Viral Threat on Respiratory Failure
Younsuck Koh, MD, PhD, FCCM
Department of Pulmonary and Critical Care Medicine
Asan Medical Center
University of Ulsan College of Medicine
Seoul, Korea
No Conflict of Interest related to this topic
A Major Cause of Unknown RF with MV
512 mechanically ventilated pts in 14 studies. Virus was most common cause of infection (42/84; CMV, Influenza, HSV, Adenovrius) Wong AK & Walkey AJ. Ann Am Thorac Soc 2015;12:1226-30
Respiratory Viruses in ICUs
Requiring ECMO
• The emergence of different clinical manifestation
Shieh W-J, et al, Am J Pathol 2010
Virus solely causes LRTI
2009 Pandemic Influenza A (H1N1): Pathology and
Pathogenesis of 100 Fatal cases in the United States
• DAD; most significant & consistent finding
- viral antigens : predominantly in the lung parenchyme
- a high amount of viral Ag observed in close association with DAD
• Also showed viral Ag in trachea, bronchi, or bronchioles
▶ target both upper and lower respiratory tract tissue
Shieh W-J, et al, Am J Pathol 2010
Viral causes seem to be popular
in bilateral lung infiltrates.
Results in inappropriate Abs use, if not considered
• 198 (CAP 64, HCAP 134) in AMC • Bronchoscopic bronchoalveolar lavage: 58.1% (115/198)
8
CAP = community-acquired pneumonia; HCAP = healthcare-associated pneumonia
Choi SH et al. Am J Respir Crit Care Med. 2012;186:325-32
Similar detection rate bwt CAP & HCAP
In severe pn requiring ICU care (AMC experience)
Identified organism Total (n = 198) CAP (n = 64) HCAP (n = 134) P value
None 65 (32.8) 16 (25.0) 49 (36.6) 0.11
Bacteria 71 (35.9) 22 (34.4) 49 (36.6) 0.87
Virus 72 (36.4) 26 (40.6) 46 (34.3) 0.43
Rhinovirus 17 (8.6) 4 (6.3) 13 (9.7) 0.59
Parainfluenza virus 15 (7.6) 3 (4.7) 12 (9.0) 0.39
hMPV 13 (6.6) 5 (7.8) 8 (6.0) 0.76
Influenza virus 12 (6.1) 6 (9.4) 6 (4.5) 0.21
RSV 10 (5.1) 7 (10.9) 3 (2.2) 0.01
CMV 8 (4.0) 0 8 (6.0) 0.056
CoV OC43 4 (2.0) 3 (4.7) 1 (0.7) 0.10
Adenovirus 1 (0.5) 1 (1.6) 0 0.32
Enterovirus 1 (0.5) 0 1 (0.7) 1.00
25.5% 26.5%
33.3%
0%
5%
10%
15%
20%
25%
30%
35%
Bacteria Virus Bacteria + virus
Choi SH et al. Am J Respir Crit Care Med. 2012;186:325-32
P = 0.82
Similar MR
In severe pn requiring ICU care (AMC experience)
11
Clinical Significance of
Rhinovirus in Viral Pn.
Rhinovirus
- The predominant cause of the common cold
- The most frequent virus to exacerbate COP
- HRV-C seems to be associated with more severe RF in
children
• M/73, Farmer • 40 PY ex-smoker • BAL: rhinovirus PCR+ • Expired
Rhinovirus
13
• F/35 • 27 weeks pregnant woman • NP PCR+ • Survived
Rhinovirus
14
Rhinovirus infection (+) Rhinovirus infection (-) COPD with Rhinovirus(+)
Mallina P, et al. Am J Respir Crit Care Med 2012: 186; 1117-1124
Rhinovirus
Kraft CS, et al. JCM. 2012;50:1061-3
Severity of Human Rhinovirus Infection in Immunocompromised
Adults Is Similar to That of 2009 H1N1 Influenza
Rhinovirus vs. Influenza virus
Factor Rhinovirus (n=27)
Influenza virus (n=51)
P value
Immunocompromised state
81.5% 33.3% < 0.001
Viral co-infection 29.6% 11.8% 0.07
Bacterial co-infection 18.5% 37.3% 0.09
Shock at admission 29.6% 54.9% 0.03
28-day mortality 29.6% 35.3% 0.61
In-hospital mortality 55.6% 51.0% 0.70
• Mar 2010 ~ Feb 2014 in AMC
17
18
Perennial distribution
Non-immunocompromised vs. Immunocompromised
Factor Non-IC (n=25)
IC (n=32)
P value
Mean age 71.9 yr 56.5 yr < 0.001
Hematologic malignancy 0 59.4% < 0.001
COPD 20.0% 0 0.01
CAP 44.0% 0 < 0.001
HCAP 36.0% 37.5% 0.91
HAP 20.0% 62.5% < 0.001
Coinfection 40.0% 43.8% 0.78
28-day mortality 8.0% 50.0% 0.001
In-hospital mortality 21.7% 68.8% 0.001
• Mar 2010 ~ Oct 2013 in AMC
Parainfluenza virus
19
MSSA with Parainfluenza
M/62 Fever and Cough s/p Kidney Transplanted
F/30 1st pregnancy with 30 weeks gestation Influenza type A, at ER and 1 & half days later
Influenza A
PCR–confirmed respiratory syncytial virus infections (n = 123) in Hong Kong - Respiratory insufficiency (52.8%), requirement for assisted ventilation (16.3%), and ICU admission/death at 60 days (12.2%/13.8%). - Nearly all (98.4%) hospitalized RSV patients had received initial antibiotics and 35.8% received systemic corticosteroid treatment.
