Despite the generally mild course of COVID-19 in children, immunocompromised patients may experience complications or severe infection. This study reports the clinical outcomes of pediatric patients treated with nirmatrelvir and ritonavir (N/R) for SARS-CoV-2 infection.

We retrospectively reported the data of children with any immunodeficiency with COVID-19 who received N/R treatment between March 2022 and June 2023 at the Bambino Gesù Children's Hospital. Patients were treated with N/R for 5 days. We compared liver and kidney function before and after treatment with N/R and looked for a relationship between the duration of COVID-19 infection and the time from positivity to administration of N/R administration.

A total of 85 pediatric immunocompromised patients with COVID-19 were included in the study, with a mean age of 10.7 years (SD 4.8), mostly males (60%). We found a significant difference in the viral load before and after N/R administration. Four patients (4.7%) experienced adverse events related to N/R therapy. One of these had to discontinue N/R administration. Three patients (3.5%) experienced negative effects of drug interactions during N/R therapy, namely an increase of sirolimus and ciclosporin serum levels. A significant positive correlation was found between the time from SARS-CoV-2 positivity to N/R administration and the duration of SARS-CoV-2 swab positivity (R = 0.78, P < 0.001), suggesting that the earlier N/R is administered, the shorter the duration of COVID-19 in the study sample.

Our experience shows that N/R is reasonably safe in the pediatric population and could favor viral clearance, thus reducing the duration of infection.

Little is known about the efficacy of COVID-19 vaccines during acute lymphoblastic leukemia therapy (ALL); data for COVID-19 vaccine immune responses in pediatric leukemia remain sparse. We conducted a single center study of patients aged 5-25 years undergoing ALL chemotherapy who received COVID-19 vaccination. Twenty-one patients were enrolled; efficacy was evaluable in 20. Twenty were vaccinated while receiving chemotherapy. Twenty received the BNT162b2 mRNA vaccine. Spike reactive antibodies (S-IgG) and/or T-cells (SRT) were detected in 16 of 20 (80%) vaccinated patients; 13 (65%) and 9 (45%) were positive for S-IgG and SRT, respectively. Six (30%) showed both spike reactive B and T-cell responses. Eleven of the 13 with S-IgG positivity were negative for anti-Nucleocapsid IgG, an antibody profile consistent with a vaccine induced immune response. All 13S-IgG+ patients showed neutralizing antibodies. SRT included CD4+ (7) and CD8+ (6) T-cells; both CD4+ and CD8+ SRT were seen in 4. SRT were multifunctional (producing multiple cytokines) in most patients (8 of 9); 4 showed SRT with triple cytokine and B-cell co-stimulatory responses, indicating a multimodal adaptive immune response. Immune responses were seen among patients vaccinated in the settings of lymphopenia (6 of 12) intensive chemotherapy (3 of 4), and Peg allergy (6 of 8). Sequencing revealed public CD4+ and CD8+ TCR sequences reactive to epitopes across the spike protein. In conclusion, COVID-19 vaccination induced B and/or T-cell responses in a majority of children and young adults undergoing ALL chemotherapy.

Chronic lymphocytic leukemia (CLL) is characterized by disease- and treatment-related immunosuppression. Patients with CLL comprise a vulnerable population to coronavirus disease 2019 (COVID-19), while the protective effect of COVID-19 vaccination remains uncertain.We conducted a systematic review to evaluate published data reporting response to COVID-19 vaccination in patients with CLL. The primary outcome was the rate of seropositivity after full primary vaccination, while secondary outcomes were rates of positive neutralizing antibodies, cellular responses, and adverse events. Response after booster doses of vaccination was also evaluated.Twenty-three studies of full primary vaccination (12 CLL-specific with 1747 patients, 11 with mixed hematologic diseases including 1044 patients with CLL) with a total of 2791 patients, and eight studies on booster doses with 389 patients were included in the analysis. The serologic response varied between studies with a median of 55%. Where reported, the median neutralizing antibody response rate was 61.2% and the cellular response rate was 44.2%. Poor serologic response was noted in patients under active treatment with anti-CD20 monoclonal antibodies, BCL2, and BTK inhibitors.The present review highlights the substantially impaired humoral and cellular response to COVID-19 vaccination in patients with CLL with patients under active treatment being the most vulnerable.

