Viral Pneumonia Cpirozzi

Viral Pneumonia
Fellows conference
Cheryl Pirozzi, MD
September 7, 2011
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Viral Pneumonia
Epidemiology
General clinical features
Specific pathogens

http://www.armageddononline.org/viruses.html
Viral pneumonia: Not just for kids!

Viral Pneumonia
Viruses recently recognized as important pathogens
in CAP due to improved diagnostic tests (PCR)
Cause of 2 - 35% of CAP in adults (more in kids)
Recent emergence of new viral respiratory pathogens

Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24
Marcos MA, Esperatti M, and Torres A. Viral pneumonia. Curr Opin Infect Dis 22:143147
Murray and Nadels Textbook of Respiratory Medicine 5
th
Edition
Risk factors for viral PNA in adults
Elderly: Higher rates of hospitalization and death
from viral PNA in persons >60 yo
COPD and asthma: frequently complicated by
respiratory viral infections
Immunocompromised pts at increased risk

Risk factors for viral PNA in adults

Who gets viral pneumonia?
Johnstone et al. Chest 2008;134;1141-1148
193 adults hospitalized with CAP, 47% with severe
CAP, 15% viral and 4% mixed viral/bacterial
Patients with viral PNA were
older (76 vs 64),
more likely to have cardiac disease (66% vs 32%),
more frail (48% vs 21% limited ambulation)
Most common viruses: influenza, hMPV, and RSV
Similar presentations, no difference in outcome
compared with bacterial PNA
Viral PNA less likely to have lobar infiltrate (62% vs 84%)
and abnl WBC, almost all Oct May
Recommended routine isolation for all PNA pts.
Clinical syndromes
Upper respiratory tract (cold, pharyngitis, bronchitis)
Bronchiolitis: acute inflammatory disorder of small
airways
obstruction with air trapping, hyperinflation, wheezing.
Most common < 2 yo
RSV most common, also human metapneumovirus,
parainfluenza viruses, influenza A and B viruses,
adenoviruses, measles virus, and rhinovirus
Pneumonia
Similar presentation to bacterial PNA
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Diagnosis
Nasal swab specimens, nasal aspirates, or combined
nose and throat swab specimens.
Sputum, endotracheal aspirate samples, or BAL
Rapid antigen detection, viral culture and PCR
methods
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Edition
Specific viral pathogens

Ruuskanen et al. Viral pneumonia. Lancet. 2011 Apr 9;377(9773):1264-75
Case 1
75 yo woman (previously healthy) presents in December with
2 days progressive f/c, dry cough, SOB, myalgias, and this CXR:

What is this most likely to be?

Case 1


A) CMV PNA
B) Influenza
C) adenovirus
D) RSV
E) CHF
Case 1


A) CMV PNA
B) Influenza
C) adenovirus
D) RSV
E) CHF
Influenza
Most common cause of viral PNA in adults
family Orthomyxoviridae, Type A,B,C
2 envelope glycoproteins, Antigenic variation in H
and N leads to epidemic nature
Hemagglutinin (H) initiates infectivity- binds to cell
Neuraminidase (N) protein cleaves new virus allowing
spread
Influenza
Annual winter epidemics x 6-8 wks
(year round in tropics)
Transmitted by small particle
aerosols
2-3 day incubation period
Max virus shedding is at onset of
illness, continues for 5 to 7 days
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Ruuskanen et al. Viral pneumonia.
Lancet. 2011 Apr 9;377(9773):1264-
75
Influenza
Influenza pandemics occur when new viruses are introduced
into the population
Historic pandemics of 1918 (H1N1- 50 million deaths
worldwide), 1957 (H1N1 and H2N2), 1968 (H3N2)
Avian influenza H5N1 1997 outbreak, 58% with PNA
Novel H1N1 influenza A virus emerged in Mexico and USA in
Spring 2009
High risk populations: infants, young kids, healthy adults
20-40s, pregnant/postpartum women,
immunocompromised, obesity, DM, COPD, asthma
Elderly less susceptible to H1N1 due to prior exposure
Mortality in hospitalized pts 7% -17%

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Influenza
Each year, 300,000 hospitalizations (63% in >65 yo),
and 36,000 deaths (85% in >65 yo) due to influenza
30% of pts hospitalized for influenza have CXR
infiltrates
secondary bacterial PNA in ? ~10%
Influenza
Clinical manifestations
Acute onset fever, chills, dry cough, dyspnea,
Pharyngeal pain, nasal congestion
HA, myalgias, malaise, anorexia, GI sxs
Altered mental status (more in older persons)

