Virus World

Question  Are Ad26.COV2.S (Janssen), BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccines associated with Guillain-Barré syndrome (GBS) within 21 or 42 days after vaccination?

Findings  This cohort study of 487 651 785 COVID-19 vaccine doses found that in observed-to-expected analyses, the observed number of GBS reports was higher than expected based on background rates within 21 and 42 days after vaccination for Ad26.COV2.S but not BNT162b2 or mRNA-1273. GBS reporting rates within 21 and 42 days of Ad26.COV2.S vaccination were 9 to 12 times higher than after BNT162b2 or mRNA-1273 vaccination.

Meaning  These findings suggest that Ad26.COV2.S vaccination was associated with GBS and that GBS after BNT162b2 and mRNA-1273 may represent background incidence.

Importance  Because of historical associations between vaccines and Guillain-Barré syndrome (GBS), the condition was a prespecified adverse event of special interest for COVID-19 vaccine monitoring.

Objective  To evaluate GBS reports to the Vaccine Adverse Event Reporting System (VAERS) and compare reporting patterns within 21 and 42 days after vaccination with Ad26.COV2.S (Janssen), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) COVID-19 vaccines.

Design, Setting, and Participants  This retrospective cohort study was conducted using US VAERS reports submitted during December 2020 to January 2022. GBS case reports verified as meeting the Brighton Collaboration case definition for GBS in US adults after COVID-19 vaccination were included.

Exposures  Receipt of the Ad26.COV2.S, BNT162b2, or mRNA-1273 COVID-19 vaccine.

Main Outcomes and Measures  Descriptive analyses of GBS case were conducted. GBS reporting rates within 21 and 42 days after Ad26.COV2.S, BNT162b2, or mRNA-1273 vaccination based on doses administered were calculated. Reporting rate ratios (RRRs) after receipt of Ad26.COV2.S vs BNT162b2 or mRNA-1273 within 21- and 42-day postvaccination intervals were calculated. Observed-to-expected (OE) ratios were estimated using published GBS background rates.

Results  Among 487 651 785 COVID-19 vaccine doses, 17 944 515 doses (3.7%) were Ad26.COV2.S, 266 859 784 doses (54.7%) were BNT162b2, and 202 847 486 doses (41.6%) were mRNA-1273. Of 295 verified reports of individuals with GBS identified after COVID-19 vaccination (12 Asian [4.1%], 18 Black [6.1%], and 193 White [65.4%]; 17 Hispanic [5.8%]; 169 males [57.3%]; median [IQR] age, 59.0 [46.0-68.0] years), 275 reports (93.2%) documented hospitalization. There were 209 and 253 reports of GBS that occurred within 21 days and 42 days of vaccination, respectively. Within 21 days of vaccination, GBS reporting rates per 1 000 000 doses were 3.29 for Ad26.COV.2, 0.29 for BNT162b2, and 0.35 for mRNA-1273 administered; within 42 days of vaccination, they were 4.07 for Ad26.COV.2, 0.34 for BNT162b2, and 0.44 for mRNA-1273. GBS was more frequently reported within 21 days after Ad26.COV2.S than after BNT162b2 (RRR = 11.40; 95% CI, 8.11-15.99) or mRNA-1273 (RRR = 9.26; 95% CI, 6.57-13.07) vaccination; similar findings were observed within 42 days after vaccination (BNT162b2: RRR = 12.06; 95% CI, 8.86-16.43; mRNA-1273: RRR = 9.27; 95% CI, 6.80-12.63). OE ratios were 3.79 (95% CI, 2.88-4.88) for 21-day and 2.34 (95% CI, 1.83-2.94) for 42-day intervals after Ad26.COV2.S vaccination and less than 1 (not significant) after BNT162b2 and mRNA-1273 vaccination within both postvaccination periods.

Conclusions and Relevance  This study found disproportionate reporting and imbalances after Ad26.COV2.S vaccination, suggesting that Ad26.COV2.S vaccination was associated with increased risk for GBS. No associations between mRNA COVID-19 vaccines and risk of GBS were observed.

Comparison of the immune response to four prominent COVID-19 vaccines is among the most thorough so far, authors say.  A rare head-to-head comparison shows that the COVID-19 vaccines made by Pfizer and Moderna outperform those from Johnson & Johnson and Novavax1. The data also provide a finely detailed picture of the immune protection that each vaccine offers — information that could be useful for designing future vaccines. The research was posted on the preprint server bioRxiv on 21 March. It has not yet been peer reviewed. The study assessed the 4 vaccines using 14 metrics, including levels of several types of immune cell such as T cells and B cells, as well as immune molecules called neutralizing antibodies. Such investigations are sorely needed to sort through the flood of COVID-19 vaccines in the research pipeline and on the market, researchers say. “It’s a really nice analysis by premier immunologists that builds upon what has been previously shown,” says Robert Seder, an immunologist at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.  Previous comparisons of COVID-19 vaccines have often brought together data from different studies, which might have been conducted with slightly varying laboratory techniques. For the latest study, by contrast, researchers applied the same techniques across all the vaccines they investigated. “When you try to compare [vaccine data] between different papers, which is what many of us have been doing for over a year now, you get apples to oranges comparisons, and you can be way off,” says Shane Crotty, an immunologist at La Jolla Institute for Immunology in California and a co-author of the preprint. The four vaccines that Crotty and his co-authors examined fall into three classes. The jabs made by Moderna in Cambridge, Massachusetts, and by Pfizer in New York City and BioNTech in Mainz, Germany, are both based on messenger RNA. Johnson & Johnson (J&J) of New Brunswick, New Jersey, has produced a ‘viral vector’ vaccine that uses a harmless virus to deliver SARS-CoV-2 genetic material into host cells. The vaccine made by Novavax in Gaithersburg, Maryland, contains pieces of the SARS-CoV-2 spike protein.

Strengths and weaknesses

Antibody levels induced by two doses of Pfizer’s or Moderna’s mRNA vaccine tended to wane substantially over six months. By contrast, antibody levels from J&J’s one-shot vaccine were stable or even increased over time. But antibody levels measured six months after vaccination with the J&J jab were still lower than those observed six months after vaccination with an mRNA vaccine. Novavax’s two-shot regimen induced antibody responses on a par with those to the mRNA vaccines. However, after the Novavax jab, levels of CD8+ T cells, which destroy infected cells, were low to undetectable, whereas the other three vaccines performed well in this metric. These results generally support the findings of previous studies. But the latest research offers a more extensive analysis of the immune system’s response than do earlier studies, and uses an apples-to-apples approach. 

No losers

“This is not meant to proclaim winners and losers,” says study co-author Alessandro Sette, an immunologist at La Jolla. Instead, the study is meant to “provide a comprehensive evaluation of the different variables”, he says. Novavax has received authorization for its vaccine in 38 countries. The vaccines made by Moderna, Pfizer and J&J have all received wide authorization globally. One caveat is that the study looked at the effects of the Novavax jab in only 12 people. It examined the other three vaccines in 30 volunteers each. Seder notes that the analysis considers the effects of only a two-dose regimen of the mRNA vaccines. It does not consider the protection provided by boosters, because the authors began the work in late 2020, before a third shot was recommended by health authorities. Crotty, Sette and their colleagues are now conducting a similar head-to-head study that includes mRNA boosters.

Cited research available at bioRxiv (March 21, 2022):

https://doi.org/10.1101/2022.03.18.484953  

Two reports released Thursday show that people who get booster doses of Johnson & Johnson's Janssen vaccine are well protected against severe disease and hospitalization from the Omicron variant of coronavirus, the company said.  Researchers said the findings indicate that most of the Covid-19 vaccines will protect people against the worst outcomes from infection -- and show some of the emphasis on how the various vaccines affect immune system components called antibodies may be misleading. One real-life study from South Africa showed vaccine effectiveness against hospitalization from Covid-19 rose to 85% after a booster dose of the J&J vaccine, even after the Omicron variant was circulating. And a lab-based study in the US indicated the vaccine stimulates a strong immune response from cells known as T-cells, which protect people against severe disease even if they don't block the virus entirely from infecting the body. Results from both studies were released by the company in a statement but the South African team posted findings online as a preprint and the results are being submitted to a peer-reviewed journal, the researchers said. Linda-Gail Bekker of the University of Cape Town and other researchers including a team at the South African Medical Research Council helped examine the results of an ongoing study of the J&J vaccine there. They looked at results from 69,000 health care workers. "We observed that vaccine effectiveness for hospitalization increased over time since booster dose, from 63% to 84% and then 85%," they wrote. The booster was given between six and nine months after the first dose of the vaccine, also known as Ad26.COV.2. 

