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Musculoskeletal manifestations of Coxiella burnetii are rare. We describe an elderly, immunosuppressed male with bilateral Coxiella burnetii extensor tenosynovitis treated with incision and debridement and chronic doxycycline and hydroxychloroquine. Additionally, disease etiology, risk factors, pertinent features of the history, testing modalities, and treatment strategies of musculoskeletal Q fever are reviewed.

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI.

Background The protective efficacy of prior coronavirus disease 2019 (COVID-19) with or without vaccination remains unknown. This study sought to understand if 2 or more messenger RNA (mRNA) vaccine doses provide additional protection in patients with prior infection, or if infection alone provides comparable protection. Methods We conducted a retrospective cohort study of the risk of COVID-19 from 16 December 2020 through 15 March 2022, among vaccinated and unvaccinated patients of all ages with and without prior infection. A Simon-Makuch hazard plot illustrated the incidence of COVID-19 between groups. Multivariable Cox proportional hazards regression was used to examine the association of demographics, prior infection, and vaccination status with new infection. Results Among 101 941 individuals with at least 1 COVID-19 polymerase chain reaction test prior to 15 March 2022, 72 361 (71.0%) received mRNA vaccination and 5957 (5.8%) were previously infected. The cumulative incidence of COVID-19 was substantially higher throughout the study period for those previously uninfected and unvaccinated, and lowest for those previously infected and vaccinated. After accounting for age, sex, and the interaction between vaccination and prior infection, a reduction in reinfection risk was noted during the Omicron and pre-Omicron phases of 26% (95% confidence interval [CI], 8%–41%; P = .0065) to 36% (95% CI, 10%–54%; P = .0108), respectively, among previously infected and vaccinated individuals, compared to previously infected subjects without vaccination. Conclusions Vaccination was associated with lower risk of COVID-19, including in those with prior infection. Vaccination should be encouraged for all including those with prior infection, especially as new variants emerge and variant-specific booster vaccines become available.

Background URIs are the most common indication for outpatient antibiotic prescribing. Given high rates of unnecessary prescribing, these indications have been identified as a high-priority target for outpatient antimicrobial stewardship programs (ASP). Our primary objective was to evaluate the impact of a system-wide, multifaceted, outpatient ASP intervention bundle on unnecessary antibiotic prescribing for URI. Methods This quasi-experimental study was conducted from 2019 to 2021. ICD-10 codes for URIs were grouped into 3 tiers (i.e., tier I = antibiotics always indicated, tier II = sometimes, tier III = never). Encounters from 5 care specialties (i.e., family medicine, community internal medicine, express care, pediatrics, and emergency department) with a tier III URI primary ICD-10 code but without a secondary tier I or tier II code were included. COVID-19 ICD-10 codes were excluded. Interventions included construction of a prescribing data model, dissemination of clinician prescribing data and education, promotion of symptom management strategies, a patient-facing commitment poster, and a pre-populated URI order panel. Tools were designed at a system level and implemented by regional champions beginning in the 3rd quarter of 2020. The primary outcome was the rate of antibiotic prescribing, and the secondary outcome and counterbalance measure was the rate of repeat URI-related healthcare contact within 14 days. Outcomes were analyzed with chi-square with an α level of 0.05. Results A total of 147403 encounters were included. The overall antibiotic prescribing rate decreased from 24.1% to 12.3% between 2019 and 2021 (p< 0.01). Significant reductions in tier III antibiotic prescribing were demonstrated for each region, care specialty, and syndrome evaluated (Table 1). A reduction in repeat healthcare contact was seen across the total cohort (9.5% in 2019 vs. 8.3% in 2021, p< 0.01); decreases in repeat contact rates were observed in those not initially receiving an antibiotic (10.3% vs. 8.6%, p< 0.01), but not in those who initially received an antibiotic (6.8% vs. 6.8%, p = 0.94). Tier III URI encounter level antimicrobial prescribing rates by region, care specialty, and syndrome Conclusion A multifaceted, outpatient ASP intervention bundle decreased rates of unnecessary antimicrobial prescribing without increasing rates of 14-day repeat URI-related healthcare contact. Disclosures Paschalis Vergidis, MD, AbbVie: DSMB|Cidara: Grant/Research Support|Scynexis: Grant/Research Support Evan Draper, PharmD, Gilead Foundation: Grant/Research Support Sara Ausman, PharmD, Gilead: Honoraria Christina G. Rivera, PharmD, Gilead: Grant/Research Support|Gilead: Honoraria|Insmed: Honoraria.

Background Myocarditis following coronavirus disease 2019 (COVID-19) mRNA vaccines (Pfizer-BioNTech and Moderna) has been increasingly reported. Incidence rates in the general population are lacking, with pericarditis rather than myocarditis diagnostic codes being used to estimate background rates. This comparison is critical for balancing the risk of vaccination with the risk of no vaccination. Methods A retrospective case series was performed using the Mayo Clinic COVID-19 Vaccine Registry. We measured the incidence rate ratio (IRR) for myocarditis temporally related to COVID-19 mRNA vaccination compared with myocarditis in a comparable population from 2016 through 2020. Clinical characteristics and outcomes of the affected patients were collected. A total of 21 individuals were identified, but ultimately 7 patients met the inclusion criteria for vaccine-associated myocarditis. Results The overall IRR of COVID-19–related myocarditis was 4.18 (95% confidence interval [CI], 1.63–8.98), which was entirely attributable to an increased IRR among adult males (IRR, 6.69; 95% CI, 2.35–15.52) compared with females (IRR 1.41; 95% CI, .03–8.45). All cases occurred within 2 weeks of a dose of the COVID-19 mRNA vaccine, with the majority occurring within 3 days (range, 1–13) following the second dose (6 of 7 patients, 86%). Overall, cases were mild, and all patients survived. Conclusions Myocarditis is a rare adverse event associated with COVID-19 mRNA vaccines. It occurs in adult males with significantly higher incidence than in the background population. Recurrence of myocarditis after a subsequent mRNA vaccine dose is not known at this time., The incidence rate ratio of myocarditis following coronavirus disease 2019 mRNA vaccination is significantly increased for adult males. Most cases occurred within 3 days (range, 1–13) following the second vaccine dose. Cases were mild, and there were no deaths.

