key: cord-0077547-np1y2fkt
authors: Ke, Ruian; Martinez, Pamela P.; Smith, Rebecca L.; Gibson, Laura L.; Achenbach, Chad J.; McFall, Sally; Qi, Chao; Jacob, Joshua; Dembele, Etienne; Bundy, Camille; Simons, Lacy M.; Ozer, Egon A.; Hultquist, Judd F.; Lorenzo-Redondo, Ramon; Opdycke, Anita K.; Hawkins, Claudia; Murphy, Robert L.; Mirza, Agha; Conte, Madison; Gallagher, Nicholas; Huai Luo, Chun; Jarrett, Junko; Conte, Abigail; Zhou, Ruifeng; Farjo, Mireille; Rendon, Gloria; Fields, Christopher J.; Wang, Leyi; Fredrickson, Richard; Baughman, Melinda E.; Chiu, Karen K.; Choi, Hannah; Scardina, Kevin R.; Owens, Alyssa N.; Broach, John; Barton, Bruce; Lazar, Peter; Robinson, Matthew L.; Mostafa, Heba H.; Manabe, Yukari C.; Pekosz, Andrew; McManus, David D.; Brooke, Christopher B.
title: Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution
date: 2022-04-13
journal: Open Forum Infect Dis
DOI: 10.1093/ofid/ofac192
sha: 228917ff6732d4af0919d3357a53cd5d05ea69e0
doc_id: 77547
cord_uid: np1y2fkt

BACKGROUND: The global effort to vaccinate people against SARS-CoV-2 during an ongoing pandemic has raised questions about how vaccine breakthrough infections compare with infections in immunologically naive individuals, and the potential for vaccinated individuals to transmit the virus. METHODS: We examined viral dynamics and infectious virus shedding through daily longitudinal sampling in 23 adults infected with SARS-CoV-2 at varying stages of vaccination, including 6 fully vaccinated individuals. RESULTS: The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. INTERPRETATION: Vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.

The durations of both infectious virus shedding and symptoms were significantly 11 reduced in vaccinated individuals compared with unvaccinated individuals. We also 12 observed that breakthrough infections are associated with strong tissue 13 compartmentalization and are only detectable in saliva in some cases. Patient consent statement 6 This study was approved by the Western Institutional Review Board, and all 7 participants provided informed consent. were also entered in the NU QI program. They were instructed to quarantine and 1 were eligible to enroll in this study for up to 5 days after their last known exposure to 2 an infected individual. All participants were also required to have received a negative 3 nasal swab LAMP assay result 7 days prior to enrollment. 4 Individuals were recruited via either a link shared in an automated text message 5 providing isolation information sent within 30 minutes of a positive test result, a call 6 from a study recruiter, or a link shared by an enrolled study participant or included in 7 information provided to all quarantining close contacts. In addition, signs/flyers were 8 used at each testing location and a website was available to inform the community 9 about the study.

Participants were required to be at least 18 years of age, have a valid university ID, 11 speak English, have internet access, and live within 8 miles of the university campus.

After enrollment and consent, participants completed an initial survey to collect 13 information on demographics, vaccination status, prior infection history, and health 14 history and were provided with sample collection supplies. Participants who tested 15 positive prior to enrollment or during quarantine were followed for up to 14 days. 16 Quarantining participants who continued to test negative by saliva RTqPCR (UIUC) or 17 nasal swab RTqPCR (NU) were followed for up to 7 days after their last exposure. All Each day, participants were remotely observed by trained study staff collecting: 4 1. 2 mL of saliva into a 50mL conical tube (UIUC study site only). 5 2. 1 nasal swab from a single nostril using a foam-tipped swab that was placed 6 within a dry collection tube. The order of nostrils (left vs. right) used for the two different swabs was randomized.

For nasal swabs, participants were instructed to insert the soft tip of the swab at least After collection, saliva samples were stored at room temperature and RTqPCR was 19 run within 12 hours of initial collection. The protocol for the covidSHIELD direct saliva-20 to-RTqPCR assay used has been detailed previously [8, 9] . In brief, saliva samples Combo kit assay.

Foam-tipped nasal swabs were placed in collection tubes, transported with cold packs, and 2 stored at 4°C overnight based on guidance from the manufacturer. The morning after 3 collection, swabs were run through the Sofia SARS antigen FIA on Sofia 2 devices according 4 to the manufacturer's protocol. 5 Nasal swab RTqPCR 6 For UIUC cohort, collection tubes containing VTM and flocked nasal swabs were 7 stored at -80°C after collection and were subsequently shipped to Johns Hopkins 8 University for RTqPCR and virus culture testing. After thawing, VTM was aliquoted for 9 RTqPCR and infectivity assays. One ml of VTM from the nasal swab was assayed on after first vaccine dose (either mRNA or J&J)), captured at two study sites through 24 daily nasal swab and saliva collection, along with symptom reporting (Fig 1A-C) .

These individuals were primarily infected with B.1.1.7 (Alpha) and P.1 (Gamma) 1 variants, as enrollment in this study concluded before the widespread circulation of 2 Delta at the study sites (Table S1). As part of the same study and recruitment 3 program, we also enrolled 60 infected unvaccinated individuals (median age = 22; age 4 range = 19-73). Details on these individuals were described previously [7] . exception of three that appeared to exhibit restricted shedding (Fig. 1C) . These data illustrate that Ct/CN values cannot be used as a simple surrogate for infectious 7 potential. 8 We next examined whether there were any differences in self-reported symptoms 9 between vaccinated and unvaccinated individuals (using the 60 unvaccinated 10 individuals previously reported[7]) (Fig. 1F) . A Poisson regression shows that those 11 who received at least one vaccine dose had significantly more days with no reported 12 symptoms than the unvaccinated (p<0.0001). The mean proportion of study days with 13 no symptoms was 0.74 in the vaccinated group dose compared with 0.37 in the 14 unvaccinated group (range: 0 to 1 for both groups).

Finally, we examined the relationship between viral culture and antigen FIA results in 16 vaccinated (fully plus partially) and newly vaccinated individuals (Fig 1G) . We This study has several limitations that must be considered. First, the study cohort size 2 is small, thus making it hard to draw firm quantitative conclusions. Second, our study 3 cohort is biased towards breakthrough infections that were detected in our on-campus 4 screening programs (saliva-based RTqPCR at UIUC, nasal swab-based LAMP assay 5 at NU). Finally, enrollment in this study concluded before the arrival of the Delta Health and Human Services. 10 sample collection and processing at the UIUC study site. 23 We also wish to thank Kate Klein, Amelia Kelly, Nour Sayegh, Michael Govern,

Mackenzie Furnari-Stickney, Sara Caudillo, Elizabeth Christain, Kristen Weber, James Newcomb, Kenyetta Sims, and Carol Govern for their efforts supporting recruitment, 5 enrollment, logistics, and/or sample collection and processing at the NU study site. 6 We also thank Jeffrey Olgin, Noah Peyser, and Xochitl Butcher for assistance with the RTqPCR test used in this study. 

Individuals cannot rely on COVID-19 herd immunity: Durable immunity to viral 2 disease is limited to viruses with obligate viremic spread

Vaccination with BNT162b2 reduces transmission of 5 SARS-CoV-2 to household contacts in Israel

Vaccinated and unvaccinated individuals have 8 similar viral loads in communities with a high prevalence of the SARS-CoV-2 delta variant

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Estimating vaccine efficacy against transmission via 19 effect on viral load

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We wish to thank Shumon Ahmed, Carly Bell, Nate Bouton,