"This data is important given the increased reliance on the Ad26.COV.2 vaccine in Africa," they wrote. "Even before you factor in the increased infectiousness of Omicron, we have to remember that healthcare workers on the frontlines are at a greatly increased risk of being affected by COVID-19 in the first place," Dr. Glenda Gray, president and CEO of the SAMRC, said in a statement. "We are therefore encouraged to see that boosting with the Johnson & Johnson COVID-19 vaccine regimen provides strong protection in a challenging real-world setting where there is an elevated risk of exposure -- not just to COVID-19, but to the highly transmissible Omicron variant." Separately, Dr. Dan Barouch and colleagues at the Beth Israel Deaconess Medical Center in Boston looked at blood taken from 65 vaccinated volunteers and tested it against the Omicron variant. They looked at both antibodies -- the first line of defense against infection -- and T-cells. Using the J&J vaccine as a booster for people who originally got two doses of Pfizer/BioNTech's vaccine generated a 41-fold increase in neutralizing antibodies and a five-fold increase in the CD8 killer T cells that destroy cells infected by the virus. That stops the virus from replicating and spreading. Boosting with the Pfizer vaccine generated a 17-fold increase in neutralizing antibodies and a 1.4-fold increase in CD8 T cells four weeks later, they found. "These data are important and these data are hopeful," Barouch told CNN. They indicate that all Covid-19 vaccines can protect people from severe disease and death, even from the Omicron variant with all its mutations, he said. "It has substantial global significance that goes well beyond J&J and goes well beyond South Africa," he added. South African researchers reported in the New England Journal of Medicine on Wednesday that protection against hospitalization from two doses of Pfizer's vaccine fell to about 70% when Omicron was circulating compared to 93% a few weeks earlier, when Delta was dominant in South Africa. Barouch said many studies look only at antibodies, which can stop the virus from infecting cells at all. He said the T-cell response, which is trickier to measure, is important in providing long-term protection from severe disease. 

"There's confusion -- not just in the media and the public but also among doctors and scientists -- that only neutralizing antibodies equate with protection, and that's just not true," he said. "What we are seeing with 70% protection with Pfizer and now 85% protection with J&J -- which is occurring at very low levels of neutralizing antibodies -- strongly suggests T-cell responses are important in the protection that we are seeing." When viruses infect cells, they take over their internal machinery and turn them into little virus factories. While antibodies attach to the outside of viruses and stop them from ever docking to cells, T-cells seek out and destroy cells after they are infected. This may not completely stop infection, but it elps stop virus from spreading and causing severe illness. Dr. Mathai Mammen, global head of research and development at J&J's Janssen vaccine arm, agreed. "We believe that the protection could be due to the robust T-cell responses induced by the Johnson & Johnson COVID-19 vaccine. Furthermore, these data suggest that Omicron is not affecting the T-cell responses generated by our vaccine," he said in a statement. The findings may also reassure the millions of people who got the Janssen vaccine. Earlier this month, the US Centers for Disease Control and Prevention endorsed the Moderna and Pfizer/BioNTech vaccines over J&J's, saying the two mRNA vaccines worked better and more safely than J&J's, which is linked with a rare type of blood clotting event. The mRNA vaccines use a newer technology that involves genetic material called messenger RNA, carried into the body by simple fatty compounds called lipids. J&J's vaccine is an adenoviral vector vaccine, which uses a crippled common cold virus to carry the genetic instructions into the body. J&J said the vaccine's design is deliberately meant to elicit a robust T-cell response.

Johnshon & Johnson Press Release (Dec. 30, 20210:

https://www.jnj.com/johnson-johnson-covid-19-vaccine-demonstrates-85-percent-effectiveness-against-hospitalization-in-south-africa-when-omicron-was-dominant 

Vaccine advisers to the US Food and Drug Administration voted unanimously Friday to recommend a booster dose of Johnson & Johnson's vaccine at least two months after people get the first dose. The FDA's Vaccines and Related Biological Products Advisory Committee voted 19-0 to recommend the extra dose for all recipients of the J&J Janssen vaccine, 18 and older. They asked to simplify the original question being posed by the FDA, which had asked the committee to say whether the data showed that waiting six months or longer after getting the first shot would provide an even stronger immune response. The FDA will now consider the committee's advice. Then the US Centers for Disease Control and Prevention's vaccine advisers will be asked to consider it.  Johnson & Johnson says studies have shown boosting at two or six months can bring that effectiveness up to 94% and it says its effectiveness does not wane over time in the same way that effectiveness from Pfizer's vaccine does. But the Johnson & Johnson vaccine has not been shown to be as protective as either the Pfizer or Moderna vaccines, noted VRBPAC chair Dr. Arnold Monto, a professor of public health and epidemiology at the University of Michigan. "So there is some urgency here to do something," he told the meeting. And the CDC's Dr. Amanda Cohn told the meeting that various studies suggested real-world efficacy of J&J's vaccine was anywhere between 50% and 68%.

"Regardless of whether or not there been waning or this is the true effectiveness after a single dose, the effectiveness or protection of a single dose of the J&J vaccine is not equivalent to protection at this time with either two doses of an mRNA vaccine and certainly not in those groups who have now been authorized to receive a booster dose of an mRNA vaccine," Cohn said.  Members of the committee said while there was not much data to show whether the efficacy of the Janssen vaccine was waning -- or was strong to begin with -- they agreed people should be given the opportunity for a booster. "I would say I agree a second dose booster is needed to boost immunity back to the 90-plus range," Dr. Archana Chatterjee, a pediatric infectious diseases expert at Rosalind Franklin University in Chicago, said before the vote. The FDA has already given EUA to a booster for Pfizer's vaccine for people who are six months out from their first two shots who are also either 65 or older or who are at least 18 and have a higher risk of severe disease because of pre-existing conditions or because of work or living conditions. And Americans are already flocking to get those boosters. Data from the US Centers for Disease Control and Prevention show close to 5% of fully vaccinated people -- about 9 million people -- have received booster shots.

On Thursday, VRBPAC members voted unanimously to recommend booster doses of Moderna's vaccine to the same groups. If the FDA gives emergency use authorization to Moderna or Johnson & Johnson boosters, CDC vaccine advisers will meet to discuss which groups to recommend them to. Typically, shots can be administered once the CDC director signs off on the recommendation. CDC's Advisory Committee on Immunization Practices is scheduled to discuss boosters on October 21.

Vaccine effectiveness against COVID-19 hospitalization among U.S. adults without immunocompromising conditions was highest for the Moderna vaccine compared with the other two available COVID-19 vaccines, researchers reported in MMWR. “Three COVID-19 vaccines are authorized or approved for use among adults in the United States,” Wesley H. Self, MD, associate professor at the Vanderbilt University School of Medicine, and colleagues wrote. “Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for a specific vaccine.” To better assess vaccine effectiveness (VE) of the three available COVID-19 vaccines in the U.S. in preventing COVID-19 hospitalization, Self and colleagues conducted a case-control analysis among 3,689 adults aged 18 years and older who were hospitalized at 21 U.S. hospitals between March 11 and Aug. 15, 2021.

According to the study, an additional analysis compared serum antibody levels to SARS-CoV-2 among 100 healthy volunteers enrolled at three hospitals 2 to 6 weeks after full vaccination with the Moderna, Pfizer-BioNTech or Johnson & Johnson vaccines. Overall, the study demonstrated that VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% CI, 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI, 85%-91%), whereas VE for both of the messenger RNA vaccines was higher than that of the Johnson & Johnson vaccine (71%; 95% CI, 56%-81%). Additionally, the study showed that protection from the Pfizer-BioNTech vaccine declined 4 months after vaccination. Researchers added that post-vaccination anti-spike IgG and anti-receptor binding domain IgG levels were significantly lower in participants who were vaccinated with the Johnson & Johnson vaccine compared with the Moderna or Pfizer-BioNTech vaccines.

Research cited published in MMWR (Sept.17, 2021):

 http://dx.doi.org/10.15585/mmwr.mm7038e1 

People who received a booster six to eight months after their initial Johnson & Johnson shots saw antibodies increase nine-fold higher than 28 days after the first shot, the comapany said. The data comes from two Phase 2 studies conducted in the United States and Europe, the company said in a statement. Some of the 2,000 or so people in the studies got booster doses six months after their first doses of J&J's Janssen vaccine.  "New interim data from these studies demonstrate that a booster dose of the Johnson & Johnson COVID-19 vaccine generated a rapid and robust increase in spike-binding antibodies, nine-fold higher than 28 days after the primary single-dose vaccination," the company said in its statement.  "We have established that a single shot of our COVID-19 vaccine generates strong and robust immune responses that are durable and persistent through eight months. With these new data, we also see that a booster dose of the Johnson & Johnson COVID-19 vaccine further increases antibody responses among study participants who had previously received our vaccine," Dr. Mathai Mammen, global head of research and development for Janssen, said in a statement. J&J said it was in discussions with the US Food and Drug Administration, US Centers for Disease Control and Prevention, European Medicines Agency, World Health Organization and other health authorities about the need for offering a booster dose of the Janssen vaccine. "We look forward to discussing with public health officials a potential strategy for our Johnson & Johnson COVID-19 vaccine, boosting eight months or longer after the primary single-dose vaccination," Mammen added.

Federal regulators concluded that the risk of developing the syndrome was low, and that the benefits of the vaccine still strongly outweigh it.  The Food and Drug Administration is planning to warn that Johnson & Johnson’s coronavirus vaccine can lead to an increased risk of a rare neurological condition known as Guillain–Barré syndrome, another setback for a vaccine that has largely been sidelined in the United States. Although regulators have found that the chances of developing the condition are low, they appear to be three to five times higher among recipients of the Johnson & Johnson vaccine than among the general population in the United States, according to people familiar with the decision. Federal officials have identified roughly 100 suspected cases of Guillain-Barré disease among recipients of the Johnson & Johnson shot through a federal monitoring system that relies on patients and health care providers to report adverse effects of vaccines. The reports are considered preliminary. Most people who develop the condition recover. The F.D.A. has concluded that the benefits of the vaccine in preventing severe disease or death from the coronavirus still very much outweigh any danger, but it plans to include the proviso in fact sheets about the drug for providers and patients.

