Immediate adverse reactions following COVID-19 vaccination among 16–65-year-old Danish citizens

IntroductionThere is sparse knowledge of immediate adverse reactions following COVID-19 vaccination.ObjectiveThis study aimed to estimate the frequency and number of immediate adverse reactions following COVID-19 vaccination in a Danish population.MethodsThe study used data from the Danish population-based cohort study BiCoVac. The frequencies of 20 self-reported adverse reactions were estimated for each vaccine dose stratified by sex, age, and vaccine type. Also, the distributions of number of adverse reactions following each dose were estimated stratified by sex, age, vaccine type, and prior COVID-19 infection.ResultsA total of 889,503 citizens were invited and 171,008 (19 %) vaccinated individuals were included in the analysis. The most frequently reported adverse reaction following the first dose of COVID-19 vaccine was redness and/or pain at the injection site (20 %) while following the second and third dose, tiredness was the most frequently reported adverse reaction (22 % and 14 %, respectively). Individuals aged 26–35 years, females, and those with a prior COVID-19 infection were more likely to report adverse reactions compared with older individuals, males, and those with no prior COVID-19 infection, respectively. Following the first dose, individuals vaccinated with ChAdOx1-2 (AstraZeneca) reported more adverse reactions compared with individuals vaccinated with other vaccine types. Individuals vaccinated with mRNA-1273 (Moderna) reported more adverse reactions following the second and third dose compared with individuals vaccinated with BNT162b2 (Pfizer-BioNTech).ConclusionThe frequency of immediate adverse reactions was highest among females and younger persons, however, most of the Danish citizens did not experience immediate adverse reactions following COVID-19 vaccination.     

Adolescents’ attitudes to the COVID-19 vaccination

Vaccines against COVID-19 are now available for adolescents in Hong Kong but vaccine hesitancy is a major barrier to herd immunity. This survey study explores Hong Kong adolescents’ attitudes towards the COVID-19 vaccination. 2609 adolescents from across Hong Kong completed an online survey focused on the intent to vaccinate and the reasons for their choice. 39% of adolescents intended to take the COVID-19 vaccination and significant factors for this decision include: having at least one parent vaccinated, knowing somebody diagnosed with COVID-19 and receiving the influenza vaccine. Adolescents’ major concerns were either the safety and efficacy of the vaccine or the risk of infection. This study has proved that even in adolescents the vaccine hesitancy model is prominent with adolescents’ intentions highly related to confidence in the vaccine and perception of disease risk. Future interventions should target these specific concerns to ensure adolescents are well educated to overcome vaccine hesitancy.     

Thrombosis with Thrombocytopenia Syndrome (TTS) following AstraZeneca ChAdOx1 nCoV-19 (AZD1222) COVID-19 vaccination – A risk–benefit analysis for people < 60 years in Australia

The AstraZeneca ChAdOx1 nCoV-19 (AZD1222) vaccine is associated with Thrombosis with Thrombocytopenia Syndrome (TTS) in 3/100,000 vaccinations with high fatality rates reported in many countries. We conducted a risk–benefit analysis for Australians aged 18–59 years, comparing the risk of vaccination versus infection, and rate of TTS to other vaccines which prompted policy change following rare adverse events – rotavirus, smallpox and oral polio vaccines. COVID-19 deaths over 12 months range from 0 to 417 in current and future worst case scenarios. In the past 15 months 20 COVID-19 deaths occurred in people < 60 years compared to 890 deaths over 60 years. The estimated possible number of TTS cases is 347, with vaccine-related deaths ranging from 17 to 153 if 80% of adults 18–59 years are vaccinated. The reported rate of TTS is in the same range as rare but serious adverse events associated with other vaccines that have been subject to policy change. In Australia, the potential risks of the AZD1222 vaccine in younger adults, who are at low risk of dying from COVID-19, may outweigh the benefits.     

