Quality of Antibodies May Be Tied to Differing COVID-19 Outcomes, Harvard Researchers Find

For patients with severe COVID-19, the key to survival may depend on the quality, rather than the quantity, of their antibody response and development, a recent study from a team of researchers at Harvard Medical School teaching hospital Massachusetts General Hospital suggests.

Medical School Professor Galit Alter, who spearheaded the study, co-leads the pathogenesis working group of the Massachusetts Consortium on Pathogen Readiness, which was borne from a $115 million collaboration between the University and Guangzhou Institute for Respiratory Diseases — a Chinese research institute — funded by Fortune Global 500 company China Evergrande Group.

Since the start of the pandemic, scientists have worked to understand the virus’s biological mechanisms, including human immune response and antibodies developed against the infection. A lack of existing therapeutics for the virus has pushed researchers to explore different methods to fight the virus beyond vaccination, including treatments using antibodies to bolster immune response.

The study — published Nov. 3 in the peer-reviewed journal Cell — profiled and compared the immune responses of 193 hospitalized COVID-19 patients over the first three weeks following onset of symptoms. To determine whether immune responses differed based on degree of disease severity, researchers stratified patients into three groups: inpatients with moderate infection who recovered, those with severe infection who recovered, and those whose underlying cause of death was the virus.

The team found that while patients in all three groups developed antibodies against the virus, the development and evolution of those antibodies differed: For the patients who did not survive, the antibody response never completely evolved.

In a Nov. 13 press release from Massachusetts General Hospital, Alter said the researchers observed a “significant defect” in immunoglobulin G — the most common type of antibody — among non-survivors.

“There was a significant defect in the development of IgG antibodies, which may be essential in the early control and elimination of the virus,” Alter said in the release. “Here, we were able to see the global impact of this defective IgG evolution, resulting in a compromised ability to promote essential viral clearing immune functions.”

The researchers also found that the immune systems of surviving patients could recognize and target the S2 domain, an area of the virus spike protein found in other human coronaviruses.

In the press release, co-first author and MIT biological engineering graduate student Tomer Zohar said the implications of this research extend beyond COVID-19 infection: The preexisting immunity developed following infection may generate killer antibodies against other coronaviruses at faster rates.

“If we can further understand the importance of cross-coronavirus immunity, researchers may be able to design vaccines able to counteract a much broader range of coronaviruses,” Zohar said in the press release.

—Staff writer Virginia L. Ma can be reached at virginia.ma@thecrimson.com.