Sections

Presentation

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 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.^[3]Most patients have cough, but in elderly persons, this may be only scant.

Ascertaining immunization status, travel history, and possible exposure is important. During outbreaks with the usual respiratory viruses, the signs and symptoms can suggest the correct diagnosis in most cases. In very elderly persons, the only complaint may be fever and change in mental status.

In immunocompromised patients, recognition of the clinical picture of viral pneumonia, risk factors, and new changes in clinical parameters is important. All of these findings can indicate the need for further imaging or other diagnostic procedures to make an etiologic diagnosis and to start early treatment.

The typical infection with influenza virus presents with 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. Influenza is usually seen in epidemics and pandemics in late winter and early spring.

Peak attack rates for respiratory syncytial virus (RSV) occur in the winter in infants younger than six months. Parainfluenza (PIV) infection most often occurs in the late fall or winter, although PIV-3 pneumonia is especially common in the spring.

Physical Examination

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

Some patients have few, if any, physical findings other than mild fever, whereas other patients may have respiratory and/or multiorgan failure. Other findings include the following:

Fever and/or chills
Cough (with or without sputum production)
Tachypnea and/or dyspnea
Tachycardia or bradycardia
Wheezing
Rhonchi
Rales
Sternal or intercostal retractions
Dullness to percussion
Decreased breath sounds
Pleurisy
Pleuarl friction rub
Cyanosis
Rash
Acute respiratory distress

Influenza virus

Influenza pneumonia especially affects the following groups of patients:

Children with cystic fibrosis or organ transplants
Adults with chronic cardiovascular or respiratory disease, diabetes mellitus, renal diseases, hemoglobinopathies, or immunosuppression
Residents of nursing homes or chronic care facilities
Healthy adults older than 65 years.

The three clinical forms of influenza pneumonia are primary influenza pneumonia, secondary bacterial pneumonia, and mixed viral and bacterial pneumonia.

Primary influenza pneumonia manifests with persistent symptoms of cough, sore throat, headache, myalgia, and malaise for more than 3-5 days. The symptoms may worsen with time, and new respiratory symptoms, such as dyspnea and cyanosis, may appear. This form is the least common but the most severe in terms of pulmonary complications.

Secondary bacterial pneumonia is characterized by the relapse of high fever, cough with purulent sputum after initial improvement, and radiographic evidence of new pulmonary infiltrates. The most common pathogen is Streptococcus pneumoniae (48%), followed by Staphylococcus aureus,^[59]Haemophilus influenzae, and Gram-negative pathogens.

Elderly persons may have a lower frequency of upper respiratory complaints. One study demonstrated 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 chronic cognitive impairment. Gastrointestinal complaints and myalgia are more common in influenza than in RSV infection.^{[50, 60]}

Avian influenza (H5N1) has an incubation period of 2-5 days, but symptoms may begin up to seven 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.^[61]

H1N1 influenza 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.

Mixed viral and bacterial pneumonia is common and can manifest as a gradual progression of disease or as a transiently improving condition followed by a worsening one. Both bacterial pathogens and an influenza virus are isolated.

Respiratory syncytial virus

Risk factors for RSV infection include age younger than six months, underlying lung disease (bronchopulmonary dysplasia or cystic fibrosis), and congenital heart disease in children with asthma. Institutionalized elderly and immunosuppressed patients (eg, those with severe combined immunodeficiency, leukemia, and/or transplant) are also at risk.

RSV infections in adults are poorly characterized and rarely diagnosed. They are accompanied by long-lasting upper respiratory tract infections and are more commonly associated with a prolonged productive or bronchitic cough and wheezing than with other features. The findings tend to mimic the decompensated underlying cardiopulmonary disease rather than the acute viral disease.

Various studies reported RSV pneumonia in recipients of solid organ transplants or HSCTs. The clinical manifestations are usually severe, and supplemental oxygen and mechanical ventilation are required.

Severe cases of RSV giant-cell pneumonia have been reported in 4-10% of cases and also during concurrent viral infections with EBV, CMV, or adenovirus.

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.

