Antonios Douros et al.

Common Vaccines and the Risk of Incident Dementia: A Population-based Cohort Study

Academic.oup ; December 2022 ; doi.org/10.1093/infdis/jiac484

Abstract

Observational studies suggesting that immunizations strongly decrease the risk of dementia had several methodological limitations. We assessed whether common vaccines are associated with the risk of dementia.

Methods

We assembled a population-based cohort of dementia-free individuals aged ≥50 years in the United Kingdom’s Clinical Practice Research Datalink between 1988 and 2018. Using a nested case-control approach, we matched each patient with dementia with 4 controls. Conditional logistic regression yielded confounder-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of dementia associated with common vaccines >2 years before the index date compared with no exposure during the study period. Moreover, we applied a 10-year lag period and used active comparators (participation in breast or prostate cancer screening) to account for detection bias.

Results

Common vaccines were associated with an increased risk of dementia (OR, 1.38 [95% CI, 1.36–1.40]), compared with no exposure. Applying a 10-year lag period (OR, 1.20 [95% CI, 1.18–1.23]) and comparing versus prostate cancer screening (1.19 [ 1.11–1.27]) but not breast cancer screening (1.37 [1.30–1.45]) attenuated the risk increase.

Conclusions

Common vaccines were not associated with a decreased risk of dementia. Unmeasured confounding and detection bias likely accounted for the observed increased risk.

AntoniosDouros et al

Common Vaccines and the Risk of Incident Dementia: A Population-based Cohort Study

Academic.oup, December 2022; doi.org/10.1093/infdis/jiac484

Abstract

Background

Observational studies suggesting that immunizations strongly decrease the risk of dementia had several methodological limitations. We assessed whether common vaccines are associated with the risk of dementia.

Methods

We assembled a population-based cohort of dementia-free individuals aged ≥50 years in the United Kingdom’s Clinical Practice Research Datalink between 1988 and 2018. Using a nested case-control approach, we matched each patient with dementia with 4 controls. Conditional logistic regression yielded confounder-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of dementia associated with common vaccines >2 years before the index date compared with no exposure during the study period. Moreover, we applied a 10-year lag period and used active comparators (participation in breast or prostate cancer screening) to account for detection bias.

Results

Common vaccines were associated with an increased risk of dementia (OR, 1.38 [95% CI, 1.36–1.40]), compared with no exposure. Applying a 10-year lag period (OR, 1.20 [95% CI, 1.18–1.23]) and comparing versus prostate cancer screening (1.19 [ 1.11–1.27]) but not breast cancer screening (1.37 [1.30–1.45]) attenuated the risk increase.

Conclusions

Common vaccines were not associated with a decreased risk of dementia. Unmeasured confounding and detection bias likely accounted for the observed increased risk.

Markus Hovd et al.

Humoral vaccine response and breakthrough infections in kidney transplant recipients during the COVID-19 pandemic: a nationwide cohort study

The lancet, june 2023; doi.org/10.1016/j.eclinm.2023.102035

Abstract

Kidney transplant recipients (KTRs) experienced reduced SARS-CoV-2 vaccine response and were at increased risk of severe COVID-19. It is unknown if level of vaccine induced anti-receptor binding domain IgG (anti-RBD IgG) correlates with protection from and survival following COVID-19. We aimed to evaluate the effect of vaccine response on risk of breakthrough infections (BTI) and COVID-19 death in KTRs.

Methods

We performed a nationwide study, examining the competing risk of SARS-CoV-2 infection, COVID-19 related/unrelated death, and vaccine efficacy as assessed by level of anti-RBD IgG response 4–10 weeks after each vaccination. The study included all KTR in Norway alive and with a functioning graft on February 20th, 2020, and events after November 11th, 2022 were right-censored. A pre-pandemic reference-cohort from January 1st 2019 to January 1st 2020 was included to evaluate excess mortality. The study was conducted at Oslo University Hospital, Rikshospitalet, Norway.

Findings

The study included 3607 KTRs (59 [48–70] years) with a functioning graft at February 20th, 2020, who received (median [IQR]) 4 [3–4] vaccines (range 2–6, 99% mRNA). Anti-RBD IgG was measured in 12 701 serum samples provided by 3213 KTRs. Vaccine response was assessed 41 [31–57] days after vaccination. A total of 1090 KTRs were infected with SARS-CoV-2, 1005 (92%) were BTI, and vaccine response did not protect against BTI. The hazard ratio for COVID-19 related death 40 days post-infection was 1.71 (95% CI: 1.14, 2.56) comparing vaccine response levels (≥5 vs. ≥5000 BAU/mL). No excess non-COVID-19 mortality was registered in KTRs surviving SARS-CoV-2 infection compared to a 2019 pre-pandemic reference.

Interpretation

Our findings suggested that SARS-CoV-2 mRNA vaccine response did not predict protection against infection, but prevention of fatal disease progression in KTRs and greater vaccine response further reduced the risk of COVID-19 death. No excess non-COVID-19 mortality was seen during the pandemic.

Ryan Ruiyang Ling et al

Carditis following COVID-19 vaccination: balancing the risks and benefits

The Lancet, April 2023; doi.org/10.1016/j.lanwpc.2023.100765

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted the world. The uniquely expeditious development of vaccines was welcomed by the medical community due to the immense scale of the pandemic. The ongoing emergence of SARS-CoV-2 variants and waning immunity after vaccination called for repeated doses of vaccination to maintain immunity against COVID-19. While the side effects of vaccination were typically mild and self-resolving, there were emerging reports of serious adverse events, one of which was carditis.1

In The Lancet Regional Health – Western Pacific, Dr Min Fan and colleagues report on a self-controlled case series (SCCS) and a case–control study in a Hong Kong cohort investigating whether homologous mRNA (BNT162b2) or inactivated (CoronaVac) vaccination against COVID-19 was associated with carditis.2 From 15 million doses of vaccines, the authors found an increase in carditis following all doses of BNT162b2 vaccination; the risks were substantially higher for males than females, and those younger than 30 years compared to those 30 years or older. They did not find any associations between carditis and CoronaVac vaccines. These results were internally validated using a case–control study design. The SCCS has been used before in assessing the safety of vaccination, and specific modifications have been made to facilitate analyses in the context of COVID-19 vaccination.3 In an SCCS, individuals with an event act as their own control group, and comparisons are made within individuals rather than between groups,4 accounting for time-fixed confounders. The authors then accounted for time-varying confounders by adjusting for the calendar month. This modified study design is particularly elegant when the event of interest (carditis) is rare, or one group (those who have not received the vaccine) is very small. In such situations, conventional cohort studies may yield imprecise estimates.5 In addition, a modified SCCS accounts for when patients do not receive subsequent vaccination following carditis. Similar efforts by the authors investigating other adverse events in COVID-19 vaccination have been published as well.6

The authors also investigated the risk of carditis in a large cohort of patients receiving an inactivated vaccine (CoronaVac), which has not been extensively reported on thus far. Studying both vaccines in the same population provides more data and facilitates open and transparent conversations about the benefits and harms of various vaccines against COVID-19. Of note, the authors report on a population which is mostly ethnically Chinese, which is in contrast to the current published literature which reports on a mostly ethnically Caucasian population.1 This is an important question to study in diverse populations, as the pre-pandemic incidence of carditis has been shown to vary based on geographical region.

