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BackgroundMore than half the global population has been exposed to SARS-CoV-2. Naturally induced immunity influences the outcome of subsequent exposure to variants and vaccine responses. We measured anti-spike IgG responses to explore the basis for this enhanced immunity. MethodsA prospective cohort study in a South African community through the ancestral/beta/delta/omicron SARS-CoV-2 waves. Health seeking behaviour/illness were recorded and post-wave serum samples probed for IgG to Spike (CoV2-S-IgG). To estimate protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter for unvaccinated and vaccinated adults. FindingsDespite little disease, 176/339 (51{middle dot}9%) participants were seropositive following wave 1, rising to 74%, 89{middle dot}8% and 97{middle dot}3% after waves 2, 3 and 4 respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection with the greatest protection for beta and the least for omicron. Vaccination induced higher CoV2-S-IgG in seropositive compared to naive vaccinees. Amongst seropositive participants, proportions above the 50% protection against infection threshold were 69% (95% CrI: 62, 72) following 1 vaccine dose, 63% (95% CrI: 63, 75) following 2 doses and only 11% (95% CrI: 7, 14) in unvaccinated during the omicron wave. InterpretationNaturally induced CoV2-S-IgG do not achieve high enough levels to prevent omicron infection in most exposed individuals but are substantially boosted by vaccination leading to significant protection. A single vaccination in those with prior immunity is more immunogenic than 2 doses in a naive vaccinee and thus may provide adequate protection. FundingUK NIH GECO award (GEC111), Wellcome Trust Centre for Infectious Disease Research in Africa (CIDRI), Bill & Melinda Gates Foundation, USA (OPP1017641, OPP1017579) and NIH H3 Africa (U54HG009824, U01AI110466]. HZ is supported by the SA-MRC. MPN is supported by an Australian National Health and Medical Research Council Investigator Grant (APP1174455). BJQ is supported by a grant from the Bill and Melinda Gates Foundation (OPP1139859). Stefan Flasche is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant number 208812/Z/17/Z). Research in context Evidence before this studyNatural infection with ancestral SARS-CoV-2 virus provides partial protection against re-infection with the same and closely related SARS-CoV-2 variants, but higher rates of re-infection have been described with Omicron. In addition, vaccination against SARS-CoV2 provides relatively lower protection against symptomatic Omicron infection than for other variants. Hybrid immunity, a combination of immunity induced by natural infection and vaccination is of critical interest due to the high incidence of natural infection in many populations and increased availability of vaccination. Vaccination following infection may provide more robust immunity than either infection or vaccination alone, but there are limited data on the impact of hybrid immunity for protection against different variants or on the optimal vaccination strategy following natural infection. Added value of this studyWe leveraged a unique South African birth cohort in a poor peri-urban area, to longitudinally investigate infection, illness and serological responses to natural exposure to SARS-CoV-2 over 4 waves of the pandemic in healthy mothers. We also investigated the impact of prior natural exposure on BNT162b2 mRNA vaccine responses. We used this information to derive estimates of levels of spike-specific IgG associated with protection for subsequent infection following natural or hybrid immunity. Despite little disease, most participants were seropositive with rates rising from 52% to 74%, 90% and 97% after waves 1, 2, 3 and 4 respectively. Antibodies to spike protein induced by natural exposure protected against subsequent infection with the greatest protection for beta and the least for omicron. Antibody levels following vaccination were significantly higher in those who were seropositive prior to vaccine, compared to those seronegative. Amongst seropositive participants, proportions above the 50% protection against infection threshold were 69% following 1 vaccine dose, 63% following 2 doses and only 11% in unvaccinated during the omicron wave. In those seropositive prior to vaccination no significant increase in antibody levels occurred after the 2nd dose of vaccine, unlike the increase in seronegative participants. A single dose of vaccine in seropositive individuals induced higher antibody concentrations than two doses in seronegative recipients. Implications of all the available evidenceNaturally induced spike antibodies do not achieve high enough levels to prevent omicron infection in most exposed individuals but are substantially boosted by vaccination leading to significant protection. A single vaccination in those with prior natural immunity is more immunogenic than 2 doses in seronegative people and may provide adequate protection against omicron and other variants. Vaccination programs in populations with high seroprevalence using a single vaccination as a primary strategy should be considered.
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The highly transmissible Omicron variant has caused high rates of breakthrough infections among vaccinated and convalescent individuals. Here, we demonstrate that a booster dose of UB-612 vaccine candidate delivered 7-9 months after primary vaccination increases neutralizing antibody levels by 131-, 61- and 49-fold against ancestral SARS-CoV-2, Omicron BA.1 and BA.2 variants, respectively. Based on the RBD protein binding antibody responses, we estimated a [~]95% efficacy against symptomatic COVID-19 caused by the ancestral strain after a UB-612 booster. Our results support UB-612 vaccine as a potent booster against current and emerging SARS-CoV-2 variants.
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Some social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations.