“It’s not surprising to find these types of adverse events associated with vaccination,” said Dr. Luciana Borio, a former acting chief scientist at the F.D.A. under President Barack Obama. The data collected so far by the F.D.A., she added, suggested that the vaccine’s benefits “continue to vastly outweigh the risks.” In a statement released Monday, the Centers for Disease Control and Prevention said the cases have largely been reported about two weeks after vaccination and mostly in males, many aged 50 years and older.  The database reports indicate that symptoms of Guillain-Barré developed within about three weeks of vaccination. One recipient, a 57-year-old man from Delaware who had suffered both a heart attack and a stroke within the last four years, died in early April after he was vaccinated and developed Guillain-Barré syndrome, according to a report filed to the database.  The Biden administration is expected to announce the new warning as early as Tuesday. European regulators may soon follow suit. No link has been found between Guillain-Barré syndrome and the coronavirus vaccines developed by Pfizer-BioNTech or Moderna, the other two federally authorized manufacturers. Those rely on a different technology. Nearly 13 million people in the United States have received Johnson & Johnson’s shot, but 92 percent of Americans who have been fully vaccinated received shots developed by Pfizer-BioNTech or Moderna. Even though it requires only one dose, Johnson & Johnson’s vaccine has been marginalized by manufacturing delays and a 10-day pause while investigators studied whether it was linked to a rare but serious blood clotting disorder in women. That investigation also resulted in a warning added to the fact sheet.

The new safety concern comes at a precipitous moment in the nation’s fight against Covid-19. The pace of vaccinations has slowed considerably just as a new, more contagious variant called Delta is spreading fast in under-vaccinated areas. Federal health officials are worried that the news could make some people even more hesitant to accept the vaccines developed by Pfizer-BioNTech or Moderna, even though well over 100 million people have received those vaccines, according to the Centers for Disease Control and Prevention.  Almost one-third of the nation’s adults remain unvaccinated. The Biden administration has shifted away from relying on mass vaccination sites and is now enlisting community workers in door-to-door campaigns, supplying doses to primary care doctors and expanding mobile clinics in an attempt to convince the unvaccinated to accept shots. Johnson & Johnson’s vaccine has played a minor role in the nation’s inoculation campaign partly because the Baltimore plant that was supposed to supply most of the doses to the United States has been shut down for three months because of regulatory violations. The factory, operated by Emergent BioSolutions, a subcontractor, has been forced to throw out the equivalent of 75 million doses because of suspected contamination, severely delaying deliveries to the federal government. Demand for the shot also plummeted after the April safety pause. At that time, 15 women in the United States and Europe who had received the Johnson & Johnson shot had been diagnosed with the disorder. Three had died. Regulators ultimately decided that the risk was remote and far outweighed by the benefits. They attached a warning to the drug and cleared it for use, but state officials have said that the perception that the vaccine might be unsafe hurt it. Alex Gorsky, Johnson & Johnson’s chief executive, said last month that he was still hopeful that the vaccine, which has been used in 27 countries so far, would help contain the pandemic overseas. The company has promised up to 400 million doses to the African Union. Separately, Covax, the global vaccine-sharing program, is supposed to receive hundreds of millions of doses. Studies have shown that the Johnson & Johnson shot protects people against more contagious virus variants, including the Delta variant, and is highly effective at preventing severe Covid-19, hospitalizations and death.

The F.D.A. shares jurisdiction over vaccines with the Centers for Disease Control and Prevention but is responsible for issuing product warnings. The Guillain-Barré cases are expected to be discussed in an upcoming meeting of a committee of outside experts who advise the C.D.C. The F.D.A. has also attached a warning to the Pfizer-BioNTech and Moderna vaccines, but some health officials described that as less serious than the warnings about Johnson & Johnson. Last month, the agency warned about an increased risk of inflammation of the heart or the tissue surrounding it — diseases known as myocarditis and pericarditis — particularly among adolescents and young adults who had received Pfizer-BioNTech or Moderna shots. But the C.D.C. said in most cases, symptoms promptly improved after simple rest or medication. The Guillian-Barré syndrome is more likely to result in medical intervention, officials said. It occurs when the immune system damages nerve cells, causing muscle weakness and occasional paralysis, according to the F.D.A. Several thousand people — or roughly 10 out of every one million residents — develop the condition every year in the United States. Most fully recover from even the most severe symptoms, but in rare cases patients can suffer near-total paralysis. The suspected cases were reported in the Vaccine Adverse Event Reporting System, or VAERS, a 30-year-old federal monitoring system. So far, researchers have not identified any particular demographic pattern, but many of the reports in the publicly available database indicate that the patients were hospitalized. Guillain-Barré syndrome has also been linked to other vaccines. The Centers for Disease Control and Prevention has said that flu vaccines, including the 1976 swine flu vaccine, led to a small increased risk of contracting the syndrome, although some studies suggested that people are more likely to develop Guillain-Barré from the flu itself than from flu vaccines. Earlier this year, the F.D.A. warned that GlaxoSmithKline’s shingles vaccine, Shingrix, could also increase the risk of the disease. Only about five million people in the U.S. have taken Johnson & Johnson’s shot since the April pause was lifted. Millions of doses that have been distributed by the federal government are sitting unused and will expire this summer....

Some people who received the Johnson & Johnson Covid-19 shot in the U.S. are seeking out added doses of a messenger-RNA vaccine, fearing their initial inoculation won’t protect them from the virus. Demand for the one-and-done J&J shot has suffered in part due to the perception that it’s inferior to the two-dose mRNA vaccines that showed higher efficacy in clinical trials. But it is unclear if mixing vaccines will safely increase protection, and there are fresh signs that J&J’s shot is a strong shield against variants. Last month, the first suggestion that mixing may be helpful came in a study that found combining the Pfizer Inc.-BioNTech SE vaccine with AstraZeneca Plc’s shot, which is based on adenovirus vector technology similar to J&J’s vaccine, can provide a formidable shield against infection. The U.S. Centers for Disease Control and Prevention recommends people don’t mix vaccines until robust clinical data validates the benefit and quells concerns about risks. Anthony Fauci, the top federal infectious-disease expert, said at a Thursday White House briefing that there’s “no real fundamental scientific reason to do that right now.” But anxiety about the highly transmissible delta variant that’s sweeping across the U.S., along with emerging data on the mix-and-match approach, has led some people, including pharmaceutical executives and the immunocompromised, to act.

Terri Leslie is a case in point. She considers herself risk-averse when it comes to Covid. She has spent most of the pandemic in quarantine, ordering groceries online and avoiding gatherings. To get the message across, she recently bought a T-shirt, stating in capital letters, “When this virus is over, I still want some of you to stay away from me.” But Leslie was willing to try the mix-and-match strategy. The Mills River, North Carolina, resident jumped at the opportunity to get the J&J shot in March when a hospital called her and offered it. Since then, she’s lamented not receiving a mRNA vaccine. Leslie, 61, takes a rheumatoid arthritis medication that’s left her immune-suppressed, and she was worried about contracting the virus.  “I don’t want to live in fear of getting sick,” Leslie said. On Tuesday, Leslie decided to take matters into her own hands. Like others before her, she’d been scrolling through tweets from biochemists, virologists and infectious-disease experts advocating that J&J recipients boost their immunity with an mRNA vaccine. Sure, there was backlash on Twitter. But with the blessing of her pediatrician husband, Leslie went to her primary care doctor and received a prescription for the Pfizer vaccine. The pharmacist hesitated when presented with the prescription, she said, and stepped aside to research the issue. His comment when he returned, according to Leslie: “We’re flying in the dark.” But he then administered the first dose, and she is set to get her second in three weeks. “Whatever we can do to protect ourselves, we must do it before it’s too late,” Leslie said. “Nobody is wearing masks anymore.”  U.S. health agencies are monitoring the phenomenon. CDC Director Rochelle Walensky said on a podcast with Andy Slavitt, a former adviser to the Biden administration on the virus response, that she’s aware of the concerns about the J&J vaccine. “Some people have said, ‘I’m just not going to tell anyone and I’m going to get an mRNA vaccine,’” she said. “We don’t have a huge amount of data on the safety or the side effect profile of getting the mRNA vaccine after Johnson & Johnson, or really the effectiveness of that approach.” Still, when pressed by Slavitt, Walensky said, “It’s probably safe. But they are generating data to inform us one way or another.” That data could come from a National Institutes of Health trial launched in June in which fully vaccinated adults will receive booster doses of different Covid-19 vaccines. Similar studies are being conducted outside the U.S. as well, with the idea that mixing vaccines may not only be able to strengthen immunity in some people, but could could help overcome shortages in areas where it may be difficult to reliably obtain vaccine supplies. “The situation right now is that people locally will be making those kinds of decisions, but you should only be making a formal recommendation based on clinical data,” said Fauci, the director of the National Institute of Allergy and Infectious Diseases, at the White House briefing. “When those data become available, you will see recommendations change according to the data.”

Delta Performance

J&J’s vaccine hasn’t yet produced efficacy data against the delta variant that was first identified in India. But on Thursday J&J said its vaccine showed strong neutralizing antibodies for at least eight months against all variants including delta in a small number of clinical-trial participants. Company officials dismissed the idea that their shot needed to be supplemented with another vaccine. “There’s no reason or indication to do that to get full protection for severe disease, hospitalization or death,” said Paul Stoffels, J&J’s chief scientific officer, in an interview. “That has been clearly studied, and I wouldn’t recommend any other approach until the data have been generated. At the moment it’s all speculation.” The company reported that the vaccine prompted a more robust immune response against the delta variant than even against the beta variant that was first detected in South Africa. Only a single shot of the J&J vaccine is currently needed to shield against variants, Stoffels said, noting that J&J will evaluate boosting protection with its own formulation down the line. Still, assurances from U.S. health officials and J&J that the vaccine continues to work haven’t stopped doctors and patients from theorizing about the potential benefits of mixing shots. Interchanging vaccines of the same type -- such as those made using mRNA technology -- isn’t likely to provide an advantage over a standard two-dose course of one of them. But mixing vaccines that use different platforms, through a process known as heterologous prime-boosting, could offer a benefit, according to some scientists. Different vaccine platforms could activate the immune system in different ways, they suggest, and mixing them up might generate immune responses that stimulate each other at a granular level.

