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Study suggests that pre-existing human antibodies to cold coronavirus interfere with SARS-CoV-2 immunity



The 2019 coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has claimed more than 5.3 million lives worldwide. This virus causes a wide range of symptoms ranging from mild to severe infection, which can also lead to death. Since the start of the pandemic, scientists have worked extremely hard to understand each phase of the virus; however, many aspects remain to be discovered.

Study: Pre-existing humoral immunity to human cold coronaviruses negatively impact protective antibody response against SARS-CoV-2. Image Credit: sdecoret / Shutterstock

Impact of the common cold on SARS-CoV-2 infection

One of the common viruses that circulated before SARS-CoV-2 is the human cold coronavirus (hCCCoV). There is no evidence linking susceptibility to COVID-19 infection and disease severity to the immune response induced after hCCCoV infection.

Four strains of the hCCCoV virus have been endemic in humans for decades. Usually these viruses infect the upper respiratory tract and cause colds or mild symptoms. Previous research has found that hCCCoV and SARS-CoV-2 share about 30% homology within their spike proteins. However, the severity of the symptoms is drastically different. These studies have also shown the presence of cross-reacting antibodies that bind to both viruses. However, as noted above, it is not yet clear whether hCCCoV antibodies have an impact on the immune response against SARS-CoV-2 infection.

Researchers believed that antibodies induced after hCCCoV infections could improve immunity against SARS-CoV-2 if they exhibit adequate cross-reactivity with SARS-CoV-2. This phenomenon was considered beneficial because these cross-reacting antibodies could enhance immune protection and promote viral clearance. However, another group of scientists claimed that pre-existing humoral immunity to hCCCoV could inhibit the production of effective SARS-CoV-2 specific antibodies by developing cross-reacting antibodies that do not neutralize SARS-CoV-2. .

They further indicated that existing immunity to hCCCoV could worsen infection by aiding virus invasion into FcR-expressing cells to cause improvement in antibody-dependent disease. This phenomenon is known as the immune fingerprint, first documented in influenza infections. Immune fingerprinting can interfere with the immune response to a new virus when pre-existing antibodies against the conserved epitopes dominate the immune response. However, these antibodies are not effective against the new virus.

Since pre-existing hCCCoV antibodies can influence the outcome of SARS-CoV-2 infection, understanding its role in COVID-19 disease is critical. Existing documents have revealed some conflicting reports. Some studies indicate that specific antibodies to hCCCoV are beneficial during SARS-CoV-2 infection, while others have denied such an effect. One reason for these inconsistent data is that most of these studies did not investigate the level of hCCCoV antibodies in the same individual before and after infection with SARS-CoV-2.

Some studies have reported that hCCCoV antibody levels do not correlate with the severity of SARS-CoV-2 disease, while other groups of researchers have contradicted this report. Recently, researchers have focused on the determination of anti-hCCCoV IgG, IgM and IgA antibodies, before and after infection with SARS-CoV-2. In this study cohort, SARS-CoV-2 infections were confirmed via RT-PCR test. This study was published on Host cell and microbe.

About the study

The authors found a significant increase in IgG antibodies to beta-coronaviruses; however, high levels of hCCCoV antibodies were not associated with the protection of an individual against infection with SARS-CoV-2. One of the interesting correlations reported in this study is that a greater increase in anti-hCCCoV antibodies is linked to higher antibody levels against SARS-CoV-2 after infection. This result is consistent with previous reports showing that memory B cells specific for hCCCoV infection impacted subsequent SARS-CoV-2 infection. These antibodies did not neutralize SARS-CoV-2.

In this study, the scientists used the mouse model, where mice were vaccinated with hCCCoV spike proteins before being introduced into the SARS-CoV-2 spike. They found that mice vaccinated with hCCCoV spike proteins before the SARS-CoV-2 spike exhibited a profound decrease in neutralizing SARS-CoV-2 antibodies compared to mice immunized only with the SARS-CoV-2 spike.

Previous studies have indicated that several factors, such as age, gender, comorbidity, etc., influence susceptibility to infection with SARS-CoV-2. The current study added to the list of factors by revealing that hCCCoV immunity inhibits effective immunity against SARS-CoV-2 infection. The B cells of a person infected multiple times with hCCCoV are refined through affinity maturation and clonal selection, resulting in the production of higher affinity hCCCoV-specific antibodies.

Because SARS-CoV-2 is a new virus, it was surprising that IgM antibodies did not precede IgG antibodies. This study hypothesizes that beta-coronavirus IgG and IgA antibody levels are the most important determinant of an individual’s cumulative response to hCCCoV rather than the timing of recent infection. Additionally, although younger age groups are more exposed to hCCCoV than older individuals, the IgM bias of hCCCoV in younger participants may be the reason younger individuals suffer from less severe disease. than older individuals.


One of the limitations of this study is the small sample size. Another limitation is that the study cohort only included employees, which restricted the age of participants, i.e. the cohort lacked individuals below 18 years of age or over 65 years old. Importantly, the present study indicates that preexisting hCCCoV IgG antibodies may inhibit the immune response to SARS-CoV-2.