Applying principles of patient blood management during COVID-19 pandemic: a literature review

As of 15 December 2021, coronavirus disease 2019 (COVID-19) affected approximately 271 million and killed 5.3 million people globally. COVID-19 pandemic had a tremendous impact on world healthcare systems and blood supply. While principles of patient blood management (PBM) may have been previously implemented in many jurisdictions, their widespread adoption has become imperative during the pandemic. This review will discuss the impact of the COVID-19 pandemic on the Canadian blood supply and how the principles of PBM could be applied during a pandemic or other disruptions to healthcare delivery or blood supply. We described the local blood system and how it adapted during the pandemic. We also included a discussion of pandemic-associated local PBM challenges and solutions. We conducted a brief review of English language literature with a specific focus on the application of PBM to reduce unnecessary red blood cell (RBC) transfusions in elective major surgery, hematological malignancies, elective major gynecological surgery and obstetrics between January 2020 and April 2022. The common themes included anemia diagnosis and management, restrictive RBC transfusion strategies and reduction in blood loss. Anemia is common, is frequently caused by iron deficiency and can be treated with oral or intravenous iron. Erythropoiesis stimulating agents are effective in raising hemoglobin and may be indicated in certain perioperative settings. Evidence supports the use of restrictive RBC transfusion thresholds and single unit transfusions in most patient populations. Hemostatic therapy, such as tranexamic acid, is generally safe and effective in reducing bleeding. Diagnostic phlebotomy contributes to anemia and should be restricted to tests that are necessary and likely to change management. In conclusion, PBM interventions are generally effective and safe. Prioritization of PBM during the pandemic or a blood shortage may help sustain the blood supply and lead to improved patient outcomes.Copyright © Annals of Blood. All rights reserved.

Diamond-blackfan anemia in an adult

Case Report: A 25-year-old woman with history of Diamond-Blackfan anemia (DBA) presented with a 3- week history of weakness and fatigue. The patient was in her usual state of health until 3 weeks prior when she was diagnosed with COVID-19, at which time she experienced cough, congestion, weakness, and fatigue. She reported that the cough and congestion improved after a few days, but the fatigue and weakness progressively worsened. Admission labs were notable for a hemoglobin of 5.5 g/dL with a MCV of 119.3 fL. She received 2 units of packed RBCs with improvement in hemoglobin to 8.9 g/dL. The patient was diagnosed with DBA at birth via bone marrow biopsy and had been stable on chronic prednisone with a baseline hemoglobin around 8 g/dL. Prior to this admission, she has only required one transfusion at 3 months old. Her outpatient management involved close monitoring of her hemoglobin and increasing/decreasing prednisone based on her trending hemoglobin. She had been stable on 15 mg/day of prednisone for the past few years. Her hematologist was consulted, and the decision was made to increase her dose of prednisone to 20 mg/day resulting in resolution of symptoms and stabilization of her hemoglobin level. Discussion(s): We present a rare case of DBA with worsening anemia in the setting of a recent COVID-19 infection. The literature regarding the risk and complications of COVID-19 in these patients is severely limited, with no current data on disease management, outcomes, or predictors of morbidity. DBA is a rare, congenital erythroid red cell aplasia that typically presents in infancy with an estimated incidence of 5 cases per 1 million births. DBA is characterized by progressive macrocytic anemia, congenital malformations, and increased risk of endocrine dysfunction and malignancies. Glucocorticoids are the first-line therapy for DBA, although the exact mechanism of how they stimulate erythropoiesis in DBA remains unknown. In terms of patient prognosis, approximately 40% are steroid-dependent, 40% are transfusiondependent, and 20% go into remission by age 25 years. Copyright © 2023 Southern Society for Clinical Investigation.

Recent updates of stem cell-based erythropoiesis.

Blood transfusions are now an essential part of modern medicine. Transfusable red blood cells (RBCs) are employed in various therapeutic strategies; however, the processes of blood donation, collection, and administration still involve many limitations. Notably, a lack of donors, the risk of transfusion-transmitted disease, and recent pandemics such as COVID-19 have prompted us to search for alternative therapeutics to replace this resource. Originally, RBC production was attempted via the ex vivo differentiation of stem cells. However, a more approachable and effective cell source is now required for broader applications. As a viable alternative, pluripotent stem cells have been actively used in recent research. In this review, we discuss the basic concepts related to erythropoiesis, as well as early research using hematopoietic stem cells ex vivo, and discuss the current trend of in vitro erythropoiesis using human-induced pluripotent stem cells.