PURPOSE: The goal of this study was to assess the impact of an interdisciplinary remote patient monitoring (RPM) program on clinical outcomes and acute care utilization in cancer patients with COVID-19. METHODS: This is a cross-sectional analysis following a prospective observational study performed at Mayo Clinic Cancer Center. Adult patients receiving cancer-directed therapy or in recent remission on active surveillance with polymerase chain reaction–confirmed SARS-CoV-2 infection between March 18 and July 31, 2020, were included. RPM was composed of in-home technology to assess symptoms and physiologic data with centralized nursing and physician oversight. RESULTS: During the study timeframe, 224 patients with cancer were diagnosed with COVID-19. Of the 187 patients (83%) initially managed in the outpatient setting, those who did not receive RPM were significantly more likely to experience hospitalization than those receiving RPM. Following balancing of patient characteristics by inverse propensity score weighting, rates of hospitalization for RPM and non-RPM patients were 2.8% and 13%, respectively, implying that the use of RPM was associated with a 78% relative risk reduction in hospital admission rate (95% CI, 54 to 102; P = .002). Furthermore, when hospitalized, these patients experienced a shorter length of stay and fewer prolonged hospitalizations, intensive care unit admissions, and deaths, although these trends did not reach statistical significance. CONCLUSION: The use of RPM and a centralized virtual care team was associated with a reduction in hospital admission rate and lower overall acute care resource utilization among cancer patients with COVID-19.

The precision health era is likely to reduce and respond to antimicrobial resistance (AMR). Our stewardship and precision efforts share terminology, seeking to deliver the “right drug, at the right dose, at the right time.” Already, rapid diagnostic testing, phylogenetic surveillance, and real-time outbreak response provide just a few examples of molecular advances we dub “precision stewardship.” However, the AMR causal factors range from the molecular to that of global health policy. Mirroring the cross-sectoral nature of AMR science, the research addressing the ethical, legal and social implications (ELSI) of AMR ranges across academic scholarship. As the rise of AMR is accompanied by an escalating sense of its moral and social significance, what is needed is a parallel field of study. In this paper, we offer a gap analysis of this terrain, or an agenda for “the ELSI of precision stewardship.” In the first section, we discuss the accomplishments of a multi-decade U.S. national investment in ELSI research attending to the advances in human genetics. In the next section, we provide an overview of distinct ELSI topics pertinent to AMR. The distinctiveness of an ELSI agenda for precision stewardship suggests new opportunities for collaboration to build the stewardship teams of the future.

Background Several vaccines are now available under emergency use authorization in the United States and have demonstrated efficacy against symptomatic COVID-19. Vaccine impact on asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is largely unknown. Methods We conducted a retrospective cohort study of consecutive, asymptomatic adult patients (n = 39 156) within a large US healthcare system who underwent 48 333 preprocedural SARS-CoV-2 molecular screening tests between 17 December 2020 and 8 February 2021. The primary exposure of interest was vaccination with ≥1 dose of an mRNA COVID-19 vaccine. The primary outcome was relative risk (RR) of a positive SARS-CoV-2 molecular test among those asymptomatic persons who had received ≥1 dose of vaccine compared with persons who had not received vaccine during the same time period. RR was adjusted for age, sex, race/ethnicity, patient residence relative to the hospital (local vs nonlocal), healthcare system regions, and repeated screenings among patients using mixed-effects log-binomial regression. Results Positive molecular tests in asymptomatic individuals were reported in 42 (1.4%) of 3006 tests and 1436 (3.2%) of 45 327 tests performed on vaccinated and unvaccinated patients, respectively (RR, .44; 95% CI, .33–.60; P 10 days after the first dose (RR, .21; 95% CI, .12–.37; P 0 days after the second dose (RR, .20; 95% CI, .09–.44; P Conclusions COVID-19 vaccination with an mRNA-based vaccine showed a significant association with reduced risk of asymptomatic SARS-CoV-2 infection as measured during preprocedural molecular screening. Results of this study demonstrate the impact of the vaccines on reduction in asymptomatic infections supplementing the randomized trial results on symptomatic patients.

Background Fluoroquinolones (FQs) are known to be accompanied by significant risks. However, the incidence of adverse events (ADEs) resulting in unplanned drug discontinuation when used for periprosthetic joint infections (PJIs) is currently unknown. Methods This study included 156 patients over the age of 18 treated for staphylococcal PJI with debridement, antibiotics, and implant retention between 1 January 2007 and 21 November 2019. Of the 156 patients, 64 had total hip arthroplasty (THA) and 92 had total knee arthroplasty (TKA) infections. The primary outcome was rate of unplanned drug discontinuation. Secondary outcomes included incidence of severe ADEs, unplanned rifamycin discontinuation, mean time to unplanned regimen discontinuation, and all-cause mortality. Results Overall, unplanned drug discontinuation occurred in 35.6% of patients in the FQ group and 3% of patients in the non-FQ group. The rate of unplanned discontinuation of FQ regimens as compared with non-FQ regimens was 27.5% vs 4.2% (P = .021) in THA infections and 42% vs 2.4% (P Conclusions A significantly higher rate of unplanned drug discontinuation was associated with FQ as compared with non-FQ regimens. This provides a real-world view of the implications of FQ-related ADEs on unplanned discontinuation when used in prolonged durations for the management of staphylococcal PJIs.

COVID-19 vaccines are effective, but breakthrough infections have been increasingly reported. We conducted a test-negative case-control study to assess the durability of protection against symptomatic infection after vaccination with mRNA-1273. We fit conditional logistic regression (CLR) models stratified on residential county and calendar date of SARS-CoV-2 PCR testing to assess the association between the time elapsed since vaccination and the odds of symptomatic infection, adjusted for several covariates. There were 2,364 symptomatic individuals who had a positive SARS-CoV-2 PCR test after full vaccination with mRNA-1273 (“cases”) and 12,949 symptomatic individuals who contributed 15,087 negative tests after full vaccination (“controls”). The odds of symptomatic infection were significantly higher 250 days after full vaccination compared to the date of full vaccination (Odds Ratio [OR]: 2.47, 95% confidence interval [CI]: 1.19–5.13). The odds of non-COVID-19 associated hospitalization and non-COVID-19 pneumonia (negative control outcomes) remained relatively stable over the same time interval (Day 250 ORNon-COVID Hospitalization: 0.68, 95% CI: 0.47–1.0; Day 250 ORNon-COVID Pneumonia: 1.11, 95% CI: 0.24–5.2). The odds of symptomatic infection remained significantly lower almost 300 days after the first mRNA-1273 dose as compared to 4 days after the first dose, when immune protection approximates the unvaccinated state (OR: 0.26, 95% CI: 0.17–0.39). Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. In summary, mRNA-1273 robustly protected against symptomatic SARS-CoV-2 infection at least 8 months after full vaccination, but the degree of protection waned over this time period.

