COVID-19 virus triggers antibody response from prior coronavirus infections

According to the results of a study, the immune systems of COVID-19 patients may depend on antibodies that were produced during infections from previous coronaviruses to help combat the disease.

John Altin. Image Credit: The Translational Genomics Research Institute

The study was headed by Northern Arizona University and the Translational Genomics Research Institute (TGen)—an affiliate of the City of Hope.

For humans, COVID-19 is not their first encounter with a coronavirus—so named because of the presence of crown-like, or corona, protein spikes on their surface.

Prior to SARS-CoV-2—the virus that is responsible for causing the COVID-19 disease—human beings have navigated a minimum of six other forms of coronaviruses.

The new study set out to interpret how coronaviruses (CoVs) are able to trigger the human immune system and perform a deeper dive into the internal workings of the antibody reaction. The findings were recently published in the Cell Reports Medicine journal.

Our results suggest that the COVID-19 virus may awaken an antibody response that existed in humans prior to our current pandemic, meaning that we might already have some degree of pre-existing immunity to this virus.”

John Altin, PhD, Study Senior Author Assistant Professor, Infectious Disease Branch, The Translational Genomics Research Institute

This understanding could help scientists design novel diagnostics, develop novel therapeutic treatments, assess the healing powers of convalescent plasma, and—most significantly—help develop upcoming monoclonal antibody therapies or vaccines that can protect against mutations that may manifest in the COVID-19 virus.

The investigators employed a tool known as PepSeq to finely plot the reactions of the antibodies to all coronaviruses that infect humans.

Being designed at TGen and NAU, PepSeq is an innovative technology that helps build extremely diverse pools of peptides (that is, short chains of amino acids) attached to DNA tags. When integrated with high-throughput sequencing, the PepSeq molecule pools enable deep interrogation of the antibody reaction to viruses.

The data generated using PepSeq allowed for broad characterization of the antibody response in individuals recently infected with SARS-CoV-2 compared with those of individuals exposed only to previous coronaviruses that now are widespread in human populations,”

Jason Ladner, PhD, Assistant Professor, Pathogen and Microbiome Institute, Northern Arizona University

The Pathogen and Microbiome Institute integrates the translational genomics capacity of TGen and the academic genomic research focus of NAU. Dr Ladner is the lead author of the study.

In addition to SARS-CoV-2, scientists analyzed the antibody reactions from two other coronaviruses that are potentially lethal—SARS-CoV-1, the first pandemic coronavirus that was responsible for causing the 2003 outbreak in Asia of Severe Acute Respiratory Syndrome, and MERS-CoV, which was responsible for causing the 2012 outbreak in Saudi Arabia of Middle East Respiratory Syndrome.

All three pathogens are examples of coronaviruses that infect animals, but emerged to make humans sick and became novel human pathogens.

Besides defining antibodies that detect SARS-CoV-2, the team also studied the antibody reactions of four older coronaviruses—that is, alphacoronavirus NL63; alphacoronavirus 229E; betacoronavirus HKU1; and betacoronavirus OC43.

While the so-called “common” coronaviruses are endemic across human populations, they are generally not lethal and cause only mild upper respiratory infections analogous to those of the common cold.

The researchers compared the reactivity patterns against these diverse coronaviruses and showed that SARS-CoV-2 may summon immune system antibodies that were initially produced in response to previous infections caused by coronaviruses.

This cross-reactivity took place at two locations in the SARS-CoV-2 Spike protein; this protein is found on the surface of virus particles that binds to ACE2 proteins on human cells to ease the entry of cells and thus infections.

Our findings highlight sites at which the SARS-CoV-2 response appears to be shaped by previous coronavirus exposures, and which have potential to raise broadly-neutralizing antibodies. We further demonstrate that these cross-reactive antibodies preferentially bind to endemic coronavirus peptides, suggesting that the response to SARS-CoV-2 at these regions may be constrained by previous coronavirus exposure.”

John Altin, PhD, Study Senior Author Assistant Professor, Infectious Disease Branch, The Translational Genomics Research Institute

Dr Altin added that more studies are required to figure out the implications of these discoveries. The findings may allow scientists to describe the extensively varying reactions displayed by COVID-19 patients toward the disease; ranging from mild symptoms to no symptoms, to severe infections that require hospitalization, and even leading to death in some cases.

Another possibility is that variations in the pre-existing antibody response detected in the new research work could help describe certain differences in how severely COVID-19 disease manifests in old people versus young people, who will have diverse histories of infections with the common coronaviruses.

“Our findings raise the possibility that the nature of an individual’s antibody response to prior endemic coronavirus infection may impact the course of COVID-19 disease,” concluded Dr Ladner.