One-year dynamics of antibody titers after three doses of SARS-CoV-2 BNT162b2 vaccine

BackgroundA third dose of the BNT162b2 SARS-CoV-2 vaccine leads to a significant increase in antibody levels, however, concerns regarding the long-term persistence of this response exist. We assessed the humoral response for one year following vaccination.MethodsA prospective study among immunocompetent healthcare workers (HCW) who received three doses of BNT162b2. anti-spike antibody titers were measured at six predefined timepoints, from before the second vaccine dose, and up to one year afterwards, which is 4–6 months after the third dose. HCW with a history of SARS-CoV-2 infection were excluded.ResultsSeventy-six HCW had all the six serological measurements. Antibody titers significantly increased shortly following the third vaccine dose, and while declining, remained higher from all previous measurements for up to six months.ConclusionsA third dose of BNT162b2 leads to a profound humoral response, which remains significantly higher than previous measurements, even after 6 months.     

Effectiveness of BNT162b2 Vaccine Booster against SARS-CoV-2 Infection and Breakthrough Complications,Israel

We estimated vaccine effectiveness (VE) of the BNT162b2 (Pfizer-BioNTech, https://www.pfizer.com) booster dose against SARS-CoV-2 infection and reduction of complications (hospitalization, severe disease, and death) among breakthrough cases in persons in Israel >16 years of age for <20 weeks. VE estimates reached 96.8% (95% CI 96.0%–97.5%) for persons 16–59 years of age and 93.1% (95% CI 91.8%–94.2%) for persons >60 years of age on week 3. VE estimates remained at these levels for 8 weeks in the 16–59 age group and 11 weeks in those >60. A slow decline followed, becoming more pronounced in the last 2–3 weeks of evaluation. Estimates in the last week of evaluation were 77.6% (95% CI 68.4%–84.2%) and 61.3% (52.5%–68.4%) for persons 16–59 years and >60 years, respectively. The more pronounced VE decline coincided with rapid increase in Omicron variant activity. Rate reduction of breakthrough complications remained moderate to high throughout the evaluation.     

Evaluation of potential adverse events following COVID-19 mRNA vaccination among adults aged 65 years and older: Two self-controlled studies in the U.S.

BackgroundOur near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevation in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluation of potential associations.MethodsWe conducted two self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged ≥ 65 years. Adjusted incidence rate ratio (IRRs) and 95 % confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following monovalent booster doses for AMI, PE, ITP, Bell’s Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri).ResultsThe primary series study included 3,360,981 individuals who received 6,388,542 primary series doses; the booster study included 6,156,100 individuals with one monovalent booster dose. The AMI IRR following BNT162b2 primary series and booster was 1.04 (95 % CI: 0.91 to 1.18) and 1.06 (95 % CI: 1.003 to 1.12), respectively; for mRNA-1273 primary series and booster, 1.01 (95 % CI: 0.82 to 1.26) and 1.05 (95 % CI: 0.998 to 1.11), respectively. The hospital inpatient PE IRR following BNT162b2 primary series and booster was 1.19 (95 % CI: 1.03 to 1.38) and 0.86 (95 % CI: 0.78 to 0.95), respectively; for mRNA-1273 primary series and booster, 1.15 (95 % CI: 0.94 to 1.41) and 0.87 (95 % CI: 0.79 to 0.96), respectively. The studies’ results do not support that exposure to COVID-19 mRNA vaccines elevate the risk of ITP, DIC, Myo/Peri, and BP.ConclusionWe did not find an increased risk for AMI, ITP, DIC, BP, and Myo/Peri and there was not consistent evidence for PE after exposure to COVID-19 mRNA primary series or monovalent booster vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the U.S. elderly population.     

SIRVA (Shoulder Injury Related to Vaccine Administration) following mRNA COVID-19 Vaccination: Case discussion and literature review

Shoulder injury related to vaccine administration (SIRVA) is an increasingly recognised complication after vaccination and presents with significant shoulder pain and stiffness. SIRVA is thought to occur as a result of improper administration of vaccine into the subdeltoid bursa or shoulder joint. This results in an inflammatory cascade that damages the structures in the shoulder region. The incidence of SIRVA is relatively higher for influenza vaccination due its widespread administration. We present a reported case of SIRVA following a mRNA COVID-19 vaccination and review the current literature. As we embark on a worldwide scale of COVID-19 vaccination, it is of utmost important that we use proper vaccination techniques and screen patients at risk of SIRVA. This would improve the efficacy of the vaccine and improve the outcomes of the vaccination programme.     

