Virus World

Purpose

Since the worldwide spread of SARS-CoV-2, different strategies have been followed to combat the pandemic and limit virus transmission. In the meantime, other respiratory viruses continued to circulate, though at decreased rates.

Methods

This study was conducted between June and July 2022, in a hospital in the metropolitan region of Rio Grande do Sul state, in the southernmost state of Brazil. The 337 hospitalized patients included those with respiratory symptoms without delimitation of age. Reverse transcription-quantitative real-time polymerase chain reaction detected 15 different respiratory viruses and confirmed coinfections in the samples. Different statistical tests were applied to evaluate the association between associations of clinical characteristics and coinfection.

Results

Sampling corresponds to 337 selected and 330 patients analyzed. The principal clinical outcome found was hospital discharge in 309 (94%) cases, while 21 (6%) resulted in death. The principal viral agents related to coinfections were Human rhinovirus, Human enterovirus, and Respiratory syncytial virus. The most frequent viral agent detected was SARS-CoV-2, with 60 (18%) infections, followed by 51 (15%) cases of Respiratory syncytial virus B (15%) and 44 (13%) cases of Human rhinovirus 1. Coinfection was mainly observed in children, while adults and the elderly were more affected by a single infection. Analyzing COVID-19 vaccination, 175 (53%) were unvaccinated while the remainder had at least one dose of the vaccine.

Conclusions

This study presents information to update the understanding of viral circulation in the region. Furthermore, the findings clarify the behavior of viral infections and possible coinfections in hospitalized patients, considering different ages and clinical profiles. In addition, this knowledge can help to monitor the population’s clinical manifestations and prevent future outbreaks of respiratory viruses.

Published in Respiratory Research (FEb. 5, 2024):

https://doi.org/10.1186/s12931-024-02708-2 

GETTING a cough, fever or sore throat at this time of year could be down to any number of things, from a common cold to Covid-19. With a new strain of swine flu being detected in the UK

The London Medical Laboratory said its test can be taken at 95 selected pharmacies, drop-in clinics and health stores nationwide. You can find a full list of the places they're sold here. Otherwise, you can also order the test online to be delivered to your home. Dr Narayanan said: "The current strains of flu that are circulating may produce only mild illness in one person but may cause severe symptoms and even prove fatal to others. "This is particularly important in people with pre-existing health conditions and long-term diseases. Similarly, while the RSV virus may only produce chesty cold symptoms in some people, it can severely affect elderly people and children. "All of these viruses, including swine flu, display very similar initial symptoms to the common cold, but these symptoms may quickly escalate."

Taking a test to identify which virus is causing your symptoms could bring "peace of mind" to some or ensure "they are not endangering anyone in their family this festive season", the clinical lead claimed. The fact that the UKHSA is still working to ascertain the source of the H1N2 strain spotted in the North Yorkshire resident is another reason people might want to get tested, Dr Narayanan added.

Where else can I get these test?

The 95 pharmacies and clinics aren't the only place you can take a test telling the difference between the viruses. Online pharmacy Chemist Connect sells a kit by the brand CordX that claims to test for Covid, influenza A and B and RSV. It carries a much lower price tag too - £37.95, along with a delivery charge. Granted, that's still a fair amount pay for a test. Alternatively, you can nab Flowflex Flu Test and Covid Test Bundle at your local Boots. It won't be able to test for RSV - but you'll only have to shell out £4 for the two kits that come in the bundle. You can buy a five-pack of Influenza A/B Rapid Test at Tesco for £12. You can't get a free Covid-19 PCR test any more and rapid lateral flow tests are no longer free for most people. But according to NHS guidance, you might be eligible to get them for free if:

• You have a health condition which means you're at high risk of getting seriously ill from Covid
• You work in healthcare settings or in a hospice

Highlights

Summary

Advisers to the agency overwhelmingly agreed that a new treatment would help to prevent a potentially lethal respiratory illness in very young children. A Food and Drug Administration advisory panel recommended approval of a monoclonal antibody shot aimed at preventing a potentially lethal pathogen, respiratory syncytial virus, or R.S.V., in infants and vulnerable toddlers. The treatment, called Beyfortus by its developers Sanofi and AstraZeneca, would be the second such therapy that the F.D.A. has allowed to be given to very young children to prevent R.S.V., which is a leading killer of infants and toddlers globally. A similar treatment approved more than 20 years ago is given in multiple doses and is only approved for high-risk infants. The 21-member panel voted unanimously in favor of giving the treatment to infants born during or entering their first R.S.V. season. The advisers voted 19-2 for giving the shot to children up to 24 months of age who remain vulnerable to severe disease.

Why It Matters: R.S.V. is a global killer of infants.

Though many people experience this common virus as a routine cold, it can be serious in young infants and older adults. According to the Centers for Disease Control and Prevention, up to 80,000 children younger than 5 are hospitalized with the virus each year and up to 300 die. R.S.V. played a role in filling children’s hospitals during this winter’s “tripledemic,” which also included the flu and Covid-19. For adults 65 and older, as many as 160,000 hospitalizations are attributed to R.S.V., and about 10,000 deaths. Vaccines for older adults have also recently been approved.

BACKGROUND

Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)–associated lower respiratory tract illness in newborns and infants is uncertain.

METHODS

In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks’ gestation to receive a single intramuscular injection of 120 μg of a bivalent RSV prefusion F protein–based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points.

RESULTS

At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively).

CONCLUSIONS

RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316. opens in new tab.)

Published in NEJM (April 5, 2023): https://doi.org/10.1056/NEJMoa2216480 

Over the course of a two-day meeting, vaccine advisers to the US Food and Drug Administration voted in favor of approval for RSV vaccines for adults over the age of 60. The vaccine candidates, made by Pfizer and GlaxoSmithKline, could become the world's first approved vaccines against the common virus. On Wednesday, committee members voted 10-2 in support of the safety and unanimously in support of the effectiveness of GSK’s vaccine for the prevention of lower respiratory tract disease caused by RSV among older adults. For Pfizer’s shot, committee members voted on Tuesday with 7-4 with one abstention that there is adequate data to support the vaccine’s safety and effectiveness. The FDA, which typically follows the committee’s recommendations, is expected to decide on approval of the vaccines in May, ahead of RSV’s typical winter surge. Respiratory syncytial virus is a highly contagious virus that causes flu-like illness in people of all ages that increases in severity with age. According to the US Centers for Disease Control and Prevention, RSV is responsible for an estimated 177,000 hospitalizations and 14,000 deaths per year among adults 65 or older. GSK’s RSV vaccine candidate for older adults was 82.6% effective in preventing lower respiratory tract disease defined by either two or more symptoms or and one or more signs or three or more symptoms. The shot was 94.1% effective at preventing severe disease. The Pfizer vaccine was 66.7% effective at preventing moderated lower respiratory tract illness with two or more symptoms and 85.7% effective at preventing illness with three or more symptoms, according to Pfizer.

Focus on safety

Though a majority of the committee voted in support of the vaccines, some committee members expressed concerns over both vaccines’ risk of Guillain-Barre syndrome, a rare neurological disorder in which the immune system attacks its own nerves, causing muscle weakness and sometimes paralysis. The incidence of Guillain-Barre is about 1.5 to 3 cases for 100,000 adults over age 60 in the US annually, according to the FDA. Two adults among 20,000 vaccine recipients in Pfizer’s Phase 3 clinical trial developed symptoms consistent with the rare neurological disorder within nine days of receiving the shot. Of roughly 15,000 vaccine recipients of GSK’s Phase 3 clinical trial, one man developed Guillain-Barre syndrome within nine days of vaccination. “It seems to me that one case is a red flag. Two cases is very concerning,” said Dr. Marie Griffin, professor of health policy at Vanderbilt University Medical Center, who voted that the data demonstrated that both vaccines are effective but not safe

The FDA has called Guillain-Barre syndrome an “important potential risk” of Pfizer and recommended the company conduct a safety study for further evaluation of Guillain-Barre syndrome and other immune-mediated demyelinating conditions after potential vaccine approval, which the company has agreed to.

