Association between Causative Pathogen and Occurrence of Infection-Related Glomerulonephritis in Infective Endocarditis.

Among patients with pathologically-proven infective endocarditis, the association of pathogen with occurrence of infection-related glomerulonephritis (IRGN) was examined in 48 cases of IRGN and 192 propensity score-matched controls. Bartonella was very strongly associated with IRGN (OR 38.2, 95% C.I. 6.7-718.8, p-value <.001); other microorganisms were not.

Effectiveness of the 2023-2024 Formulation of the Coronavirus Disease 2019 mRNA Vaccine.

BACKGROUND: The purpose of this study was to evaluate whether the 2023-2024 formulation of the COVID-19 mRNA vaccine protects against COVID-19. METHODS: Employees of Cleveland Clinic in employment when the 2023-2024 formulation of the COVID-19 mRNA vaccine became available to employees, were included. Cumulative incidence of COVID-19 over the following 17 weeks was examined prospectively. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with time-dependent coefficients used to separate effects before and after the JN.1 lineage became dominant. The analysis was adjusted for the propensity to get tested, age, sex, pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses. RESULTS: Among 48210 employees, COVID-19 occurred in 2462 (5.1%) during the 17 weeks of observation. In multivariable analysis, the 2023-2024 formula vaccinated state was associated with a significantly lower risk of COVID-19 before the JN.1 lineage became dominant (HR, .58; 95% C.I., .49-.68, p-value < .001), and lower risk but one that did not reach statistical significance after (HR, .81; 95% C.I., .65-1.01, p-value 0.06). Estimated vaccine effectiveness (VE) was 42% (95% C.I., 32%-51%) before the JN.1 lineage became dominant, and 19% (C.I., -1%-35%) after. Risk of COVID-19 was lower among those previously infected with an XBB or more recent lineage, and increased with the number of vaccine doses previously received. CONCLUSIONS: The 2023-2024 formula COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 before the JN.1 lineage became dominant, and less protection after.

Understanding Patient Utilization Patterns of Cochlear Implant Processors.

OBJECTIVE: To evaluate the extent of benefit the second processor provides and to better understand utilization patterns regarding cochlear implant (CI) sound processors. BACKGROUND: Institutional contracts determine the external CI sound processor hardware that a patient is eligible for. Despite the high prevalence of CI worldwide, there is a paucity in the literature regarding patient preferences and how patients utilize provided external hardware. METHODS: A close-ended, multiple-choice survey was mailed to all patients over the age of 18 years who underwent CI between 2016 to 2020 at a tertiary academic medical center. Patients who received their CI hardware prior to 2018 were provided 2 processors, whereas those who received their hardware in 2018 or later were provided 1 processor. RESULTS: A total of 100/263 surveys were returned for a response rate of 38.0%. Of the cohort with 1 processor, 31.3% experienced a period without a functioning processor and access to sound compared to 5.6% of the cohort with 2 processors (P = -.003). Of the cohort with 2 processors, 24.3% noted that they often or always utilize their second processor. When asked how important having a second processor was, 62.9% of the 2-processor group responded that it was very important (P = .001). The most common reason for utilizing the second processor was a damaged primary processor. Patients who received 2 processors had a significantly lower number of postoperative audiology clinic visits for device troubleshooting (P < .001). CONCLUSION: Patients who have 2 CI external processors identify this as being very important to them and experience significantly less time without access to sound due to lack of a functioning processor. As institutional contracts often dictate whether a patient will receive 1 or 2 sound processors with their CI hardware, it is important to understand patient preferences and utilization patterns in order to guide patient-centric policies.

Infective Endocarditis in Patients Addicted to Injected Opioid Drugs.

