Diagnostic Considerations

Studies document that patients are frequently infected with both bacterial and viral pathogens, making it impossible to rule out bacterial disease even when rapid viral test results are positive. Additionally, no unique identifying clinical characteristics are present that allow the physician to differentiate viral disease from bacterial disease in the emergency department (ED).

Although the most common cause of community-acquired pneumonia remains Streptococcus pneumoniae (a fact that may change with the increasing use of pneumococcal vaccines), in as many as 40-60% of patients with community-acquired pneumonia, the etiologic agent is not identified. Furthermore, convincing associations between the patient's symptoms, physical findings, laboratory test results, and specific etiologies are lacking.

Therefore, no way of accurately determining the etiology of pneumonia during the initial visit to the ED exists. Obtaining a chest radiograph in patients with suspected pneumonia is recommended, both to find complications, such as pleural effusions, and to discourage the use of antibiotics in healthy patients with bronchitis rather than pneumonia.

Influenza viruses are the most common cause of viral pneumonia in civilian adults. Influenza usually is seen in epidemics and pandemics. Influenza A is the serotype most frequently responsible for major epidemics and pandemics; it is the most frequent cause of viral pneumonia in adults.

Influenza epidemics occur during the winter months and are associated with significant morbidity and mortality. Patients with chronic obstructive pulmonary disease (COPD), 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.

Patients with high-grade fever, myalgias, and cough during the winter months should be suspected to have influenza. If test results are negative for influenza, RSV pneumonia should also be suspected during the winter in patients with coryza, wheezing, low-grade fever, and patchy infiltrates on chest radiographs. Because clinical features and periods of activity for many viruses overlap, laboratory confirmation of influenza is recommended for cases involving patients who are seriously ill or institutionalized.

Viral pathogens and host factors

Patient age and immune status can offer a clue to the possible etiology of viral pneumonia. The following viruses commonly cause pneumonia in children:

Respiratory syncytial virus
Influenza viruses A and B
Parainfluenza virus
Adenovirus
Human metapneumovirus
Coronavirus
Measles virus (in unvaccinated children)

The following viruses commonly cause pneumonia in immunocompetent adults:

Influenza viruses A and B
Adenovirus
Respiratory syncytial virus
Parainfluenza virus
Coronavirus
Varicella-zoster virus

The following viruses commonly cause pneumonia in immunocompromised hosts:

Cytomegalovirus
Herpes simplex virus
Influenza
Respiratory syncytial virus
Parainfluenza virus
Adenovirus
Varicella-zoster virus

Differential Diagnoses

Workup

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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