GSK has said they will closely monitor cases after approval. While Pfizer did not provide data on co-administration with other vaccines, GSK’s data showed potential safety risks when the RSV and flu shots were administered together. Two adults in their 70s who received both the flu and RSV vaccine developed acute disseminated encephalitis, a rare neurological disorder that involves swelling of the brain and spinal cord, and one of the individuals died. The FDA considers these cases as possibly related to either RSV or flu vaccination, but review is ongoing. “This is a disease with incidence 0.1 in 100,000 usually, the majority being in children and then a scatter in young adults. So two cases in elders within three to four weeks post-vaccine is highly anomalous from a statistical standpoint,” said Dr. Hana El Sahly, the FDA advisory committee chair, who voted against the GSK shot based on its safety profile but in favor based on efficacy. Dr. Adam Berger, who voted in favor of GSK’s vaccine based on safety and efficacy, says it seems to be an issue with co-administration and that concerns with acute disseminated encephalitis and Guillain-Barre syndrome won’t be answered until larger studies are conducted. “I suggest a heavy reliance on the postmarketing surveillance and not only just reliance but making sure there is an enforcement around the requirements about this,” Berger said. “At the moment, I think the profile seems to be within the acceptable range.”

Search for an effective RSV vaccine

Some vaccine advisers wanted to see more data on the Pfizer vaccine’s effectiveness at preventing hospitalization or death, especially among high-risk individuals including adults over 80, those with comorbidities, or those who are immunocompromised. “I think the data does support the effectiveness of this vaccine, it’s just the population was underrepresented by people who could most benefit from the vaccine,” Griffin said of Pfizer’s clinical trial. The available safety and efficacy data is from the first season of Pfizer’s clinical trial scheduled over two RSV seasons and the first of three seasons for GSK’s trial. Some experts want to wait for more data. “I’m desperately eager to have a vaccine that works for RSV. This has been a terrible disease my whole career. I would love to see it. No doubt about it,” said Dr. Jay Portnoy, professor of pediatrics at Children’s Mercy Hospital, who voted in support of GSK’s vaccine but against Pfizer based on efficacy. Portnoy said waiting for a second season of data would provide more robust numbers and complete analysis. “It’s not an emergency use authorization. We can take the time to finish the studies and get the information we need before licensing this product going forward. So I remain a little bit skeptical given the data that we have,” he said. Others think the benefits of the candidate vaccines outweigh the potential risks of deadly RSV infection. “Despite the challenges, despite the additional hurdles, our obligation is to do what’s right for the public,” said Dr. Daniel Kim who voted in favor of both shots. “And in this case, we have a bad disease, we have a good vaccine – so far, anyway, given the clinical trials – it’s a safe vaccine, and the vaccine can be used to prevent disease.”

BACKGROUND

Respiratory syncytial virus (RSV) is an important cause of acute respiratory infection, lower respiratory tract disease, clinical complications, and death in older adults. There is currently no licensed vaccine against RSV infection.

METHODS

In an ongoing, international, placebo-controlled, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive a single dose of an AS01E-adjuvanted RSV prefusion F protein–based candidate vaccine (RSVPreF3 OA) or placebo before the RSV season. The primary objective was to show vaccine efficacy of one dose of the RSVPreF3 OA vaccine against RSV-related lower respiratory tract disease, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), during one RSV season. The criterion for meeting the primary objective was a lower limit of the confidence interval around the efficacy estimate of more than 20%. Efficacy against severe RSV-related lower respiratory tract disease and RSV-related acute respiratory infection was assessed, and analyses according to RSV subtype (A and B) were performed. Safety was evaluated.

RESULTS

A total of 24,966 participants received one dose of the RSVPreF3 OA vaccine (12,467 participants) or placebo (12,499). Over a median follow-up of 6.7 months, vaccine efficacy against RT-PCR–confirmed RSV-related lower respiratory tract disease was 82.6% (96.95% confidence interval [CI], 57.9 to 94.1), with 7 cases (1.0 per 1000 participant-years) in the vaccine group and 40 cases (5.8 per 1000 participant-years) in the placebo group. Vaccine efficacy was 94.1% (95% CI, 62.4 to 99.9) against severe RSV-related lower respiratory tract disease (assessed on the basis of clinical signs or by the investigator) and 71.7% (95% CI, 56.2 to 82.3) against RSV-related acute respiratory infection. Vaccine efficacy was similar against the RSV A and B subtypes (for RSV-related lower respiratory tract disease: 84.6% and 80.9%, respectively; for RSV-related acute respiratory infection: 71.9% and 70.6%, respectively). High vaccine efficacy was observed in various age groups and in participants with coexisting conditions. The RSVPreF3 OA vaccine was more reactogenic than placebo, but most adverse events for which reports were solicited were transient, with mild-to-moderate severity. The incidences of serious adverse events and potential immune-mediated diseases were similar in the two groups.

CONCLUSIONS

A single dose of the RSVPreF3 OA vaccine had an acceptable safety profile and prevented RSV-related acute respiratory infection and lower respiratory tract disease and severe RSV-related lower respiratory tract disease in adults 60 years of age or older, regardless of RSV subtype and the presence of underlying coexisting conditions. (Funded by GlaxoSmithKline Biologicals; AReSVi-006 ClinicalTrials.gov number, NCT04886596. opens in new tab.)

Published in NEJM (Feb. 16, 2023):

https://doi.org/10.1056/NEJMoa2209604 

The BCCDC says this year's vaccine appears to cut the risk of medically attended influenza-like illness by more than half, with an estimated vaccine effectiveness of 55 per cent. The BC Centre for Disease Control says early evaluation shows this year’s influenza vaccine formula is providing “substantial” protection against the wave of flu so far. “The earlier-than-usual influenza epidemic this season has enabled us to assess vaccine effectiveness earlier than usual,” BC CDC epidemiologist and Canadian Sentinel Practitioner Surveillance Network lead Dr. Danuta Skowronski said. “We will update our analyses in the new year, but these interim findings show a substantial reduction in the risk of influenza illness for vaccinated people who seek medical care.” Analysis for the period from Nov. 1 to Dec. 14 with samples from B.C., Alberta, Ontario and Quebec had cut the risk of medically attended influenza-like illness by more than half, with an estimated vaccine effectiveness of 55 per cent. An update from the BCCDC on Thursday also showed there had been no additional flu-related deaths among children and youth this season. Six people under the age of 18 have died so far this year, several due to suspected influenza-linked bacterial infections. That same update showed that the epidemic wave appears to be waning. About 16 per cent of samples over the week ending Dec. 17 came back positive — down from a high of 27 per cent during the week ending Nov. 26.

The BCCDC’s latest analysis shows the number of tests that came back positive for RSV for the week ending Dec. 17 jumped to 13 per cent, up from six per cent in the week ending Nov. 26. Test-positivity for both RSV (37 per cent) and influenza A (21 per cent) remains higher among children and youth younger than 18 than in the general population, the BCCDC said. According to the BCCDC, the H3 subtype of influenza A remains the dominant strain of influenza this year, accounting for more than 90 per cent of tested samples. The H3N2 subtype is often linked to more severe outbreaks and lower vaccine effectiveness, however, this year’s vaccine appears to be as good as or better than in previous years the subtype was dominant, the agency said. “Vaccine protection is especially important for people at higher risk of severe complications and for a health-care system that is managing the circulation of multiple respiratory viruses at the same time as we enter the holiday period,” Skowronski said. The province continues to recommend vaccines for anyone aged six months and older, and is urging anyone who feels unwell to stay home.

