Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine-associated myocarditis.

Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including after SARS-CoV-2 mRNA vaccines. However, the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated a cohort of patients who developed myocarditis and/or pericarditis with elevated troponin, B-type natriuretic peptide, and C-reactive protein levels as well as cardiac imaging abnormalities shortly after SARS-CoV-2 mRNA vaccination. Contrary to early hypotheses, patients did not demonstrate features of hypersensitivity myocarditis, nor did they have exaggerated SARS-CoV-2-specific or neutralizing antibody responses consistent with a hyperimmune humoral mechanism. We additionally found no evidence of cardiac-targeted autoantibodies. Instead, unbiased systematic immune serum profiling revealed elevations in circulating interleukins (IL-1ß, IL-1RA, and IL-15), chemokines (CCL4, CXCL1, and CXCL10), and matrix metalloproteases (MMP1, MMP8, MMP9, and TIMP1). Subsequent deep immune profiling using single-cell RNA and repertoire sequencing of peripheral blood mononuclear cells during acute disease revealed expansion of activated CXCR3+ cytotoxic T cells and NK cells, both phenotypically resembling cytokine-driven killer cells. In addition, patients displayed signatures of inflammatory and profibrotic CCR2+ CD163+ monocytes, coupled with elevated serum-soluble CD163, that may be linked to the late gadolinium enhancement on cardiac MRI, which can persist for months after vaccination. Together, our results demonstrate up-regulation in inflammatory cytokines and corresponding lymphocytes with tissue-damaging capabilities, suggesting a cytokine-dependent pathology, which may further be accompanied by myeloid cell-associated cardiac fibrosis. These findings likely rule out some previously proposed mechanisms of mRNA vaccine--associated myopericarditis and point to new ones with relevance to vaccine development and clinical care.

Nonsystematic Reporting Biases of the SARS-CoV-2 Variant Mu Could Impact Our Understanding of the Epidemiological Dynamics of Emerging Variants.

Developing a timely and effective response to emerging SARS-CoV-2 variants of concern (VOCs) is of paramount public health importance. Global health surveillance does not rely on genomic data alone to identify concerning variants when they emerge. Instead, methods that utilize genomic data to estimate the epidemiological dynamics of emerging lineages have the potential to serve as an early warning system. However, these methods assume that genomic data are uniformly reported across circulating lineages. In this study, we analyze differences in reporting delays among SARS-CoV-2 VOCs as a plausible explanation for the timing of the global response to the former VOC Mu. Mu likely emerged in South America in mid-2020, where its circulation was largely confined. In this study, we demonstrate that Mu was designated as a VOC ∼1 year after it emerged and find that the reporting of genomic data for Mu differed significantly than that of other VOCs within countries, states, and individual laboratories. Our findings suggest that nonsystematic biases in the reporting of genomic data may have delayed the global response to Mu. Until they are resolved, the surveillance gaps that affected the global response to Mu could impede the rapid and accurate assessment of future emerging variants.

SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity.

mRNA-based vaccines dramatically reduce the occurrence and severity of COVID-19, but are associated with rare vaccine-related adverse effects. These toxicities, coupled with observations that SARS-CoV-2 infection is associated with autoantibody development, raise questions whether COVID-19 vaccines may also promote the development of autoantibodies, particularly in autoimmune patients. Here we used Rapid Extracellular Antigen Profiling to characterize self- and viral-directed humoral responses after SARS-CoV-2 mRNA vaccination in 145 healthy individuals, 38 patients with autoimmune diseases, and 8 patients with mRNA vaccine-associated myocarditis. We confirm that most individuals generated robust virus-specific antibody responses post vaccination, but that the quality of this response is impaired in autoimmune patients on certain modes of immunosuppression. Autoantibody dynamics are remarkably stable in all vaccinated patients compared to COVID-19 patients that exhibit an increased prevalence of new autoantibody reactivities. Patients with vaccine-associated myocarditis do not have increased autoantibody reactivities relative to controls. In summary, our findings indicate that mRNA vaccines decouple SARS-CoV-2 immunity from autoantibody responses observed during acute COVID-19.

