Generalizable principles underly the evolution and shaping of population level SARS-CoV-2 immune markers (preprint)

While individual level immune responses to SARS-CoV-2 are well characterized, population immunity and the factors that drive population immune markers are largely undescribed. In this study, we examined spike antibody responses that track with infection risk amongst a household cohort in the northwest and southeast of the Dominican Republic. Our sampling period was from Aug 2021 to Nov 2022, capturing sequential waves of Delta, BA.1, BA.2, and BA.4/5 transmission. We show that population antibody levels normalized from a highly irregular to a Gaussian distribution, driven by accrued infections and antibody boosting among individuals with lower baseline immunity and waning among those with higher immunity, irrespective of interval vaccination. Using a limited number of predictor variables and out-of-sample validation methods we were able to predict S-antibody changes at the Nov 2022 timepoint with a high degree of accuracy (Pearson’s correlation coefficient 0.95 for predicted vs observed change). S-antibody level at the baseline sampling timepoint was by far the most influential predictor, demonstrated by a strong association when used as the only predictor variable (Pearson’s correlation coefficient 0.92). Findings were stable across geographically distinct study regions, suggesting drivers of immune dynamics apply equally across the Dominican Republic, and likely other countries with comparable transmission profiles. Our results suggest that given sufficient transmission, generalizable and discernable principles underly population immune dynamics. We propose that these findings can be used to delineate immune dynamics in other settings, inform transmission modeling, and guide public health priorities for SARS-CoV-2, and potentially other non-immune sterilizing emerging pathogens.

Integrated SARS-CoV-2 serological and virological screening across an acute fever surveillance platform to monitor temporal changes in anti-spike antibody levels and risk of infection during sequential waves of variant transmission - Dominican Republic, March 2021 to August 2022 (preprint)

We monitored SARS-CoV-2 antibody changes following implementation of a national COVID-19 vaccination campaign and assessed implications for immunological protection against variants of concern. Between March 2021 and August 2022, we prospectively enrolled 2,300 patients seeking care for undifferentiated febrile illnesses across two study sites in the Dominican Republic. Sera was tested for total anti-spike antibodies (anti-S) and simultaneously collected nasopharyngeal samples by RT-PCR for acute SARS-CoV-2 infection. Geometric mean anti-S titers increased from 6.6 BAU/ml (95% CI 5.1-8.7) to 1,332 BAU/ml (CI 1055-1,682) during the study period. Multivariable binomial odds ratios for acute SARS-CoV-2 infection were 0.55 (0.40-0.74), 0.38 (0.27-0.55), and 0.27 (0.18-0.40) for the second, third, and fourth versus the first anti-S quartile, with similar findings by viral strain. Integrated serological and virological screening present an opportunity to rethink existing surveillance platforms by simultaneously monitoring population-level immunological markers and implications for emerging variant transmission.

Subtle immunological differences in mRNA-1273 and BNT162b2 COVID-19 vaccine induced Fc-functional profiles (preprint)

The successful development of several COVID-19 vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants, able to evade vaccine induced neutralizing antibodies, real world vaccine efficacy has begun to show differences across the mRNA platforms, suggesting that subtle variation in immune responses induced by the BNT162b2 and mRNA1273 vaccines may provide differential protection. Given our emerging appreciation for the importance of additional antibody functions, beyond neutralization, here we profiled the postboost binding and functional capacity of the humoral response induced by the BNT162b2 and mRNA-1273 in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to WT SARS-CoV-2 and VOCs. However, differences emerged across epitopespecific responses, with higher RBD- and NTD-specific IgA, as well as functional antibodies (ADNP and ADNK) in mRNA-1273 vaccine recipients. Additionally, RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector function induced across the mRNA vaccines, providing novel insights into potential differences in protective immunity generated across these vaccines in the setting of newly emerging VOCs.

SARS-CoV-2 infection and reinfection in a seroepidemiological workplace cohort in the United States (preprint)

Identifying the extent of SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4411 US employees in four states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an adjusted odds ratio of 0.09 (95% CI: 0.005 - 0.48) for reinfection, implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 91% reduced odds of a subsequent PCR positive test. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a sixth month time period. We also highlight two major sources of bias and uncertainty to be considered when estimating reinfection risk, confounders and the choice of baseline time point, and show how to account for both in our analysis.

Epidemiological and immunological features of obesity and SARS-CoV-2 (preprint)

Background: Obesity is established as a key correlate of severe SARS-CoV-2 outcomes. Multiple other epidemiological and immunological features are less well-defined including whether obesity increases susceptibility to SARS-CoV-2, influences symptom phenotype, or impedes or alters the immune response to infection. Given the substantial global burden of obesity and given these uncertainties, we examined the epidemiology and immunology of obesity and SARS-CoV-2. Methods: Industry employees were invited to participate in a prospective SARS-CoV-2 serology-based cohort study. Blood and baseline survey measures that included demographics, comorbidities, and prior COVID-19 compatible symptoms were collected. Serological testing and interim symptom reporting were conducted monthly. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Unadjusted and adjusted analyses were used to identify differences in seroprevalence, clinical features, and immune parameters by BMI. Results: Of 4469 individuals enrolled, 322 (7.21%) were seropositive. Adjusted seroprevalence was non-significantly lower with higher BMI. Obesity was associated with increased reporting of fever (OR 3.43 [95% CI 1.58-7.60]) and multiple other symptoms and aggregate measures. There were no identifiable differences in immune response between obese and non-obese individuals. Discussion: We present benchmark data that obesity is not linked to increased risk of SARS-CoV-2 infection; that symptom phenotype is strongly influenced by obesity; and that despite evidence of obesity-associated immune dysregulation in severe infections, there is no evidence of muted or dysfunctional immune response across multiple immune measures among non-severe infections.