US CDC historical data on influenza vaccine effectiveness in past seasons available at: 

https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html 

The respiratory virus season has started early in kids this year and flooded children's hospitals in many parts of the country -- especially with respiratory syncytial virus, known as RSV. But adults can get RSV, too. Although RSV does not typically send as many adults to the hospital, it can be a serious and even deadly disease for seniors and people with underlying health conditions. And with more kids getting RSV, the chances that adults will be exposed also rise. Some doctors say they are starting to see an uptick in adult patients. This season, about 6 out of every 100,000 seniors has been hospitalized with RSV, according to data from the US Centers for Disease Control and Prevention. That’s significantly lower than the rate for children but still uncharacteristically high. In the years before the Covid-19 pandemic, hospitalization rates for seniors were about 10 times lower at this point in the season. Dr. Ann Falsey, a professor of infectious diseases at the University of Rochester Medical Center who has published research on RSV in adults, said RSV rose somewhat in children in the summer and early fall last year, but the US did not see the usual proportional increase in RSV in older adults at the time. “I think that older adults were more cautious to continue public health measures like masks and social distance last year because they were still worrying about Covid,” Falsey said. “But this year, we’re starting to see older people ending up in the hospital again with RSV, because everyone is throwing caution to the wind.”

Virus flies under the radar in adults

Too often, RSV flies under the radar in adults, she said. Many people, even doctors, overlook its impact on adults. “They think of it as strictly a pediatric disease, but you know, if you don’t test for it, you’ll never know what somebody actually is sick with,” Falsey said. In the United States, tracking viruses like RSV isn’t nearly as thorough as it is for Covid-19, so it is difficult to know exactly how many adults get sick with RSV. The numbers of RSV cases come from self reports that go to a few dozen labs that only represent about a tenth of the population, and reports are then shared with the CDC. Based on best estimates, there are between 10,000 and 15,000 adult deaths in the United States from RSV each year and around 150,000 hospitalizations for RSV, Falsey said. A 2015 study of older adults in industrialized countries said the disease burden of RSV is “substantial” and calculated that about 14.5% of the 1.5 million adults who caught RSV were admitted to hospitals. People who were 65 and older were more likely to be hospitalized than those ages 50 to 64. “When we compare it to influenza A, it’s not too far behind,” Falsey said, referring to one of the strains of seasonal flu that’s often linked with more severe illness.

RSV symptoms in adults

RSV shows up in adults the same way it does in kids. It can look like a common cold and include runny nose, decreased appetite, coughing, sneezing, fever and wheezing. The symptoms typically last a week or two, and they clear up with rest and fluids. But in some adults, RSV can become dangerous because it can lead to dehydration, breathing trouble and more serious illnesses such as pneumonia and bronchiolitis, inflammation of the tiny airways in the lungs.

Adults at risk for severe illness from RSV

The adults who are most seriously at risk for severe outcomes with RSV are those 65 and older. The virus can spread quickly through a nursing home or long-term care facility, just like Covid-19 and flu. Adults with weakened immune systems need to be careful in RSV season. This can include people undergoing treatment for cancer, transplant patients, people with HIV and those who take certain drugs that suppress the immune system for diseases like Crohn’s, lupus or rheumatoid arthritis. Adults with chronic heart or lung disease like asthma, COPD or heart failure are also more likely to have to go to the hospital if they catch RSV.

How RSV spreads

An infected person can pass on RSV through a cough or sneeze. If the respiratory droplets land on a surface like a doorknob or desk and someone else touches it and then touches their face, they can get sick. It also spreads because healthy adults often won’t know they have it. It doesn’t typically cause fatigue like the flu or Covid does, so many adults will go to work or jump on a plane or bus, chalking up their symptoms to allergies. As they interact with others, it spreads further. RSV can easily spread from children to adults, too.

What do you do if you get RSV

If you have been coughing or have any other RSV-like symptoms and you are in a high-risk category, you should go to your doctor and get it checked out, says Dr. Daphne-Dominique Villanueva. “We can’t test everybody right now – in an ideal world we would want to do that – but we want to concentrate on vulnerable people,” said Villanueva, an assistant professor in the School of Medicine at West Virginia University who has written studies about RSV. Doctors’ offices have swab tests that can determine whether an illness is flu, RSV or Covid. There are specific antivirals for flu and Covid-19 but not for RSV. The trick is getting tested early, even to rule out RSV; getting started on Covid or flu antivirals right away can shorten the time you are sick and keep the virus from progressing to something more serious. With RSV, the treatment is what’s called supportive care: Drink plenty of fluids. Get some real rest. Stay home so you don’t spread it. Wear a mask around others in your home. If you start to wheeze and feel short of breath, Falsey said, those would be clear signals that you should see a doctor or maybe even take yourself to an emergency room quickly. At the hospital, they can give you supplemental oxygen if necessary.

Protection from RSV

There’s no protection from a vaccine for RSV, but that could change by next season. In the US, there are four RSV vaccines that may be nearing review by the FDA, and more than a dozen are going through trials. Some are designed to protect infants, and some are being tested in older adults. “Since we have very limited ways of treating it effectively, you should do whatever you can to prevent getting it in the first place,” Villanueva said. Protective measures for this busy RSV season will sound familiar: Wash your hands frequently, disinfect surfaces, and wear a mask in crowded spaces. “You might want to put off that visit for a week to see your grandkids, or you might want to wear a mask if you are going into a crowded place,” Falsey said. “Masks and hand-washing work. I know people are kind of over it, but if you’re a frail person or you know you have underlying medical conditions, when we know that RSV is surging, you should do those things and use caution around children who are actively sick. It all helps.”

An oral antiviral drug that targets a key part of the respiratory syncytial virus (RSV) polymerase has been identified, a finding that could provide an effective treatment against RSV disease, according to researchers in the Center for Translational Antiviral Research at Georgia State University.  The findings, published in the journal Science Advances, identify AVG-388 as the lead drug candidate, which effectively blocks the activity of the viral RNA polymerase, an enzyme responsible for replication of the viral genome. RSV is a leading cause of lower respiratory infections in infants and immunocompromised individuals, but no efficient therapeutic exists. The virus caused an estimated 33.1 million cases worldwide in 2015 that required 3.2 million hospitalizations and resulted in 59,800 deaths. Finding effective drugs to fight RSV has been challenging. Through mutations, RSV has escaped advanced candidate classes that prevent the virus from entering a cell. To overcome this issue, recent drug development efforts have focused on the viral RNA-dependent RNA polymerase complex of RSV because of the possible broader window of opportunity to fight the virus during viral genome replication and transcription.

"We have identified the AVG class of inhibitors of RSV RNA synthesis. Through chemical optimization, we have developed the clinical candidate AVG-388, which is orally efficacious against RSV in animal models of infection." Dr. Richard K. Plemper, senior author of the study, Distinguished University Professor and director of the Center for Translational Antiviral Research in the Institute for Biomedical Sciences at Georgia State

In addition, the researchers demonstrated potent antiviral activity in human airway epithelium organoid cultures. "In this study, we have mapped an exciting druggable target in the RSV RNA-dependent RNA-polymerase and established the clinical potential of the AVG inhibitor class against RSV disease," said Dr. Julien Sourimant, first author of the study and a postdoctoral fellow in the Center for Translational Antiviral Research in the Institute for Biomedical Sciences at Georgia State. The research team investigated the effect of treatment on viral replication at different oral doses intended to prevent or cure disease. They demonstrated that treatment reduced virus load by several orders of magnitude in the different disease models. "Our results lay the foundation for formal development of the AVG class and the structure-guided identification of companion drugs with overlapping target sites but distinct resistance profiles," Plemper said. Co-authors of the study include Julien Sourimant (first author), Carolin M. Lieber, Jeong-Joong Yoon, Mart Toots and Richard K. Plemper of the Center for Translational Antiviral Research in the Institute for Biomedical Sciences at Georgia State; Mugunthan Govindarajan, Venkata Udumula and Michael G. Natchus of Emory Institute for Drug Development at Emory University; Kaori Sakamoto of the College of Veterinary Medicine at the University of Georgia; Joseph Patti of Aviragen Therapeutics Inc. (now at JP Biotech Advisors Inc.); and John Vernachio of Aviragen Therapeutics Inc. The study was funded by the National Institutes of Health.

