Sections

Treatment

Approach Considerations

All viral pneumonia patients must receive supportive care with oxygen, rest, antipyretics, analgesics, nutrition, and close observation. See Table 2 below.

Table 2. Treatment and Prevention of Common Causes of Viral Pneumonia (Open Table in a new window)

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

Supportive Care

Oxygen should be administered to patients with hypoxemia or shortness of breath. Emergency medical personnel should administer oxygen if the patient is dyspneic. Some prehospital providers can deliver aerosol treatments with beta-agonists, which may improve the patient's breathing. Patients with respiratory failure require endotracheal intubation and ventilator support.

Isotonic sodium chloride solution should be administered to patients who are in shock and have no component of heart failure.

Acute care may involve use of the following:

Oxygen, if the patient is dyspneic
Beta-agonists, if bronchospasm is present
Fluids, if dehydration is present
Acyclovir, if varicella or herpes pneumonia is suspected
Respiratory isolation
Antibiotics, if infiltrate is seen on the chest radiograph
Mechanical ventilation if respiratory failure is present or impending

Influenza Pneumonia

Antiviral therapy is available for the treatment of influenza virus infection. The treatment of uncomplicated influenza is supportive in nature, consisting of rest and administration of antipyretics and analgesics. See Table 3 below.

Table 3. Characteristics of Anti-Influenza Drugs (Open Table in a new window)

	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

Amantadine hydrochloride and rimantadine hydrochloride are approved for the prevention and treatment of influenza A virus infection. They are not active against influenza B virus infection. Both drugs are absorbed well orally, block the viral M2 protein ion channel, and inhibit the uncoating of the virus. Rimantadine is a synthetic analog of amantadine and has comparable therapeutic efficacy.

Treatment with these compounds has been associated with the emergence of viral resistance. The clinical significance of this is not known. Many of the current strains are not susceptible to amantadine/rimantadine (including H1N1 influenza virus), so empiric use of these agents as the only drug is not recommended.

Oseltamivir, zanamivir, and peramivir block the neuraminidase surface protein on both influenza A and influenza B viruses.^{[79, 80, 81, 82, 83, 84]}

These drugs trap the virus inside the infected respiratory epithelial cells and prevent spread to other cells. They are active against both influenza A and influenza B viruses. These newer drugs have a different safety profile and lower potential for inducing resistance, but they are much more expensive.

Peramivir (Rapivab) was approved by the FDA in December 2014 for use in adults as a single 600 mg IV dose. It has since been approved for children aged 6 months and older. In clinical trials, a single intravenous dose of peramivir, a sialic acid analogue and a selective inhibitor of neuraminidases produced by influenza A and B viruses, is effective and well tolerated in subjects with uncomplicated seasonal influenza virus infection. At both 300 mg and 600 mg, peramivir significantly reduced the time to alleviation of symptoms in comparison with placebo.^[85]Additional data from over 2,700 subjects treated with peramivir in 27 clinical trials also supported its approval. It was available in the United States by emergency protocol during the 2009 H1N1 influenza pandemic.

The results of zanamivir studies have confirmed its efficacy only if therapy is started within 24-48 hours of symptom onset in febrile patients. Most studies have reported a similar window of opportunity for oseltamivir. Like the older agents, they reduce the course of influenza by approximately one day. Oseltamivir resistance emerged in the United States during the 2008-2009 influenza season.

For severe influenza pneumonia, antiviral medication should be given, even after the 48-hour window.

In a double-blind, randomized controlled trial, one inhalation of laninamivir octanoate was shown as effective for the treatment of seasonal influenza in adults. Effectiveness was also shown for the oseltamivir-resistant virus.^[86]

H1N1 influenza

In the 2009-2010 H1N1 influenza epidemic, the US Centers for Disease Control and Prevention (CDC) recommended oseltamivir or zanamivir for treatment of all hospitalized patients with suspected or confirmed cases and for outpatients at increased risk for complications of H1N1 infection.

As of September 2009, only 28 of 10,000 H1N1 isolates tested were resistant to oseltamivir (11 from the United States), and all were susceptible to zanamivir.

