Practice Essentials

The reported incidence of viral pneumonia (see the image below) has
increased during the past decade. In part, this apparent increase simply
reflects improved diagnostic techniques, but an actual increase appears to
have also occurred. Depending on the virulence of the organism, as well as
the age and comorbidities of the patient, viral pneumonia can vary from a
mild, self-limited illness to a life-threatening disease.

Bilateral interstitial
infiltrates in a 31-year-old patient with influenza pneumonia.
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Signs and symptoms
The common constitutional symptoms of viral pneumonia are as follows:
 Fever
 Chills
 Nonproductive cough
 Rhinitis
 Myalgias
 Headaches
 Fatigue
During physical examination, the patient may also display the following:
 Tachypnea and/or dyspnea
 Tachycardia or bradycardia
 Wheezing
 Rhonchi
 Rales
 Sternal or intercostal retractions
 Dullness to percussion
 Decreased breath sounds
  Pleurisy
 Pleural friction rub
 Cyanosis
 Rash
 Acute respiratory distress
Influenza pneumonia
The influenza viruses are the most common viral cause of pneumonia.
Primary influenza pneumonia manifests with persistent symptoms of cough,
sore throat, headache, myalgia, and malaise for more than three to five
days. The symptoms may worsen with time, and new respiratory signs and
symptoms, such as dyspnea and cyanosis, appear.
Respiratory syncytial virus pneumonia
Respiratory syncytial virus (RSV) is the most frequent cause of lower
respiratory tract infection in infants and children and the second most
common viral cause of pneumonia in adults.
Patients with RSV pneumonia typically present with fever, nonproductive
cough, otalgia, anorexia, and dyspnea. Wheezes, rales, and rhonchi are
common physical findings.
Parainfluenza virus pneumonia
Parainfluenza virus (PIV) is second in importance only to RSV as a cause
of lower respiratory tract disease in children and pneumonia and
bronchiolitis in infants younger than 6 months. PIV pneumonia and
bronchiolitis are caused primarily by the PIV-3 strain. The signs and
symptoms include fever, cough, coryza, dyspnea with rales, and wheezing.
See Clinical Presentation for more detail.
Diagnosis
Laboratory studies
 Cytologic evaluation: Intranuclear inclusions often exist in cells
infected with a deoxyribonucleic acid (DNA) virus. Cytoplasmic
inclusions usually are present in cells infected with a ribonucleic
acid (RNA) virus.
 Viral culture
 Rapid antigen detection
 Polymerase chain reaction (PCR) assay
 Serologies: Particularly useful for definitively confirming the
diagnosis
Radiography
Chest radiography usually demonstrates bilateral lung involvement, but
none of the viral etiologies of pneumonia result in pathognomonic findings
with this modality
Lung biopsy and histologic studies
Infrequently, lung biopsy is required to establish a diagnosis in very ill
patients, who often are immunocompromised.
See Workup for more detail.
Management
All patients with viral pneumonia must receive supportive care with the
following:
 Oxygen
 Rest
 Antipyretics
 Analgesics
 Nutrition
 Close observation
 Intravenous fluids
 Mechanical ventilation
Specific treatments for the various types of viral pneumonia include the
following:
 Influenza pneumonia: Amantadine hydrochloride and
rimantadine hydrochloride are approved for the prevention and
treatment of influenza A virus infection. Their efficacy in patients
with influenza viral pneumonia or severe influenza is unknown.
 RSV pneumonia: Ribavirin is the only effective antiviral agent
available for the treatment of RSV pneumonia, [1] but there are
conflicting data regarding its efficacy.
 PIV pneumonia: Treatment is mainly supportive, but aerosolized
and oral ribavirin have been associated with reduction in PIV
shedding and clinical improvement in immunocompromised
patients.
See Treatment and Medication for more detail.
Background
Viruses account for the largest proportion of childhood pneumonia. Viral
pneumonia decreases in frequency in healthy young and middle-aged
adults, but it then increases substantially among the elderly. Studies on
community-acquired pneumonias consistently demonstrate viruses to be
the second most common etiologic cause (behind Streptococcus
pneumoniae), ranging from 13-50% of diagnosed cases. [2, 3, 4, 5, 6, 7]
The reported incidence of viral pneumonia has increased during the past
decade. In part, this apparent increase simply reflects improved diagnostic
techniques, but an actual increase has also appeared to occur. This
observation is explained by the growing population of patients who are
immunocompromised. [8] (See Epidemiology.)
Depending on the virulence of the organism as well as the age and
comorbidities of the patient, viral pneumonia can vary from a mild and self-
limited illness to a life-threatening disease. Especially in
immunocompromised patients, viral pneumonia may result in respiratory
failure, severe hypoxemia, and other pulmonary pathology.
(See Prognosis.)
The four most frequent etiologies of viral pneumonia in children and
immunocompetent adults are influenza virus, respiratory syncytial
virus (RSV), adenovirus, and parainfluenza virus (PIV). Influenza virus
types A and B are responsible for more than half of all community-acquired
viral pneumonia cases, particularly during influenza outbreaks.
(See Etiology.)
The image below depicts right-middle-lobe infiltrate in a two-month-old boy
with pneumonia due to RSV

Right-middle-lobe infiltrate
in a 2-month-old boy with pneumonia due to respiratory syncytial virus
(RSV).
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The relative importance of additional viruses (eg, parainfluenza,
rhinoviruses, coronaviruses, human metapneumovirus) will likely increase
as diagnostic tests such as reverse-transcription polymerase chain reaction
(PCR), become more widely available. [9] (See Workup.)
Outbreaks of adenovirus of various serotypes frequently occur in military
recruits. Adenovirus type 14 (Ad 14), a new variant in the United States,
has been documented to cause severe and sometimes fatal acute
respiratory illness in patients of all ages but especially the young, the old,
patients with underlying comorbid conditions, and those who are
immunocompromised.
Viral pneumonia is a subset of the pneumonitides, which were at one time
called atypical pneumonias. In the past, all pneumonias were labeled
atypical if a bacterial pathogen could not be identified with Gram staining
and if the pneumonia did not respond to antibiotics.
