Current COVID-19 vaccines significantly reduce overall morbidity and mortality and are vitally important to controlling the pandemic. Individuals who previously recovered from COVID-19 have enhanced immune responses after vaccination (hybrid immunity) compared to their naïve-vaccinated peers; however, the effects of post-vaccination breakthrough infections on humoral immune response remain to be determined. Here, we measure neutralizing antibody responses from 104 vaccinated individuals, including those with breakthrough infections, hybrid immunity, and no infection history. We find that human immune sera following breakthrough infection and vaccination following natural infection, broadly neutralize SARS-CoV-2 variants to a similar degree. While age negatively correlates with antibody response after vaccination alone, no correlation with age was found in breakthrough or hybrid immune groups. Together, our data suggest that the additional antigen exposure from natural infection substantially boosts the quantity, quality, and breadth of humoral immune response regardless of whether it occurs before or after vaccination.

Breakthrough infections after vaccination against SARS-CoV-2 are increasingly reported, possibly due to waning of vaccine-induced antibody levels. 1 Moreover, emerging variants of concern with diminished susceptibility to vaccineinduced antibodies are responsible for most new cases. 2,3 Studies have focused on determining the rate of vaccine breakthrough based on antibody levels after standard vaccination practices. 4,5 We assessed antibody levels and variant cross-neutralization after breakthrough infection.Methods | Fully vaccinated health care workers subsequently diagnosed with SARS-CoV-2 breakthrough infection based on a positive polymerase chain reaction (PCR) test result were sequentially recruited at the Oregon Health & Science University between January 31, 2021, and August 18, 2021. Only those with no history of previous infection whose test results were negative for nucleocapsid antibodies were included. Controls were fully vaccinated individuals without a breakthrough infection matched on sex, age, time between vaccine doses, and time between sample collection and most recent antigen exposure (PCR confirmation for those with breakthrough infection and final vaccine dose for controls). Fulllength viral genomic sequencing was used to determine SARS-CoV-2 variant identity. Enzyme-linked immunosorbent assays were used to determine serum dilution titers with a 50% effective concentration (EC 50 ) of IgG, IgA, and IgM antibodies specific to the SARS-CoV-2 spike receptor-binding domain. Live SARS-CoV-2 neutralizing serum dilution titers were determined by 50% focus reduction neutralization tests (FRNT 50 ) against isolates of the original SARS-CoV-2 strain (WA1) and variants of concern (Alpha, Beta, Gamma, and Delta). Median breakthrough and control sera values were calculated in GraphPad Prism and compared with the Wilcoxon matched-pairs signed rank test with the Holm-Šídák correction. Delta-neutralizing potency was determined by comparing Delta-and WA1-neutralizing titers for sequenceconfirmed Delta variant breakthrough cases, non-Delta breakthrough cases, and controls using the Kruskal-Wallis test with Dunn correction. Statistical significance was defined as 2-tailed P < .05. Additional laboratory methods are provided in the Supplement. The Oregon Health & Science University institutional review board approved this study. Written informed consent was obtained.

Background: Patients with substance use disorders admitted for severe bacterial infection are in a prime position to be screened for important co-infections. However, data suggest that standard screening for co-infections in this population during hospital admission can vary in frequency and type of testing. Methods: We performed a retrospective review of patients to evaluate screening for co-infections during admission, followed by a case–control analysis to determine factors associated with lack of any screening. Results: We identified 280 patients with 320 eligible admissions. Most were male and Caucasian with unstable housing. Only 67 (23.9%) patients had a primary-care provider. About 89% ( n = 250) of our cohort were screened for one or more co-infection during their first admission with one patient never screened despite subsequent admissions. Of those screened, the greatest proportion was HIV (219, 81.4% of those without history of HIV), HCV (94, 79.7% of those without a prior positive HCV antibody), syphilis (206, 73.6%), gonorrhea, and chlamydia (47, 16.8%) with new positive tests identified in 60 (21.4%) people. Screening for all five co-infections was only completed in 15 (14.0%) of the 107 patients who had screening indications. Overall, a high proportion of those screened had a new positive test, including three cases of neurosyphilis, highlighting the importance of screening and treatment initiation. One patient was prescribed HIV pre-exposure prophylaxis at discharge and only 37 (34.6%) of those eligible were referred for HCV treatment or follow-up. In multivariable case–control analysis, non-Medicaid insurance (OR 2.8, 95% CI: 1.2–6.6, p = 0.02), use of only 1 substance (OR 2.9, 95% CI: 1.3–6.5, p < 0.01), and no documented screening recommendations by the infectious disease team (OR 3.7, 95% CI: 1.5–8.8, p < 0.01), were statistically significantly associated with lack of screening for any co-infection during hospital admission. Conclusion: Our data suggest additional interventions are needed to improve inpatient screening for co-infections in this population.