An injection of monoclonal antibodies was nearly 75 percent effective at preventing RSV-related lower respiratory tract infection in infants, study finds.  Dorina Bryant’s baby, Jaxtyn, was almost 2 weeks old when he caught a virus that left him hospitalized last summer.  His blood oxygen levels were dangerously low and his tiny chest heaved as he breathed. He tested positive for respiratory syncytial virus, or RSV. Despite his oxygen levels falling to 84 percent — 95 percent or higher is considered normal — he was sent home.  Bryant, who lives in Broken Bow, Oklahoma, drove him more than two hours to another hospital. The baby was put on high flow oxygen while his family waited two days for him to be airlifted to a pediatric intensive care unit in a children's hospital.  It took Jaxtyn’s lungs two months to recover. “Every time he coughed, you could tell he needed more time to heal,” Bryant said.  A few months later, in November 2021, Hollie Poore found herself in a similar situation. Across the country in South Jordan, Utah, a cold had run through her family of six. The symptoms lingered in her 3-month-old daughter, Susie. The infant tested positive for RSV and, like Jaxtyn, was sent home. Poore took her to the emergency room hours after she was sent home and noticed her daughter’s lips turning blue in the waiting room. “Immediately, there were tons of doctors in the room putting an oxygen mask on her and admitting her to the ICU,” said Poore. 

Almost all children are infected with RSV by the time they turn 2. For most babies, symptoms resemble a bad cold, but the respiratory virus can be dangerous for very young infants who may be vulnerable to complications such as pneumonia.  Jaxtyn and Susie are among the nearly 60,000 children hospitalized with RSV every year, according to Centers for Disease Control and Prevention data. They both survived, but the virus kills as many as 200 children under age 5 each year. In comparison, just over 300 children age 4 and under have died from Covid-19. “Lower respiratory tract infections kill more children under 5 than anything else and RSV is the No. 1 cause of those infections,” said Dr. Anne Moscona, a virologist and infectious disease physician at Columbia University.  Researchers have tried to discover a safe and effective RSV immunization for decades. New research published Wednesday in the New England Journal of Medicine shows that a one-time injection can protect against RSV complications. The drug, called nirsevimab, was nearly 75 percent effective at preventing RSV-related lower respiratory tract infection, the most common reason for RSV hospitalization in infants, AstraZeneca researchers found. After earlier trials demonstrated the drug's safety, the late-stage trial tested how well the drug works. The study included almost 1,500 infants from around the world who were randomly assigned to a placebo or nirsevimab — 994 received the novel drug and 496 received a placebo. All babies were either full-term or late-preterm infants who were at least 35 weeks. Fewer adverse events were reported in the nirsevimab group than the placebo group. The drug, developed by AstraZeneca, is not a vaccine since it does not require the host to make antibodies against a virus, a process called active immunization. Instead, nirsevimab inoculates babies with antibodies, a process called passive immunization. With nirsevimab, the antibodies stay in the bloodstream and provide protection against severe infection and complications for months, instead of waning quickly.  For infants not considered high risk, the immunization would be given just once, at the beginning of their first RSV season. High-risk babies could get another dose before their second RSV season. 

“This protects young infants in that most vulnerable period before their immune system has matured,” said Tonya Villafana, AstraZeneca's global franchise head, infection and a senior author on the research. "When they get exposed later in life, they can cope with the disease much better." The company expects to submit the trial data to the Food and Drug Administration within a few months.  There is a monoclonal antibody that can prevent RSV called palivizumab, but it requires a series of five monthly shots and is only approved for use in high-risk infants and toddlers. An inoculation like nirsevimab, which would be available to all infants, is badly needed, said Moscona, who was not involved in the research. She called the safety and efficacy studies "rigorous." Because the antibodies in nirsevimab have been altered to stay in the body longer — and provide longer-lasting protection — the inoculation is a a “significant improvement” over other antibody therapies, she said. “We tend to think about these respiratory viruses in kids as only affecting those with underlying illnesses, but globally that’s not the case," Moscona said. "If we look at the global numbers, most kids who get sick and die with RSV have absolutely no underlying issues."

How Covid's spread may have changed RSV

RSV typically circulates with other viruses during the fall through winter. That changed with the delta surge of the pandemic when RSV began spreading last summer, prompting the CDC to issue a warning to parents and doctors. Some experts believe RSV cases could spike again as Covid restrictions are lifted.  “The challenge is that we really don’t know what an RSV season is right now,” said Dr. Michele Kong, a professor at the University of Alabama at Birmingham School of Medicine. RSV may also impact children born during the pandemic differently than pre-pandemic babies, meaning the need for prevention may be even higher.  “Infants today are largely not exposed to RSV in the way their older siblings were a few years ago,” Kong said. “It’s unknown if they may get sicker because they haven’t had this exposure that builds an immune response.”  

An outbreak of respiratory syncytial virus, combined with growing Covid-19 pediatric cases, is straining hospital resources in some U.S. cities.  U.S. health officials have expressed concern over a simultaneous rise in Delta infections and cases of respiratory syncytial virus, a highly contagious seasonal flulike illness that is more likely to affect children and older adults. Cases of R.S.V. have risen gradually since early June, with an even greater spike in the past month, according to data from the Centers for Disease Control and Prevention. The illness, which can cause symptoms that include a runny nose, coughing, sneezing and fever, normally begins to spread in the fall, making this summer spike unusual. In a series of posts on Twitter, Dr. Heather Haq, a pediatrician at Texas Children’s Hospital in Houston, described an increase in both coronavirus and R.S.V. hospitalizations. “After many months of zero or few pediatric Covid cases, we are seeing infants, children and teens with Covid pouring back into the hospital, more and more each day,” she wrote, adding that patients have ranged in age from 2 weeks to 17 years old, including some with Covid pneumonias.  “We are on the front end of a huge Covid surge,” wrote Dr. Haq, who could not be reached for comment on Sunday. “We are now having winter-level patient volumes of acutely ill infants/toddlers with R.S.V., and I worry that we will run out of beds and staff to handle the surge upon surge.”

R.S.V. cases in Texas began to increase in early June and appeared to peak in mid-July, according to data from the state’s health department. There has been a similar spike in Florida, where infections “were above those seen at this time in past years,” according to a surveillance report. In Louisiana, where cases have jumped 244 percent in the past two weeks, Our Lady of the Lake Children’s Hospital in Baton Rouge was nearing its capacity on Friday, CNN reported. “You start with the pandemic for the last 18 months, and then R.S.V. for the last couple of months,” Dr. Trey Dunbar, the hospital’s president, told the network. “It just seems to be one thing after another that’s keeping our teams very busy.” In Oklahoma, which has also had a spike in R.S.V. cases, beds are becoming scarce at hospitals. Dr. Cameron Mantor, the chief medical officer for Oklahoma Children’s Hospital at OU Health, told The Oklahoman that in the past two months R.S.V. cases in the state had been “exponentially off the charts.” “R.S.V. is a real issue right now,” he told the newspaper. “What is going to happen if we do have a surge in pediatric Covid cases?” The rise comes as new coronavirus infections have risen 148 percent in the United States in the past two weeks and hospitalizations have increased 73 percent, according to New York Times data.