Coronavirus disease 2019 is associated with multi-lineage, morphologic changes in peripheral blood cells

Introduction: The clinical course of coronavirus disease 2019 (COVID-19) varies from mild symptoms to acute respiratory distress syndrome, hyper-infammation and coagulation disorder. The hematopoietic system plays a critical role in the observed hyperinfammation, particularly in severely ill patients. Method(s): We conducted a prospective diagnostic study performing a blood differential analyzing morphologic changes in peripheral blood of COVID-19 patients. COVID-19 associated morphologic changes were defned in a training cohort and subsequently validated in a second cohort (n=45). Morphologic aberrations were further analyzed by electron microscopy (EM) and fow cytometry of lymphocytes was performed. Result(s): We included 45 COVID-19 patients in our study (median age 58 years;82% on intensive care unit). The blood differential showed a specific pattern of pronounced multi-lineage aberrations in lymphocytes (80% of patients) and monocytes (91%). 84%, 98%, and 98% of patients exhibited aberrations in granulopoiesis, erythropoiesis and thrombopoiesis, respectively. Electron microscopy revealed the ultrastructural equivalents of the observed changes and confrmed the multi-lineage aberrations already seen by light microscopy. Conclusion(s): The morphologic pattern caused by COVID-19 is characteristic and underlines the serious perturbation of the hematopoietic system. We defned a hematologic COVID-19 pattern to facilitate further independent diagnostic analysis and to investigate the impact on the he-matologic system during the clinical course of COVID-19 patients.

Predictive Value of Red Cell Distribution Width at Admission as A Marker Of ICU Requirement in COVID-19 Infection

Introduction: COVID-19 is a global pandemic disease first identified in Wuhan, China in late 2019. As of March 2022, over 450 million cases and 6 million deaths have been reported across the world, with the confirmed numbers probably being a fraction of the real numbers. Red Cell Distribution width (RDW) is a measure of anisocytosis, that is, variation in the circulating red blood cell volume. It is a nonspecific marker of acute illness. Increased RDW is suggestive of dysfunctional erythropoiesis and/or shortened RBC lifespan. Hence, it is a good predictor of clinical outcome in many disorders. Aims & Objectives: AIMS: To prove association of RDW with COVID-19 infection requiring ICU stay in a tertiary care hospital. OBJECTIVE(S): Primary Objective: To assess the predictive value of RDW on admission with requirement of ICU as a marker of severity in COVID-19 patients. Secondary Objectives: To compare RDW to other markers commonly used in COVID-19 infection, such as D-Dimer and CRP. Material(s) and Method(s): Patients over 18 years of age getting admitted at COVID ward or ICU at P.D. Hinduja Hospital, Mumbai were included in the study. RDW, CRP and D-dimer values of Ward group and ICU group patients were noted and compared. Result(s): 234 patients were screened and 190 patients were included in the final study. RDW was found to have significant association with ICU requirement (p = 0.0066). Further, an RDW value of 13 or more is found to be 85% sensitive for predicting ICU requirement. RDW of 16 or more is found to be 80% specific for predicting requirement of ICU stay. Regarding secondary objectives, RDW was found to have significant correlation with D-Dimer (p = 0.0005) but not with CRP (p = 0.12). Conclusion(s): RDW can be a potentially useful marker for risk stratification in COVID-19. A value of RDW more than 16 is associated with a significant risk of ICU requirement in COVID-19 disease. Further studies may be indicated to find a statistically significant correlation between RDW values and mortality in COVID- 19.

Hemoglobin and Clinical Outcomes in Hemodialysis: An Analysis of US Medicare Data From 2018 to 2020.