As of 2021 November 29, booster vaccination against SARS-CoV-2 infection has been recommended for all individuals aged 18 years and older in the United States. A key reason for this recommendation is the expectation that a booster vaccine dose can alleviate observed waning of vaccine effectiveness (VE). Although initial reports of booster effectiveness have been positive, the level of protection from booster vaccination is unclear. We conducted two studies to assess the impact of booster vaccination, with BNT162b2 or mRNA-1273, on the incidence of SARS-CoV-2 infection between August and December 2021. We first compared SARS-CoV-2 infection incidence in cohorts of 3-dose vaccine recipients to incidence in matched cohorts of 2-dose vaccine recipients (cohort size = 24,539 for BNT162b2 and 14,004 for mRNA-1273). Additionally, we applied a test-negative study design to compare the level of protection against symptomatic infection in 3-dose recipients to that observed in recent 2-dose primary vaccine series recipients. The 3-dose recipients experienced a significantly lower incidence rate of SARS-CoV-2 infection than the matched 2-dose cohorts (BNT162b2 Incidence Rate Ratio: 0.11, 95% CI: 0.09 to 0.13 and mRNA-1273 IRR: 0.11, 95% CI: 0.08 to 0.15). Results from the test-negative study showed the third vaccine dose mitigated waning of VE, with the risk of symptomatic infection in 3-dose recipients being comparable to that observed 7 to 73 days after the primary vaccine series. These results show that 3-dose vaccine regimens with BNT162b2 or mRNA-1273 are effective at reducing SARS-CoV-2 infection and support the widespread administration of booster vaccine doses.

IntroductionMost patients with IBD mount an antibody response to mRNA COVID-19 vaccines, but few studies have evaluated the cell mediated immune response (CMIR).MethodsWe performed a prospective study (HERCULES) to evaluate CMIR among patients with IBD and healthy controls (HC) after completion of the primary series of mRNA COVID-19 vaccines.ResultsOne hundred 158 patients with IBD and 20 HC were enrolled. The majority (89%) of IBD patients developed a CMIR which was not different than HC (94%, p=0.6667). There was no significant difference (p=0.5488) in CMIR response between those not immunosuppressed (median 255 Spike T cells/million PBMC, IQR 146, 958) and immunosuppressed (median 377, IQR 123, 1440). There was also no correlation between antibody responses and CMIR (p=0.5215)DiscussionMost patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes.

COVID-19 vaccines are effective, but breakthrough infections have been increasingly reported. We conducted a test-negative case-control study to assess the durability of protection after full vaccination with BNT162b2 against polymerase chain reaction (PCR)-confirmed symptomatic SARS-CoV-2 infection, in a national medical practice from January 2021 through January 2022. We fit conditional logistic regression (CLR) models stratified on residential county and calendar time of testing to assess the association between time elapsed since vaccination and the odds of symptomatic infection or non-COVID-19 hospitalization (negative control), adjusted for several covariates. There were 5,985 symptomatic individuals with a positive test after full vaccination with BNT162b2 (cases) and 32,728 negative tests contributed by 27,753 symptomatic individuals after full vaccination (controls). The adjusted odds of symptomatic infection were higher 250 days after full vaccination versus at the date of full vaccination (Odds Ratio [OR]: 3.62, 95% CI: 2.52 to 5.20). The odds of infection were still lower 285 days after the first BNT162b2 dose as compared to 4 days after the first dose (OR: 0.50, 95% CI: 0.37 to 0.67), when immune protection approximates the unvaccinated status. Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. The odds of non-COVID-19 associated hospitalization (negative control) decreased with time since vaccination, suggesting a possible underestimation of waning protection by this approach due to confounding factors. In summary, BNT162b2 strongly protected against symptomatic SARS-CoV-2 infection for at least 8 months after full vaccination, but the degree of protection waned significantly over this period.

Coccidioidal infection typically occurs after inhalation of arthroconidia of Coccidioides immitis or Coccidioides posadasii. The most common initial clinical presentation is a self-limited pneumonia, but disseminated disease can occur after hematogenous spread in about 1% of cases, with exposure typically occurring weeks to months before development of symptoms. The most common sites of dissemination include the skin and soft tissue, bones and joints, and the central nervous system. Disseminated coccidioidomycosis can be diagnosed by serologic screening with an enzyme immunoassay. Antifungal therapy is recommended for patients with extrapulmonary coccidioidomycosis.

Yellow fever vaccine (YFV) can have rare but severe adverse events, including YFV-associated neurologic disease (YEL-AND), YFV-associated viscerotropic disease (YEL-AVD), and anaphylaxis. Risks of YEL-AND and YEL-AVD increase with age. YEL-AND is characterized by encephalitis, meningitis, Guillain-Barré syndrome, or acute disseminated encephalomyelitis within 28 days after vaccination. Meningoencephalitis is the most common manifestation. Diagnosis can be aided by polymerase chain reaction testing of cerebrospinal fluid for YF virus or for antibodies specific to the YF virus. Most patients with YEL-AND recover without residual deficits. Treatment should be chosen based on the presenting syndrome, and a neurologic consultation is warranted.