Respiratory syncytial virus (RSV), a common infection in children and senior adults, can also infect nerve cells and trigger inflammation leading to nerve damage, according to a new Tulane University study. RSV can cause mild symptoms such as coughing, sneezing and fever or lead to more severe conditions such as pneumonia or bronchiolitis. But since the disease was first discovered in 1956, it has been thought to only infect the respiratory tract. This study, published in The Journal of Infectious Diseases, is the first to prove that RSV can penetrate nerve cells. It may provide the clearest link between RSV and reported neurological symptoms in children. RSV has been previously detected in the spinal fluid of children with seizures. Additionally, 40% of RSV-positive children under the age of 2 have shown acute encephalopathy, brain damage that can result in confusion, memory loss or cognitive difficulties. The findings underscore the potential long-term impacts of the disease, as well as the importance of preventative measures such as the two RSV vaccines approved by the FDA in 2023. "This is the most common respiratory virus in the first years of life as well as an impactful virus among the elderly," said Dr. Giovanni Piedimonte, Tulane University vice president for research and professor of pediatrics, biochemistry and molecular biology. "This adds a new dimension to the importance of RSV vaccines for both the elderly and mothers to protect their babies."

Researchers studied the virus using 3D peripheral nerve cultures grown from stem cells and rat embryos. After finding that they can be infected by RSV, researchers found that RSV induced the release of chemokines—proteins that fight infections by controlling immune cells—and caused significant inflammation. With low levels of RSV infection, the nerves became hyperreactive to stimulation. At higher levels, the team observed a progressive degeneration of the nerve and increased neurotoxicity due to excess inflammation. "Until this study, the theory was that the inflammatory response was indirectly activating the nerves," Piedimonte said. "This study shows that not only does that happen, but the virus can penetrate directly into the nerves." The nerve hyperreactivity could explain why children who get RSV are later more likely to have asthmatic symptoms, Piedimonte said.

The study also found that RSV could enter the spinal cord via peripheral nerves despite not having the ability to enter the spinal neurons directly. More research is needed to explore that mechanism, but Piedimonte theorizes that by using the peripheral nerves to enter the spinal cord, RSV can bypass the blood-brain barrier, enter the central nervous system and infect the brain. If confirmed, it could signal a connection between RSV and other neurological or developmental disorders, Piedimonte said. "If indeed it's confirmed in future studies that viruses like this are able to access the central nervous system, that opens a huge Pandora's box," Piedimonte said. Co-authors on the study include Tulane University researchers Kevin Pollard, Vicki Traina-Dorge, Stephen Medearis, Alexander Bosak, Greg Bix and Michael Moore.

Study cited published in the Journal of Infectious Diseases (Dec. 22, 2023):

https://doi.org/10.1093/infdis/jiad596 

At-home testing is becoming a thing not just for COVID-19, but for seasonal flu and other infections. Here's what you need to know. B efore COVID-19, figuring out whether a sore throat, fever, and runny nose were caused by a cold, flu, or strep wasn’t a top priority. You either powered through, knowing you’d be miserable for a few days but would probably feel better soon or you visited the doctor’s office, urgent care, or emergency room where you might get a test to figure out which virus or bacteria was behind your misery, and maybe a prescription to treat it. But even doctors often don’t order tests, preferring instead to make diagnoses based on symptoms. During the pandemic, however, it became more critical to know who was infected with SARS-CoV-2 so those people could isolate and not spread the virus. At-home test kits became household products, and most people are by now adept at squeezing out a few drops of solution onto a card, sticking a swab up their nose, swirling the swab in the testing liquid, and waiting for a result.

Tests for COVID-19

A number of companies, offer at-home test kits for COVID-19 that people can buy without a prescription. Most of these are rapid antigen tests, which pick up antigens, or substances that the SARS-CoV-2 virus makes. While they are relatively accurate, because it takes some time for levels of these antigens to build up after an infection, these tests are less reliable in the day or so immediately after exposure to the virus. That’s why doctors recommend repeating the test a couple of days apart. Then there are PCR, or molecular, tests, that are closer to the gold standard used in laboratories, and rely on finding the smallest genetic signatures of the virus and amplifying them. Cue Health sells a palm-sized COVID-19 PCR device that people can purchase for $300 that allows for 10 at-home tests and doesn’t require a prescription. The device reads a saliva sample and provides results to a smartphone app in 20 minutes. Other testing companies, such as Labcorp and Everlywell, also sell PCR-based tests for COVID-19, but they are technically collection kits, which means that you have to send a saliva sample into a lab to get results, which can mean critical days will pass before you get results.

Tests for seasonal flu

There is only one at-home test authorized by the FDA for influenza: Lucira, now owned by Pfizer, makes a combined flu and COVID-19 molecular test. The kit uses a PCR-related method of amplifying and reading any viral genes in a sample, providing a result in about 30 minutes. In coming months, eMed, a digital health company that sells test kits and telehealth services, plans to offer that kit, as well another that is currently being reviewed by the U.S. Food and Drug Administration. (The combined kit currently available on eMed’s website only tests for COVID-19 and provides a survey to help telemedicine professionals determine if a user likely has the flu.)

Tests for RSV

There currently aren’t at-home tests for RSV, because typically only infants and the elderly are at risk for severe illness. Doctors’ offices, hospitals, and urgent care centers can perform RSV tests that provide results in about 30 minutes.

The advantages of at-home testing

The currently cumbersome journey from symptoms to treatment rests on people making appointments with their doctors or at an urgent care center and could be contributing to the spread of viruses. Self-testing could reduce some of that risk since people are most infectious while they are waiting to get tested and receive treatment. Ideally, if someone tests themselves at home and finds they are positive for influenza or COVID-19, for example, they don’t necessarily have to physically visit their doctor or go into an urgent care or emergency room, where they could spread the virus to others. Instead, they could video conference with a doctor who could assess their symptoms and at-home test results, then write a prescription for, say, oseltamivir if it’s the flu, or Paxlovid if it’s COVID-19. “If you’re trying to minimize morbidity and mortality, and cut down on transmission, then [at-home] testing is an incredible tool to have,” says Thomas Denny, chief operating officer of the Duke University Human Vaccine Institute....

This fall, parents and pediatricians will have a new option to protect babies from a lung-attacking virus that is the leading cause of hospitalization in infants under a year old in the United States every year. The US Food and Drug Administration approved nirsevimab to protect newborns from respiratory syncytial virus, or RSV, on Monday. Nirsevimab, which will be sold under the brand name Beyfortus, is not a vaccine. Vaccines prompt the body to make antibodies to defend against pathogens. Instead, nirsevimab is a form of passive immunity. It’s a ready-made antibody that can bind to the virus and block it from infecting healthy cells. The immune system doesn’t have to make anything. It’s given as a single injection to an infant before RSV season, which usually peaks in the fall and winter months. The FDA approval also allows a second injection for infants up to 24 months of age who remain vulnerable through their second RSV season. “RSV can cause serious disease in infants and some children and results in a large number of emergency department and physician office visits each year,” said Dr. John Farley, director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research. “Today’s approval addresses the great need for products to help reduce the impact of RSV disease on children, families and the health care system,” Farley said in a news release.

The group of experts who advise the US Centers for Disease Control and Prevention on its vaccine recommendations will next weigh in. The Advisory Committee on Immunization Practices, or ACIP, has issued draft recommendations and clinical considerations for nirsevimab’s use, but the group is expected to formalize those with a vote at its next meeting. After the CDC signs off, nirsevimab will become the second antibody available to protect young children against RSV. The other, called palivizumab or Synagis, has been used only to protect the most vulnerable babies: those born prematurely who are younger than 6 months. It lasts only a short time in the body, so doctors give it once a month, starting just before RSV season, until the risk has passed. It has been a help, but it’s only partially effective. It keeps vulnerable babies out of the hospital about 50% of the time. The antibody in nirsevimab has been stabilized so it lasts longer in the body — four to six months — and it seems to be more potent. It’s approved for use in all infants, even healthy infants born full-term. “This virus can affect all babies, so not just babies with certain health conditions but even healthy babies. So as a pediatrician, I’m very excited about the idea of having an immunization to prevent serious illness from RSV,” said Dr. Rachel Dawkins, medical director of the pediatric and adolescent medical clinics at Johns Hopkins All Children’s Hospital in St. Petersburg, Florida.

