Virus World

The U.S. Food and Drug Administration has approved a kit that will allow women to collect their own vaginal sample for HPV screening, a move that could increase early detection in those at risk for cervical cancer. Women will be able to swab themselves in privacy at a doctor's office, clinic or pharmacy, and the sample will then be sent off for analysis. More than half of U.S. women diagnosed with cervical cancer have never been screened or screened only infrequently for the virus, the kit's maker Roche said in a news release announcing the approval on May 15 2024. "With vaccinations, innovative diagnostic tools and screening programs, achieving the WHO's goal of eliminating cervical cancer by 2030 is within reach," Roche Diagnostics CEO Matt Sause said. "Our HPV self-collection solution helps support this goal by reducing barriers and providing access to HPV screening by allowing people to privately collect their own sample for HPV testing." Each year, about 11,500 U.S. women are diagnosed with cervical cancer and about 4,000 women die from it, according to the U.S. Centers for Disease Control and Prevention. HPV is the known cause of more than 95% of cervical cancers, Roche added. "Almost all cervical cancers are caused by persistent infection with certain types of HPV," Dr. Karen Knudsen, CEO of the American Cancer Society (ACS), said in a statement. "Self-collection can expand access to screening and reduces barriers, which will give more people the opportunity to detect, treat and ultimately survive cancer."

Most primary care doctors don't test for HPV. Instead, women are most often screened by gynecologists during a pelvic exam, a procedure to which some don't have access and others find too intrusive and embarrassing. "Roche's self-collection solution can help reduce these barriers by offering an alternative to clinician collection procedures, while also providing accurate and reliable results," Roche said. The HPV test itself is already covered by private insurance, Medicare and Medicaid, Roche told the Washington Post. "This literally just opens up another option for a different demographic of people that might not feel comfortable, that might not have access [and] may not have time" to get tested otherwise, Irene Aninye, chief science officer for the Society for Women's Health Research, told the Post. The ACS recommends that cervical cancer screening begin at age 25, and that women ages 25 to 65 have an HPV test every five years.

Studies done for the past two decades have found that self-collection for HPV testing is feasible and acceptable, and that women can collect samples as well as their physicians, the ACS said. "Self-collection was not FDA-approved at the time our current guideline was released, but we now expect a minor update to the guideline to note that primary HPV testing via clinician-collected sample or self-collection is acceptable," said ACS Chief Scientific Officer Dr. William Dahut. "We anticipate self-collection will play an increasingly prominent role in cervical cancer screening once regulatory and clinical prerequisites are in place and as supporting evidence continues to accumulate," Dahut added. The approval could also open the door for at-home collection of samples. Teal Health received FDA breakthrough designation last week for an at-home cervical cancer screening device called the Teal Wand. Women would collect their own sample at home, then send it to a lab to be tested for HPV. The designation grants Teal Health priority status from regulators when clinical trials wrap up and the data is submitted to the FDA. "No more stirrups, no more speculum," the Teal Health website promises. "The Teal Wand replaces the need for an in-office pap smear using stirrups, a speculum and a hard plastic brush or broom. With self-collect, you are in control."

Roche's Press release (May 14, 2024):

https://www.roche.com/media/releases/med-cor-2024-05-15 

The USDA tested 30 samples from states with herds infected by H5N1. Tests of ground beef purchased at retail stores have been negative for bird flu so far, the U.S. Department of Agriculture announced Wednesday, after studying meat samples collected from states with herds infected by this year's unprecedented outbreak of the virus in cattle. The results "reaffirm that the meat supply is safe," the department said in a statement published late Wednesday after the testing was completed. Health authorities have cited the "rigorous meat inspection process" overseen by the department's Food Safety Inspection Service, or FSIS, when questioned about whether this year's outbreak in dairy cattle might also threaten meat eaters.    "FSIS inspects each animal before slaughter, and all cattle carcasses must pass inspection after slaughter and be determined to be fit to enter the human food supply," the department said. The National Veterinary Services Laboratories tested 30 samples of ground beef in total, which were purchased at retail outlets in states with dairy cattle herds that had tested positive.

To date, dairy cattle in at least nine states — Colorado, Idaho, Kansas, Michigan, New Mexico, North Carolina, Ohio, South Dakota and Texas — have tested positive for H5N1, which is often lethal to poultry and other animals, like cats, but has largely spared cattle aside from sometimes disrupting their production of milk for a few weeks.  A USDA spokesperson said the ground beef they tested came from stores in only eight of those states. Colorado was only confirmed to have H5N1 in a dairy cow after USDA had collected the samples. The spokesperson did not comment on whether beef from stores in additional states would be sampled. More results from the department related to bird flu in beef are expected soon. Samples collected from the beef muscle of dairy cows condemned by inspectors at slaughter facilities are still being tested for the virus. The department is also testing how cooking beef patties to different temperatures will kill off the virus. "I want to emphasize, we are pretty sure that the meat supply is safe. We're doing this just to enhance our scientific knowledge, to make sure that we have additional data points to make that statement," Dr. Jose Emilio Esteban, USDA under secretary for food safety, told reporters Wednesday.

