Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose

The emergence of the SARS-CoV-2 Omicron sublineages resulted in drastically increased transmission rates and reduced protection from vaccine-induced immunity. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remains sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed worldwide, particularly in China, and South America. However, whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses and whether these responses vary across age groups remain unknown. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals in central and south America that received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccines. We found that both IgG levels against SARS-CoV-2 spike or RBD, as well as neutralization titers against Omicron sublineages, were substantially reduced in participants that received homologous CoronaVac when compared to heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients older than 50 years of age. In this group, CoronaVac booster induced low virus-specific IgG levels and failed to elevate their neutralization titers against any omicron sublineage. Our results point to significant inefficiency in mounting protective anti-viral humoral immunity in those who were primed with CoronaVac followed by CoronaVac booster, particularly among older adults, urging a heterologous regimen in high-risk populations fully vaccinated with CoronaVac. One Sentence SummaryHomologous CoronaVac boosters do not improve neutralization responses against current VOCs in older adults in contrast to heterologous regimens.

Distinguishing features of Long COVID identified through immune profiling

SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID1-3. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions1-3; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.

Insights into the limited global spread of the immune evasive SARS-CoV-2 variant Mu

SARS-CoV-2 Variants of Concern (VOCs) continue to reshape the trajectory of the COVID-19 pandemic. However, why some VOCs, like Omicron, become globally dominant while the spread of others is limited is not fully understood. To address this question, we investigated the VOC Mu, which was first identified in Colombia in late 2020. Our study demonstrates that, although Mu is less sensitive to neutralization compared to variants that preceded it, it did not spread significantly outside of South and Central America. Additionally, we find evidence that the response to Mu was impeded by reporting delays and gaps in the global genomic surveillance system. Our findings suggest that immune evasion alone was not sufficient to outcompete highly transmissible variants that were circulating concurrently with Mu. Insights into the complex relationship between genomic and epidemiological characteristics of previous variants should inform our response to variants that are likely to emerge in the future.

Prevalence of Chronic Diseases, Depression, and Stress among U.S. Child Care Professionals during the COVID-19 Pandemic

ImportanceThere is no published national research reporting child care professionals physical health, depression, or stress during the COVID-19 pandemic. Given their central role in supporting childrens development, child care professionals overall physical and mental health is important. ObjectivesTo evaluate the prevalence of chronic diseases, depression, and stress levels during the COVID-19 pandemic among U.S. child care professionals. DesignIn this large-scale national survey, data were collected through an online survey from May 22, 2020 to June 8, 2020. We analyzed the association of sociodemographic characteristics with four physical health conditions (asthma, heart disease, diabetes, and obesity), depression, and stress weighted to national representativeness. Sociodemographic characteristics included race, ethnicity, age, gender, medical insurance status, and child care type. SettingCenter- and home-based child care. ParticipantsChild care professionals (n = 81,682) from all U.S. states and the District of Columbia. ResultsMean age was 42.1 years (standard deviation = 14.1); 96.0% (n = 78,725) were female, 2.5% (n = 2,033) were male, and 0.3% (n = 225) were non-binary. For physical health conditions, 14.3% (n = 11,717) reported moderate to severe asthma, 6.5% (n = 5,317) diabetes, 4.9% (n = 3,971) heart disease, and 19.8% (n = 16,207) being obese. Regarding mental health, 45.7% (n = 37,376) screened positive for depression and 66.5% (n = 54,381) reported moderate to high stress levels. Race, ethnicity, and gender disparities were evidenced for physical health conditions of child care professionals, but not for mental health during the pandemic. Conclusions and RelevanceOur findings highlight that child care professionals depression rates during the pandemic were much higher than before the pandemic, and depression, stress and asthma rates were higher than U.S. adult depression rates during the pandemic. Given the essential work child care professionals provide during the pandemic, policy makers and public health officials should consider what can be done to support the physical and mental health of child care professionals. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the prevalence of chronic diseases, depression, and stress among U.S. child care professionals during the COVID-19 pandemic? FindingsIn this survey of 81,682 U.S. child care professionals, 14.3% reported moderate to severe asthma, 6.5% diabetes, 4.9% heart disease, 19.8% being obese, 45.7% screening positive for depression, and 66.5% moderate to high stress levels. MeaningDuring the pandemic, child care professionals reported depression rates much higher than before the pandemic, and asthma, stress, and depression much greater than U.S. adult estimates, highlighting a need for effective supports for the wellbeing of this essential workforce.

