Italy: Hyperimmune plasma study results are published

A recent study has shown encouraging results for the use of hyperimmune plasma in COVID-19 patients, reducing mortality, improving respiratory function, and decreasing inflammatory indices.

The work of physicians from the cities of Pavia and Mantua provides promising results

A recent study has shown encouraging results for the use of hyperimmune plasma in COVID-19 patients, reducing mortality, improving respiratory function, and decreasing inflammatory indices. The research was designed to evaluate the therapy from a conceptual point of view, so the results reported should not be interpreted differently and it cannot yet be argued that the therapy is effective. However, they pave the way for future developments including the rigorous demonstration of the efficacy of hyperimmune plasma in a randomized clinical trial.

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The results of research on the administration of hyperimmune plasma in COVID-19 patients have been published in the journal Haematologica. The study was conducted by researchers from the University of Pavia, the San Matteo Hospital in Pavia, and the Carlo Poma Hospital in Mantua, Italy. Although hyperimmune plasma was used for the treatment of severe cases of SARS during the 2002-2004 epidemic, little data had been available on the use of this therapy in COVID-19 patients.

The study observed 46 patients from 25 March to 21 April 2020. Patients with COVID-19 disease with moderate to severe acute respiratory distress syndrome (ARDS), high levels of C-reactive protein (CRP), and need for mechanical ventilation and/or respiratory support with continuous positive airway pressure (CPAP) devices were enrolled. Plasma infusion took place two weeks after the onset of symptoms. Most patients had already been treated with antibiotics, hydroxychloroquine, and anticoagulants.

Between 1 and 3 units of 250-300 ml of hyperimmune plasma (donor antibody titer ≥1:160) were administered. An interesting aspect of the research was the determination of specific neutralizing antibodies in the plasma of patients cured by COVID-19, for which a special test with high sensitivity and specificity was developed.

The primary endpoint of the research was 7-day hospital mortality. Secondary endpoints were variations in PaO2/FiO2, variations in the laboratory and radiological tests, weaning from mechanical ventilation, and treatment safety.

The study, presented as a conceptual therapy trial, showed that infusion of hyperimmune plasma in COVID-19 patients with severe respiratory failure reduces short-term mortality by 2.5 times. Short-term mortality decreased from an expected 15% (i.e. about 1 in 6 patients) to 6% (i.e. about 1 in 15 patients).

During the 7-day observation, three patients died. Two of these had important comorbidities, while the third had an extremely low PaO2/FiO2 level at the time of infusion. In the surviving patients, an increase in PaO2/FiO2, a decrease in PCR (90%), ferritin (36%), and LDH (20%) was observed. Imaging showed the disappearance of signs of the disease in one-third of the study participants. CPAP weaning was achieved in 26/30 patients and 3/7 were extubated. The viral load was reduced to zero. There were 5 serious side effects in 4 patients. Two probably related to treatment.

The trial has some limitations, first of all, the lack of a randomized control arm. This explained why the trial was designed as a trial to test the potential efficacy and safety of hyperimmune plasma administration in severely compromised COVID-19 patients and to design a rigorous controlled randomized controlled trial. Secondly, the trial was designed at the very beginning of the pandemic in Italy. Patients were included under the pressure of the medical emergency, in an attempt to provide them with effective treatment in the very short term, given the high mortality rate. 

For this reason, the collection of some information was not planned, such as D-dimer levels or other markers of inflammation, and the long-term outcome was not studied. In conclusion, according to the authors, hyperimmune plasma in COVID-19 patients shows promising benefits, to be confirmed in a randomized controlled trial. This trial could open up future developments, including a hyperimmune plasma bank, the development of standardized pharmaceutical products, and monoclonal antibodies.

Perotti C, Baldanti F, Bruno R, et al. Mortality reduction in 46 severe Covid-19 patients treated with hyperimmune plasma. A proof of concept single arm multicenter trial [published online ahead of print, 2020 Jul 23]. Haematology. 2020;haematol.2020.261784. doi:10.3324/haematol.2020.261784