Managing severe warm autoimmune haemolytic anaemia after the SARS-Cov- 2 vaccine with emergency splenectomy and eculizumab

Autoimmune haemolytic anaemia (AIHA) is rare but described after the SARS-CoV- 2 Pfizer-BioNTech vaccine. We present a case of severe refractory warm AIHA after this vaccine, managed with emergency splenectomy and complement inhibition with eculizumab. A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and AIHA (aged 6 years) presented to his district general hospital with jaundice, dark urine, fatigue and chest discomfort 48 h after the first dose of SARS-CoV- 2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed haemoglobin (Hb) of 70 g/L and bilirubin of 98 mumol/L, which was treated as AIHA. The patient initially responded to prednisolone (1 mg/kg, 60 mg) but subsequently deteriorated and failed to respond to second-line rituximab (375 mg/m2) and two units of packed red blood cells (PRBC). By day 29 the patient had developed life-threatening anaemia culminating in a Hb of 35 g/L (after transfusion), lactate dehydrogenase (LD) of 1293 units/L and bilirubin of 228 mumol/L. This necessitated an immediate transfer to our tertiary centre for specialist support. Further investigations revealed a haptoglobin <0.1 g/L and direct antiglobulin test (DAT) strongly positive for IgG (4+) and negative for C3d. The peripheral blood film showed severe anaemia, nucleated red cells, anisocytosis and spherocytes with no autoagglutination, schistocytes or platelet clumps. Thrombocytopaenia (platelets 49 +/- 109/L) was present. Differentials were ruled out, such as paroxysmal nocturnal haemoglobinuria and heparin-induced thrombocytopaenia. HIV and hepatitis serology were negative, as were adenovirus, cytomegalovirus and Epstein-Barr virus PCR assays. A CT showed splenomegaly of 15.5 cm. Urinalysis found urobilinogen and bilirubin at high concentrations and negative urinary haemosiderin. Together, the investigations were consistent with warm AIHA. On day 29, four units of PRBC were transfused alongside 100 mg methylprednisolone and 1 g/kg IVIG. On day 30 the patient deteriorated despite the escalated treatment: Hb had only increased to 54 g/L, bilirubin was 200 mumol/L and LD was rising. Considering this life-threatening fulminant haemolysis, an emergency splenectomy was performed. This slowed haemolysis but did not completely ameliorate it: by day 33 the patient had received 15 units of PRBC. Thus, eculizumab, a terminal complement pathway inhibitor, was trialled to arrest intravascular haemolysis, alongside rituximab, repeat IVIG 1 g/kg, prednisolone 40 mg and tacrolimus 2 mg. This showed a favourable response, requiring less frequent transfusions and settling haemolysis. This case highlights the rare complication of warm AIHA with the SARS-CoV- 2 Pfizer-BioNTech vaccine, the use of emergency splenectomy for disease control, and the potential of eculizumab for refractory cases.

Development of warm autoimmune hemolytic anemia after initiation of Ruxolitinib in a patient with STAT1 gain-of-function mutation

