Spotlight on the impact of viral infections on Hematopoietic Stem Cells (HSCs) with a focus on COVID-19 effects.

Hematopoietic stem cells (HSCs) are known for their significant capability to reconstitute and preserve a functional hematopoietic system in long-term periods after transplantation into conditioned hosts. HSCs are thus crucial cellular targets for the continual repair of inherited hematologic, metabolic, and immunologic disorders. In addition, HSCs can undergo various fates, such as apoptosis, quiescence, migration, differentiation, and self-renewal. Viruses continuously pose a remarkable health risk and request an appropriate, balanced reaction from our immune system, which as well as affects the bone marrow (BM). Therefore, disruption of the hematopoietic system due to viral infection is essential. In addition, patients for whom the risk-to-benefit ratio of HSC transplantation (HSCT) is acceptable have seen an increase in the use of HSCT in recent years. Hematopoietic suppression, BM failure, and HSC exhaustion are all linked to chronic viral infections. Virus infections continue to be a leading cause of morbidity and mortality in HSCT recipients, despite recent advancements in the field. Furthermore, whereas COVID-19 manifests initially as an infection of the respiratory tract, it is now understood to be a systemic illness that significantly impacts the hematological system. Patients with advanced COVID-19 often have thrombocytopenia and blood hypercoagulability. In the era of COVID-19, Hematological manifestations of COVID-19 (i.e., thrombocytopenia and lymphopenia), the immune response, and HSCT may all be affected by the SARS-CoV-2 virus in various ways. Therefore, it is important to determine whether exposure to viral infections may affect HSCs used for HSCT, as this, in turn, may affect engraftment efficiency. In this article, we reviewed the features of HSCs, and the effects of viral infections on HSCs and HSCT, such as SARS-CoV-2, HIV, cytomegalovirus, Epstein-Barr virus, HIV, etc. Video Abstract.

Immune system disturbances after a new coronavirus infection COVID-19.

During the pandemic, a large number of works devoted to COVID infection have appeared, which have made it possible to understand the pathogenetic features of the disease and to accumulate significant clinical experience. However, the question remains about the degree of participation of humoral and cellular (primarily T-cell) immunity in the mechanisms of immune defense and resistance to COVID-19, the individual features of the immune response in different subjects. Post-COVID syndrome is currently a separate diagnosis included in the ICD-10 International Classification of Diseases, but the long-term effects of the SARS-CoV-2 on the immune system are not yet well established. At the same time, a long-term increased activity of the immune system can contribute to the development of autoimmune reactions. The review of the literature presents the results of studies, mainly devoted to immune system disorders after COVID infection. The changes in subpopulations of T-lymphocytes, B-lymphocytes, their functional properties, the complement system and other factors of humoral immunity, as well as the production of a number of cytokines are described. Data on immune disorders in post-COVID syndrome and during the convalescence period are presented in detail. Since COVID-19 is an infection that has a significant impact on the hematopoietic system and hemostasis, special attention is paid to the category of subjects with an increased risk of severe complications. Among the latter are elderly patients, persons suffering from diabetes mellitus, oncological and oncohematological patients, in particular, with hematopoietic and lymphoid tissue neoplasia, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma. The review pays special attention to the peculiarities of the course of COVID-19 and the response of the immune system to vaccination in patients with oncohematological diseases. Deciphering the significance of individual links of cellular and humoral immunity in patients who have undergone COVID-19 is an important issue in creating effective vaccines and improving therapeutic methods.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

A Novel Case Report of Severe Aplastic Anemia with COVID Infection.

Aplastic anemia is a rare disease of the hematopoietic system. Although some viral agents have been implicated, the association between COVID-19 and aplastic anemia is unclear. In this way, several cases of aplastic anemia have been reported following infection with COVID-19. Importantly, we reported a 16-year-old girl with severe aplastic anemia with no history of disease following an Omicron infection who did not respond well to treatment despite supportive treatment and immunosuppression.