Patients with RSV pneumonia typically present with fever, nonproductive cough, otalgia, anorexia, and dyspnea. Wheezes, rales, and rhonchi are common physical findings.

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 often associated with rhinorrhea, sputum production, and wheezing and less often associated with gastrointestinal complaints and fever.^{[1, 62]}

Immunocompromised hosts 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.

While most patients with RSV infection, including infants, have only upper respiratory symptoms, as many as 25-40% develop bronchiolitis and/or pneumonia. Statistics demonstrate that as many as 20-25% of infants with pneumonia who require hospitalization are infected with RSV.

Lower respiratory disease in infants is preceded by a prodrome of rhinorrhea and, perhaps, poor appetite. Low-grade fever, cough, and wheezing usually occur. The chest examination reveals tachypnea, rales, and fine wheezes. Disease from RSV in young, healthy adults is usually mild, although one study of community-acquired pneumonia showed RSV to be the third most common pathogen,^[62]after S pneumoniae and influenza viruses A and B.

During their first RSV infection, 25-40% of infants and young children have signs or symptoms of bronchiolitis of pneumonia, and 0.5-2% require hospitalization. Most pediatric patients hospitalized for RSV infection are younger than six months.

Parainfluenza virus

Clinical manifestations of PIV infection can range from mild upper respiratory tract infections (mainly in immunocompetent patients) to severe croup, bronchiolitis, or life-threatening pneumonia in the setting of immunosuppression. Incubation is 1-3 days. 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.

PIV-1 and PIV-2 produce croup in children that initially manifests as an upper respiratory tract infection followed by a barking cough, dyspnea, stridor, and chest-wall retractions. PIV-2 infections tend to be milder than PIV-1 infections. PIV-4 causes mild upper respiratory tract infection in both adults and children.

PIV-3 is the main strain that causes pneumonia and bronchiolitis. The signs and symptoms are nonspecific, more prominent in children, and similar to, but milder than, those of RSV pneumonia. They include fever, cough, coryza, dyspnea with rales, and wheezing.

Immunosuppression promotes the development of PIV pneumonia. Situations leading to immunosuppression include the following: BMT, solid-organ transplantation (with mild forms), severe combined immunodeficiency in children, or therapy with etanercept.

PIV infection may appear as giant-cell pneumonia. This form is most frequent in immunocompromised patients (after BMT or umbilical-cord transfusion) and rarely associated with alveolar proteinosis. The mortality rate approaches 100% in children, with a better prognosis than this in adults.

PIV pneumonia may mimic other lung infections most commonly encountered in an immunocompromised host. Several clinical findings tend to distinguish PIV or RSV lung infection from CMV or other opportunistic forms of pneumonia: upper respiratory infection before lung infection, clinical and imaging evidence of sinusitis, and wheezing.

As many as one third of children with PIV infection can have bacterial superinfection. Even if long-term sequelae are uncommon, cryptogenic organizing pneumonia is described after PIV infection.

Human metapneumovirus

Symptoms of human metapneumovirus (hMPV) infection are similar to those caused by 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.^[22]

In different studies, cough was reported in 90% of patients; dyspnea, in 83%; coryza, in 88%; and fever, in 52-92%. Among the physical signs, rales, wheezing, or stridor were found in one half of infected children. In children, hMPV is an important cause of wheezing (9% in a 132 case series). Fever, cough, dyspnea, and sore throat are commonly described in adults. In HSCT recipients, hMPV pneumonia is reported and tends to cause respiratory failure.

Coronavirus

The incubation period is 2-5 days, with a mean of 3 days. Symptoms are similar to those from other respiratory viruses, including cough, rhinorrhea, sore throat, headache, and malaise, although fever was only seen in 21-23% of cases.

Varicella-zoster virus

The initial presenting symptoms of VZV infection 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. VZV pneumonia develops in 1 in 400 cases.

VZV pneumonia starts gradually within 1-6 days after the rash appears and manifests with fever, chest tightness, tachypnea, dyspnea, dry cough, cyanosis, and (in rare cases) pleuritic chest pain and hemoptysis. Physical examination reveals minimal findings, with rare rhonchi or wheezes. New chest symptoms are strongly associated with radiologic findings. VZV pneumonia can develop as a mild disease, or it can be severe and rapidly fatal, especially in immunocompromised individuals.

