Retrospective Review of Outcomes of Multiple Myeloma (MM) Patients With COVID-19 Infection (Two-Center Study).

INTRODUCTION: COVID-19 has profound effects on patients with multiple myeloma (MM) mainly due to underlying immune dysfunction and associated therapies leading to increased susceptibility to infections. The overall risk of morbidity and mortality (M&M) in MM patients due to COVID-19 infection is unclear with various studies suggesting case fatality rate of 22% to 29%. Additionally, most of these studies did not stratify patients by their molecular risk profile. METHODS: Here, we aim to investigate the effects of COVID-19 infection with associated risk factors in MM patients and the effectiveness of newly implemented screening and treatment protocols on outcomes. After obtaining institutional review board approvals from each participating institution, we collected data from MM patients diagnosed with SARS-CoV-2 infection from March 1, 2020, to October 30, 2020, at 2 myeloma centers (Levine Cancer Institute & University of Kansas medical center). RESULTS: We identified a total of 162 MM patients who had COVID-19 infection. The majority of patients were males (57%) with a median age of 64 years. Most patients had an associated comorbid condition. Their myeloma disease status and prior autologous stem cell transplant at the time of infection had no impact on hospitalization or mortality. In univariate analysis, chronic kidney disease, hepatic dysfunction, diabetes, and hypertension were associated with an increased risk of hospitalization. In multivariate analysis regarding survival, increased age and lymphopenia were associated with increased COVID-19-related mortality. CONCLUSION: Our study supports the use of infection mitigation measures in all MM patients, and adjustment of treatment pathways in MM patients diagnosed with COVID-19.

Allogeneic transplant following CAR T-cell therapy for large B-cell lymphoma.

Allogeneic hematopoietic cell transplantation (alloHCT) can potentially salvage large B-cell lymphoma (LBCL) patients experiencing treatment failure after chimeric antigen receptor T-cell therapy (CAR-T). Nonetheless, data on the efficacy and toxicities of alloHCT after receipt of CAR-T are limited. We report a multicenter retrospective study assessing the safety, toxicities, and outcomes of alloHCT in LBCL patients following CAR-T failure. Eighty-eight patients with relapsed, refractory LBCL received an alloHCT following anti-CD19 CAR-T failure. The median number of lines of therapy between CAR-T infusion and alloHCT was 1 (range 0-7). Low intensity conditioning was used in 77% (n=68) and peripheral blood was the most common graft source (86%, n=76). The most common donor types were matched unrelated donor (39%), followed by haploidentical (30%) and matched related donor (26%). Median follow-up of survivors was 15 months (range 1-72). One-year overall survival, progression-free survival, and graft-versus-host disease-free relapse-free survival were 59%, 45%, and 39% respectively. One-year non-relapse mortality and progression/relapse were 22% and 33% respectively. On multivariate analysis.

Neutralizing antibody responses against SARS-CoV-2 in patients with plasma cell disorders who are on active treatment after two doses of mRNA vaccination.

Many patients with plasma cell disorder (PCD) on active treatment with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) require hospitalization, with an increased mortality rate over healthy adults. The FDA approved two mRNA vaccines against SARS-CoV-2: BNT162b2 and mRNA-1273. To assess the efficacy of vaccination in patients with PCD, retrospectively, we identified all patients on active treatment. A total of 149 patients were included. Neutralizing antibodies (NAbs) levels against SARS-CoV-2 adequate, intermediate, and no response were observed in 42%, 32%, and 26%, respectively. Low NAbs were seen in patients on daratumumab combinations or anti-BCMA therapy, low lymphocytes, and low IgG levels. Twenty-three (15%) patients have SARS CoV-2, while 8% required hospitalization, majority of these patients had intermediate or no response based on NAbs levels. Therefore, checking NAbs may be clinically helpful in identifying patients' responses. Further prospective studies should ascertain the value of a third vaccine dose in this population.