Many viral pneumonias have overlapping clinical presentations with each
other and with bacterial pneumonia—and may occur together with bacterial
pneumonia—making diagnosis on purely clinical grounds difficult or
impossible. [2] A number of rapid tests to determine viral etiologies have now
been developed, and their use in the emergency department (ED) has
allowed bedside diagnosis of the etiology of viral pneumonia.
An accurate and early etiologic diagnosis is important because specific
therapies are used against certain viruses (see Treatment and
Management). Even with currently available tests, however, in some series
a causative microorganism could not be identified in 50-80% of
symptomatic patients.
Agents used to treat cases of viral pneumonia include acyclovir,
ganciclovir, and immunoglobulin. (See Medication.)
For more information, see Medscape’s Pneumonia Resource
Center and Influenza Resource Center.
Pathophysiology
A full understanding of the pathophysiology and pathogenesis of viral
diseases does not presently exist.
After contamination, most respiratory viruses tend to multiply in the
epithelium of the upper airway and secondarily infect the lung by means of
airway secretions or hematogenous spread. Severe pneumonias may
result in extensive consolidation of the lungs with varying degrees of
hemorrhage, with some patients developing bloody pleural effusions and
diffuse alveolar damage. [10]
The mechanism of damage to tissues depends on the virus involved. Some
viruses are mainly cytopathic, directly affecting the pneumocytes or the
bronchial cells. With others, overexuberant inflammation from the immune
response is the mainstay of the pathogenic process.
Immune responses can be categorized according to patterns of cytokine
production. Type 1 cytokines promote cell-mediated immunity, while type 2
cytokines mediate allergic responses. Children infected with respiratory
syncytial virus (RSV) who develop acute bronchiolitis, rather than mild
upper respiratory infection symptoms, have impaired type 1 immunity or
augmented type 2 immunity. [11]
In addition to humoral responses, cell-mediated immunity appears to be
important for recovery from certain respiratory viral infections. [12] Impaired
type 1 response may explain why immunocompromised patients have more
severe viral pneumonias.
Respiratory viruses damage the respiratory tract and stimulate the host to
release multiple humoral factors, including histamine, leukotriene C4, and
virus-specific IgE in RSV infection and bradykinin, interleukin (IL)–1, IL-6,
and IL-8 in rhinovirus infections. RSV infections can also alter bacterial
colonization patterns, increase bacterial adherence to respiratory
epithelium, reduce mucociliary clearance, and alter bacterial phagocytosis
by host cells.
Influenza virus
Infection by influenza virus leads to cell death, especially in the upper
airway. When direct viral infection of lung parenchyma occurs, hemorrhage
is seen along with a relative lack of inflammatory cells. Mucociliary
clearance is impaired, and bacterial adherence to respiratory epithelium
occurs.
Infection with the influenza virus impairs T lymphocytes, neutrophils, and
macrophage function, which leads to impairment of host defenses and may
foster bacterial infection of normally sterile areas, including the lower
respiratory tract. This impairment of host defenses may explain why as
many as 53% of outpatients with bacterial pneumonia have a concurrent
viral infection.
Adenoviruses
Little is known regarding mechanisms of pathogenicity of adenoviruses.
Studies in children have identified increased production of cytokines,
particularly tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and
interleukin 8 (IL-8). Age, health of the patient, and other unknown host
factors are believed to play key roles.
Viral pneumonia in elderly persons
Elderly persons are at increased risk of infection and complications in viral
pneumonia because of comorbidities. Waning cellular, humoral, and innate
immune functioning may impair viral clearance, which allows spread of the
virus to the lower respiratory tract resulting in increased inflammation.
Elderly persons also have decreased respiratory muscle strength and
impaired protection of the respiratory tract from mucus. [13]
Viral transmission
The mechanism of viral transmission varies with the type of virus. Routes
include large-droplet spread over short distances (< 1 m), hand contact
with contaminated skin and fomites and subsequent inoculation onto the
nasal mucosa or conjunctiva (eg, rhinovirus, RSV), and small-particle
aerosol spread (eg, influenza, adenovirus). Some viruses are extremely
fastidious, whereas others have the capability of surviving on
environmental surfaces for as long as 7 hours, on gloves for 2 hours, and
on hands for 30 minutes.
Transmission routes for selected viral pneumonias are as follows:
 Environmental factors (adenovirus, enterovirus, rhinovirus)
 Direct contact with contaminated objects (VZV)
 Transplantation of contaminated organs (cytomegalovirus
[CMV]) or blood products (CMV)
 Lower-respiratory aspiration of virus asymptomatically shed in
the saliva (CMV, herpes simplex virus [HSV])
 Reactivation of a latent infection (HSV, CMV)
  Hematogenous spread (CMV)
 Spread by healthcare personnel (SARS, measles, adenovirus,
parainfluenza virus, RSV).
Hantavirus transmission is thought to occur primarily through inhalation of
infected excreta from diseased rodents. The virus is also present in rodent
saliva, so transmission can also occur from bites.
A number of viruses, including adenoviruses, influenza virus, measles
virus, PIV, RSV, rhinoviruses, and VZV, are easily transmitted during
hospital stays and cause nosocomial pneumonia. Adenoviruses, influenza
viruses, PIV, and RSV account for 70% of nosocomial pneumonias due to
viruses.
Pulmonary host defense
The pulmonary host defense is complex and includes the following
components:
 Mechanical barriers
 Humoral immunity
 Phagocytic cells
 Cell-mediated immunity
Mechanical barriers are hairs from the nostrils that filter particles larger
than 10 microns, mucociliary clearance, and sharp-angle branching of the
central airways that helps the 5- to 10-micron particles to become impacted
in the mucosa.
Humoral immunity is represented by mucosal immunoglobulin A (IgA),
alveolar immunoglobulin M (IgM), and immunoglobulin G (IgG) present in
transudates from the blood.
Phagocytic cells consist of polymorphonuclear (PMN) cells; alveolar,
interstitial, and intravascular macrophages; and respiratory dendritic cells.
