Outcomes of pregnant women exposed to Sotrovimab for the treatment of COVID-19 in the BA.1 Omicron predominant era (PRESTO).

BACKGROUND: Sotrovimab, a monoclonal antibody with efficacy against SARS-CoV-2 including certain Omicron variants, has been used in treatment of mild-moderate COVID-19. Limited data exists regarding its use in pregnant women. METHODS: Electronic medical record review of pregnant COVID-19 patients treated with sotrovimab from 12/30/21 - 1/31/22 (Yale New Haven Health Hospital System [YNHHS]) was performed. Included were pregnant individuals ≥ 12 years, weighing ≥ 40 kg, with positive SARS-CoV-2 test (within 10 days). Those receiving care outside YNHHS or receiving other SARS-CoV-2 treatment were excluded. We assessed demographics, medical history, and Monoclonal Antibody Screening Score (MASS). The primary composite clinical outcome assessed included emergency department (ED) visit < 24 h, hospitalization, intensive care unit (ICU) admission, and/or death within 29 days of sotrovimab. Secondarily, adverse feto-maternal outcomes and events for neonates were assessed at birth or through the end of the study period, which was 8/15/22. RESULTS: Among 22 subjects, median age was 32 years and body mass index was 27 kg/m2. 63% were Caucasian, 9% Hispanic, 14% African-American, and 9% Asian. 9% had diabetes and sickle cell disease. 5% had well-controlled HIV. 18%, 46%, and 36% received sotrovimab in trimester 1, 2, and 3, respectively. No infusion/allergic reactions occurred. MASS values were < 4. Only 12/22 (55%) received complete primary vaccination (46% mRNA-1273; 46% BNT162b2; 8% JNJ-78,436,735); none received a booster. CONCLUSIONS: Pregnant COVID-19 patients receiving sotrovimab at our center tolerated it well with good clinical outcomes. Pregnancy and neonatal complications did not appear sotrovimab-related. Though a limited sample, our data helps elucidate the safety and tolerability of sotrovimab in pregnant women.

Immunomodulatory Agents for Coronavirus Disease-2019 Pneumonia.

Morbidity and mortality from COVID-19 is due to severe inflammation and end-organ damage caused by a hyperinflammatory response. Multiple immunomodulatory agents to attenuate this response have been studied. Corticosteroids, specifically dexamethasone, have been shown to reduce mortality in hospitalized patients who require supplemental oxygen. Interleukin-6 antagonist, tocilizimab, and Janus kinase inhibitors have also been shown to reduce mortality. However, patients who have severe pulmonary end-organ damage requiring mechanical ventilation or extracorporeal membrane oxygenation appear not to benefit from immunomodulatory therapies. This highlights the importance of appropriate timing to initiate immunomodulatory therapies in the management of severe COVID-19 disease.

An outbreak of SARS-CoV-2 on a transplant unit in the early vaccination era.

BACKGROUND: Solid organ transplant recipients are at increased risk of COVID-19-associated morbidity and mortality. AIMS: We describe a nosocomial outbreak investigation on an immunocompromised inpatient unit. METHODS: Patients positive for SARS-CoV-2 were identified. An epidemiologic investigation was assisted with whole genome sequencing of positive samples. RESULTS: Two patients were identified as potential index cases; one presented with diarrhea and was initially not isolated, and the other developed hypoxemia on hospital day 18 before testing positive. Following identification of a SARS-CoV-2 cluster, the unit was closed and all patients and staff received surveillance testing revealing eight additional positive patients and staff members. Whole genome sequencing confirmed an outbreak. Enhanced infection prevention practices mitigated further spread. Asymptomatic patients with COVID-19 were successfully treated with bamlanivimab. DISCUSSION: Preventing SARS-CoV-2 outbreaks in transplant units poses unique challenges as patients may have atypical presentations of COVID-19. Immunocompromised patients who test positive for SARS-CoV-2 while asymptomatic may benefit from monoclonal antibody therapy to prevent disease progression. All hospital staff members working with immunocompromised patients should be promptly encouraged to follow infection prevention behaviors and receive SARS-CoV-2 vaccination. CONCLUSION: SARS-CoV-2 outbreaks on immunocompromised units can be mitigated through prompt identification of cases and robust infection prevention practices.

Renal and Hepatic Toxicity Analysis of Remdesivir Formulations: Does What Is on the Inside Really Count?

It has been postulated that the injectable solution formulation of remdesivir could be more nephrotoxic than the lyophilized powder since it contains twice as much sulfobutylether-ß-cyclodextrin (SBECD). Therefore, we evaluated 1,000 hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who received remdesivir lyophilized powder or solution. A logistic regression model accounting for baseline confounders identified that neither the use of the injectable solution (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.49 to 2.29; P = 0.901) nor a creatinine clearance of <30 ml/min at the time of remdesivir initiation (OR, 1.39; 95% CI, 0.51 to 3.5; P = 0.499) was significantly associated with acute kidney injury. Regarding hepatoxicity, there was no significant difference in early discontinuation of remdesivir due to abnormal liver function tests between patients who received the lyophilized powder versus those who received solution (0.9% versus 2.3%, P = 0.09).

Pharmacists leadership in a medication shortage response: Illustrative examples from a health system response to the COVID-19 crisis.

As medication experts, clinical pharmacists play an active and dynamic role in a medication shortage response. Supplementing existing guidelines with an actionable framework of discrete activities to support effective medication shortage responses can expand the scope of pharmacy practice and improve patient care. Dissemination of best practices and illustrative, networked examples from health systems can support the adoption of innovative solutions. In this descriptive report, we document the translation of published shortage mitigation guidelines into system success through broad pharmacist engagement and the adaption and implementation of targeted strategies. The profound, wide-reaching medication shortages that accompanied the coronavirus disease 2019 (COVID-19) pandemic are used to highlight coordinated but distinct practices and how they have been combined to expand the influence of the pharmacy enterprise.

Cytokine Profiles Before and After Immune Modulation in Hospitalized Patients with COVID-19.

We describe the cytokine profiles of a large cohort of hospitalized patients with moderate to critical COVID-19, focusing on IL-6, sIL2R, and IL-10 levels before and after receiving immune modulating therapies, namely, tocilizumab and glucocorticoids. We also discuss the possible roles of sIL2R and IL-10 as markers of ongoing immune dysregulation after IL-6 inhibition. We performed a retrospective chart review of adult patients admitted to a tertiary care center with moderate to critical SARS-CoV-2 infection. Disease severity was based on maximum oxygen requirement during hospital stay to maintain SpO2 > 93% (moderate, 0-3 L NC; severe, 4-6 L NC or non-rebreather; critical, HFNC, NIPPV, or MV). All patients were treated using the institution's treatment algorithm, which included consideration of tocilizumab for severe and critical disease. The most common cytokine elevations among all patients included IL-6, sIL2R, IFN-γ, and IL-10; patients who received tocilizumab had higher incidence of IL-6 and sIL2R elevations. Pre-tocilizumab IL-6 levels increased with disease severity (p = .0151). Both IL-6 and sIL2R levels significantly increased after administration of tocilizumab in all severity groups; IL-10 levels decreased in severe (p = .0203), but not moderate or critical, patients after they received tocilizumab. Cluster analysis revealed association between higher admission IL-6, sIL2R, and CRP levels and disease severity. Mean IL-6, sIL2R, and D-dimer were associated with mortality, and tocilizumab-treated patients with elevated IL-6, IL-10, and D-dimer were more likely to also receive glucocorticoids. Accessible clinical cytokine panels may be useful for monitoring response to treatment in COVID-19. The increase in sIL2R post-tocilizumab, despite administration of glucocorticoids, may indicate the need for combination therapy in order to modulate more than one hyperinflammatory pathway in COVID-19. We also discuss the role of cytokines as potential biomarkers for use of adjunct glucocorticoid therapy.

A Valid Warning or Clinical Lore: an Evaluation of Safety Outcomes of Remdesivir in Patients with Impaired Renal Function from a Multicenter Matched Cohort.

