Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection

Ivan Fn Hung, Kelvin Kw To, Cheuk-Kwong Lee, Kar-Lung Lee, Kenny Chan, Wing-Wah Yan, Raymond Liu, Chi-Leung Watt, Wai-Ming Chan, Kang-Yiu Lai, Chi-Kwan Koo, Tom Buckley, Fu-Loi Chow, Kwan-Keung Wong, Hok-Sum Chan, Chi-Keung Ching, Bone Sf Tang, Candy Cy Lau, Iris Ws Li, Shao-Haei Liu, Kwok-Hung Chan, Che-Kit Lin, Kwok-Yung Yuen, Ivan Fn Hung, Kelvin Kw To, Cheuk-Kwong Lee, Kar-Lung Lee, Kenny Chan, Wing-Wah Yan, Raymond Liu, Chi-Leung Watt, Wai-Ming Chan, Kang-Yiu Lai, Chi-Kwan Koo, Tom Buckley, Fu-Loi Chow, Kwan-Keung Wong, Hok-Sum Chan, Chi-Keung Ching, Bone Sf Tang, Candy Cy Lau, Iris Ws Li, Shao-Haei Liu, Kwok-Hung Chan, Che-Kit Lin, Kwok-Yung Yuen

Abstract

Background: Experience from treating patients with Spanish influenza and influenza A(H5N1) suggested that convalescent plasma therapy might be beneficial. However, its efficacy in patients with severe pandemic influenza A(H1N1) 2009 virus (H1N1 2009) infection remained unknown.

Methods: During the period from 1 September 2009 through 30 June 2010, we conducted a prospective cohort study by recruiting patients aged ≥ 18 years with severe H1N1 2009 infection requiring intensive care. Patients were offered treatment with convalescent plasma with a neutralizing antibody titer of ≥ 1:160, harvested by apheresis from patients recovering from H1N1 2009 infection. Clinical outcome was compared with that of patients who declined plasma treatment as the untreated controls.

Results: Ninety-three patients with severe H1N1 2009 infection requiring intensive care were recruited. Twenty patients (21.5%) received plasma treatment. The treatment and control groups were matched by age, sex, and disease severity scores. Mortality in the treatment group was significantly lower than in the nontreatment group (20.0% vs 54.8%; P = .01). Multivariate analysis showed that plasma treatment reduced mortality (odds ratio [OR], .20; 95% confidence interval [CI], .06-.69; P = .011), whereas complication of acute renal failure was independently associated with death (OR, 3.79; 95% CI, 1.15-12.4; P = .028). Subgroup analysis of 44 patients with serial respiratory tract viral load and cytokine level demonstrated that plasma treatment was associated with significantly lower day 3, 5, and 7 viral load, compared with the control group (P < .05). The corresponding temporal levels of interleukin 6, interleukin 10, and tumor necrosis factor α (P < .05) were also lower in the treatment group.

Conclusions: Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.

Figures

Figure 1.
Figure 1.
Temporal changes of viral load and IL-6 level in treatment and control groups
Figure 2.
Figure 2.
Temporal changes of viral load and IL-10 level in treatment and control groups
Figure 3.
Figure 3.
Temporal changes of viral load and TNF-a level in treatment and control groups

