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.

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 PARTICIPANTSThis 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 MEASURESThe 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.

BACKGROUND. On 28 June 2005, numerous cases of febrile illness were reported among 322 students and employees of a boarding high school located in an urban area in central Israel. Subsequent investigation identified a large outbreak of Q fever which started 2 weeks earlier. We describe the investigation of this outbreak and its possible implications. METHODS. We conducted a case-control study to identify risk factors for Q fever disease. Environmental sampling was conducted to identify the source and the mode of transmission of Coxiella burnetii, the infectious agent. RESULTS. Of 303 individuals, 187 (62%) reported being ill between 15 June and 13 July 2005. Serological evidence for C. burnetii infection was evident in 144 (88%) of the 164 tested individuals. Being a student, dining regularly at the school dining room, and boarding at school during a June religious holiday and the preceding weekend were all significant risk factors for contracting Q fever. C. burnetii DNA was detected using polymerase chain reaction on samples from the school dining room's air conditioning system, supporting contribution of the air conditioning system to the aerosol transmission of the infectious agent. CONCLUSIONS. We report a large outbreak of Q fever in an urban school, possibly transmitted through an air conditioning system. A high level of suspicion for C. burnetii infection should be maintained when investigating point source outbreaks of influenza-like disease, especially outside the influenza season.

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