Long-term Effects Of Vaccination Research Articles

Mpox in people with HIV: A narrative review.

The 2022 global mpox outbreak disproportionately impacted people living with HIV. This review explores recent evidence on mpox in this group, focusing on clinical presentation, complications, treatment modalities and vaccine strategies. Recent studies have suggested that people with HIV diagnosed with mpox have a greater risk of proctitis and hospitalization compared with people without HIV. In addition, those with advanced immunosuppression face an elevated risk of severe mpox infection, which can lead to mortality. Comprehensive and prompt supportive care using antiretrovirals and mpox antivirals is crucial in this group. Although results from randomized clinical trials are still forthcoming, recent studies suggest that early initiation of tecovirimat can prevent disease progression in people with HIV. The non-replicative attenuated smallpox vaccine is well tolerated and effective in preventing monkeypox virus infections in people with HIV. Further studies are needed regarding long-term vaccine effectiveness for this population. Evaluating the risk of severe mpox in people living with HIV requires assessing the level of immune suppression and viral control. Universal access to vaccination is imperative to prevent the resurgence of future outbreaks.

Transmission Modelling for Human Non-Zoonotic Schistosomiasis Incorporating Vaccination: Guiding Decision- and Policymaking

Schistosomiasis, acquired by skin-penetrating cercariae of dioecious digenean schistosomes during freshwater contact, afflicts nearly 260 and 440 million people with active infections and residual morbidity, respectively. About 10 million women at reproductive age contract schistosomiasis during gestation every year. Acute schistosomiasis is characterized by pre-patent pro-inflammatory CD4+ T-helper 1 or CD4+ Th1/T-helper 17 reactivity against immature schistosomulae. Chronic schistosomiasis is dominated by post-patent anti-inflammatory CD4+ T-helper 2 reactivity against ova epitopes. Flukes co-exist in immunocompetent definitive hosts as they are capable of evading their defense mechanisms. Preventive measures should be complemented by vaccination, inducing long-term protection against transmission, infection, and disease recurrence, given the latest advancements in schistosomal vaccines. Vaccines become pivotal when considering constraints of chemotherapy, i.e., lack of protection against re-infection, and evolving resistance or reduced sensitivity. Transmission models for human non-zoonotic schistosomiasis incorporating vaccination available in PubMed, Embase and Web of Science up to 31 December 2023 are presented. Besides conceptual model differences, predictions meant to guide decision- and policymaking reveal continued worm harboring that facilitates transmission besides residual infections. In addition, increased susceptibility to re-infection and rebound morbidity, both shifted to later life stages following the intervention, are forecasted. Consequently, a vaccination schedule is pivotal that considers the optimal age for initial immunization, i.e., pre-schoolchildren or schoolchildren in a cohort-based or population-based manner, while incorporating potential non-adherers promoting ongoing transmission. Longevity over magnitude of vaccine protection to antigenic schistosomal moieties is crucial. Accounting for pre-acquired immunity from natural exposure, in utero priming in addition to herd immunity, and induced by chemotherapy is crucial. Combining, as a multi-component approach, long-term effects of vaccination with short-term effects of chemotherapy as regular repeated vaccine-linked therapy seems most promising to achieve WHO’s endpoints of transmission elimination and morbidity control.

Comparison of Time to Report the Side Effects after AstraZeneca and Sinopharm Vaccinations in Users of the COVID-19 Symptom Study App: A Survey in South Iran.

Concerns about the side effects of SARS-CoV-2 vaccines have been raised nationwide. We aimed to compare the time to report the side effects of the Oxford-AstraZeneca and Sinopharm COVID-19 vaccines. Information on side effects of AstraZeneca and Sinopharm COVID-19 vaccines was obtained from the COVID-19 Symptom Study App affiliated with Shiraz University of Medical Science during 2021. A COX regression model with an adjusted Hazard Ratio and 95% Confidence Interval; HR (95% C.I) was reported at the significance level of < 0.05. 4478 and 5555 participants received the AstraZeneca and Sinopharm vaccines, respectively; more age, history of SARS-CoV-2 infection, first vaccine dose, hypertension, and hypertension with cardiovascular disease were seen in the AstraZeneca group (P < 0.05 for all). However, the AstraZeneca group had lower immune deficiency and time to report the side effects (P < 0.05 for both). There was significantly less time to pain HR(95% C.I.); 0.50 (0.47-0.52), vertigo 0.65 (0.61-0.69), weakness 0.41 (0.38-0.44), headache 0.43 (0.39-0.74), anorexia 0.31 (0.28-0.34), nausea 0.56 (0.51-0.62), severer allergy 0.71 (0.63-0.81), general inflammation 0.27 (0.23-0.31), fever > 38oC 0.12 (0.1-0.15), eye inflammation 0.45 (0.39-0.52), diarrhea 0.85 (0.73-0.99), blurred vision 0.73 (0.61-0.86), injection site redness 0.32 (0.26-0.39), fatigue/paleness 0.53 (0.50-0.57), joint pain 0.55 (0.41-0.73), auxiliary gland inflation 0.59 (0.43-0.80), convulsions 0.30 (0.17-0.52), and severe side effects 0.3 (0.27-0.33) in the AstraZeneca group; However, skin rash 0.77 (0.57-1.05) and hospitalization 0.72 (0.21-2.55) were the same. Sinopharm COVID-19 vaccine recipients reported longer times to report vaccine-related side effects than AstraZeneca; due to the lack of adverse effects like hospitalization, vaccination should continue to control the pandemic; more real-population studies are needed on the long-term effects of vaccination against COVID-19.