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

The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2-related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.

COVID-19 Vaccine Acceptance and Hesitancy Among Health Care Workers in Lebanon.

BACKGROUND: Lebanon endured its worst economic and financial crisis in 2020-2021. To minimize the impact of COVID-19 pandemic, it is important to improve the overall COVID-19 vaccination rate. Given that vaccine hesitancy among health care workers (HCWs) affects the general population's decision to be vaccinated, our study assessed COVID-19 vaccine acceptance among Lebanon HCWs and identified barriers, demographic differences, and the most trusted sources of COVID-19 information. METHODS: A cross-sectional study was conducted between January and May 2021 among HCWs across nine hospitals, the Orders of Physicians, Nurses, and Pharmacists in Lebanon. Descriptive statistics were performed to evaluate the COVID-19 vaccine acceptance, and univariate and multivariable to identify their predictors. RESULTS: Among 879 participants, 762 (86.8%) were willing to receive the COVID-19 vaccine, 52 (5.9%) refused, and 64 (7.3%) were undecided. Males (226/254; 88.9%) and those ≥ 55 years (95/100; 95%) had the highest rates of acceptance. Of the 113 who were not willing to receive the vaccine, 54.9% reported that the vaccine was not studied well enough. Participants with a previous SARS-CoV-2 infection and those who did not know if they had a previous infection (p = 0.002) were less likely to accept the vaccine compared to those with no previous infection. The most trusted COVID-19 sources of information were WHO (69.3%) and healthcare providers (68%). CONCLUSION: Lebanese HCWs had a relatively high acceptance rate for COVID-19 vaccination compared to other countries. Our findings are important in informing the Lebanese health care authorities to establish programs and interventions to improve vaccine uptake among HCWs and the general population.

Prevalence of Chronic Diseases, Depression, and Stress Among US Childcare Professionals During the COVID-19 Pandemic.

INTRODUCTION: Given their central role in supporting children's development, childcare professionals' overall physical and mental health is important. We evaluated the prevalence of chronic diseases, depression, and stress levels during the COVID-19 pandemic among US childcare professionals. METHODS: Data were obtained from US childcare professionals (N = 81,682) through an online survey from May 22, 2020, through June 8, 2020. We used multivariable logistic and linear regression models to assess the association of sociodemographic characteristics with 4 physical health conditions (asthma, heart disease, diabetes, and obesity), depression, and stress weighted to national representativeness. RESULTS: 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) obesity. For 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 sex/gender disparities were found for physical health conditions but not mental health of childcare professionals during the COVID-19 pandemic. CONCLUSION: Our findings highlighted that childcare professionals' depression rates during the pandemic were higher than before the pandemic, and depression, stress, and asthma rates were higher than rates among US adults overall during the pandemic. Given the essential work childcare professionals provided during the pandemic, policy makers and public health officials should consider what can be done to support their physical and mental health.

Factors influencing the decision to receive seasonal influenza vaccination among US corporate non-healthcare workers.