BACKGROUND: Persons who inject drugs and require surgery for infective endocarditis have 2 potentially lethal diseases. Current postoperative rehabilitation efforts seem ineffective in preventing loss to follow-up, injection drug use relapse (relapse), and death. OBJECTIVES: The purpose of this study was to characterize drug use, psychosocial issues, surgical outcome, and postoperative addiction management, as well as loss to follow-up, relapse, and mortality and their risk factors. METHODS: From January 2010 to June 2020, 227 persons who inject drugs, age 36 ± 9.9 years, underwent surgery for infective endocarditis at a quaternary hospital having special interest in developing addiction management programs. Postsurgery loss to follow-up, relapse, and death were assessed as competing risks and risk factors identified parametrically and by machine learning. CIs are 68% (±1 SE). RESULTS: Heroin was the most self-reported drug injected (n = 183 [81%]). Psychosocial issues included homelessness (n = 56 [25%]), justice system involvement (n = 150 [66%]), depression (n = 118 [52%]), anxiety (n = 104 [46%]), and post-traumatic stress disorder (n = 33 [15%]). Four (1.8%) died in-hospital. Medication for opioid use disorder prescribed at discharge increased from 0% in 2010 to 100% in 2020. At 1 and 5 years, conditional probabilities of loss to follow-up were 16% (68% CI: 13%-22%) and 59% (68% CI: 44%-65%), relapse 32% (68% CI: 28%-34%) and 79% (68% CI: 74%-83%), and mortality 21% (68% CI: 18%-23%) and 68% (68% CI: 62%-72%). Younger age, heroin use, and lower education level were predictors of relapse. CONCLUSIONS: Infective endocarditis surgery can be performed with low mortality in persons who inject drugs, but addiction is far more lethal. Risk of loss to follow-up and relapse require more effective addiction strategies without which this major loss to society will continue.

Risk of Coronavirus Disease 2019 (COVID-19) among those up-to-date and not up-to-date on COVID-19 vaccination by US CDC criteria.

BACKGROUND: The CDC recently defined being "up-to-date" on COVID-19 vaccination as having received at least one dose of a COVID-19 bivalent vaccine. The purpose of this study was to compare the risk of COVID-19 among those "up-to-date" and "not up-to-date". METHODS: Employees of Cleveland Clinic in Ohio, USA, in employment when the COVID-19 bivalent vaccine first became available, and still employed when the XBB lineages became dominant, were included. Cumulative incidence of COVID-19 since the XBB lineages became dominant was compared across the"up-to-date" and "not up-to-date" states, by treating COVID-19 bivalent vaccination as a time-dependent covariate whose value changed on receipt of the vaccine. Risk of COVID-19 by vaccination status was also evaluated using multivariable Cox proportional hazards regression adjusting for propensity to get tested for COVID-19, age, sex, most recent prior SARS-CoV-2 infection, and number of prior vaccine doses. RESULTS: COVID-19 occurred in 1475 (3%) of 48 344 employees during the 100-day study period. The cumulative incidence of COVID-19 was lower in the "not up-to-date" than the "up-to-date" state. On multivariable analysis, being "up-to-date" was not associated with lower risk of COVID-19 (HR, 1.05; 95% C.I., 0.88-1.25; P-value, 0.58). Results were very similar when those 65 years and older were only considered "up-to-date" after 2 doses of the bivalent vaccine. CONCLUSIONS: Since the XBB lineages became dominant, adults "up-to-date" on COVID-19 vaccination by the CDC definition do not have a lower risk of COVID-19 than those "not up-to-date", bringing into question the value of this risk classification definition.

Effectiveness of the Coronavirus Disease 2019 Bivalent Vaccine.

Background: The purpose of this study was to evaluate whether a bivalent coronavirus disease 2019 (COVID-19) vaccine protects against COVID-19. Methods: The study included employees of Cleveland Clinic in employment when the bivalent COVID-19 vaccine first became available. Cumulative incidence of COVID-19 over the following 26 weeks was examined. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with change in dominant circulating lineages over time accounted for by time-dependent coefficients. The analysis was adjusted for the pandemic phase when the last prior COVID-19 episode occurred and the number of prior vaccine doses. Results: Among 51 017 employees, COVID-19 occurred in 4424 (8.7%) during the study. In multivariable analysis, the bivalent-vaccinated state was associated with lower risk of COVID-19 during the BA.4/5-dominant (hazard ratio, 0.71 [95% confidence interval, .63-79]) and the BQ-dominant (0.80 [.69-.94]) phases, but decreased risk was not found during the XBB-dominant phase (0.96 [.82-.1.12]). The estimated vaccine effectiveness was 29% (95% confidence interval, 21%-37%), 20% (6%-31%), and 4% (-12% to 18%), during the BA.4/5-, BQ-, and XBB-dominant phases, respectively. The risk of COVID-19 also increased with time since the most recent prior COVID-19 episode and with the number of vaccine doses previously received. Conclusions: The bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 while the BA.4/5 lineages were the dominant circulating strains, afforded less protection when the BQ lineages were dominant, and effectiveness was not demonstrated when the XBB lineages were dominant.

Left ventricular assist device infection on 18F-flourodeoxyglucose positron emission tomography.