Recent reports on waning of COVID-19 vaccine induced immunity have led to the approval and roll-out of additional dose and booster vaccinations. At risk individuals are receiving additional vaccine dose(s), in addition to the regimen that was tested in clinical trials. The risks and the adverse event profiles associated with these additional vaccine doses are currently not well understood. Here, we performed a retrospective study analyzing vaccine-associated adverse events using electronic health records (EHRs) of individuals that have received three doses of mRNA-based COVID-19 vaccines (n = 47,999). By comparing symptoms reported in 2-week time periods after each vaccine dose and in a 2-week period before the 1st vaccine dose, we assessed the risk associated with 3rd dose vaccination, for both BNT162b2 and mRNA-1273. Reporting of severe adverse events remained low after the 3rd vaccine dose, with rates of pericarditis (0.01%, 0%-0.02% 95% CI), anaphylaxis (0.00%, 0%-0.01% 95% CI), myocarditis (0.00%, 0%-0.01% 95% CI), and cerebral venous sinus thrombosis (no cases), consistent with earlier studies. Significantly more individuals (p-value < 0.05) report low-severity adverse events after their 3rd dose compared with after their 2nd dose, including fatigue (4.92% after 3rd dose vs 3.47% after 2nd dose), lymphadenopathy (2.89% vs 2.07%), nausea (2.62% vs 2.04%), headache (2.47% vs 2.07%), arthralgia (2.12% vs 1.70%), myalgia (1.99% vs 1.63%), diarrhea (1.70% vs 1.24%), fever (1.11% vs 0.81%), vomiting (1.10% vs 0.80%), and chills (0.47% vs 0.36%). Our results show that although 3rd dose vaccination against SARS-CoV-2 infection led to increased reporting of low-severity adverse events, risk of severe adverse events remained comparable to the standard 2-dose regime. This study provides support for the safety of 3rd vaccination doses of individuals that are at high-risk of severe COVID-19 and breakthrough infection.

SARS-CoV-2 breakthrough infections have been increasingly reported in fully vaccinated individuals. We conducted a test-negative case-control study to assess the durability of protection after full vaccination with BNT162b2, defined as 14 days after the second dose, against polymerase chain reaction (PCR)-confirmed symptomatic SARS-CoV-2 infection, in a national medical practice between February 1, 2021 and August 22, 2021. We fit conditional logistic regression (CLR) models stratified on residential county and calendar time of testing to assess the association between time elapsed since vaccination and the odds of symptomatic infection or non-COVID-19 hospitalization (negative control), adjusted for several covariates. The primary population included 652 individuals who had a positive symptomatic test after full vaccination with BNT162b2 (cases) and 5,946 individuals with at least one negative symptomatic test after full vaccination (controls). The adjusted odds of symptomatic infection were higher 120 days after full vaccination versus at the date of full vaccination (Odds Ratio [OR]: 3.21, 95% confidence interval [CI]: 1.33-7.74). Importantly, the odds of infection were still lower 150 days after the first BNT162b2 dose as compared to 4 days after the first dose (OR: 0.3, 95% CI: 0.19-0.45), when immune protection approximates the unvaccinated status. Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. The odds of experiencing a non-COVID-19 hospitalization decreased with time since vaccination, suggesting a possible underestimation of waning protection by this approach due to confounding factors. Taken together, these data constitute an early signal for waning protection against symptomatic illness while also providing reassurance that BNT162b2 continues to protect against symptomatic SARS-CoV-2 infection several months after full vaccination. Continued surveillance of COVID-19 vaccine durability, particularly against severe disease, is critical to guide effective and equitable strategies to respond to the pandemic, including distribution of booster doses, development of new vaccines, and implementation of both pharmaceutical and nonpharmaceutical interventions.

Established technology, operational infrastructure, and nursing resources were leveraged to develop a remote patient monitoring (RPM) program for ambulatory management of patients with COVID-19. The program included two care-delivery models with different monitoring capabilities supporting variable levels of patient risk for severe illness. The primary objective of this study was to determine the feasibility and safety of a multisite RPM program for management of acute COVID-19 illness. We report an evaluation of 7074 patients served by the program across 41 US states. Among all patients, the RPM technology engagement rate was 78.9%. Rates of emergency department visit and hospitalization within 30 days of enrollment were 11.4% and 9.4%, respectively, and the 30-day mortality rate was 0.4%. A multisite RPM program for management of acute COVID-19 illness is feasible, safe, and associated with a low mortality rate. Further research and expansion of RPM programs for ambulatory management of other acute illnesses are warranted.

Objective To describe the clinical features and epidemiology of leprosy in patients evaluated in a Midwestern dermatology clinic. Patients and Methods We performed a retrospective review of clinical and laboratory data from patients with leprosy who were evaluated in the Department of Dermatology at Mayo Clinic in Rochester, Minnesota, from January 1, 1994, through December 31, 2017. Results Nine patients, 7 male and 2 female, were identified, ranging in age from 15 to 63 years (mean age, 38 years). Six of the 9 patients (67%) were foreign-born: 3 from Oceania (2 from Micronesia and 1 from Guam), 1 from Southeast Asia (Indonesia), and 2 from Mexico. Three patients were born in the United States. All 9 patients presented with skin lesions (granulomatous histopathologic type), and 8 had neuropathy. Leprosy was multibacillary in 8 patients and paucibacillary in 1. Two patients experienced a type 1 treatment reaction, and 5 had type 2 reactions. Three of the 9 patients had speciation by polymerase chain reaction (Mycobacterium leprae in 2 and Mycobacterium lepromatosis in 1). Conclusion Despite its rarity in the United States, leprosy should be considered in the differential diagnosis when evaluating both foreign- and US-born patients with granulomatous dermatitis and peripheral neuropathy. Because M lepromatosis was not identified until 2008 and requires polymerase chain reaction for diagnosis, the incidence of this species among patients with leprosy diagnosed in earlier years is unknown.

