IgA Antibodies Appear to Protect Unvaccinated Against COVID-19: Study

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Findings from a study in Sweden provide one possible explanation for why some health care workers who were in contact with COVID-19 patients every day remain uninfected, even though they were not vaccinated against the disease.

“The reason why some of the staff did not contract the disease seems to have been that IgA (immunoglobulin A) was present in their respiratory tract,” announced the University of Gothenburg in a release.

“These antibodies, found naturally in the secretions of mucous membranes in the airways and gastrointestinal tract, can protect the body by binding to viruses and other invading organisms.”

Researchers at the university’s Sahlgrenska Academy examined 156 unvaccinated employees at five primary care health centers belonging to the Nötkärnan group in the Gothenburg area. The results were published in the European Journal of Immunology.

“We all have IgA. It’s found on the mucous membranes, and COVID-19 is an infection that spreads via those membranes,“ Christine Wennerås, an author of the study, said in a statement. ”We thought it was important to investigate what happened when completely healthy people encountered the coronavirus, before vaccines became available.”

Authors said their study tried to learn more about how immunity to COVID-19 develops in a relatively healthy group of people, noting that the “vast majority of published studies on COVID-19 have been cross-sectional and/or focused on hospitalized patients with severe disease.” Meanwhile, no one who contracted COVID-19 in their study was hospitalized.

Study Methods

The health workers were recruited into the study during April and May 2020, and were monitored every month for six months. Of the 156 participants, 150 completed the entire study.

In the study, researchers checked whether the participants ever contracted COVID-19. They also monitored all participants for serum IgA and IgG antibodies to the SARS-CoV-2 spike protein. Other health factors that appeared to afford protection against COVID-19 were also monitored, by having the participants take blood tests, questionnaire surveys, and more.

Authors found that a third, or 53 of the 150 health care workers had developed antibodies to COVID-19. The remaining two-thirds, or 97 of the 150 health care workers, comprise those who had a negative antibody response (no antibodies against the virus), or only borderline levels of IgA responses.

A total of 16 study participants had contracted COVID-19, verified by PCR, during the study period. Six study participants had been living with another PCR-positive person, the authors also noted.

Key Findings

Researchers said there were two main patterns of immune responses to SARS-CoV-2 among the 53 participants who developed antibodies—“an IgG-dominated and an IgA-dominated pattern.”

These people had detectable IgA and/or IgG antibodies to the SARS-CoV-2 spike protein, with 38 having antibody responses dominated by IgG (immunoglobulin G), while 15 showed antibody responses dominated by IgA.

“Only individuals with IgG responses developed T-cell responses to SARS-CoV-2. IgG responsiveness was associated with SARS-CoV-2 PCR positivity and self-reported typical COVID-19 symptoms,” researchers wrote. “In contrast, IgA responsiveness was associated with limited T-cell responses to SARS-CoV-2, autoimmunity, airborne allergy, and not contracting COVID-19.”

T cells, like antibodies, play an important role in the adaptive immune system to help prevent infection.

Authors said the first key finding was that the 15 people who had IgA-dominated responses—that is, one in ten study participants—never showed any symptoms of COVID-19 nor tested positive for the disease.

“SARS-CoV-2 IgA-only responders constituted 10 [percent] of our cohort which is in line with other studies, and 87 [percent] of them were already IgA-positive at the start of the study ... Interestingly, none of the IgA-only responders reported any COVID-19-associated symptoms nor had PCR-confirmed SARS-CoV-2 infection, which implies that SARS-CoV-2-specific IgA-responses may protect against contracting COVID-19,” the authors wrote.

“It is possible that this IgA response constituted cross-reactive IgA antibodies generated in response to other coronaviruses,” the authors noted.

A limitation of the study was that it only looked at serum IgA levels and did not look at nasal IgA levels, authors said. “The serum IgA we have monitored in this study may be said to be a surrogate marker of nasal IgA, the latter of which confers protection from Covid-19 by preventing virus entry into the body. A limitation of our study is that we did not investigate corresponding nasal IgA antibody levels to SARS-CoV-2 and their neutralizing capacity.”

The second key finding was that IgG-dominated antibody responses were “strongly associated” with T-cell responses and had PCR-confirmed COVID-19, authors reported. Being an IgG-responder was also “associated with PCR-positive COVID-19 and cohabitation with a PCR-positive person.”

Wennerås said that most other COVID-19 related research has been about IgG antibodies and T cells.

“The interesting thing is that when we now examine other people’s articles and tables, we find evidence for the conclusion we’ve arrived at about IgA ourselves,” she noted. “But it’s not something those studies have highlighted.”