Inactivated Vaccine Dosage and Serum IgG Levels Correlate with Persistent COVID-19 Infection in Hematologic Malignancy Patients During the Omicron Surge in China (preprint)

In hematologic malignancies (HM) patients, COVID-19 infections carry a significant risk of mortality due to disease status, treatment, and other factors.The risk factors of the severity and persistence of COVID-19 infections remains unclear. A study observed adults with HM diagnosed with COVID-19 from November 2022 to February 2023. Patient blood samples yielded biochemical data, with COVID-19 confirmed via RNA or antigen testing. In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Using advanced multivariate logistic regression, high C-reactive protein levels (≥100mg/L) significantly increased the risk of severe/critical conditions in HM patients with COVID-19 (OR: 3.415, 95% CI: 1.294-9.012; p=0.013). Patients enduring Omicron infection beyond 30 days were deemed persistent, in contrast to those achieving infection control within this duration. The research indicated that taking ＜2 vaccine doses (OR: 0.202, 95% CI: 0.048-0.857; p=0.030), having low IgG levels (＜1000 mg/dl) (OR: 0.129, 95% CI: 0.027-0.607; p=0.010), and increased interleukin-6 levels (≥12pg/ml) (OR: 5.098, 95% CI: 1.118-23.243; p=0.035) were key indicators of ongoing infection. A significant difference in survival rates was observed between patients with persistent and non-persistent infections, with the latter showing better survival outcomes (P<0.001). In conclusion, increased C-reactive protein levels had a higher likelihood of severe health outcomes for HM patients with COVID-19 infection. Persistent infections tended to be more prevalent in those with lower vaccine dosages, diminished IgG levels, and escalated interleukin-6 levels.

Analysis of coinfections in patients with hematologic malignancies and COVID-19 by next-generation sequencing of bronchoalveolar lavage fluid (preprint)

Background Coinfections in patients with coronavirus disease 2019 (COVID-19) affect patient prognosis. Patients with hematologic malignancies (HMs) are usually immunosuppressed and may be at high risk of coinfection, but few related data have been reported. Here, we conducted a retrospective study to explore coinfections in patients with HMs and COVID-19 by next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF).Methods The data of hospitalized patients with pneumonia who underwent NGS analysis of BALF were reviewed. COVID-19 patients with HMs were enrolled in the HM group, and those without HMs were enrolled in the non-HM group. The coinfections of the two groups identified by NGS were analyzed.Results Fifteen patients were enrolled in the HM group, and 14 patients were enrolled in the non-HM group. The coinfection rates in the HM group and non-HM group were 80.0% and 85.7%, respectively. The percentage of coinfected bacteria in the HM group was significantly lower than that in the non-HM group (20.0% vs 71.4%, p = 0.005). The coinfection rates of fungi and viruses were 60.0% and 35.7%, respectively, in the HM group and 35.7% and 78.6%, respectively, in the non-HM group, with no significant differences. The most common coexisting pathogen in patients with HMs was Pneumocystis jirovecii (33.3%), and the most common coexisting pathogen in patients without HMs was human gammaherpesvirus 4 (50%). Coinfection with herpesviruses occurred frequently in both groups.Conclusions Our study showed that hospitalized patients with COVID-19 had a high incidence of coinfection. Pneumocystis jiroveci and herpesvirus are commonly coinfected pathogens in patients with HMs. Bacterial coinfection is rare in patients with HMs but is more common in patients without HMs.

Evaluation of the patients with hematologic malignancies and coronavirus disease 2019 (COVID-19): A single center retrospective study (preprint)