Multistate Outbreak of SARS-CoV-2 Infections,Including Vaccine Breakthrough Infections,Associated with Large Public Gatherings,United States

During July 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 variant infections, including vaccine breakthrough infections, occurred after large public gatherings in Provincetown, Massachusetts, USA, prompting a multistate investigation. Public health departments identified primary and secondary cases by using coronavirus disease surveillance data, case investigations, and contact tracing. A primary case was defined as SARS-CoV-2 detected <14 days after travel to or residence in Provincetown during July 3–17. A secondary case was defined as SARS-CoV-2 detected <14 days after close contact with a person who had a primary case but without travel to or residence in Provincetown during July 3–August 10. We identified 1,098 primary cases and 30 secondary cases associated with 26 primary cases among fully and non–fully vaccinated persons. Large gatherings can have widespread effects on SARS-CoV-2 transmission, and fully vaccinated persons should take precautions, such as masking, to prevent SARS-CoV-2 transmission, particularly during substantial or high transmission.     

Humoral response to the SARS-CoV-2 BNT162b2 mRNA vaccine: Real-world data from a large cohort of healthcare workers

BackgroundThe SARS-CoV-2 pandemic was responsible for the death of millions of people around the world, which accelerated the study of vaccines. The BNT162b2 mRNA COVID-19 is a messenger RNA vaccine that encodes the spike protein of the virus. However, the duration of the protection conferred by this vaccine and factors associated with immune responses require validation in large cohorts.MethodsHere, we present data of humoral immune response to vaccination in 4264 healthcare workers, tested before (T0) and 15 and 90 days (T1 and T2, respectively) following vaccination. Peripheral blood was collected for immunological analysis using the Quant SARS-CoV-2 IgG II Chemiluminescent Microparticle Immunoassay (CMIA) to determine anti-spike IgG, receptor binding domain (RBD), S1 subunit of SARS-CoV-2.FindingsAt T0, 96·8% (n = 4129) of participants had IgG antibodies non-reactive to anti-SARS-CoV-2. Fifteen days after completing the vaccination, the IgG overall median titer was significantly elevated (21·7x10³ AU/mL). Both for uni- and multivariate logistic regression analyses women presented higher antibody levels than men, independent of age. Titers were significantly altered among age groups, decreasing by each increase in 10-year of age. At 3 months after completing the vaccination, anti-SARS-CoV-2 IgG titers were 6·3-fold diminished.This real-world post-vaccination data confirmed production of a frequent and elevated anti-SARS-CoV-2 IgG titers, associated with high protection rates. Females and younger participants had higher titer 15 days after vaccination, and despite the significant reduction from 15-to-90 days, those with higher pre-vaccination titers maintained higher levels throughout the remaining timepoints.InterpretationThese findings support the need to track humoral immunity kinetics to uncover viral susceptibility and eventually implement re-vaccination, particularly in groups prone to lower humoral immune response.FundingNo external funding was received to conduct this study.     

Cross-Variant Neutralizing Serum Activity after SARS-CoV-2 Breakthrough Infections

To determine neutralizing activity against the severe acute respiratory syndrome coronavirus 2 ancestral strain and 4 variants of concern, we tested serum from 30 persons with breakthrough infection after 2-dose vaccination. Cross-variant neutralizing activity was comparable to that after 3-dose vaccination. Shorter intervals between vaccination and breakthrough infection correlated with lower neutralizing titers.     

Neutralizing antibody responses in healthcare personnel after three doses of mRNA BNT162b2 vaccine and association with baseline characteristics and past SARS-CoV-2 infection

AimTo estimate neutralizing antibody (NAb) immunity against SARS-CoV-2 in 739 healthcare personnel (HCP) vaccinated with three doses of BNT162b2 mRNA vaccine.MethodsSerum samples were collected at 3, 6, and 9 months after the second vaccine dose and at 7–55 days after the third dose. Samples were tested for NAbs against SARS-CoV-2 receptor binding domain.ResultsThe mean inhibition rates at 3, 6, and 9 months after the second dose were 86.33%, 73.38%, and 61.18%, and increased to 95.57% after the booster dose. Younger HCP and HCP with past SARS-CoV-2 infection had higher inhibition rates while there was an inverse correlation between NAb levels and comorbidities or tobacco use (p-values < 0.001). Increased NAb titers were also noticed in women (p-value = 0.033), especially at the end of the 9-month study period.ConclusionNAb levels increased considerably after a booster mRNA vaccine dose. Host factors and past SARS-CoV-2 infection influence NAb titers.     