We aimed to investigate risk factors for COVID-19 pneumonia in patients with hematological malignancies (HM) after Omicron infection.

Data from a registered multi-center, prospective, observational study (ChiCTR2300071830) during the latest Omicron BA.5.2 wave in Chongqing, China was used for analysis.

A total of 475 HM patients enrolled in this study. COVID-19 pneumonia was observed in 15.8% (75/475) of patients, with a median age of 58 years (interquartile range [IQR], 48-69 years) and males accounting for 61.3%. Risk factors associated with COVID-19 pneumonia included: 1) Active disease status of HM at infection, with an odds ratio (OR) of 3.42 (95% confidence interval [CI]: 1.59-7.37, P=0.002) compared to complete remission (CR); 2) Incomplete COVID-19 vaccination, 1-2 doses of the vaccine (OR=2.55, 95% CI: 1.28-5.10, P=0.008) or no vaccination (OR=4.81, 95% CI: 2.45-9.43, P<0.001), as opposed to 3 doses (booster); 3) chemotherapy prior to infection, <6 months (OR=2.58, 95% CI: 1.12-5.96, P=0.027) or ≥ 6 months (OR=2.93, 95% CI: 1.31-6.53, P=0.009) compared to no chemotherapy history; 4) NK-cell reduction (< 150/μL) (OR=2.19, 95% CI: 1.27-3.79, P=0.005) versus a normal range of NK cells. During the 6-week follow-up period, 12 patients (2.5%) died, accounting for 16% of COVID-19 pneumonia patients.

Our study investigated risk factors for COVID-19 pneumonia in HM patients after Omicron BA.5.2 infection. Highlights that HM patients with these risk factors may be susceptible to lung involvement after Omicron BA.5.2 infection and need to be taken seriously in clinical practice.

https://www.chictr.org.cn/bin/project/edit?pid=195998, identifier ChiCTR2300071830.

An increasing body of evidence suggests a close association between COVID-19 infection and the safety of PD-1/PD-L1 inhibitor therapy in cancer patients. However, the available data concerning these impacts remain limited and occasionally contradictory.

We conducted a retrospective analysis of cancer patients who received PD-1/PD-L1 inhibitor therapy at the same institution from November 2022 to May 2023. After excluding patients with missing information, a total of 224 cases were included. In our study, immune-related adverse events (irAEs) that occurred during the hospitalization of patients were included in the analysis. Further analysis of inter-subgroup differences was conducted following a 1:2 propensity score matching. Statistical analyses were performed using the Fisher's exact, chi-squared, and Mann-Whitney U-tests.

The results showed that no statistically significant differences between the two subgroups in the incidence of irAEs, changes in immune function before and after using PD-1/PD-L1 inhibitors, and alterations in hepatic and renal function (p > 0.05).

Our findings suggest that infection with COVID-19 does not significantly impact the safety of PD-1/PD-L1 inhibitors in cancer patients. Most cancer patients used PD-1/PD-L1 inhibitors during COVID-19 infection (asymptomatic or mild infection) did not experience exacerbation of their underlying condition, nor did they exhibit a substantial increase in toxic side effects.

