New Antibody Analysis Predicts Severe-COVID-19 Outcomes

After more than a year from the start of the COVID-19 pandemic, there is still a lack of personalized predictors of the course of the disease and its outcomes. Also, the immunological drivers of mortality and survival outcomes within severe COVID-19 patients remain unclear.

Recently, a group of researchers led by the University of Pittsburgh, Georgia Institute of Technology and Emory University researchers, published a study in which they performed a comprehensive analysis of COVID-19 antibodies in a set of patients with severe disease. 

The team found that antibody profiles of internal viral proteins, including those conserved across coronaviruses, predicted which patients survived or diet just as well as corresponding profiles for surface proteins. 

Previous studies have mainly focused on the spike protein and the receptor-binding domain. In this study, the team found concrete evidence that specific antibodies against internal proteins are also positively associated with survival in severe COVID-19. 

Potential Target for New Therapies and Vaccines

Canonical antibodies include spike, receptor-binding domain, and nucleocapsid antigens, while non-canonical antibodies include orf3a, oft8, nsp3, nps13, and membrane antigens. 

To find out if the immune response to these non-canonical antigens could predict survival in severe COVID-19, the team analyzed blood samples of 21 hospitalized patients with severe disease in 2020, prior to vaccines, and analyzed their antibodies to three canonical and four non-canonical antigens. 

In the end, the team found that both canonical and non-canonical antibodies were equally predictive of survival outcomes, suggesting that non-canonical antibodies may play a role in recovery from severe disease. 

According to the researchers, most monoclonal antibodies to treat COVID-19 have become less effective, and far fewer mutations have accumulated in the virus’s internal proteins, which suggests that they are a potential target for future therapies and vaccines. 


Sai Preetham Peddireddy, et al. Antibodies targeting conserved non-canonical antigens and endemic coronaviruses associate with favorable outcomes in severe COVID-19. Cell Reports, 2022; 111020 DOI: 10.1016/j.celrep.2022.111020 

University of Pittsburgh. “Beyond the spike: New antibody analysis predicts severe COVID-19 outcomes.” ScienceDaily. ScienceDaily, 27 June 2022. <>. 

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