EHR-based Case Identification of Pediatric Long COVID: A Report from the RECOVER EHR Cohort.

Objective: Long COVID, marked by persistent, recurring, or new symptoms post-COVID-19 infection, impacts children's well-being yet lacks a unified clinical definition. This study evaluates the performance of an empirically derived Long COVID case identification algorithm, or computable phenotype, with manual chart review in a pediatric sample. This approach aims to facilitate large-scale research efforts to understand this condition better. Methods: The algorithm, composed of diagnostic codes empirically associated with Long COVID, was applied to a cohort of pediatric patients with SARS-CoV-2 infection in the RECOVER PCORnet EHR database. The algorithm classified 31,781 patients with conclusive, probable, or possible Long COVID and 307,686 patients without evidence of Long COVID. A chart review was performed on a subset of patients (n=651) to determine the overlap between the two methods. Instances of discordance were reviewed to understand the reasons for differences. Results: The sample comprised 651 pediatric patients (339 females, M age = 10.10 years) across 16 hospital systems. Results showed moderate overlap between phenotype and chart review Long COVID identification (accuracy = 0.62, PPV = 0.49, NPV = 0.75); however, there were also numerous cases of disagreement. No notable differences were found when the analyses were stratified by age at infection or era of infection. Further examination of the discordant cases revealed that the most common cause of disagreement was the clinician reviewers' tendency to attribute Long COVID-like symptoms to prior medical conditions. The performance of the phenotype improved when prior medical conditions were considered (accuracy = 0.71, PPV = 0.65, NPV = 0.74). Conclusions: Although there was moderate overlap between the two methods, the discrepancies between the two sources are likely attributed to the lack of consensus on a Long COVID clinical definition. It is essential to consider the strengths and limitations of each method when developing Long COVID classification algorithms.

Recent advances in wearable sensors and data analytics for continuous monitoring and analysis of biomarkers and symptoms related to COVID-19.

The COVID-19 pandemic has changed the lives of many people around the world. Based on the available data and published reports, most people diagnosed with COVID-19 exhibit no or mild symptoms and could be discharged home for self-isolation. Considering that a substantial portion of them will progress to a severe disease requiring hospitalization and medical management, including respiratory and circulatory support in the form of supplemental oxygen therapy, mechanical ventilation, vasopressors, etc. The continuous monitoring of patient conditions at home for patients with COVID-19 will allow early determination of disease severity and medical intervention to reduce morbidity and mortality. In addition, this will allow early and safe hospital discharge and free hospital beds for patients who are in need of admission. In this review, we focus on the recent developments in next-generation wearable sensors capable of continuous monitoring of disease symptoms, particularly those associated with COVID-19. These include wearable non/minimally invasive biophysical (temperature, respiratory rate, oxygen saturation, heart rate, and heart rate variability) and biochemical (cytokines, cortisol, and electrolytes) sensors, sensor data analytics, and machine learning-enabled early detection and medical intervention techniques. Together, we aim to inspire the future development of wearable sensors integrated with data analytics, which serve as a foundation for disease diagnostics, health monitoring and predictions, and medical interventions.

COVID-19 Associated Myocarditis Clinical Outcomes among Hospitalized Patients in the United States: A Propensity Matched Analysis of National Inpatient Sample.

Coronavirus-19 (COVID-19), preliminarily a respiratory virus, can affect multiple organs, including the heart. Myocarditis is a well-known complication among COVID-19 infections, with limited large-scale studies evaluating outcomes associated with COVID-19-related Myocarditis. We used the National Inpatient Sample (NIS) database to compare COVID-19 patients with and without Myocarditis. A total of 1,659,040 patients were included in the study: COVID-19 with Myocarditis (n = 6,455, 0.4%) and COVID-19 without Myocarditis (n = 1,652,585, 99.6%). The primary outcome was in-hospital mortality. Secondary outcomes included mechanical ventilation, vasopressor use, sudden cardiac arrest, cardiogenic shock, acute kidney injury requiring hemodialysis, length of stay, health care utilization costs, and disposition. We conducted a secondary analysis with propensity matching to confirm results obtained by traditional multivariate analysis. COVID-19 patients with Myocarditis had significantly higher in-hospital mortality compared to COVID-19 patients without Myocarditis (30.5% vs. 13.1%, adjusted OR: 3 [95% CI 2.1-4.2], p < 0.001). This cohort also had significantly increased cardiogenic shock, acute kidney injury requiring hemodialysis, sudden cardiac death, required more mechanical ventilation and vasopressor support and higher hospitalization cost. Vaccination and more research for treatment strategies will be critical for reducing worse outcomes in patients with COVID-19-related Myocarditis.

