eMedicine Specialties > Pulmonology > Infectious Lung Diseases

Pneumonia, Viral

Author: Arthur Jeng, MD, Assistant Professor of Clinical Medicine, University of California at Los Angeles School of Medicine
Coauthor(s): Nader Kamangar, MD, FACP, FCCP, FAASM, Associate Professor of Clinical Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Multi-campus Pulmonary and Critical Care Fellowship Program, University of California, Los Angeles, David Geffen School of Medicine; Medical Director, Hospitalist/Intensivist Program, Olive View-UCLA Medical Center; Associate Program Director, Combined Pulmonary and Critical Care Fellowship Program, Cedars-Sinai/Olive View-UCLA Medical Center/West Los Angeles Veterans Affairs Medical Center; Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital
Contributor Information and Disclosures

Updated: Jan 22, 2010

Introduction

Background

Viral respiratory tract infections are the most common cause of symptomatic human disease among children and adults. They account for more time lost from school and work than any other infection. Approximately 1-3 respiratory tract illnesses occur in adults, compared with 2-7 respiratory tract illnesses in children, each year. These infections may cause a wide variety of diseases, from the common cold to severe pneumonia, and may result in significant morbidity and mortality.

The incidence of viral pneumonia has increased during the past decade. The increase primarily is because of improved diagnostic techniques and the growing population of patients who are immunocompromised.

In the past, the diagnosis of viral pneumonia was made essentially on clinical grounds. Over the past 10 years, new biotechnology has greatly facilitated the diagnosis of viral pneumonias. Clinicians are able to obtain a virologic diagnosis with a high degree of sensitivity and specificity, often within a few hours of the diagnostic procedure. Furthermore, improved approaches to prevention and treatment of viral pneumonias have also become available.

Although widely recognized that viruses are the most frequent cause of pneumonia in children, most clinicians do not appreciate that viral pneumonia in adults is also relatively common, with studies on community-acquired pneumonias consistently demonstrating viruses to be the second most common etiologic cause (behind Streptococcus pneumoniae), ranging from 13-50% of diagnosed cases.1,2,3,4

The 4 most frequent etiologies of viral pneumonia in adults are influenza virus, respiratory syncytial virus (RSV), adenovirus, and parainfluenza virus (PIV). Influenza virus types A and B are responsible for more than one of community-acquired viral pneumonia cases, particularly during influenza outbreaks. RSV ranks second among the common causes of viral pneumonia in adults, followed by adenovirus and PIV.

Pathophysiology

A brief description of the viruses known to cause pneumonia in adult humans is provided below.

Main viruses causing community-acquired 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. They are classified as types A, B, and C and are distinguished by the antigenic differences in the internal proteins. The influenza A virus can be subtyped further based on the antigenic qualities of surface glycoproteins, hemagglutinin, or neuraminidase. Influenza virus is capable of undergoing minor or major changes in antigenicity, which allows the virus to evade the preexisting immunity in the population.

Influenza epidemics occur during the winter months and are associated with significant morbidity and mortality. Patients with chronic obstructive pulmonary disease (COPD), congestive heart failure, hemoglobinopathies, and immunosuppression are at increased risk for severe disease, which can lead to death. Influenza virus is transmitted from person to person primarily by droplet and aerosol exposure to the virus. The incubation period is 1-5 days after exposure.

Two influenza types have emerged of particular importance: H5N1 avian influenza strain and the novel H1N1 swine influenza strain; these 2 strains are discussed in separate sections.

Respiratory syncytial virus

Respiratory syncytial virus (RSV) is the second most common viral cause of pneumonia. It is a medium-sized virus of the Paramyxoviridae family but 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 the most frequent cause of lower respiratory tract infection among infants and children and is highly contagious, spreading via droplet and fomite exposure. Most children are infected before age 5 years, but the immunity is incomplete, and reinfection may occur later in life; the likelihood of more severe disease and pneumonia increases with advancing age. RSV is a well-established cause of pneumonia in the elderly population and in adults who are immunocompromised. Infection may occur seasonally during the winter months or as outbreaks in hospitals and nursing homes.