Rationale & Objective: Anemia management in patients treated with maintenance dialysis remains a challenge. We sought to update information in this area by evaluating the association between hemoglobin and various outcome and utilization measures using data-rich Medicare sources. Study Design: Observational cohort study using data from the Consolidated Renal Operations in a Web-enabled Network and Medicare claims. Setting & Participants: We studied 371,250 prevalent patients treated with hemodialysis, covering 3,326,072 patient-months in 2019. Exposure: Monthly patient hemoglobin concentrations. Outcomes: We examined several outcomes, including mortality, all-cause hospitalization, cause-specific hospitalization, and emergency department utilization in the month following the exposure measurement. Analytical Approach: For each monthly observation period, we calculated unadjusted and adjusted (for demographics and comorbid condition) hazard ratios using Cox regression. Results: The hemoglobin concentration was <10.5 g/dL for 40% of observations. We found an inverse association between mortality and hemoglobin measured over a range from <9 g/dL (HR, 2.53; 95% CI, 2.45-2.61; P < 0.0001, reference = 10.5-11 g/dL) to 11-11.5 g/dL (HR, 0.92; 95% CI, 0.89-0.96; P < 0.0001). Mortality risk started to increase at hemoglobin levels >11.5 g/dL. All-cause hospitalization, cause-specific hospitalization (including cardiovascular, infection, and several subcategories including coronavirus disease 2019 hospitalization), and emergency department utilization were inversely associated with hemoglobin concentration, with risk reduction stabilizing at hemoglobin levels of approximately 11.5-12 g/dL and higher. Limitations: As with prior observational studies, the observed associations are not necessarily causal. Conclusions: In a large US hemodialysis population, there were better clinical outcomes at higher hemoglobin concentrations over short exposure and follow-up periods, consistent with other observational studies that generally used longer exposure and follow-up times. Mortality risk increased at hemoglobin concentrations >11.5 g/dL, consistent with findings from erythropoiesis-stimulating agent clinical trials. The apparently beneficial short-term effects associated with higher hemoglobin concentrations suggest that hemoglobin measurements capture unmeasured elements of patient risk.

Haematological Malignancy Presenting in an Unusual Manner

Chronic lymphocytic leukaemia is a haematological malignancy that occurs due to an increased proliferation of mature B lymphocytes. It is considered to be the most common leukaemia in adults. Hyponatremia is commonly seen in such patients. This case report is about a 75-year-old male, who presented with giddiness, followed by altered sensorium. However, the patient had no motor weakness or sensory loss. Initially, a diagnosis of posterior circulation stroke was made but Magnetic Resonance Imaging (MRI) brain did not show associated signs. The routine investigations showed highly elevated total leukocyte count and hyponatremia. The patient was worked up for malignancy and diagnosed with Chronic lymphocytic leukaemia. Oncology reference was taken and treated with tablet Ibrutinib. On discharge, the patient's mentation improved, and he is on regular follow-up.

Differential Impact of SARS-CoV-2 Isolates, Namely, the Wuhan Strain, Delta, and Omicron Variants on Erythropoiesis.

SARS-CoV-2 variants exhibit different viral transmissibility and disease severity. However, their impact on erythropoiesis has not been investigated. Here, we show SARS-CoV-2 variants differentially affect erythropoiesis. This is illustrated by the abundance of CD71+ erythroid cells (CECs) in the blood circulation of COVID-19 patients infected with the original Wuhan strain followed by the Delta and Omicron variants. We observed the CD45+CECs are the dominant subpopulation of CECs expressing the receptor, ACE2, and coreceptor, TMPRSS2, and thus, can be targeted by SARS-CoV-2. Also, we found CECs exhibit immunosuppressive properties, specifically CD45+CECs are the dominant immunosuppressive cells and via reactive oxygen species (ROS) and arginase I expression can impair CD8+ T cell functions. In agreement, we observed CECs suppress CD8+ T cell effector (e.g., Granzyme B expression and degranulation capacity [CD107]), which was partially but significantly reversed with l-arginine supplementation. In light of the enriched frequency of CECs, in particular, CD45+CECs in patients infected with the original (Wuhan) strain, we believe this strain has a more prominent impact on hematopoiesis compared with the Delta and Omicron variants. Therefore, our study provides an important insight into the differential impact of SARS-CoV-2 variants on erythropoiesis in COVID-19 patients. IMPORTANCE Silent hypoxia has been the hallmark of SARS-CoV-2 infection. Red blood cells (RBCs) work as gas cargo delivering oxygen to different tissues. However, their immature counterparts reside in the bone marrow and normally absent in the blood circulation. We show SARS-CoV-2 infection is associated with the emergence of immature RBCs so called CD71+ erythroid cells (CECs) in the blood. In particular, we found these cells were more prevalent in the blood of those infected with the SARS-CoV-2 original strain (Wuhan) followed by the Delta and Omicron variants. This suggests SARS-CoV-2 directly or indirectly impacts RBC production. In agreement, we observed immature RBCs express the receptor (ACE2) and coreceptor (TMPRSS2) for SARS-CoV-2. CECs suppress T cells functions (e.g., Granzyme B and degranulation capacity) in vitro. Therefore, our study provides a novel insight into the differential impact of SARS-CoV-2 variants on erythropoiesis and subsequently the hypoxia commonly observed in COVID-19 patients.