RSV
22
Lee N, et al. JID 2015;21:1237-40
Zoonotic Viral Threat on Resp. Failure
- Hantaviruses by rodents - Dengue (the Flavirididae family) by Mosquitoes - Ebolar virus (Filoviridae family) by a monkey - Coronavirues: SARS by a bat (?), MERS by camel
7 days
7 days
N=14
N=34
40 yr
35 yr
June 7th, 2015
MERS Epidemic in Korea
Clinical Manifestations of Viral Pneumonia
• Prodromal sx: Rhinorrhea
• Absence of purulent sputum
• Diffuse infiltration
• Bilaterality
• Ground-glass opacity
• Centrilobular nodules
• Interstitial pneumonitis
26
Co-infection is not rare
2ndary bacterial infection followed by viral infection
- 2009 H1N1: 4-24%
Concomitant virus-bacterial infection
- 14-15 % in reported 2 CAP studies
- rhino/S. pn, influenza A/S. pn, influenza/S. aureus
Concomitant viruses infection
- two viruses identified; 9 among 63 pts (14%) in our study*
*Choi SH et al. Am J Respir Crit Care Med. 2012;186:325-32
Pneumonia
Bacterial/Fungal Viral Mixed
Epidemics, seasonality
Age
Sx & signs
Labs
CRP/WBC/CXR pattern
Culture
Procalcitonin
How to diagnose viral pn?
Choi SH et al. Am J Respir Crit Care Med. 2012;186:325-32
Seasonality
Lung infiltrate with RF
Pneumonia
Unilateral Bilateral
Usual Approach with CXR infiltrates with RF in ICU
Bilateral lung infiltrate with Pn.
Usual Approach with Bilateral Infiltrate
Noninfectious
Toxic
Edema, Hemorrhage
Immunologic Others
Bilateral lung infiltrate with Pn.
CAP/HCAP Opportunistic Severity
Usual Approach with Bilateral Infiltrate
CMV Influenza
Noninfectious
Pneumonia
Bacterial/Fungal Viral Mixed
Epidemics, seasonal
Age
Sx & signs
Labs
CRP/WBC/CXR pattern
Culture
Procalcitonin
RT-PCR (BAL, nasopharyngel specimen)
Recent Advance in Molecular Diagnostic Technology
Needs BAL?
• Only + in BAL specimen: about 15% among 94 + cases in AMC data.
34
*N: nasopharyngeal specimen, B: BAL specimen
concordance
PREDICTORS FOR THE DIAGNOSIS OF BACTERIAL
PNEUMONIA compared with viral pn in matched cases
Choi SH et al. J Clin Microbiol 2015; 53:1310-6
• Obligate airborne - TB
• Preferential or obligate airborne - measles, smallpox
• Opportunistic airborne -SARS-CoV, MERS-CoV?
“…the aerosol becomes so dilute as it travels away from the source that most secondary infections occur in the immediate vicinity of the index patient…a dilute aerosol mimics that expected with large-droplet or surface contact…it should be also not be dismissed out of hand.”
Roy CJ, et al. NEJM 2004;350:1710-2
Prevention
KCDC
Lessons, you may already know: Appropriate use of personal protective equipment (Gown-Mask-Goggles-Gloves)
From CDC
• Neuraminidase inhibitors: oseltamivir, zanamivir
• M2 ion channel blockers: amantadine or rimantadine
Antivirals for Treatment of Influenza
A Systematic Review and Meta-analysis of
Observational Studies
J Hsu, et al. Ann Intern Med. 2012;156:512-524.
Treatments
Role of Steroid in Viral Pn.
without steroid
with steroid
Kim SH, et al. Am J Respir Crit Care Med 2011 ;183:1207-14
Steroid therapy seems to be harmful in H1N1 virus pneumonia
• 36 fatal children analysis
• 10 of 23 pts with culture results (43%) detected bacterial infection
• 5 S. aureus
• 3 pneumococcus
• 1 S. pyogenes, 1 S. constellatus
“Empiric antibacterial therapy, when indicated, should be directed at
likely…”
Empirical Antibiotics Use
DK Oh, et al. J Crit Care 2013
PRONE POSITIONING
Referral to an Extracorporeal Membrane Oxygenation
Center and Mortality Among Patients With Severe
2009 Influenza A (H1N1). Noah et al. JAMA 2011 36(15):1659
Non-ECMO-referred Pts (85 hospitals)
ECMO-referred Pts (UK ECMO centers)
H1N1-related ARDS
VS.
by matching patients
Conclusion
• Significant?
Truly, significant problem.
Conclusion
• The emergence of new subtype viruses enhanced
intensivists’ awareness about viral pn.
• Viral cause is not rare in severe RF with pn even in
HCAP.
• Molecular diagnostic methods improved our
understanding about viral pn.
• Needs of a Global Collaboration in case of global
viral epidemics
• Further studies are needed to address questions.
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