The studies come after the USDA ramped up testing requirements on dairy cattle moving across state lines last month in response to the outbreak.  Officials said that was in part because it had detected a mutated version of H5N1 in the lung tissue of an asymptomatic cow that had been sent to slaughter. While the cow was blocked from entering the food supply by FSIS, officials suggested the "isolated" incident raised questions about how the virus was spreading. Signs of bird flu have also made its way into the retail dairy supply, with as many as one in five samples of milk coming back positive in a nationwide Food and Drug Administration survey.  The FDA has chalked those up to harmless fragments of the virus left over after pasteurization, pointing to experiments showing that there was no live infectious virus in the samples of products like milk and sour cream that had initially tested positive. But the discovery has worried health authorities and experts that cows could be flying under the radar without symptoms, given farms are supposed to be throwing away milk from sick cows. One herd that tested positive in North Carolina remains asymptomatic and is still actively producing milk, a spokesperson for the state's Department of Agriculture and Consumer Services told CBS News.  It remains unclear how H5N1 has ended up in the milk supply. Don Prater, the FDA's top food safety official, said Wednesday that milk processors "can receive milk from hundreds of different farms, which may cross state lines," complicating efforts to trace back the virus. "This would take extensive testing to trace it that far," Bailee Woolstenhulme, a spokesperson for the Utah Department of Agriculture and Food, told CBS News.  Woolstenhulme said health authorities are only able to easily trace back milk to so-called "bulk tanks" that bottlers get. "These bulk tanks include milk from multiple dairies, so we would have to test cows from all of the dairies whose milk was in the bulk tank," Woolstenhulme said.

The FDA has approved the world’s first medicine based on CRISPR gene-editing technology, a groundbreaking treatment for sickle cell disease that delivers a potential cure for people born with the chronic and life-shortening blood disorder. The new medicine, called Casgevy, is made by Vertex Pharmaceuticals and CRISPR Therapeutics. Its authorization is a scientific triumph for the technology that can efficiently and precisely repair DNA mutations — ushering in a new era of genetic medicines for inherited diseases. In a clinical trial, Casgevy was shown to eliminate recurrent episodes of debilitating pain caused by sickle cell, which afflicts approximately 100,000 people in the U.S., a vast majority of whom are Black.

The therapy, whose scientific name is exa-cel, is described as a potential cure because the genetic fix enabled by CRISPR is designed to last a lifetime, although confirmation will require years of follow-up. The FDA decision comes three weeks after regulators in the U.K. were the first to clear the drug. Approval in the European Union is expected next year. The FDA is also expected to rule on exa-cel as a treatment for beta thalassemia, another inherited blood disorder, by March 30. The FDA on Friday also approved another sickle cell treatment, a gene therapy from Bluebird Bio called Lyfgenia. Patients will now have the option of two cutting-edge therapies that provide potentially curative benefits....

FDA Approvl letters (Dec.08, 2023):

https://www.fda.gov/media/174618/download 

https://www.fda.gov/media/174617/download 

On May 25, the FDA approvedopens in a new tab or window nirmatrelvir-ritonavir (Paxlovid) for treating adult outpatients with mild to moderate COVID-19 who are at risk for severe disease. Until then, nirmatrelvir-ritonavir had only received emergency use authorizationopens in a new tab or window. Upon approval, the Center for Drug Evaluation and Research director Patrizia Cavazzoni, MD, proclaimedopens in a new tab or window, "Today's approval demonstrates that Paxlovid has met the agency's rigorous standards for safety and effectiveness." But, just how rigorous were the standards? This question matters in terms of the risk-benefit analysis for prescribing nirmatrelvir-ritonavir to patients, as well as for the standard it sets for approval of other drugs. 

The approval was based on two studies. Published in February 2022, the EPIC-HR (HR is for High Risk) randomized trial reportedopens in a new tab or window that nirmatrelvir-ritonavir reduces the risk of hospitalization and death at 28 days by 86% compared to placebo. The 86% relative risk was calculated from hospitalizations and deaths among those taking nirmatrelvir-ritonavir in relation to the rate for those randomly assigned to placebo. Eight of 1,039 (0.77%) patients who started nirmatrelvir-ritonavir within the first 5 days of COVID symptom onset were hospitalized within 28 days. None died. In contrast, 66 out of 1,046 (6.3%) people who took the placebo were hospitalized and 7 died.

Notably, this study was completed during the dangerous Delta waveopens in a new tab or window -- and it was against this backdrop that the 6.3% hospitalization rate in the control group resulted. Times have now changed, with cases at a significantly lower level than pandemic peaks. During the EPIC-HR study in fall 2021, hospitalizations peaked at 25.4/100,000. For the week ending June 3, 2023, CDC reportedopens in a new tab or window 2.17/100,000 hospitalizations -- a rate approximately 12 times lower than during the EPIC-HR study. Furthermore, EPIC-HR exclusion criterionopens in a new tab or window turned away people who had been vaccinated or previously infected. According to CDC estimates, 96% of the U.S. populationopens in a new tab or window now meet these exclusion criteria. In 2023, it is difficult to find people like the participants in the EPIC-HR study....

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.

• The US FDA has revoked the emergency use authorization for Johnson & Johnson Janssen unit's COVID vaccine. Read more here.
• Janssen voluntarily requested the withdrawal on May 22.
• The company noted that the last lots purchased by the US Government have expired, there is no additional demand in the US, and they do not intend to update the strain composition for emerging variants.
• mRNA vaccines made by Moderna (MRNA) and Pfizer (PFE)/BioNTech (BNTX) account for almost all of the COVID shots administered in the US now.

FDA Letter June 1, 2023:

https://www.fda.gov/media/169003/download 

The Food and Drug Administration (FDA) on Thursday granted full approval to Pfizer’s COVID-19 oral antiviral pill Paxlovid for use in adults who are at high risk for progression to severe disease. The agency’s approval comes nearly a year and a half after the drug received an emergency use authorization, and as hospitalization and deaths from the virus continue to decline. The agency’s approval comes nearly a year and a half after the drug received an emergency use authorization, and as hospitalization and deaths from the virus continue to decline. Paxlovid is given as a 5-day treatment course, and FDA said it should be initiated as soon as possible after a diagnosis of COVID-19 has been made, but no more than five days after symptom onset.  The drug is specifically advised for use in people aged 50 and older as well as those who suffer from certain medical conditions that put them at high risk of developing complications, including hospitalization and severe disease from COVID-19. In March, an FDA independent advisory committee recommended the agency fully approved Paxlovid, finding the medicine was safe and effective for treating COVID-19 in high-risk adults based on three of Pfizer’s clinical trials.  The agency further said Paxlovid does not cause “rebound” COVID-19 infection. 

