Nine months into the COVID-19 pandemic, researchers are continuing to find new insights into the mechanisms of the virus behind the disease, called SARS-CoV-2.

An October study published by researchers at U of T and Mount Sinai Hospital in the journal Science Immunology showed that SARS-CoV-2 antibodies can be detected in COVID-19 patients’ blood and saliva for up to three months after the first onset of symptoms. This indicates a sustained response to the viral infection. This study was also one of the first to investigate SARS-CoV-2 antibodies in saliva.

Saliva tests for the presence of SARS-CoV-2 are already widely available, and these results raise the possibility of also testing for COVID-19 immunity with saliva.

Antibody detection in the fight against COVID-19

Antibodies are an important part of the body’s immune response and can provide information about an individual’s immunity and stage of infection. There are three main types of antibodies involved in COVID-19 antibody tests: IgG, IgA, and IgM. These antibodies can target specific viruses to help fight infection. For instance, anti-SARS-CoV-2 viruses bind to and “neutralize” proteins characteristic of the virus, inhibiting their function.

Jennifer Gommerman in U of T’s Department of Immunology and Anne-Claude Gringas at Mount Sinai Hospital’s Lunenfeld-Tanenbaum Research Institute were senior authors of the paper. The Gingras Laboratory had been working with techniques in immunology and proteomics — the study of proteins — prior to the pandemic. When COVID-19 hit, the lab made a swift transition to direct their resources and expertise to study blood and saliva antibodies for SARS-CoV-2.

The researchers detected SARS-CoV-2 antibodies using a standard procedure called an enzyme-linked immunosorbent assay, also used in HIV detection and some pregnancy tests. The researchers detected anti-SARS-CoV-2 IgG, IgA, and IgM antibodies that were capable of binding and neutralizing specific viral proteins and measured their concentrations in blood and saliva. 

Blood samples from 439 individuals and saliva from 128 individuals were collected over the course of 115 days and analyzed for their antibody levels over time. Three groups were compared: acute COVID-19 patients who were recently infected, patients who had recently recovered, and uninfected individuals who had never contracted COVID-19.

IgG antibodies detected up to three months after first onset of symptoms

Anti-SARS-CoV-2 IgG, IgA, and IgM antibodies were detected in COVID-19 patients, but only IgG antibodies persisted, while IgA and IgM decayed rapidly after infection. For most patients, IgG remained in both blood and saliva for up to 105 days after the first COVID-19 symptoms were reported.

The question of whether SARS-CoV-2 antibodies persist or decay over time has faced contradicting results from scientists, likely due to differences in research methodologies. In an interview with The Varsity, Gommerman said that it’s unclear exactly how long COVID-19 immunity lasts, as studies are still ongoing and long-term data is not yet available. 

Gommerman expressed that the persistence of IgG antibodies for three months thus far suggests a lasting immune response, during which reinfection is unlikely. “When a vaccine does come along, we’re going to make a strong robust antibody response to a vaccine,” she said. “And it’s not just going to die right away. It’s going to be a sustained antibody response.”

Some unexposed individuals found to possess SARS-CoV-2 antibodies

Some aspects of the antibody response to SARS-CoV-2 remain unclear. In an interview with The Varsity, co-author and PhD candidate Baweleta Isho describes early COVID-19 research, which found that the IgA response to the virus occurred before the IgG response, an unusual occurrence for viral infections.

“In a viral infection, normally we see the IgM response first, followed by an IgG response, and later on, we would see an IgA response,” Isho explained. “This is why we really wanted to explore why we were seeing this IgA… response before the IgG response.”

Interestingly, Isho and her colleagues found that while the unexposed individuals — as expected — had low IgG and IgM antibodies against SARS-CoV-2, a small percentage of uninfected individuals were found to have anti-SARS-CoV-2 IgA antibodies. The reason for this remains unclear and requires further research.

Antibody levels in saliva are reflective of antibodies in blood

Previous research has demonstrated detection of SARS-CoV-2 antibodies in blood and viral RNA in saliva; however, this study was one of the first to examine SARS-CoV-2 antibodies in saliva.

Saliva antibodies were found to be well-correlated with blood serum antibodies, especially for IgG. As such, saliva antibody tests could be developed as a convenient, non-invasive alternative to blood tests when assessing COVID-19 immunity. 

“Since we found that IgG — and a lot of other papers have come out saying — that IgG is detectable up to six months post-symptom-onset, this would be a good way to determine the degree of immunity toward the virus that a certain population would have,” PhD candidate Michelle Zuo, another co-author of the paper, said in a Zoom interview with The Varsity

“And since saliva is an easy biofluid to collect, this could be turned into home testing kits that we could send out to the population and just have them report the results. This way we would get a better grasp on who is actually developing a new response to the virus and might have had it already,” Zuo said.

Gommerman also noted that saliva tests could be particularly advantageous in circumstances where blood tests are difficult to obtain, for example in pediatrics.

However, a drawback of saliva tests is that antibody concentrations are typically lower in saliva than in blood. As such, sensitivity must be improved and tests must be standardized before saliva antibody tests can be used clinically or in home testing kits.