Adenoviruses

Adenoviruses are enveloped DNA viruses that cause upper and lower respiratory tract infections. Pneumonia is less common in adults outside of military recruit camps and similar facilities, but fulminant disease has been described in the immunocompromised population and can occur in apparently healthy hosts.5 Although 51 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. Adenoviruses are spread through droplet and fomite transmission; close living arrangements (eg, college campuses, military camps) are likely places for outbreaks.

A newly identified, more virulent strain, serotype 14 (subgroup B), has been reported to cause severe respiratory illness and pneumonia. In 2005, surveillance of civilian and military populations initially reported emergence of this strain, 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, in a residential care facility in Washington State more recently, and in a community-wide setting in Oregon.6,7,8,9 In the Oregon community outbreak, 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.

Parainfluenza virus

Parainfluenza virus (PIV) is also from the family Paramyxoviridae and is characterized by nucleocapsids, which develop in the cytoplasm of infected cells, with hemagglutinin present in the virion envelope. These can be separated into 4 subtypes based on antigenic characteristics. This virus is spread via droplet and fomite exposure.

Parainfluenza is a common virus that infects most persons during childhood. PIV type 3 is endemic year round, and 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 hosts who are immunocompromised can result in life-threatening pneumonia with lung injury and respiratory failure.

Human metapneumovirus

Human metapneumovirus (hMPV) is a relatively newly discovered respiratory pathogen, initially described in the Netherlands in 2001.10 It is also 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 5 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 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 COPD exacerbations, bronchitis, and pneumonia.11 In immunocompromised hosts (eg, hematologic malignancies), severe pneumonitis requiring intensive care or resulting in death has been reported.12,13

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; strains 229E and OC43 have been shown to cause pneumonia in adults.3

However, it was the severe acute respiratory syndrome (SARS) pandemic in 2003 that brought the ability of this virus to cause life-threatening pneumonia to worldwide attention. The SARS coronavirus (SARS-CoV) quickly spread from China to the rest of the world, affecting more than 8000 patients in 29 countries and resulting in 774 deaths. The mode of transmission was thought to be primarily via droplet and/or fomite. After intensive infection control measures by the World Health Organization, the global transmission was halted in June 2003.14

Viral isolation and genomic sequencing have revealed that this 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.

Newer strains of coronaviruses have been identified in the Netherlands (NL63) and Hong Kong (HKU1), causing respiratory tract infections, including severe pneumonia.15,16 These discoveries raise the possibility that novel coronaviruses may play an increasing role in causing pneumonias in the future.

Viruses causing pneumonia with rash

 Varicella-zoster virus

Varicella-zoster virus (VZV) is a highly contagious herpes virus. Primary infection manifests as chickenpox; the reactivation results in zoster (shingles). Pneumonia is a common complication in adults and can result in significant morbidity and mortality. Hosts who are immunocompromised (including pregnant hosts) are especially prone to developing pneumonia and its complications, which 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.

Viruses causing pneumonia in immunocompromised hosts
Cytomegalovirus

Cytomegalovirus (CMV) is a common, usually asymptomatic, herpesvirus seen in the general population. In hosts who are immunocompetent, acute CMV infection causes a mononucleosislike syndrome; transmission is primarily through body fluid contact. CMV pneumonia is seen and is often fatal in individuals who are immunocompromised, primarily hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients; the severity of pneumonia is related to the intensity of immunosuppression. When transmitted through blood transfusion or organ transplantation, the incidence of clinically significant CMV disease is higher. 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/are neutropenic, or those who have congenital immunodeficiency. 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.

Zoonotic viruses causing pneumonia
Hantavirus17,18

Hantavirus is a genus of enveloped RNA viruses in the family Bunyaviridae, the majority of which use arthropod vectors for transmission. Hantaviruses, however, are harbored by rodents, with each viral species having one major rodent host species.