Paxlovid has been shown to be most effective among patients who have not received a COVID-19 vaccine and those who have not been previously infected. One of Pfizer’s clinical trials showed Paxlovid significantly reduced the proportion of people with COVID-19 related hospitalization or death by 86 percent compared to placebo among patients treated within five days of symptom onset, and 89 percent in those treated within three days, “Today’s approval demonstrates that Paxlovid has met the agency’s rigorous standards for safety and effectiveness, and that it remains an important treatment option for people at high risk for progression to severe COVID-19, including those with prior immunity,” said Patrizia Cavazzoni, director for the FDA’s Center for Drug Evaluation and Research. “The FDA remains committed to working with sponsors to facilitate the development of new prevention and treatment options for COVID-19,” she said. The federal government owns 1.1 million doses of Paxlovid that it already purchased, that are available at pharmacies nationwide. Once that stockpile is used up, distribution will shift to the private sector, and Pfizer will sell directly to health providers. The company sells to the government for about $530 for a 5-day course of treatment, but has not said what it will charge commercially.

FDA Press Release (May 25, 2023):

https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-antiviral-treatment-covid-19-adults 

The FDA approved the first oral fecal microbiota productopens in a new tab or window for preventing recurrent Clostridioides difficile infections in adults, the agency announced on Wednesday. Developed as SER-109 and given the trade name of Vowst, the therapy is indicated for patients who have already received a course of antibiotics for recurrent C. difficile infections. SER-109 -- which involves four pills taken once a day for 3 consecutive days -- contains live bacteria from donor fecal matter, with the donors and stool screened for a slew of pathogens. Despite that, the agency still warns that the product carries the potential risk of transmitting infectious agents or food allergens. "Today's approval provides patients and healthcare providers a new way to help prevent recurrent C. difficile infection," Peter Marks, MD, PhD, director of the FDA's Center for Biologics Evaluation and Research, said in a statement. "The availability of a fecal microbiota product that can be taken orally is a significant step forward in advancing patient care and accessibility for individuals who have experienced this disease that can be potentially life-threatening."

Approval was supported by the randomized ECOSPOR III trialopens in a new tab or window and an open-label studyopens in a new tab or window conducted in the U.S. and Canada. In ECOSPOR III, which involved 182 patients with recurrent infections but with symptoms under control following a course of antibiotics, patients assigned to SER-109 had significantly lower recurrence rates of C. difficile infection through 8 weeks compared with those assigned to placebo (12.4% vs 39.8%, P<0.001). Results were consistent across age groups and largely held up at 24 weeks, at 21.3% in the SER-109 group and 47.3% for the placebo group. C. difficile infections can cause a host of symptoms (diarrhea, abdominal pain, fever) and organ failure or death in severe cases. One of the most common healthcare-associated infections, these infections are linked with anywhere from 15,000 to 30,000 deaths each year. While standard treatment involves antibiotics, these can alter the microbiome and allow C. difficile to return, and few treatments exist for recurrent infections, which are more likely to affect immunocompromised individuals, people over 65, and those who are hospitalized or living in nursing homes. Recurrent C. difficile infection is a highly debilitating and life-threatening disease," said Carl Crawford, MD, of Weill Cornell Medical College in New York City, in a statementopens in a new tab or window from developer Seres Therapeutics, adding that antibiotics alone do not address the underlying cause of recurrent infections -- "dysbiosis of the gut microbiome."

FDA Press release (April 26, 2023):

https://www.fda.gov/news-events/press-announcements/fda-approves-first-orally-administered-fecal-microbiota-product-prevention-recurrence-clostridioides 

Covid-19 antibody drug developers have had a rough time. One by one, antibody medicines that reached the market under emergency use saw their authorized indications narrowed and then revoked by the FDA due to ineffectiveness against newer strains of the virus. By the end of last year, no Covid-19 antibody drugs remained authorized for use in the U.S. InflaRx is showing that Covid-19 antibody drug research is still alive. The FDA this week authorized the biotech’s antibody, vilobelimab, as a treatment for Covid-19 in hospitalized adults. The drug is meant for severe cases. The authorization specifies treatment must start within 48 hours of the patient receiving mechanical ventilation or artificial life support. Jena, Germany-based InflaRx will market its new product under the name “Gohibic.” The antibody drugs whose authorizations were revoked all targeted some part of SARS-CoV-2 in order to prevent it from infecting cells. InflaRx’s target isn’t on the virus. The biotech’s antibody addresses a part of the immune response believed to play a role in the inflammation that leads to Covid-19 progression. The drug targets C5a, a protein of the complement system, which is a part of the immune system.