Although intravenous peramivir had not been formally FDA approved for the treatment of influenza during the 2009-2010 H1N1 pandemic, the FDA issued an emergency use authorization (EUA) for its use in hospitalized patients who had potentially life-threatening suspected or laboratory confirmed infection with H1N1. Under the EUA, treatment with IV peramivir was approved for patients who had not responded to either oral or inhaled antiviral therapy and/or drug delivery by a route other than IV that was not expected to be dependable or feasible.

Early administration of corticosteroids in patients with H1N1 who are admitted to the ICU has no apparent benefit.^[87]

Avian influenza

Avian H5N1 influenza should be treated with oseltamivir, even after the 48-hour window, because a reduction in mortality of hospitalized persons with seasonal influenza or avian influenza A (H5N1) virus infection was reported even when oseltamivir treatment was initiated later. The optimal duration and dose is not clear, but the WHO recommends consideration of higher dosage (eg, 150 mg PO bid) and longer duration in severe infections.

Avian H5N1 influenza has exhibited resistance to oseltamivir (clade 1 and subclade 2.1 with H274Y and N294S mutations). These resistant strains maintained susceptibility to zanamivir. Some viruses circulating in birds (subclade 2.3.4) demonstrated reduced susceptibility to zanamivir but sensitivity to the adamantanes (amantadine/rimantadine). Thus, for resistant strains (especially subclades 2.2 and 2.3.4), consideration for combination therapy with neuraminidase inhibitor-adamantane or oseltamivir-ribavirin, or even triple therapy with neuraminidase inhibitor-adamantane-ribavirin, should be given.^[61]

Respiratory Syncytial Virus Pneumonia

As with influenza, treatment of uncomplicated respiratory syncytial virus (RSV) infection is supportive in nature.

Ribavirin, a nucleoside analog of guanosine, is the only effective antiviral agent currently available for the treatment of RSV pneumonia.^[1]Ribavirin acts by interfering with viral transcription. This drug is delivered as a small-particle aerosol. Data conflict regarding the efficacy of ribavirin therapy in RSV pneumonia. Overall, the preponderance of data suggests a benefit of ribavirin therapy in high-risk patients, such as hematopoietic stem cell transplant (HSCT) recipients.

Current recommendations are that ribavirin therapy should be considered only for severe illness and in high-risk patients for whom RSV infection is associated with high mortality, such as HSCT recipients.^[62]In these hosts, high-dose, short-duration aerosolized ribavirin (60 mg/mL for 2 h given by mask tid) has been used.

RSV-specific intravenous immunoglobulin, such as palivizumab (Synagis), which is a monoclonal antibody directed against the RSV fusion (F) glycoprotein, has also been used with aerosolized and oral ribavirin in high-risk patients, such as HSCT recipients, because this combination has been shown to increase survival in this group.^[57]Its use is endorsed in some guidelines, although not universally accepted or recommended.^{[88, 89]}

Also, see Prevention regarding RSV vaccines

Adenovirus Pneumonia

Cidofovir has demonstrated good in vitro activity against adenoviruses, including serotype 14. Cidofovir has shown some efficacy in treating adenovirus infection in immunocompromised patients, especially HSCT recipients.^[90]The dose is 5 mg/kg/wk for two weeks, then every two weeks plus probenecid 1.25 g/m² given three hours before cidofovir and three and nine hours after each infusion. Alternate dosing is 1 mg/kg IV three times a week.

The in vitro activity of ribavirin against adenovirus, however, has been variable. For example, in one study, species C was susceptible to ribavirin, while other species were more variable.^[91]Some anecdotal reports exist regarding improvement in some patients with HSCT and leukemia, although other studies have not shown any efficacy. Thus, routine use of ribavirin is not recommended.^{[92, 93, 94]}

Parainfluenza Virus Pneumonia

Treatment is mainly supportive in nature. Ribavirin has documented in vitro activity against parainfluenza virus (PIV), and aerosolized and oral ribavirin were associated with reduction in PIV shedding and clinical improvement in immunocompromised patients. Thus, in this latter, high-risk group, the use of ribavirin may be reasonable.^[95]

Human Metapneumovirus Pneumonia

Although ribavirin has activity against human metapneumovirus (hMPV) similar to that which it has against RSV and although animal data have shown some promise, treatment data in humans are lacking, being confined to occasional case reports predominantly in the transplantation population.^{[96, 97]}