Nirsevimab may not be the only option for preventing the infection this fall. The FDA is weighing whether to approve Pfizer’s vaccine for pregnant women that would also protect babies. In that case, the mom makes the antibodies, which cross the placenta to safeguard the fetus and are expected to last through an infant’s first few months of life. That vaccine would protect babies from the moment they are born, a benefit if the infection shows up out of season. Vaccines also prompt the mom’s body to make more than one kind of antibody, which would provide broader-spectrum protection. “I would say any strategy that we can use to help prevent RSV and infants is a great one,” Dawkins said. “So if moms are able to be vaccinated to hopefully protect their newborns, that’s great. Or if the babies are able to be given this antibody, also great, and I think there is some evidence that they work together.” In a presentation at their June meeting, the ACIP committee thinking through the potential use of the antibody said that it may make sense to give both types of protection in certain circumstances but that most healthy babies will need only one or the other. “Obviously, they need to consider how both of those preventive products for RSV infection will coexist,“ said Dr. Michael Greenberg, a pediatrician who is North American medical head of vaccines for Sanofi, the company that is marketing the antibody. “Nirsevimab is really the first that’s going to be able to offer the protection for all infants, sort of irrespective of when they’re born, because there’s the flexibility in the timing of the administration,” Greenberg told CNN. In the clinical trials that led to its approval, nirsevimab was about 70% effective at cutting the risk that a baby would need a doctor’s visit for RSV, and it was about 78% effective at preventing hospitalizations due to RSV compared with a placebo, according to an FDA analysis.

That means nirsevimab would prevent 1 RSV hospitalization for every 56 infants treated. So even though antibodies like this tend one to be pricey, doctors say that if it keeps babies out of the hospital, that will probably make it worth the cost. In studies, the therapy was generally safe and well-tolerated. A few infants — less than 1% — had skin reactions after their shots, but these went away with treatment. “We run this gauntlet every year — RSV season,” said Dr. Frank Esper, a pediatric infectious disease specialist at the Cleveland Clinic in Ohio. “We see a lot of these infants. They come in; they can’t breathe. That’s the problem. That’s what RSV does. It causes so much swelling and secretions in their breathing tubes, called the bronchioles, that they just can’t get enough oxygen.” RSV is the leading cause of hospitalization in infants up to 1 year old. Most babies with RSV need extra oxygen; doctors help support their breathing for two or three days, and then they get better. “Babies are small, and because babies are small, their airways are small, and so it takes just a little amount of inflammation to clog them all up, and that’s what RSV does,” Esper said. In rare cases, RSV can be deadly. According to the CDC, it kills between 100 and 300 infants each year. And it’s not just a threat to young children; RSV sickens and kills elderly adults each year, too. Vaccines geared toward seniors have just been approved. “So anything that we have that can fight that problem, then the better,” Esper said. Eight years ago, Cheryl Meany enrolled in an early study testing nirsevimab when she was pregnant with twin girls. The babies were born a little early, at 33 weeks, as twins often are, and their early arrival meant they were more vulnerable to infections. She said she felt cautious about enrolling in the study, but her doctor told her he would absolutely do it if they were his own kids. Her newborns were given injections shortly after birth, but she didn’t find out that they’d gotten the active antibodies until almost five years later. “I kind of had an inkling,” Meany said. “They were born in December, and we live in upstate New York, where cold and flu season is rampant around here. And I’m a teacher, and my husband at the time was working in the hospital as a respiratory therapist, our older daughter was in school, so … just germs everywhere.” She says her twins were in day care at the time, “and they never got sick.” “This was just the best start for them and being preemies and all of the things that could have happened,” Meany said. “I really do believe that this kept them healthy in order to grow and thrive.”

FDA press release (July 17, 2023):

https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-prevent-rsv-babies-and-toddlers 

At least 58,000 children younger than 5 years old are hospitalized each year with RSV infections. A Pfizer vaccine given to pregnant people could help protect their infants from severe RSV illness. Advisers to the Food and Drug Administration recommended that the agency should approve the first vaccine to protect infants from RSV, or respiratory syncytial virus. But some of the experts expressed reservations about the adequacy of data in support of the vaccine's safety. In a two-part vote, the experts voted unanimously, 14-0, that the available data support the effectiveness of the Pfizer vaccine in preventing severe RSV-related respiratory illness. They then voted 10-4 that the data supports the vaccine's safety. RSV is a leading cause of infant hospitalization in the U.S. From 58,000 to 80,000 children younger than 5 years old are hospitalized each year with RSV infections, according to the Centers for Disease Control and Prevention. Infants 6 months old and younger are at elevated risk for severe RSV illness. The votes came after a day of testimony and discussion during a public meeting of the agency's expert panel on vaccines. The FDA isn't bound to follow the advice of its expert panels, but it usually does. A decision on the vaccine for infants is expected by late August.

The vaccine isn't given to babies. Instead, pregnant people are immunized during the late second to third trimester of pregnancy. The antibodies they develop against RSV pass to the fetus in the womb and later protect the newborn. A clinical study involving 7,400 people found the vaccine had 81.8% efficacy in preventing severe respiratory illness caused by RSV within three months after birth and 69.4% in the first six months. There was some evidence that those who got vaccinated might have been more likely to give birth prematurely. And committee members worried about pregnant people getting the vaccine at the same time as some other vaccines, such as TDAP (tetanus-diphtheria-pertussis), because it could interfere with their effectiveness. "I worry that if preterm births are in any way a consequence of this vaccine, that would be tragic," said Dr. Paul Offit, professor of pediatrics at The Children's Hospital of Philadelphia. He voted no on the adequacy of safety data. The same Pfizer vaccine is under FDA review to protect people 60 and older people from RSV. Advisers voted to support approval of the vaccine at February meeting. Separately, in a first, the agency approved an RSV vaccine from drugmaker GSK in early May for people 60 and older.

The shots would be the first vaccines available against a respiratory virus that kills thousands and leads to many more hospitalizations each year.

Why It Matters: R.S.V. can be lethal

The F.D.A. estimates that R.S.V. is associated with 6,000 to 10,000 deaths each year in adults 65 and older and at least 60,000 hospitalizations in that age group. It is a leading killer of children worldwide.

This winter, R.S.V. contributed to the “tripledemic” also involving flu and Covid cases that swamped children’s hospitals and some I.C.U. wards.

Announcing the approval, Dr. Peter Marks, the agency’s vaccine division chief, said: “Older adults, in particular those with underlying health conditions, such as heart or lung disease or weakened immune systems, are at high risk for severe disease caused by R.S.V.”

Background: Benefits and risks of the shots

On March 1, an F.D.A. advisory panel reviewed data from trials for two R.S.V. vaccines aimed at older adults, one from GSK and one from Pfizer. The panel recommended that the agency approve both.

The GSK vaccine was nearly 83 percent effective in preventing lower respiratory tract illness in adults 60 and older in a study of about 25,000 patients, according to data published in The New England Journal of Medicine. The virus can lead to pneumonia, which is far more worrisome for the elderly.

Pfizer’s R.S.V. vaccine for older adults is also expected to receive F.D.A. approval this month. In a large study of that shot, it was found to be nearly 67 percent effective in preventing R.S.V.-related illness.

The Pfizer and GSK vaccines were even more effective in treating older and sicker patients.

The advisers did learn of some rare side effects from the vaccine trials. In the days after the shots were given, two recipients of the Pfizer vaccine and one recipient of the GSK shot developed cases of Guillain-Barré, a condition where the immune system attacks the nervous system, according to data presented to the F.D.A. panel.

Once the shots become available to the public, the agency said it would require GSK to monitor the incidence of Guillain-Barré and another rare condition that was possibly related to the shot.

Moderna is also developing an R.S.V. vaccine for this age group, and said it expected authorization in the first half of this year. A trial of 37,000 older adults showed 82 percent efficacy of its shot, the company said, with “no safety concerns identified” thoughanalyses were continuing.