Antiretrovirals for People with HIV on Dialysis.

In the era of widespread use of antiretroviral therapy (ART), people with HIV (PWH) have a near-normal life expectancy. However, PWH have high rates of kidney diseases and progression to end-stage renal disease at a younger age. PWH have multiple risks for developing acute and chronic kidney diseases, including traditional risk factors such as diabetes, hypertension, and HIV-related factors such as HIV-associated nephropathy and increased susceptibility to infections and exposure to nephrotoxic medications. Despite an improvement in access to kidney transplant among PWH, the number of PWH on dialysis continues to increase. The expansion of the number of antiretrovirals (ARVs) and kidney replacement modalities, the absence of pharmacokinetic data, and therapeutic drug monitoring make it very challenging for providers to dose ARVs appropriately leading to medication errors, adverse events, and higher mortality. Most of the recommendations are either based on small sample size studies or extrapolated based on physiochemical characteristics of ART. We aim to review the most available and most current literature on ART in PWH with renal insufficiency and ART dosing recommendations on dialysis to ensure that PWH are provided with the safest and most effective ART regimen.

Clinical outcomes after IL-6 blockade in patients with COVID-19 and HIV: a case series.

BACKGROUND: In hospitalized people with HIV (PWH) there is an increased risk of mortality from COVID-19 among hospitalized PWH as compared to HIV-negative individuals. Evidence suggests that tocilizumab-a humanized monoclonal interleukin (IL)-6 receptor inhibitor (IL-6ri) antibody-has a modest mortality benefit when combined with corticosteroids in select hospitalized COVID-19 patients who are severely ill. Data on clinical outcomes after tocilizumab use in PWH with severe COVID-19 are lacking. CASE PRESENTATION: We present a multinational case series of 18 PWH with COVID-19 who were treated with IL-6ri's during the period from April to June 2020. Four patients received tocilizumab, six sarilumab, and eight received an undocumented IL-6ri. Of the 18 patients in the series, 4 (22%) had CD4 counts < 200 cells/mm3; 14 (82%) had a suppressed HIV viral load. Eight patients (44%), all admitted to ICU, were treated for secondary infection; 5 had a confirmed organism. Of the four patients with CD4 counts < 200 cells/mm3, three were treated for secondary infection, with 2 confirmed organisms. Overall outcomes were poor-12 patients (67%) were admitted to the ICU, 11 (61%) required mechanical ventilation, and 7 (39%) died. CONCLUSIONS: In this case series of hospitalized PWH with COVID-19 and given IL-6ri prior to the common use of corticosteroids, there are reports of secondary or co-infection in severely ill patients. Comprehensive studies in PWH, particularly with CD4 counts < 200 cells, are warranted to assess infectious and other outcomes after IL-6ri use, particularly in the context of co-administered corticosteroids.

Cancer immunotherapy in adult patients with HIV.

The availability of antiretroviral therapy (ART) has increased the life expectancy of people with HIV (PWH) and reduced the incidence of AIDS-associated malignancies, yet PWH have a significantly increased incidence of malignancy and less favorable outcomes of cancer treatment compared with the general population.Immunotherapy has revolutionized cancer therapy, becoming the standard of care for various malignancy treatments. However, PWH are an underserved population with limited access to clinical trials and cancer treatment.This review of the available evidence on different classes of cancer immunotherapy in PWH is mostly based on case reports, case series, but few prospective studies and clinical trials due to the exclusion of PWH from most oncologic clinical trials. The results of the available evidence support the safety of immunotherapy in PWH. Immunotherapy has similar effectiveness in PWH, an acceptable toxicity profile, and has no clinically significant impact on HIV viral load and CD4-T cell count. In addition, there is no reported change in the incidence of opportunistic infections and other complications for PWH with well-controlled viremia.This review aims to briefly summarize the current state of immunotherapy in cancer, guide clinicians in the management of immunotherapy in cancer PWH, and encourage the inclusion of PWH in clinical trials of cancer immunotherapy.

Staphylococcus lugdunensis as Cause of Septic Pericarditis.