Hematopoietic responses to SARS-CoV-2 infection.

Under physiological conditions, hematopoietic stem and progenitor cells (HSPCs) in the bone marrow niches are responsible for the highly regulated and interconnected hematopoiesis process. At the same time, they must recognize potential threats and respond promptly to protect the host. A wide spectrum of microbial agents/products and the consequences of infection-induced mediators (e.g. cytokines, chemokines, and growth factors) can have prominent impact on HSPCs. While COVID-19 starts as a respiratory tract infection, it is considered a systemic disease which profoundly alters the hematopoietic system. Lymphopenia, neutrophilia, thrombocytopenia, and stress erythropoiesis are the hallmark of SARS-CoV-2 infection. Moreover, thrombocytopenia and blood hypercoagulability are common among COVID-19 patients with severe disease. Notably, the invasion of erythroid precursors and progenitors by SARS-CoV-2 is a cardinal feature of COVID-19 disease which may in part explain the mechanism underlying hypoxia. These pieces of evidence support the notion of skewed steady-state hematopoiesis to stress hematopoiesis following SARS-CoV-2 infection. The functional consequences of these alterations depend on the magnitude of the effect, which launches a unique hematopoietic response that is associated with increased myeloid at the expense of decreased lymphoid cells. This article reviews some of the key pathways including the infectious and inflammatory processes that control hematopoiesis, followed by a comprehensive review that summarizes the latest evidence and discusses how SARS-CoV-2 infection impacts hematopoiesis.

A Phase 2a Study Evaluating the Safety and Pharmacokinetics (PK) of Luspatercept in Pediatric Patients with Transfusion-Dependent β-Thalassemia (TDT)