Influenza causes significant mortality and morbidity in the United States (US). Employees are exposed to influenza at work and can spread it to others. The influenza vaccine is safe, effective, and prevents severe outcomes; however, coverage among US adults (50.2%) is below Healthy People 2030 target of 70%. These highlights need for more effective vaccination promotion interventions. Understanding predictors of vaccination acceptance could inform vaccine promotion messages, improve coverage, and reduce illness-related work absences. We aimed to identify factors influencing influenza vaccination among US non-healthcare workers. Using mixed-methods approach, we evaluated factors influencing influenza vaccination among employees in three US companies during April-June 2020. Survey questions were adapted from the WHO seasonal influenza survey. Most respondents (n = 454) were women (272, 59.9%), 20-39 years old (n = 250, 55.1%); white (n = 254, 56.0%); had a college degree (n = 431, 95.0%); and reported receiving influenza vaccine in preceding influenza season (n = 297, 65.4%). Logistic regression model was statistically significant, X (16, N = 450) = 31.6, p = .01. Education [(OR) = 0.3, 95%CI = 0.1-0.6)] and race (OR = 0.4, 95%CI = 0.2-0.8) were significant predictors of influenza vaccine acceptance among participants. The majority had favorable attitudes toward influenza vaccination and reported that physician recommendation would influence their vaccination decisions. Seven themes were identified in qualitative analysis: "Protecting others" (109, 24.0%), "Protecting self" (105, 23.1%), "Vaccine accessibility" (94, 20.7%), "Education/messaging" (71, 15.6%), "Policies/requirements" (15, 3.3%), "Reminders" (9, 2.0%), and "Incentives" (3, 0.7%). Our findings could facilitate the development of effective influenza vaccination promotion messages and programs for employers, and workplace vaccination programs for other diseases such as COVID-19, by public health authorities.

Influenza causes significant mortality and morbidity in the United States (US).The US working-age group (18­64-year-old) bears a huge burden of influenza annually.Influenza vaccination coverage in the working-age group is low.Physicians and employers can influence vaccine acceptance of working adults.Employers can consider practical steps, e.g., incentivizing, or offering vaccine onsite.

COVID-19 vaccine acceptance among healthcare workers in the United Arab Emirates.

Background: COVID-19 vaccine hesitancy among healthcare workers (HCWs) is a threat to any healthcare system. Vaccine hesitancy can increase infection risk among HCWs and patients, while also impacting the patients' decision to accept the vaccine. Our study assessed COVID-19 vaccine acceptance among HCWs in United Arab Emirates (UAE). Methods: Using purposive sampling, UAE HCWs registered in the Abu Dhabi Department of Health (DOH) email database were invited to complete an online questionnaire, between November 2020 and February 2021, to understand COVID-19 vaccine acceptance and hesitancy, and trust in sources of information. Simple logistic regression was used to assess the associations between demographic factors with COVID-19 vaccine acceptance. Results: Of the 2832 HCWs who participated in the study, 1963 (69.9%) were aged between 25 and 44 years and 1748 (61.7%) were females. Overall, 2525 (89.2%) of the HCW population said they would accept a COVID-19 vaccine. HCWs who were 55+ years of age, male, and physicians/surgeons were more likely to accept a COVID-19 vaccine (OR 3.1, 95% CI 1.5-6.2, p = 0.002; OR 1.8, 95% CI 1.3-2.4, p < 0.001; and OR 1.8, 95% CI 1.1-2.9; p = 0.01, respectively). The most reliable sources for COVID-19 vaccine information were the UAE government (91.6%), healthcare providers (86.8%), health officials (86.3%), and the World Health Organization (WHO; 81.1%). Conclusions: COVID-19 vaccine acceptance was high among the UAE HCW population. Several factors were identified as significant determinants of vaccine acceptance. UAE healthcare authorities can utilize these findings to develop public health messaging campaigns for HCWs to best address COVID-19 vaccine concerns - particularly when the government is vaccinating its general population.

The balancing role of distribution speed against varying efficacy levels of COVID-19 vaccines under variants.

During a pandemic, vaccination plays an important role in reducing the infection spread or adverse outcomes such as hospitalizations and deaths. However, a vaccine's overall public health impact depends not only on its initial efficacy, but also its efficacy against emerging variants and ease and speed of distribution. For example, mutations in SARS-CoV-2 raised concerns about diminishing vaccine effectiveness against COVID-19 caused by particular variants. Furthermore, 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 COVID-19 pandemic has occurred due to the variants. Hence, we evaluated the interactions between the speed of distribution and efficacy against infection of multiple vaccines when variants emerge by utilizing a Susceptible-Infected-Recovered-Deceased model and assessing the level of infection attack rate. Our results show that speed is a key factor to a successful immunization strategy to control the pandemic even when the emerging variants may reduce the efficacy of a vaccine. Understanding the interactions between speed and efficacy and distributing vaccines that are available as quickly as possible are crucial to eradicate the pandemic before new variants spread.