The Implications of COVID-19 Infection on Hematologic Parameters and Coagulation Activity: A Review

Wuhan, China, substantially is the epicenter of the COVID-19 pandemic in December 2019. Coronavirus, the confounder virus, a zoonotic in origin was the causative agent of the disseminated disease worldwide. Structural similarities and convergence points were demonstrated between the coronavirus, SARS, and MERS viruses. Aberrantly, a subset of patients developed a serious acute respiratory distress syndrome or diffuse alveolar injury whereas the rest of the patients encountered mild or no symptoms. The pathological clinical laboratory findings are not only critical in the diagnosis of the COVID-19 infection, on the contrary, but they are also crucial in the prognostic predictions about disease prognosis and therapeutic response. This review aims to give some historical context for the pandemic, demonstrate the laboratory's important role in the screening of COVID-19 infection, and review the current phase of biomarker examination in COVID-19 infection, focusing on markers derived directly from the hematological laboratory, reflecting the implications of COVID-19 on the hematological system and coagulation pathways. In conclusion, there is a direct significant correlation between infection severity, the death rate in COVID-19 patients, and the low number of either WBCs or a high number of WBCs with a low number of lymphocytes. Copyright This is an Open Access article licensed under a Creative Commons license: Attribution 4.0 International (CC-BY). Published by Oriental Scientific Publishing Company © 2022.

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.

[89Zr]Df-crefmirlimab PET/CT imaging to assess the in vivo distribution of CD8+ T-cells in hospitalized COVID-19 patients

Aim/Introduction: COVID-19 patients may present with lymphopenia. The degree of lymphopenia, in particular reduced CD8+ T-cell numbers, is strongly correlated with clinical deterioration and ICU admission [1,2]. It has been postulated that lymphopenia in COVID-19 is caused by;1) sequestration of CD8+ T-cells in peripheral tissues (e.g. lung) [3], 2) accelerated maturation and exhaustion [4,5] or 3) decreased lymphopoiesis [6]. The lack of data on in vivodistribution of CD8+ T-cells hampers a more thorough understanding of this critical prognostic factor. We aim to assess differences in the in vivo distribution of CD8+ T-cells in patients with proven SARS-CoV-2 presenting with lymphopenia or with normal lymphocyte counts, using [89Zr]Df-crefmirlimab PET/CT imaging. Material(s) and Method(s): This is a prospective, observational non-randomized pilot study in hospitalized patients with microbiologically proven SARS-CoV-2 infection. The prior use of immune suppressive medication was an exclusion criterion. Whole body [89Zr]Df-crefmirlimab PET/CT scan were acquired at 24 hrs after intravenous injection of 1.5mg protein dose labelled with 37 MBq (1 mCi)89Zr. Peripheral blood samples were collected for multi-colour flowcytometry to phenotype homing receptors and immune senescence markers, and transcriptomics. Result(s): Three patients were enrolled (all male, average 83 yrs (78-89 yrs)), admitted at 5.3 days (2-10 days) after onset of symptoms and scanned at 2.7 days (2-4 days) after admission. Two patients completed vaccination (2x plus booster), one patient was not vaccinated. Two patients had with lymphocyte count <1.0 x10e9/L and one patient had normal lymphocyte counts on admission. One patient required oxygen suppletion 3L/min. PET/CT scans showed remarkable differences in uptake in the upper respiratory tract versus lower respiratory tract, involvement of distant organs and distribution of CD8+ T-cells across secondary lymphoid organs, spleen and hematopoietic system. Quantification of the scans, flow cytometry and transcriptomic analyses are ongoing. Conclusion(s): In vivo imaging of CD8+ T-cells in hospitalized COVID-19 patients reveals distinct patterns of CD8+ T-cell distribution in early stages of localized infection versus systemic involvement at later stages. Translational data on T-cell phenotyping is currently processed and will be presented.

