Virus World

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 Unpublished data links the jab to heart inflammation.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 Sweden's Public Health Agency says that the unpublished data signals 'an increased risk of side effects such as inflammation of the heart muscle or the pericardium' - the double-walled sac containing the heart and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.

The U.S. Food and Drug Administration said on Wednesday it plans to move quickly to add a warning about rare cases of heart inflammation in adolescents and young adults to fact sheets for the Pfizer/BioNTech (PFE.N), and Moderna (MRNA.O) COVID-19 vaccines. U.S. Centers for Disease Control and Prevention (CDC) advisory groups, meeting to discuss reported cases of the heart condition after vaccination, found the inflammation in adolescents and young adults is likely linked to the vaccines, but that the benefits of the shots appeared to clearly outweigh the risk. Moderna shares closed down 4.2%, while Pfizer fell 1.4%. 

Health regulators in several countries have been investigating whether the Pfizer/BioNTech and Moderna shots using new mRNA technology present a risk and, if so, how serious. The CDC said that patients with heart inflammation following vaccination generally recover from the symptoms and do well. The U.S. Department of Health And Human Services, joined by leading U.S. doctors groups and public health officials, put out a statement underscoring that the vaccines are safe and effective and that the heart side effect is "extremely rare." "We strongly encourage everyone age 12 and older who are eligible to receive the vaccine under Emergency Use Authorization to get vaccinated," it said. Doctors and hospitals have been warned by the CDC to watch for symptoms of myocarditis or pericarditis, and the FDA warning will further raise awareness. Concerns about the more highly transmissible Delta coronavirus variant taking hold in the United States, and its impact on younger people, have added to the urgency to increase vaccinations even as the inoculation effort here has slowed considerably. read more The number of Americans receiving their first dose of COVID-19 vaccine is down about 85% since peaking in mid-April, and will likely fail to meet President Joe Biden's goal to have delivered at least one shot to 70% of adults by July 4. 

"Based on the available data, a warning statement in the factsheets for both healthcare providers and vaccine recipients and caregivers would be warranted," FDA official Doran Fink said at the advisory committee meeting. Fink, deputy director of the agency's vaccines division, said the FDA expects to move quickly to add the warning after the meeting concludes. The cases of heart inflammation appear to be notably higher in the week after the second vaccine dose and in males. The CDC identified 309 hospitalizations from the heart inflammation in persons under the age of 30, of which 295 have been discharged. Dr. Tom Shimabukuro, deputy director of the CDC's Immunization Safety Office, said in a presentation that data from one of the agency's safety monitoring systems - Vaccine Safety Datalink (VSD) – suggests a rate of 12.6 cases per million in the three weeks after the second shot in 12- to 39-year-olds. "We're observing this in the younger age groups, mainly in people in the teens and early 20s, and observing it more in males, compared to females," Shimabukuro said. "This effect largely kind of disappears once you get into these older age groups - individuals 50 and over." The CDC has been investigating heart inflammation cases mainly in young men for several months.

The Israeli health ministry earlier this month said it saw a possible link between such cases and Pfizer's COVID-19 vaccine. read more The CDC said it was still assessing the risk from the condition and did not specifically confirm a causal relationship between the vaccines and the heart issue. It did, however, say that a much-higher-than expected number of young men between the ages of 12 and 24 have experienced heart inflammation after their second vaccine dose. According to data from the U.S. Vaccine Adverse Event Reporting System (VAERS), there were 347 observed cases of heart inflammation in the week after the second vaccine dose in males aged 12 to 24. That compares with expectations of 12 or fewer cases for males in that age range based on U.S. population background incidence rates, the CDC said. Pfizer, whose vaccine has been authorized for use in Americans as young as 12, previously said it had not observed a higher rate of heart inflammation than would normally be expected in the general population. read more Moderna said it is aware of reports of heart inflammation cases following administration of mRNA vaccines. It said it is working with public health and regulatory authorities to assess the issue. Over 138 million Americans have so far been fully vaccinated with one of the two mRNA vaccines, according to CDC data as of Monday.

Infected cats and dogs experience serious symptoms, but it’s unclear whether the virus is causing them.  The variants of SARS-CoV-2 that keep emerging aren’t just a human problem. Two reports released this week have found the first evidence that dogs and cats can become infected by B.1.1.7, a recent variant of the pandemic coronavirus that transmits more readily between people and also appears more lethal in them. The finds mark the first time one of the several major variants of concern has been seen outside of humans. B.1.1.7 was first identified in the United Kingdom and that’s where some of the variant-infected pets were found. The U.K. animals suffered myocarditis—an inflammation of the heart tissue that, in serious cases, can cause heart failure. But the reports offer no proof that the SARS-CoV-2 variant is responsible, nor that it’s more transmissible or dangerous in animals. “It’s an interesting hypothesis, but there’s no evidence that the virus is causing these problems,” says Scott Weese, a veterinarian at the University of Guelph’s Ontario Veterinary College who specializes in emerging infectious diseases.