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. Rodents, which are chronically infected, excrete hantaviruses from urine, saliva, and feces, and contact with such excreta (which are oftentimes aerosolized) can cause human disease. Hantaviruses originally were recognized in the 4-corners region of the southwestern United States (New Mexico, Arizona, Utah, and Colorado) in May 1993, where the deer mouse (Peromyscus maniculatus) was found to be the reservoir.
 
The disease causes rapidly progressive respiratory failure, noncardiogenic pulmonary edema, intravascular volume contraction, and hemoconcentration, lactic acidosis, depressed cardiac output, and cardiac dysrhythmias. Continued reports of HPS have been reported in the United States, with 9 confirmed cases in 2006 in Arizona, New Mexico, North Dakota, Texas, and Washington and 2 in Los Angeles counties,19 and, as of March 2007, 465 cases of HPS have been reported in the United States from 32 states.

Avian influenza20,21,22

An influenza virus (H5N1 virus) previously known to infect only birds was found to infect humans, causing disease and death in Hong Kong in 1997. Prior to the human outbreak, the H5N1 virus caused widespread deaths in chickens on 3 farms in Hong Kong. The 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. All severe cases presented with lower respiratory tract infection and lymphopenia, and 6 people eventually died in the initial report.

The H5N1 influenza viruses isolated from China and Hong Kong had a range of genotypes (10 different clades), but so far, 4 clades (0, 1, 2, 7) and 3 subclades (2.1, 2.2, 2.3) have crossed the species barrier and infected humans. The rising incidence and widespread reporting of disease 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 June 2009, 433 cases of H5N1 human infections have been reported from 15 countries, with 262 deaths (61% mortality).23

Swine influenza

On April 26th, 2009 the US Department of Health and Human Services issued a nationwide public health emergency regarding human cases of novel swine-origin influenza A (H1N1) virus (S-OIV) infection.24 Initially reported as an outbreak in Mexico and, subsequently, the United States, the virus rapidly spread to become a worldwide pandemic. As of September 2009, a total of 122 countries had reported 318,925 cases of S-OIV infection, 3,917 of which were fatal23 ; in the United States, 9,079 hospitalizations and 593 deaths have been confirmed by the US Centers for Disease Control and Prevention (CDC) as of August 2009.19 This new strain of influenza virus contained a combination of swine, avian, and human influenza virus genes.

Numerous cases of pneumonia have been reported with H1N1 influenza, which have included rapidly progressive disease resulting in respiratory failure, acute respiratory distress syndrome (ARDS), and prolonged ICU admissions.25 Unlike traditional, seasonal influenza, the severity of disease and mortality rates have been higher in younger (age 5-59 y) patients, with 87% of deaths and 71% of severe pneumonia cases seen in this age group.26

Frequency

United States

Community-acquired viral pneumonias

The chief causes of viral pneumonia in adults are influenza viruses types A and B, RSV, adenovirus, and PIV. Traditionally, viruses were felt to cause approximately 8% of cases of community-acquired pneumonia for which patients are hospitalized. Investigations have shown 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.1,2,3,4

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.1,2,3,4

Viral pneumonias in immunocompromised patients
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.27,28 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.29 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.30

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.31

Mortality/Morbidity

Influenza virus

Influenza epidemics occur during the winter months and are associated with 10,000-40,000 deaths in the United States during severe outbreaks. Of these, 80% occur in people older than 65 years. The highest rates of hospitalization 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.

The H5N1 avian influenza seems to be more virulent than seasonal influenza, with a 61% mortality rate in cases reported thus far and a median time from disease onset to death of 9 days; the majority of these patients had no underlying medical problems.

Also in contrast with seasonal influenza, mortality is higher in younger patients with novel S-OIV infection, with 87% of deaths and 71% of severe pneumonia seen in the age group of 5-51 years,26 and the majority of deaths (41%) were in persons aged 25-49 years. The higher mortality in patients younger than 60 years may reflect the risk of the cohort who were born after the 1957 (and earlier) H1N1 influenza strains, the exposure to which may confer some immunity in the older population. Also of interest is that a report from Michigan has identified obesity as a possible risk factor for more severe disease/mortality; of the 10 patients with severe novel S-OIV infection, 9 were obese (body mass index [or ≥30), 7 of whom were extremely obese (body mass index ≥40). Of these patients, 5 had pulmonary emboli, 9 had multiorgan dysfunction syndrome, and 3 died.25