Estimating long-term vaccine effectiveness against SARS-CoV-2 variants: a model-based approach

With the ongoing evolution of the SARS-CoV-2 virus updated vaccines may be needed. We fitted a model linking immunity levels and protection to vaccine effectiveness data from England for three vaccines (Oxford/AstraZeneca AZD1222, Pfizer-BioNTech BNT162b2, Moderna mRNA-1273) and two variants (Delta, Omicron). Our model reproduces the observed sustained protection against hospitalisation and death from the Omicron variant over the first six months following dose 3 with the ancestral vaccines but projects a gradual waning to moderate protection after 1 year. Switching the fourth dose to a variant-matched vaccine against Omicron BA.1/2 is projected to prevent nearly twice as many hospitalisations and deaths over a 1-year period compared to administering the ancestral vaccine. This result is sensitive to the degree to which immunogenicity data can be used to predict vaccine effectiveness and uncertainty regarding the impact that infection-induced immunity (not captured here) may play in modifying future vaccine effectiveness.

A FluoroSpot B assay for the detection of IgA and IgG SARS-CoV-2 spike-specific memory B cells: Optimization and qualification for use in COVID-19 vaccine trials

BackgroundThe generation of antigen-specific memory B cells is crucial to the long-term effectiveness of vaccines. When the protective antibodies circulating in the blood wane, memory B cells (MBC) can be rapidly reactivated and differentiated into antibody-secreting cells during a new infection. Such MBC responses are considered to be key in providing long-term protection after infection or vaccination. Here, we describe the optimization and qualification of a FluoroSpot assay to measure MBCs directed against the SARS-CoV-2 spike protein in the peripheral blood, for use in COVID-19 vaccine trials. MethodsWe developed a FluoroSpot assay enabling simultaneous enumeration of B cells secreting IgA or IgG spike-specific antibodies after polyclonal stimulation of peripheral blood mononuclear cells (PBMCs) with interleukin-2 and the toll-like receptor agonist R848 for 5 days. The antigen coating was optimized using a capture antibody directed against the spike subunit-2 glycoprotein of SARS-CoV-2 to immobilize recombinant trimeric spike protein onto the membrane. ResultsCompared to a direct spike protein coating, the addition of a capture antibody increased the number and the quality of detected spots for both spike-specific IgA and IgG secreting cells in PBMCs from COVID-19 convalescents. The qualification showed good sensitivity of the dual-color IgA-IgG FluoroSpot assay, with lower limits of quantitation of 18 background-subtracted (BS) antibody-secreting cells (ASCs)/well for spike-specific IgA and IgG responses. Linearity was demonstrated at values ranging from 18 to 73 and from 18 to 607 BS ASCs/well for spike-specific IgA and IgG, respectively, as was precision, with intermediate precision (percentage geometric coefficients of variation) of 12% and 26% for the proportion of spike-specific IgA and IgG MBCs (ratio specific/total IgA or Ig). The assay was specific, since no spike-specific MBCs were detected in PBMCs from pre-pandemic samples; the results were below the limit of detection of 17 BS ASCs/well. ConclusionsThese results show that the dual-color IgA-IgG FluoroSpot provides a sensitive, specific, linear, and precise tool to detect spike-specific MBC responses. This MBC FluoroSpot assay is a method of choice for monitoring spike-specific IgA and IgG MBC responses induced by COVID-19 candidate vaccines in clinical trials.