Introduction: One of the most important risk factor for COVID-19 infection is malignancy especially hematologic ones. Focusing on the clinical, radiological and laboratory characteristics of COVID-19 infected cancer patients remain largely important. Materials and Methods: In this retrospective study, we analyzed the data of 194 patients with hematologic malignancy and COVID-19 pneumonia. We categorized patients based on the type of the hematologic malignancy and phase of the treatment. All associated and important laboratory data including complete blood count, pro-inflammatory markers, and computerized tomography scan findings were reported to assess the risk factors associated mortality. Results: From January 2020 to March 2021, a total of 194 COVID-19 infected patients with hematologic malignancies were included in different phase of treatments. Median age was 44 (15-81) years. 135 of the cases were male and 59 of the cases were female. Acute myeloid leukemia was the most frequent cancer type (43.8%). A total of 119 patients had severe COVID-19 and 61 patients were admitted to intensive care unit. A total of 92 deaths occurred among all cases for an overall case fatality rate of 47%. Male gender (P=0.03), pre-induction and induction phase of the treatment (P<0.001), Intensive care unit admission (P<0.001), low level of oxygen saturation at the onset of COVID-19 disease (P<0.001) and high level of fibrinogen (P=0.002) were associated with COVID-19 mortality among patients with hematologic malignancies. Conclusion: The results of this study showed male gender, pre-induction and induction phase of the treatment, Intensive care admission, low levels of oxygen saturation at the onset of COVID-19 disease, RH positivity and higher fibrinogen level were associated with the risk of death. Identification of factors potentially associated with mortality for cancer patients are important in assessment strategy in these high risk group.

Clinical Characteristics and Outcomes of Children and Adolescents with cancer infected with SARS-CoV2 at a Tertiary Care Medical Center in Jordan. (preprint)

Background: Our knowledge about SARS-CoV2 infection is still evolving, its effects and complications on children and adolescents with cancer need to be studied more. The aim of this study is to present our experience with SARS-CoV2 infection in this population and to highlight specific complications and outcomes. Methods: This is a retrospective and prospective observational study, involved 21 cancer patients below the age of 18 years in north Jordan. Data regarding age, sex, cancer type, phase of treatment, duration between infection and chemotherapy and others were collected and reviewed. Results: A total of 21 patients with malignancy were included. Mean age of 8.5 years. Two patients (9.5%) had died; 4.7% is COVID related mortality and 4.7% related to cancer progression. Four patients had disease progression following SARS-CoV2 infection. Six cases developed hematological malignancy weeks to months after SARS-CoV2 infection and one patient was diagnosed with malignancy concomitantly with COVID-19 infection. Out of 15 patients with pre-existing malignancy, 1 patient (7%) developed pulmonary embolism, 4 (27%) patients were diagnosed with pneumonia and one patient was diagnosed with pericarditis (7%), 2 (13%) patients were admitted to pediatric intensive care unit. Regarding oxygen requirements; a total of 3 (20%) patients required some form of Oxygen supplementation. Conclusion: Diagnosis of COVID19 should not distract physicians from investigating new malignancy or relapse as they may come together or may be the result of COVID-19 infection. More studies and investigations are needed to identify the contribution of corona virus in pathogenesis of cancer.

Comprehensive procedure for injecting Evusheld® for hematological diseases in a single institute (preprint)

Tixagevimab and cilgavimab (EVA, Evusheld®), monoclonal antibody combination treatments, consisted of two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). EVA showed prophylactic and therapeutic effects against coronavirus disease 2019. The Japanese Society of Hematology recommended EVA for such patients with active treatment, but each institution decided on comprehensive administration. We develop a systematic procedure for comprehensive EVA injection in patients with hematological malignancies without any over/under-indication. We listed all patients with the required indications from November 2022 to March 2023. We included 178 cases, 84 females and 94 males, with a median age of 70 (range: 19–90) years. Underlying diseases are myeloid neoplasms in 36 (20%), lymphoid neoplasms in 75 (73%), and others. Indications were intensively hematological malignancy treatment, rituximab treatment within 12 months, burton kinase inhibitor treatment, after chimeric antigen receptor T cell immunotherapy, and after stem cell transplantation in 74 (41%), 73 (41%), 3 (2%), 5 (3%), and 23 (13%) cases, respectively. Of the 178 cases, 22 (12.4%) refused EVA injection. Further, 42 and 136 cases were administered outpatient and inpatient, respectively. Over 95% of the listed cases received EVA injection within 3 months. No severe toxicities were observed among them (N = 156), and 8 (5.2%) cases had breakthrough SARS-CoV-2 infection, which was significantly lower (P = 0.02) than those without EVA (4 [18.2%] of 22 cases). Both groups showed no moderate or severe infection cases. This single-center experience showed that comprehensive EVA injection management effectively generated safer completion with preferable clinical impact.

