key: cord-0704604-9llrpgdu authors: Siedner, M. J.; Boucau, J.; Gilbert, R.; Uddin, R.; Luu, J.; Haneuse, S.; Vyas, T.; Reynolds, Z.; Iyer, S.; Chamberlin, G.; Goldstein, R. H.; North, C. M.; Sacks, C. A.; Regan, J.; Flynn, J. P.; Choudhary, M. C.; Vyas, J. M.; Barczak, A. K.; Lemieux, J.; Li, J. Z. title: Duration of viral shedding and culture positivity with post-vaccination breakthrough delta variant infections date: 2021-10-17 journal: nan DOI: 10.1101/2021.10.14.21264747 sha: f4dadc9b494451bde2dca66b94dd04de266b2627 doc_id: 704604 cord_uid: 9llrpgdu Isolation guidelines for SARS-CoV-2 are largely derived from data collected prior to emergence of the delta variant. We followed a cohort of ambulatory patients with post-vaccination breakthrough SARS-CoV-2 infections with longitudinal collection of nasal swabs for SARS-CoV-2 viral load quantification, whole genome sequencing, and viral culture. All delta variant infections (8/8, 100%) in our cohort were symptomatic, compared with 64% (9/14) of non-delta variant infections. Delta variant breakthrough infections were characterized by higher initial viral load, longer duration of virologic shedding by PCR (median 13.5 vs 4 days, hazard ratio [HR] 0.45, 95%CI 0.17-1.17), greater likelihood of replication competent virus at early stages of infection (6/8 [75%] vs 3/14 [23%], P=0.03), and longer duration of culturable virus (median 7 vs 3 days, HR 0.38, 95%CI 0.14-1.02) compared to non-delta variants. Nonetheless, no individuals with delta variant infections had replication competent virus by day 10 after symptom onset or 24 hours after resolution of symptoms. These data support current US Center for Disease Control isolation guidelines and reinforce the importance of prompt testing and isolation among symptomatic individuals with delta variant breakthrough infections. Additional data are needed to evaluate these relationships among asymptomatic and more severe delta variant 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 (which was not certified by peer review) Similarly, we found evidence that time to negative viral load by PCR was longer for individuals 100 infected more than 3 months after completion of vaccination compared to those infected within 3 101 months of vaccination (median time 13.5 vs 3 days, HR 0.23, 95%CI 0.08, 0.65, Figure 2C 119 120 Unlike our study, a prior study showed similar trajectories and duration of virologic shedding as 121 detected by PCR between delta and alpha viral variants, and shorter duration of shedding among 122 delta variant infections than we found (median 6 vs 13.5 days) (11). We suspect that this difference 123 is explained by distinct features of our study populations. Whereas that former study included 124 relatively young individuals being tested as part of their affiliation with a sports league, study 125 subjects with breakthrough delta infections in our study population were comparatively older adults 126 and accessing SARS-CoV-2 testing through a healthcare system. Our data are in keeping with current guidelines recommending isolation for 10 days or until 129 symptom resolution for symptomatic post-vaccination breakthrough infections and add new 130 evidence in support of these guidelines in the delta variant era. These results also reinforce that 131 . 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 preprint this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21264747 doi: medRxiv preprint post-vaccination breakthrough delta infections should be considered contagious and highlight the 132 critical importance of prompt testing for symptomatic vaccinated individuals due to the high ambulatory individuals. We did not perform ongoing contact tracing in our study. Therefore, our is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21264747 doi: medRxiv preprint resuspended it in DEPC-treated water (ThermoFisher). We quantified SARS-CoV-2 RNA virus forward and reverse primers, and the probe. We quantified viral copy numbers using N1 qPCR 183 standards in 16-fold dilutions to generate standard curves. Each sample was run in triplicate with 184 two non-template control (NTC) wells that were included as negative controls. Additionally, we is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21264747 doi: medRxiv preprint conduct cDNA synthesis. To exclude PCR artifacts, we used two strategies to amplify the SARS- . 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 preprint this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21264747 doi: medRxiv preprint . 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 preprint this version posted October 17, 2021. ; . 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. 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