There are some limitations of this study. The SCCS only provides relative, and not absolute, measures of risk.4 As such, a large incidence rate ratio could reflect a truly large increase in carditis, or be a result of very low baseline incidence rates of carditis. In this study, Dr Fan and colleagues report an incidence rate of 18.9 per million doses for BNT162b2 vaccination, and 5.22 per million doses for CoronaVac vaccination, which are comparable to previous studies.1 It is therefore unclear if the absolute increase in the risk of carditis is clinically significant, which requires estimating the clinical morbidity and long-term complications of carditis post vaccination, and even comparing it to that of COVID-19 infection. Ultimately, the final decision to vaccinate does not solely depend on the risk of carditis. Other side effects of vaccines (arrhythmias7 and thromboembolic events8,9 for example) and benefits including protection from serious SARS-CoV-2 infections, including ongoing morbidity, are also important considerations.

There are certain points which remain unanswered despite the novelties of this study. First, the study was limited by sample size in drawing any meaningful inferences in the female population, and those of younger age groups. It is unclear whether this reflects a lack of association, or that carditis is so rare in these subpopulations that the study was underpowered to detect a risk signal. Second, this cohort may not reflect the baseline pre-pandemic incidence of carditis in a population who was not exposed to COVID-19. As such, increases in detection and surveillance of carditis during the observation period may confound the incidence rate ratios, and the increase in carditis risk may be larger than expected when compared to a pre-pandemic observation period. Importantly, the authors did not look at vaccine response or efficacy for either vaccine.

Taken together, it would be unreasonable to enact blanket policies that mRNA COVID-19 vaccination should be avoided in the whole population in view of the excess risk of carditis. As this study shows, the incidence rate ratio of post-vaccination carditis depends on the baseline risk, and absolute risks are just as important when deciding on vaccination. Rather, there should be ongoing discussions at the physician and individual level for those who are at higher risk of carditis after vaccination. They need to balance their individual risk of morbidity from COVID-19 itself and the efficacy of the vaccine, against the side effects of vaccination. Avoiding mRNA COVID-19 vaccination and opting for alternative vaccines which confer a lower risk of carditis may be a solution. Ultimately, the decision for which vaccine to choose will evolve and will depend on many factors including: the circulating variant, the severity of COVID-19 for that individual and society, the efficacy of the vaccine, balanced against many short and long terms risks associated with COVID-19 infection (which include cardiovascular side effects10), and the various side effects of each vaccine beyond carditis alone.

Christine S. Benn et al.

Randomized clinical trials of COVID-19 vaccines: do adenovirus-vector vaccines have beneficial non-specific effects?

Cell, April 2023; doi.org/10.1016/j.isci.2023.106733

Abstract

We examined the possible non-specific effects of novel mRNA- and adenovirus-vector COVID-19 vaccines by reviewing the randomized control trials (RCTs) of mRNA and adenovirus-vector COVID-19 vaccines. We calculated mortality risk ratios (RR) for mRNA COVID-19 vaccines vs. placebo recipients and compared them with the RR for adenovirus-vector COVID-19 vaccine recipients vs. controls. The RR for overall mortality of mRNA vaccines vs. placebo was 1.03 (95% CI: 0.63-1.71). In the adenovirus-vector vaccine RCTs, the RR for overall mortality was 0.37 (0.19-0.70). The two vaccine types differed significantly with respect to impact on overall mortality (p=0.015). The RCTs of COVID-19 vaccines were unblinded rapidly and controls were vaccinated. The results may therefore not be representative of the long-term effects.However, the data argues for performing RCTs of mRNA and adenovirus-vector vaccines head-to-head comparing long-term effects on overall mortality.

Ali Rafati et al.

Association of SARS-CoV-2 Vaccination or Infection With Bell Palsy. A Systematic Review and Meta-analysis

JAMA, April 2023; doi:10.1001/jamaoto.2023.0160

Abstract

Importance Bell palsy (BP) has been reported as an adverse event following the SARS-CoV-2 vaccination, but neither a causative relationship nor a higher prevalence than in the general population has been established.

Objective To compare the incidence of BP in SARS-CoV-2 vaccine recipients vs unvaccinated individuals or placebo recipients.

Data Sources A systematic search of MEDLINE (via PubMed), Web of Science, Scopus, Cochrane Library, and Google Scholar from the inception of the COVID-19 report (December 2019) to August 15, 2022.

Study Selection Articles reporting BP incidence with SARS-CoV-2 vaccination were included.

Data Extraction and Synthesis This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and was conducted with the random- and fixed-effect models using the Mantel-Haenszel method. The quality of the studies was evaluated by the Newcastle-Ottawa Scale.

Main Outcomes and Measures The outcomes of interest were to compare BP incidence among (1) SARS-CoV-2 vaccine recipients, (2) nonrecipients in the placebo or unvaccinated cohorts, (3) different types of SARS-CoV-2 vaccines, and (4) SARS-CoV-2–infected vs SARS-CoV-2–vaccinated individuals.

Conclusions and Relevance This systematic review and meta-analysis suggests a higher incidence of BP among SARS-CoV-2–vaccinated vs placebo groups. The occurrence of BP did not differ significantly between recipients of the Pfizer/BioNTech vs Oxford/AstraZeneca vaccines. SARS-CoV-2 infection posed a significantly greater risk for BP than SARS-CoV-2 vaccination.

Min Fan et al.

Risk of carditis after three doses of vaccination with mRNA (BNT162b2) or inactivated (CoronaVac) covid-19 vaccination: a self-controlled cases series and a case–control study

The Lancet, March 2023; doi.org/10.1016/j.lanwpc.2023.100745

Abstract

Large-scale comparative research exploring the risk after the third dose and after inactivated covid-19 vaccination is limited. This study aimed to assess the risk of carditis following three doses of BNT162b2 or CoronaVac.

Interpretations

We detected increased carditis risks within 28 days after all three doses of BNT162b2 but the risk after the third doses were nothigher than that of the second dose when compared with baseline period. Continuous monitoring of carditis after both mRNA and inactivated covid-19 vaccines is needed.

Marie-JoelleJabagi et al.