Three Concessions

Paul Sax, clinical director of the division of infectious diseases at Brigham and Women’s Hospital in Boston, continues to be approached by his peers and patients on what J&J recipients should do to bolster protection. When advising them, he makes three concessions: First, J&J’s shot is less effective than the mRNA doses. Second, data from the U.K. show those most protected from the delta variant got two doses. And third, a study suggested you can boost an adenovirus-based vaccine like J&J’s with an mRNA version and see a good response. After being presented with that information, one of Sax’s patients chose to move forward with a J&J-plus-mRNA regimen. Another decided to wait to see what happens over the summer since so few virus cases are currently being reported in New England. “There’s a very good argument to be made that it’s worth doing, but since we don’t have any definitive data yet I can understand why it’s not formally in the guidelines,” Sax said.

Unvaccinated America

The Biden administration, meanwhile, is focused on increasing the number of people getting shots in unvaccinated pockets of the country. The gap between the most vaccinated and least vaccinated places in the U.S. has widened despite efforts to convince more Americans to get a Covid-19 shot. Health-care providers in areas where interest is low see a significant role for the J&J vaccine. It can be stored in a refrigerator for long periods, making it a useful tool for pop-up clinics and mobile vaccine units. And because it’s a single shot, it’s an appealing option to those who can’t take multiple days off work. “The public health goal is to prevent hospitalization, severe disease, and death, and so far, Johnson & Johnson has held up as 100% effective against those things,” said Shereef Elnahal, the chief executive officer of University Hospital in Newark, New Jersey. “Our main focus now should be to get J&J to more people in the community. We shouldn’t lose focus on that.”

— With assistance by Angelica LaVito, Shira Stein, and Jeannie Baumann

In light of the massive and rapid vaccination campaign against COVID-19, continuous real-world effectiveness and safety assessment of the FDA-authorized vaccines is critical to amplify transparency, build public trust, and ultimately improve overall health outcomes. In this study, we leveraged large-scale longitudinal curation of electronic health records (EHRs) from the multi-state Mayo Clinic health system (MN, AZ, FL, WN, IA). We compared the infection rate of 2,195 individuals who received a single dose of the Ad26.COV2.S vaccine from Johnson & Johnson (J&J) to the infection rate of 21,950 unvaccinated, propensity-matched individuals between February 27th and April 14th 2021. Of the 1,779 vaccinated individuals with at least two weeks of follow-up, only 3 (0.17%) tested positive for SARS-CoV-2 15 days or more after vaccination compared to 128 of 17,744 (0.72%) unvaccinated individuals (4.34 fold reduction rate). This corresponds to a vaccine effectiveness of 76.7% (95% CI: 30.3-95.3%) in preventing SARS-CoV-2 infection with onset at least two weeks after vaccination.

This data is consistent with the clinical trial-reported efficacy of Ad26.COV2.S in preventing moderate to severe COVID-19 with onset at least 14 days after vaccine administration (66.9%; 95% CI: 59.0-73.4%). Due to the recent authorization of the Ad26.COV2.S vaccine, there are not yet enough hospitalizations, ICU admissions, or deaths within this cohort to robustly assess the effect of vaccination on COVID-19 severity, but these outcomes will be continually assessed in near-real-time with our platform. Collectively, this study provides further evidence that a single dose of Ad26.COV2.S is highly effective in preventing SARS-CoV-2 infection and reaffirms the urgent need to continue mass vaccination efforts globally.

Available in medRxiv (April 30, 2021):

 https://doi.org/10.1101/2021.04.27.21256193

The United States can immediately resume use of Johnson & Johnson's (JNJ.N) COVID-19 vaccine, top health regulators said on Friday, ending a 10-day pause to investigate its link to extremely rare but potentially deadly blood clots. The Centers for Disease Control and Prevention (CDC) and Food and Drug Administration said the risks of experiencing the syndrome involving severe blood clots and low platelets as a result of the vaccine was very low. They found 15 cases in the 8 million shots given. "We are no longer recommending a pause in the use of this vaccine," CDC Director Rochelle Walensky told a news briefing. "Based on the in-depth analysis, there is likely an association but the risk is very low."  Top U.S. FDA officials said the decision was effective immediately, clearing the way for shots in arms as early as Saturday. The agency said it would warn of the risk in an updated fact sheet given to vaccine recipients and providers. The agencies made the decision following a meeting of outside advisers to the CDC who recommended that the vaccine pause be ended. In an analysis presented at the meeting, CDC staff said that the cases of the syndrome that they had found occurred at a rate of seven per one million doses in women under age 50, with the highest risk occurring among women ages 30 to 39. For women over age 50 and for all men, the clots appeared at a rate of one per one million doses, the analysis showed. In all, there were three deaths, officials said.

After a day-long meeting, the CDC panel voted 10-4 that the J&J vaccine be used as recommended in people 18 years of age and older, the parameters of its current FDA authorization. Dr. Jesse Goodman, an infectious disease expert at Georgetown University in Washington and a former chief scientist at the FDA, said the risk was not trivial, but still small. "But we should keep it in perspective. I mean the risk of dying from a car accident in your life is something like one in 100, the risk of being struck by lightning is something like one in 15,000," Goodman said. Unlike the highly effective vaccines by Pfizer Inc (PFE.N) and Moderna Inc (MRNA.O), which require two doses and must be kept frozen at ultra-cold temperatures, J&J's vaccine can be given in a single dose and stored at regular refrigeration temperatures, making it a better option for hard-to-reach areas. Johnson & Johnson shares closed up 0.2% at $165.52.  "We will collaborate with health authorities around the world to educate healthcare professionals and the public to ensure this very rare event can be identified early and treated effectively," J&J's Chief Scientific Officer Paul Stoffels said in a statement after the agencies made their announcement. When the agencies first announced the pause, they urged doctors to avoid using the blood thinner heparin, commonly given to patients to break up blood clots, in people who had received the J&J vaccine and were experiencing blood clots and low blood platelets.  In the cases of the vaccine-induced blood clots, however, heparin appears to make the condition worse. Walensky said doctors heeded that warning, noting that the drug had not been used in any of the cases identified after the pause began.

The U.S. decision follows a similar one by the European Medicines Agency, which on Tuesday said the benefits of the J&J shot outweighed its risks and recommended adding a warning about unusual blood clots with low blood platelet counts to the vaccine’s product label. J&J resumed its rollout there.  The J&J probe followed an investigation in Europe of the AstraZeneca PLC(AZN.L) vaccine, with which similar cases of blood clots were first identified. Dr. Peter Marks of the FDA said the cases appear so similar that a doctor would not be able to tell which vaccine caused them.  Both the J&J and AstraZeneca vaccine use different versions of a cold virus to deliver instructions for making coronavirus proteins into cells to produce an immune response. Marks said studies are underway to determine whether the adenovirus or something else is behind the rare blood clots. Dr. William Moss, executive director of the International Vaccine Access Center at the Johns Hopkins Bloomberg School of Public Health, said the J&J vaccine will help advance the vaccination effort. "Giving people the choice to receive a single-dose vaccine will help get more people vaccinated faster and will better protect some populations, such as those who are homeless or incarcerated," Moss said by email. J&J has faced several setbacks since its vaccine gained U.S. emergency authorization in February, including drawing scrutiny over production shortfalls. In the United States, 35% of adults are fully vaccinated and 53% have received at least one shot, according to CDC data. The United States leads the world with roughly 570,000 COVID-19 deaths.

Federal health officials called for a halt in the use of the company’s coronavirus vaccine while they study serious illnesses that developed in six American women.

WASHINGTON — Injections of Johnson & Johnson’s coronavirus vaccine came to a sudden halt across the country on Tuesday after federal health agencies called for a pause in the vaccine’s use as they examine a rare blood-clotting disorder that emerged in six recipients. All six were women between the ages of 18 and 48, and all developed the illness within one to three weeks of vaccination. One woman in Virginia died, and a second woman in Nebraska has been hospitalized in critical condition. More than seven million people in the United States have received Johnson & Johnson shots so far, and another 10 million doses have been shipped out to the states, according to data from the Centers for Disease Control and Prevention. “We are recommending a pause in the use of this vaccine out of an abundance of caution,” Dr. Peter Marks, the director of the Food and Drug Administration’s Center for Biologics Evaluation and Research, and Dr. Anne Schuchat, the principal deputy director of the C.D.C., said in a joint statement. “Right now, these adverse events appear to be extremely rare.” While they framed the move as a recommendation to health practitioners, the impact was immediate. By Tuesday evening, every state, the District of Columbia and Puerto Rico had announced a pause in Johnson & Johnson vaccine injections.  The same went for the U.S. military, federally run vaccination sites, and CVS and Walgreens, two pharmacy giants that participate in the federal program, officials said. Rite Aid, Walmart and Publix also announced that they had paused Johnson & Johnson injections.