Chemotherapy-induced febrile neutropenia (FN) in the US: healthcare resource utilization (HCRU) and costs (preprint)

Purpose Febrile neutropenia (FN) is a known side effect of chemotherapy, often requiring hospitalization. Economic burden increases with an FN episode and estimates of cost per episode should be updated from real-world data.Methods A retrospective claims analysis of FN episodes in patients with non-myeloid malignancies from 2014 to 2021 was performed in IQVIA PharMetrics® Plus database. FN episodes were defined as having same-day claims for neutropenia and fever or infection, plus antibiotic in outpatient settings, following a claim for chemotherapy; index date was defined as the first claim for neutropenia/fever/infection. Patients receiving bone marrow/stem cell transplant and CAR-T therapy were excluded, as were select hematologic malignancies or COVID-19. Healthcare utilization and costs were evaluated and described overall, by episode type (w/wo hospitalization), index year, malignancy type, NCI comorbidity score, and age group.Results 7,033 FN episodes were identified from 6,825 patients. Most episodes had a hospitalization (91.2%) and 86% of patients had ≥ 1 risk factor for FN. Overall, FN episodes had a mean (SD) FN-related cost of $25,176 ($39,943). Episodes with hospitalization had higher average FN-related costs versus those without hospitalization ($26,868 vs $7,738), and costs increased with comorbidity score (NCI = 0: $23,095; NCI > 0–2: $26,084; NCI ≥ 2: $26,851).Conclusions FN continues to be associated with significant economic burden, and varied by cancer type, comorbidity burden, and age. In this analysis, most FN episodes were not preceded by GCSF prophylaxis. The results of this study highlight the opportunity to utilize GCSF in appropriate oncology scenarios.

Changes in respiratory infection trends during the COVID-19 pandemic in the haematologic malignancy patients (preprint)

Background: The coronavirus disease 2019 (COVID-19) pandemic globally changed respiratory infection patterns. However, its impact on community-acquired pneumonia (CAP) in high risk patients with haematological malignancies (HM) is uncertain. We aimed to examine CAP aetiology changes in patients with HM pre- and post-COVID-19 pandemic. Methods: This retrospective study included 524 HM patients hospitalised with CAP between March 2018 and February 2022. Those who underwent bronchoscopy within 24 hours after admission to identify CAP aetiology were included. Data on patient characteristics, laboratory findings, and results of bronchioalveolar lavage fluid cultures and PCR tests were analysed to compare etiological changes and identify in-hospital mortality risk factors. Results: Patients were divided into pre-COVID-19 (44.5%) and post-COVID-19 (55.5%) groups. This study found a significant decrease in viral CAP in the post-COVID-19 era, particularly for influenza A, parainfluenza, adenovirus, and rhinovirus (3.0% vs. 0.3%, respectively, P = 0.036; 6.5% vs. 0.7%, respectively, P = 0.001; 5.6% vs. 1.4%, respectively, P = 0.015; 9.5% vs. 1.7%, respectively, P < 0.001). Bacterial, fungal, and unknown CAP aetiologies remain unchanged. Higher Sequential Organ Failure Assessment scores and lower platelet count correlated with in-hospital mortality after adjusting for potential confounding factors. Conclusion: The incidence of CAP in HM patients did not decrease after COVID-19. Additionally, CAP aetiology among patients with HM changed following the COVID-19 pandemic, with a significant reduction in viral pneumonia while bacterial and fungal pneumonia persisted. Further studies are required to evaluate the impact of COVID-19 on the prognosis of patients with HM and CAP.

SARS-CoV-2 Viral Clearance and Evolution Varies by Extent of Immunodeficiency (preprint)

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged SARS-CoV-2 infection, but the immune defects that predispose to persistent COVID- 19 remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median time to nasal viral RNA and culture clearance in the severe hematologic malignancy/transplant group (S-HT) were 72 and 21 days, respectively, which were significantly longer than clearance rates in the severe autoimmune/B-cell deficient (S-A), non-severe, and non-immunocompromised groups (P<0.001). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and higher risk of developing antiviral treatment resistance. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral, while only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.

