Plasma from patients who recovered from 2009 H1N1 influenza may be an option in the treatment of patients with a severe case of the disease, a case-control study showed.
The 20 patients in the study who received convalescent plasma therapy had a reduced viral load in the respiratory tract, a blunted cytokine response, and a lower mortality rate than those who refused the treatment, Kwok-Yung Yuen, MD, PhD, of the University of Hong Kong, and colleagues reported in the Feb. 15 issue of Clinical Infectious Diseases.
The study “very much supports the concept that plasma therapy can be of benefit,” according to John Treanor, MD, a vaccine researcher at the University of Rochester, who noted in an e-mail to MedPage Today that the treatment was used nearly a century ago during the 1918 influenza pandemic.
Yuen and his colleagues also noted that plasma therapy appeared to improve outcomes among patients infected with avian influenza (A/H5N1).
In the current study, the researchers recruited 93 adult patients (median age 53.5) who required intensive care for a laboratory-confirmed case of pandemic H1N1 influenza from Sept. 1, 2009, through June 30, 2010. All had deteriorated clinically in spite of optimal antiviral treatment.
Although 73 patients refused plasma therapy, 20 patients or their next-of-kin agreed to try it.
The plasma was obtained by apheresis from patients who had recovered from H1N1 influenza at least two weeks previously. Only plasma with a high neutralizing antibody titer (≥1:160) was used.
The treatment involved an infusion of 500 mL of plasma over a four-hour period on day two of the stay in the intensive care unit.
To the extent possible, the treatment and control groups were matched by age, sex, comorbidities, and disease severity at ICU admission.
Nonetheless, patients in the treatment group had more risk factors for severe disease, including a lower lymphocyte count, greater prevalence of obesity, and presentation with more severe symptoms.
Even so, the mortality rate was significantly lower among those who received convalescent plasma therapy (20% versus 54.8%, P=0.01), a benefit that remained after multivariate adjustment (OR 0.20, 95% CI 0.06 to 0.69).
At ICU admission, there was no significant between-group difference in viral load and cytokine level. A subgroup analysis, however, revealed that there were significant reductions in viral load on days three, five, and seven in the treatment group (P<0.05).
There were also reductions in cytokine levels in the treatment group — interleukin 6 and tumor necrosis factor-alpha on day five and interleukin 10 on days five, seven, and nine (P<0.05).
It is unknown exactly how the plasma therapy benefits patients, according to Yuen and his colleagues, who noted that they could not exclude the possibility that factors in the plasma might have reduced the harmful effect of undetected pathogens other than influenza.
Convalescent plasma therapy, which is safer now than in the early half of the 20th century because of donor screening, virological and microbiological testing, and apheresis, may have some advantages over antivirals, the researchers added in their paper.
Neutralizing antibodies, they explained, are not subject to drug resistance, and antigenic drift leading to loss of effectiveness is unlikely to affect treatment efficacy within the timescale of the H1N1 pandemic.
Yuen and his colleagues added, “The effect of convalescent plasma may be quite immediate in terminating the infective process and dampening down the cytokine response, whereas adamantanes and neuraminidase inhibitors or even newer antivirals active against the viral nucleoprotein cannot neutralize any virus that [has] already entered the host cells.”
According to Treanor, collecting convalescent plasma presents some feasibility issues during the course of an epidemic because the plasma will not be available at the beginning of the outbreak.
Some possible alternatives, he said, are collecting plasma from individuals who had a robust response to vaccination or using monoclonal antibody therapies, especially those that can neutralize multiple strains.
He added that, “if antibody is good, and it looks like it is, then the best strategy is an effective vaccine that induces high levels of antibody, obviously.”
The study was supported by the Ted Sun Foundation, the Research Fund for the Control of Infectious Diseases of the Food and Health Bureau, and the Hospital Authority of the Hong Kong Special Administrative Region.
The study authors reported that they had no conflicts of interest.
Treanor has made the following disclosure: “I am very significantly funded by industry to perform studies of experimental vaccines. This funding is in the form of contracts to my institution for my lab to conduct lab assays or for my clinical staff to enroll subjects and follow them in a variety of clinical studies. The sponsors of these studies currently include Protein Sciences Corporation, Bavarian Nordic, GlaxoSmithKline, Pfizer, Sanofi-Pasteur, Vaxinnate, Mercia Pharma, Paxvax, and Ligocyte. I am also considering attending a scientific advisory board for Novartis, for which I would receive an honorarium, and I am on the scientific advisory board for Immune Targeting Systems (ITS) and also received an honorarium in 2009 from Abbott for an advisory meeting. We also conduct clinical trials of experimental live vaccines through a contract with NIH, but the vaccines are supplied by MedImmune through a cooperative research and development agreement (CRADA) with NIAID.”