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Influenza
Imaging
CXR may have bilateral reticulonodular infiltrates, sometimes
lower zone predominant
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Influenza
Secondary bacterial PNA
Mst common in elderly, or underlying pulm or cardiac dz
Period of improvement followed by increased cough,
sputum production, and consolidation
Mst common Strep pneumo, then S. aureus and Grp A
Strep
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Treatment of Influenza
Vaccines:
Inactivated virus vaccines: inactivated purified virions
or partially purified HA and NA preparations
Efficacy 70% to 90% in healthy adults/children if good
antigenic match
Live, attenuated vaccine
More effective in children
In adults equal or less effective than inactivated vaccine
Contraindicated in pregnant or immunosuppressed
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Treatment of Influenza
Antivirals
reduce severity and duration of illness
M2 inhibitors (M2Is) amantadine and rimantadine
Only influenza A
Neuraminidase inhibitors (NIs) oseltamivir and
zanamivir
both influenza A and B
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Available treatment for influenza

Case 2
Previously healthy 27 yo man with mild asthma p/w dry
cough, SOB, and wheezing, with O2 sats 80%/RA. The ER did
this chest CT:
Nasal swab had + RSV PCR

How should he be treated?
A) high dose steroids
B) supportive care
C) inhaled ribavirin
D) IVIG
Case 2
Previously healthy 27 yo man with mild asthma p/w dry
cough, SOB, and wheezing, with O2 sats 80%/RA. The ER did
this chest CT:
Nasal swab had + RSV PCR

How should he be treated?
A) high dose steroids
B) supportive care
C) inhaled ribavirin
D) IVIG

Respiratory syncytial virus (RSV)
2
nd
most common cause of viral PNA in older adults
Common in winter (November April, peak Jan-Feb)
Major cause of serious lower respiratory tract
infections in young children
Primary RSV infection is nearly universal by age 2 and
repeat infections are common due to incomplete
immunity.
Also important pathogen in adults, esp elderly,
chronic lung disease, or immunocompromised
Approx 10,000 deaths in persons > age 65 in the
United States each year from RSV (2
nd
to influenza)

Falsey A. Respiratory Syncytial Virus Infection in Adults. Semin Respir Crit Care Med. 2007;28(2):171-181
RSV- Pathogenesis
RSV is a single-stranded, enveloped RNA virus
Paramyxovirus family, A and B subtypes
Begins as upper respiratory tract infection, then can
spread to lower respiratory tract and cause
bronchiolitis, bronchospasm, pneumonia, and acute
respiratory failure

RSV in adults
Risk factors in adults
Immunocompromised patients (eg, severe combined
immunodeficiency, leukemia, BMT or lung
transplant)
Asthma
Other cardiopulmonary disease
Elderly, esp institutionalized or with chronic
pulmonary disease or functional disability

Influenza vs RSV

RSV: Imaging
CXR: diffuse bilat interstitial
CT: Bronchitis-bronchiolitis pattern: bronchial wall
thickening and tree-in-bud opacities
Multifocal ground glass opacities or consolidation
Miller W T , Shah R M AJR 2005;184:613-622
RSV Testing
Culture: Not sensitive or specific in adults
Serologically: RSV-specific IgM or rise in IgG
Antigen detection by DFA or EIA
Sensitivity depends on specimen: nasal wash (15%),
endotracheal secretions (71%), BAL (89%)
Reverse transcription-PCR (RT-PCR)
In adult nasal swabs: 73% sensitive and 99% specific
Recommendation:
Send nasopharyngeal swab for culture, + PCR if pt is
severely ill / immunocompromised
Consider DFA if BAL or endotracheal specimen

Falsey, Walsh. Clin Microbiol Rev. 2000 July; 13(3): 371384.
Treatment of RSV
Generally supportive: fluids, oxygen, and antipyretics
No data to support steroids or bronchodilators
Ribavirin (aerosolized, IV, PO)
IVIG or RSV-IVIG
Immunomodulators: Palivizumab (PVZ)
RSV-specific monoclonal Ab
Treatment with ribavirin IVIG and/or palivizumab
is indicated in BMT or transplant pts, but there is
insufficient data to support treating healthy adults

Shah et al. Blood. 2011;117(10):2755-2763
Treatment of RSV
Prevention
Droplet precautions
No licensed RSV vaccination at this time; however, in
progress
Human metapneumovirus (hMPV)
Paramyxovirus, closely related to RSV
Common in children, but also common cause of PNA
in immunocompromised and elderly adults
Often coinfection with RSV and other resp viruses
Droplet transmission
Winter outbreaks

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Human metapneumovirus (hMPV)
Clinical: ranges from mild URI to severe bronchiolitis
and pneumonia
In general similar presentation to RSV, though less
severe
Diagnosis: PCR most sensitive, also serology and
culture
Treatment:
Supportive
No effective antivirals or vaccines, though ribavirin has in
vitro activity and has been used
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Parainfluenza
Paramyxovirus RNA virus
Outbreaks fall-spring, every 2-3 yrs
Direct contact by respiratory secretions or large
aerosols
Incubation 3-6 days
Common cause of croup, bronchiolitis, or PNA in
kids, but can also cause PNA in adults, elderly, and
immunosuppressed, esp BMT pts

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Parainfluenza
Diagnosis
Ag or PCR in respiratory secretions or BAL
Treatment and prevention
aerosolized ribavirin has been used in children and BMT
pts, but no trials showing efficacy
No vaccine

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Coronaviruses
Enveloped RNA viruses
Frequent cause of common cold
4-15% of acute respiratory disease in adults, but rarely PNA
Most common winter and early spring, outbreaks q. 2-3 yrs
Incubation period 3 to 4 days

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Severe Acute Respiratory Syndrome (SARS)
HuCoV-SARS: group II coronovirus
emerged in southern China in spring
2003 and rapidly spread worldwide.
incubation period 2 to 10 days
Clinical presentation:
Cough and dyspnea, fever, chills /rigors, myalgias, diarrhea
20% of patients required respiratory support.
Mortality 11% for all ages but much higher in older adults
Some developed pulmonary fibrosis after acute illness
Pathology: diffuse alveolar damage

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bryanking.net
Hsu H et al. Chest 2004;126:149-158
Top: 37-yo man
with bilateral
patchy GGO
without evidence
of fibrosis, with
random
distribution in
the transverse
plane.

Bottom: 22-year-
old female SARS
patient with
random
distribution of
fibrosis, traction
bronchiectasis
(arrowheads), and
lung distortion,
with concomitant
GGO

SARS Imaging
Chest CT:
unilateral or
bilateral GGO,
interstitial
thickening, Mst
common
peripheral lower
lung zones

Severe Acute Respiratory Syndrome (SARS)
Diagnosis
(PCR) detection in sputum, also blood and stool
Serum Abs (rise at 2-3 weeks)
Treatment during the outbreak, treatment with:
ribavirin, protease inhibitors (lopinavir/ritonavir)
High dose steroids
type I interferons, chloroquine (unclear mechanism)
In retrospect unclear that any were effective, recommended
treatment is supportive

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Cytomegalovirus (CMV)
gammaherpesvirus subfamily of the herpesviruses
Transmitted through direct contact
Virus excreted in urine, saliva, stool, tears, breast milk,
vaginal secretions, and semen
No seasonal patterns

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In immunocompetent persons, most infections are
subclinical: can cause pharyngitis, rarely PNA
In immunocompromised, important cause of PNA
In BMT pts, mst common infectious cause of
interstitial PNA, with high mortality
Greatest risk of CMV PNA 30-90 days after BMT
Lung transplant recipients: can cause PNA,
pneumonitis, and lead to bronchiolitis obliterans

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Clinical: fever, nonproductive cough, dyspnea,
Crackles, tachypnea, hypoxemia
May have mild neutropenia, thrombocytopenia, and
elevated liver enzymes
Imaging: bilat diffuse miliary or interstitial infiltrates,
middle and lower lung fields
On CT small nodules,
consolidation, and GGOs
Path: eosinophilic intranuclear
viral inclusions

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bjr.birjournals.org
Treatment: PNA is difficult to treat
Ganciclovir and IV CMV immune globulin reduces mortality
from approx 90% to 50%
Cidofovir and foscarnet unclear efficacy
Prevention in high risk pts
No vaccines
CMV-Seronegative BMT pts should only get leukocyte
reduced/CMV-seroneg blood products
In CMV mismatched solid organ transplant recipients,
posttransplant prophylaxis with ganciclovir

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Case 3
18 yo man p/w acute respiratory failure 10 days after
cleaning out a very dirty dusty cellar (including a nice
family of deer mice)

What might you be worried about?