Stroke, Myocardial Infarction, and Pulmonary Embolism after Bivalent Booster

NEJM, April 2023; DOI: 10.1056/NEJMc2302134

Abstract

A bivalent messenger RNA vaccine targeting both the ancestral and omicron BA.4–BA.5sublineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Pfizer–BioNTech) was introduced in France in early October 2022 and recommended for booster vaccination in vulnerable populations. Between October 6 and November 9, both monovalent and bivalent vaccines were available for administration to persons who were 50 years of age or older. In January 2023, the Vaccine Safety Datalink of the Centers for Disease Control and Prevention alerted the public about a possible increased risk of ischemic stroke within the 21 days after the bivalent injection in persons 65 years of age or older.1 We previously found no increase in the incidence of stroke, acute myocardial infarction, or pulmonary embolism after administration of the monovalent vaccine.2,3 Thus, we wanted to assess whether the risk of such events differed after receipt of the bivalent booster as compared with the monovalent booster.

Comparison between the Bivalent Booster and the Original Monovalent Booster in the Risk of Cardiovascular Events.

Of a total of 470,962 vaccine recipients (mean [±SD] age, 72.6±10.4 years), 97,234 (20.6%) received the monovalent vaccine and 373,728 (79.4%) received the bivalent vaccine (Fig. S2 and Table S1). After inverse probability of treatment weighting, sociodemographic and health-status characteristics were well balanced between the two groups (Fig. S3). At 21 days after the booster dose, we found no evidence of an increased risk of cardiovascular events among the recipients of the bivalent vaccine as compared with recipients of the monovalent vaccine. The evaluated events included ischemic stroke (hazard ratio, 0.86; 95% confidence interval [CI], 0.58 to 1.27), hemorrhagic stroke (hazard ratio, 0.86; 95% CI, 0.46 to 1.61), myocardial infarction (hazard ratio, 0.92; 95% CI, 0.62 to 1.36), pulmonary embolism (hazard ratio, 0.83; 95% CI, 0.49 to 1.40), and all four events combined (hazard ratio, 0.87; 95% CI, 0.69 to 1.09) (Table 1). Thus, our results provide reassurance regarding the continued use of this bivalent vaccine.

VahéNafilyan et al.

Risk of death following COVID-19 vaccination or positive SARS-CoV-2 test in young people in England

Nature, March 2023; doi.org/10.1038/s41467-023-36494-0

Abstract

Several studies have reported associations between COVID-19 vaccination and risk of cardiac diseases, especially in young people; the impact on mortality, however, remains unclear. We use national, linked electronic health data in England to assess the impact of COVID-19 vaccination and positive SARS-CoV-2 tests on the risk of cardiac and all-cause mortality in young people (12 to 29 years) using a self-controlled case series design. Here, we show there is no significant increase in cardiac or all-cause mortality in the 12 weeks following COVID-19 vaccination compared to more than 12 weeks after any dose. However, we find an increase in cardiac death in women after a first dose of non mRNA vaccines. A positive SARS-CoV-2 test is associated with increased cardiac and all-cause mortality among people vaccinated or unvaccinated at time of testing.

Jillian R. Jaycox et al.

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

Nature, March 2023; doi.org/10.1038/s41467-023-36686-8

Abstract

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

Jason M. Devgun et al.

Identification of Bradycardia Following Remdesivir Administration Through the US Food and Drug Administration American College of Medical Toxicology COVID-19 Toxic Pharmacovigilance Project

Jamanetwork, February 2023; doi:10.1001/jamanetworkopen.2022.55815

Abstract

Importance  The rapid spread and mortality associated with COVID-19 emphasized a need for surveillance system development to identify adverse events (AEs) to emerging therapeutics. Bradycardia is a remdesivir infusion–associated AE listed in the US Food and Drug Administration–approved prescribing information.

Objective  To evaluate the magnitude and duration of bradycardic events following remdesivir administration.

Design, Setting, and Participants  Amulticenter cohort study of patients with recorded heart rate less than 60 beats per minute within 24 hours after administration of a remdesivir dose was conducted between November 23, 2020, and October 31, 2021. Participants included patients hospitalized with COVID-19 at 15 medical centers across the US. Patients excluded had AEs unrelated to bradycardia, AEs in addition to bradycardia, or first onset of bradycardia after 5 remdesivir doses.

Exposures  Remdesivir administration.

Main Outcomes and Measures  Linear mixed-effect models for the minimum HR before starting remdesivir and within 24 hours of each dose included doses as fixed effects. Baseline covariates were age (≥65 years vs <65 years), sex (male vs female), cardiovascular disease history (yes vs no), and concomitant use of bradycardia-associated medications. The interactions between variables and doses were considered fixed-effects covariates to adjust models.

Conclusions and Relevance  In this cohort study, bradycardia occurred during remdesivir infusion and persisted. Given the widespread use of remdesivir, practitioners should be aware of this safety signal.

Brambilla M. et al.

Head-to-head comparison of four COVID-19 vaccines on platelet activation, coagulation and inflammation. The TREASURE study

Thrombosisresearch, January 2023; doi.org/10.1016/j.thromres.2023.01.015

Abstract

Introduction

Studies exploring alterations in blood coagulation and platelet activation induced by COVID-19 vaccines are not concordant. We aimed to assess the impact of four COVID-19 vaccines on platelet activation, coagulation, and inflammation considering also the immunization dose and the history of SARS-CoV-2 infection.

Methods

TREASURE study enrolled 368 consecutive subjects (161 receiving viral vector vaccines -ChAdOx1-S/Vaxzevria or Janssen- and 207 receiving mRNA vaccines -Comirnaty/Pfizer-BioNTech or Spikevax/Moderna). Blood was collected the day before and 8 ± 2 days after the vaccination. Platelet activation markers (P-selectin, aGPIIbIIIa and Tissue Factor expression; number of platelet-monocyte and -granulocyte aggregates) and microvesicle release were analyzed by flow cytometry. Platelet thrombin generation (TG) capacity was measured using the Calibrated Automated Thrombogram. Plasma coagulation and inflammation markers and immune response were evaluated by ELISA.

Results

Vaccination did not induce platelet activation and microvesicle release. IL-6 and CRP levels (+30%), D-dimer, fibrinogen and F1+2 (+13%, +3.7%, +4.3%, respectively) but not TAT levels significantly increased upon immunization with all four vaccines, with no difference among them and between first and second dose. An overall minor post-vaccination reduction of aPC, TM and TFPI, all possibly related to endothelial function, was observed. No anti-PF4 seroconversion was observed.

Conclusion

This study showed that the four COVID-19 vaccines administered to a large population sample induce a transient inflammatory response, with no onset of platelet activation. The minor changes in clotting activation and endothelial function might be potentially involved at a population level in explaining the very rare venous thromboembolic complications of COVID-19 vaccination.