Respiratory syncytial virus

RSV infections occur as seasonal community-based upper respiratory tract infections during winter months or as outbreaks in hospitals, nursing homes, and long-term care facilities. 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.32 In immunocompromised patients, particularly HSCT recipients, the mortality rate for RSV pneumonia is high, at 41%.30

Adenovirus

Adenovirus infection has been associated with low mortality in healthy adults, but death from 2009 community outbreak of serotype 14 pneumonia was 18%.9 In immunocompromised patients, adenovirus can not only be acquired 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.30

Parainfluenza virus

Parainfluenza has been associated with 10% of acute respiratory illnesses in healthy adults and 10-50% in transplant recipients, for which the mortality rates range from 15-73%.30 One study showed that 56% of parainfluenza isolates were associated with upper respiratory symptoms in HSCT recipients, but that 44% developed pneumonia, of which 37% died.33

Human metapneumovirus

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.13,34 Mortality rates in transplant recipients have ranged from 50% in lung transplant to 80% in HSCT recipients.35 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.36

Coronavirus

Coronavirus was previously thought to only rarely cause pneumonia, with very little mortality, but the SARS outbreak has shown the high virulence of certain strains. The SARS-CoV was associated with an overall mortality rate of 10%, but this rate increases to 50% in persons older than 65 years; 25% of those infected with SARS-CoV progressed to ARDS.

Varicella-zoster virus

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%.

Measles

During a large measles outbreak in military recruits, the rate of pneumonia was reported to be 3.3%. However, in a different study using different diagnostic criteria, pneumonia was found in 50% of recruits with measles. In the United States, pneumonia is responsible for 60% of the measles mortality in infants, and this virus has historically caused 450 reported cases of death and 4,000 cases of encephalitis annually before a measles vaccine became available in the mid 1960s. A 2008 outbreak and spike in US measles cases (131 reported cases) between January and July 2008 was not associated with any deaths.25

Cytomegalovirus

The mortality rate for CMV pneumonia in severely immunosuppressed patients is very high, ranging from 31-100% in HSCT recipients to 54-100% in SOT recipients.37

Herpes simplex virus

HSV pneumonia has been reported in 0.8-2.9% of liver transplant recipients, in 1-10% of cardiac transplant recipients, and in 1.5% of renal transplant recipients. This virus will almost universally reactivate after HSCT or SOT. Like CMV, the mortality rate is high if disease remains untreated in immunosuppressed patients (>80% mortality).38

Hantavirus

As of March 2007, 465 cases of HPS have been reported in the United States from 32 states, mostly New Mexico, Colorado, Arizona, California, Texas, Washington, and Utah (in decreasing order of prevalence). The mortality rate for HPS is 35%.

Sex

  • All of the viruses cause pneumonia in both sexes.

Age

  • Most viruses 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.39 The main exception to this is being seen in the current novel S-OIV pandemic, whereby severe infection is more common in the younger population (aged 5-59 years), thought to be from lack of exposure, and thus immunity, to the 1957 (and earlier) H1N1 influenza strain(s).26

Clinical

History

The clinical manifestations of viral pneumonia vary because of the number of diverse etiologic agents. Their presentations are described briefly below. Various viral pneumonias typically occur during specific times of the year, among close populations, or in populations with underlying cardiopulmonary or immunocompromising disease. The common constitutional symptoms of all viral pneumonias are fever, chills, nonproductive cough, rhinitis, myalgias, headaches, and fatigue. Symptoms of viral pneumonia are similar to that of bacterial pneumonia, although studies have shown a lower probability of having chest pain and rigors in viral pneumonias.2