Immunogenicity of heterologous BNT162b2 booster in fully vaccinated individuals with CoronaVac against SARS-CoV-2 variants Delta and Omicron: the Dominican Republic Experience

The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and by its numerous spike mutations with potential to evade neutralizing antibodies elicited by COVID-19 vaccines. The Dominican Republic was among the first countries in recommending the administration of a third dose COVID-19 vaccine to address potential waning immunity and reduced effectiveness against variants. Here, we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants that had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that heterologous CoronaVac prime followed by BNT162b2 booster regimen induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and Delta variant, resembling the titers obtained after two doses of mRNA vaccines. While neutralization of Omicron was undetectable in participants that had received a two-dose regimen of CoronaVac vaccine, BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron, compared to two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 6.3-fold and 2.7-fold for Omicron compared to ancestral and Delta variant, respectively. Surprisingly, previous SARS-CoV-2 infection did not affect the neutralizing titers for Omicron in participants that received the heterologous regimen. Our findings have immediate implications for multiples countries that previously used a two-dose regimen of CoronaVac and reinforce the notion that the Omicron variant is associated with immune escape from vaccines or infection-induced immunity, highlighting the global need for vaccine boosters to combat the impact of emerging variants.

No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination

The impact of coronavirus disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated two of the most widely propagated claims to determine 1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities, and 2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from vaccinated murine pregnancies exhibit high circulating levels of anti-Spike and anti-RBD antibodies to SARS-CoV-2 consistent with maternal antibody status, indicating transplacental transfer. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes.

COVID-19 Vaccine Uptake among U.S. Child Care Providers

STRUCUTRED ABSTRACTO_ST_ABSObjectivesC_ST_ABSEnsuring a high COVID-19 vaccine uptake among U.S. child care providers is crucial to mitigating the public health implications of child-to-staff and staff-to-child transmission of SARS-CoV-2; however, the vaccination rate among this group is unknown. MethodsTo characterize the vaccine uptake among U.S. child care providers, we conducted a cross-sectional survey of the child care workforce. Providers were identified through various national databases and state registries. A link to the survey was sent via email between May 26 and June 23, 2021. Out of 44,771 potential respondents, 21,663 responded (48.4%). ResultsOverall COVID-19 vaccine uptake among U.S. child care providers (78.1%, 95% CI [77.3% to 78.9%]) was higher than that of the U.S. adult population (65%). Vaccination rates varied from 53.5% to 89.4% between states. Vaccine uptake differed significantly (p < .01) based on respondent age (70.0% for ages 25-34, 91.5% for ages 75-84), race (70.0% for Black or African Americans, 92.5% for Asian-Americans), annual household income (70.7% for <$35,000, 85.0% for>$75,000), and childcare setting (72.9% for home-based, 79.7% for center-based). ConclusionsCOVID-19 vaccine uptake among U.S. child care providers was higher than that of the general U.S. adult population. Those who were younger, lower income, Black or African American, resided in states either in the Mountain West or the South, and/or worked in home-based childcare programs reported the lowest rates of vaccination; state public health leaders and lawmakers should prioritize these subgroups for placement on the policy agenda to realize the largest gains in vaccine uptake among providers. Tables of Contents SummaryThis article describes the results of a national survey of childcare providers to determine the overall COVID-19 vaccine uptake and the gaps in vaccine coverage. Whats Known on This SubjectEnsuring a high COVID-19 vaccine uptake among U.S. child care providers is crucial to mitigating the public health implications of child-to-staff and staff-to-child transmission of SARS-CoV-2; however, the vaccination rate among this group is unknown. What This Study AddsWhile the vaccine uptake among U.S. child care providers was higher than that of U.S. adults, certain subgroups continue to warrant focused attention for outreach and/or placement on the policy agenda.

Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity in uninfected and previously infected individuals

The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1-6. We analysed the development of anti-SARS-CoV-2 antibody and T cell responses in previously infected (recovered) or uninfected (naive) individuals that received mRNA vaccines to SARS-CoV-2. While previously infected individuals sustained higher antibody titers than uninfected individuals post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain than previously infected individuals 7 days after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination in the time-points analysed. Comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants revealed a range of reduction in the neutralization capacity associated with specific mutations in the spike gene: lineages with E484K and N501Y/T (e.g., B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (e.g., B.1.617.2) or with E484K (without N501Y/T). While both groups retained neutralization capacity against all variants, plasma from previously infected vaccinated individuals displayed overall better neutralization capacity when compared to plasma from uninfected individuals that also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the impact of emerging variants on antibody neutralizing activity.

