Compassionate Use of Remdesivir in Pregnant Women With Severe Coronavirus Disease 2019.

BACKGROUND: Remdesivir is efficacious for severe coronavirus disease 2019 (COVID-19) in adults, but data in pregnant women are limited. We describe outcomes in the first 86 pregnant women with severe COVID-19 who were treated with remdesivir. METHODS: The reported data span 21 March to 16 June 2020 for hospitalized pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection and room air oxygen saturation ≤94% whose clinicians requested remdesivir through the compassionate use program. The intended remdesivir treatment course was 10 days (200 mg on day 1, followed by 100 mg for days 2-10, given intravenously). RESULTS: Nineteen of 86 women delivered before their first dose and were reclassified as immediate "postpartum" (median postpartum day 1 [range, 0-3]). At baseline, 40% of pregnant women (median gestational age, 28 weeks) required invasive ventilation, in contrast to 95% of postpartum women (median gestational age at delivery 30 weeks). By day 28 of follow-up, the level of oxygen requirement decreased in 96% and 89% of pregnant and postpartum women, respectively. Among pregnant women, 93% of those on mechanical ventilation were extubated, 93% recovered, and 90% were discharged. Among postpartum women, 89% were extubated, 89% recovered, and 84% were discharged. Remdesivir was well tolerated, with a low incidence of serious adverse events (AEs) (16%). Most AEs were related to pregnancy and underlying disease; most laboratory abnormalities were grade 1 or 2. There was 1 maternal death attributed to underlying disease and no neonatal deaths. CONCLUSIONS: Among 86 pregnant and postpartum women with severe COVID-19 who received compassionate-use remdesivir, recovery rates were high, with a low rate of serious AEs.

AIDS-Associated Cryptosporidial and Cytomegalovirus Cholangiopathy.

Acquired immune deficiency syndrome (AIDS)-associated cholangiopathy is a biliary tract condition seen in AIDS patients who are severely immunosuppressed, contributing to significant mortality in this population, even in developed countries with access to highly active antiretroviral therapy (HAART).  We discuss a thirty-six-year-old human immunodeficiency virus (HIV)-positive male, non-compliant with HAART therapy, who presented with a one-year history of weight loss, persistent fatigue, and chronic diarrhea, which had worsened significantly in the past few weeks. Routine laboratory studies on presentation indicated elevated liver enzymes and alkaline phosphatase, a CD4 count of 2 cells/mm3, and a high HIV RNA count of 8.8 million. Imaging via CT of the abdomen and pelvis and ultrasound of the abdomen both displayed thickening and edema in the gallbladder without evidence of gallstones, raising concerns of acalculous cholecystitis. The patient subsequently decompensated, requiring intravenous vasopressors to maintain hemodynamic stability, broad-spectrum antibiotics, and resumption of antiretroviral therapy. Biliary fluid drainage was performed, and Cryptosporidium and cytomegalovirus (CMV) were detected via polymerase chain reaction (PCR) testing. The diagnosis of AIDS cholangiopathy was established; however, the patient's diarrhea worsened upon the introduction of tube feeds. Despite ongoing antimicrobial treatment, the patient developed a fever of 101.4°F, became asystolic and subsequently passed away. This case highlights the diagnostic, management, and therapeutic challenges of AIDS cholangiopathy. Also, it underscores the importance of thorough investigation into even mild or intermittent diarrhea and abnormal liver function tests in all HIV-infected patients, particularly in severely immunosuppressed patients. AIDS cholangiopathy should be considered in AIDS patients with diarrhea and abnormal liver function tests, irrespective of age, due to its associated morbidity across all age groups. Laboratory investigations often reveal markedly elevated alkaline phosphatase, gamma-glutamyltransferase, and mild to moderate liver enzyme elevations as hallmark findings of AIDS cholangiopathy. Ultrasonography is the first-line screening modality of AIDS cholangiopathy. Cryptosporidium parvum is the most common infectious etiology of AIDS cholangiopathy and can be identified by DNA-based polymerase chain reaction (PCR) testing of the stool or biliary fluid or acid-fast staining of stool specimens. Early detection of HIV infection and the prompt initiation and adherence to highly active antiretroviral therapy (HAART), which helps with maintaining a normal CD4 count and a low HIV viral load through HAART therapy, thereby significantly reducing the risk of developing AIDS cholangiopathy in HIV patients.

Impact of Early Corticosteroids on Preventing Clinical Deterioration in Non-critically Ill Patients Hospitalized with COVID-19: A Multi-hospital Cohort Study.

INTRODUCTION: While guidelines stronglyrecommend dexamethasone in critical COVID-19, the optimal threshold to initiate corticosteroids in non-critically ill patients with COVID-19 remains unclear. Using data from a state-wide COVID-19 registry, we evaluated the effectiveness of early corticosteroids for preventing clinical deterioration among non-critically ill patients hospitalized for COVID-19 and receiving non-invasive oxygen therapy. METHODS: This was a target trial using observational data from patients hospitalized for COVID-19 at 39 hospitals participating in the MI-COVID19 registry between March 16, 2020 and August 24, 2020. We studied the impact of corticosteroids initiated within 2 calendar days of hospitalization ("early steroids") versus no early steroids among non-ICU patients with laboratory-confirmed SARS-CoV2 receiving non-invasive supplemental oxygen therapy. Our primary outcome was a composite of in-hospital mortality, transfer to intensive care, and receipt of invasive mechanical ventilation. We used inverse probability of treatment weighting (IPTW) and propensity score-weighted regression to measure the association of early steroids and outcomes. RESULTS: Among 1002 patients meeting study criteria, 231 (23.1%) received early steroids. After IPTW, to balance potential confounders between the treatment groups, early steroids were not associated with a decrease in the composite outcome (aOR 1.1, 95%CI 0.8-1.6) or in any components of the primary outcome. CONCLUSION: We found no evidence that early corticosteroid therapy prevents clinical deterioration among hospitalized non-critically ill COVID-19 patients receiving non-invasive oxygen therapy. Further studies are needed to determine the optimal threshold for initiating corticosteroids in this population.

Spontaneous pneumomediastinum, pneumopericardium, pneumothorax and subcutaneous emphysema in patients with COVID-19 pneumonia, a case report.

BACKGROUND: Spontaneous pneumomediastinum unrelated to mechanical ventilation is a newly described complication of COVID-19 pneumonia. The objective of this case presentation is to highlight an important complication and to explore potential predisposing risk factors and possible underlying pathophysiology of this phenomenon. CASE PRESENTATION: We present two patients with COVID-19 pneumonia complicated by spontaneous pneumomediastinum, pneumopericardium, pneumothorax and subcutaneous emphysema without positive pressure ventilation. Both patients had multiple comorbidities, received a combination of antibiotics, steroids and supportive oxygen therapy, and underwent routine laboratory workup. Both patients then developed spontaneous pneumomediastinum and ultimately required intubation and mechanical ventilation, which proved to be challenging to manage. CONCLUSIONS: Spontaneous pneumomediastinum is a serious complication of COVID-19 pneumonia, of which clinicians should be aware. Further studies are needed to determine risk factors and laboratory data predictive of development of spontaneous pneumomediastinum in COVID-19 pneumonia.

Viral infections of the central nervous system: a case-based review.

Three patients with viral infections of the central nervous system (CNS) were evaluated on an inpatient infectious diseases consultation service within a two-week period. These cases, caused by herpes simplex virus, varicella zoster virus and enterovirus, highlight the importance of viral pathogens in causing debilitating infections of the CNS and provide examples of the utility of molecular diagnostics in evaluating patients with encephalitis and meningitis. The importance of antiviral therapy is particularly underscored by these cases, as is the variability in response of patients to such agents.

Staphylococcus aureus bloodstream infections in older adults: clinical outcomes and risk factors for in-hospital mortality.

OBJECTIVES: To assess clinical outcomes and identify risk factors for mortality in older adults with Staphylococcus aureus bloodstream infection (SAB). DESIGN: Retrospective review. SETTING: University of Michigan Health System, Ann Arbor. PARTICIPANTS: All patients aged 80 and older with SAB between January 2004 and July 2008. MEASUREMENTS: Clinical data, including comorbid conditions, SAB source, echocardiography results, Charlson Comorbidity Index, mortality (in-hospital and 6-month), and need for rehospitalization or chronic care after discharge. RESULTS: Seventy-six patients aged 80 and older (mean 85.5 +/- 4.2) with SAB were identified. Infection sources included 14 (18.4%) vascular catheter associated, 16 (21.1%) wound related, seven (9.2%) endocarditis, five (6.6%) intravascular, and 19 (25%) with unknown source; 46 (60.5%) patients had methicillin-resistant strains. Twenty-two (28.9%) patients underwent surgery or device placement within 30 days of developing SAB; 10 of these 22 had SAB associated with surgical site infection (SSI). Twenty two (28.9%) patients died in the hospital or were discharged to hospice care; at least 43 (56.6%) patients died within 6 months of presentation, and eight were lost to follow-up. Unknown source of bacteremia (odds ratio=5.2, P=.008) was independently associated with in-hospital death. Echocardiography was not pursued in 45% of patients. Of surviving patients, 40 (74.1%) required skilled care after discharge; eight (20%) required rehospitalization. CONCLUSION: SAB was associated with high mortality rates in patients aged 80 and older. The observed association between SAB and SSI may direct preventive strategies such as perioperative decolonization or antimicrobial prophylaxis. Interventions to optimize clinical care practices in elderly patients with SAB are essential given the associated morbidity and mortality.