coronaviruses.
 Other viruses, such as measles virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), varicella-
zoster VZV), herpes simplex virus (HSV), can also cause respiratory symptoms
Epstein-Barr virus: (EBV)
 EBV target the B lymphocytes which carry the CR2 molecule a specific receptor for
the virus It causes infectious mononucleosis .It is associated with Burkitt‘s lymphoma
(BL), B cell lymphoma , and nasopharyngeal carcinoma(NPC) .

 Over 90% of the population is seropositive for EBV worldwide. In developing

countries, most children are infected by the age of 2 years, whereas in the developed
world EBV infection occurs more often in late childhood or adolescence.

 The virus can be routinely cultured from saliva in 10% to 20% of healthy adults and is
intermittently recovered from most seropositive individuals.

Transmission:
EBV is spread by direct contact of oropharyngeal secretions.

Pathogenesis & Immunity:

-Although EBV initially infects epithelial cells in the oral environment, the hallmark of EBV
disease involves subsequent infection of B lymphocytes and polyclonal B-lymphocyte
activation. Cytotoxic T lymphocytes react against the infected B cells. The T cells are the
(atypical lymphocytes) seen in the blood smear.
-Virus induced IM is associated with circulating antibodies against specific viral antigens, as
well as against unrelated antigens found in sheep, horse, and some bovine red blood cells.
The latter, referred to as heterophile antibodies, are a heterogeneous group of
predominantly IgM antibodies long known to correlate with episodes of IM, and are
commonly used as diagnostic tests for the disease.
- They do not cross-react with antibodies specific for EBV, and there is no good correlation
between the heterophile antibody titer and the severity of illness.

- Viral Antigens:
1- EBNA (EB nuclear antigen)
2- LYDMA (lymphocyte detected membrane antigen) the target for T cytotoxic cell.
3-EA (early antigen).
4- VCA (viral capsid antigen): the most important antigen because it is used in diagnostic
tests.
DIAGNOSIS
 Early in acute disease, a transient rise in IgM antibodies to viral capsid antigen (VCA)
occurs, replaced within weeks by IgG antibodies to this antigen, which persist for life.

 The presence of antibody of the IgM type to the viral capsid antigen is indicative of
current infection. Antibody of the IgG type to the viral capsid antigen is a marker of
past infection.

 Early antigen antibodies are generally evidence of current viral infection, although
such antibodies are often found in patients with Burkitt lymphoma or
nasopharyngeal carcinoma.

 Antibodies to the EBNA antigens reveal past infection with EBV. Not all persons
develop antibody to EBNA.

Respiratory complications:
1-Upper airway obstruction:
Significant airway obstruction affects approximately 1-3.5% of cases. Suspicion should be
raised in the presence of odynophagia, cervical lymphadenopathy,and symptoms of
respiratory distress .In severe cases, acute tonsillectomy, endotracheal intubation, or
tracheostomy may be mandatory in order to secure the airway

2-Pneumonia:
Pulmonary involvement is found in 5---10% of the (mono) cases in children.

The pathophysiological mechanism includes lymphocytes infected by EBV, which infiltrate

the lung during acute (mono), induces temporary immunosuppression, causing
susceptibility to another infection. Infection with EBV can affect both cell-mediated and
humoral immunity, may be severe enough to cause secondary infections in some EBV
infected individuals

Adenoviruses:
A nonenveloped DNA virus. The only virus with a fiber protruding from the capsid.
(molecular study) .
Diseases: cause a variety of upper, lower respiratory tract diseases ,GIT ,conjunctiva
..cancer??

Transmission: respiratory, fecal oral route. The fecal oral route is the most common
mode of transmission among young children.
Pathogenesis:
Adenoviruses infect and replicate in epithelial cells of the respiratory tract, eye, GIT, and
UB. They usually do not spread beyond the regional lymph nodes.

Clinical Findings:
- a single serotype may cause different clinical diseases and, more than one type may cause
the same clinical illness.
- Adenoviruses are responsible for about 5% of acute respiratory disease in young children,
but they account for much less in adults. Most infections are mild and self-limited.
-Adenoviruses are the cause of an acute respiratory disease syndrome among military .
- The most common problem caused by adenovirus infection in transplant patients is
respiratory disease that may progress to severe pneumonia
-Diagnosis: PCR, antigen detection, virus isolation or serology.

Rhinoviruses:
-Rhinoviruses are known as the common cold viruses. They are the major causes of mild URI
in all age groups, especially older children and adults. Lower respiratory tract disease
caused by rhinoviruses is uncommon. Acute symptoms commonly last 3 to 7 days.
-More than 150 types are known.

-Pathogenesis and Pathology:

- The virus enters via the upper respiratory tract. The primary site of rhinovirus infection is
in the nasal epithelium. Rhinovirus bind to ICAM-1 (Inter-Cellular Adhesion Molecule 1)
receptors on respiratory epithelial cells. As the virus replicates and spreads, infected cells
release cytokines (which in turn activate inflammatory mediators).
- High titers of virus in nasal secretions which can be found as early as 2–4 days after
exposure are associated with maximal illness. Thereafter, viral titers fall. There is a direct
correlation between the amount of virus in secretions and the severity of illness.
- Antibody develops 7–21 days after infection.
- Rhinoviruses rarely cause lower respiratory tract disease in healthy individuals, they are
associated with the acute asthma exacerbations.
-Rhinovirus shows antigenic drifting which result in emergence of a new strain.

-Diagnosis: is usually clinical .To make a specific diagnosis ,culture and isolation is
required ; nasal secretions are the best specimen for culture .