Cerebral venous sinus thrombosis (CVST) has been reported in a small number of individuals who have received the mRNA vaccines1or the adenoviral vector vaccines for COVID-19 in the US2and Europe3. Continued pharmacovigilance is integral to mitigating the risk of rare adverse events that clinical trials are underpowered to detect, however, these anecdotal reports have led to the pause or withdrawal of some vaccines in many jurisdictions and exacerbated vaccine hesitancy at a critical moment in the fight against the COVID-19 pandemic. We investigated the frequencies of CVST seen among individuals who received FDA-authorized COVID-19 vaccines from Pfizer-BioNTech (n = 94,818 doses), Moderna (n = 36,350 doses) and Johnson & Johnson - J&J (n = 1,745 doses), and among individuals receiving one of 10 FDA-approved non-COVID-19 vaccines (n = 771,805 doses). Comparing the incidence rates of CVST in 30-day time windows before and after vaccination, we found no statistically significant differences for the COVID-19 vaccines or any other vaccines studied in this population. In total, we observed 3 cases of CVST within the 30 days following Pfizer-BioNTech vaccination (2 females, 1 male; Ages (years): [79, 80, 84]), including one individual with a prior history of thrombosis and another individual with recent trauma in the past 30 days. We did not observe any cases of CVST among the patients receiving Moderna or J&J vaccines in this study population. We further found the baseline CVST incidence in the study population between 2017 and 2021 to be 45 to 98 per million patient years. Overall, this real-world evidence-based study highlights that CVST is rare and is not significantly associated with COVID-19 vaccination. In addition, there is a need for a concerted international effort to monitor EHR data across diverse patient populations and to investigate the underlying biological mechanisms leading to these rare clotting events.

In a large cohort of United States healthcare personnel without prior coronavirus disease 2019 (COVID-19) infection, 94 382 doses of messenger RNA (mRNA) COVID-19 vaccine were administered to 49 220 individuals. The adjusted vaccine effectiveness following 2 doses of each of the 2 available brands of mRNA vaccine exceeded 96%.

Background Two US Food and Drug Administration (FDA)-authorized coronavirus disease 2019 (COVID-19) mRNA vaccines, BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna), have demonstrated high efficacy in large phase 3 randomized clinical trials. It is important to assess their effectiveness in a real-world setting. Methods This is a retrospective analysis of 136,532 individuals in the Mayo Clinic health system (Arizona, Florida, Iowa, Minnesota, and Wisconsin) with PCR testing data between December 1, 2020 and April 20, 2021. We compared clinical outcomes for a vaccinated cohort of 68,266 individuals who received at least one dose of either vaccine (nBNT162b2 = 51,795; nmRNA-1273 = 16,471) and an unvaccinated control cohort of 68,266 individuals propensity matched based on relevant demographic, clinical, and geographic features. We estimated real-world vaccine effectiveness by comparing incidence rates of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR testing and COVID-19-associated hospitalization and intensive care unit (ICU) admission starting 7 days after the second vaccine dose. Findings The real-world vaccine effectiveness of preventing SARS-CoV-2 infection was 86.1% (95% confidence interval [CI]: 82.4%–89.1%) for BNT162b2 and 93.3% (95% CI: 85.7%–97.4%) for mRNA-1273. BNT162b2 and mRNA-1273 were 88.8% (95% CI: 75.5%–95.7%) and 86.0% (95% CI: 71.6%–93.9%) effective in preventing COVID-19-associated hospitalization. Both vaccines were 100% effective (95% CIBNT162b2: 51.4%–100%; 95% CImRNA-1273: 43.3%–100%) in preventing COVID-19-associated ICU admission. Conclusions BNT162b2 and mRNA-1273 are effective in a real-world setting and are associated with reduced rates of SARS-CoV-2 infection and decreased burden of COVID-19 on the healthcare system. Funding This study was funded by nference., Graphical abstract, Context and significance This is a study of the COVID-19 vaccines developed by Pfizer/BioNTech and Moderna. Although these vaccines have been shown to be effective in clinical trials, it is important to confirm that they work well in practice. The results from this study show that these vaccines are effective in reducing the risk of COVID-19 infection, COVID-19-associated hospitalization, and COVID-19-associated ICU admission. As one of the largest real-world evidence studies of COVID-19 vaccine effectiveness in the United States to date, this study provides strong evidence that COVID-19 vaccines work well in practice., Pawlowski et al. assess the real-world effectiveness of the BNT162b2 and mRNA-1273 COVID-19 vaccines among 136,532 individuals. They compare infection, hospitalization, and ICU admission rates between vaccinated and propensity-matched unvaccinated individuals. They find that both vaccines protect against SARS-CoV-2 infection and severe COVID-19.

Background As the coronavirus disease 2019 (COVID-19) vaccination campaign unfolds, it is important to continuously assess the real-world safety of Food and Drug Administration (FDA)-authorized vaccines. Curation of large-scale electronic health records (EHRs) enables near-real-time safety evaluations that were not previously possible. Methods In this retrospective study, we deployed deep neural networks over a large EHR system to automatically curate the adverse effects mentioned by physicians in over 1.2 million clinical notes between December 1, 2020 and April 20, 2021. We compared notes from 68,266 individuals who received at least one dose of BNT162b2 (n = 51,795) or mRNA-1273 (n = 16,471) to notes from 68,266 unvaccinated individuals who were matched by demographic, geographic, and clinical features. Findings Individuals vaccinated with BNT162b2 or mRNA-1273 had a higher rate of return to the clinic, but not the emergency department, after both doses compared to unvaccinated controls. The most frequently documented adverse effects within 7 days of each vaccine dose included myalgia, headache, and fatigue, but the rates of EHR documentation for each side effect were remarkably low compared to those derived from active solicitation during clinical trials. Severe events, including anaphylaxis, facial paralysis, and cerebral venous sinus thrombosis, were rare and occurred at similar frequencies in vaccinated and unvaccinated individuals. Conclusions This analysis of vaccine-related adverse effects from over 1.2 million EHR notes of more than 130,000 individuals reaffirms the safety and tolerability of the FDA-authorized mRNA COVID-19 vaccines in practice. Funding This study was funded by nference., Graphical abstract, Context and significance This is a study of the mRNA COVID-19 vaccines developed by Pfizer/BioNTech and Moderna. Although these vaccines have been shown to be safe and tolerated in clinical trials, it is important to confirm their safety profiles in practice. The results from this study show that individuals receiving these vaccines are likely to experience muscle and joint soreness, but they are not more likely to seek out emergent clinical care or experience severe medical events than unvaccinated individuals. As one of the largest real-world safety studies of COVID-19 vaccines to date, these data reinforce that we should continue expanding efforts to deliver more vaccines with high confidence in their safety., McMurry et al. assess the real-world safety of the BNT162b2 and mRNA-1273 COVID-19 vaccines. Using natural language processing, they compare the rates of specified adverse effects between 68,266 vaccinated individuals and 68,266 matched unvaccinated individuals. They find that both vaccines are safe and tolerated in clinical practice.