The rising prevalence of heart failure with limited transplant availability has resulted in increased use of continuous left ventricular assist device (LVAD) support. LVAD driveline remains exposed to environment which predisposes it to high rates of infection. We describe a case of a persistent driveline infection in a patient for which 18F-FDG PET/CT was utilized to diagnose deep-seated infection.

Abnormal thrombosis and neutrophil activation increase hospital-acquired sacral pressure injuries and morbidity in COVID-19 patients.

Hospitalized patients have an increased risk of developing hospital-acquired sacral pressure injury (HASPI). However, it is unknown whether SARS-CoV-2 infection affects HASPI development. To explore the role of SARS-CoV-2 infection in HASPI development, we conducted a single institution, multi-hospital, retrospective study of all patients hospitalized for ≥5 days from March 1, 2020 to December 31, 2020. Patient demographics, hospitalization information, ulcer characteristics, and 30-day-related morbidity were collected for all patients with HASPIs, and intact skin was collected from HASPI borders in a patient subset. We determined the incidence, disease course, and short-term morbidity of HASPIs in COVID-19(+) patients, and characterized the skin histopathology and tissue gene signatures associated with HASPIs in COVID-19 disease. COVID-19(+) patients had a 63% increased HASPI incidence rate, HASPIs of more severe ulcer stage (OR 2.0, p<0.001), and HASPIs more likely to require debridement (OR 3.1, p=0.04) compared to COVID-19(-) patients. Furthermore, COVID-19(+) patients with HASPIs had 2.2x increased odds of a more severe hospitalization course compared to COVID-19(+) patients without HASPIs. HASPI skin histology from COVID-19(+) patients predominantly showed thrombotic vasculopathy, with the number of thrombosed vessels being significantly greater than HASPIs from COVID-19(-) patients. Transcriptional signatures of a COVID-19(+) sample subset were enriched for innate immune responses, thrombosis, and neutrophil activation genes. Overall, our results suggest that immunologic dysregulation secondary to SARS-CoV-2 infection, including neutrophil dysfunction and abnormal thrombosis, may play a pathogenic role in development of HASPIs in patients with severe COVID-19.

The Ultra fit community mask-Toward maximal respiratory protection via personalized face fit.

Effective masking policies to prevent the spread of airborne infections depend on public access to masks with high filtration efficacy. However, poor face-fit is almost universally present in pleated multilayer disposable face masks, severely limiting both individual and community respiratory protection. We developed a set of simple mask modifications to mass-manufactured disposable masks, the most common type of mask used by the public, that dramatically improves both their personalized fit and performance in a low-cost and scalable manner. These modifications comprise a user-moldable full mask periphery wire, integrated earloop tension adjusters, and an inner flange to trap respiratory droplets. We demonstrate that these simple design changes improve quantitative fit factor by 320%, triples the level of protection against aerosolized droplets, and approaches the model efficacy of N95 respirators in preventing the community spread of COVID-19, for an estimated additional cost of less than 5 cents per mask with automated production.

Aortic allograft infection risk.

OBJECTIVE: Intrinsic risk of infection of cryopreserved allograft aortic root replacements remains poorly understood despite their long history of use. The objective of this study was to determine this intrinsic risk of allograft infection and its risk factors when allografts are implanted for both nonendocarditis indications and infective endocarditis. METHODS: From January 1987 to January 2017, 2042 patients received 2110 allograft aortic valves at a quaternary medical center, 1124 (53%) for nonendocarditis indications and 986 (47%) for endocarditis indications (670 [68%] prosthetic valve endocarditis). Staphylococcus aureus caused 193 of 949 cases of endocarditis (20%), 71 (7.3%) in persons who injected drugs. Periodic surveillance and cross-sectional follow-up achieved 85% of possible follow-up time. The primary end point was allograft infection in patients with nonendocarditis and endocarditis indications. Risk factors were identified by hazard function decomposition and machine learning. RESULTS: During follow-up, 30 allografts (26 explanted) became infected in patients in the nonendocarditis group and 49 (41 explanted) in patients with endocarditis. At 20 years, the probability of allograft infection was 5.6% in patients in the nonendocarditis group and 14% in patients with endocarditis. Risk factors for allograft infection in patients in the nonendocarditis group were younger patient age and older donor age. Risk factors for allograft infection in patients with endocarditis were earlier implant year, injection drug use, and younger age. In patients with endocarditis, 18% of allograft infections were caused by the original organism. CONCLUSIONS: The low infection rates, both in patients without and with endocarditis, support continued use of allografts in the modern era, in particular for the treatment of invasive endocarditis of the aortic root.