SARS-CoV-2 Breakthrough Infections after introduction of 4 COVID-19 Vaccines,South Korea, 2021

We conducted a nationwide retrospective cohort study to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection among recipients of 4 different vaccines in South Korea. Age-adjusted breakthrough infection rate per month was highest for Janssen (42.6/100,000 population), followed by AstraZeneca (21.7/100,000 population), Pfizer-BioNTech (8.5/100,000 population), and Moderna (1.8/100,000 population).     

Patients with history of covid-19 had more side effects after the first dose of covid-19 vaccine

IntroductionCOVID-19 vaccination seems to be the most pertinent pharmacologic public health measure to control the pandemic. Reactogenicity symptoms were frequent in vaccine recipients mostly mild to moderate and commonly reported after the second dose. However, there is a lack of data in patients with a previous diagnosis of Covid-19.MethodsWe analysed side effects of 311 patients after the first dose of Pfizer-BioNTech COVID-19 vaccine, in a french university hospital. We compared patients with COVID-19 history to naive individuals. All the data collected are based on self-reported, including COVID-19 exposure status.ResultsOverall, 229 (74%) patients reported at least one side effect. Among participants with history of Covid-19, 95% reported at least one adverse event versus 70% in naive patients (p < 0.01). However, symptom intensity was not different between the 2 groups.ConclusionVaccine recipients with prior COVID-19 reported more, but no more serious, side effects than naive participants.     

Induced humoral immunity of different types of vaccines against most common variants of SARS-CoV-2 in Egypt prior to Omicron outbreak

The diversity of SARS-CoV-2 continues to lead to the emergence of new SARS-CoV-2 variants. SARS-CoV-2 antibody assays are crucial in managing the COVID-19 pandemic by determining the neutralizing antibody response. This study aims to investigate vaccine-induced antibodies against most common variants of SARS-CoV-2 in Egypt. Sera samples were collected from vaccinated participants and neutralizing activity against the SARS-CoV-2 variants was determined using microneutralization assay. Our results show that the BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCov-19 (AstraZeneca), and Ad26.COV2.S COVID-19 (Janssen) vaccines elicited neutralizing antibody responses more than the BBIBP-CorV vaccine (Sinopharm) against B.1, C.36.3, and AY.32 (Delta) variants. While vaccines remain highly effective in managing the COVID-19 pandemic, ongoing monitoring of vaccine effectiveness is needed.     

Resident Factors Associated With Breakthrough SARS-CoV-2 Infections

ObjectiveTo examine incidence of and resident characteristics associated with breakthrough infections (BTIs) and severe illness among residents with 2 messenger RNA (mRNA) vaccinations.DesignRetrospective cohort study.Setting and ParticipantsNursing home (NH) residents who completed their primary series of mRNA COVID-19 vaccination by March 31, 2021.MethodsElectronic health records and Minimum Data Set assessments from a multistate NH data consortium were used to identify BTI and severe illness (a composite measure of hospitalization and/or death within 30 days of BTI) occurring prior to November 24, 2021. A t test for differences in means was used to compare covariates for residents with and without BTI. Finally, we estimated incidence rate ratios (IRRs) for BTI with 95% CIs using a modified Poisson regression approach, comparing residents with BTI vs residents without. We adjusted for facility fixed effects in our model.ResultsOur sample included 23,172 residents from 984 NHs who were at least 14 days past their second mRNA vaccine dose. Of those, 1173 (5%) developed an incident COVID-19 BTI (mean follow-up time: 250 days). Among residents with BTI, 8.6% were hospitalized or died within 30 days of BTI diagnosis. Factors associated with severe illness included age ≥85 years (IRR 2.08, 95% CI 1.08-4.02, reference age <65 years), bowel incontinence (IRR 1.73, 95% CI 1.01-2.99), coronary artery disease (IRR 1.96, 95% CI 1.31-2.94), chronic kidney disease (IRR 1.65, 95% CI 1.07-2.54), and schizophrenia (IRR 2.38, 95% CI 1.19-4.75).Conclusions and ImplicationsAmong vaccinated NH residents, BTIs and associated severe illness are rare. Residents aged ≥85 years and with certain comorbidities appear to be the most vulnerable. Given that the pandemic continues and testing policies have relaxed, these data provide prognostic information for NH facilities faced with continued outbreaks.     

