SARS-CoV-2 viral load dynamics and real-time RT-PCR cycle threshold interpretation in symptomatic non-hospitalised individuals in New Zealand: a multicentre cross sectional observational study

Abstract

We conducted a multicentre cross sectional observational study of laboratory, public health and hospitalisation data for PCR-confirmed COVID-19 cases within the New Zealand Northern Region, between 12 February and 8 June 2020. The aim of this study was to describe population level SARS-CoV-2 upper respiratory tract (URT) viral load dynamics by stratifying positivity rates and polymerase chain reaction (PCR) cycle threshold (Ct) values of URT samples from COVID-19 cases by days since symptom onset, and to explore utility of Ct values in determining length of time post-infection and thus potential infectivity. Of 123,124 samples tested for SARS-CoV-2 by PCR, 579 samples (407 positive and 172 negative) from 368 symptomatic non-hospitalised individuals with PCR-confirmed infection were included. Sample positivity rate was 61.5% (8/13) for pre-symptomatic samples, rising to 93.2% (317/340) for samples collected during the purported symptomatic infectious period (days 0-10 post-symptom onset), and dropping to 36.3% (82/226) for postinfectious period samples (day 11 onwards). URT viral load peaked shortly after symptom onset, with median Ct values ranging 20.00-29.99 until 15 days post-symptom onset, and >30.00 after this time. Of samples with a Ct value of <20.00, 96.1% were collected during the symptomatic infectious period. However, of samples with a Ct value 30.00 and 35.00, 46.9% and 18.5%, respectively, were also collected during the symptomatic infectious period. The findings of this study indicate that at or soon after symptom onset represents the optimum time to test for SARS-CoV-2 in the URT, with median Ct values suggesting the useful testing window extends until around 15 days post-symptom onset. In asymptomatic individuals or those with unknown dates of symptom onset, Ct values <20.00 imply recent onset/potential infectivity, but Ct values 30.00 or 35.00 do not exclude recent onset/potential infectivity. Individual sample Ct values should not be used as an absolute marker of length of time post-infection or to exclude infectivity where date of symptom onset is unavailable.

Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2

“…Viral shedding time was defined from the first positive nucleic acid test to the first negative test (in two consecutive, intervals of 24 h) ( 5 ). The time from the onset of diagnosis to patient enrollment was considered to be the time from the first positive nucleic acid test to the date of first hospitalization ( 23 , 24 ).…”

Clinical associations of SARS-CoV-2 viral load using the first WHO International Standard for SARS-CoV-2 RNA

“…These findings are consistent with a report from New Zealand where Ct values ranged from <20 to >35 more than 10 days from symptom onset in non-hospitalised patients. 17 Apart from differences in the virus behaviour between individuals, the heterogeneity of respiratory samples and variability in collection method likely contribute to these poorly reproducible quantitative results which is not a problem encountered with quantitative testing of blood, serum or plasma. Nucleic acid extraction, amplification and detection are not the cause of quantitative variability, as we found excellent performance of serial dilution of the First WHO IS SARS-CoV-2 RNA, and very strong correlation of the two gene targets of the cobas SARS-CoV-2 PCR assay.…”

Evaluating the Ability to ID (COVID-19) NOW: a Large Real-World Prospective Evaluation of the Abbott ID NOW COVID-19 Assay

“…( 17 – 20 ). However, several attempts have been made to determine correlating C T values with infectivity, giving variable results ( 21 – 27 ). We therefore feel that any extrapolation as to whether these 21 patients are infectious or not cannot be verified by the information we have collected this study.…”