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

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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

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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

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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.

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*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.