Mayo's plasma program shows first signs of COVID-19 benefit

Preliminary research by Mayo Clinic shows that high-dose plasma therapy is correlated with fewer deaths in patients with severe COVID-19.

A 10 percentage point difference in deaths was found when comparing hospitalized COVID-19 patients who received donor plasma with high concentrations of virus-fighting antibodies compared with those who received lower concentrations, Mayo reported.

The findings are good news in the fight against a global pandemic with few proven treatments and an infectious disease that as of Wednesday had caused 57,779 known infections and 1,629 deaths in the state, according to the Minnesota Department of Health.

"I'm just grateful as an American and a doctor that we are seeing some potential benefit, because our patients and our country need some help with COVID," said Dr. R. Scott Wright, who is coordinating Mayo's national COVID-19 convalescent plasma program.

Mayo launched the program with support from the U.S. Food and Drug Administration this spring to provide plasma from donors who have recovered from COVID-19 as an experimental therapy at smaller or nonacademic hospitals that otherwise wouldn't have access to it.

More than 2,700 sites have registered and more than 56,000 patients with COVID-19 have already received plasma infusions, according to the program's website.

HealthPartners has enrolled more than 150 COVID-19 patients at Regions Hospital in St. Paul and Methodist Hospital in St. Louis Park, and North Memorial Health in Robbinsdale has enrolled 98.

The preliminary results are based on samples of donor plasma sent to Mayo and clinic results from 3,000 COVID-19 patients. A key finding was that plasma was associated with fewer deaths when administered in three or fewer days of the patients' COVID-19 diagnoses.

Among patients who received the therapy this quickly, the death rate after seven days was 6.6% in those who received plasma with high antibody concentrations but 15.4% in those who received low concentrations. That gap persisted 30 days after treatment — with a death rate of 17.6% in the high concentration group and 27.6% in the low concentration group.

The results come loaded with caveats, including that Mayo hadn't intended them for public review yet. They were presented to the FDA as the agency considers whether to grant an emergency use authorization for broader use of convalescent plasma in COVID-19 patients with severe and potentially fatal cases. Mayo then presented the data in a webinar for clinicians this weekend that was leaked to the media.

The observational design of the program also means that there was no comparison group of patients who didn't receive plasma, and no way to know for sure if patients benefited from the plasma or any other type of treatment that they received for COVID-19.

Infectious disease experts in the Twin Cities nonetheless viewed the results as encouraging and consistent with their understanding of severe COVID-19 and the need to intervene with therapy before the infection produces an overzealous and sometimes fatal immune system response.

"It's sort of like a little head start or a little boost in starting to beat the illness," said Dr. Clara Zamorano, a critical care physician who has treated COVID-19 patients with donor plasma at Abbott Northwestern Hospital in Minneapolis.

Minnesota is at a sensitive stage in the pandemic. The case count in Minnesota has doubled from six cases per 100,000 people per day on June 16 to 12 cases per 100,000 now, according to the state's COVID-19 dashboard.

Health officials are concerned that a recent rise in cases among teenagers and young adults will spread the virus to older people and residents of long-term care facilities who are at greater risk of complications or deaths.

Medical advances are "urgently needed," said Jan Malcolm, state health commissioner. "Mayo's work on convalescent plasma is really encouraging ... It has been shown to work in other types of illnesses so I think there was good hope that it also might be successful for COVID."

The clear liquid in blood, plasma has been extracted from recovered patients to treat other infectious diseases, including SARS in 2003 and Ebola in 2014. Mayo reported safety data earlier this year showing a rate of less than 1% of serious adverse events in 20,000 initial COVID-19 patients who received it.

HCMC in Minneapolis and Regions routinely screen COVID-19 patients shortly after admission for their interest and eligibility for convalescent plasma.

Patients with severe and potentially critical COVID-19 cases usually receive a combination of therapies, including the antiviral remdesivir that has shown a benefit when given early on, and the steroid dexamethasone.

"We have certainly noticed a big change," said Dr. Michael Schnaus, a Regions hospitalist and a member of HealthPartners' COVID-19 expert research panel. "Patients that get these interventions up front ... tend to get better and they tend to get discharged home quicker. They tend not to be progressing like they did in May when they escalated in their course very quickly and required intubation in our ICU."

Schnaus said he doubts any one therapy is providing all the benefit and that severe COVID-19 cases require a "cocktail" of drugs.

HealthPartners also is participating in a national study by which it gives donor plasma on an outpatient basis to COVID-19 patients to prevent complications or their need for hospital admissions. Patients are prioritized for the study if they are 50 or older or have conditions such as diabetes that increase the risk of COVID-19 complications.

Convalescent plasma for the Mayo program is obtained at blood donor sites and tested for antibody levels before it is shipped to hospitals for therapeutic use. The American Red Cross has four collection sites in the Twin Cities and a processing center for preparing the plasma in St. Paul.

Even so, doctors said antibody levels vary in the plasma products they receive — which could affect the results based on the Mayo findings.

"We're all kind of waiting for more standard products to come out where you know how much antibody that someone is getting," said Dr. Anne Frosch, who is leading HCMC's COVID-19 convalescent plasma program.

Another concern is that donor plasma is limited in its supply. The Red Cross last week issued a plea for more recovered patients to donate and offered $5 Amazon gift cards. Demand for donor plasma doubled last month, the organization said.