Long-term effectiveness of COVID-19 vaccines against infections, hospitalisations, and mortality in adults: findings from a rapid living systematic evidence synthesis and meta-analysis up to December, 2022

Synthesising evidence on the long-term vaccine effectiveness of COVID-19 vaccines (BNT162b2 [Pfizer-BioNTech], mRNA-1273 [Moderna], ChAdOx1 nCoV-19 [AZD1222; Oxford-AstraZeneca], and Ad26.COV2.S [Janssen]) against infections, hospitalisations, and mortality is crucial to making evidence-based pandemic policy decisions. In this rapid living systematic evidence synthesis and meta-analysis, we searched EMBASE and the US National Institutes of Health's iSearch COVID-19 Portfolio, supplemented by manual searches of COVID-19-specific sources, until Dec 1, 2022, for studies that reported vaccine effectiveness immediately and at least 112 days after a primary vaccine series or at least 84 days after a booster dose. Single reviewers assessed titles, abstracts, and full-text articles, and extracted data, with a second reviewer verifying included studies. The primary outcomes were vaccine effectiveness against SARS-CoV-2 infections, hospitalisations, and mortality, which were assessed using three-level meta-analytic models. This study is registered with the National Collaborating Centre for Methods and Tools, review 473. We screened 16 696 records at the title and abstract level, appraised 832 (5·0%) full texts, and initially included 73 (0·4%) studies. Of these, we excluded five (7%) studies because of critical risk of bias, leaving 68 (93%) studies that were extracted for analysis. For infections caused by any SARS-CoV-2 strain, vaccine effectiveness for the primary series reduced from 83% (95% CI 80-86) at baseline (14-42 days) to 62% (53-69) by 112-139 days. Vaccine effectiveness at baseline was 92% (88-94) for hospitalisations and 91% (85-95) for mortality, and reduced to 79% (65-87) at 224-251 days for hospitalisations and 86% (73-93) at 168-195 days for mortality. Estimated vaccine effectiveness was lower for the omicron variant for infections, hospitalisations, and mortality at baseline compared with that of other variants, but subsequent reductions occurred at a similar rate across variants. For booster doses, which covered mostly omicron studies, vaccine effectiveness at baseline was 70% (56-80) against infections and 89% (82-93) against hospitalisations, and reduced to 43% (14-62) against infections and 71% (51-83) against hospitalisations at 112 days or later. Not enough studies were available to report on booster vaccine effectiveness against mortality. Our analyses indicate that vaccine effectiveness generally decreases over time against SARS-CoV-2 infections, hospitalisations, and mortality. The baseline vaccine effectiveness levels for the omicron variant were notably lower than for other variants. Therefore, other preventive measures (eg, face-mask wearing and physical distancing) might be necessary to manage the pandemic in the long term. Canadian Institutes of Health Research and the Public Health Agency of Canada.

Kinetics of Neutralizing Antibodies against Omicron Variant in Vietnamese Healthcare Workers after Primary Immunization with ChAdOx1-S and Booster Immunization with BNT162b2.

We studied the development and persistence of neutralizing antibodies against SARS-CoV-2 ancestral strain, and Delta and Omicron (BA.1 and BA.2) variants in Vietnamese healthcare workers (HCWs) up to 15 weeks after booster vaccination. We included 47 HCWs, including group 1 (G1, N = 21) and group 2 (G2; N = 26) without and with breakthrough Delta variant infection before booster immunization, respectively). The study participants had completed primary immunization with ChAdOx1-S and booster vaccination with BNT162b2. Neutralizing antibodies were measured using a surrogate virus neutralization assay. Of the 21 study participants in G1, neutralizing antibodies against ancestral strain, Delta variant, BA.1, and BA.2 were (almost) abolished at month 8 after the second dose, but all had detectable neutralizing antibodies to the study viruses at week 2 post booster dose. Of the 26 study participants in G2, neutralizing antibody levels to BA.1 and BA.2 were significantly higher than those to the corresponding viruses measured at week 2 post breakthrough infection and before the booster dose. At week 15 post booster vaccination, neutralizing antibodies to BA.1 and BA.2 dropped significantly, with more profound changes observed in those without breakthrough Delta variant infection. Booster vaccination enhanced neutralizing activities against ancestral strain and Delta variant compared with those induced by primary vaccination. These responses were maintained at high levels for at least 15 weeks. Our findings emphasize the importance of the first booster dose in producing cross-neutralizing antibodies against Omicron variant. A second booster to maintain long-term vaccine effectiveness against the currently circulating variants merits further research.

Longer-term effectiveness of a heterologous coronavirus disease 2019 (COVID-19) vaccine booster in healthcare workers in Brazil.

