Respiratory Viral Infections in Recipients of Cellular Therapies: A Review of Incidence, Outcomes, Treatment, and Prevention.

Respiratory viral infections (RVIs) are of major clinical importance in immunocompromised patients and represent a substantial cause of morbidity and mortality in patients with hematologic malignancies and those who have undergone hematopoietic cell transplantation. Similarly, patients receiving immunotherapy with CD19-targeted chimeric antigen receptor-modified T cells, natural killer cells, and genetically modified T-cell receptors are susceptible to RVIs and progression to lower respiratory tract infections. In adoptive cellular therapy recipients, this enhanced susceptibility to RVIs results from previous chemotherapy regimens such as lymphocyte-depleting chemotherapy conditioning regimens, underlying B-cell malignancies, immune-related toxicities, and secondary prolonged, profound hypogammaglobulinemia. The aggregated risk factors for RVIs have both immediate and long-term consequences. This review summarizes the current literature on the pathogenesis, epidemiology, and clinical aspects of RVIs that are unique to recipients of adoptive cellular therapy, the preventive and therapeutic options for common RVIs, and appropriate infection control and preventive strategies.

Nosocomial COVID-19 at a comprehensive cancer center during the first year of the pandemic: Lessons learned.

BACKGROUND: The spread of coronavirus disease 2019 (COVID-19) in health care settings endangers patients with cancer. As knowledge of the transmission of COVID-19 emerged, strategies for preventing nosocomial COVID-19 were updated. We describe our early experience with nosocomial respiratory viral infections (RVIs) at a cancer center in the first year of the pandemic (March 2020-March 2021). METHODS: Nosocomial RVIs were identified through our infection control prospective surveillance program, which conducted epidemiologic investigations of all microbiologically documented RVIs. Data was presented as frequencies and percentages or medians and ranges. RESULTS: A total of 35 of 3944 (0.9%) documented RVIs were determined to have been nosocomial acquired. Majority of RVIs were due to SARS CoV-2 (13/35; 37%) or by rhinovirus/enterovirus (12/35; 34%). A cluster investigation of the first 3 patients with nosocomial COVID-19 determined that transmission most likely occurred from employees to patients. Five patients (38%) required mechanical ventilation and 4 (31%) died during the same hospital encounter. CONCLUSIONS: Our investigation of the cluster led to enhancement of our infection control measures. The implications of COVID-19 vaccination on infection control policies is still unclear and further studies are needed to delineate its impact on the transmission of COVID-19 in a hospital setting.

COVID-19 Vaccination in Patients With Cancer and Recipients of Cellular Therapy.

COVID-19 continues to disproportionately affect patients with cancer because of their underlying immunocompromised state. Strategies to mitigate the impact of COVID-19 on patients with cancer include vaccination, which has demonstrated some level of protection, at least against serious complications such as respiratory failure and death, with limited safety concerns. In this narrative review, we discuss the current COVID-19 vaccines that are available in the United States, the published data regarding vaccine efficacy and safety in patients with cancer, current vaccination guidelines, and future directions.

Frequently Asked Questions on Coronavirus Disease 2019 Vaccination for Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Recipients From the American Society for Transplantation and Cellular Therapy and the American Society of Hematology.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disproportionately affects immunocompromised and elderly patients. Not only are hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR) T-cell recipients at greater risk for severe COVID-19 and COVID-19-related complications, but they also may experience suboptimal immune responses to currently available COVID-19 vaccines. Optimizing the use, timing, and number of doses of the COVID-19 vaccines in these patients may provide better protection against SARS-CoV-2 infection and better outcomes after infection. To this end, current guidelines for COVID-19 vaccination in HCT and CAR T-cell recipients from the American Society of Transplantation and Cellular Therapy Transplant Infectious Disease Special Interest Group and the American Society of Hematology are provided in a frequently asked questions format.

International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship.

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03). Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality. Funding: National Cancer Institute and National Institutes of Health.

Revised Guidelines for Coronavirus Disease 19 Management in Hematopoietic Cell Transplantation and Cellular Therapy Recipients (August 2022).

This document is intended as a guide for diagnosis and management of Coronavirus Disease 2019 (COVID-19), caused by the virus SARS-CoV-2, in adult and pediatric HCT and cellular therapy patients. This document was prepared using available data and with expert opinion provided by members of the (ASTCT) Infectious Diseases Special Interest Group (ID-SIG) and is an update of pervious publication. Since our original publication in 2020, the NIH and IDSA have published extensive guidelines for management of COVID-19 which are readily accessible ( NIH Guidelines , IDSA Guidelines ). This update focuses primarily on issues pertaining specifically to HCT/cellular therapy recipients. Information provided in this manuscript may change as new information becomes available.