Expanding Understanding of Electrocochleography in Cochlear Implantation: Auditory Neuropathy Spectrum Disorder With Normal Pure Tone Average.

Objective: Describe the preoperative decision-making, intraoperative electrocochleographic (ECoG) findings, and outcome of cochlear implantation (CI) in a patient with auditory neuropathy spectrum disorder (ANSD) and normal pure-tone thresholds. Patients: A 19-year-old with a history of hypoxic ischemic encephalopathy and seizures was referred for hearing rehabilitation in the setting of typical hearing by pure tone audiometry but poor speech understanding. A diagnosis of ANSD was made based on acoustic brainstem response (ABR), distortion product otoacoustic emission, and acoustic reflex testing. Imaging revealed no central cause of hearing impairment. Interventions: Right-sided CI. Main Outcome Measures: Preoperative and postoperative audiometric data. Intraoperative ECoG. Results: Preoperatively the patient underwent comprehensive audiologic testing with behavioral audiometry, ABR testing, and CI candidacy evaluation. In the right ear, the pure tone average (PTA) was 15 dB and word recognition score was 36%. ABR confirmed ANSD. Preoperative CNC and AzBio in quiet were 8% and 0%, respectively. Intraoperative ECoG amplitudes and audiometry showed responses in the 100 uV range and estimated PTA of 42 dB HL. Postoperative testing at 1-month post-initial activation revealed PTA of 45 dB HL and unchanged word and sentence scores. However, the patient cites an improved ability to communicate and increased confidence and averages over 14 hours of device use daily. Conclusions: To our knowledge, this is the first reported case of CI in an ear with normal PTA. Given that nearly all presently available ECoG data comes from patients with greater degrees of hearing loss, this unique case adds to our understanding of hearing preservation in CI.

Factors associated with hearing outcomes after a middle fossa approach in 131 consecutive patients with vestibular schwannomas.

OBJECTIVE: The middle fossa approach is an effective option for the treatment of small (Koos grade I and II) vestibular schwannomas (VSs) when the goal is hearing preservation. The authors evaluated the rates of hearing preservation and examined the factors associated with improved hearing outcomes after the middle fossa approach for VSs. METHODS: In this retrospective, single-center cohort study evaluating the clinical outcomes after resection of small VSs using the middle fossa approach, consecutive adult patients (> 18 years) who underwent surgery between January 2000 and December 2021 were included. Clinical and imaging characteristics were analyzed, including baseline hearing status, duration of surgery, anesthetic parameters, and imaging characteristics of the surgically treated tumors. RESULTS: Among the 131 included patients, 102 had valid and discoverable pre- and postoperative audiology assessments. The mean follow-up was 26 months (range 1-180 months). There were 85 patients with serviceable hearing preoperatively, defined as American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) class A or B, of whom 78% retained class A or B hearing at the last follow-up. Binary logistic regression demonstrated that preoperative hearing AAO-HNS class (OR 0.19, 95% CI 0.05-0.77; p = 0.02), overlap between fundus and cochlea (OR 0.32, 95% CI 0.11-0.96; p = 0.04), and duration of anesthesia (OR 0.98, 95% CI 0.97-0.99; p = 0.03) were independent predictors of hearing outcomes. Additionally, 75% of patients with high diffusion-weighted imaging signal in the tumor (p = 0.009) and 67% of patients with the tumor originating at the modiolus of the cochlea (p = 0.004) had poor hearing outcomes. CONCLUSIONS: The hearing preservation rates after microsurgical resection of small VSs using the middle fossa approach are high, with 78% of patients maintaining AAO-HNS class A or B hearing. Poor hearing status at baseline, longer duration of anesthesia, and large overlap between the fundus of the internal auditory canal and the cochlea were independently associated with unfavorable hearing outcomes. Imaging characteristics can be used to stratify patients' risk of hearing loss.

Cochlear Implantation in Patients With Known Cognitive Impairment: What Are the Benefits?