Alveolar macrophages provide the first defense involved in internalizing
and degrading the viral pathogens. They act as antigen-presenting and
opsonin-producing cells.
Respiratory dendritic cells undergo maturation, activation, and early
migration into the regional lymph nodes after the viral exposure. They act
as antigen-presenting cells and are involved in the activation and
differentiation of CD8+ T cells.
Cell-mediated immunity is the most important defense mechanism against
the intracellular viral pathogens. This immunity is involved in antibody
production, cytotoxic activity, and cytokine production. CD8+ memory or
effector T cells tend to dominate the lymphocyte component of the virus-
induced inflammatory component.
Experimental models demonstrated that 30-90% of CD8+ T cells recovered
from bronchoalveolar lavage (BAL) are virus specific at the peak of the
primary response. Studies in transgenic mice infected with influenza
viruses documented that the CD8+ T cells are not recruited in the lung
during the viral infection. They are resting memory cells formed after a
previous encounter with the antigen, or they are acutely activated T cells
after a nonrespiratory infection that undergo early migration in the lung and
that are maintained there by specific ligands.
A substantial number of peripheral CD8+ memory T cells reside in the lung
after a viral infection.
A secondary infection induces extensive renewal of CD8+ T cells in both
lymphoid nodes and lungs. This replacement takes place in the absence of
substantial inflammation or a substantial effector-cell population in the
lungs. Respiratory infection allows numerous T cells to enter the airways
and may permanently alter the permeability of the lung and mediastinal
lymph nodes to lymphocytes.
Etiology
Both DNA and RNA viruses are involved in the etiology of viral pneumonia.
Some are well-known lung pathogens that produce common clinical and
radiologic manifestations. Others are rarely involved as lung pathogens.
Etiologic viruses include various families, as follows:
 Adenoviridae ( adenoviruses)
 Coronaviridae (coronaviruses) - SARS, MERS, 2019 novel
coronavirus (2019-nCoV) [14]
 Bunyaviridae (arboviruses) - Hantavirus
 Orthomyxoviridae (orthomyxoviruses) - Influenza virus
 Papovaviridae (polyomavirus) - JC virus, BK virus
 Paramyxoviridae (paramyxoviruses) - Parainfluenza virus (PIV),
respiratory syncytial virus (RSV), human metapneumovirus
(hMPV), measles virus
 Picornaviridae (picornaviruses) - Enteroviruses, coxsackievirus,
echovirus, enterovirus 71, rhinovirus
 Reoviridae ( rotavirus)
 Retroviridae (retroviruses) - Human immunodeficiency virus
(HIV), human lymphotropic virus type 1 (HTLV-1)
Most of the members of Herpesviridae family are documented lung
pathogens in hosts with compromised cell immunity and include the
following:
 Herpes simplex virus 1 (HSV-1) and herpes simplex virus 2
(HSV-2), also called human herpesvirus 1 (HHV-1) and human
herpesvirus 2 (HHV-2), respectively
 Herpesvirus 6, herpesvirus 7, and herpesvirus 8
 Varicella-zoster virus (VZV)
 Cytomegalovirus (CMV)
 Epstein-Barr virus (EBV)
Influenza virus, respiratory syncytial virus, adenovirus, parainfluenza virus,
coronavirus, rhinovirus, and human metapneumovirus may cause
community-acquired viral pneumonia.
Influenza virus
The influenza viruses are enveloped, single-stranded, RNA viruses of the
family Orthomyxoviridae and are the most common viral cause of
pneumonia. Three serotypes of influenza virus exist: A, B, and C.
Influenza type A can alter surface antigens and infect livestock. This
characteristic may account for its ability to create a reservoir for infection
and cause epidemics in humans. The virus is spread by means of small-
particle aerosol and targets the columnar epithelial cells along the entire
respiratory tract.
Influenza type B causes illness that usually is seen in relatively closed
populations such as boarding schools. Influenza type C is less common
and occurs as sporadic cases.
Influenza type A is usually the most virulent pathogen. The influenza virus
has two envelope glycoproteins, hemagglutinin (H) and neuraminidase (N),
which are important for a number of reasons. The hemagglutinin initiates
infectivity by binding to cellular sialic acid residues, whereas the N protein
cleaves newly synthesized virus from sialic acid on cell surfaces, thus
allowing spread of the virus to other cells.
The influenza virus maintains its infectivity by undergoing antigenic drift
(small number of amino acid substitutions) and shift (large number of amino
acid substitutions) due to changes in the protein structure of the surface
protein, hemagglutinin. Epidemics occur when a viral drift occurs, and
pandemics are seen with viral shift (two influenza A viruses exchange H or
N genes during infection of the same hosts) because most people have no
prior immunity to the virus.
Two influenza types have emerged of particular importance: H5N1 avian
influenza strain and the novel H1N1 swine influenza strain.
Respiratory syncytial virus
Respiratory syncytial virus (RSV) is the most frequent cause of lower
respiratory tract infection among infants and children and the second most
common viral cause of pneumonia in adults. It is a medium-sized virus of
the Paramyxoviridae family that consists of only 1 serotype. Structurally,
RSV has 10 unique viral polypeptides, 4 of which are associated with virus
envelope, and 2 of these (F and G) are important for infectivity and
pathogenicity. Classic RSV infection causes syncytia formation in cell
culture, giving the virus its name.
RSV is highly contagious, spreading via droplet and fomite exposure. Most
children are infected before age 5 years—the infection rate during an
epidemic approaches 100% in certain settings such as daycare centers—
but the resulting immunity is incomplete. Reinfection in older children and
young adults is common but mild. However, the likelihood of more severe
disease and pneumonia increases with advancing age.
