Virus World

Background

Methods

Findings

Interpretation

The pause of use of the Moderna COVID-19 vaccine in Sweden will be extended beyond the initial December 1 end date, health officials announced. Unpublished data links the jab to heart inflammation.  Swedish health officials are extending the pause of Moderna's COVID-19 vaccine in young people over continued concerns that the shot causes rare heart inflammation cases.  The pause was initially supposed to last until December 1, but will now last beyond that to a date that is yet to be announced.  Sweden is one of four Nordic nations that restricted the use of the jab in young people this month, with a fifth, Norway, also discouraging younger males from getting the Moderna shot. Despite the concerns arising about the vaccine in Europe, the U.S. Food and Drug Administration (FDA) has stood by its authorization of the shots, and even authorized booster shots of the vaccine earlier this week.  Sweden paused usage of the Moderna COVID-19 shot in everyone born after 1990 earlier this month. The decision came after health officials viewed data that found the shots were causing cases of myocarditis in young people who got the vaccine. Sweden's Public Health Agency says that the unpublished data signals 'an increased risk of side effects such as inflammation of the heart muscle or the pericardium' - the double-walled sac containing the heart and the roots of the main vessels. It added: 'The risk of being affected is very small.' 

That data is still not publicly available. 

Denmark followed Sweden's lead, and restricted access to the vaccine to anyone under the age of 18 as well. The Finnish Institute for Health and Welfare said earlier this month that authorities won't give the vaccine to males under age 30, and they will be offered the Pfizer-BioNTech immunization instead, also citing the heart inflammation data.  Iceland also paused use of the vaccine citing concerns from the same data. Norway, another Nordic country, has not taken as drastic action as its neighbors, with health officials urging people under 30 to opt for the Pfizer vaccine instead.   Heart inflammation is also a symptom of many viral infections like COVID-19, though, and the likelihood of developing the inflammation after infection is much higher than it is after vaccination. Those conditions involve an inflammation of the heart or its lining.  On Thursday, data on the Moderna vaccines likelihood to cause heart inflammation was presented to a CDC advisory panel.  The presentation showed that males were much more likely to develop the condition than females - with those aged 18 to 24 at most risk, and the 25 to 29 group at risk as well. The second dose of the vaccine is also the one that usually causes the condition.  Myocarditis risk falls off after age 30, though. The data also shows that people who receive the Moderna shot are more likely to develop myocarditis.  For every one million doses of the Moderna shot administered, there are 13.3 more cases of myocarditis detected compared to every one million of the Pfizer jab. The reason for this is now yet known. The increased risk seems to appear for both males and females. 'The connection is especially clear when it comes to Moderna's vaccine Spikevax, especially after the second dose,' the Swedish health agency said.

A Moderna spokesperson said in an email last week that the company was aware of the decisions by regulators in Denmark and Sweden to pause the use of its vaccine in younger individuals because of the rare risk of myocarditis and or pericarditis.

'These are typically mild cases and individuals tend to recover within a short time following standard treatment and rest,' they wrote.  'The risk of myocarditis is substantially increased for those who contract COVID-19, and vaccination is the best way to protect against this.'  According to one U.S. study that has yet to undergo peer review, young males under agr 20 are up to six times more likely to develop myocarditis after contracting COVID-19 than those who have been vaccinated. Denmark said that, while it used the Pfizer vaccine as its main option for people aged 12 to 17 years, it had decided to pause giving the Moderna vaccine to people below 18 according to a 'precautionary principle'.  In June, the CDC issued a warning that young males were at an increased risk of myocarditis after receiving the vaccine. The label for both the Pfizer and Moderna vaccines were changed in the U.S. to reflect the warning, though usage was never paused. Cases of inflammation after vaccination are rare, though they do occur often enough to concern regulators. A recent study from Kaiser Permanente Southern California found that around seven out of every one million people that receive a two-shot COVID-19 vaccine will develop myocarditis. The same study found that 47.5 out of every one million Covid patients experience heart inflammation. While myocarditis will often resolve itself, it can be dangerous.  Heart inflammation can often lead to fatigue, shortness of breath and chest pain for patients. People with inflamed hearts are at a higher risk for heart failure, heart attacks and strokes. Attempting strenuous physical activity with an inflamed heart could also potentially lead to sudden cardiac arrest, or even death.

Two recent studies were unable to rule out that H1N1 ("swine flu") vaccination ("Pandemrix") and seasonal influenza vaccination given to pregnant women might be associated with autism-spectrum disorder in the offspring. Now, a large study by researchers at Karolinska Institutet in Sweden, published in the journal Annals of Internal Medicine, refutes any such association.  Autism spectrum disorder is a severe neurodevelopmental childhood disorder characterized by impaired communication, lack of social skills and repetitive behavior. The disease has its onset in childhood.  While some studies indicate that influenza vaccination during pregnancy protects against morbidity in both the woman and her offspring, the long-term risks of H1N1 vaccination during fetal life have not been examined in detail. However two recent studies were unable to rule out that offspring to women undergoing influenza or H1N1 influenza vaccination during pregnancy, and especially during the first trimester, were at increased risk of autism-spectrum disorder.  Researchers from Karolinska Institutet, linked vaccination data in pregnant women from seven Swedish healthcare regions in 2009-2010 to the Swedish Medical Birth Register and the Swedish National Patient Register to identify autism-spectrum disorder in the offspring.

