DAYTON — The U.S. surpassed the 4 million infected mark during a second wave of COVID-19 cases which has caused business re-openings to be delayed and masks to now be fully or partially required in 33 states. Treatment options are urgent. For those who have contracted a serious case of the disease and are hospitalized, immediate therapies are being investigated, including COVID-19 convalescent plasma (CCP).
“With the advent of summer and people becoming lax in social distancing, wearing masks, and washing their hands, we’re seeing the consequences of that,” said Patrick Lytle, vice president of Clinical Outcomes at Kettering Health in Dayton, Ohio.
Lytle also reported seeing an increase in the severity of cases admitted to Kettering Health during this second wave. “The intensity of the illness is greater now than back in March and April,” he said. Lytle noted that in severe cases among young people obesity appears to be a driving factor.
Since it is administered to only the most severe cases, “successes with convalescent plasma seems very, very promising so far,” he said. One success story Lytle recalled involved a patient well enough after treatment to be released home without requiring rehab.
The first use of convalescent plasma therapy occurred in Japan during the late nineteenth century Emile von Behring (and Kitasato Shibasaburō) against Hong Kong’s outbreak of the Bubonic Plague in 1894, for which the very first Nobel Prize in Physiology or Medicine was awarded in 1901. It was again applied to treat some of the 500 million, roughly 1/3 the world’s population became infected with the H1N1 virus (Spanish flu) during a three-year pandemic which lasted from 1918 to 1920. In the 1930s it was used to treat an outbreak of the measles. Then in the early 1950s it was used to treat soldiers for Hantavirus infections during the Korean War. More recently, convalescent plasma was used to treat Ebola-Zaire patients. But how well it works with COVID-19 is not yet known.
In one of the most comprehensive efficacy studies to date was conducted by Mayo Clinic. It analyzed 20,000 COVID-19 patients infused with convalescent plasma, the fluid part of blood from recovered patients. The study — composed of doctors, researchers and patients across the country—combined the efforts of the Mayo Clinic with Johns Hopkins University, Washington University, Einstein Medical Center, Icahn School of Medicine at Mount Sinai, Michigan State University, and government agencies like The Food and Drug Administration.
“The goal of plasma therapy is to reduce mortality and save lives,” while waiting for a successful vaccine, said lead convalescent plasma researcher Arturo Casadevall, chair of Molecular Microbiology & Immunology at Johns Hopkins Bloomberg School of Public Health.
A recently released South Korean study of nearly 60,000 infected individuals by that country’s CDC, showed that during school closure, the highest transmitters of the disease to their family (32.3%) were 20–29 years old. A Chinese study cited in that study showed that the lowest transmitters (5.3%) were children up to the age of nine. But this demographic may change once schools reopen. If COVID-19 follows the same pattern as the seasonal flu in China, the figure for teens and children as transmitters could jump to 13% or higher. The study recommended, then, in lieu of continued school closures, that “personal protective measures should be used at home” when young people may be in close contact with other family members.
The implications of the study suggest that in the U.S. school closure is ideal for prevention. However, it comes with other costs, especially for children from low income and minority backgrounds. For them, school closures can have devastating effects, including learning loss for those without internet connections in their homes to receive virtual instruction, a safe haven from dangerous neighborhoods, and adequate food and nutrition provided through school breakfast and lunch programs.
Before this summer ends and fall classes begin at preK-12 schools and colleges, then, many parents, teachers, and students want a promising vaccine. With that happening just one month ahead, the fact is it is just is too soon to guarantee one that is both safe and effective for school-aged children. Therefore, the safety, efficacy, and availability of therapies like CCP, for use in adults (especially the most vulnerable) to whom they transmit COVID-19, are now paramount.
According to Mark Pompilio of the Community Blood Center (CBC) in Dayton, Ohio, one of the national COVID-19 convalescent plasma (CCP) distribution centers, finding donors can be difficult. Populations in nearby geographic areas that are amazing blood donors simply have not become infected with COVID-19 and are not able to participate in the CCP program.
“The number of dedicated donors from Shelby County is unusually high. Of those eligible to donate, about one of four are blood donors,” said Pompilio. But there were just four CCP program donors. This is partially because there have been only 103 cases of COVID-19 in Shelby County as of June 23. Also, CBC previously required a positive viral RNA nasal swab test, being symptom free for 14 days, and a negative RNA test. But, to increase the number of units they can supply, Pompilio indicated the CBC is now accepting donors who tested positive by the antibody blood test. They can donate if they have been symptom free for 28 days.
According to British-American virologist Paul Bieniasz of the Rockefeller University, “When SARS-COV2 began to spread around the world, it became obvious to us and obvious to many people that antibodies were going to be a key component of how we eventually get through this pandemic,” Bieniasz explained. “Whether that’s through herd immunity, through vaccination, or through actually using the antibodies themselves as a protection against the infection or a treatment, antibodies were going to be a crucial part of our response, our fight, against this virus … What neutralizing antibodies do, in effect, is to interfere with this recognition event between the SARS-COV2 spike and/or subsequent events (interactions) between the spike protein and the target cell that allow the virus to enter and infect cells.”
The modern science of immunology includes the synthetic production of antibodies for COVID-19 convalescent plasma (CCP). Once it is determined how antibodies found in convalescent plasma bind to the virus’s protein spike (shown in the image “Infection mechanism of SARS-COV2”), it is possible to use one of the “elite” neutralizers to begin to clone antibodies created in a lab, instead of having to rely on many donors. These lab-made antibodies are called monoclonal antibodies.
According to Kenneth Mayer, a professor of medicine at Harvard Medical School, in addition to a shortage of donors, the problem with scaling up the use of convalescent serum is that, although the procedure is well-characterized and generally safe, it is very labor intensive, and thus, expensive. How well convalescent serum performs will help inform work being done to develop bioengineered monoclonal antibodies as a therapy or preventative vaccine.
Recently, a systematic review study of living survivors of convalescent plasma published in the Cochrane database revealed that adverse effects and negative outcomes can include allergic reaction (anaphylaxis), transfusion-associated breathing difficulties (dyspnoea), transfusion-related acute lung injury (TRALI), and death. To place the mortality risk in context, among 5,201 patients (most of whom were from a single non-controlled study), 15 died, of which just four were “potentially” or “probably” related to their CCP treatment.
One example of a monoclonal antibody that seems to work against COVID-19 in a lab and is a very hopeful vaccine candidate for human trials is called the “S309 neutralizing antibody.”
Further study is needed as we head into unfamiliar territory to know how long the effects of convalescent therapy will last. As Dr. Casadevall says, “This virus has been known to science for only 6 months. We don’t know if immunity will be long lasting or temporary. We have to wait for this data from ongoing studies.”
CCP therapy and vaccines hold great promise, but what they cannot do is reverse damage to the body following infection. According to Lytle, some complications include blood clots, blood pressure drops, and excessive fluid in the lungs which reduce oxygen flow so that a respirator is required. Because COVID-19 resembles other acute lung infections, like pneumonia, it can permanently damage lung tissue.
Getting convalescent plasma to those in need is essential. If you have recently had COVID-19 but are now negative, consider becoming a plasma donor. For details on the national effort, visit uscovidplasma.org. To find out how to contribute locally as a male or female plasma donor to the CCP program, reach out to the Community Blood Center in Dayton by visiting givingblood.org or calling 937-461-3220.