Relationship between the use of nonpharmaceutical interventions and COVID-19 vaccination among U.S. child care providers: A prospective cohort study.

BACKGROUND: The relationship between the use of nonpharmaceutical interventions and COVID-19 vaccination among U.S. child care providers remains unknown. If unvaccinated child care providers are also less likely to employ nonpharmaceutical interventions, then a vaccine mandate across child care programs may have larger health and safety benefits. METHODS: To assess and quantify the relationship between the use of nonpharmaceutical interventions and COVID-19 vaccination among U.S. child care providers, we conducted a prospective cohort study of child care providers (N = 20,013) from all 50 states, the District of Columbia, and Puerto Rico. Child care providers were asked to complete a self-administered email survey in May-June 2020 assessing the use of nonpharmaceutical interventions (predictors) and a follow-up survey in May-June 2021 assessing COVID-19 vaccination (outcome). Nonpharmaceutical interventions were dichotomized as personal mitigation measures (e.g., masking, social distancing, handwashing) and classroom mitigation measures (e.g., temperature checks of staff/children, symptom screening for staff/children, cohorting). RESULTS: For each unendorsed personal mitigation measure during 2020, the likelihood of vaccination in 2021 decreased by 7% (Risk Ratio = 0.93 [95% CI 0.93 - 0.95]). No significant association was found between classroom mitigation measures and child care provider vaccination (Risk Ratio = 1.01 [95% CI 1.00-1.01]). CONCLUSIONS: Child care providers who used fewer personal mitigation measures were also less likely to get vaccinated for COVID-19 as an alternative form of protection. The combined nonadherence to multiple types of preventative health behaviors, that is, both nonpharmaceutical interventions and vaccination, among some child care providers may support a role for mandatory vaccination to achieve pandemic control.

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 2 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 these murine pregnancies vaccinated prior to the formation of the definitive placenta exhibit high circulating levels of anti-spike and anti-receptor-binding domain (anti-RBD) antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) consistent with maternal antibody status, indicating transplacental transfer in the later stages of pregnancy after early immunization. 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.

The Impact of Testing Capacity and Compliance With Isolation on COVID-19: A Mathematical Modeling Study.

Introduction: Diagnostic tests can play an important role in reducing the transmission of infectious respiratory diseases, particularly during a pandemic. The potential benefit of diagnostic testing depends on at least 4 factors: (1) how soon testing becomes available after the beginning of the pandemic and (2) at what capacity; (3) compliance with isolation after testing positive; and (4) compliance with isolation when experiencing symptoms, even in the absence of testing. Methods: To understand the interplay between these factors and provide further insight into policy decisions for future pandemics, we developed a compartmental model and simulated numerous scenarios using the dynamics of COVID-19 as a case study. Results: Our results quantified the significant benefits of early start of testing and high compliance with isolation. Early start of testing, even with low testing capacity over time, could significantly slow down the disease spread if compliance with isolation is high. By contrast, when the start of testing was delayed, the benefit of testing on reducing infection spread was limited, even when testing capacity was high; the additional testing capacity required increased superlinearly for each day of delay to achieve a similar infection attack rate as in starting testing earlier. Conclusions: Our study highlighted the importance of the early start of testing and public health messaging to promote isolation compliance when needed for an ongoing effective response to COVID-19 and future pandemics.

Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age.