  • Influenza 
    • The typical infection with influenza virus consists of a sudden onset of fever, chills, myalgia, arthralgia, cough, sore throat, and rhinorrhea. The incubation period is 1-2 days, and symptoms normally last 3-5 days. These symptoms are common to other respiratory viral infections but are highly suggestive of influenza virus infection when an outbreak is occurring in the community. Normally, influenza is self-limited; however, people with underlying cardiopulmonary disease or immunosuppression may develop severe life-threatening pneumonia.
    • Influenza pneumonia is associated with fever, malaise, respiratory distress, and hypoxemia. These patients are predisposed to secondary bacterial pneumonia requiring hospitalization.
    • Elderly persons may have a lower frequency of upper respiratory complaints; one study showed that the triad of cough, fever, and acute onset had only a 30% positive predictive value, in contrast to 78% in young adults. Fever and altered mental status may be the only signs of influenza pneumonia in an older patient with cognitive impairment. Influenza also tends to present with more gastrointestinal complaints and myalgia when compared with RSV infection.32,40
    • Avian influenza (H5N1) has an incubation period of 2-5 days, but it may be up to 7 days after exposure. The primary initial symptom is fever, and symptoms of cough, malaise, myalgia, headache, sore throat, abdominal pain, vomiting, and diarrhea are also common. The gastrointestinal complaints may initially suggest gastroenteritis. When pneumonia develops, cough, followed by dyspnea, tachypnea, and chest pain, are reported. In severe cases, encephalitis/encephalopathy, cardiac failure, renal failure, multiorgan failure, and disseminated intravascular coagulation can occur.41
    • Novel S-OIV (H1N1) presents similarly to seasonal influenza. Fever and cough are almost universal symptoms. Shortness of breath (54%), fatigue/weakness (40%), chills (37%), myalgias (36%), rhinorrhea (36%), sore throat (31%), headache (31%), vomiting (29%), wheezing (24%), and diarrhea (24%) are the most common other symptoms.
  • Respiratory syncytial virus 
    • In healthy hosts, RSV causes upper respiratory tract illness, tracheal bronchitis, bronchiolitis, and pneumonia.
    • Upper respiratory tract symptoms, such as coryza and pharyngitis, precede lower respiratory tract involvement.
    • Pneumonia and bronchiolitis often are difficult to differentiate, and both can be associated with wheezing, rales, and hypoxemia. Dyspnea and cough are seen in 60-80% of cases. Compared with influenza, RSV is more associated with rhinorrhea, sputum production, and wheezing and less associated with gastrointestinal complaints and fever.42,43
    • Hosts who are immunocompromised may have a range of respiratory involvement. These patients develop fever, cough, rhinorrhea, sinus congestion, and respiratory difficulties; nearly half report wheezing. In these patients, the symptoms range from mild dyspnea to severe respiratory distress and respiratory failure.
  • Adenovirus 
    • Symptoms include fever, malaise, headache, sore throat, hoarseness, and cough. The incubation period is 4-5 days. Keratoconjunctivitis and diarrhea may or may not be seen, depending on the serotype (8, 19, 37 causing former and 2, 3, 5, 40, 41 causing latter).
    • Serotype 14 pneumonia is associated most commonly with fever (89%) and cough (82%). Other common symptoms include shortness of breath (58%), vomiting (42%), diarrhea (34%), headache (29%), myalgias (29%), coryza (26%), chills (26%), sore throat (21%), and chest pain (16%).33
    • In adults who are immunocompromised, fever is predominant and gastrointestinal symptoms can be severe. Although adenovirus is almost always isolated from the respiratory tract, pulmonary symptoms may not be prominent and dissemination can occur without significant evidence of pneumonia (by symptoms or radiographs). Dissemination can lead to gastroenteritis, hepatitis, and hemorrhagic cystitis.30
  • Parainfluenza 
    • The clinical syndrome is similar to other viruses, consisting of fever, rhinorrhea, cough, and sore throat. The classic croup symptoms of barking cough, hoarseness, and stridor commonly seen in children is less commonly seen in adults.
    • In adults who are immunocompromised, cough is the hallmark. In one study, 44% of HSCT patients with PIV progressed to develop pneumonia, of which 37% died.33
  • Human metapneumovirus 
    • Symptoms are similar to other viruses; nasal congestion and cough are present in 82-100% of cases. Other symptoms include rhinorrhea (69-82%), dyspnea (69%), wheezing (62%), sputum production (55%), hoarseness (46-91%), and sore throat (23-45%). The incubation period is 5-6 days.