Paul A. Offit

Bivalent Covid-19 Vaccines — A Cautionary Tale

NEJM, January 2023; doi/full/10.1056/NEJMp2215780

Abstract

In November 2019, a bat coronavirus made its debut in humans in Wuhan, China. Two months later, the original strain of SARS-CoV-2, called the Wuhan-1 or ancestral strain, was isolated and sequenced. It was now possible to make a vaccine. All the vaccines, including the mRNA vaccines made by Pfizer–BioNTech and Moderna, the viral vector vaccines made by Johnson & Johnson–Janssen and AstraZeneca, and the purified protein vaccine made by Novavax, were designed to prevent disease caused by the ancestral strain.

As the virus evolved, the ancestral strain was soon replaced by a series of variants. In the United States in 2020 and 2021, such variants included D614G, alpha, and delta, each of which was more contagious than the previous variant. In a U.S. study involving 8100 immunocompetent adults conducted between March and December 2021, two doses of mRNA vaccines — which were authorized by the Food and Drug Administration (FDA) and recommended by the Centers for Disease Control and Prevention (CDC) in December 2020 — continued to protect against hospitalization caused by these three virus variants.1 For vaccines against SARS-CoV-2, a mucosal infection with a short incubation period, protection from severe disease is the only reasonable and attainable goal.

In November 2021, a new variant, called omicron (subvariant BA.1), was detected in southern Africa. The omicron variant contained an alarming number of mutations (more than 30) in the spike protein, including at least 15 mutations in the receptor-binding domain, the primary target of neutralizing antibodies. Researchers found that serum samples obtained from people who were vaccinated against or previously infected with SARS-CoV-2 exhibited substantially lower neutralizing activity against BA.1 than against the ancestral strain and other strains. Furthermore, many commercially available monoclonal-antibody preparations were ineffective against this variant. Although it was reassuring that early data from southern Africa showed that previous infection or vaccination protected against severe disease caused by omicron,2 public health officials worried that the BA.1 strain posed a serious threat to the effectiveness of existing Covid-19 vaccines and therapies.

Given the ability to use mRNA technology to respond quickly to variant strains, bivalent vaccines were created to counter this new threat. In January and February 2022, Pfizer–BioNTech produced a bivalent vaccine containing 15 μg of mRNA directed against the ancestral strain of SARS-CoV-2 and 15 μg directed against BA.1. Moderna used 25 μg of mRNA directed against each of the same two strains. The combined quantities mirrored the amount of mRNA in each company’s monovalent booster dose for adults (30 μg for Pfizer–BioNTech and 50 μg for Moderna).

On June 28, 2022, researchers from Pfizer–BioNTech and Moderna presented data on their bivalent vaccines to the FDA’s Vaccines and Related Biological Products Advisory Committee (of which I am a member). The results were underwhelming. Bivalent boosters resulted in levels of neutralizing antibodies against BA.1 that were only 1.5 to 1.75 times as high as those achieved with monovalent boosters. Previous experience with the companies’ vaccines suggested that this difference was unlikely to be clinically significant. Safety data were reassuring. At the time of the FDA presentation, BA.1 was no longer circulating in the United States, having been replaced by more immune-evasive and contagious omicron subvariants. But winter was around the corner. The FDA advisory committee, sensing the urgency of responding to these immune-evasive strains, voted to authorize bivalent vaccines with an understanding that they would target omicron subvariants BA.4 and BA.5, which at the time had accounted for more than 95% of circulating strains.

A series of rapid-fire policy decisions followed. On June 29, 2022, the day after the advisory committee meeting, the Biden administration agreed to purchase 105 million doses of Pfizer–BioNTech’s bivalent vaccine containing BA.4 and BA.5 mRNA. One month later, on July 29, 2022, the administration agreed to purchase 66 million doses of Moderna’s bivalent vaccine, intending to offer both vaccines in the fall and winter. On September 1, 2022, the FDA withdrew its emergency use authorization for monovalent vaccine boosters and the CDC recommended bivalent vaccine boosters for everyone 12 years of age or older. On October 12, 2022, the CDC extended this recommendation to include everyone 5 years of age or older. At that point, no data from humans, including immunogenicity data, were available for comparing the relative capacities of the monovalent and bivalent vaccines to protect against BA.4 and BA.5.

On October 24, 2022, David Ho and colleagues released the results of a study examining levels of neutralizing antibodies against BA.4 and BA.5 after receipt of a monovalent or bivalent booster dose. They found “no significant difference in neutralization of any SARS-CoV-2 variant,” including BA.4 and BA.5, between the two groups.3 One day later, Dan Barouch and colleagues released the results of a similar study, finding that “BA.5 [neutralizing-antibody] titers were comparable following monovalent and bivalent mRNA boosters.” Barouch and colleagues also noted no appreciable differences in CD4+ or CD8+ T-cell responses between participants in the monovalent-booster group and those in the bivalent-booster group.4 Neither research group found the bivalent boosters to elicit superior immune responses. The results are now published in the Journal.

Why did the strategy for significantly increasing BA.4 and BA.5 neutralizing antibodies using a bivalent vaccine fail? The most likely explanation is imprinting. The immune systems of people immunized with the bivalent vaccine, all of whom had previously been vaccinated, were primed to respond to the ancestral strain of SARS-CoV-2. They therefore probably responded to epitopes shared by BA.4 and BA.5 and the ancestral strain, rather than to new epitopes on BA.4 and BA.5. This effect could possibly be moderated by immunizing people either with BA.4 and BA.5 mRNA alone or with a greater quantity of BA.4 and BA.5 mRNA. Evidence in support of these strategies can be found in Pfizer–BioNTech’s data regarding its BA.1-containing bivalent vaccine, which showed that BA.1-specific neutralizing-antibody responses were greater in persons who were injected with a monovalent vaccine containing 30 μg or 60 μg of BA.1 mRNA or a bivalent vaccine containing 30 μg of BA.1 mRNA and 30 μg of ancestral-strain mRNA than in those who received a bivalent vaccine containing 15 μg of each type of mRNA.

On November 22, 2022, the CDC published data on the effectiveness of the BA.4 and BA.5 mRNA vaccines for preventing symptomatic infection within 2 months after receipt of the booster dose. For people who had received a monovalent vaccine 2 to 3 months earlier, the extra protection associated with the bivalent booster dose ranged from 28 to 31%. For those who had received a monovalent vaccine more than 8 months earlier, the extra protection ranged from 43 to 56%.5 Given the results of previous studies, it’s likely that this moderate increase in protection against probably generally mild disease will be short lived. As of November 15, 2022, only about 10% of the population for whom the bivalent vaccine had been recommended had received it.5 By December 2022, the BA.4 strain was no longer circulating, and BA.5 accounted for less than 25% of circulating SARS-CoV-2 strains, having been partially replaced by more immune-evasive strains, such as BQ.1, BQ.1.1, BF.7, XBB, and XBB.1.

