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Background Longitudinal serology studies can assist in analyzing kinetics of antibodies to the SARS-CoV-2 virus, helping to inform public health decision-making. Our study aims to characterize circulating antibody trends over 18 months in vaccinated participants with and without evidence of COVID-19 infection. Methods A cohort of healthcare workers employed at Boston Medical Center were followed, collecting serum samples and survey data over six timepoints from July 2020 through December 2021 (n = 527). History of SARS-CoV-2 infection, vaccination and booster status were confirmed, where possible, using electronic medical records. Serum was assessed for the qualitative detection of anti-N IgG and the semi-quantitative detection of anti-S IgG antibody levels. Piecewise regression models were utilized to characterize the antibody kinetics overtime. Results Anti-S IgG titers remained above the positivity threshold following infection and/or vaccination throughout the 18-month follow-up. Among participants with no evidence of COVID-19 infection, titers declined significantly faster in the initial 90 days post-full vaccination (β=-0.056) from December 2020 to March 2021 compared to the decline observed following booster dose uptake (β=-0.023) (p Conclusions These findings provide novel 18-month kinetics of anti-S IgG antibodies and further highlight the durability of hybrid immunity, underlining the strong humoral response stimulated by combined infection and vaccination.

Objective To examine if iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D). Research Design and Methods In “The Environmental Determinants of Diabetes in the Young” (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron. Results We found a U-shaped association between iron intake and risk of GADA as first autoantibody. In subjects with GRS>=2 iron risk alleles, high iron intake was associated with increased risk of IA with insulin as first autoantibody [adjusted hazard ratio (HR, 95% CI): 1.71 (1.14; 2.58), as compared to moderate iron intake. Conclusions Iron intake may alter the risk of islet autoimmunity in children with high-risk HLA haplogenotypes.

The recently identified, globally predominant SARS-CoV-2 Omicron variant (BA.1) is highly transmissible, even in fully vaccinated individuals, and causes attenuated disease compared with other major viral variants recognized to date1–7. The Omicron spike (S) protein, with an unusually large number of mutations, is considered the major driver of these phenotypes3,8. We generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron in the backbone of an ancestral SARS-CoV-2 isolate and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escapes vaccine-induced humoral immunity, mainly due to mutations in the receptor-binding motif (RBM), yet unlike naturally occurring Omicron, efficiently replicates in cell lines and primary-like distal lung cells. In K18-hACE2 mice, while Omicron causes mild, non-fatal infection, the Omicron S-carrying virus inflicts severe disease with a mortality rate of 80%. This indicates that while the vaccine escape of Omicron is defined by mutations in S, major determinants of viral pathogenicity reside outside of S.

Background Boston Medical Center (BMC) is a safety net hospital in Boston, and from the initial wave of COVID-19 there has been an overwhelming concern about the exposure of healthcare workers (HCWs) to SARS-CoV-2. Methods We conceived a study to follow a cohort of BMC HCWs, beginning in July 2020 and continuing for 15 months, collecting survey data and serum samples at approximately 3-month intervals. Serum samples were analyzed using the Abbott Architect i2000 for SARS-CoV-2 antibodies (anti-spike1-Receptor Binding Domain IgG and anti-nucleoprotein IgG). Positive anti-n IgG results were used, in addition to reverse transcription-PCR results, for identifying cases of infection. History of COVID-19 and vaccination status were confirmed, where possible, using electronic medical records. Participants were grouped according to vaccination and infection status in September 2021 for analysis of anti-s IgG trends. Results A majority of HCWs remain well above the positivity threshold for anti-spike IgG antibodies for up to 11 months post-vaccination and 15 months post-infection, regardless of combinations and permutations of vaccination and infection. Those with COVID-19 infection before vaccination had significantly higher median serum antibody concentrations in comparison to HCWs with no prior infection at each follow-up time point. Conclusions These findings further support what is known regarding the decline in serum antibody concentrations following natural infection and vaccination, adding knowledge of serum antibody levels for up to 15 months post- infection and 11 months post-vaccination.

Over 15-months we found that anti-spike RBD SARS-CoV-2 antibody concentrations follow different trends with combinations and permutations of COVID-19 infection and vaccination among healthcare workers in Boston, MA. A majority of HCWs remain well above the positivity threshold for anti-spike RBD IgG antibodies for at least 9 months following vaccination regardless of infection history. Of interest, those with COVID-19 infection before vaccination had significantly higher median serum antibody concentrations in comparison to HCWs with no prior infection at each follow-up timepoint. These findings further support what is known regarding the decline in serum antibody concentrations following natural infection and vaccination, adding knowledge of serum antibodies up to 15 months post infection and 11 months post vaccination.ImportanceBoston Medical Center (BMC) is a safety net hospital in Boston and from the initial wave of COVID-19 there has been overwhelming concern about the exposure of healthcare workers to SARS-CoV-2. We conceived a longitudinal study to assess virus exposure and trends in SARS-CoV-2 antibodies amongst healthcare workers at BMC over 15 months. We have followed HCWs through three waves of COVID-19, including the Delta variant wave from June through mid-December 2021, assessing anti-spike receptor binding domain IgG, anti-nucleocapsid IgG, and anti-spike IgM at approximately three-month intervals. Current literature largely describes antibody durability six months post vaccination. These data add to the literature by describing antibody durability and trend differences according to infection history and vaccination status. These longitudinal data contribute to a greater understanding of the ongoing COVID-19 pandemic and can help inform future research and public health decision-making regarding vaccine uptake, breakthrough infections, and overall pandemic response.

BackgroundAccurate measurement of antibodies is a necessary tool for assessing exposure to SARS-CoV-2 and facilitating understanding of the role of antibodies in immunity. Most assays are qualitative in nature and employ a threshold to determine presence of antibodies. Semi-quantitative assays are now available. Here we evaluate the semi-quantitative SARS-CoV-2 IgG II (anti-spike (S)) assay. We aim to reassess the seroprevalence using anti-S assay and subsequently compare it to the previously measured IgG (anti-nucleoprotein (N)) in health care workers at an academic medical center in Boston.Methods1743 serum samples from HCWs at Boston Medical Center were analyzed for SARS-CoV-2 anti-S IgG and IgM using the Abbott SARS-CoV-2 IgG II and□Abbott AdviseDx□SARS-CoV-2 IgM assay, respectively. Precision, linearity, positive and negative concordance with prior RT-PCR test were evaluated for anti-S IgG. Seroprevalence and its association with demographics variables was also assessed.ResultsLinearity and precision results were clinically acceptable. The positive and negative concordance for anti-S IgG with RT-PCR was 88.2% (95% CI: 79.4% - 94.2%) and 97.43% (95% CI: 95.2% - 98.8%), respectively. Overall, 126 (7.2%) of 1,743 participants were positive by anti-S IgG. Among the 1302 participants with no prior RT-PCR, 40 (3.1%) were positive for anti-S IgG antibody. The original agreement in this population with the qualitative, anti-N IgG assay was 70.6%. Upon optimizing the threshold from 1.4 to 0.49 S/CO of the anti-N IgG assay, the positive agreement of the assay increases to 84.7%.ConclusionThe anti-S IgG assay demonstrated reproducible and reliable measurements. This study highlights the presence of asymptomatic transmission among individuals with no prior history of positive RT-PCR. It also highlights the need for optimizing thresholds of the qualitative SARS-CoV-2 IgG assay for better agreement between assays by the same vendor.