    • In one study, hoarseness was more common in hMPV than in RSV infection. Hoarseness, dyspnea, and wheezing were significantly more common among the elderly older than 65 years than among adults younger than 40 years.11
  • Coronavirus 
    • The incubation period is 2-5 days, with a mean of 3 days. Symptoms are similar to other respiratory viruses, including cough, rhinorrhea, sore throat, headache, and malaise, although fever was only seen in 21-23% of cases.
    • SARS-CoV (in contrast) has a longer incubation period (2-14 d), and fever was the first sign of illness, usually then accompanied by headache, malaise, and/or myalgia. In days to 1 week later, nonproductive cough would follow, which often progressed to dyspnea. About 25% of patients had diarrhea, which occurred 1 week after the onset of illness. Of note, rhinorrhea and sore throat were uncommon.44
  • Varicella zoster Virus 
    • The initial presenting symptoms are low-grade fever, malaise, and a rash that is typically vesicular, starts on the trunk and face, spreads centrifugally to other parts of the body, and usually is in various stages of evolution (from vesicles to crusted scabs) by the time of presentation.
    • One in 400 cases can be complicated by pneumonia, which typically appears 3-5 days into the illness and is associated with tachypnea, cough, dyspnea, and fever, although some patients may be asymptomatic; one study in military personnel noted that only 25% of those with VZV pneumonitis experienced cough and 10% had tachypnea.45
  • Measles 
    • Incubation period is 10-14 days after exposure, after which a prodrome of fever, malaise, anorexia, conjunctivitis, cough, and coryza ensue. Toward the end of the prodrome, Koplik spots (small white punctate lesions) may appear on the buccal mucosa. The rash is an erythematous, maculopapular eruption that may become confluent, beginning on the face, then progressing down the body to involve the extremities last, including palms and soles. Duration of the rash is approximately 5 days, after which it may desquamate. Duration of symptoms is usually 10 days, and the cough may be the last symptom to disappear.
    • In adults, 3% of measles cases are complicated by significant pneumonia requiring hospitalization, whereby 17% of patients had bronchospasm and 30% experienced bacterial superinfection. The pulmonary findings parallel the cutaneous signs, and the severity of pneumonia correlates with worsening rash.
  • Cytomegalovirus 
    • Symptoms in the immunosuppressed host are rapid onset of fever, nonproductive cough, dyspnea, and hypoxia.
    • In allogeneic HSCT recipients, CMV disease presents post engraftment (30-99 d after transplantation) and late (>100 d) in those with graft versus host disease and/or on higher-dose immunosuppressive therapy. CMV pneumonia is seen in 10-30% of such patients, and the median time to occurrence is 44 days after transplantation.
    • Autologous HSCT recipients are at much lower risk for CMV pneumonia, seen in only 1-9% of cases, oftentimes with milder symptoms.
    • Among SOT recipients, CMV pneumonia is most common in lung transplantations, ranging from 15-55% of cases. Typically, this pneumonia develops between day 15-60 post transplantation and is characterized by fever, cough, and hypoxia. In CMV donor-positive/recipient-negative cases, the onset and progression can be rapid.
    • Other solid organ transplantations are associated with low rates of CMV pneumonia: liver, 9.2%; heart, 0.8-6.6%; and kidney less than 1%.
  • Herpes simplex virus 
    • This virus only causes pneumonia in the most severely immunocompromised patients.
    • The spectrum of respiratory diseases due to HSV infection ranges from oral pharyngitis to membranous tracheobronchitis and diffuse or localized pneumonia, which can proceed to ARDS.
    • Dyspnea, cough, fever, tachypnea, intractable wheezing, chest pain, and hemoptysis are common symptoms of HSV pneumonia.
  • Hantavirus 
    • HPS is characterized by 4 clinical phases, as follows: (1) prodrome, (2) noncardiogenic pulmonary edema/adult respiratory distress syndrome and shock, (3) diuresis, and (4) convalescence.
    • Fever and myalgia are prominent in almost all phases and precede the onset of respiratory symptoms by 1-10 days.
    • These patients often complain of severe back and hip pain, and they develop nausea, vomiting, abdominal pain, and diarrhea.
    • Dry cough and shortness of breath herald the development of pulmonary edema. The onset of the shock and pulmonary edema phase is abrupt and dramatic.
    • The interval between the onset of dyspnea and respiratory failure requiring ventilatory support may be a few hours; the earliest indication is hypoxemia.