To compare the long-term vaccine effectiveness between those receiving viral vector [Oxford-AstraZeneca (ChAdOx1)] or inactivated viral (CoronaVac) primary series (2 doses) and those who received an mRNA booster (Pfizer/BioNTech) (the third dose) among healthcare workers (HCWs). We conducted a retrospective cohort study among HCWs (aged ≥18 years) in Brazil from January 2021 to July 2022. To assess the variation in the effectiveness of booster dose over time, we estimated the effectiveness rate by taking the log risk ratio as a function of time. Of 14,532 HCWs, coronavirus disease 2019 (COVID-19) was confirmed in 56.3% of HCWs receiving 2 doses of CoronaVac vaccine versus 23.2% of HCWs receiving 2 doses of CoronaVac vaccine with mRNA booster (P < .001), and 37.1% of HCWs receiving 2 doses of ChAdOx1 vaccine versus 22.7% among HCWs receiving 2 doses of ChAdOx1 vaccine with mRNA booster (P < .001). The highest vaccine effectiveness with mRNA booster was observed 30 days after vaccination: 91% for the CoronaVac vaccine group and 97% for the ChAdOx1 vaccine group. Vacine effectiveness declined to 55% and 67%, respectively, at 180 days. Of 430 samples screened for mutations, 49.5% were SARS-CoV-2 delta variants and 34.2% were SARS-CoV-2 omicron variants. Heterologous COVID-19 vaccines were effective for up to 180 days in preventing COVID-19 in the SARS-CoV-2 delta and omicron variant eras, which suggests the need for a second booster.

Durability of Protection Post-Primary COVID-19 Vaccination in the United States.

The durability of immune responses after COVID-19 vaccination will drive long-term vaccine effectiveness across settings and may differ by vaccine type. To determine durability of protection of COVID-19 vaccines (BNT162b2, mRNA-1273, and Ad26.COV2.S) following primary vaccination in the United States, a matched case-control study was conducted in three cohorts between 1 January and 7 September 2021 using de-identified data from a database covering 168 million lives. Odds ratios (ORs) for developing outcomes of interest (breakthrough SARS-CoV-2 infection, hospitalization, or intensive care unit admission) were determined for each vaccine (no direct comparisons). In total, 17,017,435 individuals were identified. Relative to the baseline, stable protection was observed for Ad26.COV2.S against infections (OR [95% confidence interval (CI)], 1.31 [1.18–1.47]) and hospitalizations (OR [95% CI], 1.25 [0.86–1.80]). Relative to the baseline, protection waned over time against infections for BNT162b2 (OR [95% CI], 2.20 [2.01–2.40]) and mRNA-1273 (OR [95% CI], 2.07 [1.87–2.29]) and against hospitalizations for BNT162b2 (OR [95% CI], 2.38 [1.79–3.17]). Baseline protection remained stable for intensive care unit admissions for all three vaccines. Calculated baseline VE was consistent with published literature. This study suggests that the three vaccines in three separate populations may have different durability profiles.

COVID-19 vaccination effectiveness rates by week and sources of bias: a retrospective cohort study

ObjectiveTo examine COVID-19 vaccine effectiveness over six 7-day intervals after the first dose and assess underlying bias in observational data.Design and settingRetrospective cohort study using Columbia University Irving Medical Center...

Myths, misconceptions, and hesitancy in people residing in Qatar toward mRNA COVID-19 vaccines: An experience exchange from Qatar University health center.

The hesitancy in taking COVID-19 vaccines is a complex process influenced by several factors, including individual, social, and cultural. Health literacy and community awareness around mRNA COVID-19 vaccines are critical for successfully combating the pandemic. Healthcare professionals, including family physicians and nurses, can help increase community awareness and mitigate some misconceptions and hesitancy regarding mRNA COVID-19 vaccines in people's attitudes. Therefore, in this study, we aimed to explore how the interaction between an individual's social identities such as gender, ethnicity, culture, knowledge, and belief impact their hesitancy and attitudes toward mRNA COVID-19 vaccines. We aimed to describe our experience in dealing with people residing in Qatar from the perspective of healthcare practitioners from the Qatar University Health Center during the period when mRNA COVID-19 vaccines was introduced in a time frame of 6 months (April to October, 2021).We identified several factors associated with the reluctance to receive mRNA COVID-19 vaccines once vaccination services were available, affordable, and accessible to everyone in Qatar (Table 1). Most individuals were hesitant and refused to take mRNA COVID-19 vaccines owing to the unjustified myths and fear about potential side effects of vaccines in general and unknown long-term effects of vaccination, especially among women who were uneducated. We believe we have been able to put forth a fair, unbiased, and balanced argument between an individual's right to take or refuse the vaccine and the overall benefits to the public and community health in terms of the overall community immunity when the vast majority of the population will be vaccinated. Our experience could assist in developing culturally sensitive and tailored community outreach programs to increase community awareness as it is the cornerstone on which public health can fight the irrational myths, fear, misconceptions, vaccine hesitancy, and improve vaccination coverages. Moreover, our shared experiences might be able to better prepare future launching of pandemic vaccination campaigns in order to minimize vaccine hesitancy.