Background: β-thalassemia is an inherited hemoglobinopathy caused by mutations in the gene encoding the β-globin chain of hemoglobin (Hb), resulting in ineffective erythropoiesis, impaired red blood cell (RBC) maturation, and anemia. Patients (pts) with severe disease require regular, lifelong RBC transfusions and iron chelation therapy (ICT) shortly after diagnosis in early childhood. There is an unmet need for safe and effective treatments for pediatric pts to address the underlying pathophysiology of β-thalassemia and reduce the burden of chronic RBC transfusions early to prevent secondary iron overload and associated morbidity. Luspatercept is a first-in-class erythroid maturation agent approved in the USA and EU for the treatment of anemia in adult pts with β-thalassemia who require regular RBC transfusions. In previous studies, treatment with luspatercept resulted in clinically significant reductions in RBC transfusion burden in adults with TDT (phase 3 BELIEVE;Cappellini MD, et al. N Engl J Med 2020;382:1219-1231) and increased Hb levels in adults with non-TDT (phase 2 BEYOND study;Taher AT, et al. HemaSphere 2021;5[Suppl 2];S101). This phase 2a study (NCT04143724, EudraCT 2019-000208-13) will evaluate the safety and PK of luspatercept in pediatric pts with β-thalassemia who require regular RBC transfusions. The results will determine a recommended dose (RD) for each age group. Study Design and Methods: Eligible pts will be 6 to < 18 years of age;diagnosed with β-thalassemia, Hb E/β-thalassemia, or α-thalassemia/β-thalassemia;require ≥ 4 RBC units in the 24 weeks prior to enrollment (with no transfusion-free period ≥ 42 days and with a regular history of transfusions for ≥ 2 years);and have Karnofsky (≥ 16 years of age) or Lansky (< 16 years of age) performance status score ≥ 50 at baseline. Exclusion criteria include: a Hb S/β-thalassemia or α-thalassemia diagnosis, chronic anticoagulant therapy ≤ 28 days prior to enrollment, erythropoiesis-stimulating agent or hydroxyurea use ≤ 24 weeks prior to enrollment, ICT initiation ≤ 8 weeks prior to enrollment, use of any investigational drug ≤ 28 days prior to enrollment, or have undergone or are scheduled for transplant or gene therapy. A total of 54 pts will be enrolled in a staggered study design by age, beginning with a 12-week screening/run-in period. During Part A, pts 12 to < 18 years of age will receive luspatercept at 0.75 mg/kg (n = 6;Cohort 1) or 1.0 mg/kg (n = 6;Cohort 2) subcutaneously (s.c.) once every 21 days for ≤ 4 cycles (Figure A). The RD will be determined for each age group strata at the time of enrollment using descriptive statistics or frequency tabulations between and in aggregate across age-group arms. An expansion cohort (n = 30 pts 12 to < 18 years of age;Cohort 3) will then receive luspatercept for at least 1 year at the RD based on tolerability and safety data from Cohorts 1 and 2;if the RD is 1 mg/kg, titration up to 1.25 mg/kg is allowed in the expansion cohort based on erythroid response during the previous 2 dose cycles. Part B will be initiated following completion of Part A and review of overall safety data with the Data Monitoring Committee, Scientific Steering Committee, and health authorities. Pts 6 to < 12 years of age will be treated with luspatercept at 1.0 mg/kg (n = 6;Cohort 4) or 1.25 mg/kg (n = 6;Cohort 5) s.c. once every 21 days for ≤ 4 cycles (Figure B). Any pt who benefits from treatment can continue to receive luspatercept for ≤ 5 years from first dose and will be monitored for 5 years from first dose or 3 years from last dose, whichever occurs later. Pts may receive best supportive care, including RBC transfusions, ICT, antibiotics, antifungal or antiviral therapy, and/or nutritional support, as needed. The primary objectives are to determine the RD of luspatercept that is safe and tolerable and the PK of luspatercept in pediatric pts with TDT. Key secondary objectives include evaluating mean change in RBC transfusion burden, change in Hb levels, mean change in daily dose of ICT, mean change in serum ferritin, and the immunogenicity and safety of luspatercept in pediatric pts. Safety endpoints include evaluating the type, frequency, seriousness, and severity of adverse events and their relationship to luspatercept treatment. Exploratory endpoints include evaluating exposure-response, health-related quality of life, biomarkers/markers of iron overload and ineffective erythropoiesis, and SARS-CoV-2 serology. [Formula presented] Disclosures: Viprakasit: Bristol Myers Squibb: Research Funding. Coates: Celgene: Consultancy, Honoraria, Research Funding;Forma Pharma: Consultancy;Sangamo: Consultancy;UpToDate: Patents & Royalties;Vifor Pharma: Consultancy;Apo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Bluebird Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Chiesi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Musallam: Celgene, Bristol Myers Squibb: Consultancy;Novartis: Consultancy;Agios Pharmaceuticals: Consultancy;CRISPR Therapeutics: Consultancy;Vifor Pharma: Consultancy. Vienne Buerki: Bristol Myers Squibb: Current Employment. Patturajan: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Holot: Bristol Myers Squibb: Current Employment. Aydinok: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Bristol Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding;Resonance Health: Research Funding;CRISPR Therapeutics: Consultancy;SLN Therapeutics: Consultancy;Imara: Research Funding;Protagonist: Membership on an entity's Board of Directors or advisory committees, Research Funding;Ionis Pharmaceuticals: Research Funding;La Jolla: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Differential Redox State and Iron Regulation in Chronic Obstructive Pulmonary Disease, Acute Respiratory Distress Syndrome and Coronavirus Disease 2019.

