Regular exercise may reduce people's risk of hospitalization and death from Covid-19, CDC is partnering with a genomics company to study severe breakthrough infections, and more in this week's roundup of Covid-19 news.

• Smell "retraining" did not significantly improve olfactory symptoms in patients with Covid-19-related smell loss, according to a new study published in JAMA Otolaryngology—Head & Neck Surgery. In a randomized trial, 275 patients with smell loss from Covid-19 were equally assigned to four different interventions: bimodal patient-preferred, bimodal physician assigned, unimodal patient-preferred, and unimodal physician-assigned scents. Among the patients, the average duration of smell loss was six months, and most reported their sense of smell as either poor (62%) or absent (19%). Overall, the researchers found that none of the study groups had a meaningful change in their University of Pennsylvania Smell Identification Test (UPSIT) scores from pre-intervention to post-intervention. However, the researchers noted that "when the percentage of participants who experienced a clinically meaningful improvement in absolute [UPSIT] score was defined and compared between groups, the highest percentage of participants experiencing improvement was in the bimodal arms." In addition, participants who received any of the interventions were more likely to report clinically meaningful improvement compared to a control group. In general, "[t]he variations in this study's results based on chosen [semi-objective versus subjective] outcome measure can make it difficult to place these findings in clinical context and further highlight a challenge in the field of olfactory research," wrote Carol Yan from the University of California, San Diego, in an accompanying editorial. "The definition of olfactory improvement remains nuanced." Although the benefits of olfactory training are not clear cut, Yan said "these techniques can be considered while developing a treatment plan for an individual patient, somewhat similar to developing a physical therapy regimen" since the training is "a noninvasive therapeutic with minimal risk and low cost." (Kneisel, MedPage Today, 12/29)

• A regular exercise regimen may significantly reduce the risk of hospitalization or death from Covid-19, according to a new study published in the American Journal of Preventive Medicine. For the study, researchers examined the records of 194,191 adult patients at Kaiser Permanente who had received a positive Covid-19 test between January 2020 and May 2021. Of these patients, around 2% were vaccinated before they were infected. Each patient was asked to report their exercise patterns at least three times in the two years before they were infected by the virus. Patients were divided into five groups based on their weekly activity levels: always inactive (10 minutes or less), mostly inactive (10-60 minutes), some activity (60-150 minutes), consistently active (a median of 150 minutes or more), and always active (more than 150 minutes). Overall, the researchers found that patients in the always inactive group were 91% more likely to be hospitalized from Covid-19 and 291% more likely to die from the disease than patients who were consistently active. "The benefits of reducing physical inactivity should lead to its recommendation as an additional pandemic control strategy for all, regardless of demographics or chronic disease status," the researchers wrote. (Archie, NPR, 12/23)

• An experimental oral antiviral (VV116) performed similarly to Paxlovid in treating mild-to-moderate Covid-19 in adults with a risk of severe disease from the virus and may even be safer, according to the results of a Phase III trial from China. The trial, which was conducted between April 4 and May 2, included 882 patients who were randomly assigned to receive either VV116 or Paxlovid for five days. Many of the patients had risk factors for severe illness, including being 60 or older, cardiovascular disease, and obesity. After excluding any patients for discontinuations, non-adherence, or non-administration, a total of 771 patients were included in the final analysis and completed 28-day assessments. Overall, the researchers found that VV116 performed similarly to Paxlovid on time to sustained clinical recovery, but the proportion was higher for those who had received VV116. Patients on VV116 also recovered a median of four days after starting the treatment, while patients on Paxlovid recovered a median of five days after treatment. In addition, patients who received VV116 reported fewer adverse events over the course of 28 days than those who had received Paxlovid (67.4% vs. 77.3%, respectively). According to the researchers, these results suggest that VV116 is noninferior to Paxlovid when it comes to treating mild-to-moderate Covid-19 in high-risk patients. However, some limitations of the study include the lack of a placebo group and limited diversity among the patients. (Hein, MedPage Today, 1/3)

• A long Covid rehabilitation program in the United Kingdom has shown "impressive" results, according to a new study published in the Journal of Medical Virology. The program, which focuses on gradual or paced increases in physical activity, was administered to long Covid patients as part of the Leeds Community Healthcare National Health Service Trust. In the study, 31 patients followed the World Health Organization CR-10 Borg pacing protocol, which includes five activity levels and rates how active a patient is as well as their level of exertion. Before starting the program, the patients had had long Covid for an average of 17 months and experienced three "crashes" per week where they felt exhausted after mild physical or mental exertion. By the end of the six-week program, the average number of crashes patients experienced declined from 3.4 to 1.1. The patients also experienced an average 16% decrease in crashes each week and saw a reduction in three exertional triggers (physical, cognitive, and emotional). Other symptoms, such as breathlessness, headache/migraine, and palpitations, also declined each week. "The findings of this research are exciting because this is the first time that crashing episodes have been used as a marker for the condition and a structured pacing programme has now been shown to substantially reduce symptoms and improve quality of life," said Manoj Sivan, an associate clinical professor in the University of Leeds School of Medicine who led the study. (Hou, "Changing America," The Hill, 12/15; University of Leeds press release, 12/15)

• CDC on Wednesday awarded Helix, a population genomics and viral surveillance company, a contract to study how human genetics may impact the efficacy of Covid-19 vaccines. In the study, researchers will analyze up to 10,000 people who have experienced severe breakthrough infections despite being fully vaccinated. "The new research conducted by Helix and CDC will uncover meaningful information to better understand and inform what we know of long COVID and other adverse effects," said Daniel Lee, SVP of life sciences and growth at Helix. "This includes the durability of vaccine-induced immunity, spacing between vaccine doses and more, all against the backdrop of emerging viral variants within the context of an individual's underlying human genetics." According to Becker's Hospital Review, this new study further deepens CDC's partnership with Helix, which has helped the agency track Covid-19 variants. (Bean, Becker's Hospital Review, 1/4)