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.^[63]

Risk factors related to VZV pneumonia are smoking, pregnancy (third trimester), immunosuppression, and male gender. The presence of more than 100 spots during the skin eruption, prolonged fever, a history of contact with an index case, and chest symptoms at presentation are also reported risk factors.

Measles virus

The incubation period of measles 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.

Atypical measles occurs in patients who were immunized from 1963-1967 with a killed vaccine and are exposed to measles virus or live measles virus vaccine. In these cases, the rash starts in the hands and feet rather than in a central distribution.

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, with 17% of patients experiencing bronchospasm and 30%, bacterial superinfection. Bacterial superinfection most often occurs 5-10 days after the onset of the rash. The pulmonary findings parallel the cutaneous signs, and the severity of pneumonia correlates with worsening rash.

Persons at risk for measles-virus pneumonia are those with T-cell immunosuppression (eg, those taking steroids), BMT recipients, and those with HIV infection, lymphoma, leukemia, or Epstein-Barr virus infection. Others at risk are children and the elderly, pregnant women, those with vitamin A deficiency, and persons not vaccinated or those in whom primary vaccination failed.

Four types of measles-associated pneumonia are encountered. The first, measles-virus pneumonitis, usually appears within a few days after the onset of rash. High levels of KL6 (a glycoprotein secreted by pneumocyte-2) are markers for interstitial pneumonia and are associated with a poor prognosis.

The second form, bacterial superinfection, usually develops several days after rash appears. This type manifests with cough, fever, purulent expectoration, tachycardia, and pleural pain.

Third, giant cell pneumonia typically develops before or with the peak of viral exanthema. In rare cases, it develops after five months or longer. Rash may be absent. Cough may persist for 1-2 weeks during recovery. Lung biopsy may be needed for final diagnosis.

Fourth, pneumonia of atypical measles is described in adults. These patients developed a potentially fatal illness, with increased fever (7-14 d after exposure), minimal or absent rashes, headache, arthralgias, hepatitis, interstitial or nodular infiltrates, hilar lymphadenopathy, and occasional pleural effusions.

Cytomegalovirus

CMV pneumonia is usually mild in otherwise healthy individuals. It starts as a mononucleosis-like syndrome (eg, malaise, fever, myalgias) with mild hepatitis and no lymphadenopathy or splenomegaly.

In immunocompromised people, the clinical picture may vary. Most commonly, asymptomatic shedding affects pulmonary secretions, blood, and urine, with no clinical significance and low mortality rates.

CMV syndrome manifests with self-limited fever and constitutional symptoms (fever, malaise, anorexia, myalgias, arthralgias, fatigue). CMV syndrome precedes CMV pneumonitis by 1-2 weeks and usually has a sudden onset, with respiratory complaints (cough, dyspnea, tachypnea), fever, an increased A-a gradient, and radiologic infiltrates. The duration is less than two weeks. See the A-a Gradient calculator.

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 solid organ transplant 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%.

For BMT recipients, risk factors include pretreatment seropositivity, total-body irradiation, certain immunosuppressive treatment, severe acute or chronic graft-versus-host disease, underlying disease (acute lymphoblastic leukemia [ALL] or chronic lymphocytic leukemia [CLL]). Patients with primary CMV infection and allogeneic HSCT are at increased risk for severe disease.

In HIV patients, the pathogenic significance of CMV is considered low, even in the condition of common identification of viruses in bronchoalveolar lavage (BAL) and biopsy specimens. CMV pneumonia is found in HIV patients with a CD4 count of less than 200 cells/µL. CMV is thought to be a co-pathogen to Pneumocystis jiroveci and a cause of alveolar hemorrhage in HIV patients (due to thrombotic microangiopathy).

Clinical outcomes range from mild, self-limited illness to rapidly fatal infection with multiorgan involvement (retinitis, colitis, hepatitis). The mortality rate can be high.

