Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study (preprint)

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 the 14 sub-study participants, sensitivity and specificity of 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 masking for a full 10 days is necessary to prevent transmission from the 17% of individuals who remain culture positive after isolation.

Evaluation of the role of home rapid antigen testing to determine isolation period after infection with SARS-CoV-2 (preprint)

Importance Recent 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. Objective Understand 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. Design In 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 Measures Day 6 SARS-CoV-2 RAT result, symptoms and viral culture. Results 40 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 Relevance RATs 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.

Comparison of BinaxNOW TM and SARS-CoV-2 qRT-PCR detection of the Omicron Variant from Matched Anterior Nares Swabs (preprint)

The COVID-19 pandemic has increased the use of rapid antigen tests such as the Abbott BinaxNOWTM COVID-19 Antigen Self-Test. In winter of 2021-2022, the omicron variant surge made it quickly apparent that although rapid diagnostic tests (RDTs) are less sensitive than qRT-PCR, the accessibility, ease of use, and rapid read-outs of RDTs made them a sought after and often sold-out item at local suppliers. Here, we sought to qualify the BinaxNOWTM test for use in our university testing program as a method to rule-in positive or rule-out negative individuals quickly when they seek care at our priority qRT-PCR testing site. To perform this qualification study, we collected matched additional swabs from individuals attending this test site for standard of care qRT-PCR testing. All matched swabs were tested using the BinaxNOWTM RDT. Initially as part of a feasibility study, test period 1 (n=110) samples were put in cold storage prior to testing. In follow-on test period (n=209), we tested samples real-time at the test facility. Combined, 102 of 319 samples tested positive for SARS-CoV-2. All samples for which genome sequence could be collected were omicron (n=92). We observed a calculated sensitivity of 53.9%, specificity of 100%, a positive predictive value (PPV) of 100%, and a negative predictive value (NPV) of 82.2% for the BinaxNOWTM tests (n=319). Sensitivity improved (75.3%) by changing the qRT-PCR positivity threshold from a CT of 40 to a CT of 30. The ROC curve shows that for qRT-PCR positive CT values between 24-40, the BinaxNOWTM test is of limited value diagnostically. Our results suggest that RDT tests could be used in our setting to confirm SARS-CoV-2 infection in individuals with substantial viral load, but that a significant fraction of infected individuals would be missed if we used RDT tests exclusively to rule out infection.

Early introduction and rise of the Omicron SARS-CoV-2 variant in highly vaccinated university populations (preprint)

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.

Macrophages govern antiviral responses in human lung tissues protected from SARS-CoV-2 infection (preprint)

The majority of SARS-CoV-2 infections among healthy individuals result in asymptomatic to mild disease. However, the immunological mechanisms defining effective lung tissue protection from SARS-CoV-2 infection remain elusive. Unlike mice solely engrafted with human fetal lung xenograft (fLX), mice co-engrafted with fLX and a myeloid-enhanced human immune system (HNFL mice) are protected against SARS-CoV-2 infection, severe inflammation, and histopathology. Effective control of viral infection in HNFL mice associated with significant macrophage infiltration, and the induction of a potent macrophage-mediated interferon response. The pronounced upregulation of the USP18-ISG15 axis (a negative regulator of IFN responses), by macrophages was unique to HNFL mice and represented a prominent correlate of reduced inflammation and histopathology. Altogether, our work shed light on unique cellular and molecular correlates of lung tissue protection during SARS-CoV-2 infection, and underscores macrophage IFN responses as prime targets for developing immunotherapies against coronavirus respiratory diseases.

COVID-19 vaccine impact on rates of SARS-CoV-2 cases and post vaccination strain sequences among healthcare workers at an urban academic medical center: a prospective cohort study (preprint)

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.