Beyond American shores, Johnson & Johnson said it would delay the rollout of its vaccine in Europe, where several countries were poised to start administering it this week. South Africa, devastated by a more contagious variant of the virus that emerged there, also suspended use of the vaccine. Australia announced it would not purchase any doses. The Biden administration tried to portray itself as well prepared for the setback. President Biden said he would meet his goal to have enough doses to vaccinate every American adult who wanted it by the end of next month. “There is enough vaccine, that is basically 100 percent unquestionable, for every single, solitary American,” he insisted. The reaction prompted an intense debate among public health experts about whether guarding against such a rare disorder was worth the cost. Scores of vaccine appointments were canceled this week, and some public health officials feared that by fueling vaccine hesitancy and conspiracy theorists, the pause could prompt fewer Americans to get vaccinated — and expose them to far more risk.  Others said the F.D.A. and the C.D.C. simply had no choice. “It’s incredibly challenging, but to ignore it would have been worse,” said Rachael Piltch-Loeb, an expert in health risk communication at the N.Y.U. School of Global Public Health. If the public suspected that the government was concealing serious potential side effects, she said, far more people might decide against vaccination.

Dr. Janet Woodcock, the acting commissioner of the F.D.A., said at a news conference that the pause might last only “a matter of days,” although she said that depended on “what we learn in the next few days.” Dr. Schuchat said the pause was enacted partly to “prepare the health care system to recognize and treat patients appropriately.” Scientists with the F.D.A. and the C.D.C. will jointly examine possible links between the vaccine and the disorder and determine whether the F.D.A. should continue to allow emergency use of the vaccine for all adults or modify the authorization, possibly by limiting the vaccine to certain population groups. An emergency meeting of the C.D.C.’s outside vaccine advisory committee has been scheduled for Wednesday. Despite Mr. Biden’s assurance, the pause will complicate the nation’s vaccination efforts at a time when many states are confronting a surge in new cases and seeking to address vaccine hesitancy. Regulators in Europe and elsewhere are concerned about a similar issue with another coronavirus vaccine, developed by AstraZeneca and Oxford University researchers. At the news conference, Dr. Marks drew a link between the two vaccines, saying the clotting cases were “very, very similar.” The vaccines are based on similar technology, but AstraZeneca’s has not yet been authorized for emergency use in the United States....

Johnson & Johnson release on the above issue (April 13):

https://www.jnj.com/johnson-johnson-statement-on-covid-19-vaccine-updated 

FDA-CDC Announcement on Janssen's vaccine:

https://www.fda.gov/news-events/press-announcements/joint-cdc-and-fda-statement-johnson-johnson-covid-19-vaccine 

Data have demonstrated vaccine protects against COVID-19 related hospitalization in broad geographic regions, including those with emerging variants. Decision follows the European Medicines Agency recommendation of the J&J COVID-19 vaccine. The Company aims to begin delivery of its vaccine to the EU in the second half of April and is committed to supply 200 million doses in 2021. 

NEW BRUNSWICK, N.J., March 11, 2021 – Johnson & Johnson (NYSE: JNJ) (the Company) today announced that the European Commission (EC) has granted a Conditional Marketing Authorization (CMA) for its single-dose COVID-19 vaccine, developed by the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), to prevent COVID-19 in individuals 18 years of age and older. The CMA follows a Positive Opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). The CMA is valid in all 27 member states of the European Union (EU), plus Norway, Iceland and Liechtenstein. Data from the Phase 3 ENSEMBLE study showed that the Johnson & Johnson COVID-19 vaccine was well tolerated and demonstrated a 67 percent reduction in symptomatic COVID-19 disease in participants who received the vaccine in comparison to participants given the placebo. The onset of protection was observed from day 14 and was maintained 28 days post-vaccination.1 The data also demonstrated the vaccine was 85 percent effective in preventing severe disease across all regions studied, and showed protection against COVID-19 related hospitalisation and death, beginning 28 days after vaccination.

“For more than a year, we have been working around the clock – leveraging the scientific minds, scale and resources of our global organisation to bring forward a COVID-19 vaccine,” said Alex Gorsky, Chairman and Chief Executive Officer at Johnson & Johnson. “We are thrilled with today’s Conditional Marketing Authorization by the European Commission, which enables our single-dose vaccine to reach many more communities in need, as we continue to do everything we can to help bring an end to this pandemic.” Johnson & Johnson is committed to making its COVID-19 vaccine available on a not-for-profit basis for emergency pandemic use. The Company aims to begin delivery of its single dose COVID-19 vaccine to the EU in the second half of April and to supply 200 million doses to the EU, plus Norway and Iceland in 2021. “This vaccine is the result of more than a decade of investment in research and development and deep commitment by our scientists. We appreciate the collaboration and the support of the European Commission in this monumental effort,” said Paul Stoffels, M.D., Vice Chairman of the Executive Committee and Chief Scientific Officer at Johnson & Johnson. “With this Conditional Marketing Authorization, we are proud to bring our single-shot vaccine to help protect millions of people across EU member states.”

In December 2020, the Company announced that Janssen initiated a rolling submission with the EMA for its single-dose COVID-19 vaccine candidate, enabling an expedited CHMP review process. The COVID-19 vaccine candidate has also been filed for an Emergency Use Listing (EUL) with the World Health Organization. Rolling submissions for our vaccine candidate have also been initiated in several countries worldwide. “This latest major regulatory milestone would not have been possible without the hard work and dedication of everyone involved in our COVID-19 vaccine clinical trial programme, including our J&J team, our partners and study participants,” said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson. “We are delighted by today’s announcement and remain fully committed to continuing our COVID-19 vaccine clinical programme as we strive to provide our single-dose COVID-19 vaccine to people all over the world.” The Company received Emergency Use Authorization (EUA) in the United States on February 27, following a unanimous vote by the U.S. Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee on February 26, 2021. The Johnson & Johnson single-dose COVID-19 vaccine has also been granted Interim Order authorisation in Canada.

EMA Press Release (March 11, 2021):

https://www.ema.europa.eu/en/news/ema-recommends-covid-19-vaccine-janssen-authorisation-eu 

Yet another experimental HIV vaccine has failed. The National Institute of Allergy and Infectious Diseases reported Wednesday that a phase 3 clinical trial of an HIV vaccine was stopped because the vaccine was ineffective at preventing infection. The vaccine was being developed by Janssen, the vaccine division of Johnson & Johnson. The Mosaico trial, which enrolled 3,900 volunteers in multiple countries, was halted after a scheduled data review by a data and safety monitoring board found there were roughly as many new HIV infections among people in the vaccine arm as in the placebo arm. The trial was studying the vaccine in cisgender men and transgender people who have sex with cisgender men and/or transgender people. “We are disappointed with this outcome and stand in solidarity with the people and communities vulnerable to and affected by HIV,” Penny Heaton, Janssen’s global therapeutic area head for vaccines, said in a statement. “We remain steadfast in our commitment to advancing innovation in HIV, and we hope the data from Mosaico will provide insights for future efforts to develop a safe and effective vaccine.” In 2021, a Phase 2b trial of a similar candidate HIV vaccine was halted when a data and safety monitoring board determined that it was not preventing infections. The Imbokodo trial was studying the vaccine in women in sub-Saharan Africa.

“For our research partners and others who have waged a decades-long effort to develop vaccines to end the HIV/AIDS pandemic, these results are disappointing,” Susan Buchbinder, co-chair of the Mosaico trial, said in a statement. “Although HIV continues to prove uniquely challenging for development of a vaccine, the HIV research community remains fully committed to doing just that, and each study brings us a step closer to this realization,” she said. Buchbinder is director of Bridge HIV, a grant-funded research unit at the San Francisco Department of Public Health, and a clinical professor at the University of California, San Francisco. The trial was conducted by the HIV Vaccine Clinical Trials Network based at the Fred Hutchinson Cancer Center in Seattle. Veteran HIV vaccine trialist Larry Corey acknowledged yet another setback in the decades-long quest to find an effective HIV vaccine. “HIV is a constantly changing and very challenging adversary. We can become disappointed when our best efforts don’t produce the results we’re looking for,” said Corey, principal investigator of the network’s leadership and operations center. “We have, however, come a long way and made many discoveries since the time when life expectancy was very short following an HIV diagnosis.” The vaccine was based on “mosaic” immunogens targeting HIV subtypes. The goal was to induce immune responses to a broad range of HIV strains. It was given in four injections over the course of a year. The vaccine used the same antigen delivery system employed by J&J’s Covid-19 vaccine, a common cold virus known as adenovirus 26. Volunteers were enrolled in the trial only after they were offered HIV pre-exposure prophylaxis, the antiretroviral drugs that can prevent infection. Those who accepted PrEP were steered towards services where they could access the drugs. People who did not want them, however, were considered for the study. Anyone in the trial who later changed their mind and wanted to use PrEP was also given access to the drugs, but remained in the trial.

At least five experimental HIV vaccines, tested over nine trials, have failed to show efficacy at the Phase 3 stage of development, said Mitchell Warren, executive director of AVAC, the AIDS Vaccine Advocacy Coalition. This latest failure hangs a big question mark over this field of research, he suggested. “I’m not sure we know exactly where the next big investment is going to come from because there’s not an obvious vaccine candidate in HIV that is next up in our efficacy pipeline,” Warren said. “This is another reason why this result is disappointing. This was the last true product in development. And the other activities in the field, which are very exciting … [are] quite upstream. Important upstream science, but not products that are going to be in efficacy trials anytime soon.” Stephaun Wallace, director of external relations for the HIV Vaccine Trials Network, noted work is being done on a candidate HIV vaccine using messenger RNA, the platform successfully used by Pfizer and its partner BioNTech as well as by Moderna to create their Covid-19 vaccines. The HIV work uses the Moderna platform. Exploration of the mRNA platform as a possible basis for an HIV vaccine is still in the safety testing phase, he said. Warren questioned, though, whether the answer is a different vaccine delivery system, suggesting the problem is probably the immune targets at which the various vaccines have aimed. He noted, for instance, that the J&J platform — adenovirus 26 — worked against Covid, but not against HIV. “These are the harsh reminders that it’s not that we don’t have great [vaccine] platforms,” he said. “Our challenge is figuring out exactly what is the target, what is the insert? … We have the vehicles. We don’t even know what passengers to put in the vehicles.” Wallace acknowledged the path ahead will be difficult, but said he remains optimistic that at some point, HIV vaccine efforts will meet success. “I’m pretty certain that with continued public support and interest in this area that we will see the day that an HIV vaccine is developed,” he said.