Adenoviruses
Adenoviruses are enveloped DNA viruses that cause a wide spectrum of
clinical illnesses depending on the serotype of the infecting agent. These
include asymptomatic illness, conjunctivitis, febrile upper respiratory
disease, pneumonia, gastrointestinal illness, hemorrhagic cystitis, rash, and
neurologic disease. Pneumonia is less common in adults outside of military
recruit camps and similar facilities, but fulminant disease has been
described in infants and in the immunocompromised population and can
occur in apparently healthy hosts. [15]
Although 52 serotypes exist, classified into 7 subgroups or species (A-G),
pulmonary disease is predominantly caused by serotypes 1, 2, 3, 4, 5, 7,
14, and 21. Type 7 viruses can cause bronchiolitis and pneumonia in
infants. Types 4 and 7 viruses are responsible for outbreaks of respiratory
disease in military recruits.
Adenovirus serotype 14 (subgroup B) is a more virulent strain that has
been reported to cause severe respiratory illness and pneumonia.
Emergence of this strain was reported in 2005 among civilian and military
populations, with outbreaks occurring subsequently at military training
centers throughout the United States.
In 2007, adenovirus serotype 14 caused a large, sustained outbreak of
febrile respiratory illness among military trainees in Texas and, more
recently, in a residential care facility in Washington State. [16, 17, 18] In a
community outbreak in Oregon, the median age was 52 years, and 76%
required hospitalization, 47% required critical care, 24% required
vasopressors, and 18% died. The majority of these patients were otherwise
immunocompetent adults. [19]
Spread of adenovirus is by respiratory secretions, infectious aerosols,
feces, and fomites. Neonates may acquire infection from exposure to
cervical secretions at birth.
Contaminated environmental surfaces can harbor virus capable of causing
infection for weeks. The virus is resistant to lipid disinfectants but is
inactivated by heat, formaldehyde, and bleach.
Adenoviruses are extremely contagious. Studies of new military recruits
have shown seroconversion rates of 34-97% over a 6-week period. [16] The
majority of children have serologic evidence of prior adenovirus infection by
the age of 10.
Parainfluenza virus
Parainfluenza virus (PIV) is a common virus that infects most persons
during childhood. PIV is second in importance to only RSV in causing lower
respiratory tract disease in children and pneumonia and bronchiolitis in
infants younger than six months. Transmission is through direct person-to-
person contact or large-droplet spread.
PIV is characterized by nucleocapsids, which develop in the cytoplasm of
infected cells, with hemagglutinin present in the virion envelope.
There are four subtypes of PIV, based on antigenic characteristics. PIV
type 3 is endemic year-round, while types 1 and 2 peak during the fall
season. Immunity is short term, and recurrent upper or lower respiratory
tract infections occur throughout life. The infections vary from a mild illness
to life-threatening croup, bronchiolitis, or pneumonia. Infection in
immunocompromised hosts can result in life-threatening pneumonia with
lung injury and respiratory failure. In one study, 44% of hematopoietic stem
cell transplant (HSCT) patients with PIV progressed to develop pneumonia,
of which 37% died. [20]
Rhinovirus
Some authors report that rhinovirus accounts for up to 30% of cases of all
virus-related pneumonia. Clinical studies show that rhinovirus is the second
most frequently recognized agent associated with pneumonia and
bronchiolitis in infants and young children. Rhinovirus infection is linked to
asthma hospitalizations in both adults and children.
A study of 211 French children with rhinovirus infection revealed
bronchiolitis or bronchitis in 25.6% and pneumonia in 6.2%, after cases of
dual bacterial or viral infections were eliminated.
A study from the Netherlands demonstrated that rhinoviruses cause 32% of
all lower respiratory tract infections with an identified pathogen in the
elderly (> 60 y) symptomatic population. Rhinoviruses were identified more
frequently than coronaviruses (17%) or influenza viruses (7%).
Human metapneumovirus
Human metapneumovirus (hMPV) is a relatively newly discovered
respiratory pathogen, initially described in the Netherlands in
2001. [21] hMPV is in the Paramyxoviridae family (like RSV and PIV) and is a
pleomorphic-shaped virus surrounded by surface protein projections. This
virus is a ubiquitous organism, and most surveys indicate that by age five
years, almost all children have been exposed to it. However, reinfection
occurs throughout life, including in adults. This virus is spread via droplet
and fomite exposure.
As a human pathogen, hMPV may have been underestimated. In children
and infants, hMPV was reported to be a notable cause of lower respiratory
tract infections such as bronchiolitis (59%), croup (18%), asthma (14%),
and pneumonia (8%).
As with other viruses, the severity of infection increases with older age and
with comorbid (cardiopulmonary disease) or immunosuppressive
conditions. The most common diagnoses associated with adult
hospitalizations with hMPV infection are chronic obstructive pulmonary
disease (COPD) exacerbations, bronchitis, and pneumonia. [22] In
immunocompromised hosts (eg, hematologic malignancies), severe
pneumonitis requiring intensive care or resulting in death has been
reported. [23, 24]
Coronavirus
Coronaviruses are from the family Coronaviridae and are single-stranded
RNA viruses, the surface of which is covered by crownlike projections,
giving the virus its name. This virus is spread via droplet and fomite
exposure. Long known to cause upper respiratory infections, coronaviruses
were not felt to significantly cause pneumonia until relatively recently.
However, the severe acute respiratory syndrome (SARS) pandemic in 2003
brought the ability of this virus to cause life-threatening pneumonia to
worldwide attention (see Zoonotic Viral Pneumonia, below).
Seven human coronaviruses (HCoVs) have now been identified: HCoV-
229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-COV (which causes
severe acute respiratory syndrome), MERS-COV (Middle East respiratory
syndrome), and 2019-nCoV. All but 2019-nCoV appear to be established
human pathogens with worldwide distribution, causing upper and lower
respiratory tract infections, especially in children. Typically, HCoV infection
follows a seasonal pattern similar to that of influenza, although Hong Kong
researchers found that HCoV-NL63 infections mainly occurred in early
summer and autumn. [25]
A novel coronavirus (2019-nCoV) was first reported in late 2019 and early
2020 in China. [14]
Varicella-zoster virus
Varicella-zoster virus (VZV) is a highly contagious herpes virus that is
spread by the respiratory route or direct contact with skin lesions. Primary
infection manifests as chickenpox. The reactivation results in zoster
(shingles).