What lessons can be learned from our experience with bivalent vaccines?

Fortunately, SARS-CoV-2 variants haven’t evolved to resist the protection against severe disease offered by vaccination or previous infection. If that happens, we will need to create a variant-specific vaccine. Although boosting with a bivalent vaccine is likely to have a similar effect as boosting with a monovalent vaccine, booster dosing is probably best reserved for the people most likely to need protection against severe disease — specifically, older adults, people with multiple coexisting conditions that put them at high risk for serious illness, and those who are immunocompromised. In the meantime, I believe we should stop trying to prevent all symptomatic infections in healthy, young people by boosting them with vaccines containing mRNA from strains that might disappear a few months later.

Flacco M.E. et al.

COVID-19 Vaccination Did Not Increase the Risk of Potentially Related Serious Adverse Events: 18-Month Cohort Study in an Italian Province

MDPI, December 2022; doi.org/10.3390/vaccines11010031

Abstract

This cohort study on the entire population of an Italian Province assessed the incidence of potentially vaccine-related serious adverse events (PVR-SAEs) by COVID-19 vaccination status. From January 2021 to July 2022, we extracted all deaths and hospitalizations due to several cardiovascular diseases, pulmonary embolism, and deep vein thrombosis from National Healthcare System official data. During the follow-up, 5743 individuals died, and 2097 were hospitalized for PVR-SAEs. Vaccinated subjects (n = 259,821) did not show an increased risk of all-cause death, non-COVID death, or any PVR-SAEs, as compared to the unvaccinated (n = 56,494). These results were consistent across genders, age-classes, vaccine types, and SARS-CoV-2 infection status and did not vary in Cox models adjusting for age, gender, SARS-CoV-2 infection, and selected comorbidities. In the infected population, any dose of vaccine was associated with a lower likelihood of death and PVR-SAE. In the uninfected population, subjects who received one or two doses showed a significantly higher incidence of most outcomes, likely due to a large selection bias introduced by the Italian restriction policies targeting uninfected subjects who received less than three doses. In conclusion, COVID-19 vaccination was not associated with an increase of mortality or selected PVR-SAEs incidence. Further research is warranted to evaluate the long-term safety of COVID-19 vaccines.

Butt A.A. et al.

Evaluation of mortality attributable to SARS-CoV-2 vaccine administration using national          data from Qatar level

Nature, January 2023; doi.org/10.1038/s41467-022-35653-z

Abstract

Accurate determination of mortality attributable to SARS-CoV-2 vaccination is critical in allaying concerns about their safety. We reviewed every death in Qatar that occurred within 30 days of any SARS-CoV-2 vaccine administration between January 1, 2021 and June 12, 2022. Probability of association with SARS-CoV-2 vaccination was determined by four independent trained reviewers using a modified WHO algorithm. Among 6,928,359 doses administered, 138 deaths occurred within 30 days of vaccination; eight had a high probability (1.15/1,000,000 doses), 15 had intermediate probability (2.38/1,000,000 doses), and 112 had low probability or no association with vaccination. The death rate among those with high probability of relationship to SARS-CoV-2 vaccination was 0.34/100,000 unique vaccine recipients, while death rate among those with either high or intermediate probability of relationship to SARS-CoV-2 vaccination was 0.98/100,000 unique vaccine recipients. In conclusion, deaths attributable to SARS-CoV-2 vaccination are extremely rare and lower than the overall crude mortality rate in Qatar.

Calvert C et al.

A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection

Nature, January 2023; doi.org/10.1038/s41467-022-35771-8

Abstract

Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. Here we report a national, population-based, matched cohort study using linked electronic health records from Scotland (May 2020-April 2022) to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any major congenital anomaly and [2] any non-genetic major congenital anomaly. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any anomaly and 120 had a non-genetic anomaly. Primary analyses find no association between any vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83-1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81-1.22). Primary analyses also find no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66-1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57-1.54). Findings are robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.

Jun Yasuhara et al.

Myopericarditis After COVID-19 mRNA Vaccination Among Adolescents and Young Adults A Systematic Review and Meta-analysis

JAMA, December 2022; doi:10.1001/jamapediatrics.2022.4768

Abstract

Importance Published data on COVID-19 mRNA vaccine–associated myopericarditis in adolescents and young adults have been derived from small case series, national populationbased studies, or passive reporting systems. Pooled evidence from a larger, international cohort is scarce.

Objective

To investigate the clinical features and early outcomes associated with myopericarditis after COVID-19 mRNA vaccination in a heterogeneous population of adolescents and young adults. Data Sources PubMed and EMBASE were searched through August 2022. Language restrictions were not applied. Study Selection Observational studies and case series describing COVID-19 vaccine– associated myopericarditis in adolescents and young adults aged 12 to 20 years and reporting clinical characteristics and early outcomes were included.

Conclusions and Relevance

This systematic review and meta-analysis found low incidence rate and largely favorable early outcomes of COVID-19 mRNA vaccine–associated myopericarditis in adolescents and young adults from a wide range of populations. These findings are reassuring but continued follow-up is warranted

Bettinger J.A. et al.

Adverse Events Following Immunization with mRNA and Viral Vector Vaccines in Individuals with Previous SARS-CoV-2 Infection from the Canadian National Vaccine Safety Network

CID, October 2022; doi.org/10.1093/cid/ciac852

Abstract

Adults previously infected with SARS-CoV-2 develop short-term immunity and may have increased reactogenicity to COVID-19 vaccines. This prospective, multi-center active surveillance cohort study examined the short-term safety of COVID-19 vaccines in adults with a prior history of SARS-CoV-2.

Hermann E.A. et al.

Association of Symptoms After COVID-19 Vaccination With Anti–SARS-CoV-2 Antibody Response in the Framingham Heart Study

JAMA, October 2022; doi:10.1001/jamanetworkopen.2022.37908

Abstract

The authors studied the association of self-reported postvaccination symptoms with anti–SARS-CoV-2 antibody response among Framingham Heart Study (FHS) participants contributing to the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) study.

L. Thurner et al.

IL-1RA antibodies in myocarditis after SARS-CoV-2 vaccination

The New Wngland J of Medicine, September 2022; doi: 10.1056/NEJMc2205667

Abstract

Myocarditis associated with messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects male adolescents and young male adults (14 to <30 years of age) and occurs after receipt of the second vaccine dose. This study evaluated the prevalence of antibodies neutralizing IL-1RA and progranulin, which inhibits tumor necrosis factor signaling, in who had clinically suspected myocarditis after SARS-CoV-2 vaccination.

