By Carol A. Kemper, MD, FIDSA
Medical Director, Infection Prevention, El Camino Hospital, Palo Alto Medical Foundation
SOURCE: Frediani JK, Parsons R, McLendon KB, et al. The new normal: Delayed peak SARS-CoV-2 viral loads relative to symptom onset and implications for COVID-19 testing programs. Clin Infect Dis 2023; Sep 28:ciad582. doi: 10.1093/cid/ciad582. [Online ahead of print].
Many times over the past year, I have heard friends and patients who have had symptomatic respiratory infection exclaim that serial home COVID antigen (Ag) tests were repeatedly negative for COVID, but then on the third or fourth day of symptoms, tested positive. This is a different experience than that observed during the earlier years of the pandemic, when kits were first available, and we depended on people to provide home testing results on the first or second day of illness. This apparent change in the performance of the rapid Ag test has not been well characterized — nor really communicated to the public.
In an effort to characterize the hypothetical utility of rapid Ag kits, these authors examined cycle threshold (CT) values in symptomatic adults infected with SARS-CoV-2 relative to the onset of symptoms. From April 2022 to April 2023 (during Omicron), adults presenting with respiratory symptoms had nasal swabs obtained for multiplex Xpert Xpress testing (Cepheid GeneXpert Xpress SARS-CoV-2/Flu/RSV RT-PCR assay). Information on the type and duration of symptoms and history of COVID vaccination was collected, along with information on prior testing within the previous two weeks. SARS-CoV-2 CT values ≤ 30 or ≤ 25 were used as cut-offs for assessing the potential hypothetical performance of rapid Ag testing. No information on influenza vaccination was available.
A new SARS-CoV-2 infection was diagnosed in 348 individuals: 65% were women, the median age was 39 years, and 91% gave a history of vaccination, prior infection, or both. Symptoms included cough (81%), sore throat (79%), and rhinorrhea/congestion (75%). CT values rose from the first day of symptom onset and peaked at day 4-5 of illness. Based on CT values ≥ 30, the estimated sensitivity of rapid Ag testing would be about 30% to 60% on the first day of symptoms, 59% to 75% on the third day of symptoms, and 80% to 93% on the fourth day of symptoms.
For comparison, there were 273 symptomatic adults who reported a positive COVID test within the previous 14 days (by any method). Prior vaccination and/or infection was reported in 87.5% of this group. CT values peaked at the third to fourth day of symptoms.
A smaller group of 74 individuals were PCR+ for influenza. CT values for two influenza targets peaked shortly after symptom onset on day 1 and generally decreased on day 2-3, although some patients remained positive for five to seven days.
Home Ag kits may perform differently than previously expected, with reduced sensitivity at days 1-3 of symptom onset and peak utility at days 4-5 of symptoms. Whether this delayed peak in detection is due to changes in immunity from prior vaccination and/or infection or differences in SARS-CoV-2 strains is not understood. This finding has significant implications for home use of these kits, as well as the use of these kits in the institutional setting when attempting to “clear” individuals. Multiplex kits being developed for use in the home would provide very different sensitivities for influenza and COVID depending on the day of testing relative to symptom onset. This may be difficult to explain to the public, but at the least would require serial testing to improve test reliability.