Obesity and sleep apnea as a significant comorbidities in COVID-19 — A case report

In our paper we aimed to increase the awareness among physicians, concerning coronavirus disease 2019 (COVID-19) severity, especially in patients with specific underlying comorbidities. Obesity is the second most common condition in hospitalized COVID-19 patients. Furthermore it has a major role in the development of obstructive sleep apnoea (OSA), which is highly involved in a severe COVID-19 development and its serious outcomes. Even though obese OSA patients had an increased pulmonary embolism (PE) risk, there is no enough evidence to support the interaction between obesity and OSA regarding PE development in the setting of COVID-19. Our patient is a 45-year-old obese male with COVID-19, who was admitted to the intensive care unit (ICU) with acute respiratory failure requiring high-flow nasal oxygenation. Clinical, laboratory and diagnostic findings pointed on severe COVID-19 form, complicated with PE. After recovery, the diagnosis of OSA was established. With this case, we wanted to alert the physicians on comorbidities, such as obesity and OSA, while those conditions, to some extent, may contribute to worse COVID-19 clinical presentation.     

Policies and innovations to battle Covid-19 – A case study of South Korea

ObjectivesTo describe how health care crisis resulting from the COVID-19 pandemic in South Korea has led to innovation and changes to government policy. This paper presents the significant cluster events, relevant developments of innovation, and economical impact in Korea that could inform policy makers on how to respond to health crises in the future.MethodsHealth care, economy, epidemiological data are collected from various sources including the Korea Centers for Disease Control and Prevention (KCDC) or other government sources.ResultsThe KCDC jointly with medical professionals developed a series of innovations such as 1) Full contact tracing and rapid testing with a 12 h turnaround and 10 min movement tracking systems, 2) transparent disclosure of all contract tracing data to the public through a central database, 3) Drive-Through and Walk-Through testing methods, and 4) a 4 tier patient severity index and community treatment isolation centers. Korea moved from the 4th in the world for total confirmed cases in March down to 76th in August.ConclusionsExpedited enforcement of amended legislation acts to protect the healthcare workforce resulted in only 10 healthcare professionals contracting the virus while caring for Covid-19 patients. This has resulted in minimal human capital loss and the government was able to re-direct existing medical workforce to areas in need. The quarantine strategies implemented resulted in little need to lock down the whole economy but also limited the cost spent to gain a year of life to 193,848 Won (US$163).     

A tailored COVID-19 vaccination pathway for children 5–11 years in Victoria,Australia

BackgroundProcedural anxiety was anticipated in children 5–11 years during the COVID-19 vaccine rollout in Victoria, Australia, as children in this age group receive few routine vaccines. Therefore, the Victorian state government designed a tailored, child-friendly vaccine program. This study aimed to assess parental satisfaction with elements of the bespoke vaccination pathway.MethodsThe Victorian government and state-run vaccination hubs in Victoria facilitated an online immunisation plan to help parents identify their child’s support needs, and utilised experienced paediatric staff and additional supports for children with severe needle distress and/or disability. All parents/guardians of children 5–11 years who received a COVID-19 vaccine in a vaccination hub were sent a 16-item feedback survey via text message.ResultsBetween 9 February and 31 May 2022 there were 9203 responses; 865 children (9.4%) had a first language other than English, 499 (5.4%) had a disability or special needs, and 142 (1.5%) were Aboriginal or Torres Strait Islander. Most parents (94.4%; 8687/9203) rated their satisfaction with the program as very good or excellent. The immunisation plan was used by 13.5% (1244/9203) of respondents, with usage more common for Aboriginal or Torres Strait Islander children (26.1%; 23/88) or families with a first language other than English (23.5%; 42/179). The child-friendly staff (88.5%, 255/288) and themed environment (66.3%, 191/288) were the most valued measures for vaccination. Additional support measures were required by 1.6% (150/9203) of children in the general population and 7.9%, (17/261) of children with a disability and/or special needs.ConclusionA tailored COVID-19 vaccination program for children 5–11 years, with additional support for children with severe needle distress and/or disability, had high parental satisfaction. This model could be utilised for COVID-19 vaccination in pre-school children and for routine childhood vaccination programs to provide optimal support to children and their families.     