Of the 39,726 vaccine-exposed children, 394 (cumulative incidence, 1.0%) had a diagnosis of autism-spectrum disorder during the six-year follow-up compared with 330 (1.1%) among 29,293 unexposed children. Adjusting for potential confounders, H1N1 vaccine exposure during fetal life was not associated with a later childhood diagnosis of autism-spectrum disorder (adjusted hazard ratio=0.95; 95%CI=0.81-1.12). Results were similar for vaccinations in the first pregnancy trimester.  “Our null findings are important since some people have suspected that vaccinations could cause autism, and the anti-vaccine movement seems to be growing in the Western world,” says lead author, Professor Jonas F Ludvigsson, pediatrician at Örebro University Hospital and professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “H1N1 vaccination has previously been linked to an increased risk of narcolepsy in young people, but vaccinating pregnant women does not seem to influence the risk of autism-spectrum disorder in the offspring,”  He continues: “Vaccination research has never been more important. Anticipating a vaccine against COVID-19, millions of pregnant women are likely to be offered such a vaccination. While our research group did not study COVID-19 vaccine effects, our research on H1N1 vaccination adds to the current knowledge about vaccines, pregnancy, and offspring disease in general.”

Original study in Annals Int. Medicine (Sept. 1 , 2020):

https://doi.org/10.7326/M20-0167 

Background: Whether vaccine effectiveness against Coronavirus disease 2019 (Covid-19) lasts longer than 6 months is unclear.

Methods: A retrospective cohort study was conducted using Swedish nationwide registries. The cohort comprised 842,974 pairs (N=1,684,958), including individuals vaccinated with 2 doses of ChAdOx1 nCoV-19, mRNA-1273, or BNT162b2, and matched unvaccinated individuals. Cases of symptomatic infection and severe Covid-19 (hospitalization or 30-day mortality after confirmed infection) were collected from 12 January to 4 October 2021. 

Findings: Vaccine effectiveness of BNT162b2 against infection waned progressively from 92% (95% CI, 92-93, P<0·001) at day 15-30 to 47% (95% CI, 39-55, P<0·001) at day 121-180, and from day 211 and onwards no effectiveness could be detected (23%; 95% CI, -2-41, P=0·07). The effectiveness waned slightly slower for mRNA-1273, being estimated to 59% (95% CI, 18-79) from day 181 and onwards. In contrast, effectiveness of ChAdOx1 nCoV-19 was generally lower and waned faster, with no effectiveness detected from day 121 and onwards (-19%, 95% CI, -97-28), whereas effectiveness from heterologous ChAdOx1 nCoV-19 / mRNA was maintained from 121 days and onwards (66%; 95% CI, 41-80). Overall, vaccine effectiveness was lower and waned faster among men and older individuals. For the outcome severe Covid-19, effectiveness waned from 89% (95% CI, 82-93, P<0·001) at day 15-30 to 42% (95% CI, -35-75, P=0·21) from day 181 and onwards, with sensitivity analyses showing notable waning among men, older frail individuals, and individuals with comorbidities.

Interpretation: Vaccine effectiveness against symptomatic Covid-19 infection wanes progressively over time across all subgroups, but at different rate according to type of vaccine, and faster for men and older frail individuals. The effectiveness against severe illness seems to remain high through 9 months, although not for men, older frail individuals, and individuals with comorbidities. This strengthens the evidence-based rationale for administration of a third booster dose.

Preprint available (Oct. 25, 2021) at:

https://dx.doi.org/10.2139/ssrn.3949410

Finland on Thursday paused the use of Moderna's COVID-19 vaccine for younger males due to reports of a rare cardiovascular side effect, joining Sweden and Denmark in limiting its use.  Mika Salminen, director of the Finnish health institute, said Finland would instead give Pfizer's vaccine to men born in 1991 and later. Finland offers shots to people aged 12 and over. "A Nordic study involving Finland, Sweden, Norway and Denmark found that men under the age of 30 who received Moderna Spikevax had a slightly higher risk than others of developing myocarditis," he said. Swedish and Danish health officials had announced on Wednesday they would pause the use of the Moderna vaccine for all young adults and children, citing the same unpublished study.  Norwegian health officials reiterated on Wednesday that they recommended men under the age of 30 opt for Pfizer's vaccine. The Finnish institute said the Nordic study would be published within a couple of weeks and preliminary data had been sent to the European Medicines Agency (EMA) for further assessment.

The EMA's safety committee concluded in July that such inflammatory heart conditions could occur in very rare cases following vaccination with Spikevax or the Pfizer/BioNTech Comirnaty jab, more often in younger men after the second dose. Regulators in the United States, EU and the World Health Organization have however stressed that the benefits of shots based on the mRNA technology used by Moderna and Pfizer-BioNTech in preventing COVID-19 continue to outweigh the risks. A Moderna spokesperson said late on Wednesday it was aware of the decisions by the Swedish and Danish regulators. "These are typically mild cases and individuals tend to recover within a short time following standard treatment and rest. The risk of myocarditis is substantially increased for those who contract COVID-19, and vaccination is the best way to protect against this." Italy's Health Minister Roberto Speranza told reporters Italy was not planning to suspend the Moderna vaccine and said European countries should work together more closely to coordinate better. "We have to trust international authorities, starting with EMA which is our reference agency and has expressed very clear judgments on the matter," he said.