The long-term effectiveness of coronavirus disease 2019 (COVID-19) vaccines: A systematic literature review and meta-analysis.

Although multiple studies revealed high vaccine effectiveness of coronavirus disease 2019 (COVID-19) vaccines within 3 months after the completion of vaccines, long-term vaccine effectiveness has not been well established, especially after the δ (delta) variant became prominent. We performed a systematic literature review and meta-analysis of long-term vaccine effectiveness. We searched PubMed, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 2019 to November 15, 2021, for studies evaluating the long-term vaccine effectiveness against laboratory-confirmed COVID-19 or COVID-19 hospitalization among individuals who received 2 doses of Pfizer/BioNTech, Moderna, or AstraZeneca vaccines, or 1 dose of the Janssen vaccine. Long-term was defined as >5 months after the last dose. We calculated the pooled diagnostic odds ratio (DOR) with 95% confidence interval for COVID-19 between vaccinated and unvaccinated individuals. Vaccine effectiveness was estimated as 100% × (1 - DOR). In total, 16 studies including 17,939,172 individuals evaluated long-term vaccine effectiveness and were included in the meta-analysis. The pooled DOR for COVID-19 was 0.158 (95% CI: 0.157-0.160) with an estimated vaccine effectiveness of 84.2% (95% CI, 84.0- 84.3%). Estimated vaccine effectiveness against COVID-19 hospitalization was 88.7% (95% CI, 55.8%-97.1%). Vaccine effectiveness against COVID-19 during the δ variant period was 61.2% (95% CI, 59.0%-63.3%). COVID-19 vaccines are effective in preventing COVID-19 and COVID-19 hospitalization across a long-term period for the circulating variants during the study period. More observational studies are needed to evaluate the vaccine effectiveness of third dose of a COVID-19 vaccine, the vaccine effectiveness of mixing COVID-19 vaccines, COVID-19 breakthrough infection, and vaccine effectiveness against newly emerging variants.

22. An Innovative Approach to Examining the Waning of Vaccine Effectiveness Using Automated Healthcare Data

BackgroundWe conducted a large real-world study of the long-term vaccine effectiveness (VE) of the live attenuated zoster vaccine (Zostavax; ZVL). Using an innovative approach with automated observational data we measured VE for incident herpes zoster (HZ) and severe HZ outcomes including post-herpetic neuralgia (PHN), herpes zoster ophthalmicus (HZO), and hospitalized HZ. This approach could be useful in long-term effectiveness studies of other vaccines.MethodsWe assessed VE against HZ, PHN, HZO and hospitalized HZ for up to 10+ years after vaccination at Kaiser Permanente Northern California. We identified incident cases using diagnoses, laboratory tests and prescriptions, and validated a sample by chart review. For each outcome, we used a Cox regression model with a calendar timeline to estimate VE in relation to year since vaccination. The model for HZ included 11 time-varying vaccination status indicators to denote -- at each timepoint during follow-up -- either the number of years since ZVL vaccination (30 days to < 1 year, 1 to < 2 years, . . ., and 10+ years) or that the individual is unvaccinated (reference group). Analyses were adjusted for demographics and time-varying measures of immune compromise status, healthcare use and comorbidities. ResultsFrom 2007-2018, 1.5 million people contributed to analyses; 507,000 (34%) were vaccinated. During 9 million person-years of follow-up, we observed 75,135 HZ cases, including 4,982 (7%) with PHN, 4,418 (6%) with HZO, and 555 (< 1%) who were hospitalized. VE for HZ was 67% (95% Confidence Interval [CI]: 65-69%) in the first year after vaccination, waned to 50% (CI: 47-52%) in the second year after vaccination, and then waned more gradually to 15% (CI: 5-24%) by 10+ years after vaccination. Initial VE was higher against PHN (83%; CI: 78-87%) and hospitalized HZ (89%; CI: 67-97%) with less waning observed over time (42% by Year 8 for PHN and 53% in Years 5 to < 8 for hospitalized HZ). VE against HZO was 71% in Year 1 and waned to 29% in Years 5 to < 8. ConclusionOur large population, long follow-up and innovative methods let us estimate VE against HZ, PHN, HZO and hospitalized HZ for 10+ years after vaccination. Our approach could help assess waning and need for boosters for vaccines against other agents including COVID-19.Disclosures Morgan Marks, PhD, ScM, Merck & Co Inc. (Employee) Patricia Saddier, MD, PhD, Merck & Co Inc (Employee) Nicola P. Klein, MD, PhD, GlaxoSmithKline (Grant/Research Support)MedImmune (Grant/Research Support)Merck & Co Inc (Grant/Research Support)Pfizer (Grant/Research Support)Protein Sciences (now Sanofi Pasteur) (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)

