Research led by Johns Hopkins University has found that early treatment using plasma from recovered COVID-19 patients reduces the risk of "Long-COVID" and that inflammation-inducing interleukin-6 (IL6) plays a key role in the development of symptoms.
Results of a national, multicenter study led by the Johns Hopkins University School of Medicine and the Johns Hopkins Bloomberg School of Public Health suggest that if COVID-19 patients are treated early with plasma from convalescent (convalescent) COVID patients, they are less likely to suffer from the sequelae of COVID-19, commonly known as LongCOVID, because their plasma contains antibodies against SARS-CoV-2, the virus that causes COVID-19.
The new study, first published online on September 19 in mBio, the journal of the American Society for Microbiology, is a follow-up investigation of a 2021 clinical trial that showed convalescent plasma to be an effective and safe option as an early outpatient treatment for COVID-19. The latest study looked at long-term efficacy among a large number of participants in a 2021 clinical trial.
"After our initial study, health care professionals kept SARS-CoV-2 antibody-rich plasma in their blood banks as a treatment option for immunocompromised individuals to fight COVID-19; now, our new findings suggest it may also reduce the risk of COVID sequelae," said study co-first author David Sullivan, MD, professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health and professor of infectious diseases at the Johns Hopkins University School of Medicine.
The initial outpatient early treatment clinical trial was conducted between June 2020 and October 2021. Researchers gave 1,181 randomized participants one unit each of polyclonal high-titer convalescent plasma (a concentrated mixture containing SARS-CoV-2-specific antibodies) or placebo control plasma (containing no SARS-CoV-2 antibodies). Participants were 18 years of age and older who had tested positive for SARS-CoV-2 within eight days prior to transfusion. A successful outcome was defined as freedom from hospitalization within 28 days of transfusion.
The original clinical trial found that 17 of 592 participants (2.9%) who received convalescent plasma required hospitalization within 28 days of transfusion, compared with 37 of 589 participants (6.3%) who received placebo-controlled plasma. This represents a 54% reduction in the relative risk of hospitalization.
As part of the clinical trial, 882 participants were also screened and assessed for levels of 21 different cytokines and chemokines 14 and 90 days after receiving convalescent or placebo-controlled plasma. Cytokines and chemokines are signaling proteins secreted by cells in response to infection that activate specific immune system functions such as inflammation. In turn, excessive or uncontrolled inflammation is thought to be a key factor in post-COVID illness.
In the latest study, researchers used measurements of cytokines and chemokines, as well as patients' reports of any post-COVID symptoms at the 90-day check-up, to determine whether there is an association between early convalescent plasma therapy and long-term COVID symptoms. Statistical analyzes were performed to validate the findings after adjusting for other factors that may make a person more susceptible to post-COVID symptoms, such as demographic factors such as age and race, competing medical conditions such as diabetes, and vaccination status.
Ninety days after receiving convalescent or control plasma, 590 participants (66.9%) had no post-COVID symptoms and 292 participants (33.1%) had post-COVID symptoms. The most common symptoms of the latter are fatigue and loss of smell.
"Most study participants had elevated levels of cytokines and chemokines at screening, while those who received convalescent plasma had elevated levels of Levels of cytokines and chemokines declined more at 90 days. Additionally, study participants with higher than normal levels of interleukin-6 (IL6), which is known to trigger inflammatory responses in humans, were more likely to develop post-COVID symptoms at 90 days.
"Our study is the first to show that elevated IL6 early after infection is associated with post-COVID symptoms," said Kelly Gebo, MD, MPH, co-first author of the study and professor of medicine at the Johns Hopkins University School of Medicine. "While cytokine levels declined across the entire study population from infection to day 90, the decline in cytokine levels was more pronounced in those who received convalescent plasma early in the disease. Therefore, it appears that when IL6 levels are persistently elevated during the COVID-19 recovery phase, it is likely that this will lead to post-COVID conditions."
Gebo said future studies could examine the impact of anti-IL6 agents in combination with other treatments for COVID-19 in outpatients.