Faculty Bibliography

BACKGROUND:Neuraminidase inhibitors, including oseltamivir, are the treatment standard for influenza. Baloxavir, a novel antiviral, demonstrated comparable outcomes to oseltamivir in outpatients with influenza. Baloxavir was equally effective as oseltamivir in a retrospective study of hospitalized patients with influenza at our institution. However, the efficacy of baloxavir in immunocompromised patients is unclear. METHODS:We conducted a retrospective cohort study of immunocompromised adult patients hospitalized with influenza A who received baloxavir from January 2019 to April 2019 or oseltamivir from January 2018 to April 2018. Demographic and clinical outcomes were assessed. Primary outcomes were time from antiviral initiation to resolution of hypoxia and fever. Secondary outcomes were length of stay (LOS), intensive care unit (ICU) care, ICU LOS, and 30-day mortality. RESULTS:Of 95 total patients, 52 received baloxavir and 43 received oseltamivir. Other than younger age (57.5 vs. 65; p = .035) and longer duration between vaccination and symptom onset (114 vs. 86 days; p = .001) in the baloxavir group, baseline characteristics did not differ. H1 was the predominant subtype in the baloxavir group (65.3%) versus H3 in the oseltamivir group (85.7%). When comparing baloxavir to oseltamivir, there was no significant difference in median time from antiviral initiation to resolution of hypoxia (59.9 vs. 42.5 h) and to resolution of fever (21.6 vs. 26.6 h). There were no differences in secondary outcomes. CONCLUSION/CONCLUSIONS:Baloxavir was not associated with longer time to resolution of hypoxia or fever in comparison to oseltamivir. Results must be taken in context of variations in seasonal influenza subtype and resistance rates.

Purpose of Review: The COVID-19 pandemic has greatly impacted solid organ transplant recipients (SOTr). Strategies to improve outcomes in this population include active immunization through vaccination and passive immunity through monoclonal antibodies and convalescent plasma. Unfortunately, the response to vaccination is greatly impacted by immunosuppression in SOTr, and monoclonal antibodies are no longer effective against circulating variants. Recent Findings: This review summarizes the decreased immune response to vaccination in SOTr and the clinical efficacy of vaccination. Strategies to bolster immune response to vaccination include administration of booster doses, immunomodulation, timing of vaccination, type and dose of vaccine, and use of adjuvants. In addition to active immunization, we briefly describe passive immunization strategies that have a role in SARS-CoV2 prevention. Summary: Active and passive immunization is vital in reducing poor outcomes, including hospitalization and mortality, in SOTr. Further studies on optimization of immune response to SARS-CoV2 vaccine are needed.

This retrospective matched cohort study describes 30 solid organ transplant (SOT) patients with Coronavirus Disease 2019 (COVID-19) matched 1:2 to 60 non-SOT patients (control group) based on age, body mass index (BMI), and comorbidities (hypertension and diabetes mellitus with hemoglobin A1c > 8.0%). The SOT group had a higher proportion of cardiovascular disease (P < .05). During the index hospitalization, there were no significant differences with regard to disease severity or critical care needs (mechanical intubation, vasopressors, and renal replacement therapy). At 28 days, 4 (13%) patients died in the SOT group and 8 (13%) patients died in the control group (P = 1.0). Nineteen patients received tocilizumab in the SOT group compared to 29 patients in the control group. Among these patients, interleukin-6 (IL-6) and soluble interleukin-2 receptor (sIL2R) levels increased after tocilizumab and interleukin-10 (IL-10) levels decreased after tocilizumab. Overall, SOT patients had comparable mortality to non-SOT patients, although numerically more SOT patients received tocilizumab (63% vs 48%) and steroids (37% vs 20%). Larger, multi-center studies are needed to ascertain these findings. Lastly, the complex cytokine release syndrome in COVID-19 remains an area of intense research and the analysis of key interleukin levels (IL-6, IL-10, and sIL2R) in this study contributes to the understanding of this process.