Physical

The physical examination findings are similar to those of pyogenic pneumonia and are nonspecific. Physical examination demonstrates wheezing, crackles, increased fremitus, and bronchial breath sounds over the involved regions of the lungs.

  • In varicella zoster, pneumonia usually develops 2-5 days after the onset of fever and rash. The characteristic chickenpox rash is a clue to pulmonary involvement.
  • Patients with measles develop a characteristic erythematous macular rash, which becomes confluent and starts from the face and then progresses to the trunk and extremities; desquamation occurs in the latter phase. In atypical measles, which occurs in patients immunized from 1963-1967 with a killed vaccine, the rash starts in the hands and feet rather than in a central distribution. Patients with measles also develop conjunctivitis and Koplik spots (small white punctate lesions of the buccal mucosa) that generally appear before the rash.
  • HSV pneumonia often is preceded by oral mucocutaneous lesions or esophagitis. Therefore, the presence of cutaneous, genital, or oral lesions may herald pulmonary or disseminated disease.

Causes

The following are the common viruses known to cause pneumonia in healthy or immunocompromised children and adults:

  • Children 
    • Respiratory syncytial virus
    • Influenza viruses A and B
    • Parainfluenza virus
    • Adenovirus
    • Human Metapneumovirus
    • Coronavirus
    • Measles virus (if not vaccinated)
  • Immunocompetent adults 
    • Influenza viruses A and B
    • Adenovirus
    • Respiratory syncytial virus
    • Parainfluenza virus
    • Coronavirus
    • Varicella-zoster virus
  • Immunocompromised hosts 
    • Cytomegalovirus
    • Herpes simplex virus
    • Influenza
    • Respiratory syncytial virus
    • Parainfluenza virus
    • Adenovirus
    • Varicella-zoster virus

More on Pneumonia, Viral

Overview: Pneumonia, Viral
Differential Diagnoses & Workup: Pneumonia, Viral
Treatment & Medication: Pneumonia, Viral
Follow-up: Pneumonia, Viral
Multimedia: Pneumonia, Viral
References
Further Reading
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References

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Keywords

viral pneumonia, viral respiratory tract infections, influenza virus, respiratory syncytial virus, RSV, parainfluenza virus, PIV, Orthomyxoviridae, severe acute respiratory syndrome, SARS, avian influenza, swine flu

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Contributor Information and Disclosures

Author

Arthur Jeng, MD, Assistant Professor of Clinical Medicine, University of California at Los Angeles School of Medicine
Arthur Jeng, MD is a member of the following medical societies: Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Nader Kamangar, MD, FACP, FCCP, FAASM, Associate Professor of Clinical Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Multi-campus Pulmonary and Critical Care Fellowship Program, University of California, Los Angeles, David Geffen School of Medicine; Medical Director, Hospitalist/Intensivist Program, Olive View-UCLA Medical Center; Associate Program Director, Combined Pulmonary and Critical Care Fellowship Program, Cedars-Sinai/Olive View-UCLA Medical Center/West Los Angeles Veterans Affairs Medical Center
Nader Kamangar, MD, FACP, FCCP, FAASM is a member of the following medical societies: American Academy of Sleep Medicine, American Association of Bronchology, American College of Chest Physicians, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, California Thoracic Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital
Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Mark R Wallace, MD, FACP, FIDSA, Clinical Professor of Medicine, Florida State University College of Medicine; Infectious Disease Fellowship Director, Orlando Regional Medical Center
Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Tropical Medicine and Hygiene, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

 
 
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