Authorization of InflaRx’s drug provides an alternative to Olumiant, an Eli Lilly drug. Like Gohibic, Olumiant is also authorized for treating hospitalized patients within 48 hours of starting mechanical ventilation or artificial life support. This Lilly drug works by blocking JAK proteins associated with inflammation. But Olumiant is a small molecule made into a pill—a challenging formulation for patients receiving breathing assistance. Olumiant can be dissolved in water and swallowed or administered via a gastrointestinal tube. But InflaRx’s Gohibic provides yet another dosing option, as that drug is administered as an intravenous infusion. InflaRx initially developed its antibody as a treatment for hidradenitis suppurativa, a rare inflammatory skin disorder. In 2019, the antibody drug failed a Phase 2b test in that indication. With the onset of the pandemic the following year, InflaRx began a clinical trial testing the antibody in Covid-19 patients. The Gohibic EUA request was based on data from a placebo-controlled Phase 3 study that enrolled 369 mechanically ventilated patients in intensive care units. According to study results, after 28 days, the treatment group showed a 23.9% reduction in death from all causes compared to the placebo arm. The most common adverse reactions reported in the study included pneumonia, sepsis, delirium, and pulmonary embolism. The FDA also said serious infections have been reported in Covid-19 patients who received Gohibic. Now that InflaRx has emergency authorization for Gohibic, the company said it is communicating with the FDA about the next steps for a biologics license application seeking full regulatory approval. The company is having similar discussions with regulators in Europe.

FDA Press Release (April 4, 2023):

https://www.fda.gov/drugs/drug-safety-and-availability/fda-authorizes-gohibic-vilobelimab-injection-treatment-covid-19 

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.”

Under new rules just issued by the Food and Drug Administration (FDA), you no longer need a positive COVID-19 test to get a prescription for Paxlovid, an antiviral drug that treats the virus.   The FDA revised the emergency use authorization (EUA) for both Paxlovid and Lagevrio on Wednesday. Fact sheets regarding the updated EUA note a “removal of the requirement for SARS-CoV-2 viral testing.” The reason why a test is no longer necessary is unclear. While removing this barrier to prescription may help to make antivirals more accessible to those who need them, experts say giving COVID medication to someone who may not really need it isn’t a great idea. When Verywell asked for clarification, an FDA spokesperson said “the agency continues to recommend that providers use…viral testing to help diagnose COVID-19.” Recommend, of course, is different than require. Some physicians have voiced concern about the change because COVID symptoms can be similar to other viruses, like RSV. Certain viruses may need very different treatment approaches than Paxlovid or Lagevrio in order to prevent them from progressing to something more severe. “It is impossible to distinguish COVID-19 clinically (without a test) from influenza, RSV, and a myriad of other respiratory viruses,” Amesh Adalja, MD, senior scholar at the Center for Health Security at the Johns Hopkins Bloomberg School of Public Health, told Verywell.

“Regardless of the EUA, best medical practice is to actually confirm COVID-19 before prescribing an antiviral. I don’t think the FDA should be dictating to physicians how to practice medicine, so I would advise my colleagues to ignore the change the FDA made and continue to practice sound, evidence-based medicine.” Others believe the change eliminates an unnecessary barrier to getting people treatment when it’s clear they’re sick. “Although it will still be at the provider’s discretion, we believe these EUA changes will make providers comfortable with prescribing Paxlovid in cases where a participant self-attests to a positive result but is not able to show proof of that result,” Home Test to Treat program director Andrew Weitz, PhD, told Verywell. Home Test to Treat is a new project from the National Institutes of Health (NIH) aimed at providing exclusively virtual COVID care for free, including rapid tests, telehealth sessions, treatments. “This is helpful because some participants may have tested positive but no longer have their test available; perhaps because it was thrown away.”  The change may also be hedging against a future lack of tests. Easy access to free COVID tests will end in May when the COVID-19 public health emergency declaration is lifted, taking federal funding along with it.  

“If the delinking of tests and prescriptions had not happened, the uninsured could face cost barriers if and when they can’t find a free rapid home test or a center offering a PCR test when the public health emergency ends or when the federal supply of tests is depleted,” Jen Kates, PhD, senior vice president at nonprofit health policy group the Kaiser Family Foundation, told Verywell.

[11/30/2022] The U.S. Food and Drug Administration today announced bebtelovimab is not currently authorized for emergency use in the U.S. because it is not expected to neutralize Omicron subvariants BQ.1 and BQ.1.1., according to data included in the Health Care Provider Fact Sheet.  

Nowcast data from the Centers for Disease Control and Prevention published last week estimates that the combined proportion of COVID-19 cases caused by the Omicron BQ.1 and BQ.1.1 subvariants to be above 57% nationally, and already above 50% in all individual regions but one, and data shows a sustained trend of increasing prevalence across all regions. Given that a COVID-19 infection is likely to be caused by a non-susceptible SARS-CoV-2 variant, and consistent with the terms and conditions of the Letter of Authorization, bebtelovimab is not currently authorized for emergency use in any U.S. region at this time.   Eli Lilly and its authorized distributors have paused commercial distribution of bebtelovimab until further notice by the Agency. Additionally, the Administration for Strategic Preparedness and Response (ASPR) has paused the fulfillment of any pending requests under its Bebtelovimab Product Replacement Initiative.  The U.S. Government recommends all product be retained in the event that SARS-CoV-2 variants susceptible to bebtelovimab, which are currently circulating at lower prevalence, become more prevalent in the future in the United States. Retained product must be appropriately held in accordance with storage conditions detailed in the authorized Fact Sheet for Health Care Providers and the Letter of Authorization for bebtelovimab.  Health care providers should use other approved or authorized products that are expected to retain activity against BQ.1 and BQ.1.1 as they choose appropriate treatment options for patients, which include the following: 

• Paxlovid is authorized for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death. 
• Veklury is approved for the treatment of adults and pediatric patients (28 days of age and older and weighing at least 3 kg) with positive results of direct SARS-CoV-2 viral testing, who are not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death. 
• Lagevrio is authorized for the treatment of mild-to-moderate COVID-19 in adults with positive results of direct SARS-CoV-2 viral testing who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate. 