Staphylococcus lugdunensis (S. lugdunensis) is a coagulase-negative gram-positive bacterium, considered part of skin flora, which can simultaneously cause human diseases. S. lugdunensis has been reported in the literature as one of the causative agents for infective endocarditis.1 Although one of the coagulasenegative staphylococci, S. lugdunensis shares many virulent characteristics with Staphylococcus aureus (S. aureus), including biofilm formation. It has been associated with various foreign body-related infections such as prosthetic joint infections,2 in addition to bacteremia, osteomyelitis, septic arthritis, central nervous system, urinary tract infections, peritonitis, infective endocarditis and others. Given the association with severe and aggressive infections, it is important to treat S. lugdunensis as true infection rather than a contaminant, particularly in a suspect clinical context.3-6 Currently, there are no reported cases in the literature on pericarditis secondary to S. lugdunensis. We present a case of a 69-year-old woman with pericarditis, sepsis and disseminated intravascular coagulopathy (DIC) due to S. lugdunensis.

Electronic Vaping-Induced Methicillin-Sensitive Staphylococcus Aureus Pneumonia and Empyema.

Pneumonia is a severe acute inflammation of the lower respiratory tract due to infectious pathogens. Pathogens responsible include bacteria, viruses, fungi, and parasites. Pneumonia categorizations include community-acquired pneumonia (CAP), hospital-acquired pneumonia, and ventilator-associated pneumonia. It is the single most common cause of infection-related mortality in the United States. Among the typical bacterial CAP causes, Staphylococcus aureus (S. aureus) is responsible for less than 5% of all cases. Among the S. aureus, methicillin-susceptible S. aureus (MSSA) is slightly more common than the methicillin-resistant S. aureus (MRSA). CAP caused by S. aureus is associated with worse clinical outcomes compared to streptococcal pneumoniae. Although S. aureus CAP occurs throughout the year, it is less common except during the influenza season when there is a spike. Multiple studies have stratified risk factors for MRSA infection. MSSA pneumonia in immunocompetent young patients is uncommon due to healthy host defense mechanisms. However, certain individual risk factors promote infection, such as intravenous drug abuse. Recent multiple research studies implicate increased virulence of S. aureus in colonized patients after exposure to electronic cigarette vapor exposure (ECVE), resulting in pneumonia. A PubMed search revealed no MSSA community-acquired bacterial pneumonia due to ECVE. We report a 38-year-old female who developed acute MSSA pneumonia, which was complicated by left empyema due to ECVE from JUUL device with third-party compatible cannabidiol pods. The patient completed treatment successfully with a chest tube placement followed by fibrinolysis and intravenous antibiotics.

COVID-19 Convalescent Plasma: from donation to treatment - A Systematic Review & Single Center Experience.

Convalescent plasma is an old treatment for a new disease. The coronavirus disease 2019 (COVID-19) pandemic caused the analysis of convalescent plasma to reemerge as a possible treatment. First, a systematic review summarizes the available research examining the use of convalescent plasma for the treatment of patients with COVID-19. Second, we describe our experience in establishing a single-center convalescent plasma donation program.

Acceptability and preferences for long-acting antiretroviral formulations among people with HIV infection.

The study evaluates the acceptability and preferences for long-acting antiretroviral therapy (LA-ART) among a diverse cohort of people with HIV infection (PWH). It consists of a self-administered survey and chart review of PWH presenting to an HIV clinic in Houston, Texas, between February and June 2018; 374 participants were included; 61% indicated that they were likely or very likely to use LA-ART formulations. When asked about preference, 41% preferred pills, 40% preferred injections, and 18% preferred an implant. The most common benefit reported was eliminating the need to remember taking daily HIV pills (74%); 43% were worried that LA-ART will not be as effective as pills. Participants with a college degree, men who have sex with men, and ART-experienced were more willing to use LA-ART. Participants who reported poor or fair health, or who screened positive for depression or anxiety were significantly less willing to use LA-ART. The likelihood of using LA-ART did not correlate with self-reported adherence and HIV suppression. Patients with difficulty scheduling and attending clinic visits preferred injections and implant over pills. Most participants indicated a willingness to use new LA ART formulations. However, 41% still prefers pills, and those more interested in LA-ART were not less adherent.

Characteristics, Comorbidities, and Outcomes in a Multicenter Registry of Patients With Human Immunodeficiency Virus and Coronavirus Disease 2019.