As the COVID-19 vaccination campaign unfolds as one of the most rapid and widespread in history, it is important to continuously assess the real-world safety of the FDA-authorized vaccines. Curation from large-scale electronic health records (EHRs) allows for near real-time safety evaluations that were not previously possible. Here, we advance context- and sentiment-aware deep neural networks over the multi-state Mayo Clinic enterprise (Minnesota, Arizona, Florida, Wisconsin) for automatically curating the adverse effects mentioned by healthcare providers in over 108,000 EHR clinical notes between December 1st2020 and February 8th2021. We retrospectively compared the clinical notes of 31,029 individuals who received at least one dose of the Pfizer/BioNTech or Moderna mRNA vaccine to those of 30,933 unvaccinated individuals who were propensity matched by demographics, residential location, and history of prior SARS-CoV-2 testing. We find that vaccinated and unvaccinated individuals were seen in the clinic at similar rates within 21 days of the first or second actual or assigned vaccination date (first dose Odds Ratio = 1.14, 95% CI: 1.10-1.18; second dose Odds Ratio = 0.91, 95% CI: 0.86-0.96). Further, the incidence rates of all surveyed adverse effects were similar or lower in vaccinated individuals compared to unvaccinated individuals after either vaccine dose, although myalgia was modestly increased within 7 days of the second dose when considering only pairs of matched individuals who each had at least one clinical note in this time window (Incidence Rate Ratio = 2.5, 95% CI: 1.1-6.7). Finally, the most frequently documented adverse effects within 7 days of each vaccine dose were fatigue (Dose 1: 1.75%, Dose 2: 1.18%), nausea (Dose 1: 1.03%, Dose 2: 0.84%), myalgia (Dose 1: 0.41%; Dose 2: 0.43%), diarrhea (Dose 1: 0.65%; Dose 2: 0.45%), arthralgia (Dose 1: 0.64%; Dose 2: 0.57%), erythema (Dose 1: 0.56%; Dose 2: 0.44%), vomiting (Dose 1: 0.44%, Dose 2: 0.29%) and fever (Dose 1: 0.21%; Dose 2: 0.18%). These frequencies of adverse event documentation in EHR notes are 2.1 times (95% CI: [1.5, 3.0]) to 1500 times (95% CI: [670, 2800]) lower than the frequencies of adverse events recorded via active solicitation during clinical trials or post-marketing surveillance, with headache after second vaccination showing the highest ratio of trial reporting to EHR documentation. This rapid and timely analysis of EHR notes from 31,029 vaccinated individuals highlights the rarity of vaccine-associated adverse effects requiring clinical attention and reaffirms the tolerability of the FDA-authorized COVID-19 vaccines in practice.

Large Phase 3 clinical trials of the two FDA-authorized COVID-19 vaccines, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech), have demonstrated efficacies of 94.1% (n = 30,420, 95% CI: 89.3-96.8) and 95% (n = 43,448, 95% CI: 90.3-97.6) in preventing symptomatic COVID-19, respectively. Given the ongoing vaccine rollout to healthcare personnel and residents of long-term care facilities, here we provide a preliminary assessment of real-world vaccination efficacy in 62,138 individuals from the Mayo Clinic and associated health system (Arizona, Florida, Minnesota, Wisconsin) between December 1st2020 and February 8th2021. Our retrospective analysis contrasts 31,069 individuals receiving at least one dose of either vaccine with 31,069 unvaccinated individuals who are propensity-matched based on demographics, location (zip code), and number of prior SARS-CoV-2 PCR tests. 8,041 individuals received two doses of a COVID-19 vaccine and were at risk for infection at least 36 days after their first dose. Administration of two COVID-19 vaccine doses was 88.7% effective in preventing SARS-CoV-2 infection (95% CI: 68.4-97.1%) with onset at least 36 days after the first dose. Furthermore, vaccinated patients who were subsequently diagnosed with COVID-19 had significantly lower 14-day hospital admission rates than propensity-matched unvaccinated COVID-19 patients (3.7% vs. 9.2%; Relative Risk: 0.4; p-value: 0.007). Building upon the previous randomized trials of these vaccines, this study demonstrates their real-world effectiveness in reducing the rates of SARS-CoV-2 infection and COVID-19 severity among individuals at highest risk for infection.

Recent reports on waning of COVID-19 vaccine-induced immunity have led to the approval and rollout of additional doses and booster vaccinations. Individuals at increased risk of SARS-CoV-2 infection are receiving additional vaccine doses in addition to the regimen that was tested in clinical trials. Risks and adverse event profiles associated with additional vaccine doses are currently not well understood.To evaluate the safety of third-dose vaccination with US Food and Drug Administration (FDA)-approved COVID-19 mRNA vaccines.This cohort study was conducted using electronic health record (EHR) data from December 2020 to October 2021 from the multistate Mayo Clinic Enterprise. Participants included all 47 999 individuals receiving 3-dose COVID-19 mRNA vaccines within the study setting who met study inclusion criteria. Participants were divided into 2 cohorts by vaccine brand administered and served as their own control groups, with no comparison made between cohorts. Data were analyzed from September through November 2021.Three doses of an FDA-authorized COVID-19 mRNA vaccine, BNT162b2 or mRNA-1273.Vaccine-associated adverse events were assessed via EHR report. Adverse event risk was quantified using the percentage of study participants who reported the adverse event within 14 days after each vaccine dose and during a 14-day control period, immediately preceding the first vaccine dose.Among 47 999 individuals who received 3-dose COVID-19 mRNA vaccines, 38 094 individuals (21 835 [57.3%] women; median [IQR] age, 67.4 [52.5-76.5] years) received BNT162b2 (79.4%) and 9905 individuals (5099 [51.5%] women; median [IQR] age, 67.7 [59.5-73.9] years) received mRNA-1273 (20.6%). Reporting of severe adverse events remained low after the third vaccine dose, with rates of pericarditis (0.01%; 95% CI, 0%-0.02%), anaphylaxis (0%; 95% CI, 0%-0.01%), myocarditis (0%; 95% CI, 0%-0.01%), and cerebral venous sinus thrombosis (no individuals) consistent with results from earlier studies. Significantly more individuals reported low-severity adverse events after the third dose compared with after the second dose, including fatigue (2360 individuals [4.92%] vs 1665 individuals [3.47%]; P .001), lymphadenopathy (1387 individuals [2.89%] vs 995 individuals [2.07%]; P .001), nausea (1259 individuals [2.62%] vs 979 individuals [2.04%]; P .001), headache (1185 individuals [2.47%] vs 992 individuals [2.07%]; P .001), arthralgia (1019 individuals [2.12%] vs 816 individuals [1.70%]; P .001), myalgia (956 individuals [1.99%] vs 784 individuals [1.63%]; P .001), diarrhea (817 individuals [1.70%] vs 595 individuals [1.24%]; P .001), fever (533 individuals [1.11%] vs 391 individuals [0.81%]; P .001), vomiting (528 individuals [1.10%] vs 385 individuals [0.80%]; P .001), and chills (224 individuals [0.47%] vs 175 individuals [0.36%]; P = .01).This study found that although third-dose vaccination against SARS-CoV-2 infection was associated with increased reporting of low-severity adverse events, risk of severe adverse events remained comparable with risk associated with the standard 2-dose regime. These findings suggest the safety of third vaccination doses in individuals who were eligible for booster vaccination at the time of this study.