COVID-19 Impact on Australian Patients with Substance Use Disorders: Emergency Department Admissions in Western Sydney before Vaccine Roll Out.

BACKGROUND: In this study, we determined the impact of the COVID-19 pandemic on Western Sydney patients with substance use disorders (SUD) by comparing emergency department (ED) admission rates before and after the onset of the COVID-19 pandemic and before the rollout of COVID-19 vaccination. METHODS: ED admission data for patients with SUD were retrieved from the local electronic medical record (eMR) on the hospital central database. ED data collected from 25 January to 25 July 2019 (before the COVID-19 pandemic) were compared with data from 25 January to 25 July 2020 (early pandemic). ED admission reasons were categorised based on the presenting complaints and ED diagnoses. RESULTS: Despite an overall reduction in ED admissions during the early pandemic, compared to the pre-pandemic period, admissions for patients with SUD increased significantly (1.7% to 3.4%, p < 0.01). ED admission rates related to infection (0.05% to 0.12%, p < 0.01), local infection (0.02% to 0.05%, p < 0.01), trauma (0.06% to 0.12%, p < 0.01), alcohol (0.01% to 0.03%, p < 0.05), and other issues (0.06% to 0.10%, p < 0.05) increased significantly among Indigenous patients with SUD. ED admission rates related to drugs (0.12% to 0.39%, p < 0.01), infection (0.21% to 0.34%, p < 0.01), local infection (0.07% to 0.18%, p < 0.01), gastrointestinal (0.15% to 0.23%, p < 0.05), trauma (0.14% to 0.25%, p < 0.01), alcohol (0.36% to 0.74%, p < 0.01), and 'other' issues (0.47% to 0.91%, p < 0.01) increased significantly among non-Indigenous patients with SUD. Four cases of COVID-19 were reported among these patients. CONCLUSIONS: There was an increase in ED admissions for patients with SUD in the initial six months of the COVID-19 pandemic (before vaccine rollout), mainly for drugs, systemic infection, local infection, trauma, and alcohol-related reasons. Now that most people in New South Wales have been vaccinated against COVID-19, a further study is needed to quantify the effect of the pandemic on patients with SUD in the post-vaccine era.

Impact of COVID-19 in hematopoietic stem cell transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients are at increased risk of mortality and morbidity with coronavirus disease 2019 (COVID-19) due to severe immune dysfunction. METHODS: A literature search was performed on PubMed, Cochrane, and Clinical trials.gov from the date of inception to 12/08/2021. We identified 19 original studies reporting data on COVID-19 in HSCT recipients after screening 292 articles. Data were extracted following preferred reporting items for systematic reviews and meta-analysis guidelines. Quality evaluation was done using the National Institutes of Health (NIH) quality assessment tool. Inter-study variance was calculated using Der Simonian-Laird Estimator. Pooled analysis was conducted using MetaXL. A random-effects model was used to estimate the proportions with 95% confidence intervals (CI). RESULTS: Of 6711 patients in 19 studies, 2031 HSCT patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were analyzed. The median age of patients was 56.9 (range 1-81.6) years, and 63% patients were men according to 14 studies. The median time from transplant to SARS-CoV-2 infection for autologous (auto) and allogeneic (allo) HSCT patients was 23.2 (0.33-350.5) months and 16.4 (0.2-292.7) months, respectively. The median follow-up time after COVID-19 diagnosis was 28 (0-262) days. The COVID-19 mortality rate was 19% (95% CI 0.15-0.24, I2  = 76%, n = 373/2031). The pooled mortality rate was 17% (95% CI 0.12-0.24, I2  = 78%, n = 147/904) in auto-HSCT patients and 21% (95% CI 0.16-0.25, I2  = 60%, n = 231/1103) in allo-HSCT patients. CONCLUSIONS: HSCT recipients have a high risk of mortality and clinical complications due to COVID-19. There is a need for ongoing vigilance, masks, and social distancing, vaccination, and aggressive management of SARS-CoV-2 infection in HSCT recipients.