Immune responses to primary COVID-19 vaccination were investigated in 58 patients with follicular lymphoma (FL) as part of the PETReA trial of frontline therapy (EudraCT 2016-004010-10). COVID-19 vaccines (BNT162b2 or ChAdOx1) were administered before, during or after cytoreductive treatment comprising rituximab (depletes B cells) and either bendamustine (depletes CD4+ T cells) or cyclophosphamide-based chemotherapy. Blood samples obtained after vaccine doses 1 and 2 (V1, V2) were analysed for antibodies and T cells reactive to the SARS-CoV-2 spike protein using the Abbott Architect and interferon-gamma ELISpot assays respectively. Compared to 149 healthy controls, patients with FL exhibited lower antibody but preserved T-cell responses. Within the FL cohort, multivariable analysis identified low pre-treatment serum IgA levels and V2 administration during induction or maintenance treatment as independent determinants of lower antibody and higher T-cell responses, and bendamustine and high/intermediate FLIPI-2 score as additional determinants of a lower antibody response. Several clinical scenarios were identified where dichotomous immune responses were estimated with >95% confidence based on combinations of predictive variables. In conclusion, the immunogenicity of COVID-19 vaccines in FL patients is influenced by multiple disease- and treatment-related factors, among which B-cell depletion showed differential effects on antibody and T-cell responses.

Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. Severe acute respiratory syndrome coronavirus 2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic messenger RNA vaccine response in retrospective and prospective cohorts with lymphoma and chronic lymphocytic leukemia, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active treatment, but nonresponse was also common within observation and posttreatment groups. Total immunoglobulin A and immunoglobulin M correlated with successful vaccine response. In individuals treated with anti-CD19-directed chimeric antigen receptor-modified T cells, nonresponse was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to individualize vaccine timing.

The effect of COVID-19 on the high number of immunocompromised people living with HIV-1 (PLWH), particularly in Africa, remains a critical concern. Here, we identify key areas that still require further investigation, by examining COVID-19 vaccine effectiveness, and understanding antibody responses in SARS-CoV-2 infection and vaccination in comparison with people without HIV-1 (PWOH). We also assess the potential impact of pre-existing immunity against endemic human coronaviruses on SARS-CoV-2 responses in these individuals. Lastly, we discuss the consequences of persistent infection in PLWH (or other immunocompromised individuals), including prolonged shedding, increased viral diversity within the host, and the implications on SARS-CoV-2 evolution in Africa.

Cancer patients often have weakened immune systems, resulting in a lower response to vaccines, especially those receiving immunosuppressive oncological treatment (OT). We aimed to assess the impact of OT on the humoral and T-cell response to the B.1 lineage and Omicron variant following COVID-19 vaccination in patients with solid and hematological neoplasms.

We conducted a prospective study on cancer patients, stratified into OT and non-OT groups, who received a two-dose series of the COVID-19 mRNA vaccine and a booster six months later. The outcomes measured were the humoral (anti-SARS-CoV-2 S IgG titers and ACE2-S interaction inhibition capacity) and cellular (SARS-CoV-2 S-specific T-cell spots per million PBMCs) responses against the B.1 lineage and Omicron variant. These responses were evaluated four weeks after the second dose (n = 98) and eight weeks after the booster dose (n = 71).

The humoral response after the second vaccine dose against the B.1 lineage and Omicron variant was significantly weaker in the OT group compared to the non-OT group (q-value<0.05). A booster dose of the mRNA-1273 vaccine significantly improved the humoral response in the OT group, making it comparable to the non-OT group. The mRNA-1273 vaccine, designed for the original Wuhan strain, elicited a weaker humoral response against the Omicron variant compared to the B.1 lineage, regardless of oncological treatment or vaccine dose. In contrast, T-cell responses against SARS-CoV-2, including the Omicron variant, were already present after the second vaccine dose and were not significantly affected by oncological treatments.

Cancer patients, particularly those receiving immunosuppressive oncological treatments, should require booster doses and adapted COVID-19 vaccines for new SARS-CoV-2 variants like Omicron. Future studies should evaluate the durability of the immune response and the efficacy of individualized regimens.