OBJECTIVE: To evaluate the outcomes of cochlear implantation (CI) in adults with preoperatively diagnosed cognitive impairment. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic center. PATIENTS: Adults undergoing CI with preexisting cognitive impairment. INTERVENTIONS: Cochlear implantation. MAIN OUTCOME MEASURES: 1) Hearing improvement after CI; 2) morbidity and mortality associated with surgery. RESULTS: Eight patients met inclusion criteria with mean age 77.8 years (SD, 9.6 y) at time of implantation; 7 were included in subsequent analysis as one did not have speech recognition scores. Average preoperative MoCA cognitive score of 22.6 (SD, 3.9, ≤25 demonstrates cognitive impairment). Average follow-up was 29.0 months (SD, 33.3 mo). Two patients passed away at an average 58.0 months (SD, 31.1 mo) after surgery. Median preoperative pure tone average was 86.3 dB HL ( interquartile range 31.3 dB HL) compared with 33.8 dB HL (IQR 5.0 dB HL) postoperatively ( p = <0.001). Median preoperative speech testing score (AzBio/HINT) was 21% (IQR, 24%) compared with 44% (IQR, 21%) postoperatively ( p = <0.001). There were no observed surgical complications during the follow-up period. CONCLUSIONS: This study demonstrates that patients with cognitive impairment before CI can experience improved hearing, no increased risk of complications, and good longevity after CI. Further prospective studies are needed to further define the utility of CI in patients with impaired cognition.

Advanced Cardiovascular Imaging for the Diagnosis of Mycobacterium chimaera Prosthetic Valve Infective Endocarditis After Open-heart Surgery: A Contemporary Systematic Review.

Mycobacterium chimaera is an opportunistic and emerging pathogen, which has been recognized to cause prosthetic valve infective endocarditis and disseminated infection following open-chest cardiac surgery with certain contaminated heater-cooler systems. Diagnostic evaluation of suspected prosthetic valve infective endocarditis due to M chimaera is challenging and requires a very high index of suspicion. This systematic review aims to evaluate prosthetic valve infective endocarditis due to M chimaera. Based on the current literature review, transesophageal echocardiography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography are the most common imaging modalities used to establish the diagnosis. Based on 22 published cases, the reported cases of M chimaera endocarditis have occurred almost entirely in males. Within this cohort, the patients developed endocarditis on average 2.7 years after exposure to contaminated heater-cooler systems during cardiac surgery. M chimaera infection is associated with significant morbidity and mortality.

Who Helps Refugees in South Africa? An Examination of Cultural and Social Factors.

Pro-refugee philanthropy is beneficial for refugee integration and an important contributor to intergroup relations in a South African context. No study, however, has provided an in-depth quantitative analysis of what factors drive this type of behaviour. This article investigates what cultural, social and religious factors may predict participation in charitable behaviour towards refugees in South Africa. Three types of behaviours were examined: (i) material donations; (ii) volunteer activities; and (iii) information sharing. Using data from a 2019 Ipsos Migration Survey, the study found that intergroup threat was a robust predictor of charitable behaviour of all kinds. Friendship contact with a pro-refugee volunteer was also positively associated with philanthropic behaviour. Institutional trust and religious orientation were correlated with volunteer activities and information sharing but not donations. Study findings can be utilised to design interventions that increase public participation in actions that help refugees in an African context.

Coronavirus Disease 2019 Vaccine Boosting in Previously Infected or Vaccinated Individuals.

BACKGROUND: The purpose of this study was to determine whether boosting previously infected or vaccinated individuals with a vaccine developed for an earlier variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protects against the Omicron variant. METHODS: Employees of Cleveland Clinic, previously infected with or vaccinated against coronavirus disease 2019 (COVID-19) and working the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over 2 months during an Omicron variant surge. Protection provided by boosting was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate SARS-CoV-2 exposure. RESULTS: Among 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since proximate SARS-CoV-2 exposure, and boosting protected those >6 months since prior infection or vaccination. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those vaccinated but not previously infected (hazard ratio [HR], .43; 95% confidence interval [CI], .41-.46) as well as those previously infected (HR, .66; 95% CI, .58-.76). Among those previously infected, receipt of 2 compared with 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21-1.97). CONCLUSIONS: Administering a COVID-19 vaccine not designed for the Omicron variant >6 months after prior infection or vaccination protects against Omicron variant infection. There is no advantage to administering more than 1 dose of vaccine to previously infected persons.

Delayed cochlear implantation in congenitally deaf children-identifying barriers for targeted interventions.