新型冠状病毒疫苗对新型冠状病毒德尔塔变异株预防效果的Meta分析

目的 运用循证医学Meta分析方法,探究和评价新型冠状病毒疫苗对新型冠状病毒德尔塔变异株的预防效果,为新冠肺炎的防控提供循证支持。方法 以新型冠状病毒德尔塔毒株、疫苗及其同义词、近义词作为检索词,系统检索中国知网、万方数据库、维普数据库、中国生物医学文献服务系统、PubMed、考科蓝图书馆、Web of Science、BioRxiv、MedRxiv和Europe PMC关于新型冠状病毒疫苗保护效果(Vaccine Effectiveness,VE)的文献,使用纽卡斯尔-渥太华风险评分量表对纳入的队列研究和病例对照研究文献进行质量评价,对纳入的随机对照试验则使用Jadad评分进行质量评价,运用Stata 12.0进行异质性检验、总效应值和发表性偏倚估计。结果 共纳入文献14篇,其中病例对照研究文献5篇,队列研究文献8篇,随机对照实验1篇。Meta分析显示,接种一剂新冠疫苗的合并VE(95%CI)为34.57%(95%CI:21.70%～47.44%),接种两剂新型冠状病毒疫苗的合并VE(95%CI)为70.56%(95%CI: 64.29%～76.82%)。漏斗图分析表明存在发表偏倚风险。结论 接种新型冠状病毒疫苗对预防新型冠状病毒德尔塔变异株有保护作用,且2剂疫苗保护作用明显比1剂疫苗强。后续仍需要收集更多的疫苗保护率研究,提供发表性偏倚风险小的证据。     

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Moderna COVID-19 Vaccine (mRNA-1273)

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group has prepared standardized templates to describe the key considerations for the benefit-risk assessment of several vaccine platform technologies, including nucleic acid (RNA and DNA) vaccines. This paper uses the BRAVATO template to review the features of a vaccine employing a proprietary mRNA vaccine platform to develop Moderna COVID-19 Vaccine (mRNA-1273); a highly effective vaccine to prevent coronavirus disease 2019 (Covid-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In response to the pandemic the first in human studies began in March 2020 and the pivotal, placebo-controlled phase 3 efficacy study in over 30,000 adults began in July 2020. Based on demonstration of efficacy and safety at the time of interim analysis in November 2020 and at the time of trial unblinding in March 2021, the mRNA-1273 received Emergency Use Authorization in December 2020 and full FDA approval in January 2022.     

Factors influencing acceptance of the COVID-19 vaccine in Malaysia: a web-based survey

ObjectivesThe coronavirus disease 2019 (COVID-19) pandemic has set a precedent for the fastest-produced vaccine as a result of global collaboration and outreach. This study explored Malaysians’ acceptance of the COVID-19 vaccine and its associated factors.Methods A cross-sectional anonymous web-based survey was disseminated to Malaysian adults aged ≥18 years old via social media platforms between July 10, 2020 and August 31, 2020.Results In the analysis of 4,164 complete responses, 93.2% of participants indicated that they would accept the COVID-19 vaccine if it was offered for free by the Malaysian government. The median out-of-pocket cost that participants were willing to pay for a COVID-19 vaccine was Malaysian ringgit (MYR) 100 (interquartile range [IQR], 100) if it was readily available and MYR 150 (IQR, 200) if the supply was limited. Respondents with a low likelihood of vaccine hesitancy had 13 times higher odds of accepting the COVID-19 vaccine (95% confidence interval [CI], 8.69 to 19.13). High perceived risk and severity were also associated with willingness to be vaccinated, with adjusted odds ratios of 2.22 (95% CI, 1.44 to 3.41) and 2.76 (95% CI, 1.87 to 4.09), respectively. Age and ethnicity were the only independent demographic characteristics that predicted vaccine uptake.Conclusion Public health strategies targeting perceived risk, perceived susceptibility and vaccine hesitancy could be effective in enhancing vaccine uptake.     

SARS-CoV-2 Breakthrough Infections among US Embassy Staff Members,Uganda, May–June 2021

The SARS-CoV-2 Delta variant emerged shortly after COVID-19 vaccines became available in 2021. We describe SARS-CoV-2 breakthrough infections in a highly vaccinated, well-monitored US Embassy community in Kampala, Uganda. Defining breakthrough infection rates in highly vaccinated populations can help determine public health messaging, guidance, and policy globally.     

Safety and immunogenicity of an egg-based inactivated Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Interim results of a randomized,placebo-controlled,phase 1/2 trial in Vietnam

Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus (NDV) vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Wuhan-Hu-1. The spike protein was stabilized and incorporated into NDV virions by removing the polybasic furin cleavage site, introducing the transmembrane domain and cytoplasmic tail of the fusion protein of NDV, and introducing six prolines for stabilization in the prefusion state. Vaccine production and clinical development was initiated in Vietnam, Thailand, and Brazil. Here the interim results from the first stage of the randomized, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial conducted at the Hanoi Medical University (Vietnam) are presented. Healthy adults aged 18–59 years, non-pregnant, and with self-reported negative history for SARS-CoV-2 infection were eligible. Participants were randomized to receive one of five treatments by intramuscular injection twice, 28 days apart: 1 μg +/- CpG1018 (a toll-like receptor 9 agonist), 3 μg alone, 10 μg alone, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited adverse events (AEs) during 7 days and subject-reported AEs during 28 days after each vaccination. Investigators further reviewed subject-reported AEs. Secondary outcomes were immunogenicity measures (anti-spike immunoglobulin G [IgG] and pseudotyped virus neutralization). This interim analysis assessed safety 56 days after first vaccination (day 57) in treatment-exposed individuals and immunogenicity through 14 days after second vaccination (day 43) per protocol. Between March 15 and April 23, 2021, 224 individuals were screened and 120 were enrolled (25 per group for active vaccination and 20 for placebo). All subjects received two doses. The most common solicited AEs among those receiving active vaccine or placebo were all predominantly mild and included injection site pain or tenderness (<58%), fatigue or malaise (<22%), headache (<21%), and myalgia (<14%). No higher proportion of the solicited AEs were observed for any group of active vaccine. The proportion reporting vaccine-related AEs during the 28 days after either vaccination ranged from 4% to 8% among vaccine groups and was 5% in controls. No vaccine-related serious adverse event occurred. The immune response in the 10 μg formulation group was highest, followed by 1 μg + CpG1018, 3 μg, and 1 μg formulations. Fourteen days after the second vaccination, the geometric mean concentrations (GMC) of 50% neutralizing antibody against the homologous Wuhan-Hu-1 pseudovirus ranged from 56.07 IU/mL (1 μg, 95% CI 37.01, 84.94) to 246.19 IU/mL (10 μg, 95% CI 151.97, 398.82), with 84% to 96% of vaccine groups attaining a ≥ 4-fold increase over baseline. This was compared to a panel of human convalescent sera (N = 29, 72.93 95% CI 33.00–161.14). Live virus neutralization to the B.1.617.2 (Delta) variant of concern was reduced but in line with observations for vaccines currently in use. Since the adjuvant has shown modest benefit, GMC ratio of 2.56 (95% CI, 1.4–4.6) for 1 μg +/- CpG1018, a decision was made not to continue studying it with this vaccine. NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 μg dose was advanced to phase 2 along with a 6 μg dose. The 10 μg dose was not selected for evaluation in phase 2 due to potential impact on manufacturing capacity. ClinicalTrials.gov NCT04830800.     

IgG antibody production and persistence to 6 months following SARS-CoV-2 vaccination: A Northern Ireland observational study

BackgroundThis study evaluates spike protein IgG antibody response following Oxford-AstraZeneca COVID-19 vaccination using the AbC-19? lateral flow device.MethodsPlasma samples were collected from n = 111 individuals from Northern Ireland. The majority were >50 years old and/or clinically vulnerable. Samples were taken at five timepoints from pre-vaccination until 6-months post-first dose.Results20.3% of participants had detectable IgG responses pre-vaccination, indicating prior COVID-19. Antibodies were detected in 86.9% of participants three weeks after the first vaccine dose, falling to 74.7% immediately prior to the second dose, and rising to 99% three weeks post-second vaccine. At 6-months post-first dose, this decreased to 90.5%. At all timepoints, previously infected participants had significantly higher antibody levels than those not previously infected.ConclusionThis study demonstrates that strong anti-spike protein antibody responses are evoked in almost all individuals that receive two doses of Oxford-AstraZeneca vaccine, and which largely persist beyond six months after first vaccination.     

Effectiveness of 3 COVID-19 Vaccines in Preventing SARS-CoV-2 Infections,January–May 2021, Aragon,Spain

Reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is a worldwide challenge; widespread vaccination could be one strategy for control. We conducted a prospective, population-based cohort study of 964,258 residents of Aragon, Spain, during December 2020–May 2021. We used the Cox proportional-hazards model with vaccination status as the exposure condition to estimate the effectiveness of 3 coronavirus disease vaccines in preventing SARS-CoV-2 infection. Pfizer-BioNTech had 20.8% (95% CI 11.6%–29.0%) vaccine effectiveness (VE) against infection after 1 dose and 70.0% (95% CI 65.3%–74.1%) after 2 doses, Moderna had 52.8% (95% CI 30.7%–67.8%) VE after 1 dose and 70.3% (95% CI 52.2%–81.5%) after 2 doses, and Oxford-AstraZeneca had 40.3% (95% CI 31.8%–47.7%) VE after 1 dose. All estimates were lower than those from previous studies. Results imply that, although high vaccination coverage remains critical to protect people from disease, it will be difficult to effectively minimize transmission opportunities.