Determining the Incidence of Asymptomatic SARS-CoV-2 Among Early Recipients of COVID-19 Vaccines (DISCOVER-COVID-19): A Prospective Cohort Study of Healthcare Workers Before, During and After Vaccination

North, Crystal M.; Barczak, Amy K.; Goldstein, Robert H.; Healy, Brian C.; Finkelstein, Dianne M.; Ding, Delaney D; Kim, Andy; Boucau, Julie; Shaw, Bennett; Gilbert, Rebecca F; Vyas, Tammy D.; Reynolds, Zahra; Siddle, Katherine J.; MacInnis, Bronwyn; Regan, James; Flynn, James P.; Choudhary, Manish; Vyas, Jatin M.; Laskowski, Karl; Dighe, Anand S.; Lemieux, Jacob E.; Li, Jonathan Z.; Baden, Lindsey R.; Siedner, Mark J.; Sacks, Chana A.

doi:10.1093/cid/ciab643

Cited by 29 publications

(26 citation statements)

References 11 publications

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“…BNT162b2 administration coincided with a significant decrease in wastewater positivity for SARS-CoV-2 RNA concurrent with a decreasing incidence of COVID-19 as observed via clinical testing. This is consistent with observations from clinical samples that found that breakthrough infections of vaccinated individuals were associated with lower virus loads, faster clearance, and the absence of culturable virus . Because of the observational study design, the effects of secular trends on COVID-19 cases on campus, such as changes in campus activity due to reading days and final exams, changes in COVID-19 incidence among the community outside the university, and changes in behavior associated with weather, could not be assessed.…”

Section: Resultssupporting

confidence: 71%

Wastewater Surveillance during Mass COVID-19 Vaccination on a College Campus

Bivins

Bibby

2021

Environ. Sci. Technol. Lett.

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The suitability of wastewater monitoring following widespread vaccination against COVID-19 remains uncertain. SARS-CoV-2 RNA levels were monitored in wastewater solids during a university mass vaccination campaign in which >90% of the 12280 students were fully vaccinated (Pfizer-BioNTech, BNT162b2). SARS-CoV-2 RNA levels in wastewater solids correlated with the 7-day average of COVID-19 cases when lagged by 1–3 days (ρ = 0.51–0.55; p = 0.023–0.039). During and after the second vaccine dose, SARS-CoV-2 RNA was not detected in wastewater solids on 19 of 21 days (12 consecutive days of nondetection at the end of the semester), a significant decrease ( p = 0.027) in positivity rate. A large influx of outside visitors (move out and commencement) led to an immediate increase in wastewater SARS-CoV-2 RNA positivity (seven detections over seven days). Wastewater solids offer a sensitive matrix for environmental surveillance of COVID-19 at the subsewershed level (50% probability of RNA detection with two cases) both during and after mass vaccination. Mass vaccination was coincident with decreased shedding of SARS-CoV-2 RNA into wastewater. This suggests the absence of a large population of shedding infections, symptomatic or not, following mass vaccination among a university campus population.

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Section: Resultssupporting

confidence: 71%

Wastewater Surveillance during Mass COVID-19 Vaccination on a College Campus

Bivins

Bibby

2021

Environ. Sci. Technol. Lett.

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“…Viral load quantification and sequencing was conducted as previously reported ( 14 ). Briefly, we pelleted virions from nasal swab fluids after centrifugation at 21,000 g for 2 hours at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…We additionally performed spike gene amplification, as previously described ( 14 ), to determine variant types for specimens with low viral load to determine variants when whole-genome sequencing was unsuccessful. We used Superscript IV reverse transcriptase (Invitrogen) to conduct cDNA synthesis.…”

Section: Methodsmentioning

confidence: 99%

“…We performed viral culture as previously reported in the BSL3 laboratory of the Ragon Institute of MGH, MIT and Harvard ( 14 , 21 ). Briefly, we detached Vero-E6 cells (ATCC) maintained in DMEM (Corning) supplemented with HEPES (Corning), 1X Penicillin (100 IU/mL)/Streptomycin (100 μg/mL) (Corning), 1X Glutamine (Glutamax, Thermo Fisher Scientific), and 10% FBS (MilliporeSigma) using Trypsin-EDTA (Thermo Fisher Scientific) and seeded the cells at 75,000 cells per well in 24-well plates or 20,000 cells per well in 96-well plates 16–20 hours before infection.…”

Section: Methodsmentioning

confidence: 99%

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Duration of viral shedding and culture positivity with postvaccination SARS-CoV-2 delta variant infections

Siedner¹,

Boucau²,

Gilbert³

et al. 2022

JCI Insight

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Isolation guidelines for severe acute respiratory syndrome-cornavirus-2 (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 (10/10, 100%) in our cohort were symptomatic, compared with 64% (9/14) of non-delta variant infections. Symptomatic delta variant breakthrough infections were characterized by higher initial viral load, longer duration of virologic shedding by PCR, greater likelihood of replication-competent virus at early stages of infection, and longer duration of culturable virus compared to non-delta variants. The duration of time since vaccination was also correlated with both duration of PCR positivity and duration of detection of replication-competent virus. Nonetheless, no individuals with symptomatic 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.

