ABSTRACT
Infant antibody responses to viral infection can differ from those in adults. However, data on the specificity and function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in infants, and direct comparisons between infants and adults are limited. We characterized antibody binding and functionality in convalescent plasma from postpartum women and their infants infected with SARS-CoV-2 from a vaccine-naive prospective cohort in Nairobi, Kenya. Antibody titers against SARS-CoV-2 Spike, receptor binding domain and N-terminal domain, and Spike-expressing cell-surface staining levels were significantly higher in infants than in mothers. Plasma antibodies from mothers and infants bound to similar regions of the Spike S2 subunit, including the fusion peptide (FP) and stem helix-heptad repeat 2. However, infants displayed higher antibody levels and more consistent antibody escape pathways in the FP region compared to mothers. Finally, infants had significantly higher levels of antibody-dependent cellular cytotoxicity (ADCC), though, surprisingly, neutralization titers between infants and mothers were similar. These results suggest infants develop distinct SARS-CoV-2 binding and functional antibody repertoires and reveal age-related differences in humoral immunity to SARS-CoV-2 infection that could be relevant to protection and COVID-19 disease outcomes.
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , COVID-19 , Drug-Related Side Effects and Adverse ReactionsABSTRACT
Background: The COVID-19 pandemic resulted in disruptions to routine HIV services for youth living with HIV (YLH), provoking rapid adaptation to mitigate interruptions in care. The Adolescent Transition to Adult Care for HIV-infected Adolescents (ATTACH) study (NCT03574129) was a hybrid I cluster randomized trial testing the effectiveness of a healthcare worker-delivered disclosure and transition intervention – the Adolescent Transition Package (ATP). During the pandemic, HCWs leveraged phone delivery of the ATP and were supported to make adaptations. We characterized real-time, provider-driven adaptations made to support phone delivery of the ATP. Methods: We conducted continuous quality improvement (CQI) meetings with healthcare workers (HCWs) involved in phone delivery of the ATP at 10 intervention sites. CQI meetings used plan-do-study-act (PDSA) cycles and were audio-recorded. Adaptations were coded by two-independent coders using the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS). Adaptation testing outcomes (adopt, retest or abandon) and provider experience implementing the adaptations were also recorded. We summarized adaptation characteristics, provider experience and outcomes. Results: We identified 72 adaptations, 32 were unique. Overall, adaptations included modification to context (53%, n=38), content (49%, n=35), and evaluation processes (13%, n=9). Context adaptations primarily featured changes to personnel, format and setting, while content and evaluation adaptations were frequently achieved by simple additions, repetition, and tailoring/refining of the phone delivery strategy. Nine adaptations involved abandoning, then returning to phone delivery. HCWs sought to increase reach, improve fidelity, and intervention fit within their context. Most adaptations (96%, n=69) were perceived to increase the feasibility of phone delivery when compared to before the changes were introduced, and HCWs felt 83% (n=60) of adaptations made phone delivery easier. Most adaptations were either incorporated into routine workflows (47%) or tested again (47%). Conclusion: Adaptation of phone delivery was a feasible and effective way of addressing challenges with continuity of care for YLH during the COVID-19 pandemic. Adaptations were primarily context adaptions. While FRAME-IS was apt for characterizing adaptations, more use cases are needed to explore the range of its utility. Incorporating for a strategy for tracking outcomes within FRAME-IS may further our understanding of how adaptations influence implementation. Trial Registration: Trial registered on clinicaltrial.gov as NCT03574129.
Subject(s)
COVID-19 , HIV InfectionsABSTRACT
ABSTRACT Background HIV may increase SARS-CoV-2 infection risk and COVID-19 severity generally, but data are limited about its impact on postpartum women and their infants. As such, we characterized SARS-CoV-2 infection among mother-infant pairs in Nairobi, Kenya. Methods We conducted a nested study of 53 HIV-uninfected and 51 healthy women living with HIV, as well as their HIV-exposed uninfected (N=41) and HIV-unexposed (N=48) infants, participating in a prospective cohort. SARS-CoV-2 serology was performed on plasma collected between 1 May-31 December 2020 to determine the incidence, risk factors, and symptoms of infection. SARS-CoV-2 RNA PCR and sequencing was also performed on stool samples from seropositive participants. Results SARS-CoV-2 seropositivity was found in 38% of the 104 mothers and in 17% of the 89 infants. There was no significant association between SARS-CoV-2 infection and maternal HIV (Hazard Ratio [HR]=1.51, 95% CI: 0.780-2.94) or infant HIV exposure (HR=1.48, 95% CI: 0.537-4.09). Maternal SARS-CoV-2 was associated with a >10-fold increased risk of infant infection (HR=10.3, 95% CI: 2.89-36.8). Twenty percent of participants had symptoms, but no participant experienced severe COVID-19 or death. Seroreversion occurred in ∼30% of mothers and infants. SARS-CoV-2 sequences obtained from stool were related to contemporaneously circulating variants. Conclusions These data indicate that postpartum Kenyan women and their infants were at high risk for SARS-CoV-2 infection in 2020, and that antibody responses waned rapidly. However, most cases were asymptomatic and healthy women living with HIV did not have a substantially increased risk of infection or severe COVID-19.
Subject(s)
COVID-19 , HIV Infections , Postpartum HemorrhageABSTRACT
Pre-existing antibodies that bind endemic human coronaviruses (eHCoVs) can cross-react with SARS-CoV-2, the betacoronavirus that causes COVID-19, but whether these responses influence SARS-CoV-2 infection is still under investigation and is particularly understudied in infants. In this study, we measured eHCoV and SARS-CoV-1 IgG antibody titers before and after SARS-CoV-2 seroconversion in a cohort of Kenyan women and their infants. Pre-existing eHCoV antibody binding titers were not consistently associated with SARS-CoV-2 seroconversion in infants or mothers, though we observed a very modest association between pre-existing HCoV-229E antibody levels and lack of SARS-CoV-2 seroconversion in infants. After seroconversion to SARS-CoV-2, antibody binding titers to endemic betacoronaviruses HCoV-OC43 and HCoV-HKU1, and the highly pathogenic betacoronavirus SARS-CoV-1, but not endemic alphacoronaviruses HCoV-229E and HCoV-NL63, increased in mothers. However, eHCoV antibody levels did not increase following SARS-CoV-2 seroconversion in infants, suggesting the increase seen in mothers was not simply due to cross-reactivity to naively generated SARS-CoV-2 antibodies. In contrast, the levels of antibodies that could bind SARS-CoV-1 increased after SARS-CoV-2 seroconversion in both mothers and infants, both of whom are unlikely to have had a prior SARS-CoV-1 infection, supporting prior findings that SARS-CoV-2 responses cross-react with SARS-CoV-1. In summary, we find evidence for increased eHCoV antibody levels following SARS-CoV-2 seroconversion in mothers but not infants, suggesting eHCoV responses can be boosted by SARS-CoV-2 infection when a prior memory response has been established, and that pre-existing cross-reactive antibodies are not strongly associated with SARS-CoV-2 infection risk in mothers or infants.