AstraZeneca and Sanofi are seeking F.D.A. approval of a monoclonal antibody treatment to protect infants and toddlers up to 2 years old from R.S.V. infections. Findings of a major study showed the therapy reduced confirmed illnesses by 75 percent after one shot, according to AstraZeneca.

Pfizer has applied for separate approval of an R.S.V. vaccine to be given in the later stages of pregnancy to protect young infants.

What’s Next: When will the shots be available?

It will still be months before the adult vaccine is publicly available in the United States.

The Centers for Disease Control and Prevention is expected to follow the F.D.A.’s approval, most likely issuing its recommendation in June.

GSK said its vaccine would then be available in the fall at U.S. pharmacies, clinics and other health care settings.

GSK executives have said that supplies of the vaccine, which is manufactured mainly at a plant in Belgium, should be readily available. For Medicare patients with Part D drug coverage, there would be no out-of-pocket expense, Alison Hunt, a GSK spokeswoman, said. But the company has not released a price, although insurers typically cover much of the cost of many vaccines.

Last week, the European Medicines Agency recommended approval of GSK’s vaccine for adults 60 and older. The company said it hoped the shots would also be approved later for use in Japan and China.

The pharma, once a frontrunner in the race to develop the first vaccine for the respiratory virus, said it will end a 23,000-person study of its experimental shot amid a restructuring of its infectious disease division.

Dive Brief:

• Johnson & Johnson will stop developing its experimental vaccine for respiratory syncytial virus in an unexpected retreat from a high-profile research effort that had put the pharmaceutical giant among the leading companies seeking to win the first approval of a preventive shot.
• The company said Wednesday it will discontinue a 23,000-person Phase 3 trial, called Evergreen, of its RSV vaccine in adults following a review of its drug pipeline. The company does not plan to develop the shot for pregnant women or infants, a spokesperson confirmed.
• J&J’s pullback comes amid a restructuring of its infectious disease division, which was reported by Fierce Pharma in February. Its decision also thins the RSV vaccine competition, leaving GSK and Pfizer in the lead with shots that are currently under review by the Food and Drug Administration. Moderna is also developing an RSV vaccine and could file for approval this year.

Two people who received Pfizer's respiratory syncytial virus (RSV) vaccine during a clinical trial were later diagnosed with Guillain-Barre syndrome, and the US Food and Drug Administration has asked Pfizer to conduct a safety study if the shot is approved, according to agency documents released Friday. The cases were confirmed in two adults in their 60s who were among 20,000 vaccine recipients in Pfizer’s Phase 3 clinical trial. One person’s illness had completely resolved after three months, and another was improving after six months. There were no Guillain-Barre cases among people who didn’t receive the shot. “Given the temporal association and biological plausibility, FDA agrees with the assessments of the investigators that these events were possibly related to study vaccine. … Therefore, [Guillain-Barre] is being considered an important potential risk,” the FDA says in the documents, which were released ahead of a meeting of its independent vaccine advisers, the Vaccines and Related Biological Products Advisory Committee, on Tuesday and Wednesday.

The committee is scheduled to discuss and make recommendations on RSV vaccines for adults 60 and older from Pfizer and GSK. Guillain-Barre syndrome is a rare neurological disorder in which the immune system attacks its own nerves, causing muscle weakness and sometimes paralysis. Although most people recover completely, some cases can be fatal or have lasting effects. The incidence of Guillain-Barre is about 1.5 to 3 cases for 100,000 adults over age 60 in the US annually, according to the FDA.

“Given the higher than background rate of GBS observed in the Phase 3 study, FDA will recommend a postmarketing study and enhanced surveillance for further evaluation of GBS and other immune-mediated demyelinating conditions with postmarketing use,” the FDA says. In a briefing document submitted for next week’s meetings, Pfizer says that the cases have other possible explanations and that its shot is a “well-tolerated and safe vaccine, with a benefit-to-risk ratio that is favorable.” The company says it will conduct a safety study on Guillain-Barre syndrome if its RSV shot is approved. RSV is a highly contagious virus that causes flu-like illness in people of all ages that increases in severity with age. According to the US Centers for Disease Control and Prevention, RSV is responsible for an estimated 177,000 hospitalizations and 14,000 deaths per year among adults 65 or older. There are no vaccines approved for immunization against RSV in either children or with adults. The Pfizer vaccine was 66.7% effective at preventing moderated lower respiratory tract illness with two or more symptoms and 85.7% effective at preventing severe illness, the FDA documents say. GSK’s RSV vaccine candidate for older adults was 83.5% effective at preventing severe lower respiratory tract disease. The company similarly reported a potential case of Guillain-Barre syndrome among vaccine recipients but said there was insufficient evidence to confirm a diagnosis. The FDA considers the case to be related to the vaccine and said it will review GSK’s safety plan. Data from both vaccines was discussed Thursday during a meeting of the CDC’s Advisory Committee on Immunization Practices. The working group concluded that the vaccines “demonstrated significant efficacy against lower respiratory tract illness caused by RSV among older adults” but that “post licensure surveillance for both safety and vaccine effectiveness will be critical” if the vaccines are approved by the FDA.

US biotech company Moderna on Tuesday announced positive interim trial results for its vaccine against respiratory syncytial virus (RSV) in adults over the age of 60. There are no jabs currently available for the virus, which is a top cause of lower respiratory diseases, commonly leading to bronchiolitis in children and pneumonia in the elderly. However numerous vaccines and treatments are under development, most notably by Moderna's rival COVID-19 vaccine maker Pfizer. Moderna's vaccine was found to be nearly 84 percent effective against RSV-linked diseases in Phase III trials—the final stage of human testing—the firm said in a statement. The trial of the vaccine, which uses the new mRNA technology from Moderna's COVID jab, involves some 37,000 adults over 60 in 22 countries including the United States.

The company released the findings of an interim analysis, which has not been peer-reviewed. In the placebo group, there were 55 cases of RSV-linked lower respiratory tract disease with at least two symptoms, compared to nine in the group that received the vaccine, it said. The vaccine had no serious side effects, the company added. Moderna plans to apply for regulatory approval for the vaccine in the US, Europe and other regions in the coming months. This could make it available for the RSV season in the Northern Hemisphere's winter this year, Moderna's chief medical officer Paul Burton told AFP. The company is also testing the vaccine for use in children, but those trials are still at the first phase.

'Good news'

In high-income countries, RSV caused 5.2 million cases of severe disease among adults over 60 in 2019, Moderna said. Up to 30,000 elderly patients die every year in G7 countries due to the virus, Burton added. He said that the number of doses required for Moderna's vaccine was yet to determined. The positive results come after Pfizer announced in December that its own RSV vaccine for over-60s was granted priority review status by the US Food and Drug Administration. The previous month, Pfizer said another of its RSV vaccines, which is given to pregnant mothers, was effective at protecting newborns. Also in November, the European Union approved a preventative treatment which works similarly to a vaccine made by AstraZeneca and Sanofi which has been shown to prevent severe illness from RSV in infants. When asked about other RSV vaccines being developed by Moderna's rivals, Burton said "it's good news". "The public has gone seven decades with nothing" to fight the virus, and soon could have multiple options, he said. Moderna is also looking at whether the RSV jab can be combined with COVID and even influenza vaccines, after soaring cases of all three in recent months was dubbed a "tripledemic".

