Myocarditis rate higher in younger people following mRNA vaccination

5th December 2022

Although the myocarditis rate after mRNA vaccination is low these rates appear to higher in those aged 18 – 30 compared to older adults

The overall myocarditis rate following a mRNA vaccination for COVID-19 is generally low but is higher than expected among those aged 12 to 29 years of age according to the findings of a post-marketing observational study by Canadian researchers.

Although there has been a huge uptake of COVID-19 vaccines, hesitancy remains a significant challenge with acceptance rates ranging from 53.6 to 84.4%. In fact, a US survey of 5,088,772 individuals identified that almost half (49.2%) of vaccine hesitant respondents reported fear of side effects. One such adverse effect following vaccination and which was not identified during the clinical trials was myocarditis with one US surveillance study concluding that the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and highest after the second vaccination dose in adolescent males and young men. However, little is known about the incidence of the condition following a third vaccination dose and this was the subject of the current study in which the Canadian team compared the myocarditis rate after a first, second and third dose compared to the background or expected rate.

The team used an integrated COVID-19 surveillance platform which contained all COVID-19-related data including infections and hospital or intensive care admissions. They focused on individuals aged 12 years and older and set the primary outcome as hospital admission or an emergency department visit for myocarditis.

Myocarditis rate and mRNA vaccination

During the study period (December 2020 to March 2022), a total of 1,025,385 doses of an mRNA vaccine (mRNA-1273 and BNT162b) were administered.

A total of 99 incident cases of myocarditis were identified within 7 days of vaccination, giving a rate per 100,000 of 0.97 (95% CI 0.78 – 1.17). The expected rate was 0.13 (95% CI 0.06 – 0.28) so that the observed:expected (OE) ratio was 14.81. The observed rate was higher in males than females (1.64 vs 0.35) and occurred in younger men (median age males = 28 vs median age females = 45).

Within 21 days following vaccination, there were 141 cases of myocarditis with an OE ratio of 7.03 (95% CI 5.92 – 8.29). As with the 7-day risk period, the 21-day incidence rate was higher in men than women (2.15 vs 0.67). In fact, when researchers looked at the incidence rate across different ages, the rates were much higher among those aged 12 – 29. For example, the incidence rate was 2.95 (ages 12 – 17) and 2.97 (ages 18 – 29) compared to 0.77 (ages 50 – 59) and 0.71 (ages 60 – 69).

Interestingly, the incidence myocarditis in both the 7 and 21-day post-vaccination periods reduced after the second dose. For example, the incidence rate during the first 7 days after the first vaccination was 0.18, 1.90 after the second dose but 0.76 after the third dose.

When comparing vaccines, there was a much higher rate of myocarditis following mRNA-1273 compared to BNT162b (1.44 vs 0.74). In addition, the incidence rate was highest among males aged 18 – 29 after the second dose (22.97 vs 5.84, mRNA vs BNT162b).

The authors concluded that although absolute rates of myocarditis were low, their findings support the preferential use of the BNT162b2 vaccine over the mRNA-1273 vaccine for people aged 18-29 years.

Citation
Naveed Z et al. Observed versus expected rates of myocarditis after SARS-CoV-2 vaccination: a population-based cohort study. CMAJ 2022

Booster COVID-19 vaccination improves immune response in cancer patients undergoing treatment

21st January 2022

A booster COVID-19 dose administered to cancer patients on active treatment leads to an improved immune response in those fully vaccinated

A booster COVID-19 dose to cancer patients with solid tumours in receipt of active treatment, improves their immune response, according to the results of a study by a team from the University Paris Est Créteil, Paris, France.

Since the start of the COVID-19 pandemic, cancer patients have been deemed to be at high risk and thus a priority group for access to available vaccines. Nevertheless, as cancer patients were excluded from the vaccine efficacy trials, the nature and level of the immunogenic response to vaccination among cancer patients was uncertain.

Data from a study among cancer patients on treatment has shown that after a first dose, 29% of patients were seropositive and that this rate increased to 86% after the second dose. But there appears to be only one study in patients with cancer who have received a third dose of vaccine and which appeared to show greater immunogenicity.

For the present study, the French team wanted to evaluate the immunogenicity of two and three doses of a COVID-19 vaccine in cancer patients currently receiving chemotherapy and how this was affected by the type of oncology treatment and the timing of vaccination.

Using a prospective, observational design, the team included patients with solid organ active cancer, which they defined as ‘histologic confirmation of solid cancer under treatment within the previous 6 weeks or starting treatment during the next 2 weeks.’

The researchers collected information on the patient’s cancer diagnosis, therapy and cancer stages. All patients had received two doses of BNT162b2 on days 0 and 21 and those who had a prior history of COVID-19 infection or evidence of antibodies before vaccination were excluded.

A booster COVID-19 (i.e., third) dose was offered to all of those who had a weak humoral response one month after the second dose, which was defined by an anti-spike protein antibody level below 1000 units.

Findings

In total, 163 patients with a median age of 66 years (53% male) were included in the analysis. The most common form of treatment was chemotherapy (75%), followed by targeted therapy (16%) and immunotherapy (9%).

One month after the first vaccine, only 15% of patients had anti-spike antibody titres > 1000, although one month after the second dose, this proportion increased to 65%. A booster COVID-19 dose was offered to 36 patients whose antibody level remained below 1000 units, one month after the second dose. This resulted in 75% of these patients, achieving antibody levels > 1000, one month after their third dose.