BACKGROUND: People living with human immunodeficiency virus (HIV) may have numerous risk factors for acquiring coronavirus disease 2019 (COVID-19) and developing severe outcomes, but current data are conflicting. METHODS: Health-care providers enrolled consecutively, by nonrandom sampling, people living with HIV (PWH) with lab-confirmed COVID-19, diagnosed at their facilities between 1 April and 1 July 2020. Deidentified data were entered into an electronic Research Electronic Data Capture (REDCap) system. The primary endpoint was a severe outcome, defined as a composite endpoint of intensive care unit (ICU) admission, mechanical ventilation, or death. The secondary outcome was the need for hospitalization. RESULTS: There were 286 patients included; the mean age was 51.4 years (standard deviation, 14.4), 25.9% were female, and 75.4% were African American or Hispanic. Most patients (94.3%) were on antiretroviral therapy, 88.7% had HIV virologic suppression, and 80.8% had comorbidities. Within 30 days of testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 164 (57.3%) patients were hospitalized, and 47 (16.5%) required ICU admission. Mortality rates were 9.4% (27/286) overall, 16.5% (27/164) among those hospitalized, and 51.5% (24/47) among those admitted to an ICU. The primary composite endpoint occurred in 17.5% (50/286) of all patients and 30.5% (50/164) of hospitalized patients. Older age, chronic lung disease, and hypertension were associated with severe outcomes. A lower CD4 count (<200 cells/mm3) was associated with the primary and secondary endpoints. There were no associations between the ART regimen or lack of viral suppression and the predefined outcomes. CONCLUSIONS: Severe clinical outcomes occurred commonly in PWH with COVID-19. The risks for poor outcomes were higher in those with comorbidities and lower CD4 cell counts, despite HIV viral suppression. CLINICAL TRIALS REGISTRATION: NCT04333953.

Reliability and Validity of a Brief Self-Report Adherence Measure among People with HIV Experiencing Homelessness and Mental Health or Substance Use Disorders.

The study examines the reliability and validity of a 3-item self-report adherence measure among people with HIV (PWH) experiencing homelessness, substance use, and mental health disorders. 336 participants were included from nine sites across the US between September 2013 and February 2017. We assessed the validity of a self-report scale for adherence to antiretroviral therapy by comparing it with viral load (VL) abstracted from medical records at baseline, 6, 12, and 18 months. The items had high internal consistency (Cronbach's alpha coefficients at each time point were > 0.8). The adherence scale scores were higher in the group that achieved VL suppression compared to the group that did not. The c-statistic for the receiver-operating characteristic curves pooled across time points was 0.77 for each adherence sub-item and 0.78 for the overall score. The self-report adherence measure shows good internal consistency and validity that correlated with VL suppression in homeless populations.

Are We Prescribing Enough HIV Pre-Exposure Prophylaxis in Missouri?: A Cross-Sectional Study at University of Missouri Health Care.

Despite the proven efficacy and safety of HIV pre-exposure prophylaxis (PrEP), it remains underutilized. PrEP use among Missouri providers has increased as the rate of new HIV infections grows statewide, but remains lower than the Midwest and United States (U.S.) averages. Because the Centers for Disease Control and Prevention (CDC) identify Missouri as at-risk for an HIV outbreak, we seek to characterize HIV testing practices and PrEP knowledge and use among Missouri healthcare providers.

Acute Streptococcus constellatus Pyogenic Liver Abscess Due to an Atypical Presentation of Sigmoid Diverticulitis Complicated by Pericolonic Abscess.

Diverticulitis is a result of diverticulum inflammation that involves protrusion of the colonic wall. It is considered to be complicated when associated with an abscess, fistula, perforation of large bowel, or obstruction. The incidence of diverticulitis increases with age, and it most commonly presents as constant abdominal pain in the left lower quadrant. We report a case of a 54-year-old male with a history of hypertension who was admitted to our hospital with systemic symptoms and right shoulder pain noted to have Streptococcus constellatus bacteremia and an incidental finding of a single large hepatic abscess on chest imaging. Additional imaging studies revealed the presence of acute sigmoid diverticulitis complicated by pericolonic abscess. He had no known risk factors and had not experienced any abdominal pain before admission.  A liver abscess due to S. constellatus is a rare complication from sigmoid diverticulitis, and there are only a few cases reported as per the PubMed medical literature review. Only four other unique cases with few or no risk factors were discovered to have a pyogenic liver abscess initially, and later source was found to be due to perforated diverticulitis. Due to this rare clinical presentation, diagnosis is often delayed leading to complications requiring surgical intervention. This can result in higher mortality. Our patient had ultrasound-guided drainage of the abscess and completed a six-week course of intravenous antibiotics (ceftriaxone and metronidazole) with successful recovery.