Hantavirus
Bunyavirus family, single strand RNA virus
Many different viruses associated with different rodent
hosts
Sin Nombre Virus (SNV) associated with deer mouse
Transmission by contact with infected rodent poop
(infectious for 150 days post-rodent infection!)
No person-person, except possibly in one outbreak in
South America
Incubation 8-20 days
SW outbreak in 1993

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forces.si.edu
Hantavirus
Severe, often fatal PNA
Clinical: f/c, myalgias, GI sxs, then after a few days progressive
nonproductive cough, dyspnea
Pathogenesis: capillary leak and noncardiogenic pulmonary
edema
Labs: thrombocytopenia, left shift with circulating
myeloblasts, mildly elevated LFTs
CXR: bilateral infiltrates c/w ARDS
Mortality 30-40%
Also causes cardiopulmonary and
hemorrhagic fever with renal disease
syndrome

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cdc.gov
Hantavirus
Diagnosis
Hantavirus IgM and IgG at time of presentation
Serum PCR
Treatment:
Supportive
High dose steroids, ECMO possibly effective
Ribavirin effective in vitro, no good trials showing efficacy

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Herpes Simplex Viruses (HSV)
HSV-1 most associated with respiratory disease
Transmitted by respiratory secretions, vesicle fluid on
close contact
30-100% of adults are seropositive, asymptomatic
respiratory shedding in 1-2% of seropositive adults
Cause of PNA in neonates, and in severely
immunocompromised adults esp on mechanical
ventilation, eg malignancy, burns, transplant pts
Extension of infection from tracheobronchial tree to
the lung or hematogenous dissemination
Associated with ARDS

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Herpes Simplex Viruses (HSV)
Can cause focal PNA or diffuse interstitial PNA
CT: multifocal GGOs, nonspecific
Diagnosis
Frequently found in BAL (by PCR or culture) of critically ill
pts due to spread/aspiration from oropharynx, but unclear
if true pathogen
Treatment
IV acyclovir, alternative foscarnet
Inconsistent data to support effectiveness of antiviral
treatment on the outcome of critically-ill patients

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Simoons-Smit et al.Herpes simplex virus type 1 and respiratory disease in critically-ill patients: Real pathogen
or innocent bystander? Clin Microbiol Infect. 2006 Nov;12(11):1050-9.
Measles
Uncommon here due to vaccination, but in resource-
poor countries (and damn hippies) can cause fatal
PNA
Morbillivirus genus of the Paramyxoviridae family
Epidemics q. 2-5 yrs
Airborne transmission, highly contagious
Incubation 9-14 days
Mortality 0.1% in developed coutries, 2-25% in
developing countries, due to respiratory or
neurologic dz
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Measles- clinical
Prodrome 2-8 days: fever, cough, anorexia,
conjunctivitis, coryza, Kopliks spots
Then maculopapular erythematous rash
from face/neck trunk extremities
Few days after rash appears,
defervescence and sx improvement
Lower respiratory tract involvement in 4-
50% with bronchitis, PNA, or bronchiolitis
In immunocompromised, can cause lethal
giant-cell PNA, incl pregnant, HIV pts (40%
mortality) and oncology pts (70%
mortality)

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www.nlm.nih.gov/
http://missinglink.ucsf.edu
Measles- clinical
CXR: multilobar reticulonodular infiltrate
Secondary bacterial infection in 30% to 50%
Haemophilus influenzae, Neisseria meningitidis, and S.
pneumoniae
Other complications: hepatitis, encephalitis, keratitis,
mesenteric adenitis, severe diarrhea

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Measles
Diagnosis:
respiratory secretions or urine show multinucleated giant
cells, + immunoflourescent staining
Prevention:
live attenuated virus = >90% durable immunity
Treatment:
Supportive care
Vitamin A improves mortality and recovery time
Ribavirin in vitro activity, but no proven clinical efficacy

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Adenovirus
Nonenveloped DNA viruses
Common cause of pharyngitis, tracheitis, and bronchitis
Rare cause of pneumonia in adults and children
Clinical characteristics similar to those of other pneumonias
In transplant patients and other immunosuppressed pts can
cause fatal pneumonia and disseminated infection, with
hepatitis, hemorrhagic cystitis, and renal failure

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Adenovirus
Treatment and prevention
No proven antiviral treatment
Cidofovir has the most in vitro activity and has been used with
some success in seriously ill and/or immunocompromised
patients (case reports, no RCTs)
Effective live oral vaccines were developed for military, but
are no longer produced

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Rhinovirus
The most common cause of URIs, sinusitis, OM, and
bronchitis
Causes PNA and bronchiolitis in infants and severe
PNA in adult transplant and oncology pts
Diagnosis: culture, rapid Ag or PCR tests
Treatment: symptomatic
Pleconaril? not currently available.

