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COVID-19 Antibody Immunity May Last Only a Few Weeks

A new study adds to growing concern about short immunity duration and the potential for reinfection.

As the recent headlines about the case of COVID-19 reinfection in Nevada suggest, the human body’s antibody response—and thus immunity—to SARS-CoV-2 appears to be fleeting.

A new analysis published on September 10 by the journal PLOS Pathogens does nothing to dispel this observation—or concern.

Unfortunately, the results show that the neutralizing activity of antibodies from recovered patients is typically not strong and it declines sharply within one month after hospital discharge.

►Antibody immunity is not the only story when it comes to COVID-19 — Learn More: Emerging Data Support Lasting COVID-19 Immunity Via T Cells

For their analysis, the researchers—from the Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School in Nanjing, China—continuously monitored SARS-CoV-2-specific antibody responses in 19 patients with mild to moderate COVID-19 and 7 patients with severe disease for 7 weeks from disease onset.

Although most patients generated antibody responses against SARS-CoV-2, including the viral nucleoprotein (NP) and 3 parts of the spike protein (the receptor-binding domain, S1 protein, and ectodomain), 80.7% of those who recovered had varying levels of antibody neutralization activity against the virus (with S1-specific and ECD-specific IgA responses) and only a small portion of patients elicited a potent level of neutralization activity, according to the researchers.

“Our study demonstrated that the majority of COVID-19 patients generated a distinct profile of immune response against NP and spike protein-related antigens in both time and magnitude aspects,” wrote the researchers, who did not respond to requests for comment on their findings. “Therefore, combining NP and ECD as detecting antigens could further enhance the sensitivity of the serological assay.”

In addition, “a rapid decline in these neutralizing activities was observed, accompanied by a sharply reduced RBD-specific IgA response,” they added.

Overall, 3 to 4 weeks following hospital discharge, the neutralizing activity of antibodies from recovered patients declined significantly, placing them at risk for reinfection, the researchers said. Meanwhile, the 7 patients with severe COVID-19 had high titers of non-neutralizing antibodies that may contribute to antibody-dependent enhancement of infection.

According to the authors, the study provides important insights for serological testing, antibody-based intervention, and vaccine design.

“The majority of patients generated potent humoral responses recognizing spike protein-related antigens, including RBD, S1 and ECD proteins, implying their high immunogenicity makes them vaccine candidates,” the researchers wrote. “Additionally, our correlation analyses showed that the neutralizing activities were strongly correlated with ECD-specific IgA and S1-specific IgA responses, compared to RBD-specific IgA responses. Collectively, our study and others [suggest] that the antibodies targeting at diverse domains of the spike protein might greatly contribute to higher neutralization activities. Consequently, the inclusion of the full-length spike protein might be ideal to elicit humoral responses targeting to the major neutralizing targets. Moreover, the IgG subclass responses in COVID-19 patients were skewed toward IgG1 and IgG3, and induction of optimal antibody isotypes such as IgA and certain IgG subclasses such as IgG2 might be desired in vaccine studies of SARS-CoV-2.”

Perhaps a “silver lining” in a black cloud of data when it comes to duration of immunity.

Editorial Note: This study did not concern T cell immunity, only the upfront antibody response.