Respiratory tract infections (RTIs) drive many outpatient encounters and, despite being predominantly viral, are associated with high rates of antibiotic prescriptions. With rising antibacterial resistance, optimization of prescribing of antibiotics in outpatients with RTIs is a critical need. Fortunately, this challenge arises at a time of increasing availability of novel RTI diagnostics to help discern which patients have bacterial infections warranting treatment. Effective implementation of antibiotic stewardship is needed, but optimal approaches for ambulatory settings are unknown. Future research needs are reviewed in this summary of a research summit convened by the Infectious Diseases Society of America in the fall of 2019.

Background Current guidelines from the American Heart Association (AHA) recommend repeating transesophageal echocardiography (TEE) in three to five days if there is high suspicion of IE despite an initial TEE that was negative. This recommendation, however, is based on limited published data. Objectives This investigation attempts to identify specific factors that prompted repeat TEE and evaluate the yield of IE-related findings demonstrated by repeat TEE as compared to initial or prior TEE. Methods A retrospective cohort who had at least one repeat TEE during an index hospitalization or initial course of antimicrobial therapy for IE between January 2014 and September 2018. We assessed the impact of repeat TEE on IE diagnosis and patient management and included a comparative analysis of patients with initial TEE only. Results Overall, 59 (44.7%) of 132 IE patients underwent repeat TEE. In a comparative analysis that involved patients who had undergone an initial TEE only versus those who had repeat TEE, male gender (P = .029) and presence of a prosthetic valve or annuloplasty ring (P = .017) were significantly associated with repeat TEE. Importantly, 8 (17.4%) of repeat TEE were critical for IE diagnosis, 8 (17.4%) impacted antimicrobial management, and 11 (23.9%) supported cardiovascular surgical intervention. Conclusions From a population-based cohort of incident IE cases, repeat TEE was more frequently (44.7%) done in patients with suspect or proven IE and associated complications than anticipated. Repeat TEE remains pivotal in a contemporary practice that involves critical aspects of IE diagnosis and management.

Background Rapid blood culture diagnostics are of unclear benefit for patients with gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, randomized, controlled trial comparing outcomes of patients with GNB BSIs who had blood culture testing with standard-of-care (SOC) culture and antimicrobial susceptibility testing (AST) vs rapid organism identification (ID) and phenotypic AST using the Accelerate Pheno System (RAPID). Methods Patients with positive blood cultures with Gram stains showing GNB were randomized to SOC testing with antimicrobial stewardship (AS) review or RAPID with AS. The primary outcome was time to first antibiotic modification within 72 hours of randomization. Results Of 500 randomized patients, 448 were included (226 SOC, 222 RAPID). Mean (standard deviation) time to results was faster for RAPID than SOC for organism ID (2.7 [1.2] vs 11.7 [10.5] hours; P Conclusions Rapid organism ID and phenotypic AST led to faster changes in antibiotic therapy for gram-negative BSIs. Clinical Trials Registration NCT03218397.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which presents an unprecedented challenge to medical providers worldwide. Although most SARS-CoV-2-infected individuals manifest with a self-limited mild disease that resolves with supportive care in the outpatient setting, patients with moderate to severe COVID-19 will require a multidisciplinary collaborative management approach for optimal care in the hospital setting. Laboratory and radiologic studies provide critical information on disease severity, management options, and overall prognosis. Medical management is mostly supportive with antipyretics, hydration, oxygen supplementation, and other measures as dictated by clinical need. Among its medical complications is a characteristic proinflammatory cytokine storm often associated with end-organ dysfunction, including respiratory failure, liver and renal insufficiency, cardiac injury, and coagulopathy. Specific recommendations for the management of these medical complications are discussed. Despite the issuance of emergency use authorization for remdesivir, there are still no proven effective antiviral and immunomodulatory therapies, and their use in COVID-19 management should be guided by clinical trial protocols or treatment registries. The medical care of patients with COVID-19 extends beyond their hospitalization. Postdischarge follow-up and monitoring should be performed, preferably using telemedicine, until the patients have fully recovered from their illness and are released from home quarantine protocols.

BackgroundThe American Heart Association (AHA) guidelines for infective endocarditis (IE) management recommend end-of-therapy (EOT) echocardiography (ETE) to “establish a new baseline” and based on “expert opinion.”MethodsMedical records of IE patients treated between January 2005 and December 2011 were reviewed. Utilization of ETE and cumulative incidence of re-treatment with antimicrobials or cardiovascular surgery (re-Rx/CVS) within 1 year after EOT were evaluated.ResultsA total of 243 patients completed clinical follow-up at EOT and 170 at 1 year after EOT. One hundred seventy-seven of 243 (72.8%) underwent ETE, the majority (51.4%) transthoracic echocardiography. One hundred thirty-three of 177 (75.1%) were without new/worsened signs or symptoms (new/w-SSx). One hundred forty-one of 177 (79.7%) overall and 117/133 (87.9%) patients without new/w-SSx had no new ETE findings as compared with initial echocardiography. Among 36/177 (20.3%) with new ETE findings, 20/36 (55.6%) had new/w-SSx; ETE findings were more likely in patients with new/w-SSx (39.2% vs 8.3%; P ConclusionsThe majority of patients without new/w-SSx at EOT will not have new ETE findings or need re-Rx/CVS within 1 year after EOT. EOT new/w-SSx is associated with new ETE findings and predicts the need for re-Rx/CVS. Further study is needed to determine whether patients without new/w-SSx need ETE.