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Case 4
30 yo woman 30 wks pregnant p/w SOB, dry cough,
hemoptysis, hypoxia, and this funny rash:

Case 4

And this CXR:
Case 4

How should she be treated?
A) supportive
B) high dose steroids
C) ribavirin
D) acyclovir
E) oseltamivir

Case 4

How should she be treated?
A) supportive
B) high dose steroids
C) ribavirin
D) acyclovir
E) oseltamivir

Varicella-Zoster Virus (VZV)
Highly contagious herpesvirus
Incubation period 2 weeks
Varicella (chickenpox) outbreaks usually winter-
spring
Respiratory tract infection leads to viremic
dissemination
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Clinical
Usually fever, malaise, or pharyngitis, then rash from head to
trunk/extremities (lesions in various stages)
VZV PNA in 1/400 cases, with 10-30% mortality
In immunocompromised children and adults, more severe
course with high fevers, PNA , meningoencephalitis, hepatitis
Severe PNA in 10% of varicella infections during pregnancy
PNA can occur in healthy adults (25x more frequently than
kids)
Smoking is RF
Sxs usually 1-6 d after rash onset
Cough, dyspnea, pleuritic CP, hemoptysis

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CXR: diffuse nodular infiltrates, which can resolve with miliary
calcific densities, also hilar adenopathy, pleural effusions,
peribronchial infiltrates

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Diagnosis
Clinical (rash + PNA)
Lesion scrapings (Tzank smear) sensitivity 70% to 85%
Direct immunofluorescence for VZV antigen in lesions
BAL PCR
Treatment
IV acyclovir x 5-7 days is effective
Steroids controversial; no good data
Prevention
Live, attenuated varicella vaccine 50-90% effective
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Characteristics of specific viral pathogens
Table
CID 2006:42
Summary of antiviral treatment
Influenza amantadine, oseltamivir
RSV ribavirin
Human metapneumovirus supportive
Parainfluenza supportive
SARS supportive (ribavirin and lopinavir unclear)
CMV ganciclovir
Hantavirus maybe ribavirin
HSV acyclovir
Measles vitamin A, maybe ribavirin
Adenovirus Cidofovir
Rhinovirus supportive
Varicella-Zoster Virus acyclovir

Conclusions
Viral PNA is a big deal for adults too, especially
elderly and immunocompromised
Clinical presentation of viral PNAs are similar
to each other and to bacterial PNA think
about viral testing and isolation
Only some have effective antivirals
References
Johnstone J, Majumdar SR, Fox JD, Marrie TJ. Viral infection in adults hospitalized with
community-acquired pneumonia: prevalence, pathogens, and presentation. Chest. 2008
Dec;134(6):1141-8. Epub 2008 Aug 8
Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb
15;42(4):518-24. Epub 2006 Jan 6.
Jordi Rello and Aurora Pop-Vicas. Clinical review: Primary influenza viral pneumonia. Crit
Care. 2009; 13(6): 235.
Rothberg MB, Haessler SD. Complications of seasonal and pandemic influenza. Crit Care Med.
2010 Apr;38(4 Suppl):e91-7.
Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet. 2011 Apr
9;377(9773):1264-75. Epub 2011 Mar 22.
Falsey A. Respiratory Syncytial Virus Infection in Adults. Semin Respir Crit Care Med.
2007;28(2):171-181
Shah J, Chemaly R. Management of RSV infections in adult recipients of hematopoietic stem
cell transplantation. Blood. 2011;117(10):2755-2763
Hsu et al. Correlation of HRCT, symptoms, and pulmonary function in patients during
recovery from Severe Acute Respiratory Syndrome. Chest 2004; 126:149-158
Simoons-Smit AM, Kraan EM, Beishuizen A, Strack van Schijndel RJ, Vandenbroucke-Grauls
CM.Herpes simplex virus type 1 and respiratory disease in critically-ill patients: Real pathogen
or innocent bystander? Clin Microbiol Infect. 2006 Nov;12(11):1050-9.

Available treatment for viral PNAs

Ruuskanen et al. Viral pneumonia. Lancet. 2011 Apr 9;377(9773):1264-75


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