CMV complicated by obstructive bronchiolitis in heart-lung and double-lung recipients affected 47% of 36 patients in a study in France. Risk factors were CMV seropositivity among donors and CMV pneumonia or CMV recurrence.

Herpes simplex virus

Herpes simplex virus causes pneumonia in only the most severely immunocompromised patients. HSV is not usually isolated from immunocompetent patients, or even from BAL fluid from HIV-infected patients. The rate of HSV pneumonia can be as high as 70-80% in HSCT recipients not receiving prophylaxis, and it can be decreased to 5% with acyclovir prophylaxis.

HSV pneumonia often is preceded by oral mucocutaneous lesions or esophagitis. The presence of mucocutaneous disease, esophagitis, or tracheitis, especially with endotracheal intubation, increases the likelihood of this pneumonia. 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.

In BMT recipients, the usual presentation of HSV pneumonitis consists of dyspnea, fever, cough, and hemoptysis with associated dysphagia, liver, and CNS involvement. HSV pneumonia in organ-transplant recipients is reported.

In ICU patients, HSV pneumonia manifests as an unexplained dyspnea or as a failure of weaning the patient from a ventilator. One study showed that most ICU patients had been intubated (95%) or had undergone thoracic surgery (73%) at the time of diagnosis. Blood transfusions, use of corticosteroids and other immunosuppressants, local trauma, smoking, and burns are risk factors.

Dyspnea, cough, fever, tachypnea, intractable wheezing, chest pain, and hemoptysis are common symptoms of HSV pneumonia.

Hantavirus

Hantavirus pulmonary syndrome (HPS) has an incubation period of 9-35 days.

HPS is characterized by four clinical phases, as follows:

Prodrome
Noncardiogenic pulmonary edema/adult respiratory distress syndrome and shock
Diuresis
Convalescence

Fever and myalgia are prominent in almost all phases and precede the onset of respiratory symptoms by 1-10 days. Cough and upper respiratory symptoms are uncommon, in contrast to many of the other viral prodromes to pneumonia. 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.

Onset and rapid progression of cough, shortness of breath, fever, and hypotension herald the cardiopulmonary phase of the disease. Progressive pulmonary edema and respiratory failure can occur in 80-90% of patients within two days of hospitalization. The interval between the onset of dyspnea and respiratory failure requiring ventilatory support may be a few hours. The earliest indication is hypoxemia.

In addition to the rapidly progressive, fulminant, and often fatal form of HPS, there is also a limited, less severe form associated with mild interstitial edema and minimal airspace disease.

Adenovirus

Symptoms of adenovirus infection 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 the former, and 2, 3, 5, 40, 41 causing the 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%).^[18]

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.^[42]

Avian influenza

Avian influenza has a fulminant course and a high mortality rate. The clinical symptoms of avian influenza depend on the etiologic agent. Those infected with A/H7N7 have conjunctivitis and/or an influenzalike illness. In the 1997 outbreak of A/H5N5, 11 of 18 patients were younger than 14 years. Gastrointestinal symptoms of abdominal pain, diarrhea, and vomiting were prominent. Seven recovered, but 11 progressed to pneumonia and six died of ARDS or multiorgan failure.

In the 2004 outbreak, the young were affected more frequently, diarrhea was again prominent, fever was universally present, and the main presenting syndrome was community-acquired pneumonia. Lymphopenia and thrombocytopenia were common findings in all series of outbreaks and were prognostic indicators of ARDS and death. The case-fatality rate ranged from 64-80%. The incidence of asymptomatic or mild infection is unknown.

Epstein-Barr virus

Lung involvement secondary to EBV infection is rare and can occur as a complication of infectious mononucleosis. In healthy individuals, pulmonary manifestations, such as dyspnea and cough, are rare. Chronic interstitial lung disease is reported in immunocompetent patients.

In children with cystic fibrosis, EBV can cause deterioration in pulmonary function that lasts longer than six months after the infection is diagnosed.

In HIV patients, relatively few studies have been conducted to investigate EBV-related pulmonary disease. EBV seems to be related to the development of AIDS-associated non-Hodgkin lymphoma. BAL fluid samples from 72 European patients with AIDS were positive for EBV in five. The patients had fever and low PaO₂, with no radiographic infiltrates, and recovery was the rule.