OBJECTIVES: Age of cochlear implantation (CI) is an important predictor of language development in those with congenital sensorineural hearing loss. Despite universal newborn hearing screening initiatives and the known benefits of early CI, a subset of congenitally deaf children continue to be evaluated for cochlear implants later in childhood. This study aims to identify the barriers to early cochlear implantation in these children. METHODS: A retrospective review was conducted for all pediatric cochlear implants aged 3 years or older performed at a single academic institution between 2013 and 2017. Children implanted before the age three, those with a prior unilateral cochlear implant, and those with progressive or sudden hearing loss were excluded. Variables included newborn hearing screen results, age at hearing loss diagnosis, time of initiation and documented benefit of hearing aids, age of implantation, pre/post-implantation evaluation scores, and reason for delayed referral for cochlear implantation. RESULTS: Thirty-one patients were identified meeting these inclusion criteria. Twenty-one children were subject to UNBS in the U.S. Fourteen of those children failed their newborn hearing screening. Average age at implantation was 6.2 years. Four reasons were identified for increased age at cochlear implantation. Two categories represent delays related to (1) Amplification continually prescribed even though the range of hearing loss and speech development assessment suggests CI may have been more appropriate well before referral (N = 13) (2) Patients were not subject to newborn hearing screening and/or timely diagnosis of their hearing loss (N = 8). In other cases, patients were appropriately fit with hearing aids until evidence that they derived limited benefit and then referred for CI (N = 8). Lastly, in a few cases, records were indeterminate with regards to the timing and appropriate diagnosis of their hearing loss (N = 2). CONCLUSION: Understanding the reasons for delayed cochlear implantation in congenitally deaf children might allow the development of targeted interventions to improve outcomes. Specifically, those children who were not referred before age 3 despite use of amplification with limited benefit offer one potential target population for earlier CI.

Necessity of Coronavirus Disease 2019 (COVID-19) Vaccination in Persons Who Have Already Had COVID-19.

BACKGROUND: The aim was to evaluate the necessity of coronavirus disease 2019 (COVID-19) vaccination in persons with prior COVID-19. METHODS: Employees of the Cleveland Clinic working in Ohio on 16 December 2020, the day COVID-19 vaccination was started, were included. Anyone who tested positive for COVID-19 at least once before the study start date was considered previously infected. One was considered vaccinated 14 days after receiving the second dose of COVID-19 mRNA vaccine. Cumulative incidences of COVID-19, symptomatic COVID-19, and hospitalizations for COVID-19 were examined over the next year. RESULTS: Among 52 238 employees, 4718 (9%) were previously infected and 36 922 (71%) were vaccinated by the study's end. Cumulative incidence of COVID-19 was substantially higher throughout for those previously uninfected who remained unvaccinated than for all other groups, lower for the vaccinated than unvaccinated, and lower for those previously infected than those not. Incidence of COVID-19 increased dramatically in all groups after the Omicron variant emerged. In multivariable Cox proportional hazards regression, both prior COVID-19 and vaccination were independently associated with significantly lower risk of COVID-19. Among previously infected subjects, a lower risk of COVID-19 overall was not demonstrated, but vaccination was associated with a significantly lower risk of symptomatic COVID-19 in both pre-Omicron (HR, .60; 95% CI, .40-.90) and Omicron (HR, .36; 95% CI, .23-.57) phases. CONCLUSIONS: Both previous infection and vaccination provide substantial protection against COVID-19. Vaccination of previously infected individuals does not provide additional protection against COVID-19 for several months, but after that provides significant protection at least against symptomatic COVID-19.

Ototoxicity and Teprotumumab.

OBJECTIVES: Teprotumumab, a novel monoclonal antibody, targets the insulin-like growth factor 1 (IGF-1) receptor. IGF-1 receptors, found in muscle and fat adjacent to the eye and implicated in Graves Ophthalmopathy, are also in the cochlea. In clinical trials, 5 participants reported self-limited audiologic symptoms but there are no objective data in the literature. The aim of this report is to describe one of the first known cases of teprotumumab-induced irreversible sensorineural hearing loss. METHODS: Case report at a tertiary referral center. RESULTS: A 61 year old female with Graves ophthalmopathy presented with bilateral hearing loss, sound distortion, and tinnitus following treatment with teprotumumab. Audiogram showed mild sloping to moderately-severe sensorineural hearing loss. Repeat audiometry obtained 4 months after cessation of teprotumumab and treatment with oral corticosteroids was unchanged. CONCLUSIONS: This is one of the first descriptive cases of ototoxicity resulting in irreversible sensorineural hearing loss in the setting of treatment with teprotumumab. Periodic audiologic evaluations should be recommended to patients on teprotumumab.