The advent of tumor necrosis factor-α (TNF-α) inhibitor therapy has transformed inflammatory bowel disease management; however, these medications carry a boxed warning for risk of serious infections, including invasive fungal infections.We aimed to study the clinical features, severity, and outcomes of histoplasmosis in patients on TNF-α inhibitors for IBD.We performed a retrospective review of IBD patients receiving TNF-α inhibitors who developed histoplasmosis from January 1, 2001, to May 31, 2018. Patients with drug indications other than ulcerative colitis or Crohn's disease were excluded. IBD was diagnosed histologically, radiographically, or endoscopically.We identified 49 patients (median age 44 years; range 19-76) with histoplasmosis on TNF-α inhibitors. Patients with disseminated disease had a median urine antigen of 10.76 ng/mL compared with pulmonary disease alone 0.375 ng/mL (p 0.001). Charlson Comorbidity Index and urine antigen levels showed a trend toward predicting disease severity (p 0.05). Median length of stay was 9.5 days. Itraconazole was used for maintenance in all patients. Median follow-up was 4.7 years. Total treatment duration ranged from 3 to 15 months. TNF-α inhibitor therapy was continued in nine and resumed in ten patients after completing antifungals. Three deaths occurred (6%).Histoplasmosis outcomes were mostly favorable. Many patients were young with few comorbidities; however, those with more comorbidities experienced more severe histoplasmosis. Compared to prior studies, many of these patients resumed or continued biologic therapy. There were no histoplasmosis recurrences after resuming TNF-α inhibitor therapy. Vigilance for disseminated fungal infections in this patient population is essential.

Background mRNA COVID-19 vaccines are safe and effective, but increasing reports of breakthrough infections highlight the need to vigilantly monitor and compare the effectiveness of these vaccines. Methods We retrospectively compared protection against symptomatic infection conferred by mRNA-1273 and BNT162b2 at Mayo Clinic sites from December 2020 to September 2021. We used a test-negative case-control design to estimate vaccine effectiveness (VE) and to compare the odds of symptomatic infection after full vaccination with mRNA-1273 versus BNT162b2, while adjusting for age, sex, race, ethnicity, geography, comorbidities, and calendar time of vaccination and testing. Findings Both vaccines were highly effective over the study duration (VEmRNA-1273: 84.1%, 95% CI: 81.6-86.2%; VEBNT162b2: 75.6%, 95% CI: 72.2-78.7%), but their effectiveness was reduced during July-September (VEmRNA-1273: 75.6%, 95% CI: 70.1-80%; VEBNT162b2: 63.5%, 95% CI: 55.8-69.9%) as compared to December-May (VEmRNA-1273: 93.7%, 95% CI: 90.4-95.9%; VEBNT162b2: 85.7%, 95% CI: 81.4-88.9%). Adjusted for demographic characteristics, clinical comorbidities, time of vaccination, and time of testing, the odds of experiencing a symptomatic breakthrough infection were lower after full vaccination with mRNA-1273 than with BNT162b2 (Odds Ratio: 0.60, 95% CI: 0.55-0.67). Conclusions Both mRNA-1273 and BNT162b2 strongly protect against symptomatic SARS-CoV-2 infection. It is imperative to continue monitoring and comparing available vaccines over time and with respect to emerging variants to inform public and global health decisions., Graphical Abstract, Puranik et al. compare the real world effectiveness of BNT162b2 and mRNA-1273 in a population of over 180,000 vaccinated individuals. While both vaccines strongly protected against symptomatic infection, their effectiveness declined in recent months. Throughout the study period, mRNA-1273 recipients had lower rates of COVID-19 diagnosis than BNT162b2 recipients.

Importance: Continuous assessment of the effectiveness and safety of the US Food and Drug Administration-authorized SARS-CoV-2 vaccines is critical to amplify transparency, build public trust, and ultimately improve overall health outcomes. Objective: To evaluate the effectiveness of the Johnson & Johnson Ad26.COV2.S vaccine for preventing SARS-CoV-2 infection. Design, Setting, and Participants: This comparative effectiveness research study used large-scale longitudinal curation of electronic health records from the multistate Mayo Clinic Health System (Minnesota, Arizona, Florida, Wisconsin, and Iowa) to identify vaccinated and unvaccinated adults between February 27 and July 22, 2021. The unvaccinated cohort was matched on a propensity score derived from age, sex, zip code, race, ethnicity, and previous number of SARS-CoV-2 polymerase chain reaction tests. The final study cohort consisted of 8889 patients in the vaccinated group and 88 898 unvaccinated matched patients. Exposure: Single dose of the Ad26.COV2.S vaccine. Main Outcomes and Measures: The incidence rate ratio of SARS-CoV-2 infection in the vaccinated vs unvaccinated control cohorts, measured by SARS-CoV-2 polymerase chain reaction testing. Results: The study was composed of 8889 vaccinated patients (4491 men [50.5%]; mean [SD] age, 52.4 [16.9] years) and 88 898 unvaccinated patients (44 748 men [50.3%]; mean [SD] age, 51.7 [16.7] years). The incidence rate ratio of SARS-CoV-2 infection in the vaccinated vs unvaccinated control cohorts was 0.26 (95% CI, 0.20-0.34) (60 of 8889 vaccinated patients vs 2236 of 88 898 unvaccinated individuals), which corresponds to an effectiveness of 73.6% (95% CI, 65.9%-79.9%) and a 3.73-fold reduction in SARS-CoV-2 infections. Conclusions and Relevance: This study's findings are consistent with the clinical trial-reported efficacy of Ad26.COV2.S and the first retrospective analysis, suggesting that the vaccine is effective at reducing SARS-CoV-2 infection, even with the spread of variants such as Alpha or Delta that were not present in the original studies, and reaffirm the urgent need to continue mass vaccination efforts globally.