In patients affected by Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD) and Coronavirus Disease 2019 (COVID-19), unclear mechanisms negatively interfere with the hematopoietic response to hypoxia. Although stimulated by physiological hypoxia, pulmonary hypoxic patients usually develop anemia, which may ultimately complicate the outcome. To characterize this non-adaptive response, we dissected the interplay among the redox state, iron regulation, and inflammation in patients challenged by either acute (ARDS and COVID-19) or chronic (COPD) hypoxia. To this purpose, we evaluated a panel of redox state biomarkers that may integrate the routine iron metabolism assays to monitor the patients' inflammatory and oxidative state. We measured redox and hematopoietic regulators in 20 ARDS patients, 20 ambulatory COPD patients, 9 COVID-19 ARDS-like patients, and 10 age-matched non-hypoxic healthy volunteers (controls). All the examined pathological conditions induced hypoxia, with ARDS and COVID-19 depressing the hematopoietic response without remarkable effects on erythropoietin. Free iron was higher than the controls in all patients, with higher levels of hepcidin and soluble transferrin receptor in ARDS and COVID-19. All markers of the redox state and antioxidant barrier were overexpressed in ARDS and COVID-19. However, glutathionyl hemoglobin, a candidate marker for the redox imbalance, was especially low in ARDS, despite depressed levels of glutathione being present in all patients. Although iron regulation was dysfunctional in all groups, the depressed antioxidant barrier in ARDS, and to a lesser extent in COVID-19, might induce greater inflammatory responses with consequent anemia.

The role of CD71+ erythroid cells in the regulation of the immune response.

Complex regulation of the immune response is necessary to support effective defense of an organism against hostile invaders and to maintain tolerance to harmless microorganisms and autoantigens. Recent studies revealed previously unappreciated roles of CD71+ erythroid cells (CECs) in regulation of the immune response. CECs physiologically reside in the bone marrow where erythropoiesis takes place. Under stress conditions, CECs are enriched in some organs outside of the bone marrow as a result of extramedullary erythropoiesis. However, the role of CECs goes well beyond the production of erythrocytes. In neonates, increased numbers of CECs contribute to their vulnerability to infectious diseases. On the other side, neonatal CECs suppress activation of immune cells in response to abrupt colonization with commensal microorganisms after delivery. CECs are also enriched in the peripheral blood of pregnant women as well as in the placenta and are responsible for the regulation of feto-maternal tolerance. In patients with cancer, anemia leads to increased frequency of CECs in the peripheral blood contributing to diminished antiviral and antibacterial immunity, as well as to accelerated cancer progression. Moreover, recent studies revealed the role of CECs in HIV and SARS-CoV-2 infections. CECs use a full arsenal of mechanisms to regulate immune response. These cells suppress proinflammatory responses of myeloid cells and T-cell proliferation by the depletion of ʟ-arginine by arginase. Moreover, CECs produce reactive oxygen species to decrease T-cell proliferation. CECs also secrete cytokines, including transforming growth factor ß (TGF-ß), which promotes T-cell differentiation into regulatory T-cells. Here, we comprehensively describe the role of CECs in orchestrating immune response and indicate some therapeutic approaches that might be used to regulate their effector functions in the treatment of human conditions.

Human Erythroid Progenitors Are Directly Infected by SARS-CoV-2: Implications for Emerging Erythropoiesis in Severe COVID-19 Patients.

We document here that intensive care COVID-19 patients suffer a profound decline in hemoglobin levels but show an increase of circulating nucleated red cells, suggesting that SARS-CoV-2 infection either directly or indirectly induces stress erythropoiesis. We show that ACE2 expression peaks during erythropoiesis and renders erythroid progenitors vulnerable to infection by SARS-CoV-2. Early erythroid progenitors, defined as CD34-CD117+CD71+CD235a-, show the highest levels of ACE2 and constitute the primary target cell to be infected during erythropoiesis. SARS-CoV-2 causes the expansion of colony formation by erythroid progenitors and can be detected in these cells after 2 weeks of the initial infection. Our findings constitute the first report of SARS-CoV-2 infectivity in erythroid progenitor cells and can contribute to understanding both the clinical symptoms of severe COVID-19 patients and how the virus can spread through the circulation to produce local inflammation in tissues, including the bone marrow.