In their analysis, age, sex, cancer type, lymphopenia and use of corticosteroids four or more weeks before vaccination, were not associated with the level of immune response at the time of the second dose or even 28 days after the second dose.

However, patients receiving either chemotherapy or targeted therapy had a lower anti-spike level than those given immunotherapy (odds ratio, OR = 5.4, 95% CI 1.5 – 20.2, p = 0.02). Other factors such as the time between vaccination and intravenous chemotherapy administration were also not associated with the intensity of the humoral response.

The authors concluded that a booster COVID-19 dose among those with solid tumours and in receipt of treatment, improved the immune response, highlighting the importance of a third dose in this patient cohort.

Citation

Fenioux C et al. SARS-CoV-2 Antibody Response to 2 or 3 Doses of the BNT162b2 Vaccine in Patients Treated With Anticancer Agents JAMA Oncol 2022.

Three doses of BNT162b2 able to neutralise Omicron variant

13th December 2021

Three doses of the Pfizer-BioNTech COVID-19 vaccine, BNT162b2 have been shown in a preliminary study to neutralise the Omicron variant

In a press release, Pfizer and BioNTech have announced that serum antibodies induced after three doses of their COVID-19 vaccine (BNT162b2) are able to neutralise the Omicron variant.

The company’s laboratory study involved testing human sera obtained from the blood of individuals who had received two or three 30-µg doses of the BNT162B2 using a pseudovirus neutralisation test, which used to study the effect of antibodies to neutralise the capability of viruses to enter cells and thus prevent infection. The sera were collected from subjects 3 weeks after receiving the second dose or one month after receiving the third dose of their vaccine

In the study, each sample of serum was simultaneously tested for its neutralising antibody titre against the original (or wild-type) COVID-19 spike protein as well as the Omicron spike variant. The researchers found that after a third vaccine dose, there was a significant, 25-fold increased level of neutralising antibody titres against the Omicron strain spike protein. In fact, antibody titre levels against the Omicron variant were comparable to the neutralisation against the wild-type strain observed in sera from individuals who received two doses of the companies’ COVID-19 vaccine. However, data on the persistence of these neutralising antibodies over time is uncertain and will be determined over time.

At the present time, there is still much to learn about the Omicron variant although a preliminary study from South Africa in 12 people has provided some answers. The study included 12 individuals with a mean age of 57 years (66% male), 6 of whom had been vaccinated with the remaining 6 having been both vaccinated and previously infected. The purpose of the study was to examine whether the Omicron variant still required the ACE2 receptor to gain entry to cells and if plasma from those vaccinated with BNT162b2 were able to neutralise the variant. The results showed that the ACE2 receptor was still required to gain entry to cells but also that there was a 41-fold reduction in antibody neutralisation against Omicron compared with the original wild-type. However, on the plus side, escape was much less in those who had been previously infected the COVID-19.

There is still much to learn about the Omicron variant, in particular its transmissibility and whether it results in more severe infections and hospitalisations.

However, one point reassuring point mentioned in Pfizer-BioNTech press release was how 80% of the regions of the spike protein that are recognised by cytotoxic (killer) T (CD8 +) cells are unchanged in the variant. It is possible therefore, that three doses, i.e., full vaccination and a booster, will hopefully provide an enhanced immune response and which may be sufficient to prevent the variant from causing more severe disease. 

Vaccine efficacy of BNT162b significantly reduced after 5 months

11th October 2021

A large retrospective study has found that while the BNT162b vaccine efficacy is initially high it significantly reduces over 5 months.

In the first clinical trial, the BNT162b COVID-19 vaccine was shown to provide 95% protection against COVID-19 in those 16 years of age and older. In addition, a real-world study has confirmed the efficacy observed in the trial, with two doses of BNT162b2 being highly effective in preventing both symptomatic and asymptomatic infections, COVID-19-related hospitalisations, severe disease and death. However, there have been concerns that approved COVID-19 vaccines might show reduced efficacy over time prompting the need for a booster dose.

In an attempt to provide answers as to whether vaccine efficacy wanes over time, a team from the Department of Research and Evaluation, Kaiser Permanente, California, USA, undertook a retrospective cohort study. The team analysed electronic health records for individuals 12 years and older to assess BNT162b effectiveness against COVID-19 infection and related hospitalisations for up to six months. The study outcomes were COVID-19 infections (based on a positive PCR test) and COVID-19-related hospitalisations over a 6 month period.

Findings

A total of 3,436,957 individuals with a median age of 45 years (52.4% female) were included in the final analysis. There were 184 041 (5·4%) participants infected with COVID-19, of whom, 12130 (6·6%) were admitted to hospital. Among those fully vaccinated, the vaccine efficacy against infection was 73% (95% CI 72 – 74) and against hospital admission 90% (95% CI 89 – 92). Over a period of 5 months however, vaccine efficacy against infection reduced from 88% (in the first month) to 47% after 5 months. Despite this, vaccine efficacy against hospitalisation remained stable over the study period.

The study also examined vaccine efficacy against the COVID-19 delta variant and 4 months after full vaccination, vaccine effectiveness against this variant declined from 93% to 53%.

The authors concluded that their findings underscored the importance of monitoring vaccine efficacy over time and suggested that a booster dose might be needed to restore high levels of protection.

Citation

Tartof SY et al. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study. Lancet 2021