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BackgroundEthnic and religious minorities have been disproportionately affected by SARS-CoV-2 worldwide. The UK strictly-Orthodox Jewish community has been severely affected by the pandemic. This group shares characteristics with other ethnic minorities including larger family sizes, higher rates of household crowding and relative socioeconomic deprivation. We studied a UK strictly-Orthodox Jewish population to understand how COVID-19 had spread within this community. MethodsWe performed a household-focused cross-sectional SARS-CoV-2 serosurvey specific to three antigen targets. Randomly-selected households completed a standardised questionnaire and underwent serological testing with a multiplex assay for SARS-CoV-2 IgG antibodies. We report clinical illness and testing before the serosurvey, seroprevalence stratified by age and gender. We used random-effects models to identify factors associated with infection and antibody titres. FindingsA total of 343 households, consisting of 1,759 individuals, were recruited. Serum was available for 1,242 participants. The overall seroprevalence for SARS-CoV-2 was 64.3% (95% CI 61.6-67.0%). The lowest seroprevalence was 27.6% in children under 5 years and rose to 73.8% in secondary school children and 74% in adults. Antibody titres were higher in symptomatic individuals and declined over time since reported COVID-19 symptoms, with the decline more marked for nucleocapsid titres. InterpretationIn this tight-knit religious minority population in the UK, we report one of the highest SARS-CoV-2 seroprevalence levels in the world to date. In the context of this high force of infection, all age groups experienced a high burden of infection. Actions to reduce the burden of disease in this and other minority populations are urgently required. FundingThis work was jointly funded by UKRI and NIHR [COV0335; MR/V027956/1], a donation from the LSHTM Alumni COVID-19 response fund, HDR UK, the MRC and the Wellcome Trust. The funders had no role in the design, conduct or analysis of the study or the decision to publish. The authors have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Research In ContextO_ST_ABSEvidence before the studyC_ST_ABSIn January 2020, we searched PubMed for articles on rates of SARS-CoV-2 infection amongst ethnic minority groups and amongst the Jewish population. Search teams included "COVID-19", "SARS-CoV-2", seroprevalence, "ethnic minority", and "Jewish" with no language restrictions. We also searched UK government documents on SARS-CoV-2 infection amongst minority groups. By January 2020, a large number of authors had reported that ethnic minority groups experienced higher numbers of cases and increased hospitalisations due to COVID-19. A small number of articles provided evidence that strictly-Orthodox Jewish populations had experienced a high rate of SARS-CoV-2 infection but extremely limited data was available on overall population level rates of infection amongst specific ethnic minority population groups. There was also extremely limited data on rates of infection amongst young children from ethnic minority groups. Added value of the studyWe report findings from a population representative, household survey of SARS-CoV-2 infection amongst a UK strictly Orthodox Jewish population. We demonstrate an extremely high seroprevalence rate of SARS-CoV-2 in this population which is more than five times the estimated seroprevalence nationally and five times the estimated seroprevalence in London. In addition the large number of children in our survey, reflective of the underlying population structure, allows us to demonstrate that in this setting there is a significant burden of disease in all age groups with secondary school aged children having an equivalent seroprevalence to adults. Implications of the available evidenceOur data provide clear evidence of the markedly disproportionate impact of SARS-CoV-2 in minority populations. In this setting infection occurs at high rates across all age groups including pre-school, primary school and secondary school-age children. Contextually appropriate measures to specifically reduce the impact of SARS-CoV-2 amongst minority populations are urgently required.
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BackgroundThe emergence of SARS-CoV-2 has led to the development of new serological assays that could aid in diagnosis and evaluation of seroprevalence to inform an understanding of the burden of COVID-19 disease. Many available tests lack rigorous evaluation and therefore results may be misleading. ObjectivesThe aim of this study was to assess the performance of a novel multiplexed immunoassay for the simultaneous detection of antibodies against SARS-CoV-2 trimeric spike (S), spike receptor binding domain (RBD), spike N terminal domain and nucleocapsid antigen and a novel pseudo-neutralisation assay. MethodsA multiplexed solid-phase chemiluminescence assay (Meso Scale Discovery) was evaluated for the simultaneous detection of IgG binding to four SARS-CoV-2 antigens and the quantification of antibody-induced ACE-2 binding inhibition (pseudo-neutralisation assay). Sensitivity was evaluated with a total of 196 COVID-19 serum samples (169 confirmed PCR positive and 27 anti-nucleocapsid IgG positive) from individuals with mild symptomatic or asymptomatic disease. Specificity was evaluated with 194 control serum samples collected from adults prior to December 2019. ResultsThe specificity and sensitivity of the binding IgG assay was highest for S protein with a specificity of 97.4% and sensitivity of 96.2% for samples taken 14 days and 97.9% for samples taken 21 days following the onset of symptoms. IgG concentration to S and RBD correlated strongly with percentage inhibition measured by the pseudo-neutralisation assay. ConclusionExcellent sensitivity for IgG detection was obtained over 14 days since onset of symptoms for three SARS-CoV-2 antigens (S, RBD and N) in this multiplexed assay which can also measure antibody functionality.