In addition, COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies is authorized for the treatment of COVID-19 in patients with immunosuppressive disease or receiving immunosuppressive treatment, in inpatient or outpatient settings. Individuals for whom COVID-19 vaccination is recommended should consider getting vaccinated with the primary series or, if vaccinated with the primary series, boosted with an updated bivalent vaccine when eligible to increase protection against the most serious consequences of COVID-19, including hospitalization and death. For more information related to the therapeutic management of non-hospitalized patients with mild-to-moderate COVID-19, refer to the NIH COVID-19 Treatment Guidelines.  

All treatment sites can continue ordering Paxlovid, Veklury, and Lagevrio by following the existing ordering processes and reporting procedures, as applicable.  FDA will continue to work with ASPR, the CDC, and the National Institutes of Health on surveillance of variants that may impact the use of the therapies authorized for emergency use. We will provide further updates and consider additional action as new information becomes available.

An outbreak of H5N1 highly pathogenic influenza A virus (HPIAV) has been detected in dairy cows in the United States. Influenza A virus (IAV) is a negative-sense, single-stranded, RNA virus that has not previously been associated with widespread infection in cattle. As such, cattle are an extremely under-studied domestic IAV host species. IAV receptors on host cells are sialic acids (SAs) that are bound to galactose in either an α2,3 or α2,6 linkage. Human IAVs preferentially bind SA-α2,6 (human receptor), whereas avian IAVs have a preference for α2,3 (avian receptor). The avian receptor can further be divided into two receptors: IAVs isolated from chickens generally bind more tightly to SA-α2,3-Gal-β1,4 (chicken receptor), whereas IAVs isolated from duck to SA-α2,3-Gal-β1,3 (duck receptor).

We found all receptors were expressed, to a different degree, in the mammary gland, respiratory tract, and cerebrum of beef and/or dairy cattle. The duck and human IAV receptors were widely expressed in the bovine mammary gland, whereas the chicken receptor dominated the respiratory tract. In general, only a low expression of IAV receptors was observed in the neurons of the cerebrum. These results provide a mechanistic rationale for the high levels of H5N1 virus reported in infected bovine milk and show cattle have the potential to act as a mixing vessel for novel IAV generation.

Preprint in bioRxiv (May 3, 2024):

https://doi.org/10.1101/2024.05.03.592326 

Testing conducted by the FDA on pasteurized commercially purchased milk has found genetic evidence of the H5N1 bird flu virus, the agency confirmed Tuesday. But the testing, done by polymerase chain reaction, or PCR, cannot distinguish between live virus or fragments of viruses that could have been killed by the pasteurization process. The agency said it has been trying to see if it could grow virus from milk found to contain evidence of H5N1, which is the gold standard test to see if there is viable virus in a product. The lengthy statement the agency released does not explicitly say FDA laboratories were unable to find live virus in the milk samples, but it does state that its belief that commercial, pasteurized milk is safe to consume has not been altered by these findings. “To date, we have seen nothing that would change our assessment that the commercial milk supply is safe,” the statement said.

The document was long on assurances but short on details of what has been undertaken or found. It does not specify how many commercial samples were taken or in how many markets, nor does it indicate what percentage of the samples were PCR-positive for H5N1. The statement did not indicate if the testing suggested the amounts of viral genetic material in the milk were low or high. Furthermore, the statement did not reveal if the milk products were purchased in parts of the country where outbreaks have occurred, or in areas where cows haven’t been seen to have been infected. The FDA did say it is testing milk from infected animals, in the processing system, and from store shelves with the goal of producing a “large representative national sample” of the milk supply. Beyond assessing the safety of the supply, such a sample could enable the agency to construct a more robust picture of H5N1’s spread among dairy cows nationally. The agency emphasized that testing of commercially available milk is ongoing, and this includes efforts to discern any potential differences between different dairy products, such as cream and whole milk....

For cardiologist Eric Topol, this week’s vaccine news presented a personal dilemma. Topol, who directs the Scripps Research Translational Institute and is a popular commenter on COVID-19 research, had hoped to get an updated COVID-19 vaccine from Novavax, rather than a messenger RNA (mRNA) shot from Pfizer or Moderna. Novavax relies on an older, protein-based approach that has shown long-lasting effects against other pathogens, and Topol wondered whether it might produce more durable protection. On Tuesday, it seemed he might get his chance: a drugstore he visited for an mRNA vaccine ran out of doses, and hours later the U.S. Food and Drug Administration authorized a Novavax shot well-matched to current COVID-19 variants. The green light marks the first time Novavax will be widely available to teens and adults. “It’s hard to know how it compares” to mRNA vaccines, Topol admits; there are no head-to-head studies to rely on. In clinical trials, Novavax appeared less likely than mRNA shots to cause side effects like headache and fatigue. But how does it stack up against mRNA vaccines when it comes to protection against SARS-CoV-2? The question has been vexingly difficult to answer.

Some hints are emerging, including the first large study of Novavax in the real world, published this week by a team in Italy. The results are far from definitive, but they suggest “there aren’t massive differences” between the vaccines, says Alberto Mateo Urdiales, an epidemiology and infectious disease researcher at the Italian National Institute of Health, who led the study. Whereas mRNA vaccines carry instructions for making a SARS-CoV-2 protein, Novavax directly delivers a fragment of that viral spike protein with an adjuvant for boosting immune response. Such protein subunit vaccines have yielded durable protection against various pathogens including hepatitis B and shingles, along with some respiratory ailments such as pneumonia. A version of the Novavax vaccine targeting the original SARS-CoV-2 variant was approved as a primary vaccination series and first booster in the United States in 2022; it also became available in Europe that year. Its tried-and-true technology appealed to some people wary of the new mRNA approach. And unlike the more fragile mRNA shots, it lasts for months in the refrigerator. But uptake has been low and the company is banking on more shots in arms this fall.

