Neutralizing antibody responses over time in a demographically and clinically diverse cohort of individuals recovered from SARS-CoV-2 acquisition in Africa: A cohort study

Abstract

COVID-19 has affected millions worldwide. Research characterized immune responses of individuals who acquired SARS-CoV-2 and identified co-factors, such as HIV, associated with greater likelihood of poor clinical outcomes. SARS-CoV-2-specific neutralizing antibodies (nAbs) are a strong correlate of protection but their elicitation in people living with HIV (PLWH), and particularly in southern Africa, is less well characterized. HVTN 405/HPTN 1901 was an observational cohort study of individuals recently recovered from SARS-CoV-2. We describe 323 participants enrolled early in the pandemic (June 2020 to January 2021) in Zambia (n = 12), Malawi (n = 13), Zimbabwe (n = 59), and South Africa (n = 239), profiling their SARS-CoV-2-specific nAb responses and associations with demographics, comorbidities, disease severity, and time since diagnosis based on linear and logistic regression. Participants' median age was 39 years, 63.5% were assigned female sex at birth, 71.2% were black African, and 39 (12.1%) were PLWH. Approximately one in four participants (25.7%) had asymptomatic SARS-CoV-2, 47.4% were symptomatic but not hospitalized, and 26.9% were hospitalized with COVID-19. Participants in these groups were enrolled at a median of 51.5 days, 53 days, and 60 days post-SARS-CoV-2 diagnosis, respectively. SARS-CoV-2 nAbs were measured in serum using one of two calibrated assays. Most (291/322, 90.4%) participants had positive nAb responses at enrollment. Across all participants, nAb responses generally declined in magnitude between enrollment and 2-3 months thereafter, then increased through month 12 coincident with epidemiologically observed new waves of acquisition. In a multivariate model adjusted for potentially confounding factors, PLWH had a 65% lower geometric mean (GM) nAb ID50 titer compared to people without HIV (PWOH) (GMR: 0.35, p = 0.003, q = 0.006). Greater disease severity, older age (>55 years), high BMI (≥30) and diabetes were associated with higher nAb ID50 titers (all p < 0.05, all q < 0.20).These findings are important, as nAb titers are predictive of vulnerability to COVID-19.

Fig 1. Estimated SARS-CoV-2 neutralizing antibody (nAb) response rate and geometric mean (GM) nAb ID50 titers at enrollment by select baseline participant characteristics.

Points show estimated response rates and GM ID50 titers; lines show 95% confidence intervals. Y = yes; N = no. The number of participants in each category is given in parentheses in the labels along the x-axis.

Fig 2. Distribution and traces of individual SARS-CoV-2 neutralizing antibody (nAb) responses over time by participant HIV status and COVID-19 severity. nAb ID50 titers were measured at enrollment (V1) and approximately 2 months (V2), 4 months (V3), and 12 months (V4) thereafter.

Boxplots indicate the median (middle bar), interquartile range (box length), the most extreme data points that are no more than 1.5 times the interquartile range, or if no value meets this criterion, to the data extremes (whiskers).

Fig 3. Average SARS-CoV-2 neutralizing antibody trajectory by HIV status and COVID-19 severity group.

Individual nAb ID50 titers are shown as well as population geometric mean trajectories and 95% confidence bands estimated using a generalized additive mixed model (GAMM). Bottom panel shows the total number of COVID-19 cases reported to the WHO in the countries included in this analysis over calendar time, with the study visit intervals overlaid. Symptomatic participants and participants hospitalized due to COVID-19 were eligible to enroll 1-8 weeks after COVID-19 disease resolution. Asymptomatic participants were eligible to enroll 2-10 weeks after SARS-CoV-2 acquisition diagnosis. Visit 1 was the enrollment visit. Visits 2, 3, and 4 occurred at 2, 4, and 12 months after enrollment, respectively.