Longitudinal study finds SARS-CoV-2 neutralizing antibodies decline a year after infection

By Jocelyn Solis-MoreiraJun 23 2021

Now that coronavirus vaccination efforts are underway, the next question for the public is: how long will immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the causative virus of coronavirus disease 2019 (COVID-19) – last? There has been some evidence of neutralizing antibodies specific for SARS-CoV-2 in individuals who recovered from prior infection. But is immunity gained from natural infection enough against SARS-CoV-2? New research published in the journal Frontiers in Immunology suggests antibodies gained from natural infection are not enough for sustained immunity.

Research led by Xin Zheng of Huazhong University of Science and Technology in Wuhan, China, found that about 90% of patients who recovered from COVID-19 continued to have IgG antibodies targeting the N-domain and receptor-binding domain of the spike protein. However, approximately 43% of patients showed signs of neutralizing antibody activity.

Study: Declining Levels of Neutralizing Antibodies Against SARS-CoV-2 in Convalescent COVID-19 Patients One Year Post Symptom Onset. Image Credit: ktsdesign / Shutterstock

The results suggest individuals who recovered from infection should get vaccinated to stimulate a long-term immune response against SARS-CoV-2.

Collecting data

The researchers compiled 162 serum samples from 76 patients who were infected with COVID-19 from December 2019 and March 2020. About 23 patients had severe symptoms, and 53 had mild symptoms. Patients were followed for a year after symptom onset. All patients showed evidence of at least one positive IgG antibody test while hospitalized or in the follow-up period.

Exclusion criteria included patients with fever, runny nose, cough, and upper respiratory tract infection symptoms within one month of the follow-up period. The researchers also excluded patients who were immunosuppressed because of HIV, patients with autoimmune disease taking oral hormonal or immunosuppressive drugs, patients who had convalescent plasma therapy, vaccinated individuals, and pregnant women.

To test neutralizing activity against variants of concern with the E484K mutation, the team also collected 53 samples 6 months after infection.

IgM versus IgG antibodies one year after SARS-CoV-2 infection

Immediately after recovering from COVID-19, patients had moderately high S- (96.8%) or N-specific (54.8%) IgM levels. After one year, only four cases tested positive for IgM antibodies targeting either the N protein (5.3%) or the receptor-binding domain of the S protein (1.3%).

The IgM levels peaked 1 to 2 months after presenting with symptoms. But this decreased over time, with IgM levels plummeting the most after 5 to 6 months.

In contrast, IgG antibodies stayed fairly consistent after a year. People with severe COVID-19 symptoms were more likely to have higher anti-N IgG antibody titers than those with mild symptoms. There were an observed 90.8% of anti-S and 88.2% anti-N IgG levels. IgG titers declined over time, but antibody levels remained positive.

There was no difference in IgG titers 9 to 10 months after infection. Similarly, there was no difference in IgM titers 11-12 months after infection — indicating the rate of decline slows down as time progressed.

Neutralizing antibodies decline after a year

About 57.5% of patients did not show neutralizing activity against SARS-CoV-2 one year after infection. People tended to have the highest titers for neutralizing activity after 3 to 4 months.

While 42.5% of patients still had detectable neutralizing antibodies after a year, they were very low neutralizing titers.

The results suggest that after a year, nonvaccinated individuals with prior infection become less protected against reinfection.

Factors potentially affecting neutralizing potency

Results showed patients who were men, younger than 65, and experienced a mild COVID-19 infection were more likely to have a high neutralizing antibodies.

About 44% of patients with mild symptoms had high neutralizing titers compared to 39.1% of patients with severe infection.

Neutralizing activity against B.1.351

Serum samples collected from 53 patients 6 months after infection were exposed to the B.1.351 variant. Of the 53, 12 (22.6%) displayed neutralizing activity against B.1.351.

Thus, when re-exposure does not occur, and humoral immunity wanes over time, VOC harbouring immune evasive capacities pose a particular danger for populations that acquired their SARS-CoV-2-specific immunity through natural infection,” wrote the team.

The results suggest neutralizing titers against the variant significantly waned over time. Though, more research is needed to test neutralizing activity against other variants harboring the E484K mutation, such as the B.1.617 variant spreading rapidly in India.