Determining the impact of vaccination on SARS-CoV-2 RT-PCR cycle threshold values and infectious viral titres

As the COVID-19 pandemic continues, efforts to better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding and transmission in both unvaccinated and vaccinated populations remain critical to informing public health policies and vaccine development. The utility of using real time RT-PCR cycle threshold values (C_T values) as a proxy for infectious viral litres from individuals infected with SARS-CoV-2 is yet to be fully understood. This retrospective observational cohort study compares quantitative infectious viral litres derived from a focus-forming viral titre assay with SARS-CoV-2 RT-PCR C_T values in both unvaccinated and vaccinated individuals infected with the Delta strain.

Nasopharyngeal swabs positive for SARS-CoV-2 by RT-PCR with a C_T value <27 collected from 26 June to 17 October 2021 at the University of Vermont Medical Center Clinical Laboratory for which vaccination records were available were included. Partially vaccinated and individuals <18 years of age were excluded. Infectious viral litres were determined using a micro-focus forming assay under BSL-3 containment.

In total, 119 specimens from 22 unvaccinated and 97 vaccinated individuals met all inclusion criteria and had sufficient residual volume to undergo viral titring. A negative correlation between RT-PCR C_T values and viral litres was observed in both unvaccinated and vaccinated groups. No difference in mean C_T value or viral titre was detected between vaccinated and unvaccinated groups. Viral litres did not change as a function of time since vaccination.

Our results add to the growing body of knowledge regarding the correlation of SARS-CoV-2 RNA levels and levels of infectious virus. At similar C_T values, vaccination does not appear to impact an individual's potential infectivity when infected with the Delta variant.