There is a knowledge gap concerning the proper timing for COVID-19 vaccination in cancer patients undergoing chemotherapy. We aimed to evaluate the suitability of the guidelines that recommend waiting at least three months after undergoing chemotherapy before receiving a COVID-19 vaccine. This retrospective cohort study used aggregated data from the TriNetX US Collaboratory network. Participants were grouped into two groups based on the interval between chemotherapy and vaccination. The primary outcome assessed was infection risks, including COVID-19; skin, intra-abdominal, and urinary tract infections; pneumonia; and sepsis. Secondary measures included healthcare utilization and all causes of mortality. Kaplan-Meier analysis and the Cox proportional hazard model were used to calculate the cumulative incidence and hazard ratio (HR) and 95% confidence intervals for the outcomes. The proportional hazard assumption was tested with the generalized Schoenfeld approach. Four subgroup analyses (cancer type, vaccine brand, sex, age) were conducted. Sensitivity analyses were performed to account for competing risks and explore three distinct time intervals. Patients receiving a vaccine within three months after chemotherapy had a higher risk of COVID-19 infection (HR: 1.428, 95% CI: 1.035-1.970), urinary tract infection (HR: 1.477, 95% CI: 1.083-2.014), and sepsis (HR: 1.854, 95% CI: 1.091-3.152) compared to those who adhered to the recommendations. Hospital inpatient service utilization risk was also significantly elevated for the within three months group (HR: 1.692, 95% CI: 1.354-2.115). Adhering to a three-month post-chemotherapy waiting period reduces infection and healthcare utilization risks for cancer patients receiving a COVID-19 vaccine.

Several population-level studies have described individual clinical risk factors associated with suboptimal antibody responses following COVID-19 vaccination, but none have examined multimorbidity. Others have shown that suboptimal post-vaccination responses offer reduced protection to subsequent SARS-CoV-2 infection; however, the level of protection from COVID-19 hospitalisation/death remains unconfirmed. We use national Scottish datasets to investigate the association between multimorbidity and testing antibody-negative, examining the correlation between antibody levels and subsequent COVID-19 hospitalisation/death among double-vaccinated individuals. We found that individuals with multimorbidity ( ≥ five conditions) were more likely to test antibody-negative post-vaccination and 13.37 [6.05-29.53] times more likely to be hospitalised/die from COVID-19 than individuals without conditions. We also show a dose-dependent association between post-vaccination antibody levels and COVID-19 hospitalisation or death, with those with undetectable antibody levels at a significantly higher risk (HR 9.21 [95% CI 4.63-18.29]) of these serious outcomes compared to those with high antibody levels.

Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 ("vax-plasma"). Thus, we report the clinical outcome of 386 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19-specific therapeutics (standard-of-care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 2.2% (5 of 225 patients) in the vax-plasma group and 6.2% (10 of 161 patients) in the standard-of-care group, which corresponded to a relative risk reduction of 65% (P = 0.046). Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (361 of 386 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19-specific therapies reduced the risk of disease progression leading to hospitalization.IMPORTANCEAs SARS-CoV-2 evolves, new variants of concern (VOCs) have emerged that evade available anti-spike monoclonal antibodies, particularly among immunosuppressed patients. However, high-titer COVID-19 convalescent plasma continues to be effective against VOCs because of its broad-spectrum immunomodulatory properties. Thus, we report clinical outcomes of 386 immunocompromised outpatients who were treated with COVID-19-specific therapeutics and a subgroup also treated with vaccine-boosted convalescent plasma. We found that the administration of vaccine-boosted convalescent plasma was associated with a significantly decreased incidence of hospitalization among immunocompromised COVID-19 outpatients. Our data add to the contemporary data providing evidence to support the clinical utility of high-titer convalescent plasma as antibody replacement therapy in immunocompromised patients.

