key: cord-0996711-f3mvdpq1 authors: Acharya, C. B.; Schrom, J.; Mitchell, A. M.; Coil, D. A.; Marquez, C.; Rojas, S.; Wang, C. Y.; Liu, J.; Pilarowski, G.; Solis, L.; Georgian, E.; Petersen, M.; DeRisi, J.; Michelmore, R.; Havlir, D. title: No Significant Difference in Viral Load Between Vaccinated and Unvaccinated, Asymptomatic and Symptomatic Groups Infected with SARS-CoV-2 Delta Variant date: 2021-09-29 journal: nan DOI: 10.1101/2021.09.28.21264262 sha: 861360d207b83faf1a47511e3b12284bb5645216 doc_id: 996711 cord_uid: f3mvdpq1 We found no significant difference in cycle threshold values between vaccinated and unvaccinated, asymptomatic and symptomatic groups infected with SARS-CoV-2 Delta. Given the substantial proportion of asymptomatic vaccine breakthrough cases with high viral levels, interventions, including masking and testing, should be considered for all in settings with elevated COVID-19 transmission. 2 Abstract: We found no significant difference in cycle threshold values between vaccinated and unvaccinated, asymptomatic and symptomatic groups infected with SARS-CoV-2 Delta. Given the substantial proportion of asymptomatic vaccine breakthrough cases with high viral levels, interventions, including masking and testing, should be considered for all in settings with elevated COVID-19 transmission. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264262 doi: medRxiv preprint 3 Vaccines reduce infection, severe disease, and death from SARS-CoV-2 (COVID-19) [1] , yet breakthrough cases occur [2] . Several reports show no difference in cycle threshold values (Ct-values) between vaccinated and unvaccinated individuals [2, 3, 4] ; however, others have suggested that breakthrough infections, particularly among asymptomatic individuals, have a lower viral load and therefore may be less likely to result in transmission [5, 6] . Data was collected on individuals who voluntarily sought testing for SARS-CoV-2 from two demographically distinct populations in California during a two-month period from June 17 to August 31, 2021, during which Delta was the predominant variant. HYT: As part of the response to the COVID-19 pandemic, UC Davis deployed an extensive free asymptomatic testing program that included the City of Davis and Yolo County (Healthy Yolo Together). Asymptomatic individuals over the age of 2 were eligible for testing. Asymptomatic cases were classified as individuals not reporting symptoms at the time of testing. Samples were collected through a supervised method in which individuals transferred their saliva into a barcoded tube (COVID-19 Testing | Campus Ready). Smaller numbers of symptomatic . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264262 doi: medRxiv preprint 4 individuals were processed using a different workflow and an antigen test; therefore, they were not included in this study. UeS: The study population included individuals who sought SARS-CoV-2 testing at the UeS walk-up site, an ongoing academic (UC San Francisco, CZ Biohub, and UC Berkeley), community organization (Latino Task Force), and government (SFDPH) partnership. The outdoor, free BinaxNOW™ testing site was located at a public transport and commercial hub in the Mission District, a setting of ongoing transmission in San Francisco [7] . Individuals one year of age and older, with or without symptoms, were eligible for testing. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. and variant/lineage determination as previously described [8, 9] . Ct-values for the detection of N and E genes [8] were determined via the single threshold Cq-determination mode using Bio-Rad CFX Maestro v4.1 (Bio-Rad Inc). SARS-CoV-2 genomes were sequenced using the Illumina NovaSeq platform. Consensus genomes were generated via the COVID module of the IDseq pipeline (https://idseq.net) as described [9] . Ct-values were plotted, stratified by site; fully vs. not vaccinated; and symptom status. Partially vaccinated samples and stratification by age and vaccine type are reported in supplementary materials. Ct-values between strata were compared using a two sided t-test. HYT: The Genome Center laboratory that conducted COVID-19 testing was CLIA approved as an extension to the Student Health Center's laboratory. The UC Davis IRB . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264262 doi: medRxiv preprint 6 Administration determined that the study met criteria for public health reporting and was exempt from IRB review and approval. UeS: The UC San Francisco Committee on Human Research determined the study met criteria for public health surveillance. All participants provided informed consent for testing. A total of 869 samples, 500 from HYT and 369 from UeS, were included in the analysis. samples, overall or stratified by vaccine status (Fig. 1B) . Similar Ct-values were also found among different age groups, between genders, and vaccine types (Supplemental Figure 1) . In all groups, there were individuals with low Ct-values indicative of high viral loads. A total of 69 fully vaccinated individuals had Ct-values <20. Of these, 24 were asymptomatic at the time of testing. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264262 doi: medRxiv preprint In our study, mean viral loads as measured by Ct-value were similar for large numbers of asymptomatic and symptomatic individuals infected with SARS-Cov-2 during the Delta surge, regardless of vaccine status, age, or gender. This contrasts with a large ongoing UK community cohort in which the median Ct-value was higher for vaccinated individuals (27.6) than for unvaccinated individuals (23.1) [5] . Also, a study from San Francisco reported that 10 fully vaccinated asymptomatic individuals had significantly lower viral loads than 28 symptomatic, vaccinated individuals [6] . Our study is consistent with other recent reports showing similar viral loads among vaccinated and unvaccinated individuals in settings with transmission of the Delta variant. In a Wisconsin study, Ct-values were similar and culture positivity was not different in a subset of analyses between 11 vaccinated and 24 unvaccinated cases [4] . In both Massachusetts and Singapore, individuals with vaccination breakthroughs caused by the Delta variant had similar Ct-values as unvaccinated individuals [3, 10] . Our findings are supported by consistency across large sample sets using different assays from two distinct locations. A substantial proportion of asymptomatic, fully vaccinated individuals in our study had low Ct-values, indicative of high viral loads. Given that low Ct-values are indicative of high levels of virus, culture positivity, and increased transmission [11] , our detection of low Ct-values in asymptomatic, fully vaccinated individuals is consistent with the potential for transmission from breakthrough infections prior to any emergence of symptoms. Interestingly, the viral loads decreased more rapidly in vaccinated than unvaccinated individuals in Singapore [3] , suggesting that vaccinated individuals may remain infectious for shorter periods of time. Over 20% of positive, vaccinated individuals had low Ct-values (<20), a third of which were asymptomatic when tested. This highlights the need for additional studies of the immunological status of such vaccine escapes and how infectious they are. If such individuals . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The data gathered in this study during the surge of the Delta variant strongly support the notion that neither vaccine status nor the presence or absence of symptoms should influence the recommendation and implementation of good public health practices, including mask wearing, testing, social distancing, and other measures designed to mitigate the spread of SARS-CoV-2. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264262 doi: medRxiv preprint National Study Group for C-V. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study Despite Vaccination REACT-1 round 13 final report: exponential growth, high prevalence of SARS-CoV-2 and vaccine effectiveness associated with Delta variant in England during Predominance of antibody-resistant SARS-CoV-2 variants in vaccine breakthrough cases from the Performance Characteristics of a Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Detection Assay at a Public Plaza Testing Site in San Francisco Rapid deployment of SARS-CoV-2 testing: The CLIAHUB Estimation of secondary household attack rates for emergent spike L452R SARS-CoV-2 variants detected by genomic surveillance at a communitybased testing site in San Francisco Outbreak of SARS-CoV-2 infections, including COVID-19 vaccine breakthrough infections CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted Dr. DeRisi reports being a scientific advisor to the Public Health Co. and a scientific advisor to Allen & Co. Dr. Havlir reports non-financial support from Abbott outside of the submitted work. The other authors declare no competing interests.. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprintThe copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264262 doi: medRxiv preprint