Convalescent Plasma Therapy Improves Outcomes for Severely Ill COVID-19 Patients in Small Study

By Linda Carroll

April 09, 2020

(Reuters Health) - A pilot study in which convalescent plasma (CP) was used to treat severely ill COVID-19 patients in China found the therapy raised antibody titers, reduced viral load, and led to symptom improvement within three days.

Among the 10 patients who received the plasma transfusions, symptoms such as fever, cough, shortness of breath and chest pain significantly improved within three days, and lung lesions were absorbed to "varying degrees" within seven days, according to the report in Proceedings of the National Academy of Sciences.

"This pilot study on CP therapy shows a potential therapeutic effect and low risk in the treatment of severe COVID-19 patients," the team of researchers led by Kai Duan of the China National Biotec Group Company, Ltd., write. "One dose of CP with a high concentration of neutralizing antibodies can rapidly reduce the viral load and tends to improve clinical outcomes. The optimal dose and treatment time point, as well as the definite clinical benefits of CP therapy, need to be further investigated in randomized clinical trials."

Duan and his colleagues report on 10 severely ill patients who received CP from January 23, 2020 to February 19, 2020. The patients' average age was 52.5 years and they received CP transfusion an average of 16.5 days after onset of illness.

All patients were transfused with one dose of 200 mL of CP derived from recently recovered donors with neutralizing antibody titers above 1:640 in addition to "maximal supportive care and antiviral agents," the study team writes.

Along with the CP, nine of the patients received arbidol monotherapy or combination therapy with remdesivir or ribavirin or peramivir. One patient received ribavirin monotherapy. Antibacterial or antifungal treatment was used when patients had coinfection. Six of the patients received IV methylprednisolone.

Within one to three days, all symptoms - including fever, cough, shortness of breath and chest pain - disappeared or largely improved in the 10 patients and oxyhemoglobin saturation also improved.

Prior to CP treatment, three patients were on mechanical ventilation, three were receiving high-flow nasal cannula oxygenation and two were receiving conventional low-flow nasal cannula oxygenation.

After treatment, two patients were weaned from mechanical ventilation to high-flow nasal cannula, one patient discontinued high-flow cannula and one patient receiving continuous oxygenation through conventional nasal cannula was able to shift to intermittent oxygenation.

Within seven days of treatment radiological exams revealed varying degrees of absorption of lung lesions. By the end of the study, the viral load was undetectable in seven patients who previously had viremia.

While the researchers did not run a randomized controlled trial, they randomly selected historical patients who did not receive CP to serve as controls. Those patients were selected from the cohort treated in the same hospitals and were matched in age, gender and severity of disease with the 10 patients who received CP. Clinical outcomes of the two groups were markedly different: in the CP treated group, three patients were discharged and the other seven were improved enough that they were ready for discharge; in the historical control group, there were three deaths, six remained the same and one improved.

The study is the third to describe the use of CP in severely ill Chinese patients within the past few weeks. The previous two detailed outcomes for four and five cases each without a control group.

While the results from the CP studies look promising, they are from a small number of patients, said Dr. Micheal Ison, a professor in the division of infectious diseases at the Northwestern University Feinberg School of Medicine, in Chicago.

To know for sure that the therapy is the reason patients are getting better you really need a trial with hundreds of patients randomly assigned to get CP or a placebo, Ison said. Randomized controlled trials of CP for treatment of seasonal influenza did not show a benefit, he added.

"But it was used in the pandemics of 1918 and 2009 and it showed a benefit there," Ison said. "I think the biggest challenge in the U.S. is going to be finding patients who have completely recovered. Most have been getting sick over the last couple of weeks."

The new study is "important," said Dr. John McDyer, director of the UPMC Lung Transplantation Translational Research Program, in Pittsburgh.

"While a relatively small study in 10 patients, it shows that giving a single dose of CP was well-tolerated in these patients, supporting its safety," McDyer said in an email. "Secondly this study shows that some patients improved within a few days of CP therapy, with two of three patients coming off ventilator support. Third, this study indicates that CP therapy raises the level of circulating COVID antibodies in about half the patients and virus levels fell in some patients suggesting a direct impact on the virus."

One limitation is the fact that the patients were receiving other therapies at the same time as they were given CP, McDyer said.

The latest Food and Drug Administration guidance regarding the use of CP to treat patients says the therapy needs to be proven safe and effective before it can be routinely administered to patients (https://bit.ly/2x4MAgX).

SOURCE: https://bit.ly/3c3sGS9 PNAS, online April 6, 2020.

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