The treatment pattern and outcomes in patients with indolent B-cell lymphoma treated during the coronavirus disease 2019 (COVID-19) pandemic period compared to the prepandemic period are unclear. This was a retrospective population-based study using administrative databases in Ontario, Canada (follow-up to 31 March 2022). The primary outcome was treatment pattern; secondary outcomes were death, toxicities, healthcare utilization (emergency department [ED] visit, hospitalization) and SARS-CoV-2 outcomes. Adjusted hazard ratios (aHR) from Cox proportional hazards models were used to estimate associations. We identified 4143 patients (1079 pandemic, 3064 prepandemic), with a median age of 69 years. In both time periods, bendamustine (B) + rituximab (BR) was the most frequently prescribed regimen. During the pandemic, fewer patients received R maintenance or completed the full 2-year course (aHR 0.81, 95% CI 0.71-0.92, p = 0.001). Patients treated during the pandemic had less healthcare utilization (ED visit aHR 0.77, 95% CI 0.68, 0.88, p < 0.0001; hospitalization aHR 0.81, 95% CI 0.70-0.94, p = 0.0067) and complications (infection aHR 0.69, 95% CI 0.57-0.82, p < 0.0001; febrile neutropenia aHR 0.66, 95% CI 0.47-0.94, p = 0.020), with no difference in death. Independent of vaccination, active rituximab use was associated with a higher risk of COVID-19 complications. Despite similar front-line regimen use, healthcare utilization and admissions for infection were less in the pandemic cohort.

The mortality due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) approaches 40% in recipients of chimeric antigen receptor (CAR) T cell therapy (CAR-T). The efficacy of repeated vaccine doses, including bivalent boosters, remains unknown. We examined the efficacy of repeated vaccine doses among CAR-T recipients who received at least 2 or more vaccine doses after T cell infusion. This single-center retrospective study included adults age >18 years receiving CAR-T for relapsed/refractory (R/R) B cell hematologic malignancies targeting CD19, BCMA, or CD19 and CD20 between September 2018 through March 2022 and were alive beyond 2021 to receive incremental SARS-CoV-2 vaccine doses with available seroconversion data. Multivariable analyses were performed using the design-adjusted Cox regression and logistic regression approaches with stratification. In multivariable analysis, seroconversion rates were significantly greater with a total of 4 or more vaccine doses (odds ratio [OR], 8.22; P = .008). CAR-T recipients with other B cell hematologic malignancies had significantly lower seroconversion rates and diminished Ab titers compared to those with R/R multiple myeloma (OR, .07; P = .003). One patient died due to COVID-19 in this vaccinated study cohort, accounting for a COVID-19-attributable mortality rate of 1.7%. The results provide baseline vaccine response data in a contemporary cohort including patients with diverse group of SARS-COV2 variants and support the latest Centers for Disease Control and Prevention guidelines for repeated vaccinations directed against the prevalent variant of concern.

Since the beginning of the COVID-19 pandemic, there has been an overall improvement in patient mortality. However, haematological malignancy patients continue to experience significant impacts from COVID-19, including high rates of hospitalization, intensive care unit (ICU) admissions, and mortality. In comparison to other haematological malignancy patients, individuals with chronic myeloid leukemia (CML) generally have better prognosis. This study, conducted using a large haematological malignancy patient database (EPICOVIDEHA), demonstrated that the majority of CML patients experienced mild infections. The decline in severe and critical infections over the years can largely be attributed to the widespread administration of vaccinations and the positive response they elicited. Notably, the mortality rate among CML patients was low and exhibited a downward trend in subsequent years. Importantly, our analysis provided confirmation of the effectiveness of vaccinations in CML patients.

Patients with lymphoid malignancies are at increased risk of death or prolonged infection due to COVID-19. Data on the influence of different antineoplastic treatment modalities on outcomes are conflicting. Anti-CD20 monoclonal antibodies increase the risk of prolonged infection. It is unclear whether this risk is affected by the choice of the antibody (rituximab vs. obinutuzumab). To elucidate the role of antineoplastic therapy on COVID-19 outcomes, KroHem collected data on patients with lymphoid malignancies diagnosed with COVID-19 between October 2020 and April 2021. A total of 314 patients were identified, 75 untreated, 61 off treatment and 178 on treatment. The mortality rate in untreated and off-treatment patients was 15% and 16%; 9% and 10% had prolonged infection. In the on-treatment group, 3% were still prolonged positive at time of data collection, 62% recovered and 35% died; 42% had prolonged infection. Disease type, use of anti-CD20 monoclonal antibodies, prior autologous stem-cell transplantation (ASCT) and line of treatment did not significantly affect mortality. Mortality was higher in older patients (p = 0.0078) and those treated with purine analogues (p = 0.012). Prolonged COVID-19 was significantly more frequent in patients treated with anti-CD20 monoclonal antibodies (p = 0.012), especially obinutuzumab, and purine analogues (p = 0.012). Age, prior ASCT and treatment line did not significantly affect risk of prolonged infection. These data suggest that increased age and use of purine analogues are main risk factors for increased mortality of COVID-19 in patients with lymphoid malignancies. Obinutuzumab further increases the risk of prolonged disease, but not of death, in comparison to rituximab. Epidemiological considerations should be taken into account when choosing the appropriate antineoplastic therapy for patients with lymphoid malignancies.