BACKGROUND

The Ad26.COV2.S vaccine was highly effective against severe–critical coronavirus disease 2019 (Covid-19), hospitalization, and death in the primary phase 3 efficacy analysis.

METHODS

We conducted the final analysis in the double-blind phase of our multinational, randomized, placebo-controlled trial, in which adults were assigned in a 1:1 ratio to receive single-dose Ad26.COV2.S (5×1010 viral particles) or placebo. The primary end points were vaccine efficacy against moderate to severe–critical Covid-19 with onset at least 14 days after administration and at least 28 days after administration in the per-protocol population. Safety and key secondary and exploratory end points were also assessed.

RESULTS

Median follow-up in this analysis was 4 months; 8940 participants had at least 6 months of follow-up. In the per-protocol population (39,185 participants), vaccine efficacy against moderate to severe–critical Covid-19 at least 14 days after administration was 56.3% (95% confidence interval [CI], 51.3 to 60.8; 484 cases in the vaccine group vs. 1067 in the placebo group); at least 28 days after administration, vaccine efficacy was 52.9% (95% CI, 47.1 to 58.1; 433 cases in the vaccine group vs. 883 in the placebo group). Efficacy in the United States, primarily against the reference strain (B.1.D614G) and the B.1.1.7 (alpha) variant, was 69.7% (95% CI, 60.7 to 76.9); efficacy was reduced elsewhere against the P.1 (gamma), C.37 (lambda), and B.1.621 (mu) variants. Efficacy was 74.6% (95% CI, 64.7 to 82.1) against severe–critical Covid-19 (with only 4 severe–critical cases caused by the B.1.617.2 [delta] variant), 75.6% (95% CI, 54.3 to 88.0) against Covid-19 leading to medical intervention (including hospitalization), and 82.8% (95% CI, 40.5 to 96.8) against Covid-19–related death, with protection lasting 6 months or longer. Efficacy against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was 41.7% (95% CI, 36.3 to 46.7). Ad26.COV2.S was associated with mainly mild-to-moderate adverse events, and no new safety concerns were identified.

CONCLUSIONS

A single dose of Ad26.COV2.S provided 52.9% protection against moderate to severe–critical Covid-19. Protection varied according to variant; higher protection was observed against severe Covid-19, medical intervention, and death than against other end points and lasted for 6 months or longer. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722. opens in new tab.)

Published in NEJM (Feb. 9, 2022):

https://doi.org/10.1056/NEJMoa2117608 

All three currently authorized COVID-19 vaccines still showed signs of a strong immune response eight months later without a booster, according to a study published Friday in the New England Journal of Medicine. The study analyzed specific markers of immunity found in the blood of people vaccinated with Pfizer, Moderna and the Johnson & Johnson vaccines.  Echoing evidence from the real world, researchers found cellular signatures suggesting that all three vaccines produce strong and long-lasting protection from severe illness. But the analysis also hinted at differences in the way the vaccines produce antibodies -- with Pfizer and Moderna antibodies spiking and then fading quickly, while Johnson & Johnson antibodies started at a lower level but remained more stable over time.  "By month eight, antibody responses were comparable for these three vaccines," said Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, who coauthored the research. Pfizer and Moderna vaccines rely on the same type of technology, called mRNA, while Johnson & Johnson uses a different technology, called viral vector. The two technologies prompt different types of immune responses. Thought the pandemic, scientists have used antibodies -- virus fighting proteins in the blood -- as one indication that vaccines are working. But antibodies are only one part of the body's overall immune response.

This new study is among the first to directly compare not just antibodies, but also T-cells, across all three vaccines. T-cells are also a crucial part of the immune system, and may offer longer-lasting protection even after antibodies fade. "We think the antibodies are often more relevant preventing against infection, and the T-cells are more relevant killing the virus -- so preventing severe disease," said Dr. Todd Ellerin, director of infectious diseases at South Shore Health and an ABC News medical contributor. "T-cell responses likely contribute to vaccine protection against severe disease," said Barouch. "T-cell responses were relatively stable for all three vaccines for eight months." This new study is among the first to directly compare not just antibodies, but also T-cells, across all three vaccines. T-cells are also a crucial part of the immune system, and may offer longer-lasting protection even after antibodies fade. "We think the antibodies are often more relevant preventing against infection, and the T-cells are more relevant killing the virus -- so preventing severe disease," said Dr. Todd Ellerin, director of infectious diseases at South Shore Health and an ABC News medical contributor. "T-cell responses likely contribute to vaccine protection against severe disease," said Barouch. "T-cell responses were relatively stable for all three vaccines for eight months."

Original findings published in NEJM (October 15, 2021):

https://doi.org/10.1056/NEJMc2115596

A two-dose version of Johnson & Johnson's coronavirus vaccine provides 94% protection against symptomatic infection, the company said Tuesday -- making a two-dose regimen of J&J's Janssen vaccine comparable to a two-dose regimen of Moderna's or Pfizer's.  Plus, the company said, adding a booster dose to a single shot of the vaccine raised immunity even more, and should also protect people strongly against infection. The company released some details of three studies looking at various aspects of its Janssen vaccine, and said that, taken together, they showed the vaccine provided long-lasting protection that could be boosted with an extra shot. "Our large real-world-evidence and Phase 3 studies confirm that the single-shot Johnson & Johnson vaccine provides strong and long-lasting protection against COVID-19-related hospitalizations," Dr. Mathai Mammen, global head of Janssen Research & Development, said in a statement.  "Our single-shot vaccine generates strong immune responses and long-lasting immune memory. And, when a booster of the Johnson & Johnson COVID-19 vaccine is given, the strength of protection against COVID-19 further increases." Johnson & Johnson's single-dose vaccine was given emergency use authorization by the US Food and Drug Administration on February 27. It has been given to about 14.8 million Americans, according to the US Centers for Disease Control and Prevention.

J&J's HIV vaccine, using the same technology as its COVID vaccine, failed to meet its goal of reducing the chance of HIV infection by 50%. An HIV vaccine using the same basic technology as Johnson & Johnson’s Covid shot failed to prevent infection, the company said Tuesday, dealing yet another blow to efforts to create a vaccine against the virus.  The study, called Imbokodo, enrolled 2,600 women in southern Africa who were at very high risk of HIV infection. J&J and its partners, including the National Institutes of Health and the Bill & Melinda Gates Foundation, launched the study in 2017 and announced that all participants had received either a vaccine or a placebo last year. The goal of the vaccine was not to completely prevent infection, but to reduce the chance of infection by half. “If a vaccine is 50% efficacious it can curb the future of the HIV pandemic,” said Paul Stoffels, J&J’s chief scientific officer and, before that, an HIV researcher. He said that the actual efficacy seen was 25.2%, meaning those that received the vaccine had their odds of becoming infected reduced that much compared to the placebo group 24 months after the first dose. That difference was not statistically significant, indicating that it is possible the result is due to chance. A second study, called Mosaico, that is testing a somewhat different vaccine regimen in men who have sex with men and transgender people in the Americas and Europe, will continue. 

“The development of a safe and effective vaccine to prevent HIV infection has proven to be a formidable scientific challenge,” Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, said in a statement. “Although this is certainly not the study outcome for which we had hoped, we must apply the knowledge learned from the Imbokodo trial and continue our efforts to find a vaccine that will be protective against HIV.” Scientists have been trying for decades to develop an HIV vaccine. After a Merck vaccine failed to prove effective in 2007, researchers looked back at the data and found it raised the risk of people developing the disease. Hopes were buoyed by a 2009 study in Thailand, which showed limited but significant efficacy, reducing the rate of infection by about 30%. But last year, an effort combining vaccines from Sanofi and GlaxoSmithKline also failed to prove effective.  J&J had repeatedly expressed optimism about its vaccine. In 2015, Johan Van Hoof, who leads J&J’s vaccine R&D, pointed to data showing that, in animals, the vaccine could reduce infection by 90%, “suggesting it might be a real breakthrough with regard to a future HIV vaccine.” On calls with financial analysts in 2020 and 2021, Stoffels listed the HIV project among the company’s vaccine efforts, calling it “very encouraging.” When the trial began five years ago, Fauci had said “the development and delivery of a preventive HIV vaccine that is safe and at least moderately effective would help bring about a durable end to the HIV/AIDS pandemic.” Imbokodo means “rock” in isiZulu, and refers to a proverb about women’s strength and the need for community. In the study, 63 of 1,109 volunteers in the placebo group developed HIV, while 51 of the 1,079 volunteers who received the vaccine developed HIV. That difference leaves a great deal of uncertainty as to whether there was an effect. The 95% confidence interval, used by researchers to define a range of likely outcomes, ranged from -10.5% to 49.3%. However, J&J said in its release that no vaccine-related safety issues were identified. Stoffels told STAT that it was clear the vaccine did not increase the risk of HIV.  Larry Corey, the principal investigator of the HIV Trials Network, which helped run the study, and a professor at the Fred Hutchinson Cancer Research Center in Seattle, said that he saw the result as a disappointment but also a sign of progress. It had been hoped that non-neutralizing antibodies – those that bound to the virus but did not entirely stop infectivity – would be enough to slow the rate of HIV infection, he said, but it is beginning to appear that vaccine developers will need to figure out how to generate antibodies that neutralize the virus.