SARS-COV-2-INDUCED COAGULOPATHY DEMONSTRATING HEMORRHAGIC CARDIAC TAMPONADE: A TIGHT SQUEEZE

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: There is a growing volume of evidence of extrapulmonary manifestations of Coronavirus disease 2019 (COVID-19), particularly within the cardiovascular and hematological systems. In this case, we describe a unique manifestation of a COVID-19 presenting with a hemorrhagic pericardial effusion and cardiac tamponade physiology with a supratherapeutic international normalized ratio (INR). CASE PRESENTATION: A 68-year-old male with coronary artery disease and atrial fibrillation on warfarin presented to the emergency department with acutely worsening shortness of breath. Upon arrival, he was hypotensive, tachypneic, and hypoxic. Physical exam findings included jugular venous distention and muffled heart sounds. A transthoracic echocardiogram demonstrated a large concentric pericardial effusion with tamponade physiology (Figure 1). Pertinent initial laboratory values included an elevated INR of 6.1, a prolonged prothrombin time of 61.2 seconds, and an elevated D-dimer level of 5.34 mg/L (Table 1). The prolonged INR was reversed with prothrombin complex concentrate (PCC). Emergent pericardiocentesis yielded 1.7L of dark-bloody appearing fluid. Pericardial fluid analysis (Table 1) demonstrated over 2.4 million red blood cells and 3,650 total nucleated cells with 94% lymphocytes. Cultures and cytology were unrevealing. Given the profound lymphocytic component, a COVID-19 nasal swab was obtained and resulted positive. Prior to contracting COVID-19, the patient's weekly INR levels were consistently at goal. DISCUSSION: The global pandemic of the COVID-19 continues to identify extrapulmonary manifestations of the disease. A rising number of publications have implicated COVID-19 with causing myocarditis, pericardial effusions, and hemorrhagic cardiac tamponade(1). Hemorrhagic cardiac effusions are typically seen with malignancy, tuberculosis, trauma, recent cardiac procedures, post-myocardial infarction, and are also seen in Coxsackie viral infections. Multiple studies implicate COVID-19 interactions with oral-vitamin K antagonists as the cause of unpredictable INR's which can lead to spontaneous bleeding2. There are fewer than 10 reported instances of hemorrhagic pericardial effusions with tamponade physiology in COVID-19 patients;however, none of the other cases presented with a super-therapeutic INR. We are also the first to demonstrate a primary lymphocytic component of the pericardial fluid suggesting viral etiology. Profound coagulopathies in COVID-19 result in an increased mortality(3). CONCLUSIONS: We propose that based on the increase in publications of case-reports describing COVID-19 viral infections and hemorrhagic pericardial effusions, that SARS-CoV-2 should be added to the list of known viral etiologies. Further, COVID-19 patients who are systemic anticoagulation with vitamin K antagonists should be monitored closely for abrupt changes in their INR. Reference #1: 1. Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nature Medicine. 2020;26(7):1017-1032. Reference #2: 2. Camilleri E, Van Rein N, Van Der Meer FJM, Nierman MC, Lijfering WM, Cannegieter SC. Stability of vitamin K antagonist anticoagulation after COVID-19 diagnosis. Research and Practice in Thrombosis and Haemostasis. 2021;5(7) Reference #3: 3. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis. 2020;18(4):844-847. DISCLOSURES: No relevant relationships by Gregory Hicks No relevant relationships by Daniel Kissau No relevant relationships by Andrew Labelle No relevant relationships by Scott Mayer No relevant relationships by Dmitriy Scherbak

Hematological profile of COVID-19 patients in Ramanagar district, Karnataka-A cross sectional study

Introduction and Aim: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which rapidly evolved into a pandemic infecting humans all over the world. Whether hematologic and immunologic responses play a crucial role in progression of COVID-19 is still not clear. Increasing scientific evidence has shown that abnormalities in routine hematological tests, have the potential to diagnose SARS-CoV-2 infection in an economical way. Major laboratory changes indicating systemic inflammation and multi-organ impairment including hematopoietic system leading to lymphocytopenia, neutrophilia, eosinopenia, mild thrombocytopenia and ratios derived from these hematological parameters indicated severe disease and/or fatal outcomes. The aim was to study the hematological profile of Covid-19 patients admitted at a tertiary care hospital at Ramanagar district. Materials and Methods: This retrospective study included 260 confirmed cases of Covid-19 diagnosed at a tertiary health care centre. Demographic, clinical, laboratory, treatment, and outcome data were extracted from the institutional electronic medical records after obtaining permission from the concerned authorities. From CBC test results obtained neutrophil lymphocyte ratio was derived. Results: The present study revealed that majority of Covid positive patients presented with lymphopenia. While a significant association was observed between N/L ratio and disease severity, no significant association was seen between platelet count and severity of the disease. Conclusion: Since the results of the present study features lymphopenia among large proportion of patients and elevated N/L ratio among critically ill patients these markers could be utilized as useful prognostic indicators during the initial assessment of disease severity and thus appropriate management can be planned for such patients before the condition of the patient deteriorates.