Cancer patients are at an increased risk of morbidity and mortality from SARS-CoV-2 infection and have a decreased immune response to vaccination. We conducted a study measuring both the neutralizing and total antibodies in cancer patients following a third dose of the mRNA-1273 COVID-19 vaccine. Immune responses were measured with an enzyme-linked immunosorbent assay (ELISA) and neutralization assays. Kruskal-Wallis tests were used to evaluate the association between patient characteristics and neutralization geometric mean titers (GMTs), and paired t-tests were used to compare the GMTs between different timepoints. Spearman correlation coefficients were calculated to determine the correlation between total antibody and neutralization GMTs. Among 238 adults diagnosed with cancer, a third dose of mRNA-1273 resulted in a 37-fold increase in neutralization GMT 28 days post-vaccination and maintained a 14.6-fold increase at 6 months. Patients with solid tumors or lymphoid cancer had the highest and lowest neutralization GMTs, respectively, at both 28 days and 6 months post-dose 3. While total antibody GMTs in lymphoid patients continued to increase, other cancer types showed decreases in titers between 28 days and 6 months post-dose 3. A strong correlation (p < 0.001) was found between total antibody and neutralization GMTs. The third dose of mRNA-1273 was able to elicit a robust neutralizing antibody response in cancer patients, which remained for 6 months after administration. Lymphoid cancer patients can benefit most from this third dose, as it was shown to continue to increase total antibody GMTs 6 months after vaccination.

This real-world study investigated the outcome of COVID-19 in lymphoma patients participating in registered clinical trials and explored potential risk factors with the outcome of COVID-19 during the first wave of the Omicron outbreak in China.

One hundred and ten patients participating in registered clinical trials and diagnosed with COVID-19 in our center between December 1, 2022, and January 31, 2023, were included.

Four (3.6%) patients were identified as severe COVID-19 and 2 (1.8%) as critical COVID-19, respectively. The mortality rate observed was 2.73% for the entire cohort, 33.3% for the severe/critical COVID-19 group, and 18.8% for the hospitalized group. The 90-day OS was 98.2% for the entire cohort, 66.7% for the severe/critical COVID-19 group, and 87.5% for the hospitalized group. Advanced age (≥70 years), comorbidities, and PI3K inhibitor-containing regimen were significantly associated with the severity of COVID-19. Patients with indolent B-cell non-Hodgkin lymphomas were less likely to be hospitalized for COVID-19.

This study reported similar clinical features of COVID-19 in our cohort with that of non-hematological malignancy (HM) patients, while the proportion of severe/critical COVID-19 and the mortality rate were relatively higher than non-HM patients. Our findings provided valuable experience to aid clinical researchers with managing lymphoma patients participating in registered clinical trials during the ongoing pandemic of the Omicron variant.