Pneumonia is a significant and life-threatening complication in otherwise
healthy adults (including pregnant women) and immunocompromised
hosts. This pneumonia is rare in otherwise healthy children but does occur
in immunocompromised children.
Complications include secondary bacterial infections, encephalitis,
hepatitis, and, with concomitant aspirin use, Reye syndrome. VZV
pneumonia also tends be more severe in individuals who smoke.
Measles virus
Measles virus is a member of the Paramyxoviridae family and the
genus Morbillivirus. It is a single-stranded RNA virus contained within a
nucleocapsid and surrounded by an envelope. Measles is a respiratory
tract virus that causes a febrile illness with rash in children. Mild pneumonia
often occurs but is usually of no consequence in healthy adults.
Measles may result in severe lower respiratory tract infection and high
morbidity in hosts who are immunocompromised and malnourished. This
virus is highly contagious and is transmitted from person to person by
droplets. The incubation period is 10-14 days and peaks in late winter and
early spring.
Cytomegalovirus
Cytomegalovirus (CMV) is a herpesvirus that is a common cause of
infections, usually asymptomatic, in the general population. In hosts who
are immunocompetent, acute CMV infection causes a mononucleosis-like
syndrome. Transmission is primarily through body fluid contact. The virus
has been found in the cervix and in human milk, semen, and blood
products. The prevalence of antibodies to CMV in adults ranges from 40-
100%, with higher rates in lower socioeconomic areas.
Reactivation of latent infection is almost universal in transplant recipients
and individuals infected with the human immunodeficiency virus. CMV
pneumonia may occur and is often fatal in immunocompromised
individuals, primarily hematopoietic stem cell transplant (HSCT) and solid
organ transplant (SOT) recipients. The severity of pneumonia is related to
the intensity of immunosuppression. Additionally, CMV infection is itself
immunosuppressive, causing further immunocompromise in these patients.
In cancer patients receiving allogeneic bone marrow transplants, CMV
pneumonia has a prevalence of 15% and a mortality rate of 85%, making it
the most common cause of death in this population. Acute graft-versus-
host disease is the major risk factor for CMV pneumonia in these patients.
Interestingly, although CMV is a well-recognized pathogen in patients with
AIDS (manifesting as retinitis, colitis, encephalitis, polyradiculitis, and/or
cholangiopathy), clinically relevant pneumonia is very uncommon in this
group, even if CMV is cultured from alveolar fluid and/or seen on lung
histology.
Herpes simplex virus
Herpes simplex virus (HSV) is a rare cause of lower respiratory tract
infections and is seen primarily in severely immunocompromised patients,
primarily HSCT and SOT recipients, patients who are undergoing
chemotherapy or are neutropenic, or those who have congenital
immunodeficiency. [26] HSV pneumonia develops either secondary to upper
airway infection (because of direct extension of the virus from the upper to
the lower respiratory tract) or following viremia secondary to dissemination
of HSV from genital or oral lesions.
Herpes simplex virus is spread by contact with active lesions or viral shed
by asymptomatic excreters. While not a classic respiratory virus, herpes
simplex virus can cause pneumonia in compromised hosts, with a mortality
rate of 80%. Pneumonia may develop from primary infection or reactivation.
Zoonotic viral pneumonias
Zoonotic viral pneumonias include those caused by the hantavirus, avian
influenza, severe acute respiratory syndrome (SARS), and H1N1 (swine)
influenza.
Hantavirus
Hantavirus is a genus of enveloped RNA viruses in the family Bunyaviridae.
The majority are transmitted by arthropod vectors. Hantaviruses, however,
are harbored by rodents, with each viral species having one major rodent
host species. Rodents, which are chronically infected, excrete hantaviruses
from urine, saliva, and feces. Infection occurs after aerosols of infectious
excreta are inhaled.
The hantavirus pulmonary syndrome (HPS) is seen in the Americas and is
an acute pneumonitis caused by the North American hantavirus, most
notably the Sin Nombre Virus. [27, 28] Two other agents, isolated in other parts
of North America, can also cause HPS.
Hantaviruses originally were recognized in the four-corners region of the
southwestern United States (New Mexico, Arizona, Utah, and Colorado) in
May 1993. The deer mouse (Peromyscus maniculatus) was identified to be
the reservoir.
Cases of HPS have continued to be reported in the United States. As of
July 2010, 545 cases of HPS had been reported in the United States from
32 states. [29]
Avian influenza
In Hong Kong in 1997, an influenza virus (H5N1 virus) previously known to
infect only birds was found to infect humans. Manifestations included
pneumonia, which in some cases led to fatal acute respiratory distress
syndrome (ARDS) or multisystem organ failure.
Prior to the human outbreak, the H5N1 virus caused widespread deaths in
chickens on three farms in Hong Kong. Epidemiologic investigations of this
outbreak demonstrated that individuals in close contact with the index case
or with exposure to poultry were at risk of being infected.
Concern is growing that avian influenza, which is a subtype of influenza A,
may result in a worldwide pandemic in the near future. The avian influenza
virus A/H5N1 has several ominous characteristics, including increased
virulence and human-to-human transmission in several cases, rather than
bird-to-human transmission, as is usually necessary. The disease causes
high mortality as a result of pneumonia and respiratory failure.
The 1997 outbreak in Hong Kong was thought to be controlled by
depopulating 1.5 million chickens in local farms and markets. However,
human infections occurred in 2001 through 2003 in other parts of Asia, and
the virus has been found in poultry and birds in Europe.
The rising incidence and widespread reporting of disease from H5N1
influenza viruses can probably be attributed to the increasing spread of the
virus from existing reservoirs in domestic waterfowl and live bird markets,
leading to greater environmental contamination. As of January 2014, 650
cases of H5N1 human infections have been reported from 16 countries
since 2003, with 386 deaths (59% mortality). [30]
Severe acute respiratory syndrome
Severe acute respiratory syndrome (SARS) was due to a novel coronavirus
(CoV) that crossed the species barrier through close contact between
humans and infected animals. Viral isolation and genomic sequencing have
revealed that the SARS virus originated in the masked palm civet cat
(Paguma larvata), raccoon dog (Nyctereutes procyonoides), and possibly
the Chinese ferret-badger (Melogale moschata), with subsequent
interspecies jumping, during which a partial loss of genome probably led to
more efficient human-to-human transmission.