“It is telling us that non-neutralizing antibodies are not decreasing acquisition and maybe demonstrates how difficult and different HIV is than Covid-19,” Corey said. Like the Covid-19 vaccine that Johnson & Johnson developed, this HIV vaccine delivers genetic code for proteins to a recipient’s cells using a type of virus called an adenovirus, which then makes proteins that the immune system learns to recognize and attack. The strain of adenovirus used, called Ad26, is also used in Johnson & Johnson’s experimental vaccine against respiratory syncytial virus, which can be very serious in infants.  The HIV vaccine regimen tested repeated dosing. It was given four times, and included genetic code for a “mosaic” of proteins from different strains of the HIV virus. Patients also received soluble protein injections at the third and fourth visit. The ongoing Mosaico study – the one in the Americas and Europe – uses a different mixture of soluble proteins at the vaccination visits three and four. Stoffels said that this is one reason that the vaccine might perform better in that study. Another is that the volunteers in the Mosaico study are at lower risk of infection, which may make the vaccine’s work less difficult. Corey also said there was hope Mosaico would succeed where Imbokodo failed. He said that the new formulation had led, in earlier studies, to higher levels of antibodies against HIV. Stoffels said that he doesn’t believe that the result should color people’s feelings about J&J’s adenovirus vaccine platform, which, he pointed out, has proven effective against Covid-19 and Ebola. (In Covid-19, the broad use of the vaccine also was linked to a rare but severe side effect that involves both the formation of clots and excessive bleeding. That side effect is so rare even large clinical trials might not detect it.) “It shows again that the HIV virus is a very special virus, very unique, escaping the immune system and finding its way to infect people and it’s very difficult to mount immunity against acquisition of HIV,” Stoffels said. But researchers will continue to try. Moderna recently began human trials of an HIV vaccine that relies on the mRNA technology behind its Covid vaccines. Corey pointed out that even under Covid lockdowns, women in the study still had a 4% chance of contracting HIV. That underscores the need for a vaccine, he said. “Vaccines really do make a difference when you have an effective vaccine, look at what happened with Covid,” Corey said. “I think we can’t give up.”

The Janssen COVID-19 vaccine has become the fifth vaccine against the pandemic to be granted emergency use approval.  Union health minister Mansukh Mandaviya tweeted today to inform that the single-dose vaccine manufactured by American pharmaceutical giant Johnson & Johnson has been given approval for Emergency Use in India.  The development comes just two days after the company had applied for Emergency Use Authorization in India. The company had said in a statement, “On August 5, 2021 Johnson & Johnson Pvt Ltd applied for EUA of its single-dose Covid-19 vaccine to the government of India.” They had submitted the application based on topline efficacy and safety data from the Phase 3 Ensemble clinical trial. The trial had shown that the single-dose vaccine is 85% effective in preventing severe Covid-19 disease across all regions studied. It had also shown protection against Covid-19 related hospitalisation and death, which begins 28 days after vaccination. Data from a clinical trial in South Africa also suggest that the vaccine is effective in preventing severe illness and death from the Delta and Beta variants of the coronavirus.

The company has tied up with Biological E for the supply of the vaccine in India. The vaccine will also be produced in India, at Biological E plant in Hyderabad. “Johnson & Johnson is working with Biological E. Limited on the manufacturing of the Johnson Covid-19 vaccine. We believe Biological E. will be an important part of our global Covid-19 vaccine supply network, where multiple manufacturing sites are involved in the production of our vaccine across different facilities, sometimes in different countries and continents, before the vaccine can be distributed”, an official statement released by Johnson and Johnson had earlier said.  The vaccine developed by Janssen Vaccines in Leiden, Netherlands, a subsidiary of J&J, is a viral vector vaccine. It is based on a human adenovirus that has been modified to contain the gene for making the spike protein of the virus that causes COVID-19. Responding to this spike protein, the immune system in the body produces antibodies that fights the virus. The four vaccines that India has already approved are Covaxin developed by Astra Zeneca and Oxford University, Covishield developed by Bharat Biotech, Sputnik V developed in Russia and the vaccine developed by Moderna in the USA.

Johnson & Johnson’s Covid-19 vaccine may trigger a rare neurological condition in a small number of people who receive the vaccine, the Food and Drug Administration said Monday.  Reports to a database operated jointly by the agency and the Centers for Disease Prevention and Control suggest there may be a link between the inoculations and Guillain-Barré syndrome, a form of progressive paralysis that is generally reversible, the FDA said in a statement. The agency said there have been about 100 preliminary reports of GBS, as the condition is often called, in people who have received the J&J vaccine. To date, about 12.8 million doses of the J&J vaccine have been used in the United States, suggesting a rate of about one case of GBS per 128,000 people vaccinated.  In most cases, the people reporting the condition developed it about two weeks after receiving the one-dose vaccine. Most are older males, which fits with the known pattern of GBS, said John Moore, an immunologist at Weill Cornell Medicine. “A rare, but very probably real consequence of the vaccine,” said Paul Offit, a vaccine expert from Children’s Hospital of Philadelphia. “Again, the benefits of the vaccine clearly and definitely outweigh its very rare risks.”

The FDA’s statement comes after a similar signal of GBS was identified with AstraZeneca’s Covid vaccine. Last week the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee recommended adding a warning to the label of the AstraZeneca vaccine, Vaxzevria, to inform health care providers. Its statement said it is not currently clear if the AstraZeneca vaccine triggers the condition. “At this stage the available data neither confirms nor rules out a possible association with the vaccine,” the EMA said. Both the AstraZeneca and J&J vaccines are what are known as viral-vectored vaccines — meaning they carry harmless genetic material from the SARS-CoV-2 virus into the body to trigger an immune response. The fact that both these vaccines now appear to be associated with GBS suggest it could be a class effect — something one might expect to see with other viral-vectored Covid vaccines, Offit said.

The FDA said to date there has been no signal to suggest the messenger RNA vaccines — those made by Moderna or Pfizer and its partner BioNTech — trigger GBS. There are multiple known causes of Guillain-Barré syndrome. Some viral infections, including influenza, have been shown to increase one’s risk of developing GBS, as have some gastrointestinal infections. And several vaccines have been shown to, on rare occasions, induce the condition. Most famously, the 1976 swine flu vaccination program in the United States was halted after a number of cases of Guillain-Barré syndrome were reported in people who received the vaccine. It was later estimated that the syndrome occurred at a rate of about one case per 100,000 doses of the swine flu vaccine. Though some flu seasons there is no signal of increased GBS cases linked to vaccination, other years there does appear to be an increase. In those cases, it has been estimated that there are one or two additional cases of GBS for every 1 million doses of vaccine given, the CDC estimates. Between 3,000 and 6,000 people in the United States develop GBS every year. The underlying cause of the condition causes nerve inflammation that can result in pain, numbness, muscle weakness, and difficulty walking.

With concerns surrounding the Delta coronavirus variant rising globally, how effective are the current vaccines in the U.S. at protecting against the new version of the virus? According to medical experts, the three vaccines currently available each offer protection. Here’s a breakdown of each vaccine and what you should know: How effective are the COVID vaccines overall? In clinical trials, Moderna’s  In clinical trials, Moderna's vaccine reported 94.1% effectiveness at preventing COVID-19 in people who received both doses. The Pfizer-BioNTech vaccine was said to be 95% effective. A new CDC study reported that a single dose of Pfizer's or Moderna's COVID vaccine was 80% effective in preventing infections. That number jumped to 90% two weeks after the second dose, the study on vaccinated health care workers showed.  "These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions," the U.S. agency wrote in the study. "COVID-19 vaccination is recommended for all eligible persons." Pfizer's vaccine, the only one currently authorized for use in children as young as 12, also showed heightened effectiveness among adolescents.  Pfizer in late March released preliminary results from a vaccine study of 2,260 U.S. volunteers ages 12 to 15, showing there were no cases of COVID-19 among fully vaccinated adolescents compared with 18 among those given dummy shots. More intriguing, researchers found the kids developed higher levels of virus-fighting antibodies than earlier studies measured in young adults. The FDA said J&J’s vaccine offers strong protection against what matters most: serious illness, hospitalizations and death. One dose was 85% protective against the most severe COVID-19 illness, in a massive study that spanned three continents — protection that remained strong even in countries such as South Africa, where the variants of most concern were spreading at the time.  The CDC reports J&J/Janssen vaccine was 66.3% effective in clinical trials at preventing COVID-19 illness in people who had no evidence of prior infection 2 weeks after receiving the vaccine. "The vaccine had high efficacy at preventing hospitalization and death in people who did get sick," the CDC notes. "No one who got COVID-19 at least four weeks after receiving the J&J/Janssen vaccine had to be hospitalized." It is not known if any of the three vaccines prevent the spread of the virus by people who are asymptomatic, though the CDC noted that "early evidence suggests that the J&J/Janssen vaccine might provide protection against asymptomatic infection." 

How effective are the vaccines against the new Delta variant?

