Version 1: Determining the impact of vaccination on SARS-CoV-2 RT-PCR cycle threshold values and infectious viral titers

Background: As the COVID-19 pandemic continues, efforts to better understand 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 RT-PCR cycle threshold values (C_T values) as a proxy for infectious viral titers from individuals infected with SARS-CoV-2 is yet to be fully understood. This retrospective observational cohort study compares quantitative infectious viral titers derived from a focus-forming viral titer assay with SARS-CoV-2 RT-PCR C_T values in both unvaccinated and vaccinated individuals infected with the Delta strain.

Methods: Nasopharyngeal swabs positive for SARS-CoV-2 by RT-PCR with a C_T value < 27 collected from June 26th to October 17th of 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 titers were determined using a micro-focus forming assay under BSL-3 containment.

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

Conclusions: 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.