Horseshoe bats (Rhinolophus sinicus) have also been found to harbor
SARS-like coronaviruses (more distantly related to SARS-CoV than that of
the palm civets), raising the possibility of bats being a reservoir for future
SARS infections.
SARS was a particularly challenging disease because its long incubation
period allowed seemingly healthy travelers who were infected with the virus
to spread it. The SARS coronavirus (SARS-CoV) quickly spread from
China to the rest of the world over a period of 1 year, affecting more than
8000 patients in 29 countries and resulting in 774 deaths.
Global transmission of SARS was halted in June 2003 after the World
Health Organization instituted traditional public health measures, including
finding and isolating case-patients, quarantining contacts, and using
enhanced infection control. [31] No cases of SARS have been reported since
2004.
H1N1 (swine) influenza
Initially reported as an outbreak in Mexico and subsequently the United
States, infection from a novel swine-origin influenza A (H1N1) virus rapidly
spread to become a worldwide pandemic in 2009. The World Health
Organization declared an end to the pandemic in August 2010.
Virus-associated hemophagocytic syndrome may play an important role in
development of multiorgan failure and ensuing death in H1N1 infection. [32]
For more information on H1N1 influenza, see H1N1 Influenza (Swine Flu).
Rare causes of viral pneumonia include Epstein-Barr virus and rotavirus.
Epstein-Barr virus
Epstein-Barr virus (EBV) is transmitted through infected saliva. Pneumonia
as a complication of mononucleosis is very uncommon. The virus can
cause pneumonia in the absence of mononucleosis.
Lung involvement secondary to EBV infections is more often reported in
immunocompromised people than in others. In 25% of pediatric patients
with HIV infection, EBV can cause lesions related to lymphocytic interstitial
pneumonia or pulmonary lymphoid hyperplasia. [33]
Rotavirus
Although upper respiratory tract infection secondary to rotavirus is
common, rotavirus pneumonia is rare. Just a few cases have been
reported.
Epidemiology
Traditionally, viruses were felt to cause approximately 8% of cases of
community-acquired pneumonia for which patients are hospitalized. More
recent investigations have demonstrated viruses to play a larger role,
causing 13-50% of pathogen-diagnosed community-acquired pneumonia
cases as sole pathogens and 8-27% of cases as mixed bacteria-virus
infections. [3, 4, 5, 34]
Influenza virus types A and B account for more than 50% of all community-
acquired viral pneumonias in adults. Various studies have reported differing
frequencies of the other viruses causing community-acquired pneumonias,
with RSV ranging from 1-4%, adenovirus 1-4%, PIV 2-3 %, hMPV 0-4%,
and coronavirus 1-14% of pathogen-diagnosed pneumonia cases. [3, 4, 5, 34]
The impact of influenza is high in elderly persons and greatest for those
with chronic illnesses. It has been estimated that at least 63% of the
300,000 influenza-related hospitalizations and 85% of 36,000 influenza-
related deaths occur in patients aged 65 years or older, despite the fact
that this group accounts for only 10% of the population. [35]
RSV is the most common etiology of viral pneumonia in infants and
children. [36] In addition, RSV has become an increasingly important
pathogen in the elderly population and is now the second most commonly
identified cause of pneumonia in elderly persons, causing 2-9% of the
annual 687,000 hospitalizations and 74,000 deaths from pneumonia in this
population. [13]
Some studies have suggested that RSV-related disease is as frequent as
influenza in elderly persons. Approximately 10% of nursing home patients
develop RSV infection annually, while 10% of these patients will develop
pneumonia.
Parainfluenza infection is the second most common viral illness, after RSV,
in infants.
Adenovirus accounts for 10% of pneumonias in children. Disease from
adenovirus can occur at any time of the year. Various adenovirus serotypes
are responsible for essentially continuous epidemics of acute respiratory
disease at military recruit training facilities in the United States and
worldwide. During the prevaccination era, up to 20% of recruits had to be
removed from duty due to illness. [37] Unfortunately, the vaccine against
adenovirus is no longer available for administration to military personnel.
In late 2019, a novel coronavirus (2019-nCoV) was identified as the cause
of viral pneumonia cases in Wuhan City, Hubei Province, China. See the
Medscape Drugs & Diseases article 2019-nCoV Coronavirus for updated
information on this outbreak.
Viral pneumonia in immunocompromised hosts
Although immunocompromised patients are at higher risk for viral
pneumonia from CMV, VZV, HSV, measles, and adenoviruses, seasonal
viruses (influenza, RSV, PIV) remain a major cause of pneumonia. HSCT
and SOT recipients are particularly at risk for acquiring lower respiratory
tract infection due to CMV and RSV. [38, 39]
CMV pneumonia has been observed in 10-30% of patients with HSCT and
15-55% of heart-lung transplant recipients, making this virus the most
common cause of viral pneumonia in the former patient group. [40] After
CMV, the frequency of viruses isolated from HSCT patients vary, with
influenza virus ranging from 14-52%, RSV 14-48%, adenovirus 2-21%, and
PIV 11-49% of viral isolates. [41]
Although HSV has been shown to cause pneumonia in this patient
population, it is relatively rare when compared with the other viral
pathogens, with one study showing HSV to cause 5% of nonbacterial
pneumonias in HSCT recipients, compared with 46% for CMV. [42]
Viral pneumonia in pregnancy
Acute viral pneumonia is common and often underdiagnosed in pregnancy.
Although the severity of bacterial pneumonia does not seem to be
increased in pregnancy, viral pneumonia can have a serious clinical
evolution.
Among the viral pathogens, influenza virus, VZV, and measles virus are
reported as etiologic agents in severe lower respiratory tract infection. The
infection may result in acute respiratory decompensation, respiratory
failure, and/or ARDS, which can lead to maternofetal hypoxia, preterm
labor, multisystem organ failure, and even death.