BACKGROUND: Vaccination of children to prevent coronavirus disease 2019 (Covid-19) is an urgent public health need. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in children 6 to 11 years of age are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled expansion evaluation of the selected dose. In part 2, we randomly assigned children (6 to 11 years of age) in a 3:1 ratio to receive two injections of mRNA-1273 (50 µg each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of the vaccine in children and the noninferiority of the immune response in these children to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives included determination of the incidences of confirmed Covid-19 and severe acute respiratory syndrome coronavirus 2 infection, regardless of symptoms. Interim analysis results are reported. RESULTS: In part 1 of the trial, 751 children received 50-µg or 100-µg injections of the mRNA-1273 vaccine, and on the basis of safety and immunogenicity results, the 50-µg dose level was selected for part 2. In part 2 of the trial, 4016 children were randomly assigned to receive two injections of mRNA-1273 (50 µg each) or placebo and were followed for a median of 82 days (interquartile range, 14 to 94) after the first injection. This dose level was associated with mainly low-grade, transient adverse events, most commonly injection-site pain, headache, and fatigue. No vaccine-related serious adverse events, multisystem inflammatory syndrome in children, myocarditis, or pericarditis were reported as of the data-cutoff date. One month after the second injection (day 57), the neutralizing antibody titer in children who received mRNA-1273 at a 50-µg level was 1610 (95% confidence interval [CI], 1457 to 1780), as compared with 1300 (95% CI, 1171 to 1443) at the 100-µg level in young adults, with serologic responses in at least 99.0% of the participants in both age groups, findings that met the prespecified noninferiority success criterion. Estimated vaccine efficacy was 88.0% (95% CI, 70.0 to 95.8) against Covid-19 occurring 14 days or more after the first injection, at a time when B.1.617.2 (delta) was the dominant circulating variant. CONCLUSIONS: Two 50-µg doses of the mRNA-1273 vaccine were found to be safe and effective in inducing immune responses and preventing Covid-19 in children 6 to 11 years of age; these responses were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).

Lack of association between pandemic chilblains and SARS-CoV-2 infection.

An increased incidence of chilblains has been observed during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and attributed to viral infection. Direct evidence of this relationship has been limited, however, as most cases do not have molecular evidence of prior SARS-CoV-2 infection with PCR or antibodies. We enrolled a cohort of 23 patients who were diagnosed and managed as having SARS-CoV-2-associated skin eruptions (including 21 pandemic chilblains [PC]) during the first wave of the pandemic in Connecticut. Antibody responses were determined through endpoint titration enzyme-linked immunosorbent assay and serum epitope repertoire analysis. T cell responses to SARS-CoV-2 were assessed by T cell receptor sequencing and in vitro SARS-CoV-2 antigen-specific peptide stimulation assays. Immunohistochemical and PCR studies of PC biopsies and tissue microarrays for evidence of SARS-CoV-2 were performed. Among patients diagnosed and managed as "covid toes" during the pandemic, we find a percentage of prior SARS-CoV-2 infection (9.5%) that approximates background seroprevalence (8.5%) at the time. Immunohistochemistry studies suggest that SARS-CoV-2 staining in PC biopsies may not be from SARS-CoV-2. Our results do not support SARS-CoV-2 as the causative agent of pandemic chilblains; however, our study does not exclude the possibility of SARS-CoV-2 seronegative abortive infections.

Association of Child Masking With COVID-19-Related Closures in US Childcare Programs.