The Balancing Role of Distribution Speed against Varying Efficacy Levels of COVID-19 Vaccines under Variants

Mutations in SARS-CoV-2 raised concerns about diminishing vaccine effectiveness against COVID-19 caused by particular variants. Even with high initial efficacy, if a vaccines efficacy drops significantly against variants, or if it cannot be distributed quickly, it is uncertain whether the vaccine can provide better health outcomes than other vaccines. Hence, we evaluated the trade-offs between the speed of distribution vs. efficacy against infection of multiple vaccines when variants emerge by utilizing a Susceptible-Infected-Recovered-Deceased (SIR-D) model and assessing the level of infection attack rate (IAR). Our results show that speed is a key factor to a successful immunization strategy to control the COVID-19 pandemic even when the emerging variants may reduce the efficacy of a vaccine. Due to supply-chain challenges, the accessibility and distribution of the vaccines have been hindered in many regions, especially in low-income countries, while the second or third wave of the pandemic has occurred due to the variants. Understanding the tradeoffs between speed and efficacy and distributing vaccines that are available as quickly as possible are crucial to eradicate the pandemic before new variants spread.

Significance of SARS-CoV-2 Specific Antibody Testing during COVID-19 Vaccine Allocation

ObjectiveTo assess the value of using SARS-CoV-2 specific antibody testing to prioritize the vaccination of susceptible individuals as part of a COVID-19 vaccine distribution plan when vaccine supply is limited. MethodsA compartmental model was used to simulate COVID-19 spread when considering diagnosis, isolation, and vaccination of a cohort of 1 million individuals. The scenarios modeled represented 4 pandemic severity scenarios and various times when the vaccine becomes available during the pandemic. Eligible individuals have a probability p of receiving antibody testing prior to vaccination (p = 0, 0.25, 0.5, 0.75, and 1). The value of serology testing was evaluated by comparing the infection attack rate, peak infections, peak day, and deaths. ResultsThe use of antibody testing to prioritize the allocation of limited vaccines reduces infection attack rates and deaths. The size of the reduction depends on when the vaccine becomes available relative to the infection peak day. The largest reduction in cases and deaths occurs when the vaccine is deployed before and close to the infection peak day. The reduction in the number of cases and deaths diminishes as vaccine deployment is delayed and moves closer to the peak day. ConclusionsAntibody testing as part of the vaccination plan is an effective method to maximize the benefit of a COVID-19 vaccine. Decision-makers need to consider relative timing between the infection peak day and when the vaccine becomes available.

Resource Allocation for Different Types of Vaccines against COVID-19: Tradeoffs and Synergies between Efficacy and Reach

ObjectiveVaccine shortage and supply-chain challenges have caused limited access by many resource-limited countries during the COVID-19 pandemic. One of the primary decisions for a vaccine-ordering decision-maker is how to allocate the limited resources between different types of vaccines effectively. We studied the tradeoff between efficacy and reach of the two vaccine types that become available at different times. MethodsWe extended a Susceptible-Infected-Recovered-Deceased (SIR-D) model with vaccination, ran extensive simulations with different settings, and compared the level of infection attack rate (IAR) under different reach ratios between two vaccine types under different resource allocation decisions. ResultsWe found that when there were limited resources, allocating resources to a vaccine with high efficacy that became available earlier than a vaccine with lower efficacy did not always lead to a lower IAR, particularly if the former could vaccinate less than 42.5% of the population (with the selected study parameters) who could have received the latter. Sensitivity analyses showed that this result stayed robust under different study parameters. ConclusionsOur results showed that a vaccine with lower resource requirements (wider reach) can significantly contribute to reducing IAR, even if it becomes available later in the pandemic, compared to a higher efficacy vaccine that becomes available earlier but requires more resources. Limited resource in vaccine distribution is significant challenge in many parts of the world that needs to be addressed to improve the global access to life-saving vaccines. Understanding the tradeoffs between efficacy and reach is critical for resource allocation decisions between different vaccine types for improving health outcomes.