Researchers have identified five immune response markers which, collectively created "antibody signatures" that could correctly classify both COVID-19 patients who recovered and those who did not survive the disease.

The team of researchers from the Ragon Institute of MGH, MIT and Harvard (Cambridge, MA, USA) and the University of Washington School of Medicine (Seattle, WA, USA) collected samples from 22 hospitalized COVID-19 patients in the earlier months of the coronavirus pandemic, out of whom 12 had recovered and 10 had died. The researchers used the systems serology technique, an approach that relies on 60-plus assays to create a detailed profile of the immune response, to compare the immune responses of those who had survived to those who had not.

SARS-CoV-2 has two main proteins - the spike (S) protein and the nucleocapsid (N) protein - that provoke a response from the humoral immune system, which is responsible for antibody production. The N protein is produced at significantly higher levels in the virus than the S protein, although previous studies have shown that an immune response to the N protein does not provide protection against SARS-CoV-2. The researchers compared the immune responses from the recovered individuals to the deceased and found that patients who had recovered had a humoral immune response that responded mostly to S protein, while patients who had died had a shift in immunodominance such that they had a stronger immune response to the N protein. This immunodominance shift could be detected by measuring five immune response markers: IgM and IgA1 responses to S protein and antibody-dependent complement deposit, IgM, and IgA2 response to N protein.

With these five markers, the researchers built a model that could correctly classify clinical samples as belonging to deceased or convalesced individuals. To verify this model, 40 clinical COVID-19 samples, including 20 from convalesced individuals and 20 from deceased patients, were assayed. The results showed the same S protein to N protein shift in immunodominance in deceased individuals as compared to convalesced ones. Furthermore, in the samples analyzed, this immunodominance shift was more predictive of recovery or death than demographic factors such as age or sex. How these predictive immune markers may be influenced by risk factors of COVID-19, time course of infection, or severity of disease is yet to be determined. Nonetheless, the study provides a potential way to identify patients at high risk for mortality based on individual immune responses and may drive help rational vaccine design.

“Finding these early antibody signatures also may have implications for assessing COVID-19 vaccine candidates to ensure they produce an immune response similar to that of individuals who survive natural infection," said Helen Chu, associate professor of medicine, Division of Allergy and Infectious Diseases, and a physician at UW Medicine.

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