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Clinical Updates

Progress Made in Using Convalescent Plasma to Treat COVID-19 Patients

The U.S. Food and Drug Administration (FDA) announced Sunday that it issued an Emergency Use Authorization (EUA) to permit the emergency use of COVID-19 convalescent plasma to treat hospitalized patients with COVID-19. Interest in the use of convalescent plasma to treat COVID-19 has been high since the early phases of the pandemic, and while some prominent members of the scientific community are enthusiastic about its use, others are more cautious.

Interest in the use of convalescent plasma to treat COVID-19 was rooted in previous promising experiences with using plasma to treat other viral pandemics and epidemics, including the 1918 influenza, the H1N1 influenza in 2009 and severe acute respiratory syndrome and Middle East respiratory syndrome (both coronaviruses) in the last two decades. An excellent short history and proposal for the development and use of convalescent plasma (sera) was published in early March by Casadevall and Pirofski.

The use of sera is based upon the donation of plasma from patients who have recovered from documented COVID-19 illness. Neutralizing antibodies should be present in this plasma, but concentration varies from none-to-low titers to high titers. Previous experience suggests that high-titer sera are more effective than plasma with low titers (lower concentrations) of neutralizing antibodies.

Early experiences in transfusing severely ill patients with COVID-19 in a small series were published in March and April. These studies showed the promising effects of the use of convalescent plasma but were uncontrolled and not blinded.

One of the first randomized trials of the use of convalescent plasma in COVID-19 treatment was published in June and failed to show a significant improvement over standard treatment without the use of convalescent plasma in patients with severe or life-threatening disease. The trial was suspended prior to planned full enrollment, as the incidence of disease in this study from China declined precipitously as the pandemic waned in many parts of the world. Subgroup analysis, however, showed that patients who were severely ill had better outcomes than patients with life-threatening illness, giving some promise and potential guidance to treating patients earlier in the disease course.

Experience with the use of convalescent plasma grew in the U.S. as the pandemic continued. Data from an expanded access program (EAP) developed in conjunction with the FDA, the Mayo Clinic, and the national blood bank community showed the safety of the use of convalescent plasma in the first 5,000 patients in June. The incidence of serious adverse events was less than 1 percent, and few of these complications could be linked directly to the plasma transfusion. Mortality was noted to be low in treated patients, but the study was not designed to be controlled or randomized, so no inference could be made to show a definite beneficial effect of the plasma.

One of the first controlled prospective propensity score matched trials (not a randomized controlled trial) in the use of convalescent plasma was reported earlier this month. Houston Methodist Hospitals reported on 136 patients transfused with convalescent plasma versus 251 non-transfused patients. Mortality declined significantly in patients with severe or life-threatening disease who received high-titer convalescent plasma within 72 hours of hospital admission.

A pre-peer-reviewed article in July reviewed data from 12 worldwide studies (three randomized clinical trials, five matched-control studies and four case series studies) and concluded that patients treated with convalescent plasma experienced reduced mortality rates compared with patients who received standard treatment.

The most recent and largest study of the use of convalescent plasma has been released as a pre-peer-reviewed manuscript. This study extracted data from a large EAP and looked at outcomes for 35,322 transfused patients receiving convalescent plasma April 4 to July 4. Investigators found that patients transfused within three days of diagnosis were significantly more likely to survive at seven days and at 28 days than patients transfused four or more days after diagnosis. In addition, patients transfused with high IgG plasma were more likely to survive than those receiving low IgG plasma—confirming a dose response relationship that would be expected. It should be noted that this study is a retrospective analysis of data collected in a large group analysis, not a randomized controlled trial.

The most recent response to this data was reported in the New York Times August 19—just days before the FDA released its authorization for the emergency use of convalescent plasma for patients with COVID-19. Concern exists that the EAP has grown so rapidly (the Mayo group database now includes more than 66,000 cases involving transfusion of convalescent plasma) that it may become difficult to perform standard randomized controlled trials because patients and physicians may refuse to accept the possibility of receiving placebo rather than convalescent plasma. We will continue to track and share updates as they are available.

3-D Printing Is Key to Global Improvements in Care: An Update from the ACS Advisory Council for Oral-Maxillofacial Surgery

The use of 3-D printing has grown exponentially in oral-maxillofacial surgery worldwide. It is becoming commonplace for practices to use in-house 3-D printing capability to assist in the reconstruction of trauma, cleft and craniofacial, pathologic, and dentofacial anomalies, assisting in fabrication of study models, surgical guides, and dental prostheses. Through point-of-care 3-D printing, head and neck reconstructive surgeons and oral-maxillofacial surgeons can now perform dental implant-retained restorations for immediate placement at the time of fibula reconstruction for oncology patients. Throughout the COVID-19 pandemic, oral-maxillofacial surgery programs have put their printers to work to fabricate nasopharyngeal swabs and shore up the shortage in testing materials. Details have been published here.