Latest COVID-19 studies show need for repeat rapid testing, targeting of antiviral prescriptions

Viral loads of SARS-CoV-2 appear to peak on the fourth day of symptoms, according to a study of patients with omicron-variant infections.

The study included adults who had been newly diagnosed with SARS-CoV-2 and had positive results on polymerase chain reaction (PCR) testing in Georgia in April 2022 to April 2023. Participants provided symptom duration and recent testing history. Nasal swabs were tested with a SARS-CoV-2/flu/respiratory syncytial virus assay and Ct values recorded. To estimate the sensitivity of antigen rapid diagnostic testing on each day after symptom onset, percentages of patients with a cycle threshold (Ct) value less than 30 or 25 were calculated. Results were published by Clinical Infectious Diseases on Sept. 28.

Of a total of 348 patients (65.5% women; median age, 39 years), 91.1% had a history of vaccination, natural infection, or both. By both Ct value and antigen concentration measurements, their median viral loads rose from the day of symptom onset and peaked on the fourth/fifth day. The authors estimated that a rapid antigen test would have sensitivity of 30% to 60.0% on the first day of symptoms, 59.2% to 74.8% on the third day, and 80.0% to 93.3% on the fourth day. An additional 74 studied patients were positive for influenza A on PCR (55.4% women; median age, 35 years), and their median viral loads peaked on the second day of symptoms.

“Our data suggest that the relationship between SARS-CoV-2 Ct value distributions (as a well-established proxy for viral load distributions) and the timing of symptom onset in a highly immune population is very different than the relationship between these parameters observed early in the pandemic—a finding with major implications for testing practice going forward. … In short, early in the pandemic, a single negative antigen test had reasonable negative predictive value early in the course of symptoms,” said the study authors.

Based on these new findings, they called for serial COVID-19 testing recommendations to be updated, potentially advising patients to test a third time if results are negative on the first and third day of symptoms. The findings also have implications for the use of masks and prescription antivirals, the authors said. Finally, the earlier peak in viral load found with influenza A versus COVID-19 will complicate the use of the new multiplex tests that report results for both SARS-CoV-2 and flu, they noted.

Another recent study, published by JAMA Network Open on Oct. 2, assessed the real-world effectiveness of nirmatrelvir/ritonavir (Paxlovid) in a cohort of 6,866 Canadian adults with COVID-19 in 2022 to 2023. It found treatment with nirmatrelvir/ritonavir was associated with statistically significant reductions in the risk of death or hospitalization among patients who were severely (n=560) or moderately (n=2,628) immunocompromised (risk difference [RD] vs. no treatment, −2.5% [95% CI, −4.8% to −0.2%] and −1.7% [95% CI, −2.9% to −0.5%], respectively). However, treatment was not associated with a significant decrease in risk among those who were not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19 or those who were high risk by some other measure, such as age older than 70 years and unvaccinated.

“Stratified analysis of individuals according to vulnerability to complications from COVID-19 is crucial to understanding which individuals should use nirmatrelvir and ritonavir,” said the authors. “In our study, lower-risk individuals, including those older than 70 years who were not moderately or severely immunocompromised, did not appear to benefit from nirmatrelvir and ritonavir.”