Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection.
BACKGROUND
Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking.


METHODS
We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile.


RESULTS
Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations.


CONCLUSIONS
The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.
Infectious Disease Division, Queen Mary Hospital, State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.
Kelvin K W
KK
To
Ivan F N
IF
Hung
Iris W S
IW
Li
Kar-Lung
KL
Lee
Chi-Kwan
CK
Koo
Wing-Wa
WW
Yan
Raymond
R
Liu
Ka-Ying
KY
Ho
Kwok-Hong
KH
Chu
Chi-Leung
CL
Watt
Wei-Kwang
WK
Luk
Kang-Yiu
KY
Lai
Fu-Loi
FL
Chow
Thomas
T
Mok
Tom
T
Buckley
Jasper F W
JF
Chan
Samson S Y
SS
Wong
Bojian
B
Zheng
Honglin
H
Chen
Candy C Y
CC
Lau
Herman
H
Tse
Vincent C C
VC
Cheng
Kwok-Hung
KH
Chan
Kwok-Yung
KY
Yuen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification*; D007251:Influenza, Human / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000821:virology; D009305:Nasopharynx / Q000821:virology; D012189:Retrospective Studies; D019562:Viral Load; D014766:Viremia; D055815:Young Adult
D016207:Cytokines