How I treat and prevent COVID-19 in patients with hematologic malignancies and recipients of cellular therapies.

Patients with hematologic malignancies and recipients of hematopoietic cell transplantation (HCT) are more likely to experience severe coronavirus disease 2019 (COVID-19) and have a higher risk of morbidity and mortality after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compared with the general population, these patients have suboptimal humoral responses to COVID-19 vaccines and subsequently increased risk for breakthrough infections, underscoring the need for additional therapies, including pre- and postexposure prophylaxis, to attenuate clinical progression to severe COVID-19. Therapies for COVID-19 are mostly available for adults and in the inpatient and outpatient settings. Selection and administration of the best treatment options are based on host factors; virus factors, including circulating SARS-CoV-2 variants; and therapeutic considerations, including the clinical efficacy, availability, and practicality of treatment and its associated side effects, including drug-drug interactions. In this paper, we discuss how we approach managing COVID-19 in patients with hematologic malignancies and recipients of HCT and cell therapy.

Guidelines for COVID-19 Management in Hematopoietic Cell Transplantation and Cellular Therapy Recipients

There are currently limited data on the epidemiology, clinical manifestations, and optimal management of Coronavirus Disease 2019 (COVID-19) in hematopoietic cell transplantation and cellular therapy recipients. Given the experience with other respiratory viruses, we anticipate that patients may develop severe clinical disease and thus provide the following general principles for cancer centers across the nation. These guidelines were developed by members of the American Society for Transplantation and Cellular Therapy Infectious Diseases Special Interest Group. Specific practices may vary depending on local epidemiology and testing capacity, and the guidance provided in this document may change as new information becomes available.

Combination of baloxavir and oseltamivir for treatment of severe influenza infection in hematopoietic cell transplant recipients: a novel treatment strategy for a high-risk population.

Baloxavir, a cap-dependent endonuclease inhibitor, was recently approved for treatment of severe influenza infections. Combining baloxavir with oseltamivir has been proposed to increase the response rate. We report 2 hematopoietic cell transplant recipients with severe influenza infections who were treated with this combination and discuss possible reasons for their different responses.

How to interpret and use COVID-19 serology and immunology tests.

BACKGROUND: Although molecular tests are considered the reference standard for coronavirus disease 2019 (COVID-19) diagnostics, serological and immunological tests may be useful in specific settings. OBJECTIVES: This review summarizes the underlying principles and performance of COVID-19 serological and immunological testing. SOURCES: Selected peer-reviewed publications on COVID-19 related serology and immunology published between December 2019 and March 2021. CONTENT: Serological tests are highly specific but heterogeneous in their sensitivity for the diagnosis of COVID-19. For certain indications, including delayed disease presentations, serological tests can have added value. The presence of antibodies against SARS-CoV-2 may indicate a recent or past COVID-19 infection. Lateral flow immunoassay (LFIA) antibody tests have the advantages of being easy and fast to perform, but many have a low sensitivity in acute settings. Enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassays (CLIAs) have higher sensitivities. Besides humoral immunity, cellular immunity is also essential for successful host defences against viruses. Enzyme-linked immunospot (ELISpot) assays can be used to measure T-cell responses against SARS-CoV-2. The presence of cross-reactive SARS-CoV-2-specific T cells in never exposed patients suggests the possibility of cellular immunity induced by other circulating coronaviruses. T-cell responses against SARS-CoV-2 have also been detected in recovered COVID-19 patients with no detectable antibodies. IMPLICATIONS: Serological and immunological tests are primarily applied for population-based seroprevalence studies to evaluate the effectiveness of COVID-19 control measures and increase our understanding of the immunology behind COVID-19. Combining molecular diagnostics with serological tests may optimize the detection of COVID-19. As not all infected patients will develop antibodies against SARS-CoV-2, assessment of cellular immunity may provide complementary information on whether a patient has been previously infected with COVID-19. More studies are needed to understand the correlations of these serological and immunological parameters with protective immunity, taking into account the different circulating virus variants.

Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study.