COVID-19 Outcomes by Cancer Status, Site, Treatment, and Vaccination.

BACKGROUND: Studies have shown an increased risk of severe SARS-CoV-2-related (COVID-19) disease outcome and mortality for patients with cancer, but it is not well understood whether associations vary by cancer site, cancer treatment, and vaccination status. METHODS: Using electronic health record data from an academic medical center, we identified a retrospective cohort of 260,757 individuals tested for or diagnosed with COVID-19 from March 10, 2020, to August 1, 2022. Of these, 52,019 tested positive for COVID-19 of whom 13,752 had a cancer diagnosis. We conducted Firth-corrected logistic regression to assess the association between cancer status, site, treatment, vaccination, and four COVID-19 outcomes: hospitalization, intensive care unit admission, mortality, and a composite "severe COVID" outcome. RESULTS: Cancer diagnosis was significantly associated with higher rates of severe COVID, hospitalization, and mortality. These associations were driven by patients whose most recent initial cancer diagnosis was within the past 3 years. Chemotherapy receipt, colorectal cancer, hematologic malignancies, kidney cancer, and lung cancer were significantly associated with higher rates of worse COVID-19 outcomes. Vaccinations were significantly associated with lower rates of worse COVID-19 outcomes regardless of cancer status. CONCLUSIONS: Patients with colorectal cancer, hematologic malignancies, kidney cancer, or lung cancer or who receive chemotherapy for treatment should be cautious because of their increased risk of worse COVID-19 outcomes, even after vaccination. IMPACT: Additional COVID-19 precautions are warranted for people with certain cancer types and treatments. Significant benefit from vaccination is noted for both cancer and cancer-free patients.

The COVID-19 Pandemic and In-Person Visit Rate Disruptions Among Patients With Hematologic Neoplasms in the US in 2020 to 2021.

Importance: The COVID-19 pandemic has led to a reduction in routine in-person medical care; however, it is unknown whether there have been any changes in visit rates among patients with hematologic neoplasms. Objective: To examine associations between the COVID-19 pandemic and in-person visits and telemedicine use among patients undergoing active treatment for hematologic neoplasms. Design, Setting, and Participants: Data for this retrospective observational cohort study were obtained from a nationwide electronic health record-derived, deidentified database. Data for patients with hematologic neoplasms who had received at least 1 systemic line of therapy between March 1, 2016, and February 28, 2021, were included. Treatments were categorized into 3 types: oral therapy, outpatient infusions, and inpatient infusions. The data cutoff date was April 30, 2021, when study analyses were conducted. Main Outcomes and Measures: Monthly visit rates were calculated as the number of documented visits (telemedicine or in-person) per active patient per 30-day period. We used time-series forecasting methods on prepandemic data (March 2016 to February 2020) to estimate expected rates between March 1, 2020, and February 28, 2021 (if the pandemic had not occurred). Results: This study included data for 24 261 patients, with a median age of 68 years (IQR, 60-75 years). A total of 6737 patients received oral therapy, 15 314 received outpatient infusions, and 8316 received inpatient infusions. More than half of patients were men (14 370 [58%]) and non-Hispanic White (16 309 [66%]). Early pandemic months (March to May 2020) demonstrated a significant 21% reduction (95% prediction interval [PI], 12%-27%) in in-person visit rates averaged across oral therapy and outpatient infusions. Reductions in in-person visit rates were also significant for all treatment types for multiple myeloma (oral therapy: 29% reduction; 95% PI, 21%-36%; P = .001; outpatient infusions: 11% reduction; 95% PI, 4%-17%; P = .002; inpatient infusions: 55% reduction; 95% PI, 27%-67%; P = .005), for oral therapy for chronic lymphocytic leukemia (28% reduction; 95% PI, 12%-39%; P = .003), and for outpatient infusions for mantle cell lymphoma (38% reduction; 95% PI, 6%-54%; P = .003) and chronic lymphocytic leukemia (20% reduction; 95% PI, 6%-31%; P = .002). Telemedicine visit rates were highest for patients receiving oral therapy, with greater use in the early pandemic months and a subsequent decrease in later months. Conclusions and Relevance: In this cohort study of patients with hematologic neoplasms, documented in-person visit rates for those receiving oral therapy and outpatient infusions significantly decreased during the early pandemic months but returned to close to projected rates in the later half of 2020. There were no statistically significant reductions in the overall in-person visit rate for patients receiving inpatient infusions. There was higher telemedicine use in the early pandemic months, followed by a decline, but use was persistent in the later half of 2020. Further studies are needed to ascertain associations between the COVID-19 pandemic and subsequent cancer outcomes and the evolution of telemedicine use for care delivery.