Pregnant women seem to be at increased risk for influenza pneumonia.
VZV pneumonia is rare but potentially lethal, with mortality rates of 35-40%
in pregnant women, compared with 10% in the general population.
Measles virus can be a considerable cause of pneumonia in pregnant
women. Further bacterial superinfection can complicate the clinical and
radiologic picture.
Despite reports of a high mortality rate during outbreaks of hantavirus
pulmonary syndrome, no cases of maternal fatalities secondary to this
disorder have been reported to date.
Sex differences in viral pneumonia
Men who are infected develop viral pneumonia at a slightly higher rate than
women. Pregnant women with viral pneumonia have a higher risk for
severe disease than other females. Pregnant patients have a
disproportionate risk of severe disease with 2009 H1N1 infection.
Treatment should be initiated as soon as the diagnosis is suspected. [43]
Age-related differences in viral pneumonia
Most viruses that can cause pneumonia generally infect children and cause
a mild illness. Healthy adults also develop mild disease. In contrast, elderly
persons and persons who are immunosuppressed develop severe viral
pneumonia, resulting in high morbidity and mortality rates. [13]
The main exception to this was seen in the 2009-2010 H1N1 influenza
pandemic, in which severe infection was more common in the population
aged 5-59 years than in the elderly. This was thought to be from lack of
exposure, and thus immunity, to the 1957 (and earlier) H1N1 influenza
strain(s). [44]
Mortality and Morbidity
The US census for 2000-2001 listed pneumonia/influenza as the seventh
leading cause of death (down from sixth) despite a 7.2% decrease in the
mortality rate for these diseases during this period. Severe influenza
seasons can result in more than 40,000 excess deaths and more than
200,000 hospitalizations.
Patients aged 65 years or older are at particular risk for death from viral
pneumonia as well as from influenza not complicated by pneumonia.
Deaths in these patients account for 89% of all pneumonia and/or influenza
deaths.
Morbidity, especially in elderly persons, is also high. Up to 10-12% of
patients older than 65 years required a higher level of assistance for
activities of daily living after hospitalization for acute respiratory illnesses. In
one nursing home outbreak, residents with acute influenza illness showed
significant functional decline. [45]
Pneumonia from adenovirus serotypes other than Ad 14 has a low fatality
rate, and most serotypes have a low morbidity rate.
Influenza virus
Influenza virus represents a common cause of pneumonia in the adult
population, affecting 4-8% of healthy adults. Rates have been 10-20%
during outbreaks and as high as 50% during epidemics. Morbidity and
mortality rates related to influenza pneumonia in both the general
population and in selected groups (eg, patients with chronic diseases, the
elderly) are substantial.
The highest rates of hospitalization for influenza occur in preschool-aged
children and in the elderly population. During outbreaks, the hospitalization
rates are 27.9 cases per 10,000 persons younger than 5 years and 55
cases per 10,000 persons older than 65 years. Between 1972 and 1992,
426,000 deaths related to influenza pneumonia were reported in United
States. Individuals 85 years or older were 16 times more likely than those
aged 65-69 years to die from influenza.
Also in contrast with seasonal influenza, mortality was higher in younger
patients with H1N1 influenza, with 87% of deaths and 71% of severe
pneumonia in the age group of 5-51 years. [44] The higher mortality in
patients younger than 60 years may reflect this cohort’s lack of exposure to
the 1957 (and earlier) H1N1 influenza strains. Exposure to those early
strains may have conferred some immunity in the older population. Also of
interest is a report that identified obesity as a possible risk factor for more
severe disease/mortality. [46]
As of February 2010, the CDC had estimated that 8,330 to 17,160 H1N1-
related deaths occurred between April 2009 and January 16, 2010 in the
United States, [47] and the World Health Organization (WHO) has estimated
that, worldwide, at least 16,226 deaths have been directly attributable to
H1N1. [48]
The H5N1 avian influenza seems to be more virulent than seasonal
influenza, with a 59% mortality rate in cases reported thus far. [30] The
median time from disease onset to death is nine days. The majority of
these patients had no underlying medical problems.
Respiratory syncytial virus
RSV pneumonia is responsible for an average of 80,000 pediatric
hospitalizations and 500 deaths every year. The mortality rate depends on
the patient's immunologic status. In healthy children, the reported mortality
rate is 0.5-1.7% but is higher in immunosuppressed patients (< 80-100% in
untreated HSCT recipients vs 22% in treated control subjects).
In adults, RSV pneumonia is associated with a mortality rate ranging from
11-78%, depending on the severity of underlying immune suppression. In
long-term care facilities, 5-27% of respiratory tract infections have been
estimated to be caused by RSV, 10% of which will develop into pneumonia
and 1-5% of which will be fatal. [49] In immunocompromised patients,
particularly HSCT recipients, the mortality rate for RSV pneumonia is high,
at 41%. [41]
Adenovirus
Adenovirus infection has been associated with low mortality in healthy
adults, but death from a 2009 community outbreak of serotype 14
pneumonia was 18%. [19] In immunocompromised patients, adenovirus can
be acquired not only by person-to-person transmission but also from
reactivation, to produce a wide variety of syndromes, including
gastroenteritis, hepatitis, and hemorrhagic cystitis (in addition to
pneumonia), with mortality rates ranging from 38-100% and with a
cumulative mortality rate of 56% in HSCT patients. [41]
Parainfluenza virus
PIV pneumonia causes 250,000 emergency visits annually, resulting in
70,000 admissions. Fully 18% of hospitalized children with respiratory tract
infections in the United States have this disease.
Rates of PIV pneumonia are increased in immunocompromised pediatric
groups, such as recipients of BMT, HSCT, lung transplantation, and solid-
organ transplantation. PIV has been associated with 10% of acute
respiratory illnesses in healthy adults and 10-50% in transplant recipients.