The Italian team tried to pin down how well the shot actually works, analyzing data on more than 20,000 Italians who had received two doses as their primary vaccine series in 2022. After 4 months, the vaccine was 55% effective at staving off symptoms from a SARS-CoV-2 infection and 28% effective at preventing infection altogether, the researchers reported in JAMA Network Open. That’s roughly comparable to how the mRNA vaccines have performed, Mateo Urdiales says. He cautions that the emergence of SARS-CoV-2 variants, repeated boosting, and swelling numbers of infections make it hard to compare numbers across the studies of effectiveness conducted to date. Smaller studies, meanwhile, have tried to address another reason a Novavax booster appeals to people like Topol: the possibility that “mixing and matching” various COVID-19 vaccines might provide better protection than any single vaccine brand. “There was theoretical hope that since these vaccines work in slightly different ways, they would have different strengths in terms of which part of the immune system they activate best,” says Angela Branche, an infectious disease specialist at the University of Rochester. She co-chairs a mix-and-match study called COVAIL that includes another protein subunit vaccine from the company Sanofi, which is not available in the U.S....

The Food and Drug Administration approved the first gene therapy for Duchenne muscular dystrophy, but limited access to those ages four and five. In an eagerly anticipated decision, the Food and Drug Administration Thursday approved the first gene therapy for muscular dystrophy. "Today's approval addresses an urgent unmet medical need and is an important advancement in the treatment of Duchenne muscular dystrophy, a devastating condition with limited treatment options, that leads to a progressive deterioration of an individual's health over time," said Dr. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, in a statement. But the agency rejected a request to make the treatment available to all children with Duchenne muscular dystrophy, the most common form of the incurable muscle disease, who could still walk. Instead, the agency restricted access to patients ages four and five until more evidence is available that the therapy is safe and effective. The decision elicited mixed reactions. Parents of children suffering from the genetic disorder, advocates and some doctors and researchers welcomed the limited approval. But some were disappointed the treatment isn't being made more widely available right away. "Today is a very important day," Debra Miller, who leads CureDuchenne, an advocacy group, told NPR in an interview. "But every single day these boys are losing muscle cells. And so when you have a son with Duchenne and you see them getting weaker right before your eyes, you know we have to get therapies to patients sooner rather than later."

FDA's accelerated approval came with limits

Others, however praised the agency's restraint, though some argued even the limited approval was premature. "This is a really critical decision for the FDA to get right," Dr. Caleb Alexander of Johns Hopkins University told NPR in an interview. Alexander voted against approval during a May meeting of an FDA advisory committee that narrowly recommended the agency grant approval. "This has implications not only for those who may receive this product. But it also sends an important signal regarding what the FDA will require for future products to treat this and similarly devastating diseases," Alexander said. The company that developed the treatment, Sarepta Therapeutics of Cambridge, Mass., said the therapy would be available as soon as possible. The treatment, called Elevidys, will cost $3.2 million for each patient, the company announced shortly after the approval. Sarepta asked the FDA to approve the gene therapy under a program that allows the agency to provide access to treatments before direct evidence is available that they are effective. But this accelerated approval process is controversial because some companies fail to follow through on their promises to confirm their treatments work. A drug approved this way to prevent premature birth was recently withdrawn after being found useless. Sarepta's muscular dystrophy treatment is the first gene therapy approved under the program. The disease, which almost exclusively affects boys, destroys muscles. Most boys end up in wheelchairs before they become teenagers. Eventually, their hearts and lungs give out. Most people with the disease die in their 30s or 40s. The gene therapy works by infusing trillions of harmless viruses in single treatment that has been genetically modified to ferry a gene to patients' muscles.

Evidence for the gene therapy is indirect

The gene produces a miniature version of a protein called dystrophin, that boys with muscular dystrophy are missing or don't have enough of. The hope is this "micro-dystrophin" will at least help slow the progression of the disease. But there's an intense debate about this. Sarepta based its request on how much micro-dystrophin it produces in patients' muscles — without direct evidence that's actually helping alleviate symptoms and prevent disease progression. During the May advisory meeting, parents and doctors showed dramatic videos of children who could barely stand and walk, running, biking and and easily climbing stairs after the treatment. But Alexander and other experts say it remains unclear the treatment is responsible and is safe. "This product is not without risks. And I think the evidence is murky," Alexander says. "The evidence really doesn't meet the bar required to reach market." And children who receive the treatment may then be ineligible to get other treatments in the pipeline that may be more effective. "That's a really non-trivial concern," Alexander said.

But others said there is sufficient evidence to warrant broader approval, including preliminary evidence the treatment is improving boys' muscles, as well as animal data and clear evidence the therapy boosts micro-dystrophin in muscles. "What's the old expression: 'Don't let perfect get in the way of good?' " said Jeffrey Chamberlain, who directs the Muscular Dystrophy Research Center at the University of Washington. That said, Chamberlain was glad the FDA at least approved the treatment for younger children pending further data. "You'd like to see approval for as broad a range of patients as possible. But we'll take what we can get at this point," Chamberlain said. Michael Kelly, the chief scientific officer for CureDuchenne, says he hopes this will lead to other, even more effective gene therapies for the disease. "This is a critical and really important step in treatment and this is going to lead the way and blaze a trail for the next round of better therapeutics," Kelly told NPR in an interview.