Multicenter cohort study of the risk factors and mortality of Omicron variant SARS-CoV-2-infected patients with hematologic malignancies in hospitals (preprint)

Purpose Evaluating risk factors of mortality and characters in patients with hematologic malignancy (HM) after anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination of China.Methods A total of 104 HMs were included with a median follow-up of 45 days.Results The overall mortality rate was 9.6%. In multivariable analyses, 1 or more comorbidities (P = 0.014), lactic dehydrogenase > 300 u/l (P = 0.014), albumin < 35 g/l (P = 0.017) and active malignancy (P = 0.009) were associated with severe and critical COVID-19. Conversely, patients who received 3 vaccinations had a lower possibility of severe infection (P = 0.022). Active malignancy and lactic dehydrogenase > 300 u/l were risk factors associated with higher mortality in multivariable analyses (P = 0.03; P = 0.038, respectively). We also found that the duration of a positive SARS-CoV-2 PCR test and the time to stable pneumonia by chest computed tomography scan in the severe and critical infection subgroups were significantly longer than those in the moderate infection group (P = 0.03 and P = 0.002, respectively).Conclusions These findings may contribute to guiding the management of HMs during the pandemic, and emphasizing the importance of starting treatment of aggressive HMs for earlier remission.

SARS-CoV-2 vaccine-induced humoral and cellular immunity in patients with hematologic malignancies.

Patients with hematologic conditions have a higher risk of severe COVID-19 and COVID-19-related death. This is related to immune deficiencies induced by hematologic conditions and/or the treatment thereof. Prospective vaccine immunogenicity studies have demonstrated that in the majority of patients, a 3-dose COVID-19 vaccination schedule leads to antibody concentrations comparable to levels obtained in healthy adults after a 2-dose schedule. In B cell depleted patients, humoral responses are poor, however vaccination did induce potent cellular immune responses. The effect of 3-dose vaccination schedules and COVID-19 booster vaccinations on the protection of patients with hematologic malignancies against severe COVID-19 and COVID-19 related death remains to be confirmed by population-based vaccine effectiveness studies.

The Importance of Facilitating Goal-Concordant Care (GCC) in a Pandemic: The MD Anderson Experience with hospitalized COVID-19 positive patients (preprint)

Purpose Provider-patient communication (PPC) about goals of care (GOC) facilitates goal-concordant care (GCC) delivery. Hospital resource limitations imposed during the pandemic made it vital to deliver GCC to a patient cohort with COVID-19 and cancer. Our aim was to understand the population and adoption of GOC-PPC along with structured documentation in the form of an Advance Care Planning (ACP) note.Methods A multidisciplinary GOC task force developed processes for ease of conducting GOC-PPC and implemented structured documentation. Data were obtained from multiple electronic medical record elements, with each source identified, data integrated and analyzed. We looked at PPC and ACP documentation pre and post implementation alongside demographics, length of stay (LOS), 30-day readmission rate and mortality.Results 494 unique patients were identified, 52% male, 63% Caucasian, 28% Hispanic, 16% African American and 3% Asian. Active cancer was identified in 81% patients, of which 64% were solid tumors and 36% hematologic malignancies. LOS was 9 days with a 30-day readmission rate of 15% and inpatient mortality of 14%. Inpatient ACP note documentation was significantly higher post-implementation as compared to pre-implementation (90% vs 8%, P < 0.05). We saw sustained ACP documentation throughout the pandemic suggesting effective processes.Conclusions The implementation of institutional structured processes for GOC-PPC resulted in rapid sustainable adoption of ACP documentation for COVID-19 positive cancer patients. This was highly beneficial for this population during the pandemic, as it demonstrated the role of agile processes in care delivery models, which will be beneficial in the future when rapid implementation is needed.