BACKGROUND: Haematopoietic stem-cell transplantation (HSCT) recipients are considered at high risk of poor outcomes after COVID-19 on the basis of their immunosuppressed status, but data from large studies in HSCT recipients are lacking. This study describes the characteristics and outcomes of HSCT recipients after developing COVID-19. METHODS: In response to the pandemic, the Center for International Blood and Marrow Transplant Research (CIBMTR) implemented a special form for COVID-19-related data capture on March 27, 2020. All patients-irrespective of age, diagnosis, donor type, graft source, or conditioning regimens-were included in the analysis with data cutoff of Aug 12, 2020. The main outcome was overall survival 30 days after a COVID-19 diagnosis. Overall survival probabilities were calculated using Kaplan-Meier estimator. Factors associated with mortality after COVID-19 diagnosis were examined using Cox proportional hazard models. FINDINGS: 318 HSCT recipients diagnosed with COVID-19 were reported to the CIBMTR. The median time from HSCT to COVID-19 diagnosis was 17 months (IQR 8-46) for allogeneic HSCT recipients and 23 months (8-51) for autologous HSCT recipients. The median follow-up of survivors was 21 days (IQR 8-41) for allogeneic HSCT recipients and 25 days (12-35) for autologous HSCT recipients. 34 (18%) of 184 allogeneic HSCT recipients were receiving immunosuppression within 6 months of COVID-19 diagnosis. Disease severity was mild in 155 (49%) of 318 patients, while severe disease requiring mechanical ventilation occurred in 45 (14%) of 318 patients-ie, 28 (15%) of 184 allogeneic HSCT recipients and 17 (13%) of 134 autologous HSCT recipients. At 30 days after the diagnosis of COVID-19, overall survival was 68% (95% CI 58-77) for recipients of allogeneic HSCT and 67% (55-78) for recipients of autologous HSCT. Age 50 years or older (hazard ratio 2·53, 95% CI 1·16-5·52; p=0·020); male sex (3·53; 1·44-8·67; p=0·006), and development of COVID-19 within 12 months of transplantation (2·67, 1·33-5·36; p=0·005) were associated with a higher risk of mortality among allogeneic HSCT recipients, and a disease indication of lymphoma was associated with a higher risk of mortality compared with plasma cell disorder or myeloma (2·41, [1·08-5·38]; p=0·033) in autologous HSCT recipients. INTERPRETATION: Recipients of autologous and allogeneic HSCT who develop COVID-19 have poor overall survival. These data emphasise the need for stringent surveillance and aggressive treatment measures in HSCT recipients who develop COVID-19. FUNDING: American Society of Hematology; Leukemia and Lymphoma Society; National Cancer Institute; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; National Institutes of Health; National Cancer Institute; Health Resources and Services Administration; Office of Naval Research.

Immune reconstitution and severity of COVID-19 among hematopoietic cell transplant recipients.

Severe acute respiratory syndrome coronavirus 2 can lead to life-threatening coronavirus disease 2019 (COVID-19) infections in patients with hematologic malignancies, particularly among hematopoietic cell transplant (HCT) recipients. We describe two patients with COVID-19 during the pre-engraftment period after HCT and review previous reports of COVID-19 in HCT recipients. Because of significant mortality from COVID-19, primarily after allogeneic HCT, early, preemptive, and optimal directed therapy may improve outcomes and reduce the mortality rate but still needs to be established in clinical trials.

Deactivation of SARS-CoV-2 with pulsed-xenon ultraviolet light: Implications for environmental COVID-19 control.

OBJECTIVES: Prolonged survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on environmental surfaces and personal protective equipment may lead to these surfaces transmitting this pathogen to others. We sought to determine the effectiveness of a pulsed-xenon ultraviolet (PX-UV) disinfection system in reducing the load of SARS-CoV-2 on hard surfaces and N95 respirators. METHODS: Chamber slides and N95 respirator material were directly inoculated with SARS-CoV-2 and were exposed to different durations of PX-UV. RESULTS: For hard surfaces, disinfection for 1, 2, and 5 minutes resulted in 3.53 log10, >4.54 log10, and >4.12 log10 reductions in viral load, respectively. For N95 respirators, disinfection for 5 minutes resulted in >4.79 log10 reduction in viral load. PX-UV significantly reduced SARS-CoV-2 on hard surfaces and N95 respirators. CONCLUSION: With the potential to rapidly disinfectant environmental surfaces and N95 respirators, PX-UV devices are a promising technology to reduce environmental and personal protective equipment bioburden and to enhance both healthcare worker and patient safety by reducing the risk of exposure to SARS-CoV-2.