The Perception and Attitudes toward COVID-19 Vaccines: A Cross-Sectional Study in Poland.

Vaccine hesitancy is a major threat to the success of COVID-19 vaccination programs. The present cross-sectional online survey of adult Poles (n = 1020) expressing a willingness to receive the COVID-19 vaccine was conducted between February and March 2021 and aimed to assess (i) the general trust in different types of vaccines, (ii) the level of acceptance of the COVID-19 vaccines already in use in Poland (BNT162b2 by BioNTech/Pfizer, mRNA-1273 by Moderna and AZD1222 by Oxford/AstraZeneca) as well as eight vaccines approved outside European Union (EU) or in advanced stages of clinical trials, (iii) level of fear of vaccination against COVID-19, and (iv) main sources of information on COVID-19 vaccination. Among all major vaccine technology, the highest level of trust was observed for the mRNA platform, with a considerable number of surveyed (>20%) not aware of the existence of vaccines produced using the traditional approach (inactivated and live attenuated vaccines). The age of participants was the main factor differentiating the level of trust in a particular vaccine type. Both BNT162b and mRNA-1273 received a high level of acceptance, contrary to AZD1222. From eight vaccines unauthorized in the EU at the moment of study, the CVnCoV (mRNA; CureVac) was met with the highest level of trust, followed by Ad26.COV2.S (vector; Janssen/Johnson&Johnson) and NVX-CoV2373 (protein; Novavax). Sputnik V (vector; Gamaleya Research Institute) was decidedly the least trusted vaccine. The median level of fear (measured by the 10-point Likert-type scale) in the studied group was 4.0, mostly related to the risk of serious allergic reactions, other severe adverse events and unknown long-term effects of vaccination. Female, individuals with a lower level of education and those not seeking any information on the COVID-19 vaccines revealed a higher fear of vaccination. Experts’ materials were the major source of information on COVID-19 vaccines in the studied group. The study shows the level of trust in COVID-19 vaccines can vary much across the producers while the mRNA vaccines are received with a high level of acceptance. It also emphasizes the need for effective and continuous science communication when fighting the pandemic as it may be an ideal time to increase the general awareness of vaccines.

COVID-19 Incidence Following Fan Attendance: A Case Study of the National Football League 2020-2021 Season

Background: The 2020/2021 National Football League (NFL) season was unique. Not just because it took place under incredibly difficult circumstances, but because of the contrasting conditions that led to some games having fans attend and others that did not. The conditions are akin to a natural experiment. The treatment, the football games that included fans, and the control, those games played behind closed doors. Here, we exploit this variation to better understand the effect of mass gatherings during sporting events on local incidence of COVID-19.Methods: We conducted a retrospective quasi-experimental study that included daily COVID-19 case reports from 11 March 2020 to 1 March 2021 for 219 U.S. counties (or parishes); attendance numbers from a total of 269 total NFL games, 117 of which had fans and were assigned to the treatment group, and the remaining unattended 152 games, assigned as controls. Separate daily time-series of COVID-19 cases and case rates (derived from 2019 Census county-level residential population estimates) were generated using three separate smoothing parameters (7-, 14-, and 21-day simple moving averages (SMAs)) for every NFL team and were plotted against the actuals (daily cases/rates) to detect potential spikes (outliers) in incidence levels following games. All approaches were applied to the county in which games took place (N = 30), contiguous counties (N = 189) where fans also likely travelled from, and acombination of both. A series of 7-, 14-, and 21-day windows were set up the day following each of the respective 269 games to identify if any potential spike (outlier) in COVID-19 incidence occurred within the incubation period.Outliers flagged in the period following games were recorded. Poisson exact tests were then used to evaluate for differences in case and rate spike (outlier) incidence between treatment and control groups. Additional testing that made use of the same methodology was also carried out to evaluate the potential influence of five different rates of attendance (dosage effect) on generating spikes in case- and rate-levels of COVID-19.Findings: A total of 72 different tests were conducted to determine if fan attended games led to a significantly greater number of cases and rates of COVID-19 at various levels of spatial aggregation than for games in which no fans were present. The evidence overwhelmingly supports that fan attendance at NFL games led to episodic spikes in the count of COVID-19 cases/rates in the 14-day window in-county (rate ratio 1·36 [95% CI 1·00–1·87], pInterpretation: The results of this primary analysis of COVID-19 incidence levels in the context of mass gatherings at sporting events provides compelling evidence that the presence of fans at NFL home games during the 2020/2021 season led to increased levels of COVID-19 cases and rates both in the counties in which the venues are nested within, and the surrounding counties in which fans likely travel from to attend. The increased spikes in COVID-19 cases and rates among those games attended by fans, particularly for large crowds of over 20,000 suggest that return to sporting and other mass gathering events should be handled with extreme caution and may indeed be premature. Within the context of large-scale sporting events, a more moderate, phased-in approach may be required to initially limit crowds until a sufficient level of herd immunity is reached. Still, even then, professional sports leagues and related large indoor/outdoor events need to continue to monitor public health data especially as variants circulate and data from the long-term effectiveness of vaccines emerges.Funding: The authors received no specific funding for this work.Conflict of Interest: None to declare.

