PASC defined, analyzed by latest COVID-19 studies

The latest research on COVID-19 looked at postacute sequelae of SARS-CoV-2 (PASC) and the authorized oral antivirals.

A new report from the RECOVER study that helps define PASC was published by JAMA on May 25. The prospective observational data included 9,764 participants from 85 sites in U.S. states and territories (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years). It assessed 44 symptoms and found that 37 symptoms had an adjusted odds ratio of 1.5 or greater associating them with COVID-19 infection. The researchers then developed a PASC score, which assigned point values to the symptoms of postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. With a threshold score of 12, 23% of study participants who had COVID-19 qualified for a diagnosis of PASC, as did 3.7% of those who were not infected. The rate of PASC was lower among those infected in omicron era, at 10%. “This study found that long-term symptoms associated with SARS-CoV-2 infection spanned multiple organ systems. The diversity of symptoms may be related to persistent viral reservoirs, autoimmunity, or direct differential organ injury,” said the study authors.

An important aspect of the study was its clustering of patients by symptoms and degrees of disability “to explore whether there might be different phenotypes of postacute sequelae,” said an accompanying editorial. “It may not be appropriate for an individual debilitated by fatigue and brain fog and another individual who is highly functioning despite loss of taste and smell to similarly be labeled as having the same single entity of PASC.” Another notable finding was the percentage of patients without a history of COVID-19 who met the cutoff for PASC, which is “almost certainly due to overlap of the PASC score criteria with other common chronic symptomatic conditions, such as depression, a disorder whose incidence has risen globally during the COVID-19 pandemic,” the editorial said, noting that the difficulty of differentiating PASC from such other conditions will likely be a limitation of any score.

Another recent study, published by The BMJ on May 31, used data from unvaccinated patients in Switzerland to look at symptoms after COVID-19 infection. It compared 1,106 patients with confirmed SARS-CoV-2 infection to 628 uninfected patients. At six months, 22.9% of infected patients were not yet fully recovered, a rate that dropped to 18.5% at 12 months and 17.2% at 24 months after infection. The point prevalence and severity of COVID-19-related symptoms also decreased over time. Compared to the controls, patients with COVID-19 had an excess risk for individual symptoms ranging from 2% to 10%, with the greatest increases seen in altered taste or smell and postexertional malaise. “Although most participants improved over the study period, some had worsening or alternating courses of health impairment and recovery,” observed the study authors, adding that “a sizable number of people might be affected by post-covid-19 condition and have protracted health issues for many months after infection.”

The results “are consistent with previous studies with similar time frames, and extend our knowledge of post-covid-19 condition to two years after infection,” said an accompanying editorial.

In other COVID-19 research, both nirmatrelvir-ritonavir (which was approved by the FDA on May 25) and molnupiravir reduced mortality in an analysis of veterans who tested positive for SARS-CoV-2 in 2022. The retrospective study, published by Annals of Internal Medicine on June 5, matched targeted cohorts who were at high risk of severe disease by their treatment as outpatients (87% men; median age, 66 years; 18% unvaccinated) and found that those treated with nirmatrelvir-ritonavir had reduced 30-day risk of hospitalization (22.07 vs. 30.32 per 1,000 participants) or death (1.25 vs. 5.47 per 1,000) compared to those receiving neither treatment. Those who got molnupiravir had lower 30-day mortality risk (3.14 vs. 13.56 per 1,000 participants) but no significant decrease in hospitalization versus untreated patients. None of the outcomes were significantly different when the two drugs were compared to each other. The study authors concluded that “nirmatrelvir-ritonavir seems to be an effective treatment for eligible persons with COVID-19 to reduce risk for short-term outcomes of severe COVID-19” but that “benefit of molnupiravir may be more limited.”