In BMT recipients, EBV-related lung manifestations are among widespread extrarenal manifestations of posttransplant lymphatic disease. A fulminant presentation soon after transplantation is associated with a dire prognosis. Young age and primary infection are risk factors. Patients with EBV infection are at subsequent risk for other viral lung superinfection (eg, severe RSV or Mycoplasma pneumoniae infection).

Human herpesvirus

HHV 6 (A and B) and HHV 7 have a limited clinical significance and prevalence as lung pathogens. HHV 6 appears in healthy individuals or HIV-infected patients with a high CD4⁺ count, in whom it may result in further immunosuppression. HHV 8 is an important pathogen in HIV patients with a 200 CD4⁺ count of less than 200 cells/µL and has been associated with Kaposi sarcoma in the lungs, sometimes with alveolar hemorrhage.

Human immunodeficiency virus

HIV pneumonitis usually manifests as several months of mild cough and dyspnea and bilateral infiltrates on chest radiograph. Transbronchial biopsy is usually required for diagnosis. The differential diagnosis includes Pneumocystis pneumonia.

Human lymphotropic virus

HTLV-1–related lung inflammatory disorders (eg, bronchopneumopathy associated with HTLV-1) encountered in HTLV-1 carriers include lymphocytic interstitial pneumonia, diffuse panbronchiolitis, bronchiectasis, and bullous lung disease.

Rhinovirus

Rhinoviruses are a common cause of upper respiratory tract infection, but in rare cases they can trigger lower respiratory tract infections, too. Rhinoviruses commonly cause exacerbations of preexisting airway disease in those with asthma, chronic obstructive pulmonary disease (COPD),^[64]or cystic fibrosis.

Rhinovirus-induced lower respiratory infections in children include bronchiolitis or bronchitis (25.6%), pneumonia (6.2%), and acute episodes of asthma (5.7%). Among 211 French children hospitalized with rhinovirus infection, 29% had ARDS. In addition, 9% of children had an associated bacterial infection, and 9% had a dual viral involvement.

Rhinoviral infection can be complicated by S pneumoniae superinfection. This might be explained by increased adherence of this virus to epithelial tracheal cells after rhinoviral infection.

Rotavirus

Rotavirus pneumonia is rare. In one study, rotaviruses were isolated in 27% of all tracheal aspirates from children with pneumonia. One case of fatal rotaviral pneumonitis with myocarditis was reported in a two-year-old boy.

Two cases of fatal rotaviral pneumonitis were reported in adults. One patient was receiving long-term steroid therapy and developed rapidly progressive respiratory distress that evolved into severe respiratory failure not responsive to supportive measures. The other patient presented with massive pulmonary edema and pleural effusions.

Transplantation-related pneumonia

In recipients of thoracic organ transplants, chest complications, though rare, may manifest as tracheobronchitis, localized viral pneumonia, or diffuse and bilateral pneumonic infiltrates involving mainly the lower lobes. These findings may develop secondary to bacterial pneumonia, bronchiolitis obliterans syndrome, or acute allograft rejection. Mild clinical manifestations occur in 64% of lung transplant recipients with lung infection due to influenza virus or PIV.

Complications

Most viral pneumonias in immunocompetent hosts resolve with few sequelae. However, respiratory failure may develop secondary to superimposed bacterial infection.

Secondary bacterial infections are common. Common organisms are Streptococcus pneumoniae, Staphylococcus aureus,Streptococcus pyogenes (group A Streptococcus), and Haemophilus influenzae.

Late sequelae of viral pneumonias include bronchitis and bronchiolitis, especially following infection with RSV and influenza viruses.

Adenovirus serotypes 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. An estimated 14-60% of these children will suffer some degree of permanent lung damage. Serious sequelae occurred in patients who survive severe infection with adenovirus 14.

A retrospective cohort study of 100 children with RSV revealed a 79% complication rate. Nearly 24% were considered serious, and 16% of children required mechanical ventilation. The authors concluded that RSV infections in children considerably lengthen their hospital stay and medical costs. In fact, hospital costs approach $1 billion annually in the United States. In addition, 20% of all patients are rehospitalized, and more than 40% develop asthma.

