Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high global morbidity and mortality risk among patients who have comorbidities. In COVID-19 patients, hypertension, obesity, and diabetes mellitus were found to be the most prevalent comorbidities

The majority of patients who have been infected with SARS-CoV-2 test negative 14-days following initial infection, whereas some patients can remain RNA positive for months. The recent emergence of re-infections, vaccine-breakthrough cases, and variants of concern VOC, such as the Delta variant, which has been observed to rise to higher virus titers, underscore the clinical imperative to interpret positive SARS-CoV-2 results from the same person.

The current gold-standard test for SARS-CoV-2 is the RT-PCR clinical diagnostic test, however, this test is not quantitative. The Ct values gained from the RT-PCR test are inversely correlated with the RNA amount present in a sample, but they are influenced by specimen, patient and diagnostic test characteristics.

In a new study, a collaboration of researchers from various institutes described the natural history of SARS-CoV-2 testing, which includes Ct values among patients who had tested positive multiple times, prior to the emergence of VOCs in the vaccine roll-out. In addition, the authors analyze the timescale of positivity and clinical features of the population of patients with prolonged SARS-CoV-2 positivity.

A preprint version of this study, which is yet to undergo peer review, is available on the medRxiv* preprint server.

Diagnostic testing characteristics of patients with multiple positive SARS-CoV-2 tests

Of the 207 patients who had multiple positive tests in this study who did not display prolonged positivity, 17 showed patterns of intermittent positivity due to having at least one negative test between their first and last positive test. This intermittent positivity was seen over three times more among the 57 patients who displayed prolonged positivity in this study.

Ct values from RT-PCR tests commonly decline over time, but variable rates of decline were observed from the patients within this study. Of patients who had displayed prolonged positivity, 123 of them had Ct values available, obtained from their first and last positive tests.

Among these patients, final positive tests were median 9.8 cycles higher when compared to the first time they tested positive, which indicates lower amounts of RNA were detected. However, 11 of these patients displayed more elevated amounts of RNA in their last positive test when compared to their first.

Overall, final positive tests ranged from 22.5 cycles lower to 31.8 cycles higher, with final positives testing near the detection limit (>35) for 21 patients. The first and last test Ct data was available for 36 of the patients who had prolonged positive tests. Final positive tests were a median of 14 cycles higher than the first positive tests.

As opposed to patients without prolonged positivity, there were no patients with prolonged positivity who had terminal test Ct values lower than their first positive test.

From the prolonged positive patients, 33 had positive tests close to the limit of detection (>35Ct), which is consistent with the decline of viral DNA over time. However, after the first positive test, by day 40, 5 patients still displayed Ct values of <35, and one patient tested positive, exhibiting a Ct value of <35 109 days after the initial positive test.