Immunoglobulin preparations (intravenous immunoglobulin [IVIG]) also seem to contain sufficient neutralizing titers, but this has not been extensively studied for use in hMPV pneumonia either—again with only isolated case reports in patients with transplantation, usually in combination with ribavirin.^[98]

Coronavirus Pneumonia

Protease inhibitors (eg, lopinavir/ritonavir) demonstrated antiviral activity against severe acute respiratory syndrome coronavirus (SARS-CoV) infection.^[99]Interferon alfa and interferon beta have activity against SARS-CoV in vitro and in animal models. Limited human data seemed to demonstrate some beneficial effect.^[100]

Ribavirin is not active against SARS-CoV in vitro, and studies have not shown clinical efficacy. Therefore, this medication is not recommended for this infection.^[100]

Varicella-Zoster Virus Pneumonia

Treatment of varicella pneumonia includes respiratory isolation until skin lesions heal, supportive care, administration of antiviral agents, and active and passive immunization. For treatment of documented varicella pneumonia in patients who are immunocompromised, acyclovir (10 mg/kg IV q8h for 7 d) has been shown to be effective.

For pregnant women in the third trimester, acyclovir at 10 mg/kg IV every eight hours for five days should be given, and consideration should be given for varicella-zoster immune globulin (VZIG) therapy.

Measles Pneumonia

Treatment of measles pneumonia generally is supportive in nature. Children infected with HIV and adults who are immunosuppressed with measles pneumonia have been treated successfully with intravenous (20-35 mg/kg/d for 7 d) and aerosolized ribavirin, similar to the therapy for severe infections with RSV.^[101]

Cytomegalovirus Pneumonia

The primary treatment for acute cytomegalovirus (CMV) pneumonia in the immunocompromised patient (both HSCT and solid organ transplant [SOT] recipients) is ganciclovir (5 mg/kg IV 12h for 14-21 d, followed by valganciclovir 900 mg PO qd for suppression). Ganciclovir prevents viral DNA replication by inhibiting the enzyme DNA polymerase.^[102]

High-dose intravenous immunoglobulin (CMV immunoglobulin or IVIG) has been used successfully in conjunction with ganciclovir for the treatment of CMV pneumonia, decreasing the mortality rate to 0-47%. Combination therapy is based on the premise that lung injury is not solely due to direct damage by the virus but is a result of virally induced immunological reaction. In lung transplant recipients, ganciclovir with CMV immunoglobulin or IVIG has been associated with increased survival.^[103]

Foscarnet sodium, an inhibitor of viral DNA polymerase and reverse transcriptase, is an alternative drug for use in ganciclovir-resistant CMV pneumonia. The combination of foscarnet with ganciclovir may provide antiviral synergy, but it requires careful monitoring.^[104]

Cidofovir represents a third option, but scant data exist regarding its use in CMV pneumonia.

Herpes Simplex Virus Pneumonia

Acyclovir inhibits viral DNA synthesis by competitively binding to viral DNA polymerase. Intravenous acyclovir (250 mg/m² q8h) currently is the treatment of choice for herpes simplex virus (HSV) pneumonia. Because a significant proportion of patients may have concomitant bacterial pneumonia, empirical broad-spectrum antibiotic therapy that includes an antistaphylococcal drug should be instituted in patients with progressive HSV pneumonia who are unresponsive to antiviral therapy.

Hantavirus Pneumonia

The treatment of hantavirus pulmonary syndrome (HPS) is supportive in nature and includes correction hypoxemia, lactic acidosis, and hypotension. Mechanical ventilation and optimal fluid management guided by hemodynamic monitoring are recommended, with avoidance of excessive administration of fluids and with use of cardiotonic drugs to counter the hemodynamic profile of decreased cardiac output and increased systemic vascular resistance. See the Cardiac Output calculator.

Although intravenous ribavirin has been associated with some success in the treatment of some Bunyaviridae viruses, such as Hantaan virus (hemorrhagic fever with renal syndrome), Rift Valley fever virus, and Crimean-Congo hemorrhagic fever virus, it has failed to show any efficacy in HPS, perhaps because death typically occurred within 24-48 hours of hospitalization.^[76]

Influenza

Annual fall vaccination of high-risk populations and healthcare workers is the most effective measure for decreasing morbidity and mortality from influenza.^[89]Each year's influenza vaccine contains the three virus strains (usually two type A strains and 1 type B strain) considered most likely to cause outbreaks based on epidemiologic surveillance.

