Drivers of adaptive evolution during chronic SARS-CoV-2 infections.

In some immunocompromised patients with chronic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, considerable adaptive evolution occurs. Some substitutions found in chronic infections are lineage-defining mutations in variants of concern (VOCs), which has led to the hypothesis that VOCs emerged from chronic infections. In this study, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of 27 chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations; however, a subset of mutations associated with successful global transmission was absent from chronic infections. We further tested the ability to associate antibody evasion mutations with patient-specific and virus-specific features and found that viral rebound is strongly correlated with the emergence of antibody evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody evasion in particular niches in a patient's body. We suggest that a tradeoff exists between antibody evasion and transmissibility and that extensive monitoring of chronic infections is necessary to further understanding of VOC emergence.

Association of a Third Dose of BNT162b2 Vaccine With Incidence of SARS-CoV-2 Infection Among Health Care Workers in Israel.

Importance: Administration of a BNT162b2 booster dose (Pfizer-BioNTech) to fully vaccinated individuals aged 60 years and older was significantly associated with lower risk of SARS-CoV-2 infection and severe illness. Data are lacking on the effectiveness of booster doses for younger individuals and health care workers. Objective: To estimate the association of a BNT162b2 booster dose with SARS-CoV-2 infections among health care workers who were previously vaccinated with a 2-dose series of BNT162b2. Design, Setting, and Participants: This was a prospective cohort study conducted at a tertiary medical center in Tel Aviv, Israel. The study cohort included 1928 immunocompetent health care workers who were previously vaccinated with a 2-dose series of BNT162b2, and had enrolled between August 8 and 19, 2021, with final follow-up reported through September 20, 2021. Screening for SARS-CoV-2 infection was performed every 14 days. Anti-spike protein receptor binding domain IgG titers were determined at baseline and 1 month after enrollment. Cox regression with time-dependent analysis was used to estimate hazard ratios of SARS-CoV-2 infection between booster-immunized status and 2-dose vaccinated (booster-nonimmunized) status. Exposures: Vaccination with a booster dose of BNT162b2 vaccine. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 infection, as confirmed by reverse transcriptase-polymerase chain reaction. Results: Among 1928 participants, the median age was 44 years (IQR, 36-52 years) and 1381 were women (71.6%). Participants completed the 2-dose vaccination series a median of 210 days (IQR, 205-213 days) before study enrollment. A total of 1650 participants (85.6%) received the booster dose. During a median follow-up of 39 days (IQR, 35-41 days), SARS-CoV-2 infection occurred in 44 participants (incidence rate, 60.2 per 100 000 person-days); 31 (70.5%) were symptomatic. Five SARS-CoV-2 infections occurred in booster-immunized participants and 39 in booster-nonimmunized participants (incidence rate, 12.8 vs 116 per 100 000 person-days, respectively). In a time-dependent Cox regression analysis, the adjusted hazard ratio of SARS-CoV-2 infection for booster-immunized vs booster-nonimmunized participants was 0.07 (95% CI, 0.02-0.20). Conclusions and Relevance: Among health care workers at a single center in Israel who were previously vaccinated with a 2-dose series of BNT162b2, administration of a booster dose compared with not receiving one was associated with a significantly lower rate of SARS-CoV-2 infection over a median of 39 days of follow-up. Ongoing surveillance is required to assess durability of the findings.

Unraveling a Nosocomial Outbreak of COVID-19: The Role of Whole-Genome Sequence Analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic poses many epidemiological challenges. The investigation of nosocomial transmission is usually performed via thorough investigation of an index case and subsequent contact tracing. Notably, this approach has a subjective component, and there is accumulating evidence that whole-genome sequencing of the virus may provide more objective insight. METHODS: We report a large nosocomial outbreak in 1 of the medicine departments in our institution. Following intensive epidemiological investigation, we discovered that 1 of the patients involved was suffering from persistent COVID-19 while initially thought to be a recovering patient. She was therefore deemed to be the most likely source of the outbreak. We then performed whole-genome sequencing of the virus of 14 infected individuals involved in the outbreak. RESULTS: Surprisingly, the results of whole-genome sequencing refuted our initial hypothesis. A phylogenetic tree of the samples showed multiple introductions of the virus into the ward, 1 of which led to a cluster of 10 of the infected individuals. Importantly, the results pointed in the direction of a specific index patient that was different from the 1 that arose from our initial investigation. CONCLUSIONS: These results underscore the important added value of using whole-genome sequencing in epidemiological investigations as it may reveal unexpected connections between cases and aid in understanding transmission dynamics, especially in the setting of a pandemic where multiple possible index cases exist simultaneously.

Antibiotic Use during the COVID-19 Pandemic in a Tertiary Hospital with an Ongoing Antibiotic Stewardship Program.

During the recent pandemic, the fact that the clinical manifestation of COVID-19 may be indistinguishable from bacterial infection, as well as concerns of bacterial co-infection, have been associated with an increased use of antibiotics. The objective of this study was to assess the effect of targeted antibiotic stewardship programs (ASP) on the use of antibiotics in designated COVID-19 departments and to compare it to the antibiotic use in the equivalent departments in the same periods of 2018 and 2019. Antibiotic consumption was assessed as days of treatment (DOT) per 1000 patient days (PDs). The COVID-19 pandemic was divided into three periods (waves) according to the pandemic dynamics. The proportion of patients who received at least one antibiotic was significantly lower in COVID-19 departments compared to equivalent departments in 2018 and 2019 (Wave 2: 30.2% vs. 45.6% and 44.9%, respectively; Wave 3: 30.5% vs. 47.8% and 50.1%, respectively, p < 0.001). The DOT/1000PDs in every COVID-19 wave was lower than during similar periods in 2018 and 2019 (179-282 DOT/1000PDs vs. 452-470 DOT/1000PDs vs. 426-479 DOT/1000PDs, respectively). Moreover, antibiotic consumption decreased over time during the pandemic. In conclusion, a strong ASP is effective in restricting antibiotic consumption, particularly for COVID-19 which is a viral disease that may mimic bacterial sepsis but has a low rate of concurrent bacterial infection.