Importance: It is not known how effective child masking is in childcare settings in preventing the transmission of SARS-CoV-2. This question is critical to inform health policy and safe childcare practices. Objective: To assess the association between masking children 2 years and older and subsequent childcare closure because of COVID-19. Design, Setting, and Participants: A prospective, 1-year, longitudinal electronic survey study of 6654 childcare professionals at home- and center-based childcare programs in all 50 states was conducted at baseline (May 22 to June 8, 2020) and follow-up (May 26 to June 23, 2021). Using a generalized linear model (log-binomial model) with robust SEs, this study evaluated the association between childcare program closure because of a confirmed or suspected COVID-19 case in either children or staff during the study period and child masking in both early adoption (endorsed at baseline) and continued masking (endorsed at baseline and follow-up), while controlling for physical distancing, other risk mitigation strategies, and program and community characteristics. Exposures: Child masking in childcare programs as reported by childcare professionals at baseline and both baseline and follow-up. Main Outcomes and Measures: Childcare program closure because of a suspected or confirmed COVID-19 case in either children or staff as reported in the May 26 to June 23, 2021, end survey. Results: This survey study of 6654 childcare professionals (mean [SD] age, 46.9 [11.3] years; 750 [11.3%] were African American, 57 [0.9%] American Indian/Alaska Native, 158 [2.4%] Asian, 860 [12.9%] Hispanic, 135 [2.0%] multiracial [anyone who selected >1 race on the survey], 18 [0.3%] Native Hawaiian/Pacific Islander, and 5020 [75.4%] White) found that early adoption (baseline) of child masking was associated with a 13% lower risk of childcare program closure because of a COVID-19 case (adjusted relative risk, 0.87; 95% CI, 0.77-0.99), and continued masking for 1 year was associated with a 14% lower risk (adjusted relative risk, 0.86; 95% CI, 0.74-1.00). Conclusions and Relevance: This survey study of childcare professionals suggests that masking young children is associated with fewer childcare program closures, enabling in-person education. This finding has important public health policy implications for families that rely on childcare to sustain employment.

Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination.

The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and its numerous spike mutations, which have the potential to evade neutralizing antibodies elicited by COVID-19 vaccines. Here we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants who had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that a heterologous CoronaVac prime vaccination of two doses followed by a BNT162b2 booster induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and the Delta variant, resembling the titers obtained after two doses of mRNA vaccines. Although neutralization of Omicron was undetectable in participants who had received a two-dose regimen of CoronaVac, the BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron compared with the two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 7.1-fold and 3.6-fold for Omicron compared with the ancestral strain and the Delta variant, respectively. These findings have immediate implications for multiple countries that previously used a CoronaVac regimen and reinforce the idea 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.

Resource allocation for different types of vaccines against COVID-19: Tradeoffs and synergies between efficacy and reach.

OBJECTIVE: Vaccine 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: Our 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.

Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity.

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. Here we analysed the development of anti-SARS-CoV-2 antibody and T cell responses in individuals who were previously infected (recovered) or uninfected (naive) and received mRNA vaccines to SARS-CoV-2. While individuals who were previously infected sustained higher antibody titres than individuals who were uninfected post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination. 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 (for example, B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (for example, B.1.617.2). While both groups retained neutralization capacity against all variants, plasma from individuals who were previously infected and vaccinated displayed overall better neutralization capacity than plasma from individuals who were uninfected and also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the effect of emerging variants on antibody neutralizing activity.

COVID-19 Vaccine Uptake Among US Child Care Providers.

OBJECTIVES: Ensuring high coronavirus disease-2019 (COVID-19) vaccine uptake among US child care providers is crucial to mitigating the public health implications of child-staff and staff-child transmission of severe acute respiratory syndrome coronavirus 2; however, the vaccination rate among this group was previously unknown. METHODS: To characterize vaccine uptake among US child care providers, we conducted a multistate 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 e-mail between May 26 and June 23, 2021. A 37.8% response yielded 21 663 respondents, with 20 013 satisfying inclusion criteria. RESULTS: Overall COVID-19 vaccine uptake among US child care providers (78.2%, 90% confidence interval: 77.5% to 78.9%) was higher than the US general adult population (65%). Vaccination rates varied between states from 53.5% to 89.4%. Vaccine uptake among respondents differed significantly (P < .01) based on respondent age (70.0% for ages 25-34, 91.6% for ages 75-84), race (70.0% for Black or African Americans, 92.5% for Asian Americans), annual household income (70.8% for <$35 000, 85.1% for >$75 000), and child care setting (73.0% for home-based, 79.7% for center-based). CONCLUSIONS: COVID-19 vaccine uptake among US child care providers was higher than the general US 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 child care programs reported the lowest rates of vaccination. State public health leaders and lawmakers should prioritize these subgroups to realize the largest gains in vaccine uptake among providers.