In the United States, specific recommendations for vaccination against influenza are issued each year by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC).^[105]

The effectiveness of the vaccine depends on the age and general health status of the recipient and the antigenic similarity to the virus causing outbreaks that year. When the vaccine matches the prevalent influenza virus strain, the efficacy of the vaccine in healthy adults is reported to be in the range of 70-90%.

The effectiveness of widespread vaccination in elderly persons has been called into question. A recent meta-analysis of the efficacy, effectiveness, and safety of the influenza vaccine in patients older than 65 years found that vaccination is of benefit to residents of long-term care facilities but is of modest value in the community.^[106]However, the Centers for Disease Control and Prevention (CDC) still recommend immunization of all elderly patients.^{[105, 107]}

The CDC has recommended chemoprophylaxis in the following situations:

Close contacts of patients who are at high risk for complications of influenza.
Healthcare personnel, public health workers, and first responders who have had recognized and unprotected close contact exposure to a person with influenza during the person's infectious period (up to 7 d after onset of illness).

Chemoprophylaxis should be considered when outbreaks occur in nursing homes. Everyone in the institution, including the unvaccinated staff and other coworkers, should receive prophylactic therapy for at least two weeks during the outbreak.

The CDC issues updated interim guidance on antiviral treatment and prophylaxis of seasonal influenza, based on resistance patterns of the circulating viral strains.

Local influenza surveillance data and laboratory testing can also assist the physician regarding the antiviral agent choice.

Vaccines for avian H5N1 influenza are currently being developed and studied, and vaccinations have been performed in avian livestock (via whole-virus inactivated vaccine, recombinant fowlpox vaccine, and recombinant Newcastle disease vaccine.)

Respiratory syncytial virus

Vaccines

The first RSV vaccine (Arexvy) for older adults was approved May 3, 2023. The vaccine contains a recombinant subunit prefusion RSV F glycoprotein antigen (RSVPreF3) combined with AS01E adjuvant. It is indicated for active immunization for prevention of lower respiratory tract disease caused by respiratory syncytial virus (RSV) infection in adults aged ≥ 60 years.

Vaccine efficacy was 94.1% against severe RSV-related lower respiratory tract disease and 71.7% against RSV-related acute respiratory infection.^[108] Data for a single dose from the first RSV season of the study were available for the FDA’s analysis for approval. The clinical trial is ongoing with participants remaining in the study through 3 RSV seasons to assess duration of effectiveness, and safety and effectiveness of repeat vaccination.

By the end of May 2023, the FDA had approved a second RSV nonadjuvanted vaccine (Abrysvo) in older adults. Approval was supported by results from the ongoing RENIOR phase 3 trial (n >34,000). Vaccine efficacy (VE) was 66.7% for protection against RSV-associated lower respiratory tract illness with at least 2 signs or symptoms. VE was 85.7% against lower respiratory tract illness with at least 3 signs or symptoms, and 62.1% against RSV-associated acute respiratory illness.^[109]

The nonadjuvanted vaccine is pending FDA approval for maternal vaccination to prevent lower respiratory tract illness caused by RSV in infants from birth to 6 months.^[110]

Monoclonal Antibodies

Recombinant human immunoglobulin G1 kappa monoclonal antibodies provide passive immunity in newborns and infants by targeting the prefusion conformation of RSV F protein.

Nirsevimab

Nirsevimab (Beyfortus) is indicated for prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in newborns and infants entering or during their first RSV season and children up to 24 months old who remain vulnerable to severe RSV disease through their second RSV season. It is a long-acting product administered as a single intramuscular injection.

In the MELODY phase 3 clinical trial, 994 infants were assigned to the nirsevimab group and 496 to the placebo group. Medically attended RSV-associated lower respiratory tract infection occurred in 12 infants (1.2%) in the nirsevimab group and in 25 infants (5%) in the placebo group. These results correspond to an efficacy of 74.5% (P < 0.001) for nirsevimab. Hospitalization for RSV-associated lower respiratory tract infection occurred in 6 infants (0.6%) in the nirsevimab group and in 8 infants (1.6%) in the placebo group (efficacy, 62.1%; P = 0.07).^[111]

Palivizumab

Palivizumab (Synagis) is approved for prophylaxis of children at high risk for severe RSV disease. Clinical trials have demonstrated efficacy and safety in premature infants younger than 6 months and those with chronic lung disease of infancy and congenital heart disease younger than 2 years at the start of the RSV season. Infants with immunodeficiency or severe neuromuscular disease have not been studied in conjunction with these products, because the numbers of such patients are limited.