Diffusion-weighted MR imaging histogram analysis in HIV positive and negative patients with primary central nervous system lymphoma as a predictor of outcome and tumor proliferation.

INTRODUCTION: Ki-67 expression, a marker of tumor proliferation, is considered a prognostic factor in primary CNS lymphoma (PCNSL). Apparent diffusion coefficient (ADC) parameters have also been proposed as imaging biomarkers for tumor progression and proliferative activity in various malignancies. The aim of this study is to investigate the correlation between ADC parameters, Ki-67 expression, overall survival (OS) and progression free survival (PFS) in PCNSL. MATERIALS AND METHODS: Patients diagnosed with PCNSL at MD Anderson Cancer Center between Mar 2000 and Jul 2016 and at Ben Taub Hospital between Jan 2012 and Dec 2016 were retrospectively studied. Co-registered ADC maps and post-contrast images underwent whole tumor segmentation. Normalized ADC parameters (nADC) were calculated as the ratio to normal white matter. Percentiles of nADC were calculated and were correlated with Ki-67 using Pearson's correlation coefficient and clinical outcomes (OS and PFS) using Cox proportional hazards models. RESULTS: Selection criteria yielded 90 patients, 23 patients living with HIV (PLWH) and 67 immunocompetent patients. Above median values for nADCmean, nADC15, nADC75 and nADC95 were associated with improved OS in all patients (p < 0.05). Above median values for nADCmin, nADCmean, nADC1, nADC5 and kurtosis were associated with improved PFS in all patients (p < 0.05). In patients with available Ki-67 expression data (n = 22), nADCmean, nADC15 and nADC75 inversely correlated with Ki-67 expression (p < 0.05). For PLWH, there was no correlation between ADC parameters and Ki-67 expression or clinical outcomes. CONCLUSIONS: ADC histogram analysis can predict tumor proliferation and survival in immunocompetent patients with PCNSL, but with limited utility in PLWH.

Laboratory Tests for COVID-19: A Review of Peer-Reviewed Publications and Implications for Clinical Use.

Diagnostic tests for the coronavirus infection 2019 (COVID-19) are critical for prompt diagnosis, treatment and isolation to break the cycle of transmission. A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR), in conjunction with clinical and epidemiologic data, is the current standard for diagnosis, but several challenges still exist. Serological assays help to understand epidemiology better and to evaluate vaccine responses but they are unreliable for diagnosis in the acute phase of illness or assuming protective immunity. Serology is gaining attention, mainly because of convalescent plasma gaining importance as treatment for clinically worsening COVID-19 patients. We provide a narrative review of peer-reviewed research studies on RT-PCR, serology and antigen immune-assays for COVID-19, briefly describe their lab methods and discuss their limitations for clinical practice.

Primary cutaneous cryptococcal infection due to fingolimod - Induced lymphopenia with literature review.

Cryptococcus. Neoformans (C. neoformans) is an encapsulated heterobasidiomycetous fungus responsible for opportunistic infections worldwide in immunocompromised patients. Clinical presentation ranges from asymptomatic respiratory tract colonization to disseminated infection in any human body part. The central nervous system (CNS) and pulmonary diseases garner most of the clinical attention. Secondary cutaneous cryptococcosis is an uncommon manifestation seen as a sentinel sign commonly in disseminated cryptococcal infection. Primary cutaneous cryptococcosis (PCC) is a rare manifestation seen in both immunocompromised and immunocompetent patients. It is a discrete infection with different epidemiological trends. Immunosuppressive therapy (corticosteroids, tacrolimus) predisposes a patient to acquire this clinical entity. We present a case of an elderly Caucasian male on fingolimod for relapsing-remitting multiple sclerosis with nonhealing scalp lesions for four years. He was a referral to our healthcare center for the presence of fungal elements seen on a scalp biopsy fungal stains. Final cultures returned positive for C. neoformans susceptible to fluconazole (MIC = 8 µg/mL). The CD4 count was 13 cells/uL, and workup for CNS and disseminated cryptococcal infection were negative. Fingolimod is an immunomodulator that acts on sphingosine 1-phosphate receptors, affecting the lymphocytes. Pubmed literature review revealed few case reports (< 5) with PCC in patients on fingolimod. To our knowledge, ours is the first case with scalp cryptococcosis, with the lowest CD4 count while being on fingolimod. No randomized controlled trial data exist for the treatment of PCC. Therapy initiated with oral luconazole for six months with significant improvement at three months.