Since December 2020, scientists have identified multiple variants of concern that appear more transmissible or are able to evade some immune response. B.1.351, for example, was first detected in South Africa, and a strain called P.1 was first found in Brazil. The B.1.1.7 variant drew early attention because of its rapid rise in the United Kingdom; it now comprises about 95% of all new infections there. So far the impact of these variants on pets has been unclear. Though there have now been more than 120 million cases of COVID-19 around the world, only a handful of pets have tested positive for the original SARS-CoV-2—probably because no one is testing them. Infected pets appear to have symptoms ranging from mild to nonexistent, and infectious disease experts say companion animals are likely playing little, if any, role in spreading the coronavirus to people. The new variants might change that equation, says Eric Leroy, a virologist at the French National Research Institute for Sustainable Development who specializes in zoonotic diseases. In one of the new studies, he and colleagues analyzed pets admitted to the cardiology unit of the Ralph Veterinary Referral Centre in the outskirts of London. The hospital had noticed a sharp uptick in the number of dogs and cats presenting with myocarditis: From December 2020 to February, the incidence of the condition jumped from 1.4% to 12.8%. That coincided with a surge of the B.1.1.7 variant in the United Kingdom. So the team looked at 11 pets: eight cats and three dogs. None of the animals had a previous history of heart disease, yet all had come down with symptoms ranging from lethargy and loss of appetite to rapid breathing and fainting. Lab tests revealed cardiac abnormalities, including irregular heartbeats and fluid in the lungs, all symptoms seen in human cases of COVID-19. Seven of the animals got polymerase chain reaction tests, and three came back positive for SARS-CoV-2—all with the B.1.1.7 variant, team reported yesterday on the preprint server bioRxiv. SARS-CoV-2 antibody tests on four of the other animals picked up evidence that two of them had been infected with the virus.

Earlier this week, researchers at Texas A&M University detected the B.1.1.7 variant in a cat and a dog from the same home in the state’s Brazos county. The Texas owner was diagnosed with COVID-19, and owners of five of the 11 U.K. pets tested positive for SARS-CoV-2—all before their animals developed symptoms. The Texas pets showed no symptoms at the time they were tested, though they both began to sneeze several weeks later. All of the U.S. and U.K. animals have since recovered, though one of the U.K. cats relapsed and had to be euthanized. Leroy says it’s unclear whether B.1.1.7 is more transmissible than the original strain between humans and animals, or vice versa. It’s “impossible to say” that pets infected with B.1.1.7 might play a more serious role in the pandemic, he adds, but “this hypothesis has to be seriously raised.” Shelley Rankin, a microbiologist at the University of Pennsylvania School of Veterinary Medicine, points out that the researchers have shown only a correlation between B.1.1.7 infection and myocarditis, and that they didn’t rule out other causes for the condition. “There is no evidence pets were sick because of the virus,” she says. Weese agrees that neither the Texas nor U.K. findings should sound any alarms about pets endangering their owners. “The risk of them being a source of infection remains very low,” he says. “If my dog has it, he probably got it from me. And I’m much more likely to infect my family and neighbors before he does.” Still, he says scientists and veterinarians should do studies on what role, if any, SARS-CoV-2 and its variants play in myocarditis among pets. There is evidence that the virus can cause the condition in people, Weese notes, so it’s worth exploring in companion animals. “It might be real,” he says, “but there’s no reason for people to freak out right now.”

Research cites posted in bioRxiv (March 18, 2021):

https://doi.org/10.1101/2021.03.18.435945

BACKGROUND

Reports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored.

METHODS

We searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer–BioNTech). The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention. We abstracted the presentation, clinical course, and outcome from the patient’s electronic health record. We performed a Kaplan–Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose.

RESULTS

Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock. After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge. Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge. Of these patients, 5 underwent subsequent testing that revealed normal heart function.

CONCLUSIONS

Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.)

Published in NEJM (Oct. 6, 2021):

https://doi.org/10.1056/NEJMoa2110737 

The U.S. Centers for Disease Control and Prevention (CDC) has not found a link between heart inflammation and COVID-19 vaccines, the agency's Director Rochelle Walensky said on Tuesday.  "We have not seen a signal and we've actually looked intentionally for the signal in the over 200 million doses we've given," Walensky said in a press briefing. She said the CDC is in touch with the U.S. Department of Defense over its investigation of 14 cases of heart inflammation or myocarditis among people who were vaccinated through the military's health services. "It is a different demographic than we normally see and we will be working with DOD to understand what is happening in those 14 cases," Walensky said.  The U.S. vaccination program targeted older Americans first, and the concerns over myocarditis are in younger vaccinated people. At least 17.9 million people in the United States under the age of 30 have received one COVID-19 shot, according to CDC data.

Israel's Health Ministry said on Sunday it was examining a small number of cases of heart inflammation in people who had received Pfizer's (PFE.N) COVID-19 vaccine, though it had not yet drawn any conclusions. Most of the cases in Israel were reported among people up to age 30. read more Pfizer has said it has not observed a higher rate of the condition than would normally be expected in the general population. COVID-19 itself has been linked to cases of myocarditis in some patients.