In the latter group, the mortality rates range from 15-73%. [41] One study
documented that 56% of PIV isolates were associated with upper
respiratory symptoms in HSCT recipients but that 44% developed
pneumonia, of whom 37% died. [20]
Human metapneumovirus
HMPV accounts for up to 10% of unexplained respiratory infections in
children. Some authors report that HMPV can account for 30% of
unidentified, suspected cases of viral pneumonia in transplant patients.
The relatively recent recognition of hMPV in causing pneumonia and the
difficulty in its diagnosis has precluded accurate estimates of mortality
rates, but case reports of deaths exist, primarily in patients with
hematologic malignancies undergoing chemotherapy or
HSCT. [24, 50] Mortality rates in transplant recipients have ranged from 50% in
lung transplant patients to 80% in HSCT recipients. [51] A 2009 hMPV
outbreak at a psychiatric ward in Taiwan, all in immunocompetent patients,
resulted in 1 (of 13 diagnosed patients) death from respiratory failure. [52]
Varicella-zoster virus
In the United States, varicella pneumonia occurs with a frequency of 0.32-
1.36 cases per 100,000 persons per year. Among Americans hospitalized
because of varicella, 1.0-2.3 in 400 develop pneumonia.
Varicella pneumonia complicates approximately 2-10% of the cases of VZV
infection in adults. At least 25% of the fatalities from varicella in adults
occur in persons who develop varicella pneumonia. The severity of
varicella pneumonia is highest in immunosuppressed persons, with
mortality rates of 15-18%, and in pregnant women in the second/third
trimesters, with a mortality rate of 41%.
The overall mortality in the general population has decreased from 19%
(range, 10-30%) in 1960-1970 to 6%. In renal transplant patients, the
mortality decreased from 53% in 1981-1990 to 22% in 1991-2000. The
mortality rate is around 50% in intubated patients with acute respiratory
failure. In HIV-infected patients, a mortality rate of 43% is reported, and in
pregnant women, the mortality rate is about 41%.
Measles virus
In the United States, pneumonia is responsible for 60% of the measles
mortality in infants. Although deaths from measles in the United States
decreased steadily throughout the 20th century—from approximately 12
per 100,000 population in 1912 to approximately 0.2 per 100,000
population in 1960—mortality rates declined markedly after a measles
vaccine was licensed in 1963. [53]
Measles is almost eradicated in the Western Hemisphere. Although only 71
cases were confirmed in the United States in 2009, a sharp increase
occurred in 2014. Through August 1, 2014, 593 confirmed measles cases
were reported to CDC's National Center for Immunization and Respiratory
Diseases (NCIRD). [54] This is the highest number of cases since measles
elimination was documented in the US in 2000. Measles-virus pneumonia
is still a notable cause of mortality and morbidity in nonvaccinated children
and immunocompromised adults.
In 1990, 6.5% of Americans with measles developed pneumonia. A study
of 3220 US military recruits demonstrated that 3.3% had measles-related
pneumonia. Most cases of pneumonia were secondary to bacterial
superinfection. No deaths were reported among these otherwise healthy
adults. However, in another study using different diagnostic criteria,
pneumonia was found in 50% of recruits with measles. A follow-up study of
Afghani children hospitalized for measles revealed an 85.4% rate of
bronchopneumonia.
The CDC reported four cases of measles pneumonia, with two fatalities,
among HIV-infected children in 1986-1987. [55] In children, mortality rates
due to measles bronchopneumonia are high (28%). The mortality rate due
to measles pneumonia is even higher in immunocompromised groups: 70%
in those with cancer and 40% in those with AIDS. Investigators reported 10
fatalities secondary to measles pneumonia in 12 children with leukemia.
Cytomegalovirus
CMV pneumonia is considered the most common life-threatening
complication of bone marrow transplantation (BMT) and solid-organ
transplantation.
The rate of CMV pneumonia in BMT recipients is 10-50%, as reported in
different studies. In patients receiving solid-organ transplants, CMV
reactivation is reported in as many 70% of patients, but only 20% develop
clinically significant infections. Studies of CMV pneumonia in BMT
recipients demonstrate a 31% mortality rate in treated patients and a
decrease from previously reported rates of 56-100% in untreated patients.
The mortality rate is reportedly 75% in untreated immunosuppressed
persons. [56]
Herpes simplex virus
HSV pneumonia develops mainly in immunocompromised patients. The
rate of HSV pneumonia can be as high as 70-80% in hematopoietic stem-
cell transplantation (HSCT) recipients not receiving prophylaxis, and it can
be decreased to 5% with acyclovir prophylaxis. As with CMV, the mortality
rate is high if disease remains untreated in immunosuppressed patients
(>80% mortality). [57]
Hantavirus
As of July 2010, 545 cases of HPS had been reported in the United States
from 32 states, mostly New Mexico, Colorado, Arizona, California,
Washington, Texas, and Utah (in decreasing order of prevalence). [29] HPS
is also reported in South America and in Canada. The mortality rate for
HPS is 35%. Of individuals with HPS, 61% are men and 39% are women,
with a mean age of 37 years. Caucasian patients account for 77%, people
of Native American descent account for about 20%, and those of Hispanic
descent account for 13%.
Prognosis
The prognosis is good in the vast majority of patients with viral pneumonia.
It is guarded in elderly or immunocompromised patients. Some adenovirus
serotypes, especially 2, 3, 7, and 21 have been the cause of serious
chronic morbidity after acute respiratory illness, including irreversible
atelectasis, bronchiectasis, bronchiolitis obliterans, and unilateral
hyperlucent lung. [17] An estimated 14-60% of these children will suffer some
degree of permanent lung damage. Many of these patients presented with
pharyngitis, tonsillitis, and bronchitis. Adenovirus 14 has a high fatality and
morbidity rate in healthy patients. Serious sequelae occurred in those who
survived.
Viral pneumonia may leave patients with residual disability from interstitial
fibrosis. Infants hospitalized with lower lung infection due to RSV are much
more likely to later develop asthma.
Patient Education
For patient education resources, see the Lung Disease & Respiratory
Health Center and the Cold and Flu Center. In addition, see the patient
education articles Viral Pneumonia and Flu in Adults.