References

    1. To KK, Hung IF, Li IW, et al. Delayed decrease of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Clin Infect Dis. 2010;50:850–9.
    1. Shiley KT, Nadolski G, Mickus T, et al. Differences in the epidemiological characteristics and clinical outcomes of pandemic (H1N1) 2009 influenza, compared with seasonal influenza. Infect Control Hosp Epidemiol. 2010;31:676–82.
    1. Chang YS, van Hal SJ, Spencer PM, et al. Comparison of adult patients hospitalised with pandemic (H1N1) 2009 influenza and seasonal influenza during the “PROTECT” phase of the pandemic response. Med J Aust. 2010;192:90–3.
    1. Echevarria-Zuno S, Mejia-Arangure JM, Mar-Obeso AJ, et al. Infection and death from influenza A H1N1 virus in Mexico: a retrospective analysis. Lancet. 2009;374:2072–9.
    1. Louie JK, Acosta M, Winter K, et al. Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. JAMA. 2009;302:1896–902.
    1. Webb SA, Pettila V, Seppelt I, et al. Critical care services and 2009 H1N1 influenza in Australia and New Zealand. N Engl J Med. 2009;361:1925–34.
    1. Subramony H, Lai FY, Ang LW, et al. An epidemiological study of 1348 cases of pandemic H1N1 influenza admitted to Singapore hospitals from July to September 2009. Ann Acad Med Singapore. 2010;39:283–8.
    1. Jain S, Kamimoto L, Bramley AM, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med. 2009;361:1935–44.
    1. Cao B, Li XW, Mao Y, et al. Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China. N Engl J Med. 2009;361:2507–17.
    1. To KK, Wong SS, Li IW, et al. Concurrent comparison of epidemiology, clinical presentation outcome between adult patients suffering from the pandemic influenza A (H1N1) 2009 virus and seasonal influenza A virus infection. Postgrad Med J. 2010;86:515–21.
    1. Hancock K, Veguilla V, Lu X, et al. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med. 2009;361:1945–52.
    1. Harter G, Zimmermann O, Maier L, et al. Intravenous zanamivir for patients with pneumonitis due to pandemic (H1N1) 2009 influenza virus. Clin Infect Dis. 2010;50:1249–51.
    1. Birnkrant D, Cox E. The Emergency Use Authorization of peramivir for treatment of 2009 H1N1 influenza. N Engl J Med. 2009;361:2204–7.
    1. Davies A, Jones D, Bailey M, et al. Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome. JAMA. 2009;302:1888–95.
    1. Luke TC, Casadevall A, Watowich SJ, et al. Hark back: passive immunotherapy for influenza and other serious infections. Crit Care Med. 2010;38:66–73.
    1. Enria DA, Briggiler AM, Sánchez Z. Treatment of Argentine hemorrhagic fever. Antivir Res. 2008;78:132–9.
    1. Nour B, Green M, Michaels M, et al. Parvovirus B19 infection in pediatric transplant patients. Transplantation. 1993;56:835–38.
    1. Yeh KM, Chiueh TS, Siu LK, et al. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. J Antimicrob Chemother. 2005;56:919–22.
    1. Luke TC, Kilbane EM, Jackson JL, et al. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006;145:599–609.
    1. Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med. 2007;357:1450–1.
    1. Simmons CP, Bernasconi NL, Suguitan AL, et al. Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza. PLoS Med. 2007;4:178.
    1. Wu JT, Lee CK, Cowling BJ, et al. Logistical feasibility and potential benefits of a population-wide passive-immunotherapy program during an influenza pandemic. Proc Natl Acad Sci U S A. 2010;107:3269–74.
    1. To KK, Chan KH, Li IW, et al. Viral load in patients infected with pandemic H1N1 2009 influenza A virus. J Med Virol. 2010;82:1–7.
    1. Li IW, Hung IF, To KK, et al. The natural viral load profile of patients with pandemic 2009 influenza A(H1N1) and the effect of oseltamivir treatment. Chest. 2010;137:759–68.
    1. Wong HK, Lee CK, Hung IF, et al. Practical limitations of convalescent plasma collection: a case scenario in pandemic preparation for influenza A (H1N1) infection. Transfusion. 2010;50:1967–71.
    1. Hung IF, To KK, Lee CK, et al. Effect of clinical and virological parameters on the level of neutralizing antibody against pandemic influenza A virus H1N1 2009. Clin Infect Dis. 2010;51:274–9.
    1. Lau SK, Chan KH, Yip CC, et al. Confirmation of the first Hong Kong case of human infection by novel swine origin influenza A (H1N1) virus diagnosed using ultrarapid, real-time reverse transcriptase PCR. J Clin Microbiol. 2009;47:2344–6.
    1. Hanson BJ, Boon AC, Lim AP, et al. Passive immunoprophylaxis and therapy with humanized monoclonal antibody specific for influenza A H5 hemagglutinin in mice. Respir Res. 2006;7:126.
    1. Chu KH, Tsang WK, Tang CS, et al. Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Kidney Int. 2005;67:698–705.
    1. Wu JT, Ma ES, Lee CK, et al. The infection attack rate and severity of 2009 pandemic influenza (H1N1) in Hong Kong. Clin Infect Dis. 2010;51:1184–91.
    1. Collection Nomogram and Adverse Events. . Accessed 13 December 2010.
    1. Song JY, Cheong HJ, Hwang IS, et al. Long-term immunogenicity of influenza vaccine among the elderly: risk factors for poor immune response and persistence. Vaccine. 2010;28:3929–35.
    1. Chen H, Cheung CL, Tai H, et al. Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China. Emerg Infect Dis. 2009;15:1970–2.
    1. Memoli MJ, Hrabal RJ, Hassantoufighi A, et al. Rapid selection of oseltamivir- and peramivir-resistant pandemic H1N1 virus during therapy in 2 immunocompromised hosts. Clin Infect Dis. 2010;50:1252–5.
    1. Kao RY, Yang D, Lau LS, et al. Identification of influenza A nucleoprotein as an antiviral target. Nat Biotechnol. 2010;28:600–5.
    1. Wells M, Albrecht P, Daniel S, et al. Host defense mechanisms against influenza virus: interaction of influenza virus with murine macrophages in vitro. Infect Immun. 1978;22:758–62.
    1. Magro M, Andreu D, Gomez-Puertas P, et al. Neutralization of human respiratory syncytial virus infectivity by antibodies low molecular weight compounds targeted against the fusion (F) glycoprotein. J Virol. 2010;84:7970–82.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren