Background: COVID-19 vaccine trials and post-implementation data suggest vaccination decreases SARS-CoV-2 infections. Objective: Estimate COVID-19 vaccinations impact on SARS-CoV-2 case rates and viral diversity among healthcare workers (HCW) during a high community prevalence period. Design, Setting, Participants: A prospective cohort study from Boston Medical Center (BMC)s HCW vaccination program, where staff received two doses of BNT162b2 or mRNA-1273. Measurements: PCR-confirmed SARS-CoV-2 cases among HCWs from December 09, 2020 to February 23, 2021. Weekly SARS-CoV-2 rates per 100,000 person-day overall and by time from first injection (1-14 and >14 days) were compared with surrounding community rates. Viral genome sequences from SARS CoV-2 positive samples. Results: SARS-CoV-2 cases occurred in 1.4% (96/7109) of HCWs given at least a first dose and 0.3% (17/5913) of HCWs given both vaccine doses. Adjusted SARS-CoV-2 infection rate ratios were 0.73 (95% CI 0.53-1.00) 1-14 days and 0.18 (0.10-0.32) >14 days from first dose. HCW SARS-CoV-2 cases >14 days from initial dose compared to within 14 days were more often older (46 versus 38 years, p=0.007), Latinx (10% versus 8%, p=0.03), and asymptomatic (48% versus 11%, p=0.0002). SARS-CoV-2 rates among HCWs fell below those of the surrounding community, with a 18% versus 11% weekly decrease respectively (p=0.14). Comparison of 48 SARS-CoV-2 genomes sequenced from post-first dose cases did not indicate selection pressure towards known spike-antibody escape mutations. Limitations: Unable to adjust for infection risk outside of the workplace. Lack follow up on symptoms post SARS-CoV-2 diagnosis. Small number of vaccinated HCW cases. Conclusion: Our results indicate a positive impact of COVID-19 vaccines on SARS-CoV-2 case rates. Post-vaccination isolates did not show unusual genetic diversity or selection for mutations of concern.

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BackgroundIn January 2022, United States guidelines shifted to recommend isolation for 5 days from symptom onset, followed by 5 days of mask wearing. However, viral dynamics and variant and vaccination impact on culture conversion are largely unknown.MethodsWe conducted a longitudinal study on a university campus, collecting daily anterior nasal swabs for at least 10 days for RT-PCR and culture, with antigen rapid diagnostic testing (RDT) on a subset. We compared culture positivity beyond day 5, time to culture conversion, and cycle threshold trend when calculated from diagnostic test, from symptom onset, by SARS-CoV-2 variant, and by vaccination status. We evaluated sensitivity and specificity of RDT on days 4-6 compared to culture.ResultsAmong 92 SARS-CoV-2 RT-PCR positive participants, all completed the initial vaccine series, 17 (18.5%) were infected with Delta and 75 (81.5%) with Omicron. Seventeen percent of participants had positive cultures beyond day 5 from symptom onset with the latest on day 12. There was no difference in time to culture conversion by variant or vaccination status. For the 14 sub-study participants, sensitivity and specificity of RDT were 100% and 86% respectively.ConclusionsThe majority of our Delta- and Omicron-infected cohort culture-converted by day 6, with no further impact of booster vaccination on sterilization or cycle threshold decay. We found that rapid antigen testing may provide reassurance of lack of infectiousness, though masking for a full 10 days is necessary to prevent transmission from the 17% of individuals who remain culture positive after isolation.Main PointBeyond day 5, 17% of our Delta and Omicron-infected cohort were culture positive. We saw no significant impact of booster vaccination on within-host Omicron viral dynamics. Additionally, we found that rapid antigen testing may provide reassurance of lack of infectiousness.

Background In January 2022, United States guidelines shifted to recommend isolation for 5 days from symptom onset, followed by 5 days of mask wearing. However, viral dynamics and variant and vaccination impact on culture conversion are largely unknown. Methods We conducted a longitudinal study on a university campus, collecting daily anterior nasal swabs for at least 10 days for RT-PCR and culture, with antigen rapid diagnostic testing (RDT) on a subset. We compared culture positivity beyond day 5, time to culture conversion, and cycle threshold trend when calculated from diagnostic test, from symptom onset, by SARS-CoV-2 variant, and by vaccination status. We evaluated sensitivity and specificity of RDT on days 4-6 compared to culture. Results Among 92 SARS-CoV-2 RT-PCR positive participants, all completed the initial vaccine series, 17 (18.5%) were infected with Delta and 75 (81.5%) with Omicron. Seventeen percent of participants had positive cultures beyond day 5 from symptom onset with the latest on day 12. There was no difference in time to culture conversion by variant or vaccination status. For 14 sub-study participants, sensitivity and specificity of day 4-6 RDT were 100% and 86% respectively. Conclusions The majority of our Delta- and Omicron-infected cohort culture-converted by day 6, with no further impact of booster vaccination on sterilization or cycle threshold decay. We found that rapid antigen testing may provide reassurance of lack of infectiousness, though guidance to mask for days 6-10 is supported by our finding that 17% of participants remained culture positive after isolation.

Background COVID-19 vaccine trials and post-implementation data suggest vaccination decreases SARS-CoV-2 infections. We examine COVID-19 vaccination’s impact on SARS-CoV-2 case rates and viral diversity among healthcare workers (HCW) during a high community prevalence period. Methods A prospective cohort study from Boston Medical Center (BMC)’s HCW vaccination program, where staff received two doses of BNT162b2 or mRNA-1273. We included PCR-confirmed SARS-CoV-2 cases among HCWs from December 09, 2020 to February 23, 2021. Weekly SARS-CoV-2 rates per 100,000 person-day overall and by time from first injection (1-14 and >14 days) were compared with surrounding community rates. Viral genomes were sequenced from SARS CoV-2 positive samples. Results SARS-CoV-2 cases occurred in 1.4% (96/7109) of HCWs given at least a first dose and 0.3% (17/5913) of HCWs given both vaccine doses. Adjusted SARS-CoV-2 infection rate ratios were 0.73 (95% CI 0.53-1.00) 1-14 days and 0.18 (0.10-0.32) >14 days from first dose. HCW SARS-CoV-2 cases >14 days from initial dose compared to within 14 days were more often older (46 versus 38 years, p=0.007), Latinx (10% versus 8%, p=0.03), and asymptomatic (48% versus 11%, p=0.0002). SARS-CoV-2 rates among HCWs fell below those of the surrounding community, with a 18% versus 11% weekly decrease respectively (p=0.14). Comparison of 50 SARS-CoV-2 genomes sequenced from post-first dose cases did not indicate selection pressure towards known spike-antibody escape mutations. Conclusions Our results indicate an early positive impact of COVID-19 vaccines on SARS-CoV-2 case rates. Post-vaccination isolates did not show unusual genetic diversity or selection for mutations of concern.

The Omicron variant of SARS-CoV-2 is transmissible in vaccinated and unvaccinated populations. Here, we describe the rapid dominance of Omicron following its introduction to three Massachusetts universities with asymptomatic surveillance programs. We find that Omicron was established and reached fixation earlier on these campuses than in Massachusetts or New England as a whole, rapidly outcompeting Delta despite its association with lower viral loads. These findings highlight the transmissibility of Omicron and its propensity to fixate in small populations, as well as the ability of robust asymptomatic surveillance programs to offer early insights into the dynamics of pathogen arrival and spread.

Background The Omicron variant of SARS-CoV-2 is highly transmissible in vaccinated and unvaccinated populations. The dynamics governing its establishment and propensity towards fixation (reaching 100% frequency in the SARS-CoV-2 population) in communities remain unknown. In this work, we describe the dynamics of Omicron at three institutions of higher education (IHEs) in the greater Boston area. Methods We use diagnostic and variant-specifying molecular assays and epidemiological analytical approaches to describe the rapid dominance of Omicron following its introduction to three IHEs with asymptomatic surveillance programs. Results We show that the establishment of Omicron at IHEs precedes that of the state and region, and that the time to fixation is shorter at IHEs (9.5-12.5 days) than in the state (14.8 days) or region. We show that the trajectory of Omicron fixation among university employees resembles that of students, with a 2-3 day delay. Finally, we compare cycle threshold (Ct) values in Omicron vs. Delta variant cases on college campuses, and identify lower viral loads among college affiliates harboring Omicron infections. Conclusions We document the rapid takeover of the Omicron variant at IHEs, reaching near-fixation within the span of 9.5-12.5 days despite lower viral loads, on average, than the previously dominant Delta variant. These findings highlight the transmissibility of Omicron, its propensity to rapidly dominate small populations, and the ability of robust asymptomatic surveillance programs to offer early insights into the dynamics of pathogen arrival and spread.

ImportanceRecent CDC COVID-19 isolation guidance for non-immunocompromised individuals with asymptomatic or mild infection allows ending isolation after 5 days if asymptomatic or afebrile with improving symptoms. The role of rapid antigen testing in further characterizing the risk of viral transmission to others is unclear.ObjectiveUnderstand rates of rapid antigen test (RAT) positivity after day 5 from a positive COVID-19 test and the relationship of this result to symptoms and viral culture.DesignIn this single center, observational cohort study, ambulatory individuals newly testing SARS-CoV-2 positive completed daily symptom logs, and RAT self-testing starting day 6 until negative. Anterior nasal and oral swabs were collected on a subset for viral culture.Main Outcomes and MeasuresDay 6 SARS-CoV-2 RAT result, symptoms and viral culture.Results40 individuals enrolled between January 5 and February 11, 2022 with a mean age of 32 years (range 22 to 57). 23 (58%) were women and 17 (42%) men. All were vaccinated. 33 (83%) were symptomatic. Ten (25%) tested RAT negative on day 6. 61 of 90 (68%) RATs performed on asymptomatic individuals after day 5 were positive. Day 6 viral cultures were positive in 6 (35%) of 17 individuals. A negative RAT or being asymptomatic on day 6 were 100% and 78% predictive respectively for negative culture, while improving symptoms was 69% predictive. A positive RAT was 50% predictive of positive culture.Conclusion and RelevanceRATs are suboptimal in predicting viral culture results on day 6. Use of routine RATs to guide end of COVID-19 isolation could result in significant numbers of culture negative, potentially non-infectious individuals undergoing prolonged isolation. However, a negative RAT was highly predictive of being culture negative. Complete absence of symptoms was inferior to a negative RAT in predicting a negative culture result, but performed better than improving symptoms. If a positive viral culture is a proxy for infectiousness, these data may help further refine a safer strategy for ending isolation.