Did the temporary suspension of Vaxzveria vaccinations influence COVID-19 vaccination intentions,vaccination perceptions and trust in the vaccination campaign? A repeated survey study in the Netherlands

In spring 2021, several countries, among which the Netherlands, suspended vaccinations against COVID-19 with the Vaxzevria vaccine from AstraZeneca after reports of rare but severe adverse events. This study investigates the influence of this suspension on the Dutch public’s perceptions of COVID-19 vaccinations, trust in the government’s vaccination campaign, and COVID-19 vaccination intentions. We conducted two surveys in a population of general Dutch public (18 + ), one shortly before the pause of AstraZeneca vaccinations and one shortly thereafter (N eligible for analysis = 2628). Our results suggest no changes in perceptions nor intentions regarding the COVID-19 vaccines in general but do suggest a decline in trust in the government’s vaccination campaign. In addition, after the suspension, perceptions of the AstraZeneca vaccines were more negative in comparison to those of COVID-19 vaccinations in general. AstraZeneca vaccination intentions were also considerably lower. These results stress the need to adapt vaccination policies to anticipated public perceptions and responses following a vaccine safety scare, as well as the importance of informing citizens about the possibility of very rare adverse events prior to the introduction of novel vaccines.     

Benefit–risk evaluation of COVID-19 vaccination in special population groups of interest

Several population groups display an increased risk of severe disease and mortality following SARS-CoV-2 infection. These include those who are immunocompromised (IC), have a cancer diagnosis, human immunodeficiency virus (HIV) infection or chronic inflammatory disease including autoimmune disease, primary immunodeficiencies, and those with kidney or liver disease. As such, improved understanding of the course of COVID-19 disease, as well as the efficacy, safety, and benefit-risk profiles of COVID-19 vaccines in these vulnerable groups is paramount in order to inform health policy makers and identify evidence-based vaccination strategies. In this review, we seek to summarize current data, including recommendations by national health authorities, on the impact and benefit-risk profiles of COVID-19 vaccination in these populations. Moving forward, although significant efforts have been made to elucidate and characterize COVID-19 disease course and vaccine responses in these groups, further larger-scale and longer-term evaluation will be instrumental to help further guide management and vaccination strategies, particularly given concerns about waning of vaccine-induced immunity and the recent surge of transmission with SARS-CoV-2 variants of concern.     

Are unexplained adverse health events following HPV vaccination associated with infectious mononucleosis? – A Danish nationwide matched case-control study

BackgroundIn Denmark, the acceptance of the HPV vaccination program has been threatened by reports of suspected adverse events. Epstein Barr Virus (EBV) infection is associated with symptoms of long-lasting tiredness and may be misinterpreted as HPV vaccine adverse events. The main aim of this study was to examine if EBV infection around time of HPV vaccination was a risk factor for later suspected vaccine adverse events.MethodsThe study was a nationwide register-based matched case-control study. Cases were females vaccinated against HPV in the period 2011 throughout 2017 with suspected adverse events. For each case, five HPV vaccinated females without suspected adverse events were selected. Information about EBV infection was obtained from the Danish Microbiology Database and assessed for three time periods: (1) before first HPV vaccination, (2) around time of HPV vaccination, and (3) any time during the study period 2010–2017. Multiple logistic regression was used to estimate the association between EBV and suspected adverse events.ResultsWe identified 1217 cases, matched to 6085 controls. A higher proportion of cases (38; 3.1%) than controls (31; 0.5%) were tested for EBV around time of HPV vaccination and cases had elevated odds for testing both EBV positive (OR 4.52, 95% CI 2.68–7.63) and EBV negative (OR 20.99, 95% CI 5.81–75.79). Only five females were classified with acute/recent EVB infection in this period.ConclusionMisinterpretation of EBV infection late symptoms is not a leading explanation for Danish females experiencing suspected adverse events after HPV vaccination. Although EBV cannot be excluded as an explanatory factor for a very small proportion of suspected adverse events, the findings are more likely explained by protopathic bias, i.e. the fact that a larger proportion of females suspecting adverse events are tested for EBV.     

