Real-world experience of tixagevimab-cilgavimab pre-exposure prophylaxis in orthotopic heart transplant recipients.

BACKGROUND: Pre-exposure prophylaxis with tixagevimab-cilgavimab (tix-cil) may be associated with cardiovascular adverse events. Also, in vitro studies have reported a reduced activity of tix-cil against emerging SARS-CoV-2 Omicron subvariants. Our study aimed to report the real-world outcomes of tix-cil prophylaxis in orthotopic heart transplant (OHT) recipients METHODS: We retrospectively studied all OHT recipients who received one dose of tix-cil (150-150 mg or 300-300 mg) at Mayo Clinic in Arizona, Florida, and Minnesota, between February 5, 2022 and September 8, 2022. We collected data on cardiovascular adverse events and breakthrough COVID-19 following tix-cil administration. RESULTS: One hundred sixty-three OHT recipients were included. The majority were male (65.6%), and the median age was 61 years (IQR 48, 69). During the median follow-up of 164 days (IQR 123, 190), one patient presented an episode of asymptomatic hypertensive urgency that was managed with outpatient antihypertensive treatment optimization. Twenty-four patients (14.7%) experienced breakthrough COVID-19 at the median of 63.5 days (IQR 28.3, 101.3) after tix-cil administration. The majority (70.8%) completed the primary vaccine series and received at least one booster dose (70.8%). Only one patient with breakthrough COVID-19 required hospitalization. All patients survived. CONCLUSIONS: In this cohort of OHT recipients, no patients developed severe cardiovascular events related to tix-cil. The high incidence of breakthrough COVID-19 could be due to the reduced activity of tix-cil against current circulating SARS-CoV-2 Omicron variants. These results emphasize the need for a multimodal prevention strategy against SARS-CoV-2 in these high-risk patients.

Genotypic and predicted phenotypic analysis of SARS-COV-2 Omicron subvariants in immunocompromised patients with COVID-19 following tixagevimab-cilgavimab prophylaxis.

BACKGROUND: Tixagevimab-cilgavimab is used for pre-exposure prophylaxis of COVID-19 in immunocompromised patients, though in vitro data has shown reduced neutralizing activity against SARS-CoV-2 Omicron subvariants. METHODS: We performed genomic sequencing of SARS-CoV-2 isolated from patients diagnosed with COVID-19 following tixagevimab-cilgavimab. Resistance-associated substitutions were used to generate a predicted phenotypic susceptibility analysis to tixagevimab-cilgavimab and bebtelovimab. Clinical data collected from these patients included SARS-CoV-2 immunization status, COVID-19-directed therapies, and outcomes. RESULTS: SARS-CoV-2 genome sequencing was performed in 25 patients. SARS-CoV-2 Omicron BA.2 was the most common identified subvariant. All patients had viral isolates with spike codon substitutions associated with reduced susceptibility to tixagevimab-cilgavimab; their predicted phenotypic analysis showed a >2-fold reduced susceptibility to tixagevimab-cilgavimab. Two patients had viral isolates with spike codon substitutions (K444N and G446D) associated with highly reduced susceptibility to bebtelovimab, although all the viral isolates had <2-fold reduced susceptibility based on predicted phenotypic analysis. Sixteen patients received rescue therapy with bebtelovimab, but one patient with BA.2 subvariant harboring K444N mutation died of COVID-19-related complications. Five patients received other COVID-19 therapies and survived. Four had mild or asymptomatic COVID-19 with an uncomplicated course despite not receiving any additional therapy. DISCUSSION: Multiple SARS-CoV-2 Omicron spike codon substitutions that correlated with reduced susceptibility to tixagevimab-cilgavimab were identified in patients with COVID-19 after receiving this monoclonal antibody. Most patients had an uncomplicated course. The identification of spike codon substitutions conferring resistance to bebtelovimab highlights the importance of performing genomic surveillance to identify new resistant SARS-CoV-2 variants.

Outcomes of bebtelovimab and sotrovimab treatment of solid organ transplant recipients with mild-to-moderate coronavirus disease 2019 during the Omicron epoch.

BACKGROUND: Solid organ transplant recipients (SOTRs) are at high-risk for severe infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Anti-spike monoclonal antibodies are currently utilized under emergency use authorization to prevent hospitalization in high-risk individuals with coronavirus disease 2019 (COVID-19), including SOTRs. However, clinical data for bebtelovimab, the sole currently available anti-spike monoclonal antibody for COVID-19, is limited. METHODS: We conducted a retrospective cohort study of adult SOTRs diagnosed with mild-to-moderate COVID-19 from January 2022 through May 2022 who received either bebtelovimab or sotrovimab. The primary outcome was COVID-19-related hospitalization within 30 days of COVID-19 diagnosis. Data were analyzed with Fisher's exact test. RESULTS: Among 361 SOTRs, 92 (25.5%) received bebtelovimab and 269 (74.5%) received sotrovimab. The most common organ transplant was a kidney (42.4%). SOTRs who received bebtelovimab had a higher proportion who had received a booster SARS-CoV-2 vaccine dose and had received their last vaccination dose more recently. Eleven (3.0%) SOTRs were hospitalized, and rates of hospitalization were similar between monoclonal antibody groups (3.3% versus 3.0%; p > .99). Three patients required admission to an intensive care unit, all of who received sotrovimab. Four (1.1%) patients died within 30 days of COVID-19 diagnosis, two from each group. CONCLUSIONS: SOTRs with mild-to-moderate COVID-19 who received bebtelovimab had similar rates of COVID-19-related hospitalization as those who received sotrovimab. While differences in vaccination rates and viral subvariants could act as confounders, bebtelovimab appears to be of similar effectiveness as sotrovimab.

Characterization of Early-Onset Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients Who Received Tixagevimab-Cilgavimab Prophylaxis.

Tixagevimab-cilgavimab is authorized for preexposure prophylaxis against coronavirus disease 2019 (COVID-19) in immunocompromised hosts. Herein, we report the clinical characteristics of 8 patients who developed COVID-19 soon after receiving tixagevimab-cilgavimab. This study emphasizes the need to maintain additional measures to prevent COVID-19 during periods of high severe acute respiratory syndrome coronavirus 2 transmission.

Characterization of early-onset SARS-CoV-2 infection in immunocompromised patients who received tixagevimab-cilgavimab prophylaxis

Tixagevimab-cilgavimab is authorized for pre-exposure prophylaxis against coronavirus disease 2019 (COVID-19) in immunocompromised hosts. Herein, we report the clinical characteristics of eight patients who developed COVID-19 soon after receiving tixagevimab-cilgavimab. This study emphasizes the need to maintain additional measures to prevent COVID-19 during periods of high SARS-CoV-2 transmission.

The COVID-19 pandemic and sleep medicine: a look back and a look ahead.

The coronavirus disease 2019 (COVID-19) pandemic is a reminder that global infectious disease outbreaks are not new and they have the potential to cause catastrophic morbidity and mortality, disrupt health care delivery, demand critical decision making in the absence of scientific certainty, interrupt trainee education, inflict economic damage, and cause a spike in demand for health care services that exceeds societal capacity. In this article, we look back at how the sleep medicine community adapted to challenges imposed by the COVID-19 pandemic. To mitigate viral transmission perhaps the single most effective and efficient adaptation was the rapid adoption of telemedicine. Many additional strategies were taken up virtually overnight, including more home sleep apnea testing, reconsideration of potential risks of positive airway pressure therapy, a reduction or cessation of laboratory services, and deployment of workers to provide frontline care to infected patients. During some periods, critical shortages in essential personal protective equipment, respiratory assist devices, and even oxygen added to logistical challenges, which were exacerbated by persistent financial threats and insufficient staffing. Through ongoing innovation, resiliency, and adaptability, breakthroughs were made in assigning staff responsibilities and designing workflows, using clinical spaces, obtaining legislative support, and achieving professional society collaboration and guidance so that the missions of providing health care, teaching, and academic pursuits could continue. Here we summarize what we have learned through these critical months and highlight key adaptations that deserve to be embraced as we move forward. CITATION: Khosla S, Beam E, Berneking M, et al. The COVID-19 pandemic and sleep medicine: a look back and a look ahead. J Clin Sleep Med. 2022;18(8):2045-2050.

Monoclonal Antibody Therapy for COVID-19 in Solid Organ Transplant Recipients.

BACKGROUND: Bamlanivimab and casirivimab-imdevimab are authorized for emergency use treatment of mild to moderate coronavirus disease 2019 (COVID-19) in patients at high risk for developing severe disease or hospitalization. Their safety and efficacy have not been specifically evaluated in solid organ transplant recipients. METHODS: We retrospectively reviewed solid organ transplant recipients who received monoclonal antibody infusion for COVID-19 at Mayo Clinic sites through January 23, 2021. Outcomes included emergency department visit, hospitalization, mortality, and allograft rejection. RESULTS: Seventy-three patients were treated, most commonly with bamlanivimab (75.3%). The median age was 59 years, 63% were male, and the median Charlson comorbidity index was 5. Transplant type included 41 kidney (56.2%), 13 liver (17.8%), 11 heart (15.1%), 4 kidney-pancreas (5.5%), 2 lung (2.7%), 1 heart-liver, and 1 pancreas. Eleven (15.1%) patients had an emergency department visit within 28 days of infusion, including 9 (12.3%) who were hospitalized for a median of 4 days. One patient required intensive care unit admission for a nonrespiratory complication. No patients required mechanical ventilation, died, or experienced rejection. Ten adverse events occurred, with 1 seeking medical evaluation. Hypertension was associated with hospital admission (P < .05), while other baseline characteristics were similar. The median time from symptom onset to antibody administration was 4 days in nonhospitalized patients compared with 6 days among hospitalized patients (P < .05). CONCLUSIONS: Monoclonal antibody treatment has favorable outcomes with minimal adverse effects in solid organ transplant recipients with mild to moderate COVID-19. Earlier administration of monoclonal antibody therapy appears to be more efficacious.

Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient.

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.