I. Kracalik  et al.

Outcomes at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults in the USA: a follow-up surveillance study

Lancet Child Adolescent Health, September 2022; doi.org/10.1016/ S2352-4642(22)00244-9

Abstract

Data on medium-term outcomes in indivduals with myocarditis after mRNA COVID-19 vaccination are scarce. The authors aimed to assess clinical outcomes and quality of life at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults.

E. Ammirati et al.

Recovery from mRNA COVID-19 vaccine-related myocarditis

Lancet Child Adolescents Health, September 2022; doi.org/10.1016/ S2352-4642(22)00272-3

Abstract

The greater number of individuals with vaccinerelated myocarditis in recent reports, compared with previous figures of vaccine-related myocarditis in the WHO pharmacovigilance database between 1967 and 2020, might relate to the high number of adolescent and young adults vaccinated with mRNA COVID-19 vaccines. Unlike previous myocarditis case series, intermediateterm outcomes and time course of recovery after mRNA COVID-19 vaccine-associated myocarditis have not yet been reported.

V. Nafilyan et al.

Evaluation of Risk Factors for Postbooster Omicron COVID-19 Deaths in England

JamaInfectiousDiseases, September2022;doi:10.1001/jamanetworkopen.2022.33446

Abstract

With the emergence of the Omicron variant, it has become critical to identify risk factors associated with COVID-19 death in individuals who have completed primary vaccination and received a messenger RNA (mRNA) booster dose. Existing evidence is based on people who have received 1 or 2 doses of a COVID-19 vaccine and were infected by the Alpha or Delta variant.Understanding which groups are at increased risk of COVID-19 death after receiving a booster is crucial for the prioritization of further booster doses and access to COVID-19 therapeutics.

R. Herrera-Comoglio et al.

Vaccine-Induced Immune Thrombocytopenia and Thrombosis after the Sputnik V Vaccine

The New Engl Journal of Medicine, September 2022; doi: 10.1056/NEJMc2210813

Abstract

Since February 2021, very rare cases of thrombosis with thrombocytopenia syndrome, later named vaccine-induced immune thrombocytopenia and thrombosis (VITT) have been reported after receipt of the adenoviral-vector vaccines ChAdOx1 nCoV-19 (Oxford–AstraZeneca) and Ad26.COV2.S (Johnson & Johnson–Janssen). Such reports have prompted regulatory actions in the United States, Europe, and other countries. A report on a large case series of 220 patients described the clinical features and diagnostic criteria of this disorder. Other adenovirus vector vaccines are available, including Ad5-nCoV (CanSinoBio Biologics) and Gam-COVID-Vac (Sputnik V); the latter uses a heterologous recombinant adenovirus approach in two injections (a rAd26 prime and a rAd5 booster) given 21 days apart.

S. Le Vu et al.

Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines

Nature Communications, June 2022; doi.org/10.1038/s41467-022-31401-5

Abstract

Cases of myocarditis and pericarditis have been reported following the receipt of Covid-19 mRNA vaccines. As vaccination campaigns are still to be extended, we aimed to provide a comprehensive assessment of the association, by vaccine and across sex and age groups. Using nationwide hospital discharge and vaccine data, we analysed all 1612 cases of myocarditis and 1613 cases of pericarditis that occurred in France in the period from May 12, 2021 to October 31, 2021. We perform matched case-control studies and find increased risks of myocarditis and pericarditis during the first week following vaccination, and particularly after the second dose, with adjusted odds ratios of myocarditis of 8.1 (95% confidence interval [CI], 6.7 to 9.9) for the BNT162b2 and 30 (95% CI, 21 to 43) for the mRNA-1273 vaccine. The largest associations are observed for myocarditis following mRNA-1273 vaccination in persons aged 18 to 24 years. Estimates of excess cases attributable to vaccination also reveal a substantial burden of both myocarditis and pericarditis across other age groups and in both males and females.

Wong H.L. et al.

Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases

Lancet, June 2022; 399: 2191–99

Abstract

Background Several passive surveillance systems reported increased risks of myocarditis or pericarditis, or both, after COVID-19 mRNA vaccination, especially in young men. We used active surveillance from large health-care databases to quantify and enable the direct comparison of the risk of myocarditis or pericarditis, or both, after mRNA-1273 (Moderna) and BNT162b2 (Pfizer–BioNTech) vaccinations.

Methods We conducted a retrospective cohort study, examining the primary outcome of myocarditis or pericarditis, or both, identified using the International Classification of Diseases diagnosis codes, occurring 1–7 days post-vaccination, evaluated in COVID-19 mRNA vaccinees aged 18–64 years using health plan claims databases in the USA. Observed (O) incidence rates were compared with expected (E) incidence rates estimated from historical cohorts by each database. We used multivariate Poisson regression to estimate the adjusted incidence rates, specific to each brand of vaccine, and incidence rate ratios (IRRs) comparing mRNA-1273 and BNT162b2. We used meta-analyses to pool the adjusted incidence rates and IRRs across databases.

Findings A total of 411 myocarditis or pericarditis, or both, events were observed among 15148369 people aged 18–64 years who received 16912 716 doses of BNT162b2 and 10631 554 doses of mRNA-1273. Among men aged 18–25 years, the pooled incidence rate was highest after the second dose, at 1·71 (95% CI 1·31 to 2·23) per 100000 person-days for BNT162b2 and 2·17 (1·55 to 3·04) per 100000 person-days for mRNA-1273. The pooled IRR in the head-to-head comparison of the two mRNA vaccines was 1·43 (95% CI 0·88 to 2·34), with an excess risk of 27·80 per million doses (–21·88 to 77·48) in mRNA-1273 recipients compared with BNT162b2.

Interpretation An increased risk of myocarditis or pericarditis was observed after COVID-19 mRNA vaccination and was highest in men aged 18–25 years after a second dose of the vaccine. However, the incidence was rare. These results do not indicate a statistically significant risk difference between mRNA-1273 and BNT162b2, but it should not be ruled out that a difference might exist. Our study results, along with the benefit–risk profile, continue to support vaccination using either of the two mRNA vaccines.

CDC Centers for Diseases Control and Prevention

Clinical Considerations: Myocarditis and Pericarditis after Receipt of mRNA COVID-19 Vaccines Among Adolescents and Young Adults

3 June 2022; https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html

Abstract

In April 2021, increased cases of myocarditis and pericarditis were reported in the United States after mRNA COVID-19 vaccination (Pfizer-BioNTech and Moderna). Data from multiple studies show a rare risk for myocarditis and/or pericarditis following receipt of mRNA COVID-19 vaccines. These rare cases of myocarditis or pericarditis have occurred most frequently in adolescent and young adult males, ages 16 years and older, within 7 days after receiving the second dose of an mRNA COVID-19 vaccine (Pfizer-BioNTech and Moderna). There has not been a similar reporting pattern observed after receipt of the Janssen COVID-19 Vaccine (Johnson & Johnson).