BACKGROUND:Clinical and virologic characteristics of COVID-19 infections in veterans in New England have not been described. The average US veteran is a male older than the general US population. SARS-CoV-2 infection is known to cause poorer outcomes among men and older adults, making the veteran population an especially vulnerable group for COVID-19. OBJECTIVE:This study aims to evaluate clinical and virologic factors impacting COVID-19 outcomes. METHODS:This retrospective chart review included 476 veterans in six New England states with confirmed SARS-CoV-2 infection between April and September 2020. Whole genome sequencing was performed on SARS-CoV-2 RNA isolated from these veterans, and the correlation of genomic data to clinical outcomes was evaluated. Clinical and demographic variables were collected by manual chart review and were correlated to the end points of peak disease severity (based on oxygenation requirements), hospitalization, and mortality using multivariate regression analyses. RESULTS:Of 476 veterans, 274 had complete and accessible charts. Of the 274 veterans, 92.7% (n=254) were men and 83.2% (n=228) were White, and the mean age was 63 years. In the multivariate regression, significant predictors of hospitalization (C statistic 0.75) were age (odds ratio [OR] 1.05, 95% CI 1.03-1.08) and non-White race (OR 2.39, 95% CI 1.13-5.01). Peak severity (C statistic 0.70) also varied by age (OR 1.07, 95% CI 1.03-1.11) and O2 requirement on admission (OR 45.7, 95% CI 18.79-111). Mortality (C statistic 0.87) was predicted by age (OR 1.06, 95% CI 1.01-1.11), dementia (OR 3.44, 95% CI 1.07-11.1), and O2 requirement on admission (OR 6.74, 95% CI 1.74-26.1). Most (291/299, 97.3%) of our samples were dominated by the spike protein D614G substitution and were from SARS-CoV-2 B.1 lineage or one of 37 different B.1 sublineages, with none representing more than 8.7% (26/299) of the cases. CONCLUSIONS:In a cohort of veterans from the six New England states with a mean age of 63 years and a high comorbidity burden, age was the largest predictor of hospitalization, peak disease severity, and mortality. Non-White veterans were more likely to be hospitalized, and patients who required oxygen on admission were more likely to have severe disease and higher rates of mortality. Multiple SARS-CoV-2 lineages were distributed in patients in New England early in the COVID-19 era, mostly related to viruses from New York State with D614G mutation.

Infective endocarditis is a common and treatable condition that carries a high mortality rate. Currently the workup of infective endocarditis relies on the integration of clinical, microbiological and echocardiographic data through the use of the modified Duke criteria (MDC). However, in cases of prosthetic valve endocarditis (PVE) echocardiography can be normal or non-diagnostic in a high proportion of cases leading to decreased sensitivity for the MDC. Evolving multimodality imaging techniques including leukocyte scintigraphy (white blood cell imaging), ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET), multidetector computed tomographic angiography (MDCTA), and cardiac magnetic resonance imaging (CMRI) may each augment the standard workup of PVE and increase diagnostic accuracy. While further studies are necessary to clarify the ideal role for each of these imaging techniques, nevertheless, these modalities hold promise in determining the diagnosis, prognosis, and care of PVE. We start by presenting a clinical vignette, then evidence supporting various modality strategies, balanced by limitations, and review of formal guidelines, when available. The article ends with the authors' summary of future directions and case conclusion.

Beta-D-glucan (BDG) testing can expedite the diagnosis of invasive fungal infections in immunocompromised hosts. Elevated BDG levels have been reported in both in-vitro studies assessing cross-reactivity with Nocardia spp. and published cases of patients with nocardiosis, but there is little data on this association in solid organ transplantation (SOT) recipients. To explore this association, we conducted a case series of SOT recipients with culture-proven nocardiosis and BDG testing who received their care at our institution between 2016 and 2021. We found thirteen cases of nocardiosis in SOT recipients, of which three cases met our case definition of an elevated BDG. Their clinical courses are detailed in the present report. We found that BDG may be elevated in SOT with nocardiosis with no identified cause of false positive BDG, though a causal association cannot be determined. Future prospective studies that better evaluate the association between nocardiosis and BDG are warranted, as are studies that better characterize the possible variability in reactivity amongst Nocardia spp.