The current pandemic of COVID-19 seems to be slowing down in various parts of the world, but is far from controlled, as incidence rates rise in new regions. In the absence of an effective vaccine or therapeutic drug, scientists have relied on supportive medical care to treat the sick.
A new study published on the preprint server medRxiv* in May 2020 deals with a new modality of treatment, the use of convalescent plasma, which could help speed up recovery and perhaps pull back critically sick patients from the edge. The study by researchers at Mayo Clinic, Michigan State University, and Johns Hopkins University is focused on assessing the safety of this therapy.
Study: Early Safety Indicators of COVID-19 Convalescent Plasma in 5,000 Patients. Image Credit: Roman Zaiets / Shutterstock
Making Passive Antibody Therapy A Reality For COVID-19
Overall, COVID-19 has been reported to have a case fatality rate of about 4%, but for those sick enough to require hospitalization, it is 14%, according to Wuhan reports. Patients admitted to the intensive care unit who are critically or severely sick have a fatality of 57%.
The U.S. has, by far, the most significant burden of COVID-19 disease in the world, with a fatality rate of over 20% in New York City. This led to the launch of the Expanded Access Program (EAP) by the U.S. Food and Drug Administration (FDA), partnering with the Mayo Clinic and a national network of blood banks.
The EAP aims to collect and disburse convalescent plasma from people who have successfully recovered from the viral illness. This is called passive antibody therapy and is not a new strategy.
Passive Antibody Therapy
First described in the last years of the 19th century, it was the sole hope of recovery from certain infections before the discovery of antibiotics and antimicrobial chemotherapy. It was successful in reducing the mortality rate in the 1918 flu pandemic.
Though its biological basis is plausible, the safety of using convalescent plasma is unverified as yet. The current study looks at key parameters to identify the risks of this therapy.
How Was the Study Done?
The study analyzed safety parameters after the transfusion of human COVID-19 convalescent plasma in 5,000 adults with severe or critical COVID-19 illness. Two-thirds of them were in the intensive care unit (ICU).
The patients included over 2,100 men and 1,800 women, from a variety of ethnicities, almost half being whites. The median age was 62 years. Over 80% of them were severely or critically ill, the rest being at high risk of progressing to such a condition.
Among the 80% with severe illness, 72% could not breathe on their own, 63% had breathlessness, the same number had poor oxygen saturation. Over 40% had evidence of pneumonia involving more than half the lung area, and over a third were having difficulty in oxygenating their blood. Almost a fifth were in multi-organ dysfunction, with 15% in septic shock.
The investigators found that the transfusion was linked to less than 1% of serious adverse events (SAEs) in the first four hours. The death rate associated with convalescent plasma transfusion was 0.3%. There were 36 SAEs reported, with 15 deaths, which accounted for 0.3% of transfusions. Only one death was probably related, and three possibly related to the transfusions. Overall, only 2 SAEs were definitely linked to the transfusions.
Among the 21 other SAEs that were not fatal, transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) in 7% and 11% respectively were predominant. It is important to note that these are very likely to be the result of the inflammatory process in COVID-19. The terminal stages of the viral illness closely resemble these SAEs, so that, according to the paper, “making an unequivocal determination of plasma-related toxicity in critically ill individuals is difficult.”
Again, TRALI and TACO may occur at a rate of almost 10% in critically ill patients who are treated by transfusion. Still, the current study shows a rate of SAEs even possibly related to transfusion, which is below 1%. The researchers comment, “The low rates of TRALI and TACO along with the “possibly related” attribution of most cases are reassuring.”
High Efficacy, Low Mortality
In short, among them, only 25 were thought to be “possibly” related to the transfusion by the treating doctor. In fact, only 2 of them were “definitely” the result of the convalescent plasma transfusion.
The mortality rate in seven days was 14.9%. This is low, considering the more typical rate of 15% to 20% among those who are hospitalized, and even higher rates among those admitted to the ICU. When it is remembered that over 80% of them were severely ill, and almost a fifth were in multi-organ dysfunction, it must be admitted that this is not an unacceptably high rate.
The researchers note that the efficacy of convalescent plasma cannot be judged from this study. Notwithstanding, it appears that the recovery rate is significantly improved in this cohort of patients.
In view of the fatality rate of severe COVID-19, and the large sample size, the researchers conclude that the transfusion of convalescent plasma appears to be a safe step in the treatment of hospitalized patients with severe COVID-19.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Joyner, M. J.. et al. (2020). Early Safety Indicators of COVID-19 Convalescent Plasma in 5,000 Patients. medRxiv preprint doi: https://doi.org/10.1101/2020.05.12.20099879. https://www.medrxiv.org/content/10.1101/2020.05.12.20099879v1