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Protein ‘signature’ linked to severe COVID-19 outcomes identified, Mass General Hospital study says

The entrance to Massachusetts General Hospital on Fruit Street in Boston. Researchers there have identified what’s known as a protein “signature” linked to severe health outcomes including death for people who contract COVID-19, according to an article published Tuesday in the Harvard Gazette.Lane Turner/Globe Staff

Massachusetts General Hospital researchers have identified what’s known as a protein “signature” linked to severe health outcomes including death for people who contract COVID-19, according to an article published Tuesday in the Harvard Gazette.

Researchers led by Dr. Marcia Goldberg, an MGH infectious disease expert, and Dr. Michael Filbin, an attending physician and head of clinical research in the hospital’s Emergency Department, recently published their findings in the journal Cell Reports Medicine.

They defined patients with severe COVID-19 as those who either required intubation or died within 28 days of admission to MGH, according to the Gazette article, the official news publication of Harvard University.


Researchers analyzed blood samples from 306 patients who tested positive for COVID-19, as well as samples from 78 patients with similar symptoms who tested negative. The team determined that “the most prevalent severity-associated protein, a pro-inflammatory protein called interleukin-6, or IL-6, rose steadily in patients who died, while it rose and then dropped in those with severe disease who survived.”

The article said early attempts by other groups to treat COVID-19 patients suffering from acute respiratory distress with IL-6 blockers “were disappointing,” though more recent studies combining these meds with a steroid called dexamethasone could be promising.

Goldberg believes the “proteomic signatures” identified in the study will be a boon to researchers.

“They are highly likely to be useful in figuring out some of the underlying mechanisms that lead to severe disease and death in COVID-19,” Goldberg, director of the Goldberg Laboratory at MGH and a professor of emergency medicine at Harvard, told the Gazette.

Researchers at MGH have long been at the center of cutting-edge research on the pandemic.

In February, researchers at the Ragon Institute of MGH, MIT, and Harvard and Massachusetts General Hospital published a study in the journal Nature Medicine that found one type of antibody may be driving severe COVID-19 in adults, while a different type may be driving a rare but dangerous condition called multisystem inflammatory syndrome in children that youngsters with COVID-19 can develop.


In the case of adults with severe COVID-19, researchers said, increased levels of different antibodies, IgA antibodies, could be the problem.

Those antibodies interact with a type of immune cells called neutrophils and cause the neutrophils to release cytokines, Galit Alter, a core member of the Ragon Institute, said in the statement.

Yannic Bartsch, the study’s first author and a research fellow at the institute, said in a February statement, “In adults with severe COVID-19, high levels of IgA antibodies could be driving neutrophils to release too many cytokines, with the potential of causing a cytokine storm.”

The study said the “unpredictable nature” of the severity of disease is “alarming.”

And it suggested “in the absence of therapeutics able to reverse these clinical manifestations, understanding the immunological mechanisms that underlie these unusual complications of [coronavirus] infection might provide critical insights for the design and delivery of therapeutics for these unique populations.”

Public health officials have also stressed that vaccines are also key to reducing bad health outcomes.

Governor Charlie Baker has touted the state’s success in vaccinating most of its senior population, a group particularly vulnerable to severe COVID-19.

And Dr. Paul Biddinger, medical director for emergency preparedness at Mass General Brigham and chair of the state’s COVID-19 vaccine advisory group, told reporters during a briefing with the governor Monday that vaccination against the virus protects all age groups from the most dire outcomes.


Biddinger said that “in all age groups, we see data that shows that fully vaccinated individuals have a decreased risk of dying, by more than 29 times what it would be if they were unvaccinated.”

Travis Andersen can be reached at