Attitudes toward vaccination among healthcare workers: a cross-sectional study from Italy

Abstract Background In Italy, the loss of confidence in vaccines has resulted in low vaccination coverage also among healthcare workers (HCWs). Low vaccination coverage among HCWs may lead to dangerous outbreaks and may increase absenteeism. The aim of this study was to investigate vaccine coverage and the attitudes toward vaccination among HCWs. Methods A multicenter cross-sectional study was conducted from August to November 2019 among HCWs referring to all the hospitals of the Local Health Authority 02 of Abruzzo Region, Italy. The survey was based on the questionnaire proposed by the H-ProImmune Project, aiming at investigating vaccination coverage and beliefs towards vaccination. Besides a descriptive analysis of the results, a logistic regression analysis was performed to evaluate the association between vaccine coverage and type of occupation (medical doctor, nurse, obstetric nurse, other). Results A total of 347 HCWs were enrolled in the study. The 57.3% reported to have missed diphtheritis-tetanus-pertussis (DTP) vaccination, the 50.1% reported to have missed measles-mumps-rubella (MPR) vaccination, and the 62.5% reported to have missed flu vaccination. In comparison with medical doctors, obstetric nurses were more likely to be associated to MPR vaccination (OR 2.8;95%CI 1.1-7.6; p = 0.047). As far as flu vaccination was concerned, both nurses and obstetric nurses showed lower confidence (respectively OR 0.2; 95%CI 0.1-0.3; p &amp;lt; 0.001 and OR 0.1; 95%CI 0.1-0.5; p = 0.003). Moreover, other healthcare professionals reported to believe in natural immunization more than in vaccination (26.5%; p &amp;lt; 0.001) and they were also worried about long-term effects of vaccination (10.2%; p = 0.044). Differently, nurses were more frequently worried about vaccine side effects (24%; p &amp;lt; 0.001). Conclusions This survey shows that the vaccination coverage taken into consideration results to be below the 95% threshold. Training on vaccine and mandatory measures may be necessary in order to achieve better coverage. Key messages Among HCW all vaccination coverage considered resulted below the threshold. Training on vaccine and mandatory measures may be needed in order to achieve better coverage.

Knowledge and Attitude towards Vaccination among Healthcare Workers: A Multicenter Cross-Sectional Study in a Southern Italian Region.

Background: In Italy, the loss of confidence towards vaccination resulted in low vaccine coverage, also among healthcare workers (HCWs). Indeed, low vaccination coverage among HCWs can lead to dangerous outbreaks of disease, reduce productivity, and increase absenteeism. The aim of this study was to investigate the vaccine coverage and attitudes toward vaccination among HCWs. Methods: A multicenter cross-sectional study was conducted among HCWs referred to all hospitals of the Local Health Authority 02 of Abruzzo Region, Italy. The survey was based on the questionnaire proposed by the H-ProImmune Project. Results: A total of 347 HCWs were enrolled in the study. Of these, 57.3% reported missing diphtheritis-tetanus-pertussis (DTP) vaccination, 50.1% reported missing measles-mumps-rubella (MMR) vaccination, and 62.5% reported missing flu vaccination. Regarding attitudes, other healthcare professionals reported to believe more in natural immunization compared to vaccination (26.5%; p < 0.001), and they were worried about long-term effects of vaccination (10.2%; p = 0.044). Conclusions: This survey showed all vaccination coverage considered resulted below the 95% threshold. Training on vaccination and mandatory measures may be needed in order to achieve better coverage.