The American Academy of Pediatrics (AAP) provides guidelines for RSV prophylaxis.^[112]

Immunoglobulins

Respiratory syncytial virus (RSV) immunoglobulin was is a pooled product containing immunoglobulin G antibodies against RSV. One such product, RespiGam, was available in the United States until 2003, when it was replaced by palivizumab.

Adenovirus

An oral live vaccine was available against serotypes 4 and 7, taking advantage of the fact that exposure of these strains to the gastrointestinal tract does not result in illness. This vaccine was used primarily in military recruit populations, with excellent results, but it has not been available since 1999. Recrudescence of adenovirus type 3, 4, and 7 has occurred in the military.

Other live and inactivated virus vaccines have been hampered by their oncogenicity in animal models. Vaccines against the capsid (and free of DNA) are currently being studied.

Parainfluenza virus

No vaccine is available, but live, attenuated, intranasally administered parainfluenza type 3 vaccines were under development.

Human metapneumovirus

No vaccine is available, although a live-attenuated bovine parainfluenza virus type 3 vaccine with human metapneumovirus F gene was being studied.^[113]

Varicella-zoster virus

A live attenuated varicella vaccine is recommended for patients who did not have varicella infection by age 13 years and for anyone who is susceptible to varicella-zoster virus (VZV) (VZV antibody negative). The vaccine should not be given to pregnant women. Children are now routinely immunized before age 12-18 months.

Intramuscular administration of varicella-zoster immunoglobulin (125 U/10 kg to 625 units maximum) is indicated as passive immunization of VZV-seronegative personnel at risk for complications within 96 hours of being exposed to VZV (eg, immunosuppressed hosts, such as those with HIV or with malignancies; those on long-term steroid therapy; pregnant patients, and neonates whose mothers acquire VZV within five days before, to 48 hours after, delivery).

Measles

The measles vaccine is a live attenuated virus vaccine (part of measles-mumps-rubella [MMR] vaccine) and should be given to everyone except pregnant women or persons who are severely immunocompromised. HIV-infected persons who are asymptomatic or only mildly symptomatic should be vaccinated.

Postexposure prophylaxis of patients who are immunocompromised with intravenous immune globulin is effective if administered within 6 days of exposure to infectious cases of measles.

Cytomegalovirus

Cytomegalovirus (CMV) infection is prevented in transplant patients by attempts to match the CMV seropositivity between the donor and the recipient and by careful administration of CMV-negative transfusions of blood and blood products.

Hematopoietic stem cell transplant (HSCT) recipients who are CMV-negative are given prophylactic ganciclovir before and after transplantation. Solid organ transplant (SOT) recipients who are CMV-negative and receiving their organ from CMV-positive donors typically receive ganciclovir for three months post transplantation.

Preemptive therapy (with ganciclovir) based on detection of CMV in bronchoalveolar lavage specimens, CMV pp65 antigenemia, and/or polymerase chain reaction (PCR) in blood after transplantation has been shown to significantly reduce the incidence of post-transplant CMV pneumonia.

Herpes simplex virus

Chemoprophylaxis of high-risk seropositive patients during induction of immunosuppression for transplantation is recommended.

Acyclovir is routinely prescribed at maintenance doses for the first month after transplantation.

Hantavirus

No vaccine is available or in development. The only means of deterrence is by avoiding rodent contact and/or inhalation/aerosolization of areas of possible rodent excreta. If contact is unavoidable (ie, need to sweep dirty areas where rodents live), use of a respiratory mask is prudent.

Hematopoietic cell transplantation recipients

An international committee has produced guidelines for preventing infectious complications among HCT recipients. These guidelines include recommendations on use of antivirals for prevention or preemptive treatment of specific infections, as well as recommendations on vaccines.^[114]

Consultations

Patients suspected of having viral pneumonia may benefit from consultation with pulmonary and infectious diseases specialists.

Medication

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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