CDC continues to recommend COVID-19 vaccination for everyone 5 years of age and older. The Advisory Committee on Immunization Practices (ACIP) and CDC have determined that the benefits (such as prevention of COVID-19 cases and its severe outcomes) outweigh the risks of myocarditis and pericarditis after receipt of mRNA COVID-19 vaccines.

L.F. Sun Cristoforo et al .

Increased emergency cardiovascular events among under-40 population in Israel during vaccine rollout and third COVID-19 wave

Nature, Scientific Reports, April 2022; doi.org/10.1038/s41598-022-10928-z

Abstract

Cardiovascular adverse conditions are caused by coronavirus disease 2019 (COVID-19) infections and reported as side-effects of the COVID-19 vaccines. Enriching current vaccine safety surveillance systems with additional data sources may improve the understanding of COVID-19 vaccine safety. Using a unique dataset from Israel National Emergency Medical Services (EMS) from 2019 to 2021, the study aims to evaluate the association between the volume of cardiac arrest and acute coronary syndrome EMS calls in the 16–39-year-old population with potential factors including COVID-19 infection and vaccination rates. An increase of over 25% was detected in both call types during January–May 2021, compared with the years 2019–2020. Using Negative Binomial regression models, the weekly emergency call counts were significantly associated with the rates of 1st and 2nd vaccine doses administered to this age group but were not with COVID-19 infection rates. While not establishing causal relationships, the findings raise concerns regarding vaccine-induced undetected severe cardiovascular side-effects and underscore the already established causal relationship between vaccines and myocarditis, a frequent cause of unexpected cardiac arrest in young individuals. Surveillance of potential vaccine side-effects and COVID-19 outcomes should incorporate EMS and other health data to identify public health trends (e.g., increased in EMS calls), and promptly investigate potential underlying causes.

C.L.F. Sun et al.

Increased emergency cardiovascular events among under-40 population in Israel during vaccine rollout and third COVID-19 wave

Nature Scientific Reports, April 2022; doi.org/10.1038/s41598-022-10928-z

Abstract

Cardiovascular adverse conditions are caused by coronavirus disease 2019 (COVID-19) infections and reported as side-effects of the COVID-19 vaccines. Enriching current vaccine safety surveillance systems with additional data sources may improve the understanding of COVID-19 vaccine safety. Using a unique dataset from Israel National Emergency Medical Services (EMS) from 2019 to 2021, the study aims to evaluate the association between the volume of cardiac arrest and acute coronary syndrome EMS calls in the 16–39-year-old population with potential factors including COVID-19 infection and vaccination rates. An increase of over 25% was detected in both call types during January–May 2021, compared with the years 2019–2020. Using Negative Binomial regression models, the weekly emergency call counts were significantly associated with the rates of 1st and 2nd vaccine doses administered to this age group but were not with COVID-19 infection rates. While not establishing causal relationships, the findings raise concerns regarding vaccine-induced undetected severe cardiovascular side-effects and underscore the already established causal relationship between vaccines and myocarditis, a frequent cause of unexpected cardiac arrest in young individuals. Surveillance of potential vaccine side-effects and COVID-19 outcomes should incorporate EMS and other health data to identify public health trends (e.g., increased in EMS calls), and promptly investigate potential underlying causes.

H. Ahmed Mushtaq et al.

A review of adverse effects of COVID-19 vaccines

Infezioni in Medicina, 2022; doi: 10.53854/liim-3001-1

Abstract

The COVID-19 pandemic has led to unanticipated pressures on all aspects of human life. Multiple approaches to eliciting protective immunity must be rapidly evaluated. Numerous efforts have been made to develop an effective vaccine for this novel coronavirus, resulting in a race for vaccine development. To combat COVID-19, all nations must focus their efforts on widespread vaccination with an effective and safe vaccine. Globally, concerns about potential long-term adverse effects of vaccines have led to some apprehension about vaccine use. A vaccine’s adverse effect has an integral role in the public’s confidence and vaccine uptake. This article reviews the current primary literature regarding adverse effects associated with different COVID-19 vaccines in use worldwide.

Oguz  S. H. et al.

SARS-CoV-2 vaccine-induced thyroiditis: Safety of Re-vaccinations and Clinical Follow-up

JCEM, https://doi.org/10.1210/clinem/dgac049

CONTENUTO E COMMENTO : studio che mira ad analizzare gli outcomes a lungo termine delle tiroiditi subacute (SAT) e morbi di graves (GD) indotti da vaccinazione antiSARS-CoV2. A questo scopo sono stati analizzati i pazienti diagnosticati con SAT o GD tra gennaio e ottobre 2021 secondo le definizioni della lineaguida della American Thyroid Association del 2016, che abbiano sviluppato i sintomi nelle 4 settimane successive la vaccinazione. Sono stati esclusi i pazienti con meno di 4 settimane di follow-up e un tampone molecolare per ricerca di SARS-CoV2 positivo.

Sono stati inoltre analizzati gli effetti della vaccinazione booster su riesacerbazioni o peggioramenti della patologia tiroidea sviluppata post ciclo vaccinale primario.

Sono pertanto stati inclusi nella coorte 19 pazienti, 15 con SAT indotta da vaccino antiSARS-CoV2 e 4 con GD indotta da vaccino antiSARS-CoV2.

Il vaccino Pfizer/BioNTech COVID-19 (BNT162b2) e’ stato associato ai sintomi della maggioranza dei SAT (53,3%) e tutti quelli con GD (100%).  La maggior parte dei pazienti con SAT (86%) e GD (75%) indotti da vaccino di questa serie erano donne. Inoltre l’eta’ mediana dei pazienti con SAT era piu’ bassa di quella descritta attualmente in letteratura (46 anni), mentre quella del gruppo GD era simile (41,5).

Il periodo di tempo mediano tra vaccinazione ed esordio dei sintomi e’ stato di 7 e 11.5 giorni, rispettivamente, mentre in 7 e 2 pazienti e’ stata necessaria terapia medica nei gruppi SAT e GD, rispettivamente.

Il tempo mediano tra l’esordio dei sintomi e la diagnosi e’ stato di 3 settimane in questa coorte. La remissione e’ stata documentata in 10 pazienti con SAT, con un tempo mediano di remissione di 11.5 settimane.

Non ci sono state ricadute/riesacerbazioni di SAT in 7 su 9 pazienti che abbiano ricevuto il booster, mentre i sintomi SAT sono peggiorati dopo somministrazione di booster in due casi, con una remissione relativamente rapida.