In this study, we aim to explore the outcomes of Covid-19 infection in patients with Hairy cell leukemia (HCL). The cohort is based on data obtained from electronic medical records. It includes 218 consecutive patients diagnosed with HCL between 16 June 1998, and 20 September 2022, out of which the coronavirus has infected 85 patients during the Omicron surge. Out of 85 patients with HCL who were infected by Covid-19; 7 patients (8.2%) have been hospitalized, and the mortality rate was 2.3% (two patients). Thirteen of the 85 patients had been infected by Covid-19 in previous waves, including 9/13 after vaccination, and none of them developed a severe disease. Humoral immune response after three doses of the BNT162b2 mRNA vaccination regimen was evaluated in 40 patients and was attained in 67.5%. Based on multivariate analysis: unfavorable outcome was significantly more common in patients with HCL above 65 years old, who had at least one cytopenia, and with comorbidity of cardiovascular disease or asplenia. Our results indicates that the course of COVID-19 in patients with HCL during the Omicron wave has been improved relatively favorable.

Amid the COVID-19 pandemic, healthcare providers (HCPs) of hematology patients face unique challenges due to the vulnerability of their patients. This study explores the lived experiences of these providers during and beyond the crisis.

Twenty-one Australian HCPs caring for hematology patients completed semi-structured interviews exploring their experiences and needs during the COVID-19 pandemic, adequacy of support and information provided by healthcare organizations, impact on hematology patients, and the benefits and challenges of telehealth care. Data were analyzed using reflexive thematic analysis.

Four themes were identified: (1) Managing an initial state of flux (unsettling uncertainty and fear, unique needs of hematology patients, getting on with the job together); (2) Concerns about care provision (questioning care efficacy, burden of compassion); (3) Disconnect between HCP needs and system-level responses (burnout, isolation, and poor work-life balance, broadcast fatigue, protecting mental health), and; (4) Reflecting on the future (ongoing challenges for hematology patients, higher staff turnover and heavier workloads, innovation in the healthcare field).

This study sheds light on the challenges that hematology HCPs face during and beyond the COVID-19 crisis, impacting their wellbeing. Addressing these challenges is paramount for the healthcare system at large. Provider-led peer support programs may be beneficial for addressing moral distress and building resilience. Additionally, specific consideration for the ongoing vulnerability of hematology patients could have positive impacts on providers' professional satisfaction.

Revaccination after receipt of a hematopoietic cell transplant (HCT) or cellular therapies is a pillar of patient supportive care, with the potential to reduce morbidity and mortality linked to vaccine-preventable infections. This review synthesizes national, international, and expert consensus vaccination schedules post-HCT and presents evidence regarding the efficacy of newer vaccine formulations for pneumococcus, recombinant zoster vaccine, and coronavirus disease 2019 in patients with hematological malignancy. Revaccination post-cellular therapies are less well defined. This review highlights important considerations around poor vaccine response, seroprevalence preservation after cellular therapies, and the optimal timing of revaccination. Future research should assess the immunogenicity and real-world effectiveness of new vaccine formulations and/or vaccine schedules in patients post-HCT and cellular therapy, including analysis of vaccine response that relates to the target of cellular therapies.

More than 3 years have passed since Coronavirus disease 2019 (COVID-19) was declared a global pandemic, yet COVID-19 still severely impacts immunocompromised individuals including those treated with hematopoietic cell transplantation (HCT) and chimeric antigen receptor-T-cell therapies who remain at high risk for severe COVID-19 and mortality. Despite vaccination efforts, these patients have inadequate responses due to immunosuppression, which underscores the need for additional preventive approaches. The optimal timing, schedule of vaccination, and immunological correlates for protective immunity remain unknown. Antiviral therapies used early during disease can reduce mortality and severity due to COVID-19. The combination or sequential use of antivirals could be beneficial to control replication and prevent the development of treatment-related mutations in protracted COVID-19. Despite conflicting data, COVID-19 convalescent plasma remains an option in immunocompromised patients with mild-to-moderate disease to prevent progression. Protracted COVID-19 has been increasingly recognized among these patients and has been implicated in intra-host emergence of SARS-CoV-2 variants. Finally, novel SARS-CoV2-specific T-cells and natural killer cell-boosting (or -containing) products may be active against multiple variants and are promising therapies in immunocompromised patients.