Influence of demographically-realistic mortality schedules on vaccination strategies in age-structured models

Because demographic realism complicates analysis, mathematical modelers either ignore demography or make simplifying assumptions (e.g., births and deaths equal). But human populations differ demographically, perhaps most notably in their mortality schedules. We developed an age-stratified population model with births, deaths, aging and mixing between age groups. The model includes types I and II mortality as special cases. We used the gradient approach (Feng et al., 2015, 2017) to explore the impact of mortality patterns on optimal strategies for mitigating vaccine-preventable diseases such as measles and rubella, which the international community has targeted for eradication. Identification of optimal vaccine allocations to reduce the effective reproduction number Rv under various scenarios is presented. Numerical simulations of the model with various types of mortality are carried out to ascertain the long-term effects of vaccination on disease incidence. We conclude that both optimal vaccination strategies and long-term effects of vaccination may depend on demographic assumptions.

Recombinant human papillomavirus nonavalent vaccine in the prevention of cancers caused by human papillomavirus.

Human papillomavirus (HPV) types 16 and 18 cause 70% of cervical cancer cases globally. The nonavalent HPV vaccine (9vHPV) was licensed in 2014 and protects against the next five most common cancer-causing HPV types (HPV 31/33/45/52/58) after HPV 16/18. Phase III clinical studies have demonstrated high vaccine efficacy (>90%) against cervical, vulvar, and vaginal precancers caused by these additional types, and have shown comparable immunogenicity to the shared genotypes to quadrivalent HPV vaccine (4vHPV). Vaccine efficacy and antibody responses for 9vHPV are found to persist for at least five years while longer-term observational studies are ongoing to monitor long-term vaccine effectiveness. The implementation of 9vHPV has the potential to prevent up to 93% of cervical cancer cases, as well as a significant proportion of other HPV-related anogenital cancers. This review article summarizes the current evidence for 9vHPV in terms of vaccine efficacy against HPV infection and related anogenital precancers, safety, and immunogenicity, as well as discussing the potential impact of this vaccine on the cervical cancer burden globally.

Molecular Evolutionary Dynamics of Respiratory Syncytial Virus Group A in Recurrent Epidemics in Coastal Kenya.

ABSTRACTThe characteristic recurrent epidemics of human respiratory syncytial virus (RSV) within communities may result from the genetic variability of the virus and associated evolutionary adaptation, reducing the efficiency of preexisting immune responses. We analyzed the molecular evolutionary changes in the attachment (G) glycoprotein of RSV-A viruses collected over 13 epidemic seasons (2000 to 2012) in Kilifi (n = 649), Kenya, and contemporaneous sequences (n = 1,131) collected elsewhere within Kenya and 28 other countries. Genetic diversity in the G gene in Kilifi was dynamic both within and between epidemics, characterized by frequent new variant introductions and limited variant persistence between consecutive epidemics. Four RSV-A genotypes were detected in Kilifi: ON1 (11.9%), GA2 (75.5%), GA5 (12.3%), and GA3 (0.3%), with predominant genotype replacement of GA5 by GA2 and then GA2 by ON1. Within these genotypes, there was considerable variation in potential N-glycosylation sites, with GA2 and ON1 viruses showing up to 15 different patterns involving eight possible sites. Further, we identified 15 positively selected and 34 genotype-distinguishing codon sites, with six of these sites exhibiting both characteristics. The mean substitution rate of the G ectodomain for the Kilifi data set was estimated at 3.58 × 10−3 (95% highest posterior density interval = 3.04 to 4.16) nucleotide substitutions/site/year. Kilifi viruses were interspersed in the global phylogenetic tree, clustering mostly with Kenyan and European sequences. Our findings highlight ongoing genetic evolution and high diversity of circulating RSV-A strains, locally and globally, with potential antigenic differences. Taken together, these provide a possible explanation on the nature of recurrent local RSV epidemics. IMPORTANCE The mechanisms underlying recurrent epidemics of RSV are poorly understood. We observe high genetic diversity in circulating strains within and between epidemics in both local and global settings. On longer time scales (∼7 years) there is sequential replacement of genotypes, whereas on shorter time scales (one epidemic to the next or within epidemics) there is a high turnover of variants within genotypes. Further, this genetic diversity is predicted to be associated with variation in antigenic profiles. These observations provide an explanation for recurrent RSV epidemics and have potential implications on the long-term effectiveness of vaccines.