COVID-19 vaccine – Long term immune decline and breakthrough infections

BackgroundSince the introduction of BNT162b2 mRNA COVID-19 vaccine by Pfizer in late 2020, efficacy and immunogenicity waning of COVID-19 vaccines was reported, and decision making regarding a booster remains a top priority worldwide, a decision that should be made based on breakthrough infection rate and antibody titer decline overtime.MethodsWe conducted a 5-month longitudinal prospective study involving vaccinated healthcare personnel, who were tested monthly for antibody titer, and sampled biweekly and on clinical indication for SARS-COV-2 polymerase chain reaction (PCR), to determine antibody decline and breakthrough infection.Results100 participants were recruited to the study. Antibody titer reached the climate after one month of the second dose of the vaccine, and declined rapidly thereafter: the median antibody levels were 895; 22,266; 9,682; 2,554 and 1,401 AU/ml in the day of the second dose, and in one month interval thereafter, respectively. In other words, four months after vaccination, the mean antibody level was 6% of the peak levels. During the study period, 4 breakthrough infections were diagnosed, 2 of which were asymptomatic, and the remaining two were mild cases; sharp elevation of antibody titer was seen after infection.ConclusionAntibody titer drops rapidly one month after the second dose of the vaccine. All infections within the study period were mild or asymptomatic, after which titer elevations were seen.     

Immunity debt or vaccination crisis? A multi-method evidence on vaccine acceptance and media framing for emerging COVID-19 variants

Renewed COVID-19 outbreaks, stemming from the highly infectious Delta and Omicron variants, prompted rising fears of a ‘pandemic among the unvaccinated’. To address this prevalent vaccination crisis, media framing communication strategies can amplify the scientific evidence on COVID-19 vaccines to reach diverse geographic and socio-economic communities. The critical role of media framing strategies to engage and encourage large populations regarding vaccine acceptance has been rarely studied, despite growing evidence on vaccine hesitancy. The present study used a multi-method approach (i.e., content analysis and quasi-experiments) that unpacked the framing practices employed by the mainstream media in Pakistan. The findings of the content analysis revealed that the media extensively used uncertainty, conflict, consequences, and action rather than new evidence and reassurance frames in its COVID-19 related campaigns. In a series of quasi-experiments involving 720 participants, we manipulated these six frames of COVID-19 related news coverage (i.e., uncertainty, conflict, consequences, action, new evidence, and reassurance) to investigate the underlying mechanism that influences vaccine acceptance. The findings established that the message-consistent effects of media frames manifesting fear (e.g., consequence and uncertainty) and action cues made receivers more supportive of vaccination. The present study findings theoretically address the calls for a more inclusive “community-health reporting model”, besides offering new evidence on the media framing strategies to deliver more targeted, meaningful, and effective campaigns to raise public acceptance for COVID-19 vaccines.     