Tixagevimab-cilgavimab is effective for the treatment of early COVID-19 in outpatients with risk factors for progression to severe illness, as well as for primary prevention and post-exposure prophylaxis. We aimed to retrospectively evaluate the hospital stay (expressed in days), prognosis, and negativity rate for COVID-19 in patients after treatment with tixagevimab-cilgavimab. We enrolled 42 patients who were nasal swab-positive for SARS-CoV-2 (antigenic and molecular)-both vaccinated and not vaccinated for COVID-19-hospitalized at the first division of the Cotugno Hospital in Naples who had received a single intramuscular dose of tixagevimab-cilgavimab (300 mg/300 mg). All patient candidates for tixagevimab-cilgavimab had immunocompromised immune systems either due to chronic degenerative disorders (Group A: 27 patients) or oncohematological diseases (Group B: 15 patients). Patients enrolled in group A came under our observation after 10 days of clinical symptoms and 5 days after testing positivite for COVID-19, unlike the other patients enrolled in the study. The mean stay in hospital for the patients in Group A was 21 ± 5 days vs. 25 ± 5 days in Group B. Twenty patients tested negative after a median hospitalization stay of 16 days (IQR: 18-15.25); of them, five (25%) patients belonged to group B. Therefore, patients with active hematological malignancy had a lower negativization rate when treated 10 days after the onset of clinical symptoms and five days after their first COVID-19 positive nasal swab.

Chronic lymphocytic leukemia (CLL) is a prevalent hematological malignancy (HM) characterized by inherent immunodeficiency, which is further pronounced by disease-directed therapy. The COVID-19 pandemic has had devastating outcomes, and although its impact has diminished over time, it continues to be a cause of significant morbidity and mortality, particularly among immunodeficient patients.

In this review, we describe mechanisms of immune dysfunction in CLL in relation to COVID-19, provide an overview of the clinical outcomes of the disease in this patient population, and identify risk factors associated with severe morbidity and mortality. Additionally, we acknowledge the influence of the rapidly evolving landscape of new disease variants. The review further delineates the humoral and cellular responses to vaccination and their clinical efficacy in preventing COVID-19 in CLL patients. Moreover, we explore potential approaches to enhance these immune responses. Pre- and post-exposure prophylaxis strategies are discussed, along with description of common agents in the treatment of the disease in both outpatient and inpatient setting. Throughout the review, we emphasize the interplay between novel therapies for CLL and COVID-19 outcomes, prevention, and treatment and describe the impact of COVID-19 on the utilization of these novel agents. This information has the potential to guide clinical decision making in the management CLL patients.

CLL patients are at risk for severe COVID-19 infection. Vaccinations and COVID-19 directed therapy have improved outcomes in patients with CLL, yet clinical challenges persist.

Patients with hematologic malignancies have both an increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and higher morbidity/mortality. They have lower seroconversion rates after vaccination, potentially leading to inferior coronavirus disease 2019 (COVID-19) outcomes, despite vaccination. We consequently evaluated the clinical outcomes of COVID-19 infections in 243 vaccinated and 175 unvaccinated patients with hematologic malignancies. Hospitalization rates were lower in the vaccinated group when compared with the unvaccinated group (31.3% vs 52.6%). However, the rates of COVID-19-associated death were similar at 7.0% and 8.6% in vaccinated and unvaccinated patients, respectively. By univariate logistic regression, females, older patients, and individuals with higher modified Charlson Comorbidity Index scores were at a higher risk of death from COVID-19 infections. To account for the nonrandomized nature of COVID-19 vaccination status, a propensity score weighting approach was used. In the final propensity-weighted model, vaccination status was not significantly associated with the risk of death from COVID-19 infections but was associated with the risk of hospitalization. The predicted benefit of vaccination was an absolute decrease in the probability of death and hospitalization from COVID-19 infections by 2.3% and 22.9%, respectively. In conclusion, COVID-19 vaccination status in patients with hematologic malignancies was associated with a decreased risk of hospitalization but not associated with a decreased risk of death from COVID-19 infections in the pre-Omicron era. Protective strategies, in addition to immunization, are warranted in this vulnerable patient population.