Complications of RSV pneumonia in children are a considerable burden on hospital costs. About 60% of the complications are respiratory and consist of respiratory failure, apnea, stridor, hemoptysis, infiltrates and/or atelectasis, hyperinflation, pneumothorax, or pleural effusions. About 15% of radiographs are described as normal in children with complications. Prematurity and congenital diseases are risk factors for complications.

Viral (mainly PIV) or bacterial (especially S pneumoniae) superinfections, tuberculosis reactivation, and subsequent bronchiectasis are complications of measles pneumonia.

Temporary decreases in the forced expiratory volume in 1 second (FEV₁) and/or forced vital capacity (FVC) or a permanent decrease in the lung transfer factor for carbon monoxide (TLCO) are reported in patients with VZV pneumonia. One case of VZV pneumonia complicated by a bacterial lung abscess in a child is reported.

Differential Diagnoses

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Media Gallery

Pneumonia, viral: A 52-year-old woman developed fever, cough, and dyspnea. She also developed a rash that was prominent over the face and the trunk. The chest radiograph showed interstitial infiltrates, with suggestion of a micronodular process. The Tzanck smear results from the skin vesicle suggest varicella-zoster virus.
Pneumonia, viral: A 52-year-old woman developed fever, cough, and dyspnea. She also developed a rash that was prominent over the face and the trunk. The chest radiograph showed interstitial infiltrates, with suggestion of a micronodular process. The Tzanck smear results from the skin vesicle suggest varicella-zoster virus. She was treated with acyclovir; resolution of varicella-zoster virus infection occurred after 7 days of therapy.
Bilateral interstitial infiltrates in a 31-year-old patient with influenza pneumonia.
Right-middle-lobe infiltrate in a 2-month-old boy with pneumonia due to respiratory syncytial virus (RSV).
High-power Papanicolaou (Pap) stain showing a virus on a bronchial wash. Viruses in general show "smudgy" nuclei, may or may not show nuclear or cytoplasmic inclusions, and may demonstrate other features such as multinucleation or margination of chromatin to the periphery of the cell nucleus. Certain features are more indicative of one virus over another. This is an example of herpes virus (cells infected are located in the center right).
High-power Papanicolaou (Pap) stain of cytomegalovirus (center). This cell has a very large, dark intranuclear inclusion.
High-power hematoxin-and-eosin stain of giant cell pneumonia following measles. A multinucleated cell (center) contains eosinophilic intranuclear inclusions.
High-power hematoxin-and-eosin stain of numerous cells infected with the cytomegalovirus (large cells with enlarged nuclei containing dark-purple intranuclear inclusions surrounded by a clear halo).
High-power hematoxin-and-eosin stained herpes simplexvirus, characterized by "smudgy" degenerating nuclei. Some cells are multinucleated with margination of the chromatin to the periphery of the nuclei and molding of the nuclei to each other.

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Table 1. Diagnostic Techniques Used for Viral Pneumonia

Virus	Viral Culture	Cytologic Evaluation	Rapid Antigen Detection	Gene Amplification
Influenza virus	HA^a, SV^b		IF^c, ELISA^d	RT-PCR^e
Adenovirus	CE^f, SV	Intranuclear inclusions	IF, ELISA	RT-PCR
Paramyxoviruses
Respiratory syncytial virus	CE, SV	Eosinophilic cytoplasmic inclusions	IF, ELISA	RT-PCR
Parainfluenza virus	HA, SV	Eosinophilic intranuclear inclusions	IF, ELISA	RT-PCR
Measles virus	HA
Herpes viruses
Herpes simplex virus	CE, SV	Cytoplasmic inclusions	IF, ELISA	PCR
Varicella-zoster virus	CE	Cytoplasmic inclusions	IF	RT-PCR
Cytomegalovirus	CE, SV	"Owl's eye" cells	IF, ELISA	RT-PCR
Hantavirus			Antibodies against FCV^g	FVC RNA by RT-PCR
^a HA - Hemaglutination ^b SV - Shell viral culture ^c IF - Immunofluorescence ^d ELISA - Enzyme-linked immunosorbent assay ^eRT-PCR - Reverse transcriptase polymerase chain reaction ^fCE - Cytopathogenic effects ^gFCV - Four corners virus