Impact of SARS-CoV-2 in Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Recipients.

Coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic in March 2020, and has caused more than 600,000 deaths in the United States at the time of this report. Hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor T cell (CAR-T) therapy recipients have a higher risk of mortality with COVID-19 owing to profound immune dysregulation. In this study, we investigated the impact of SARS-CoV-2 in HCT/CAR-T therapy recipients. This single-center prospective study included all (n = 58) adult HCT/CAR-T recipients who were diagnosed with COVID-19 at the University of Kansas Medical Center between March 2020 and May 2021. Baseline and disease-related characteristics were ascertained from medical records. Data were analyzed using SPSS version 21 (IBM, Armonk, NY). Bivariate analyses, using the chi-square and t-test, and logistic regression analyses were conducted. The study included 58 HCT/CAR-T patients who acquired SARS-CoV-2 infection, including recipients of allogeneic HCT (n = 32), autologous HCT (n = 23), and CAR-T therapy (n = 3). The median patient age was 58 years (range, 24 to 77 years), and 64% were males. The median time from HCT/CAR-T therapy to SARS-CoV-2 infection was 17.7 months (range, 0.2 to 201.9 months), and 22% of the patients acquired SARS-CoV-2 within the first 100 days post-HCT/CAR-T therapy. The primary hematologic disorders were plasma cell (36%), myeloid (38%), and lymphoid (26%) malignancies. Myeloablative conditioning was performed in 62% of patients. Donors were autologous (45%), matched sibling (15%), matched unrelated (21%), and haploidentical (19%). Prior history of grade II-IV acute graft-versus-host disease (GVHD), active GVHD, and current immunosuppressive therapy (IST) was noted in 22%, 31%, and 36% of patients, respectively. Concurrent infections were observed in 19%. Lymphopenia (P = .049) and high serum ferritin concentration (P = .020) were associated with mortality. COVID-19 severity was mild in 50% of the patients, moderate in 22%, and severe in 28%. Clinical findings included pneumonia or abnormal chest imaging (in 50%), hypoxia (28%), intensive care unit admission (19%), and mechanical ventilation (10%). Therapies included remdesivir (in 41%), convalescent plasma (35%), dexamethasone (22%), monoclonal antibodies (19%), and tocilizumab (3%). The median duration of viral shedding (positive SARS-CoV-2 PCR) was 7.7 weeks (range, 2 to 18.7 weeks), and 2 patients had a persistent infection for >5 months post-CAR-T therapy. After a median follow-up of 6.1 months (range, 0.5-13.6 months), the mortality rate was 16% in all patients and 28% in allogeneic HCT recipients. Among 9 patients who died, the median survival after SARS-CoV-2 infection was 23 days (range, 14 to 140 days). In survivors with moderate-severe COVID-19, the median time to recovery was 4.2 weeks (range, 1.1 to 24.7 weeks). Among allogeneic HCT recipients, 5 (16%) developed subsequent pulmonary chronic GVHD necessitating systemic steroids and additional IST. Significant predictors of COVID-19 severity included allogeneic HCT (odds ratio [OR], 3.6, 95% confidence interval [CI], 1.2 to 10.8; P = .020), history of grade II-IV acute GVHD (OR, 4.6; 95% CI, 1.10 to 18.86; P = .036) and concurrent IST (OR, 5.9; 95% CI, 1.8 to 19.8; P = .004). HCT and CAR-T cell therapy recipients are at an increased risk of moderate-severe COVID-19 pneumonia and higher mortality with SARS-CoV-2 infection. Our findings confirm the need for continuing vigilance with social distancing and masks, vaccination prioritization, close monitoring, and aggressive treatment of HCT/CAR-T therapy recipients.

Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage. DISCUSSION: We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions. CONCLUSION: Evidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.