Perinatally Acquired COVID-19 Requiring ECMO with Severe Hematologic Complications

Case Report: Perinatal acquisition of COVID-19 in neonates is uncommon and development of severe pulmonary disease remains extremely rare. Thus far, there have been no reports of otherwise healthy neonates requiring extracorporeal life support (ECLS) for ARDS secondary to COVID-19. Further, little is known about the hematologic implications of COVID-19 in the neonatal population. We report the first perinatally acquired case of COVID-19 requiring ECLS and describe associated hematologic complications. The patient was a 35-week gestational age twin infant, born to an asymptomatic COVID-19 positive mother. The infant was COVID-19 PCR positive just after birth, though asymptomatic. She presented on day of life 9 with respiratory distress and hypoxia. She had progressive respiratory failure and at 2 weeks of life was placed on veno-venous (VV) extracorporeal life support (ECLS). On post-operative day 1 there was development of a bi-atrial clot requiring open thrombectomy and conversion to veno-arterial (VA) ECLS with an open chest. Three days post-thrombectomy, despite therapeutic anticoagulation with heparin, the circuit oxygenator developed significant clot burden leading to oxygenator failure and requiring circuit change. Five days post-thrombectomy, patient developed severe, persistent hemorrhage after chest closure despite discontinuation of heparin anti-coagulation therapy and was transitioned to comfort care per parental request. Whole exome sequencing was negative with no evidence of innate hematologic disease. Conclusion: This case highlights the rare, though significant, risk COVID-19 infection can potentially impose on pulmonary and hematologic systems of an infected neonate.

A case of multi-system inflammatory syndrome in children presenting as acute cervical lymphadenitis

Case Report Multi-system inflammatory syndrome in children (MIS-C) is a recently described clinical syndrome in children that continues to progress in its manifestations. The syndrome is associated with the novel coronavirus disease 2019 (COVID-19), and can affect any organ system in the body, leading to a wide variety of symptoms. This syndrome is often misdiagnosed in its initial presentation, and many families require multiple evaluations before finally being diagnosed and admitted for the appropriate treatment. Symptoms are caused by overwhelming inflammation and often involve the gastrointestinal, integumentary, cardiac, and hematologic systems. A high index of suspicion at the time of initial presentation should be maintained to obtain an accurate diagnosis of MIS-C. Patient Case We report the case of a previously healthy 11-year-old male who presents with acute cervical lymphadenitis that did not respond to appropriate outpatient antibiotic therapy. He has a history of testing positive for SARS-CoV-2 via PCR, associated with mild cough and rhinorrhea, about three weeks prior to the onset of current symptoms. Upon initial presentation physical exam and laboratory results were not consistent with MIS-C, however inflammatory markers were slightly elevated which was consistent with a diagnosis of cervical lymphadenitis. Over the course of the next several days, the patient developed gastrointestinal symptoms including abdominal pain, vomiting and diarrhea. He also developed non-purulent conjunctivitis, and a generalized erythematous rash, associated with significant leukocytosis, transaminitis, and elevated coagulation markers. His electrocardiogram (EKG), and echocardiogram (ECHO) remained within normal limits despite elevated pro-BNP levels, and he later developed significant hypotension, hypoxemia, and bilateral pleural effusions requiring a short course of diuretics. The patient remained febrile despite receiving a normal saline bolus, treatment with intravenous immune globulin (IVIG), and intravenous steroids. He had ongoing symptoms, and the erythematous rash reappeared. His steroid dose was increased, and the patient had a good response in both labs, and clinical status. Leukocytosis has continued, but there is significant improvement in all other inflammatory markers, and the patient is on course to be discharged home safely. Conclusion Many patients are unfortunately misdiagnosed after multiple evaluations before the final diagnosis of MIS-C is made. Multi-system inflammatory syndrome in children (MISC) may mimic other conditions such as gastroenteritis, acute appendicitis, Kawasaki Disease, sepsis, or even lymphadenitis. Clinicians should be alert to subtle signs of inflammation, such as lymphadenitis, that may progress to more classic symptoms of MIS-C such as persistent fever, abdominal pain, and a rash.