Table 2. Treatment and Prevention of Common Causes of Viral Pneumonia

Virus	Treatment	Prevention
Influenza virus	Oseltamivir Peramivir Zanamivir	Influenza vaccine^[78] Chemoprophylaxis with: Zanamivir Oseltamivir
Respiratory syncytial virus	Ribavirin	RSV vaccine (adults ≥ 60 y) Palivizumab or nirsevimab (children < 2 y)
Parainfluenza virus	Ribavirin
Herpes simplex virus	Acyclovir
Varicella-zoster virus	Acyclovir	Varicella-zoster immunoglobulin
Adenovirus	Ribavirin
Measles virus	Ribavirin	Intravenous immunoglobulin
Cytomegalovirus	Ganciclovir Foscarnet	Intravenous immunoglobulin

Table 3. Characteristics of Anti-Influenza Drugs

	Amantadine (Symmetrel)	Rimantadine (Flumadine)	Zanamivir (Relenza)	Oseltamivir (Tamiflu)
Mechanism of action	M2 ion channel blockade inhibits HA^a cleavage beta block RNA encoding, which reduces early viral replication.		Viral NA^b inhibition prevents sialic acid cleavage from HA beta virus gets trapped inside cells, and epithelial spread is blocked.
Spectrum	Influenza A only	Influenza A only	Influenza A and B	Influenza A and B
Oral bioavailability	Good	Good	Poor	Good
Protein binding, %	67	40	None	Minimal
Half-life, h	12-18	24-36	2.5-5	1-3
Excretion	Renal (not removed by hemodialysis)		Renal and gastrointestinal	Renal
Drug interaction	Synergistic CNS toxicity with antihistamines, anticholinergics, CNS stimulants	Beta Plasma level: ASA^c, acetaminophen	None	None
Renal clearance	TMP-SMZ^d, triamterene, hydrochlorothiazide, quinine sulfate, quinidine	Cimetidine	None	None
^a HA - Hemagglutinin ^b NA - Neuraminidase ^c ASA - Acetylsalicylic acid ^d TMP-SMZ - Trimethoprim and sulfamethoxazole

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Author

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Coauthor(s)

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.

Nader Kamangar, MD, FACP, FCCP, FCCM Professor of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Pulmonary and Critical Care Medicine, Vice-Chair, Department of Medicine, Olive View-UCLA Medical Center

Nader Kamangar, MD, FACP, FCCP, FCCM is a member of the following medical societies: Academy of Persian Physicians, American Academy of Sleep Medicine, American Association for Bronchology and Interventional Pulmonology, American College of Chest Physicians, American College of Critical Care Medicine, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, Association of Pulmonary and Critical Care Medicine Program Directors, Association of Specialty Professors, California Sleep Society, California Thoracic Society, Clerkship Directors in Internal Medicine, Society of Critical Care Medicine, Trudeau Society of Los Angeles, World Association for Bronchology and Interventional Pulmonology

Disclosure: Nothing to disclose.

Chief Editor

John J Oppenheimer, MD Clinical Professor, Department of Medicine, Rutgers New Jersey Medical School; Director of Clinical Research, Pulmonary and Allergy Associates, PA

John J Oppenheimer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, New Jersey Allergy, Asthma and Immunology Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Amgen; GSK; Aquestive; Aimmune<br/>Clinical Adjudication/Data Safety Monitoring Board for AZ, GSK, Abbvie, Sanofi; Executive Editor for Annals of Allergy, Asthma & Immunology; Editor for Medscape; Reviewer for UpToDate; Honoraria from American Board of Allergy and Immunology.

Acknowledgements

Shakeel Amanullah, MD Consulting Physician, Pulmonary, Critical Care, and Sleep Medicine, Lancaster General Hospital

Shakeel Amanullah, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine