SARS-CoV-2 in immunocompromised individuals.

Immunocompromised individuals and particularly those with hematologic malignancies are at increased risk for SARS-CoV-2-associated morbidity and mortality due to immunologic deficits that limit prevention, treatment, and clearance of the virus. Understanding the natural history of viral infections in people with impaired immunity due to underlying conditions, immunosuppressive therapy, or a combination thereof has emerged as a critical area of investigation during the COVID-19 pandemic. Studies focused on these individuals have provided key insights into aspects of innate and adaptive immunity underlying both the antiviral immune response and excess inflammation in the setting of COVID-19. This review presents what is known about distinct states of immunologic vulnerability to SARS-CoV-2 and how this information can be harnessed to improve prevention and treatment strategies for immunologically high-risk populations.

Predictors of SARS-CoV-2 Omicron breakthrough infection after receipt of AZD7442 (tixagevimab-cilgavimab) for pre-exposure prophylaxis among hematologic malignancy patients.

AZD7442 (tixagevimab-cilgavimab) is a combination of two human monoclonal antibodies for pre-exposure prophylaxis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among high-risk patients who do not mount a reliable vaccine response. Foremost among these are hematologic malignancy patients with limited clinical trial or realworld experience to assess the effectiveness of this combination treatment since the emergence of Omicron and its subvariants. We performed a retrospective study of 892 high-risk hematologic malignancy patients who received AZD7442 at Memorial Sloan Kettering Cancer Center in New York City from January 1, 2022 to July 31, 2022. We evaluated demographic, clinical, and laboratory characteristics and performed regression analyses to evaluate risk factors for breakthrough infection. We also evaluated the impact of updated AZD7442 dosing regimens on the risk of breakthrough infection. Among 892 patients, 98 (10.9%) had a breakthrough infection during the study period. A majority received early outpatient treatment (82%) and eventually eight (8.2%) required hospitalization for management of Coronavirus Disease 2019 (COVID-19), with a single instance of severe COVID-19 and death. Patients who received a repeat dose or a higher firsttime dose of AZD7442 had a lower incidence of breakthrough infection. Univariate analyses did not reveal any significant predictors of breakthrough infection. While AZD7442 is effective at reducing SARS-CoV-2 breakthrough infection in patients with hematologic malignancies, no risk factors reliably predicted risk of infection. Patients who received updated dosing regimens as per Food and Drug Administration guidelines had better protection against breakthrough infection.

Long and persistent COVID-19 in patients with hematologic malignancies: from bench to bedside.

PURPOSE OF REVIEW: Cancer patients, especially those with hematologic malignancies, are at increased risk for coronavirus disease 2019 (COVID-19)-related complications and mortality. We describe the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 infection in patients with hematologic malignancies. RECENT FINDINGS: The syndrome of persistent COVID-19 in patients with hematologic malignancies manifests as a chronic protracted illness marked by waxing and waning or progressive respiratory symptoms and prolonged viral shedding. Immunosuppressed patients with lymphoid malignancies may serve as partially immune reservoirs for the generation of immune-evasive viral escape mutants. SUMMARY: Persistent COVID-19 infection is a unique concern in patients with hematologic malignancies. While vaccination against severe acute respiratory syndrome coronavirus 2 has reduced the overall burden of COVID-19 in patients with hematologic cancers, whether vaccination or other novel treatments for COVID-19 prevent or alleviate this syndrome remains to be determined.

Carbapenemase-producing Enterobacterales causing secondary infections during the COVID-19 crisis at a New York City hospital.

BACKGROUND: Patients with COVID-19 may be at increased risk for secondary bacterial infections with MDR pathogens, including carbapenemase-producing Enterobacterales (CPE). OBJECTIVES: We sought to rapidly investigate the clinical characteristics, population structure and mechanisms of resistance of CPE causing secondary infections in patients with COVID-19. METHODS: We retrospectively identified CPE clinical isolates collected from patients testing positive for SARS-CoV-2 between March and April 2020 at our medical centre in New York City. Available isolates underwent nanopore sequencing for rapid genotyping, antibiotic resistance gene detection and phylogenetic analysis. RESULTS: We identified 31 CPE isolates from 13 patients, including 27 Klebsiella pneumoniae and 4 Enterobacter cloacae complex isolates. Most patients (11/13) had a positive respiratory culture and 7/13 developed bacteraemia; treatment failure was common. Twenty isolates were available for WGS. Most K. pneumoniae (16/17) belonged to ST258 and encoded KPC (15 KPC-2; 1 KPC-3); one ST70 isolate encoded KPC-2. E. cloacae isolates belonged to ST270 and encoded NDM-1. Nanopore sequencing enabled identification of at least four distinct ST258 lineages in COVID-19 patients, which were validated by Illumina sequencing data. CONCLUSIONS: While CPE prevalence has declined substantially in New York City in recent years, increased detection in patients with COVID-19 may signal a re-emergence of these highly resistant pathogens in the wake of the global pandemic. Increased surveillance and antimicrobial stewardship efforts, as well as identification of optimal treatment approaches for CPE, will be needed to mitigate their future impact.

The solid organ transplant recipient with SARS-CoV-2 infection.

PURPOSE OF REVIEW: The COVID-19 pandemic is a major challenge to global health, particularly among vulnerable populations. Here, we describe the emerging epidemiology and relevant data on treatment options for COVID-19. We discuss the implications of current knowledge for solid organ transplant (SOT) recipients. RECENT FINDINGS: Risk factors and outcomes of COVID-19 among SOT recipients remain uncertain, but recent data suggest similar outcomes to the general population. Case reports of donor-derived SARS-CoV-2 infection are emerging. Few studies on treatment of COVID-19 among SOT recipients are available, and therefore, general recommendations are similar to the general population. Vaccine efficacy in the SOT population is uncertain. SUMMARY: COVID-19 remains a significant threat to SOT recipients and studies on treatment and prevention specific to this population are urgently needed. Although vaccines represent the greatest hope to control this pandemic, their efficacy in this immunocompromised population is uncertain.

Teaching Everyone Everywhere All at Once: Leveraging Social Media to Implement a Multisite Fungal Diagnostics Curriculum.

Background: Environmental fungi are threats to personal and public health. Fungal in vitro diagnostics help diagnose invasive fungal infections (IFIs), but clinicians remain underinformed about their use and interpretation. Given the increasing use of social media to share infectious diseases-related content, we designed and implemented a multisite Twitter-based curriculum focused on IFIs and related diagnostics. Methods: Questions were posted through a dedicated Twitter account twice weekly over 8 weeks. We surveyed clinicians at 3 US academic centers before and after completion of the curriculum and interviewed a subset of participants. We undertook quantitative and qualitative evaluations and reviewed Twitter analytics. Results: We surveyed 450 participants. One hundred twenty-one participants (27%) completed the knowledge assessment precurriculum, 68 (15%) postcurriculum, and 53 (12%) pre- and postcurriculum. We found a significant increase (72% vs 80%, P = .005) in the percentage of correct answers in the pre- versus postcurriculum knowledge assessments. Perceived benefits included a well-executed curriculum that facilitated engagement with appropriately detailed tweetorials from a dedicated Twitter account. Perceived barriers included lack of awareness of tweetorial posts and timing, competing priorities, and the coronavirus disease 2019 pandemic. The Twitter account accrued 1400 followers from 65 countries during the 8-week period. Tweets with multiple-choice questions had a median of 14 904 impressions (interquartile range [IQR], 12 818-16 963), 798 engagements (IQR, 626-1041), and an engagement rate of 6.1% (IQR, 4.2%-6.6%). Conclusions: Educators can leverage social media to share content with a large audience and improve knowledge while being mindful of the barriers associated with implementing a curriculum on social media.

Comparison of coronavirus disease 2019 (COVID-19) symptoms at diagnosis among healthcare personnel before and after the emergence of the omicron variant.

We used a self-reporting system to compare symptom frequency of hospital personnel with coronavirus disease 2019 before and after the emergence of the Omicron variant. Omicron was more likely to result in asymptomatic carriage (7% vs 12%; P = .009), and fewer symptoms were observed in those with booster vaccination.

Antivirals for COVID-19 in Solid Organ Transplant Recipients.

PURPOSE OF REVIEW: To evaluate the critical studies published so far on the most promising antiviral therapies for COVID-19, with particular emphasis on any solid organ transplant-specific information. RECENT FINDINGS: Although the literature is increasing exponentially, most clinical trials have been preliminary, thus lacking robust evidence to support many of the drugs discussed here. The main exception is remdesivir, for which several trials have been published supporting its use for patients with severe COVID-19. No solid organ transplant-specific data on remdesivir or other antiviral therapies have been published so far. SUMMARY: While further studies are urgently needed, in particular those specific to solid organ transplant recipients, the evidence so far only supports the use of remdesivir for patients with severe COVID-19.

SARS-CoV-2 neutralizing antibody responses are more robust in patients with severe disease.

We studied plasma antibody responses of 35 patients about 1 month after SARS-CoV-2 infection. Titers of antibodies binding to the viral nucleocapsid and spike proteins were significantly higher in patients with severe disease. Likewise, mean antibody neutralization titers against SARS-CoV-2 pseudovirus and live virus were higher in the sicker patients, by ∼5-fold and ∼7-fold, respectively. These findings have important implications for those pursuing plasma therapy, isolation of neutralizing monoclonal antibodies, and determinants of immunity.