La vaccinazione e’ stata associata a riesacerbazione in 3 pazienti della coorte con una pregressa diagnosi di SAT classica prima della vaccinazione, evento non precedentemente descritto in letteratura.

Nonostante questi eventi, la vaccinazione appare sicura nei pazienti con SAT indotta da vaccino e storia di SAT classica prima della vaccinazione : il gruppo che ha sviluppato SAT dopo la prima dose e il gruppo con pregressa SAT e riesacerbazione dopo vaccinazione hanno avuto un massimo di 2 episodi e una rapida remissione.

Nessun paziente e’ stato vittima di effetti avversi gravi che potessero essere associati con somministrazione di booster.

2 pazienti hanno sviluppato GD con la somministrazione di dose booster BNT162b2 6 mesi dopo un ciclo primario di CoronaVac : dato che tutti i casi di GD associati a vaccino riportati in letteratura sono stati associato a vaccinazioni a base di mRNA o con vettore adenovirus, parrebbe che i vaccini a base di SARS-CoV2 inattivato siano sicuri dal punto di vista della possibile induzione di GD.

Rispetto al decorso classico della SAT, una piu’ piccola percentuale di casi indotti da vaccino hanno avuto necessita’ di trattamento con una durata di trattamento nei casi trattati piu’ piccola rispetto a una SAT classica. Il tempo di guarigione e’ stato simile a quello di una SAT classica, ma piu’ lungo rispetto a SAT indotta da altri vaccini.

A circa 6 mesi di follow-up, un paziente del gruppo SAT ha sviluppato GD, come precedentemente descritto nel decorso clinico della SAT.

Oster M. E. et al.

Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021

JAMA, January 2022;  doi:10.1001/jama.2021.24110 

 https://jamanetwork.com/journals/jama/fullarticle/2788346?guestAccessKey=87c5550a-62ee-4cdc-a341-3027ff0f2c3b&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=etoc&utm_term=012522

CONTENUTO E COMMENTO: : studio descrittivo retrospettivo sui report di miocardite e pericardite nel Vaccine Adverse Event Reporting System (VAERS) degli Stati Uniti, occorsi dopo somministrazione di vaccini antiSARS-CoV2 a base di mRNA tra dicembre 2020 ed Agosto 2021 in soggetti sopra I 12 anni di eta’, confrontati con i tassi di miocardite aggiustati per sesso e per eta’ nel periodo 2017-2019. Per le definizioni degli outcome, si e’ fatto riferimento alle definizioni CDC di caso probabile e confermetato di miocardite. Le morti attribuite sono state incluse solo per I casi confermati che non avessero cause alternative identificabili di morte.

Tra il 14 dicembre 2020 e il 31 agosto 2021, 192 405 448 individui sopra I 12 anni di eta’ sono stati vaccinati con vaccini a base di mRNA per un totale di 354 100 845 dosi.

I report inoltrati al VAERS per miocardite sono stati 1991 (di cui 391 con pericardite) e 684 report di pericardite senza miocardite. Dei 1991 report, solo 1626 erano compatibili con le definizioni di caso CDC probabile e confermato.

1195 (73%) avevano meno di 30 anni (fascia di eta’ in cui non si sono registrate morti), 543 (33%) meno di 18 con una eta’ media di 21 years anni (IQR, 16-31 years). La maggior parte dei casi di miocardite, 82% (1265/1538, report di cui informazione sulla dose vaccinale presente) sono occorsi dopo la seconda dose ed in media dopo la seconda dose, I sintomi sono comparsi nei 2 giorni successivi e gli eventi miocarditi sono occorsi nel 90% (1081/1199) dei casi entro I 7 giorni.

I maschi comprendevano 82% (1334/1625) dei casi di miocardite in cui il sesso era riportato.

I report di miocardite sono stati maggiori dopo la seconda dose negli adolescenti maschi tra i 12 e 15 anni (70.73 [95% CI, 61.68-81.11] per millione dosi di BNT162b2), tra i 16 e 17 anni (105.86 [95% CI, 91.65-122.27] per millione dosi di BNT162b2), e tra i 18 e 24 anni(52.43 [95% CI, 45.56-60.33] per millione dosi di  BNT162b2 e 56.31 [95% CI, 47.08-67.34] per millione dosi di  mRNA-1273).

Comparati con I casi non associati a vaccino, I report di miocardite del VAERS dopo vaccino a mRNA sono simili per caratteristiche demografiche (eta’ e sesso) ma non per il decorso clinico: I casi vaccino-relati sono stati maggiormente acuti (vs l’andamento indolente delle miocarditi virali tipiche) con risoluzioni piu’ veloci e risoluzione dei sintomi con la sola terapia sintomatica senza altri interventi (vs decorso variabile con maggiori complicanze nelle miocarditi virali).

Limitazioni : VAERS e’ un report passivo, dati spesso incompleti e di qualita’ variabile, non nota storia di infezione da SARS-CoV2 previa.

Haas J.W. et al.

Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials A Systematic Review and Meta-analysis

JAMA, January 2022;  doi:10.1001/jamanetworkopen.2021.43955 

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788172

CONTENUTO E COMMENTO : Review sistematica e metanalisi eseguita con lo scopo di comparare la frequenza di reazioni avverse nei gruppi riceventi placebo dei trials vaccinali con quelle dei gruppi riceventi il vaccino per Sars-Cov2. Per la selezione degli studi sono stati considerati trial clinici randomizzati che comprendevano persone di età > di 16 anni e ovviamente con un gruppo ricevente placebo, con la registrazione degli eventi avversi per entrambi i gruppi separatamente. L’outcome primario rigurdava le proporzioni delle segnalazioni di reazioni avverse, sia locali che sistemiche, nel gruppo placebo così come i log odds ratios per valutare la differenza trai gruppi. 12 trials per un totale di 45.380 partecipanti venivano analizzati. I dati dimostrano che già dopo la prima dose un 35% dei riceventi placebo segnalava reazioni avverse sistemiche (cefalea ed astenia tra le più frequenti) mentre dopo la seconda dose un 31.8%. Il rapporto tra il braccio placebo e quello del vaccino mostra che le reazioni avverse nel primo (nocebo) rappresentano il 76% delle segnalazioni dopo la prima dose e il 51.8% dopo la seconda. In totale un numero maggiore di partecipanti sottoposti alla somministrazione vaccinale segnalava reazioni avverse, ma il rapporto delle reazioni avverse riportate nel gruppo placebo restava importante e da considerare nell’ambito delle campagne vaccinali, essendo proprio la preoccupazione per le reazioni avverse uno dei maggiori fattori di esitazione nella popolazione a sottoporsi al vaccino. Tra le limitazioni maggiori dello studio si riportano un relativo basso numero di trials analizzati e la loro elevata eterogeneità.

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