COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study

Simple Summary There are contradictory data about coronavirus disease (COVID-19) in patients with hematological malignancies. In this population-based study we evaluated severity and survival of unvaccinated patients with hematological malignancies (HM) and COVID-19 in the Madrid region, Spain, between early February 2020 and February 2021. Also, a comparison was made with non-cancer patients from the SEMI-COVID registry and post COVID-19 conditions were evaluated. Overall, 30-day mortality was 32.7%, with higher mortality among certain groups of patients (aged ≥ 60 years, presence of ≥ 3 comorbidities, diagnosis of AML/ALL, treatment with conventional chemotherapy within 30 days of COVID-19 diagnosis, recipients of systemic corticosteroids as COVID-19 therapy). Mortality rates were similar between earlier and later phases of the pandemic, not paralleling the reduction of mortality in non-cancer patients. Up to 27.3% patients had a post COVID-19 condition. These findings will be useful to understand COVID-19 morbidity and mortality in unvaccinated patients diagnosed with HM. Abstract Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020;n = 769 (66%)) and later (July 2020–February 2021;n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77;2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34;0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12;0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study.

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February-June 2020; n = 769 (66%)) and later (July 2020-February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11-0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01-3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22-0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81-1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

No changes in hemostasis after COVID-19-heterologous vaccination schedule: A subanalysis of the phase 2 CombiVacS study.

Background: Several cases of unusual thrombotic events and thrombocytopenia were described after vaccination with recombinant adenoviral vectors encoding the spike protein antigen of SARS-CoV-2. Objectives: The objective of this study was to elucidate the impact of a COVID-19 heterologous vaccination schedule, including priming with adenovirus vaccine, on hemostasis profiles. Methods: The present study is a subanalysis of the CombiVacS clinical trial initiated in April 2021 that included adult participants previously vaccinated with a single dose of ChAdOx1-S. Between 8 and 12 weeks after vaccination, they were randomly assigned (2:1) to receive either BNT162b2 vaccine (intervention group, n = 99) or continue observation (control group, n = 50). Samples drawn before and 28 days after a vaccination with BNT162b2 were analyzed for platelet count and markers of hemostasis (D-dimer, anti-PF4 antibodies, cfDNA, PAI-1, thrombin generation, and serum capacity to activate platelets). Results: Platelet count from all participants after receiving BNT162b2 was within the normal range. Anti-PF4 antibodies were present in 26% and 18% of the subjects from the control and intervention groups, respectively, at day 28. In most cases, the levels of anti-PF4 antibodies were high before receiving BNT162b2. Serum from these participants did not activate platelets from healthy controls. There were no differences between the groups in PAI-1 and cfDNA plasma levels. According to the D-dimer plasma concentration, the thrombin generation test showed that none of the participants had a procoagulant profile. Conclusion: Our data suggest that the heterologous vaccination against COVID-19 with ChAdOx1-S and a second dose with BNT162b2 might be safe in terms of haemostasis.

Therapeutic versus Prophylactic Bemiparin in Hospitalized Patients with Nonsevere COVID-19 Pneumonia (BEMICOP Study): An Open-Label, Multicenter, Randomized, Controlled Trial.

Thromboprophylaxis with low molecular weight heparin in hospitalized patients with COVID-19 is mandatory, unless contraindicated. Given the links between inflammation and thrombosis, the use of higher doses of anticoagulants could improve outcomes. We conducted an open-label, multicenter, randomized, controlled trial in adult patients hospitalized with nonsevere COVID-19 pneumonia and elevated D-dimer. Patients were randomized to therapeutic-dose bemiparin (115 IU/kg daily) versus standard prophylaxis (bemiparin 3,500 IU daily), for 10 days. The primary efficacy outcome was a composite of death, intensive care unit admission, need of mechanical ventilation support, development of moderate/severe acute respiratory distress, and venous or arterial thrombosis within 10 days of enrollment. The primary safety outcome was major bleeding (International Society on Thrombosis and Haemostasis criteria). A prespecified interim analysis was performed when 40% of the planned study population was reached. From October 2020 to May 2021, 70 patients were randomized at 5 sites and 65 were included in the primary analysis; 32 patients allocated to therapeutic dose and 33 to standard prophylactic dose. The primary efficacy outcome occurred in 7 patients (22%) in the therapeutic-dose group and 6 patients (18%) in the prophylactic-dose (absolute risk difference 3.6% [95% confidence interval [CI], -16% -24%]; odds ratio 1.26 [95% CI, 0.37-4.26]; p = 0.95). Discharge in the first 10 days was possible in 66 and 79% of patients, respectively. No major bleeding event was registered. Therefore, in patients with COVID-19 hospitalized with nonsevere pneumonia but elevated D-dimer, the use of a short course of therapeutic-dose bemiparin does not appear to improve clinical outcomes compared with standard prophylactic doses. Trial Registration: ClinicalTrials.gov NCT04604327.