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“…As of June 15, 2021, 90% of individuals living in the greater Boston area had either previously been infected by SARS-CoV-2 and/or were vaccinated. While reinfection can occur despite prior infection and vaccine breakthrough infections occur, those 90% of individuals are much less likely to be at risk of severe COVID-19 were they to now acquire SARS-CoV-2 infection [7][8][9][10][11] . Among the remaining individuals who are therefore at higher risk for severe COVID-19 infection, Black and/or Hispanic individuals are disproportionately represented.…”

Section: Discussionmentioning

confidence: 99%

At-home Testing and Risk Factors for Acquisition of SARS-CoV-2 Infection in a Major US Metropolitan Area

Dryden‐Peterson

Kim

Naz-McLean

et al. 2022

Preprint

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ImportanceUnbiased assessment of risks associated with acquisition of SARS-CoV-2 is critical to informing mitigation efforts during pandemics.ObjectiveUnderstand risk factors for acquiring COVID-19 in a large, prospective cohort of adult residents recruited to be representative of a large US metropolitan area.DesignFully remote longitudinal cohort study launched in October 2020 and ongoing; Study data reported through June 15, 2021.SettingBrigham and Women’s Hospital, Boston MA.ParticipantsAdults within 45 miles of Boston, MA.InterventionMonthly at-home SARS-CoV-2 viral and antibody testing.Main OutcomesBetween October 2020 and January 2021, we enrolled 10,289 adults reflective of Massachusetts census data. At study entry, 567 (5.5%) participants had evidence of current or prior SARS-CoV-2 infection. This increased to 13.4% by June 15, 2021. Compared to whites, Black non-Hispanic participants had a 2.2 fold greater risk of acquiring COVID-19 (HR 2.19, 95% CI 1.91-2.50; p=<0.001) and Hispanics had a 1.5 fold greater risk (HR 1.52, 95% CI 1.32-1.71; p=<0.016). Individuals aged 18-29, those who worked outside the home, and those living with other adults and children were at an increased risk. Individuals in the second and third lowest disadvantaged neighborhood communities, as measured by the area deprivation index as a marker for socioeconomic status by census block group, were associated with an increased risk in developing COVID-19. Individuals with medical risk factors for severe COVID-19 disease were at a decreased risk of SARS-CoV-2 acquisition.ConclusionsThese results demonstrate that race/ethnicity and socioeconomic status are not only risk factors for severity of disease but are also the biggest determinants of acquisition of infection. Importantly, this disparity is significantly underestimated if based on PCR data alone as noted by the discrepancy in serology vs. PCR detection for non-white participants, and points to persistent disparity in access to testing. Meanwhile, medical conditions and advanced age that increase the risk for severity of SARS-CoV-2 disease were associated with a lower risk of acquisition of COVID-19 suggesting the importance of behavior modifications. These findings highlight the need for mitigation programs that overcome challenges of structural racism in current and future pandemics.Trial RegistrationN/AKEY POINTSQuestionWhat population and occupational groups in the United States are at increased risk for acquiring COVID-19?FindingsIn this remote, longitudinal cohort study involving monthly PCR and serology self-testing of 10,289 adult residents of the Boston metropolitan area, 9257 (90.0%) of TestBoston participants acquired evidence of immunity to SARS-CoV-2 through vaccination, infection, or both as of June 15, 2021. Residents identifying as Black, Hispanic/Latinx had an increased risk of acquisition of COVID-19. Healthcare workers were not at increased risk of SARS-CoV-2 acquisition. Individuals with medical risk factors for severe COVID-19 disease were at a decreased risk of SARS-CoV-2 acquisition.MeaningThese results demonstrate that race/ethnicity and socioeconomic status are not only risk factors for severity of disease but also are the biggest determinants of acquisition of infection. These findings highlight the need to address the consequences of structural racism during the development of mitigation programs for current and future pandemics.

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Determining the Incidence of Asymptomatic SARS-CoV-2 Among Early Recipients of COVID-19 Vaccines (DISCOVER-COVID-19): A Prospective Cohort Study of Healthcare Workers Before, During and After Vaccination

Cited by 29 publications

References 11 publications

Wastewater Surveillance during Mass COVID-19 Vaccination on a College Campus

Wastewater Surveillance during Mass COVID-19 Vaccination on a College Campus

Duration of viral shedding and culture positivity with postvaccination SARS-CoV-2 delta variant infections

At-home Testing and Risk Factors for Acquisition of SARS-CoV-2 Infection in a Major US Metropolitan Area

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