Data surrounding vaccine effectiveness with the Delta variant is so far limited. While studies have shown that the available vaccines work against variants, including the Delta variant, all two-dose vaccines offer significantly more protection following their second dose. Researchers in England studied how effective the two-dose AstraZeneca and Pfizer-BioNTech vaccines were against it, compared with the Alpha variant that was first detected in the U.K. The vaccines were protective for those who got both doses but were less so among those who got one dose. One recent study showed the Pfizer vaccine was 84% effective against the variant after two doses, but only 34% effective after the first dose.  Moderna also announced Tuesday that a new study showed its vaccine also produced promising protection in a lab setting against the Delta variant and others currently circulating. “As we seek to defeat the pandemic, it is imperative that we are proactive as the virus evolves. We remain committed to studying emerging variants, generating data and sharing it as it becomes available. These new data are encouraging and reinforce our belief that the Moderna COVID-19 Vaccine should remain protective against newly detected variants,” Stéphane Bancel, chief executive officer of Moderna, said in a statement. Currently, little data has been released showing just how effective the Johnson & Johnson is at protecting against the Delta variant, though it is believed that the single-shot vaccine does offer protection against the variant. Dr. Scott Gottlieb, former Food and Drug Administration commissioner, reportedly said the Johnson & Johnson vaccine appears to be about 60% effective against the Delta variant. Still, medical experts say any of the three vaccines currently being used in the U.S. continue to show good results as far as protection. ”This will protect them against getting very sick and being hospitalized and even dying from the Delta variant,” Dr. Katherine Gergen-Barnett of Boston Medical Center recently told NBC10 Boston.

Will a booster shot be needed?

So far, there has been no recommendation from the Centers for Disease Control and Prevention surrounding booster shots with the Delta variant. Still, health experts have repeatedly cautioned that COVID-19 booster shots could be needed for fully vaccinated people, particularly as new variants spread. White House chief advisor Dr. Anthony Fauci said during an interview with MSNBC's Medhi Hasan in April that people may need to get booster shots in a year.  Pfizer CEO Albert Bourla also previously said people will "likely" need a third dose within 12 months of getting fully vaccinated.  So far, studies suggest that the vaccines currently in use can recognize the emerging variants — but they may not provide quite as much protection against the new strains. Boosters and new versions of vaccines that target the variants are already being explored. Pfizer-BioNTech was previously testing a third booster shot of its vaccine on fully vaccinated people.   "The flexibility of our proprietary mRNA vaccine platform allows us to technically develop booster vaccines within weeks, if needed," Sahin said in a release in February. Moderna was also testing a potential third dose of its current vaccine, and a possible booster shot specifically targeting the South Africa variant. Citing early data, the company recently said the booster vaccine generated a promising immune response against the B.1.351 and P.1 variants first identified in South Africa and Brazil, respectively. Meanwhile, Johnson & Johnson CEO Alex Gorsky said during an interview with CNBC's "Squawk Box" in March that the company is well-positioned to adapt its vaccine for variants, and is working on developing software that will "help address some of these new and emerging variants."

Anxiety triggered adverse reactions to the Johnson & Johnson COVID-19 vaccine in at least 64 people — including cases that resulted in jab sites being shut down, the Centers for Disease Control and Prevention said Friday.  The CDC studied the physical reactions, including dizziness and fainting, in dozens of people who received the shots in five states between April 7 and 9, officials said. Many of the people reported nausea, vomiting and chest pain in California, Colorado, Georgia, Iowa and North Carolina. Others said they had an elevated heart rate. The reactions prompted some vaccine centers to temporarily shut down while health officials investigated. But the CDC determined those reactions were brought on by anxiety caused by receiving injections. “We knew we were going to see this,” said Dr. Noni MacDonald, a Canadian researcher who has studied similar incidents. “Of the three COVID-19 vaccines authorized in the U.S., only J&J requires just one dose. That probably makes it more appealing to people who are nervous about shots and might leave them highly predisposed to anxiety-related events,” the CDC report states.

Some of the vaccine centers under review advertised that they were giving Johnson & Johnson shots, said Dr. Tom Shimabukuro, who leads the CDC’s COVID-19 vaccine safety monitoring work and is one of the study’s authors.  The CDC also found that about one-quarter of the people reporting side effects had similar reactions following past vaccinations. Some experts have referred to the phenomenon as a form of mass hysteria, but MacDonald rejected the notion. “These people are not crazy” — just feeling physical responses to psychological stress, she said. Many people who experience stress-related symptoms are younger, and past cases have involved students. Some hyperventilate and report headaches, which may at first appear to be more severe, neurological symptoms, she said. The adverse reactions in the study are not related to the rare blood-clotting condition that led federal health officials to put the brakes on the Johnson &Johnson vaccine earlier this month.

CDC Report published in MMWR (April 30, 2021):

 http://dx.doi.org/10.15585/mmwr.mm7018e3 

Scientists at Johnson & Johnson (JNJ.N) on Friday refuted an assertion in a major medical journal that the design of their COVID-19 vaccine, which is similar AstraZeneca's (AZN.L), may explain why both have been linked to very rare brain blood clots in some vaccine recipients.  The United States earlier this week paused distribution of the J&J vaccine to investigate six cases of a rare brain blood clot known as cerebral venous sinus thrombosis (CVST), accompanied by a low blood platelet count, in U.S. women under age 50, out of about 7 million people who got the shot. The blood clots in patients who received the J&J vaccine bear close resemblance to 169 cases in Europe reported with the AstraZeneca vaccine, out of 34 million doses administered there. Both vaccines are based on a new technology that uses a modified version of adenoviruses, which cause the common cold, as vectors to ferry instructions to human cells.

The U.S. Food and Drug Administration is scrutinizing this design behind both vaccines to see if it is contributing to the risk. In a letter on Friday in the New England Journal of Medicine, J&J scientists refuted a case report published earlier this week by Kate Lynn-Muir and colleagues at the University of Nebraska, who asserted that the rare blood clots "could be related to adenoviral vector vaccines." In an interview with Reuters on Thursday, Dr. Anthony Fauci, the top U.S. infectious disease expert and an adviser to the White House, said the fact that they are both adenovirus vector vaccines is a “pretty obvious clue” that the cases could be linked to the vector. "Whether that is the reason, I can't say for sure, but it certainly is something that raises suspicion," Fauci said.  In the correspondence on Friday, Macaya Douoguih, a scientist with J&J's Janssen vaccines division, and colleagues pointed out that the vectors used in its vaccine and the AstraZeneca shot are "substantially different" and that those differences could lead to "quite different biological effects." Specifically, they noted that the J&J vaccine uses a human adenovirus while the AstraZeneca vaccine uses a chimpanzee adenovirus. The vectors are also from different virologic families or species, and use different cell receptors to enter cells.

The J&J shot also includes mutations to stabilize the so-called spike protein portion of the coronavirus that the vaccine uses to produce an immune response, while the AstraZeneca vaccine does not. "The vectors are very different," said Dr. Dan Barouch of the Center for Virology and Vaccine Research at Harvard’s Beth Israel Deaconness Medical Center in Boston, who helped design the J&J vaccine.  "The implications of issues with one vector for the other one are not clear at this point," he said in an interview earlier this week. The J&J scientists said in the letter there was not enough evidence to say their vaccine caused the blood clots and they continue to work with health authorities to assess the data. A panel of advisers to the U.S. Centers for Disease Control and Prevention are expected to meet on April 23 to determine whether the pause on use of the J&J vaccine can be lifted.

Letter from J&J published in NEJM  (April 15, 2021):

https://doi.org/10.1056/NEJMc2106075 

North Carolina and Colorado sites were temporarily shut down after several people suffered reactions.  The race to vaccinate hit more roadblocks on Thursday, as several patients at a mass vaccination site in North Carolina suffered immediate reactions to the Johnson & Johnson shot. A day earlier, 11 people had adverse reactions in Denver, ranging from dizziness to nausea.  Both sites temporarily shut down. 

"At this point we have no reason to believe there's anything wrong with the vaccine itself," said Dr. Shauna Gulley, a Centura Health chief clinical officer. "This is a temporary pause of one brand of vaccine so that we can investigate further."  The news comes as distribution of the Johnson & Johnson vaccine is expected to fall 85% next week due in part to a factory mix-up.  Meanwhile, the Midwest is on the verge of a relapse. In the last week, COVID-19 hospitalizations increased 11% on average among adults under 50 compared to the prior week. But in the Midwest, those hospitalizations jumped 42%. The hardest hit state is Michigan, where one doctor tweeted a desperate plea on Thursday. "We need some help," Dr. Justin Dimick wrote.  Variants continue to complicate the country's recovery. Of all new coronavirus cases last week, children accounted for roughly one in five. Children are especially susceptible to the variant first found in the U.K., which was discovered at a recent outbreak at a Wisconsin childcare center.  "Prior to this time, young kids, particularly those in eighth grade or younger, rarely got infected or seriously ill with the virus and importantly did not transmit the virus in the community. Today that has been turned on its head," said Dr. Michael Osterholm, the director of the Center for Infectious Disease Research and Policy.  It's hitting college students, too. The University of Chicago said 50 students have tested positive. Some cases were linked to fraternity parties. 

In small-town Villa Grove, Illinois, a bar's indoor opening event was linked to 46 cases in February, spanning eight households. That led to the hospitalization of an elderly resident and forced a school to temporarily close, impacting 650 students. "Mask use was inconsistent and that six feet of distance was not maintained," said Centers for Disease Control and Prevention Director Rochelle Walensky. "These findings underscore the vast impact of a single event."