Characterization of post-vaccination SARS-CoV-2 T cell subtypes in patients with different hematologic malignancies and treatments.

Background: To evaluate the benefits of SARS-CoV-2 vaccination in cancer patients it is relevant to understand the adaptive immune response elicited after vaccination. Patients affected by hematologic malignancies are frequently immune-compromised and show a decreased seroconversion rate compared to other cancer patients or controls. Therefore, vaccine-induced cellular immune responses in these patients might have an important protective role and need a detailed evaluation. Methods: Certain T cell subtypes (CD4, CD8, Tfh, γδT), including cell functionality as indicated by cytokine secretion (IFN, TNF) and expression of activation markers (CD69, CD154) were assessed via multi-parameter flow cytometry in hematologic malignancy patients (N=12) and healthy controls (N=12) after a second SARS-CoV-2 vaccine dose. The PBMC of post-vaccination samples were stimulated with a spike-peptide pool (S-Peptides) of SARS-CoV-2, with CD3/CD28, with a pool of peptides from the cytomegalovirus, Epstein-Barr virus and influenza A virus (CEF-Peptides) or left unstimulated. Furthermore, the concentration of spike-specific antibodies has been analyzed in patients. Results: Our results indicate that hematologic malignancy patients developed a robust cellular immune response to SARS-CoV-2 vaccination comparable to that of healthy controls, and for certain T cell subtypes even higher. The most reactive T cells to SARS-CoV-2 spike peptides belonged to the CD4 and Tfh cell compartment, being median (IQR), 3.39 (1.41-5.92) and 2.12 (0.55-4.14) as a percentage of IFN- and TNF-producing Tfh cells in patients. In this regard, the immunomodulatory treatment of patients before the vaccination period seems important as it was strongly associated with a higher percentage of activated CD4 and Tfh cells. SARS-CoV-2- and CEF-specific T cell responses significantly correlated with each other. Compared to lymphoma patients, myeloma patients had an increased percentage of SARS-CoV-2-specific Tfh cells. T-SNE analysis revealed higher frequencies of γδT cells in patients compared to controls, especially in myeloma patients. In general, after vaccination, SARS-CoV-2-specific T cells were also detectable in patients without seroconversion. Conclusion: Hematologic malignancy patients are capable of developing a SARS-CoV-2-specific CD4 and Tfh cellular immune response after vaccination, and certain immunomodulatory therapies in the period before vaccination might increase the antigen-specific immune response. A proper response to recall antigens (e.g., CEF-Peptides) reflects immune cellular functionality and might be predictive for generating a newly induced antigen-specific immune response as is expected after SARS-CoV-2 vaccination.

Kinetics of cellular and humoral immunogenicity and effectiveness of SARS-CoV-2 booster vaccination in hematologic neoplasms.

Data on the effect of booster SARS-CoV-2 vaccination are mainly focused on humoral immunogenicity, while the kinetics of vaccine-induced cellular response and its correlation with effectiveness in hematologic patients are less explored. Our aim was to evaluate the longitudinal cellular and humoral immunogenicity induced by two and three doses of the mRNA-1273 SARS-CoV-2 vaccine in 270 patients with hematologic malignancies, and its relationship with the severity of breakthrough SARS-CoV-2 infection. Results indicate that at 23 weeks after the second dose, the seroconversion rate declined from 68.5% to 59.3%, with a reduction in median anti-S titers from 1577 to 456 BAU/mL, mainly in patients over 65 years of age or chronic lymphocytic leukemia (CLL) patients undergoing active therapy. Cellular immunogenicity, however, remained positive in 84.4% of cases. A third vaccine dose seroconverted 42.7% (41/96) and triggered cellular response in 36.7% (11/30) of previously negative patients. Notably, only 7.2% (15/209) of patients failed to develop both humoral and cellular response. Active therapy, anti-CD20 antibodies, lymphopenia, hypogammaglobulinemia, and low CD19+ cell count were associated with poor humoral response, while active disease, GvHD immunosuppressive therapy, lymphopenia, and low CD3+ , CD4+ , CD56+ cell count determined an impaired cellular response. After 13.8 months of follow-up, the incidence of SARS-CoV-2 infection was 24.8% (67/270), including 6 (9%) severe/critical cases associated with a weaker cellular (median interferon gamma (IFN-γ) 0.19 vs. 0.35 IU/mL) and humoral response (median anti-S titer <4.81 vs. 788 BAU/mL) than asymptomatic/mild cases. In conclusion, SARS-CoV-2 booster vaccination improves humoral response and COVID-19 severity is associated with impaired vaccine-induced immunogenicity.