The Antiviral Program for Pandemics (APP) team, along with experts from across the National Institutes of Health (NIH) and Biomedical Advanced Research and Development Authority (BARDA), has drafted Target Product Profiles (TPPs) for potential direct-acting antiviral therapeutics candidates targeting several key viruses of pandemic potential.  These TPPs should be considered ‘living documents’ that are never final but may be useful starting points for consideration by therapeutics developers who are drafting TPPs for their specific candidates.  Also, the example TPPs are not intended to provide details about product requirements for funding or other support from USG or other funders.  Instead, these sample TPPs are being provided as tools for scientists working toward therapeutics product development of direct-acting antivirals for use in potential future outbreaks or pandemics. We are happy to receive feedback on these sample TPPs and may make updates/revisions or add TPPs for additional clinical indications in the future, so please monitor this page for updates and send any feedback to APPSubmissions@mail.nih.gov

As Omicron persists, consensus grows for abandoning the ancestral coronavirus strain to improve immune responses. Earlier this year, U.S. regulators settled on a new strategy for COVID-19 vaccines. Like the annual flu shot, the vaccines will be updated each year based on the virus’ evolution, then rolled out in the fall. Accordingly, on 15 June, advisers to the U.S. Food and Drug Administration will weigh which strain or strains of SARS-CoV-2 should make up the next iteration of vaccine, so that the agency can greenlight a version for companies to mass-produce. Regulators may well jettison the original SARS-CoV-2 strain that emerged in China and is long extinct—but which people are still being vaccinated against today. Many scientists favor eliminating it. The ancestral strain “should go out of the formulation,” says William Messer, an infectious disease specialist and viral immunologist at Oregon Health & Science University. Last week, the World Health Organization (WHO) agreed. But other questions loom, including whether to bundle multiple virus strains into the vaccine or just one.

To date, COVID-19 vaccines have been modified only once, when a bivalent version based on both the original strain and the BA.5 Omicron variant was introduced in September 2022. Uptake was disappointing: Only 17% of people in the United States have rolled up their sleeves. (By comparison, about 50% get an annual flu shot.) Furthermore, many researchers say the bivalent vaccine packed less of a punch than it could have. The decision to preserve the ancestral strain sprang from worries that if an entirely new variant emerged, an Omicron-only vaccine might falter against it. This hedging proved unwarranted: All major new variants have flowed from Omicron, which was first detected in South Africa in November 2021. And evidence increasingly shows that a vaccine split between a current strain and one that’s extinct makes it harder for people to mount a strong immune response to the virus. On 4 May, for example, David Ho, a virologist at Columbia University, and his colleagues posted a preprint study of 72 people, including some who had received four doses of the original vaccine and others who’d gotten three doses and a bivalent booster. Those who got the booster didn’t produce antibodies that were notably better at neutralizing Omicron. The reason, Ho explains, is a phenomenon called immunological imprinting, in which repeatedly exposing the immune system to one strain—in this case, the ancestral one—skews the immune response in that direction. When the decision was made to keep the ancestral strain in COVID-19 vaccines, Ho says, imprinting “was probably not a dominant consideration, but it is now.”

Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai, agrees. He and his colleagues published a study this month in The Lancet Microbe in which they studied blood from 16 people 1 month before and about 2 weeks after they got a bivalent booster. After the booster, antibodies in the blood did a slightly better job of neutralizing the ancestral strain than BA.5. Krammer says his team also couldn’t find “specific” antibodies solely reactive to BA.5, which could be especially protective if they’re plentiful. Last week, a WHO advisory group said in a statement that although current COVID-19 vaccines guard against severe disease, “protection against symptomatic disease is limited and less durable.” In place of a bivalent shot, the group recommended a single-strain fall vaccine based on the XBB.1 lineage now dominating across continents, although it left the door open to other effective vaccine recipes. Whether a single-strain XBB.1 vaccine is the best bet or whether multiple Omicron strains should be included is a point of debate. In the past few months, two closely related XBB substrains, XBB.1.5 and XBB.1.16, have crowded out other Omicron variants. “We’re basically trying to guess what the next generation of variants will be, descending from which lineage,” Ho says. “From what we know now, matching the vaccine to whatever circulating variants you’re trying to protect against probably does best,” says Angela Branche, an infectious disease specialist at the University of Rochester. She co-leads a study called COVAIL that’s examining immune responses spurred by different boosters. It has found that monovalent vaccines against Omicron perform somewhat better than those that include the ancestral strain.

An important question is whether vaccines better matched to current strains could reduce not just severe illness, but also transmission—something current vaccines appear to do poorly. An April study in The New England Journal of Medicine showed that after BA.5 faded and other Omicron strains surged, the bivalent vaccine’s ability to prevent transmission peaked at about 30% 2 weeks after someone got the shot and fell to 0% at 16 weeks. “It’s not an unreasonable supposition” that a closer match could perform a bit better, though the effect is still unlikely to persist, Messer says. Some researchers also think the updated vaccines should not be limited to the messenger RNA formulations made by Pfizer and Moderna. Novavax makes a protein subunit vaccine, the technology used in hepatitis B and human papillomavirus vaccines. “It would be good to have protein vaccines for the fall,” as those may give more durable protection, Branche says. But it’s unclear whether the company would be able to mass-produce a new vaccine in time. Robert Frenck, who directs the Vaccine Research Center at Cincinnati Children’s Hospital and helped conduct trials of Pfizer’s COVID-19 vaccine, points out that most vaccines for other infectious diseases “use one methodology,” without causing concern. The strategy against COVID-19 need not be any different, he says. Messer hopes regulators and companies will stay flexible as COVID-19 knowledge continues to grow—and urges targeting the new vaccines to people at highest risk. In the fall, “vaccine fatigue, COVID fatigue, is still going to persist,” he says, and “triaging your efforts to get good vaccine uptake” will be vital.

