Pfizer and Clear Creek Bio are partnering to develop a new Covid-19 treatment, long Covid may cost the U.S. economy almost $4 trillion, and more in this week's roundup of Covid-19 news.

• According to a new study from CDC and Westat Corp, almost 42% of U.S. adults have had Covid-19—but roughly 44% of this group say they have never been infected. For the study, researchers analyzed serologic testing data from 1,574 patients who participated in the National Health and Nutrition Examination Survey between August 2021 and May 2022. In total, 91.5% of participants had SARS-CoV-2 anti-spike antibodies, which suggest either vaccination or previous infection, and 41.2% had anti-nucleocapsid antibodies, which indicate a previous infection. Among the participants who had evidence of a previous infection, 43.7% said they had never had Covid-19, which suggests that their infection was asymptomatic. In addition, 25.5% of participants who had antibodies said they were unvaccinated, which means their antibodies came from an infection. Overall, positivity rates for anti-nucleocapsid antibodies were highest in Black adults (57.1%) and in those with less than a high school education (57.8%). According to the researchers, this suggests there may be health equity concerns regarding who is experiencing unidentified infections. "Younger adults and Black adults with unidentified infections might have been more likely to lack access to testing and to have unknowingly exposed others, resulting in disparities in community transmission," the researchers wrote. "In this way, undiagnosed infections could have amplified disparities in infection rates and outcomes." (Beusekom, CIDRAP News, 12/2)

• As current Covid-19 therapeutics lose their effectiveness against new coronavirus variants, Pfizer and biotech startup Clear Creek Bio are partnering to develop a new Covid-19 treatment to keep up with the constantly evolving virus. Through the partnership, which is in the discovery stage, the companies will research SARS-CoV-2 papain-like protease (PLpro) inhibitors to potentially develop an oral Covid-19 treatment. According to Clear Creek Bio, PLpro is "a unique viral protease that cleaves important host regulators of innate immunity such as ISG15, resulting in dampened antiviral immune mechanisms," such as viral replication. If the research is successful, Pfizer said it will pay Clear Creek Bio with "an undisclosed upfront payment," milestone payments, and royalties. "As COVID-19 continues to evolve, there is a significant need for oral antivirals with novel mechanisms of action," said Vikram Sheel Kumar, CEO of Clear Creek Bio. "We explored the druggable SARS-CoV-2 genome and identified PLpro as a promising and untapped target." (Twenter, Becker's Hospital Review, 12/7; Lagasse, Healthcare Finance, 12/7)

• Long Covid, which may affect up to 23 million Americans, may end up costing the U.S. economy $3.7 trillion, according to new estimates from David Cutler, an economist at Harvard University. Of this total, $2.2 trillion is expected to come from a reduced quality of life, $997 billion from reduced earnings, and $528 billion from increased medical expenses. According to Cutler, the individual cost of medical expenses from long Covid can range from around $3,700 to almost $14,000, with an average of $9,000. Greg Vanichkachorn, medical director of Mayo Clinic's Covid Activity Rehabilitation Program, said, "I think it is important to note that this, again, is an estimate. As new treatment measures come out, things could get more expensive or, hopefully, more affordable. That's the nature of the word 'long-haul' — it can be an open box of costs for a while." (Iacurci, CNBC, 12/1)

• The updated bivalent Covid-19 boosters, which target the omicron subvariants BA.4 and BA.5, are less effective against newer subvariants such as BQ.1.1, XBB, and BA.2.75.2, according to two new studies. In one study published in Nature, researchers from the University of Texas Medical Branch analyzed 29 blood samples. When compared to BA.5, they found that antibodies were four times lower against BQ.1.1 and eight times lower against XBB.1. Another study, which was published the same day in the Lancet, tracked the booster's effectiveness against XBB sublineages and found similar results. Although both studies were small, they are the first data on how the updated boosters are performing against the newer subvariants. Currently, BQ.1.1 is the dominant Covid-19 subvariant, making up 31.9% of all new infections. XBB and BA.2.75.2 currently make up 5.5% and 0.5%, respectively. (Twenter, Becker's Hospital Review, 12/7)

• A compromise defense policy bill released Tuesday includes a requirement to end the Pentagon's vaccine mandates for troops, which was initially issued by Defense Secretary Lloyd Austin in August 2021. If passed, the Pentagon would be required to repeal the vaccine mandate within 30 days of the bill becoming law. According to White House National Security Council spokesperson John Kirby, both the White House and the Pentagon are against removing the vaccine mandate for troops. "What I would say is that we continue to believe that repealing the vaccine mandate is a mistake," Kirby said. "Making sure our troops are ready to defend this country and prepared to do so, that remains the president's priority and the vaccine requirement for Covid does just that." The House passed the bill on Thursday, and if the Senate passes the bill, it will go to President Joe Biden to be signed into law. So far, the White House has not indicated whether President Biden would consider vetoing the bill over the vaccine mandate. (O'Brien, Politico, 12/7; O'Brien, Politico, 12/6)

• One or more doses of a Covid-19 vaccine is 29% effective at preventing symptoms that persist for at least three weeks post-infection, according to a new meta-analysis published in Antimicrobial Stewardship & Healthcare Epidemiology. For the meta-analysis, researchers from the University of Iowa analyzed data from six observational studies from Israel, Italy, the United Kingdom, and the United States on vaccine effectiveness against long Covid published between Dec. 1, 2019, and April 27, 2022. Among the studies' participants, 251,123 had at least one dose of a Pfizer-BioNTech, Moderna, AstraZeneca, or Johnson & Johnson Covid-19 vaccine. In total, 37.6% of vaccinated participants reported symptoms of long Covid compared to 39.1% of unvaccinated participants, resulting in 29.2% vaccine effectiveness against long Covid. Effectiveness was slightly increased among participants who were vaccinated before contracting Covid-19 (35.3%) compared to those who were vaccinated after already being infected (27.4%). "COVID-19 vaccination both before and after having COVID-19 significantly decreased post–COVID-19 conditions for the circulating variants during the study period although vaccine effectiveness was low," the researchers wrote. "Our findings can reassure that individuals with prolonged COVID-19 symptoms who have not been vaccinated that they should do so." (Beusekom, CIDRAP News, 12/6)