Ana Citlali Márquez

Advanced age is an established risk factor for SARS-CoV-2 infection and severe disease. Older adults, having experienced recurrent infections with human endemic coronaviruses (HCoVs) throughout life, may have developed humoral immune responses that impact IgG targeting of both severe acute respiratory syndrome coronavirus (SARS-CoV) −2 and HCoVs. We profiled IgG responses in community-dwelling adults aged 50-87 years from the “PRospEctiVe EvaluatioN of immunity after COVID-19 vaccines” (PREVENT-COVID) prospective cohort study. Dried blood spot sampling occurred at baseline, prior to detected SARS-CoV-2 antigen exposure, and throughout the recommended vaccination schedule in Canada for SARS-CoV-2 seronegative and seropositive individuals. We define an HCoV-OC43-IgG high and HCoV-NL63-low baseline antibody landscape, which was unaffected by age or sex. Following COVID-19 vaccination, we observed increased anti HCoV-OC43 and HCoV-HKU1 IgG antibody titers, with substantial waning between doses. IgG specific to beta-coronaviruses and SARS-CoV-2 spike antigens positively correlated, strengthening with subsequent doses. In contrast, SARS-CoV-2 anti-nucleocapsid (N) antibodies associated most closely with HCoV-NL63 IgG levels. These findings suggest that HCoV-specific humoral immunity induced by COVID-19 vaccination or disease may impact susceptibility to future coronavirus infection. ACE2-binding assays revealed that individuals with greater HCoV-OC43- and HCoV-HKU1-specific IgG levels had the highest percent neutralization of the wildtype virus and SARS-CoV-2 variants. Together, our study highlights potential effects of COVID-19 vaccination on humoral immunity towards related coronaviruses.

Breast milk can provide passive immunity to infants, serving as a valuable source of maternal antibodies while remaining a non-invasive sample for investigating maternal immune responses. To date, no studies have evaluated SARS-CoV-2 and potentially cross-reactive HCoV antibodies in breast milk following bamlanivimab administration. A 36-year-old postpartum female was PCR-positive for SARS-CoV-2 four days post-delivery. Bamlanivimab was administered intravenously two days later. Breast milk was collected before bamlanivimab infusion, daily for two weeks post-infusion, then weekly until 102 days post-infusion. Mother and infant sera were collected only at 102 days post-infusion. All milk and serum samples were tested for IgG antibodies against SARS-CoV-2 and HCoV. We observed two distinct SARS-CoV-2 antibody peaks at days 3 and 29 post-infusion, likely representing bamlanivimab transfer and the post-infection antibody response. Beta-HCoV antibodies showed two peaks at days 6 and 29, potentially representing backboosted beta-HCoV responses and/or antibody cross-reactivity with SARS-CoV-2. Infant seropositivity for SARS-CoV-2 102 days post-infusion may represent antibodies from passive transfer via breastfeeding or a subclinical infection. This case highlights the value of breast milk as a non-invasive and repeatable sample to help understand maternal immune responses post-infection, exogenous antibody infusion, and passive antibody transfer during breastfeeding, which can provide insights into maternal–infant health research.

There is a limited understanding of the immunological differences between children and adults that protect children from developing severe coronavirus disease 2019 (COVID-19) following SARS-CoV-2 infection. Previous infection with endemic human coronaviruses (HCoVs) has been suggested as a factor. In this study, we used 100 paired residual samples collected before and during the COVID-19 pandemic from children in Bangladesh. We compared the changes in their sero-status (no COVID-19 vs. COVID-19) and quantified antibody levels to HCoVs. We found that although 45% of the children seroconverted for IgG antibodies against SARS-CoV-2, there was no correlation between evidence of previous infection with HCoVs and the magnitude of SARS-CoV-2 antibody responses post-infection. Moreover, no differences in the anti-HCoV antibody levels were found pre- and post-SARS-CoV-2 infection.

Background: Investigating antibody titers in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time. Methods: Human coronavirus (HCoV) IgG antibodies were measured longitudinally in a prospective cohort of qPCR-confirmed, COVID-19 recovered individuals (k = 57) in British Columbia pre- and post-vaccination. SARS-CoV-2 and endemic HCoV antibodies were measured in serum collected between Nov. 2020 and Sept. 2021 (n = 341). Primary analysis used a linear mixed-effects model to understand the effect of single dose vaccination on antibody concentrations adjusting for biological sex, age, time from infection and vaccination. Secondary analysis investigated the cumulative incidence of high SARS-CoV-2 anti-spike IgG seroreactivity equal to or greater than 5.5 log10 AU/mL up to 105 days post-vaccination. No re-infections were detected in vaccinated participants, post-vaccination by qPCR performed on self-collected nasopharyngeal specimens. Results: Bivariate analysis (complete data for 42 participants, 270 samples over 472 days) found SARS-CoV-2 spike and RBD antibodies increased 14–56 days post-vaccination (p < 0.001) and vaccination prevented waning (regression coefficient, B = 1.66 [95%CI: 1.45–3.46]); while decline of nucleocapsid antibodies over time was observed (regression coefficient, B = −0.24 [95%CI: −1.2-(−0.12)]). A positive association was found between COVID-19 vaccination and endemic human β-coronavirus IgG titer 14–56 days post vaccination (OC43, p = 0.02 & HKU1, p = 0.02). On average, SARS-CoV-2 anti-spike IgG concentration increased in participants who received one vaccine dose by 2.06 log10 AU/mL (95%CI: 1.45–3.46) adjusting for age, biological sex, and time since infection. Cumulative incidence of high SARS-CoV-2 spike antibodies (>5.5 log10 AU/mL) was 83% greater in vaccinated compared to unvaccinated individuals. Conclusions: Our study confirms that vaccination post-SARS-CoV-2 infection provides multiple benefits, such as increasing anti-spike IgG titers and preventing decay up to 85 days post-vaccination.