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.

Most people are still not eligible for a second booster, but the FDA will revisit the topic after an expert panel meets in June. The Food and Drug Administration on Tuesday approved a second omicron booster from Moderna and Pfizer for people over the age of 65 and immunocompromised individuals.

Why it matters: An additional dose of the bivalent vaccine can help high-risk individuals with waning immunity to COVID, the FDA said.

• Most people who have received a single shot of the bivalent vaccine aren't eligible for a second dose, but the FDA could revise criteria after an expert panel meets to discuss the topic in June.

Details: Tuesday's decision means those over 65 can get a second booster no sooner than four months after the first.

• Immunocompromised people may receive the second shot at least two months after receiving the first dose "and additional doses may be administered at the discretion of, and at intervals determined by, their health care provider," the FDA said.
• The agency made additional changes, saying that unvaccinated people may receive a single dose of the bivalent vaccine as their first shot, rather than multiple doses of the original monovalent vaccine.
• Children between six months and five years old who have received up to three doses of the monovalent vaccine may receive a bivalent vaccine shot, but the number of doses they receive "will depend on the vaccine and their vaccination history," per the FDA.
• The monovalent shots from Moderna and Pfizer are no longer authorized for use in the U.S.

What they're saying: "At this stage of the pandemic, data support simplifying the use of the authorized mRNA bivalent COVID-19 vaccines and the agency believes that this approach will help encourage future vaccination," said Peter Marks, director of FDA's Center for Biologics and Research.

• "Evidence is now available that most of the U.S. population 5 years of age and older has antibodies to SARS-CoV-2 ... either from vaccination or infection that can serve as a foundation for the protection provided by the bivalent vaccines," Marks added.

Catch up fast: An FDA advisory committee in January unanimously recommended that the U.S. replace initial doses of the original COVID monovalent shots with bivalent ones to target omicron subvariants, directing Pfizer, Moderna and Novavax to focus on bivalent vaccines.

The Biden administration is moving to make the shot available for older people and those with impaired immune systems. While federal authorities are poised to authorize a second dose of the omicron-targeting coronavirus booster for vulnerable groups, not all experts believe it is necessary. (Kristopher Radder/Brattleboro Reformer/AP) Federal regulators have decided to authorize a second omicron-specific coronavirus vaccine booster shot for people who are at least 65 or have weak immune systems — an effort to provide additional protection to high-risk individuals, according to several officials familiar with the plan. The Food and Drug Administration is expected to announce the step in the next few weeks, and the Centers for Disease Control and Prevention is expected to move quickly to endorse it, said the officials, who spoke on the condition of anonymity because they were not authorized to publicly discuss internal discussions. Eligible individuals will be able to receive the dose as long as it has been at least four months since their first shot of what’s known as the bivalent booster, which targets omicron subvariants BA.4 and BA.5 as well as the original novel coronavirus. The expectation is that consumers will consult with their health-care providers about whether to get the extra booster, the officials said. The FDA’s policy change will be “permissive” — people may get the shot but will not be told they should get it, the officials said. It’s not clear whether the CDC’s vaccine advisory committee would meet to discuss the change before CDC Director Rochelle Walensky makes a final recommendation.

But the company that created the 30-minute, over-the-counter test has filed for bankruptcy, so the product’s eventual availability to consumers remains unclear. The Food and Drug Administration issued an emergency authorization for the first over-the-counter, at-home combination flu and Covid test on Friday, just two days after the company that makes the test announced that it had filed for bankruptcy protection based, in part, on the agency’s lengthy approval timeline. The single-use test works with a self-collected nasal swab and provides a result in about 30 minutes, according to the F.D.A. The test is meant to be used by people 14 and older, or by an adult collecting a sample from someone age 2 or older. The test’s developer, Lucira Health, based in California’s Bay Area, announced its bankruptcy plan on Wednesday, noting that it had expected its emergency-use authorization for the test in August before the onslaught of the flu season. The company said the agency’s authorization process “became protracted,” and said it had high expenditures as it moved forward with manufacturing the combination tests. Without revenue that the company expected from projected sales of the tests during this year’s flu season, Lucira decided that it would pursue a sale of its business but continue operations to serve customers, according to its news release. The bankruptcy plan was reported earlier in The Wall Street Journal.

As the current crisis phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic winds down—and the world nervously awaits potentially dangerous new variants—research into the nature and treatment of so-called long coronavirus disease (COVID) is beginning to ramp up. The White House has promised funding and a federal research roadmap, and dedicated clinics have started cropping up at academic medical centers across the country.  But attempts to understand and treat long COVID have been underway almost since the pandemic began. For more than 2 years, clinicians have been coping—mostly on their own—with streams of patients complaining of persistent symptoms or mysterious new ones after a bout with COVID-19 had seemingly resolved ( 1 ). And collectively, doctors and researchers have already made headway toward identifying some of the mechanisms underlying the condition—formally known as post-acute sequelae of COVID (PASC). That’s not to say that it’s been easy; estimates of the proportion of COVID-19 patients who will report symptoms 12–24 weeks after their infection range from about 30% to 70% ( 2 – 4 ). Some 200 different symptoms have been ascribed to long COVID, and the syndrome is yet to be fully defined. The most common complaints include fatigue, shortness of breath, and a dysfunctional sense of smell ( 5 ). For many, symptoms clear up on their own within 6 months. But one large study in China found that 55% of patients infected early in the pandemic were still struggling with at least one symptom 2 years after infection ( 6 ).

Published in PNAS (September 1, 2022):

https://doi.org/10.1073/pnas.2213524119