The impact of antibodies to other coronaviruses on risk of SARS-CoV-2 infection in mothers and infants

From the Lehman and Overbaugh Labs, Human Biology Division

Our immune system has been battling coronaviruses long before the introduction of SARS-CoV-2 and has developed antibodies against these culprits of the common cold. If we already have antibodies against other coronaviruses, could these offer some form of protection against SARS-CoV-2? Researchers in the labs of Drs. Dara Lehman and Julie Overbaugh, part of the Fred Hutch Human Biology Division, recently addressed this question and went a step farther to ask how the antibody response to SARS-CoV-2 infection might be different between mothers and their infants. This work, led by postdoctoral fellow Dr. Caitlin Stoddard, was recently published in Viruses.

Recognizing that “rates of morbidity and mortality due to SARS-CoV-2 infection differ greatly across age as well as in different populations world-wide,” Stoddard et al. predicted that one contributing factor might be “differences in pre-existing immune responses that recognize the SARS-CoV-2 virus in some capacity.” This prediction was made “because SARS-CoV-2 is a human coronavirus, which is closely related to a number of other human coronaviruses that cause the common cold (endemic human coronaviruses or eHCoVs).” In their recent study, Stoddard et al. explain that they “were specifically interested in differences between adults and children, and thus we designed our study to compare the antibody response to specific eHCoVs within a cohort of mothers and their infants in Kenya.” The Overbaugh lab has a long-standing collaboration with Kenyan clinicians, known as the Kenya Research and Training Center, which conducts “interdisciplinary international HIV research with a goal of improving health and informing health policies in Kenya and other countries in Africa”. Following in that tradition, Dara Lehman and colleagues established The Linda Kizazi cohort, a mother-infant cohort to study the impact of antiretroviral-treated maternal HIV infection on transmission of all other viruses from mother-to-child. Since “this cohort was being followed throughout the COVID-19 pandemic,” it provided “an opportunity (with the participant’s consent) to study immune responses to SARS-CoV-2 and eHCoVs in both adults and infants in a Kenyan population. It is the ongoing decades long collaboration between Kenyan and US clinicians, epidemiologists and basic scientists that continues to provide opportunities for research studies like the one presented in this paper,” the researchers explain.

Comparison of eHCoV antibody levels immediately prior to and after SARS-CoV-2 infection and seroconversion in infants and mothers.
eHCoV antibody levels immediately prior to and after SARS-CoV-2 infection and seroconversion in infants and mothers. Image taken from original article.

Infants are born with passively transferred eHCoV-specific antibodies from their mothers, which may protect the infants from early HCoV infection. However, maternal antibodies begin to decline after a few months, after which it is thought that children’s immune systems lack memory responses to HCoV infection. The authors first profiled eHCoV antibodies in mothers and their infants by looking at the amount of spike protein from the four most common eHCoVs from patient blood plasma samples. Initially, mothers and infants had similar levels of antibodies against all four eHCoVs, with the median age of infants being 9.7 weeks. However, as these maternally transferred antibody levels declined in infants at around 25 weeks, the eHCoV antibody levels in the mother were higher than in the infant at this time point. This finding highlights the limited window in which maternal antibodies might offer protection against eHCoV exposure. However, since “all Coronaviruses have a spike protein on their surface which are used to enter cells and are also recognized by specific antibodies,” the authors predicted that “some antibodies that are able to bind to and protect against a specific eHCoV may also be able to bind and protect against other CoVs, such as SARS-CoV-2.” To understand if eHCoV-specific antibodies offer some protection against SARS-CoV-2 in mothers and infants, the authors identified participants that had been infected with SARS-CoV-2 and compared the levels of different eHCoV antibodies in their plasma samples prior to and after SARS-CoV2 infection. “In this study, we used seroconversion [or detection of virus specific antibodies in the blood] as an indicator for SARS-CoV-2 infection,” Dr. Stoddard states. Interestingly, Stoddard et al. found that mothers and infants had increased antibodies to SARS-CoV-1 and SARS-CoV-2 following SARS-CoV-2 infection suggesting a cross-reactive antibody response to beta-coronaviruses. Furthermore, the authors did not detect a relationship between eHCoV antibody levels and susceptibility to SARS-CoV-2 infection in mothers or infants, suggesting that previous eHCoV exposures did not produce broad-acting immunity to SARS-CoV-2.

“While our study did not find a strong association with prior eHCoV antibody levels and protection from SARS-CoV-2 infection, we did detect some antibody responses that appear to be cross-reactive and also differences in specific responses between mothers and their infants. Larger studies across different populations will need to be conducted to further evaluate whether a recent infection with a related eHCoV is associated with a reduced chance of severe SARS-CoV-2 infections,” the authors note. Future work from the Lehman and Overbaugh teams focuses on characterizing “the SARS-CoV-2-specific antibody responses in this same Kenyan mother-infant cohort to try to understand the details of the SARS-CoV-2 antibody responses and how they differ in adults in children.” The authors emphasize that “we still don’t understand the factors that contribute to risk of infection with SARS-CoV-2 and the cofactors that contribute may be different in different groups. By studying populations in Africa and also children as well as adults, we have the opportunity to begin to define factors that may play a role globally in the pandemic.”

This work was supported by the National Institutes of Health and Canadian Institutes of Health Research.

Fred Hutch/University of Washington/Seattle Children's Cancer Consortium member Julie Overbaugh contributed to this research.

Stoddard CI, Sung K, Ojee E, Adhiambo J, Begnel ER, Slyker J, Gantt S, Matsen FA 4th, Kinuthia J, Wamalwa D, Overbaugh J, Lehman DA. 2022. Distinct Antibody Responses to Endemic Coronaviruses Pre- and Post-SARS-CoV-2 Infection in Kenyan Infants and Mothers. Viruses. 14(7):1517.