As a result of the ongoing pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease, the coronavirus disease 2019 (COVID-19), the global public health at risk has never been more dire.

As a result of SARS-CoV-2 infection, antibodies are produced against a range of viral antigens, including the spike and the nucleocapsid protein. There is evidence that antibodies to the spike-S1 protein, and more specifically, the receptor-binding domain, can neutralize the virus. There’s been research showing people who had severe infections staying protected from the virus for months. But not much is known about how long immunity lasts after a mild infection.

Research led by Asa Bjorndal from the Public Health Agency of Sweden investigated people’s antibody response after mild symptoms. The findings showed Immunoglobulin G (IgG) antibodies that target the spike protein remained stable after 8 months. But antibodies targeting SARS-CoV-2’s nucleocapsid protein waned over time.

The research team writes:

“The well-characterized panel of serum samples presented here will be valuable for diagnostic performance and quality assessments of current and new serological assays.”

The study “Stable IgG-antibody levels in patients with mild SARS-CoV-2 infection” is available as a preprint on the medRxiv* server.

Study: Stable IgG-antibody levels in patients with mild SARS-CoV-2 infection. Image Credit: Corona Borealis Studio / Shutterstock

How they did it

Online ads promoting the study helped recruit participants from three Swedish counties. Potential participants filled out an online questionnaire as a prescreening on whether they would be likely to donate antibody-positive or negative serum samples and other demographic information. No participants had vaccine-induced antibodies because vaccination campaigns had not started yet in Sweden.

Patient characteristics

A total of 469 participants donated their serum from October 30 and December 8, 2020, and were eligible for the study. About 145 tested positive for previous COVID-19 infection. Initial sampling and follow-up showed there were no cases of reinfection.

Based on the follow-up visit on April 12, 2021, 28 out of the 324 who reported no previous infection were positive for SARS-CoV-2.

About 85% of patients tested positive for SARS-CoV-2 reported mild infection, with flu-like symptoms being the most common. People never infected with COVID-19 reported lung problems, and 17% believed they had COVID-19 infection in 2020.

Seropositivity and antibody testing

About 95% of people who recovered from COVID-19 showed evidence IgG antibodies specific for the SARS-CoV-2 nucleocapsid and spike protein. Four samples that were seronegative for IgG antibodies showed evidence of other antibodies targeting the nucleocapsid or spike protein.

Age and gender did not influence seropositivity or antibody levels.

Four percent that were self-reported as never been infected turned out seropositive for antibodies targeting SARS-CoV-2. From the 55 cases that reported not having been infected but suspected they were exposed to COVID-19, ten were seropositive.

Correlation of antibody levels among patient-cases and time between disease notification and serum sampling (n = 141, 4 outliers removed).

People who reported moderate to severe disease had higher antibody levels against the spike protein and nucleocapsid compared to people who reported mild symptoms.

Antibody testing showed no difference in IgG levels against the spike protein over time. However, antibody levels against the nucleocapsid protein decreased from patients diagnosed in the spring compared to when they were tested again in the fall.

The results suggest some antibodies gained after recovering from mild infection may decrease over time. Yet, the researchers note there was difficulty acquiring true negative serum samples — a limitation to the study.

Though one strength of the study was a broad collection of samples from the general population that showed recovery from mild COVID-19 disease, there is a possibility of sampling bias from online recruitment. Because of the non-random selection of participants, they suggest the study results are likely to underestimate the amount of undiagnosed COVID-19 cases.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Jocelyn Solis-Moreira

Jocelyn Solis-Moreira graduated with a Bachelor's in Integrative Neuroscience, where she then pursued graduate research looking at the long-term effects of adolescent binge drinking on the brain's neurochemistry in adulthood.