Impact of COVID-19 Pandemic on Patients with Immune Thrombocytopaenia.

Background and Objectives: The aim of this study was to determine the impact of the COVID-19 pandemic on the lives of patients with immune thrombocytopaenia (ITP) treated at our hospital. Materials and Methods: The study was conducted in the Community of Madrid, which has the highest number of COVID-19 cases in Spain. We included 143 adult patients with ITP (130 with chronic ITP, 8 with persistent ITP, and 5 with newly diagnosed ITP). We conducted a telephone survey to collect the data and created a registry. Materials and Methods: Overall, 24 patients presented symptoms suggestive of COVID-19, which was confirmed by RT-PCR in 8 cases. The cumulative incidence of confirmed SARS-CoV-2 infection was higher in the patients with ITP than in the Madrid population. There were no differences in the disease incidence or clinical course of infection in the patients treated with immunosuppressants. Almost all of the patients reported adherence to the prescribed treatment, although 49.2% of the hospital visits were either cancelled or postponed, 17.2% because of the patients' fear of coming to the centre. Nearly half of the cohort was considered vulnerable, and 17% had been granted a dependency or disability benefit. Conclusions: COVID-19 had a major impact on the psychosocial, occupational, and quality of care of patients with ITP.

Impact of hematologic malignancy and type of cancer therapy on COVID-19 severity and mortality: lessons from a large population-based registry study.

BACKGROUND: Patients with cancer have been shown to have a higher risk of clinical severity and mortality compared to non-cancer patients with COVID-19. Patients with hematologic malignancies typically are known to have higher levels of immunosuppression and may develop more severe respiratory viral infections than patients with solid tumors. Data on COVID-19 in patients with hematologic malignancies are limited. Here we characterize disease severity and mortality and evaluate potential prognostic factors for mortality. METHODS: In this population-based registry study, we collected de-identified data on clinical characteristics, treatment and outcomes in adult patients with hematologic malignancies and confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection within the Madrid region of Spain. Our case series included all patients admitted to 22 regional health service hospitals and 5 private healthcare centers between February 28 and May 25, 2020. The primary study outcome was all-cause mortality. We assessed the association between mortality and potential prognostic factors using Cox regression analyses adjusted for age, sex, comorbidities, hematologic malignancy and recent active cancer therapy. RESULTS: Of 833 patients reported, 697 were included in the analyses. Median age was 72 years (IQR 60-79), 413 (60%) patients were male and 479 (69%) and 218 (31%) had lymphoid and myeloid malignancies, respectively. Clinical severity of COVID-19 was severe/critical in 429 (62%) patients. At data cutoff, 230 (33%) patients had died. Age ≥ 60 years (hazard ratios 3.17-10.1 vs < 50 years), > 2 comorbidities (1.41 vs ≤ 2), acute myeloid leukemia (2.22 vs non-Hodgkin lymphoma) and active antineoplastic treatment with monoclonal antibodies (2·02) were associated with increased mortality; conventional chemotherapy showed borderline significance (1.50 vs no active therapy). Conversely, Ph-negative myeloproliferative neoplasms (0.33) and active treatment with hypomethylating agents (0.47) were associated with lower mortality. Overall, 574 (82%) patients received antiviral therapy. Mortality with severe/critical COVID-19 was higher with no therapy vs any antiviral combination therapy (2.20). CONCLUSIONS: In this series of patients with hematologic malignancies and COVID-19, mortality was associated with higher age, more comorbidities, type of hematological malignancy and type of antineoplastic therapy. Further studies and long-term follow-up are required to validate these criteria for risk stratification.

Paradoxical effect of SARS-CoV-2 infection in patients with immune thrombocytopenia.