COVID-19 and Other Viral Infections in Patients With Hematologic Malignancies.

COVID-19 and our armamentarium of strategies to combat it have evolved dramatically since the virus first emerged in late 2019. Vaccination remains the primary strategy to prevent severe illness, although the protective effect can vary in patients with hematologic malignancy. Strategies such as additional vaccine doses and now bivalent boosters can contribute to increased immune response, especially in the face of evolving viral variants. Because of these new variants, no approved monoclonal antibodies are available for pre-exposure or postexposure prophylaxis. Patients with symptomatic, mild-to-moderate COVID-19 and risk features for developing severe COVID-19, who present within 5-7 days of symptom onset, should be offered outpatient therapy with nirmatrelvir/ritonavir (NR) or in some cases with intravenous (IV) remdesivir. NR interacts with many blood cancer treatments, and reviewing drug interactions is essential. Patients with severe COVID-19 should be managed with IV remdesivir, tocilizumab (or an alternate interleukin-6 receptor blocker), or baricitinib, as indicated based on the severity of illness. Dexamethasone can be considered on an individual basis, weighing oxygen requirements and patients' underlying disease and their perceived ability to clear infection. Finally, as CD19-targeted and B-cell maturation (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapies become more heavily used for relapsed/refractory hematologic malignancies, viral infections including COVID-19 are increasingly recognized as common complications, but data on risk factors and prophylaxis in this patient population are scarce. We summarize the available evidence regarding viral infections after CAR T-cell therapy.

Effects of comorbidities associated with COVID-19 cases in Intensive Care Unit on mortality and disease progression.

OBJECTIVE: The patient's age, gender and the presence of certain concomitant diseases have been reported to play a part in the course and progression of COVID-19 in the literature. In this study, we aimed to compare the comorbidities causing mortality in critically ill Intensive Care Unit (ICU)-patients diagnosed with COVID-19. PATIENTS AND METHODS: The data as regards the COVID-19 cases followed up in the ICU were retrospectively reviewed. 408 COVID-19 patients with positive PCR test were included in the study. In addition, a subgroup analysis was performed in patients treated with invasive mechanical ventilation. While the primary aim of this study was to evaluate the difference in survival rates due to comorbidities in critical COVID-19 patients, we also aimed to assess the comorbidities in severely intubated COVID-19 patients in terms of mortality. RESULTS: A statistically significant increase in mortality was observed in patients with underlying hematologic malignancy and chronic renal failure (p=0.027, 0.047). Body mass index value in the mortal group was significantly higher in both the general study group and subgroup analysis (p=0.004, 0.001). CONCLUSIONS: Advanced age and comorbidities such as chronic renal failure and hematologic malignancy in COVID-19 patients are associated with poor survival prognosis in critically ill COVID-19 patients.

Infectious complications of chimeric antigen receptor (CAR) T-cell therapies.

CAR T-cells have revolutionized the treatment of many hematological malignancies. Thousands of patients with lymphoma, acute lymphoblastic leukemia, and multiple myeloma have received this "living medicine" and achieved durable remissions. Their place in therapy continues to evolve, and there is ongoing development of new generation CAR constructs, CAR T-cells against solid tumors and CAR T-cells against chronic infections like human immunodeficiency virus and hepatitis B. A significant fraction of CAR T-cell recipients, unfortunately, develop infections. This is in part due to factors intrinsic to the patient, but also to the treatment, which requires lymphodepletion (LD), causes neutropenia and hypogammaglobulinemia and necessarily increases the state of immunosuppression of the patient. The goal of this review is to present the infectious complications of CAR T-cell therapy, explain their temporal course and risk factors, and provide recommendations for their prevention, diagnosis, and management.