Moderna's Press Release:

https://investors.modernatx.com/news/news-details/2023/Moderna-Announces-mRNA-1345-an-Investigational-Respiratory-Syncytial-Virus-RSV-Vaccine-Has-Met-Primary-Efficacy-Endpoints-in-Phase-3-Trial-in-Older-Adults/default.aspx 

Introduction

As reported by the United States (US) Center for Disease Prevention and Control, the US experienced an early and severe respiratory syncytial virus (RSV) surge in autumn 2022. This increase in RSV cases relative to previous years, alongside coincident epidemics of SARS-CoV-2 and Influenza, has put intense pressure on hospitals and urgent care centers [1]; however, the factors promoting the surge in cases are unknown. A leading hypothesis suggests an increase in the susceptible population brought on by limited RSV circulation during COVID-19, particularly involving children ages one to three, who are among the most susceptible to severe RSV [2]. Alternatively, the emergence of a highly transmissible and/or virulent “variant” of RSV could account for the increase. These possibilities can be distinguished by genome sequencing of surge-associated samples because a highly-transmissible variant will appear as a cluster of closely-related sequences in a phylogenetic tree. To characterize the viral genomic basis of the 2022 RSV surge in Massachusetts (MA), we sequenced RSV genomes and analyzed clinical data from symptomatic patients who presented to the Massachusetts General Hospital (MGH), a large academic medical center in Boston, MA, and its affiliated outpatient practices in the Greater Boston Area.

Discussion

We show that the expansion of multiple clades has contributed to the RSV surge in MA in the autumn of 2022. In cases sampled during the peak of the surge at a major academic medical center and its affiliated outpatient practices in the greater Boston area, RSV-A predominates, and circulating clades have a MRCA more than 5 years before the present. The polyphyletic nature of viral genomes sequenced in eastern MA suggests that the emergence of a single, highly transmissible RSV lineage is unlikely to account for the 2022 surge. Additional genomic and immunological data are needed to fully understand the causes of the 2022 RSV surge, including pre-COVID-19 pandemic sequences to evaluate changes in RSV genomic diversity during the COVID-19 pandemic.

Published in Virological.org (Dec. 9 , 2022)

With the study only meeting one of its two primary endpoints, the result leaves scope to question how Pfizer will fare against AstraZeneca and Sanofi.  Pfizer has halted a pivotal trial of its respiratory syncytial virus (RSV) vaccine candidate early for efficacy, positioning the Big Pharma to file for approval by the end of the year. But with the study only meeting one of its two primary endpoints, the top-line result leaves scope to question how Pfizer will fare against AstraZeneca and Sanofi’s rival antibody. At the preplanned interim efficacy analysis, Pfizer linked the administration of its bivalent RSV prefusion vaccine candidate RSVpreF, also known as PF-06928316, during pregnancy to a significant reduction in the rate of severe medically attended lower respiratory tract illness (MA-LRTI) in newborns. The efficacy against severe MA-LRTI was 81.8% through the first 90 days of life, falling to 69.4% over the six-month follow-up period. The result was enough for the study to meet one of its co-primary endpoints. However, the study came up short against the second co-primary endpoint, which looked at the effect of RSVpreF on the rate of all severities of MA-LRTI. Pfizer called the 57.1% efficacy for MA-LRTI over the first 90 days of life clinically meaningful. But the figure, which slipped to 51.3% over the six-month follow-up period, wasn’t statistically significant and may suggest AstraZeneca and Sanofi’s antibody nirsevimab has an advantage over RSVpreF. The company plans to release secondary endpoint data later that includes impact on hospitalized patients, Pfizer CEO Albert Borla said during a Nov. 1 earnings call. “When you look at this dramatic effect on the severe infections, it seems very reasonable to project that we will have a dramatic impact in lowering hospitalizations,” Borla said, referring to the study.

It's estimated that more than 177,000 older adults are hospitalized from RSV in the U.S. each year, and 14,000 of them die, the CEO said.    While Pfizer is working to protect newborns from RSV using a maternal vaccine, AstraZeneca and Sanofi are developing a long-acting antibody that is administered to infants. In a phase 3 clinical trial, the Big Pharma partners linked nirsevimab to 74.5% efficacy against medically attended RSV-associated lower respiratory tract infection.  When asked about how RSVpreF could stack up to AstraZeneca and Sanofi’s RSV antibody for infants, Angela Hwang, Pfizer’s chief commercial officer and president of global biopharmaceuticals business, said Pfizer is the only company that has both an adult vaccine as well as the maternal vaccine in development. She said most infant RSV deaths are in those younger than six months old, citing 102,000 infant deaths reported worldwide each year. “So you really need that protection from day one,” Hwang said, which is where the company believes it can stand out. “Literally, from the moment of birth you have protection, and duration of protection throughout the six months, which is what we've shown in our clinical trials,” Hwang said. “While obviously, it's great to have many different options, I think that the option that we have with our vaccine is truly a unique one.”  Pfizer is hot on the heels of AstraZeneca and Sanofi, which have secured a recommendation for approval of nirsevimab in the EU but are yet to get the nod in the U.S. A filing for FDA approval of the breakthrough-designated RSVpreF is planned for this year.  With GSK halting enrollment in studies of its maternal RSV vaccine candidate, Pfizer, which said RSVpreF was well tolerated with no safety concerns for both the vaccinated individuals and their newborns, has a clear run at the vaccine market. But AstraZeneca and Sanofi are addressing the same unmet need from a different angle, suggesting RSVpreF will face competition from deep-pocketed rivals.

Pfizer Press Release (Nov. 1, 2022):

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-data-phase-3-global 

After years in development, the floodgates for RSV vaccines may open up soon, with more and more Big Pharmas piling on data. Now, Johnson & Johnson’s Janssen is adding to the fray, announcing efficacy as high as 80% in preventing severe infections in a mid-stage clinical trial.  Janssen revealed the proof-of-concept data at IDWeek Saturday, showcasing a trial called CYPRESS that featured more than 5,700 people aged 65 years and up randomized to receive the RSV vaccine candidate or placebo. The main goal was the preventing the occurrence of lower respiratory tract disease as a result of RSV infection. A dozen secondary endpoints looked for adverse events, neutralizing antibodies and other outcomes. Protection from Janssen’s vaccine ranged from 80% in preventing severe lower respiratory tract infection caused to 70% for more mild cases. The study concluded that the vaccine was effective in protecting against RSV-caused infections through the first viral season. 

While the CYPRESS data presented at IDWeek are from one RSV season, Macaya Douoguih, Ph.D., head of clinical development and medical affairs in Janssen, said trial participants will be tracked for a second season to see how long the efficacy lasts. “You never know when you need to boost from the first season so that will hopefully help give us an indication of what's needed there,” Douoguih said. Before presenting the data at the conference, Janssen had already announced Sept. 29 that the RSV vaccine would be moved to a phase 3 trial called EVERGREEN on the strength of the phase 2 data. This late-stage trial will have 23,000 participants with an expanded age group of 60 and up. Trial volunteers will be tracked for at least two seasons. Douoguih added that CYPRESS showed a 13.5-fold increase in antibody titers that occurred 14 days after vaccination, which reflects an immune response. The vaccine was also well tolerated by all participants with no safety signals. “We think that these results are quite solid,” said Douoguih.

There is no vaccine available for RSV, which according to the Centers for Disease Control and Prevention causes an average of 58,000 hospitalizations a year in the U.S., with 100-500 deaths among children younger than five years old as well as 177,000 hospitalizations with 14,000 deaths among adults aged 65 years or older. Janssen is also testing the RSV candidate in children. A phase 1 has been completed while two midstage studies are underway. Janssen’s shot could one day go up against Pfizer's candidate, which showed 100% efficacy against mild to moderate cases though in people under 50 and in a challenge trial, where study volunteers are purposely infected with the virus and then monitored. The New York-based pharma is yet to provide details on severe cases from that 62-person trial. GlaxoSmithKline and Moderna are also advancing candidates. GSK has seen a mixed journey in clinic trials, having abandoned its candidate in children back in July. The U.K. pharma is moving ahead with a maternal study to see whether vaccination can protect the mother and child. Pfizer too is investigating its candidate in pregnant women.

Janssen's Press Release (Sept. 29, 2021):

https://www.jnj.com/janssen-announces-start-of-phase-3-trial-for-investigational-respiratory-syncytial-virus-rsv-vaccine-in-older-adults