Per prescribing guidance, remdesivir is not recommended for SARS-CoV-2 in patients with renal disease given the absence of safety data in this patient population. This study was a multicenter, retrospective chart review of hospitalized patients with SARS-CoV-2 who received remdesivir. Safety outcomes were compared between patients with an estimated creatinine clearance (eCrCl) of <30 ml/min and an eCrCl of ≥30 ml/min. The primary endpoint was acute kidney injury (AKI) at the end of treatment (EOT). Of 359 patients who received remdesivir, 347 met inclusion criteria. Patients with an eCrCl of <30 ml/min were older {median, 80 years (interquartile range [IQR], 63.8 to 89) versus 62 (IQR, 54 to 74); P < 0.001}, were more likely to be on vasopressors on the day of remdesivir administration (30% versus 12.7%; P = 0.003), and were more likely to be mechanically ventilated during remdesivir therapy (27.5% versus 12.4%; P = 0.01) than those with an eCrCl of ≥30 ml/min. Despite these confounders, there was no significant difference in the frequency of EOT AKI (5% versus 2.3%; P = 0.283) or early discontinuation due to abnormal liver function tests (LFTs) (0% versus 3.9%; P = 0.374). Of the 5% of patients who developed EOT AKI on remdesivir with an eCrCl <30 ml/min, no cases were attributable to remdesivir administration per the treating physician. Comparable safety outcomes were observed when 1:1 nearest neighbor matching was applied to account for baseline confounders. In conclusion, remdesivir administration was not significantly associated with increased EOT AKI in patients with an eCrCl of <30 ml/min compared to patients with an eCrCl of ≥30 ml/min.

Tocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019: Survival and Clinical Outcomes.

BACKGROUND: Tocilizumab, an IL-6 receptor antagonist, can be used to treat cytokine release syndrome (CRS), with observed improvements in a coronavirus disease 2019 (COVID-19) case series. RESEARCH QUESTION: The goal of this study was to determine if tocilizumab benefits patients hospitalized with COVID-19. STUDY DESIGN AND METHODS: This observational study of consecutive COVID-19 patients hospitalized between March 10, 2020, and March 31, 2020, and followed up through April 21, 2020, was conducted by chart review. Patients were treated with tocilizumab using an algorithm that targeted CRS. Survival and mechanical ventilation (MV) outcomes were reported for 14 days and stratified according to disease severity designated at admission (severe, ≥ 3 L supplemental oxygen to maintain oxygen saturation > 93%). For tocilizumab-treated patients, pre/post analyses of clinical response, biomarkers, and safety outcomes were assessed. Post hoc survival analyses were conducted for race/ethnicity. RESULTS: Among the 239 patients, median age was 64 years; 36% and 19% were black and Hispanic, respectively. Hospital census increased exponentially, yet MV census did not. Severe disease was associated with lower survival (78% vs 93%; P < .001), greater proportion requiring MV (44% vs 5%; P < .001), and longer median MV days (5.5 vs 1.0; P = .003). Tocilizumab-treated patients (n = 153 [64%]) comprised 90% of those with severe disease; 44% of patients with nonsevere disease received tocilizumab for evolving CRS. Tocilizumab-treated patients with severe disease had higher admission levels of high-sensitivity C-reactive protein (120 vs 71 mg/L; P < .001) and received tocilizumab sooner (2 vs 3 days; P < .001), but their survival was similar to that of patients with nonsevere disease (83% vs 91%; P = .11). For tocilizumab-treated patients requiring MV, survival was 75% (95% CI, 64-89). Following tocilizumab treatment, few adverse events occurred, and oxygenation and inflammatory biomarkers (eg, high-sensitivity C-reactive protein, IL-6) improved; however, D-dimer and soluble IL-2 receptor (also termed CD25) levels increased significantly. Survival in black and Hispanic patients, after controlling for age, was significantly higher than in white patients (log-rank test, P = .002). INTERPRETATION: A treatment algorithm that included tocilizumab to target CRS may influence MV and survival outcomes. In tocilizumab-treated patients, oxygenation and inflammatory biomarkers improved, with higher than expected survival. Randomized trials must confirm these findings.

Case Report: Disseminated Strongyloidiasis in a Patient with COVID-19.

The SARS-CoV-2 virus has emerged and rapidly evolved into a current global pandemic. Although bacterial and fungal coinfections have been associated with COVID-19, little is known about parasitic infection. We report a case of a COVID-19 patient who developed disseminated strongyloidiasis following treatment with high-dose corticosteroids and tocilizumab. Screening for Strongyloides infection should be pursued in individuals with COVID-19 who originate from endemic regions before initiating immunosuppressive therapy.

Repurposing antimicrobial stewardship tools in the electronic medical record for the management of COVID-19 patients.

During the COVID-19 pandemic, the antimicrobial stewardship module in our electronic medical record was reconfigured for the management of COVID-19 patients. This change allowed our subspecialist providers to review charts quickly to optimize potential therapy and management during the patient surge.