Impact of influenza vaccination on healthcare utilization – A systematic review

IntroductionAlthough a vaccine-preventable disease, influenza causes approximately 3–5 million cases of severe illness and about 290,000–650,000 deaths worldwide, which occur primarily among people 65 years and older. Nonetheless, prevention of influenza and its complications rely mainly on vaccination. We aimed to systematically evaluate influenza vaccine effectiveness at reducing healthcare utilization in older adults, defined as the reduction of outpatient visits, ILI and influenza hospitalizations, utilization of antibiotics and cardiovascular events by vaccination status during the influenza season.MethodsWe searched MEDLINE, EMBASE, CINAHL, Cochrane Library and considered any seasonal influenza vaccine, excluding the pandemic (2009–10 season) vaccine. Reviewers independently assessed data extraction and quality assessment.ResultsOf the 8308 citations retrieved, 22 studies were included in the systematic review. Overall, two studies (9%) were deemed at moderate risk of bias, thirteen (59%) at serious risk of bias and seven (32%) at critical risk of bias. For outpatient visits, we found modest evidence of protection by the influenza vaccine. For all-cause hospitalization outcomes, we found a wide range of results, mostly deemed at serious risk of bias. The included studies suggested that the vaccine may protect older adults against influenza hospitalizations and cardiovascular events. No article meeting our inclusion criteria explored the use of antibiotics and ILI hospitalizations. The high heterogeneity between studies hindered the aggregation of data into a meta-analysis.ConclusionThe variability between studies prevented us from drawing a clear conclusion on the effectiveness of the influenza vaccine on healthcare utilization in older adults. Overall, the data suggests that the vaccine may result in a reduction of healthcare utilization in the older population. Further studies of higher quality are necessary.     

COVID-19 vaccine reactogenicity – A cohort event monitoring study in the Netherlands using patient reported outcomes

ObjectivesTo explore factors that are associated with reactogenicity in general and systemic after the first dose of COVID-19 vaccine in the Netherlands.DesignA web-based prospective cohort design using patient reported outcomes (PROs).SettingAny person who has been vaccinated with any brand of COVID-19 vaccine in the Dutch COVID immunization programme.Participants22,184 participants. Of these, 13,959 (62.9%) experienced reactogenicity in general and 11,979 (54.0%) systemic reactogenicity within 7 days after vaccination.Main outcome measuresFactors that are associated with the occurrence of reactogenicity after COVID-19 vaccination.ResultsCompared to the Comirnaty® vaccine, the highest odds ratio (OR) for developing reactogenicity was for the Vaxzevria® vaccine (OR 5.18) followed by Spikevax® (OR 2.16), and Janssen (OR 1.65). Participants with a history of COVID-19 disease had a 3.10 increased odds for reactogenicity. Women had a 2.08 increased odds compared to men. Older participants experienced less reactogenicity. Compared to the age group < 50, the ORs for the age groups 50–60, 61–79, and ≥80 were 0.36, 0.15, and 0.10 respectively. The use of an antipyretic drug, or a drug for nervous system disorders gave an increased odds of 1.34 and 1.16 respectively. A body mass index of 25.0–29.9 and over 30 was negatively associated with reactogenicity (OR 0.87 and OR 0.72 respectively). Comorbidities that were associated with reactogenicity were cardiac disorders (OR 1.26), respiratory disorders (OR 1.31), psychiatric disorders (1.37), reproductive disorders (OR 1.54), and eye disorders (OR 1.55). The factors associated with systemic reactogenicity were mostly comparable, but there were differences for comorbidities, drug use, and the strength of the regression coefficient.ConclusionsThis extensive study with over 22,000 vaccine recipients in the Netherlands demonstrated that, taken into account all factors in the model, the Comirnaty® vaccine gave the least and the Vaxzevria® vaccine the most reactogenicity in general and systemic after the first dose. Also a person with a history of COVID-19 disease, female sex and younger age had an increased odds for experiencing reactogenicity after vaccination.     

Western Australian health care workers’ views on mandatory COVID-19 vaccination for the workplace