Thrombocytopenia has been identified as a common complication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the general population. In an attempt to determine the impact of coronavirus disease 2019 (COVID-19) in patients with immune thrombocytopenia (ITP), a retrospective single-centre study was performed. Thrombocytosis was observed in patients with chronic ITP after SARS-CoV-2 infection, frequently needing treatment adjustment or even discontinuation of therapy. Relapses and newly diagnosed cases showed a fast response after initial treatment compared to ITP. Reduced immune activity due to lymphopenia during COVID-19 could explain this paradoxical effect, although further studies are needed.

What COVID-19 can mean for people with hemophilia beyond the infection risk.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic represents an unprecedented global health crisis. To combat its effects, many governments have opted for strategies of social isolation that involve a radical change in people's behavior. AREAS COVERED: For patients with hemophilia, the negative consequences of these measures can be greater, given they modify aspects of health care and lifestyles needed to counteract the adverse effects of hemophilia. The long-term consequences of the pandemic on patients with hemophilia are not well known. The aim of this special report is to show what COVID-19 could mean for this population, beyond the risk of infection. EXPERT OPINION: Considerations of the clinical, care, therapeutic, physical, nutritional, mental health, pain, and disability aspects that might be affected are included. Strategies are also suggested to minimize the effects that these issues can have on patients' lives. Patients, health professionals, and society as a whole must work together to mitigate the effects of the pandemic on people with hemophilia.

Registry of patients with congenital bleeding disorders and COVID-19 in Madrid.

INTRODUCTION: We present the first registry of patients with congenital bleeding disorders and COVID-19. The study has been carried out in the Community of Madrid, which has the highest number of cases in Spain. The objective is to understand the incidence of COVID-19, the course of the disease if it occurs and the psychosocial and occupational impact on this population. METHODS: We included 345 patients (246 of haemophilia, 69 of von Willebrand Disease, two rare bleeding disorders and 28 carriers of haemophilia). A telephone survey was used to collect the data. RESULTS: Forty-two patients presented symptoms suggestive of infection by COVID-19, and in six cases, the disease was confirmed by RT-PCR. The cumulative incidence of our series was 1.73%. It is worth noting the complexity of the management of COVID-19 in two patients on prophylaxis with non-factor replacement therapy. Adherence to the prescribed treatment was maintained by 95.5% of patients. Although 94% were independent for daily living activities, 42.4% had a recognized disability and 58% required assistance, provided by the Madrid Haemophilia Association (Ashemadrid) in 75% of cases. Only 4.4% of consultations were held in person. CONCLUSIONS: Patients with congenital bleeding disorders infected with SARS-CoV-2 presented a mild course of the disease that did not require admission. Their identification and treatment by a specialist team from a Haemophilia Treatment Center are essential to make a correct assessment of the risk of haemorrhage/thrombosis. COVID-19 had a major impact on the psychosocial aspects of these patients which must be remedied with recovery plans.

Managing the front-line treatment for diffuse large B cell lymphoma and high-grade B cell lymphoma during the COVID-19 outbreak.

The COVID-19 pandemic has dramatically challenged care for cancer patients, especially those with active treatment who represent a vulnerable population for SARS-CoV-2 infection. Aggressive lymphoid neoplasms, such as diffuse large B cell lymphoma and high-grade B cell lymphoma, need to be treated without delay in order to get the best disease outcome. Because of that, our clinical practice was changed to minimise the risk of SARS-CoV-2 infection while continuing haematological treatment. In this report, we analyse the management of front-line therapy in 18 patients during the COVID-19 outbreak, as well as the results of the implemented measures in their outcome.

Thromboprophylaxis in a patient with COVID-19 and severe hemophilia A on emicizumab prophylaxis.

COVID-19 can be associated with coagulopathy (CAC, COVID-19-associated coagulopathy) with a high prothrombotic risk based on an intense inflammatory response to viral infection leading to immunothrombosis through different procoagulant pathways. Emerging evidence suggests that the use of heparin in these patients could be associated with lower mortality. Emicizumab is a bispecific humanized monoclonal antibody that bridges activated factor IX and factor X, thereby restoring the function of missing factor VIIIa in hemophilia A. The use of emicizumab has been associated with thrombotic events in patients who also received high cumulative amounts of activated prothrombin complex concentrates. Although this risk is extremely low, there is a lack of evidence on whether CAC increases the thrombotic risk in patients on emicizumab prophylaxis. We present the case of a patient with severe hemophilia A in prophylaxis treatment with emicizumab; due to the potential thrombotic risk we decided to administer low molecular weight heparin as prophylaxis treatment without any thrombotic or bleeding complications.