BackgroundHealth care workers (HCWs) are at an increased risk of catching and spreading Coronavirus Disease 2019 (COVID-19) compared with the general community, putting health systems at risk. Several jurisdictions globally have mandated or are looking to mandate COVID-19 vaccines for this cohort, but little is known about the acceptability of this measure, especially in different contexts, and there is little qualitative data to explore nuance, depth, and the reasons behind HCWs’ opinions.MethodsIn-depth semi-structured qualitative interviews were undertaken with 39 HCWs in Western Australia (WA) between February-August 2021, ascertaining their views on the prospective introduction and implementation of mandates for COVID-19 vaccines. Data were thematically analysed using NVivo 20.ResultsThere was broad support for COVID-19 vaccine mandates for HCWs amongst our participants, but also different views about what such a mandate would mean (redeployment versus termination) and how it would impact the rest of the workforce. One vaccine hesitant participant said that mandates would be their prompt to get vaccinated. Other participants invoked an informal code whereby HCWs have an obligation to be seen to support vaccination and to protect public health more broadly. However, they also raised concerns about implementation and procedural and policy fairness.ConclusionPolicymakers should consider how to mobilise the informal code of health promotion and public health support if introducing mandates. They should also consider whether HCWs will bring the same attitudes and approaches to mandates for additional vaccine doses.     

Prioritization of COVID-19 vaccination. The added value of the “VALIDATE” approach

Prioritization of COVID-19 vaccines is one of the most relevant topics in the current pandemic emergency. Prioritization decisions are political decisions that are value-laden, and as such of ethical nature. Despite the clear political and ethical nature of this topic, prioritization decisions are often interpreted and presented as scientific decisions. The aim of this article is twofold. First, we aim to show critical points that characterize certain pandemic vaccination plans from the ethical viewpoint using four dimensions (problem definitions, incorporation of different perspectives, context, and specification). The four dimensions were drawn from findings of the European project “VALIDATE” (VALues In Doing Assessments of healthcare TEchnologies”, https://validatehta.eu). Second, we aim to reframe the issue about prioritization itself in the light of the four dimensions mentioned. Our conclusion is that policy-problem definitions, incorporation of different perspectives, contextual considerations and specification of moral principles seem to be common critical points of some vaccination plan documents. The European project “VALIDATE” seems to be able to provide a useful and profitable approach to address many of these critical points.     

How frequent are acute reactions to COVID-19 vaccination and who is at risk?

IntroductionOur objective was to describe and compare self-reported side effects of COVID-19 vaccines in the USA.MethodsA web-based registry enrolled volunteers who received a COVID-19 vaccine between March 19–July 15, 2021. We collected self-reported short-term side effects, medical consultation, hospitalization, and quality of life impact following completed vaccination regimens (Pfizer, Moderna, J&J).ResultsWe recruited 6,966 volunteers who completed their full course of vaccination (median age 48 years, IQR 35.0–62.0; 83.6% female): Pfizer 3,486; Moderna 2,857; J&J 623. Few (3.1%) sought medical care for post-vaccination side effects. Hospitalization (n = 17; 0.3%) and severe allergic reactions (n = 39; 0.6%) also were rare. Those with autoimmune disease or lung disease were approximately twice as likely to seek medical care (adjusted odds ratio (aOR) 2.01, 95% CI:1.39; 2.92 and aOR 1.70, 95% CI: 1.12; .58 respectively). 92.4% of participants reported ≥ 1 side effect (median 3), with injection site reactions (78.9%), fatigue (70.3%), headache (49.0%) reported most frequently. More side effects were reported after the second dose of two-dose vaccines (medians: 1 vs. 2 for Pfizer and 1 vs. 3 for Moderna for first and second doses respectively) versus 3 for J&J's single-dose vaccine. For the employed, the median number of workdays missed was one. Diabetics and those vaccinated against influenza were substantially less likely to report 3 or more symptoms (aOR 0.68, 95% CI: 0.56;0.82] and aOR 0.82, 95% CI: 0.73;0.93, respectively).DiscussionThe total side effect burden was, not unexpectedly, greater with two-dose regimens but all three vaccines appear relatively safe. Very few subjects reported side effects serious enough to warrant medical care or reported post-vaccination hospitalization. While these findings do not address possible long-term effects, they do inform on their short-term safety and tolerability and will hopefully provide some reassurance and positively inform the benefit-risk and pharmacoeconomic assessment for all three vaccines.See Clinicaltrials.gov NCT04368065.