Introduction: STAT1 gain-of-function (GOF) disease is associated with chronic mucocutaneous candidiasis (CMC) and a broad spectrum of infectious, inflammatory, and vascular manifestations. The Janus Kinase inhibitor ruxolitinib has been used successfully for CMC and autoimmune phenomena. We describe a case of warm autoimmune hemolytic anemia (WAIHA) in a patient with STAT1 GOF disease after initiating ruxolitinib. Case report: A 36-year-old man with STAT1 c.850G>A (p.Glu284Lys) mutation presented with CMC as well as recurrent viral and bacterial infections, lymphadenopathy, enteritis, nodular regenerative hyperplasia (NRH) and splenomegaly. Immune workup confirmed a combined immunodeficiency with hypogammaglobulinemia and T-cell lymphopenia. Ruxolitinib was initiated at 5 mg twice daily (due to pre-existing thrombocytopenia) with up titration over 3 months to 20 mg twice daily. He improved with weight gain, increased energy, resolution of chronic anemia, and improved lymphadenopathy and splenomegaly on imaging. Serum CXCL9 only minimally decreased from 4660 pg/ml to 3990 pg/ml. Soon after reaching ruxolitinib 20 mg twice daily, he developed JC viremia, prompting dose reduction to 15 mg BID. Within two weeks, he developed a non-COVID upper respiratory tract infection followed by fatigue, shortness of breath with ambulation, and dark urine. Emergency evaluation revealed warm antibody positive hemolytic anemia with a hemoglobin of 5 g/dL, and worsened thrombocytopenia. He was treated with blood transfusions, pulse steroids, and high-dose IVIG with stabilization but continued hemolysis. Due to the JC viremia, there was concern to give rituximab with increased PML risk. Bone marrow showed trilineage hematopoiesis, a mild increase in megakaryocytes and RBC precursors, and a loss of B-cell progenitors with retention of mature B cells. His B and T lymphocyte numbers had increased since prior to ruxolitinib, with a predominance of Tfh1-cells (58.7% of total Tfh-cells). He was started on sirolimus with a slow taper of prednisone with continued stable hemoglobin and platelets, and resolution of hemolysis after 3 months. Conclusion(s): To our knowledge, this is the first case of a STAT1 GOF patient developing WAIHA while receiving ruxolitinib therapy. Treatment choices were complicated by the risks of PML. Sirolimus combined with ruxolitinib allowed wean of corticosteroid and subsequent resolution of hemolysis.Copyright © 2023 Elsevier Inc.

Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.

Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India

Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objective(s): This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Material(s) and Method(s): This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Result(s): A total of 650 tests for COVID-19 were performed for 181 children;22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support;all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusion(s): Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.

Blood Transfusion in Covid-19 Patients: One Year Survey

Introduction: Due to the COVID-19 outbreak, many chronic patients and elective surgical procedures have been postponed to create spaces for the hospitalization of COVID-19 patients, raising issues related to this change. The objective of this study is to assess the effect of the COVID-19 pandemic on the demand for blood products transfusion. Materials ant methods: The study presents the results of a retrospective study of blood transfusions in COVID-19 patients admitted to the Constanta County Emergency Clinical Hospital. The period of study was January-December 2021. We compared the transfusion requirement for each type of blood component in COVID 19 patients versus patients with non-COVID pathology. Results and discussions: During 2021, we transfused 282 COVID-19 patients;150 patients had only Covid pneumonia (of which 19 patients with severe forms needed intensive care in ICU-Covid), and 132 patients had various co-morbidities. The maximum blood requests was registered in the period February - April 2021, with a peak of 63 patients in April 2021. The main co-morbidities in patients with Covid 19 were: severe anemia in patients with malignant hemopathies. Anemia at admission in patients with Covid pneumonia is reported in more than 40% of patients. Moderate anemia (Hb <11 g/dL) is considered as an independent risk factor for the severe course of COVID-19 infection and mortality in these patients. The transfusion requirement in these patients was greater than 1.43 RBC (units/patient), 0.81 Plasma units/patient, 0.40 Platelets concentrate units + single donor platelet concentrate units/patient, in accordance with the associated pathology. Conclusion(s): The most requested product was packed red blood cells, the correction of anaemia being an important factor in preventing the severe course of the disease. The platelet requirement was 0.15 units/patient, thrombocytopenia being present in patients with severe evolution of the infection (hospitalized in ICU-COVID). The most requested blood groups were O+ and A+. COVID-19 transfusion data will help plan and prepare for the use of blood resources during the pandemic.Copyright © 2022 Sevigean Ali et al., published by Sciendo.

Mixed Warm and Cold Autoimmune Hemolytic Anemia With Concomitant Immune Thrombocytopenia Following Recent SARS-CoV-2 Infection and Ongoing Rhinovirus Infection.

Mixed-type autoimmune hemolytic anemia (AIHA) is a term used to describe hemolysis occurring in the context of both warm and cold reactive autoantibodies to red blood cells. Immune thrombocytopenia (ITP) is an acquired form of thrombocytopenia potentially complicated by hemorrhage due to autoantibodies reactive with platelets and megakaryocytes. Diagnosis of ITP requires exclusion of other known causes of thrombocytopenia. AIHA and ITP may be primary disorders or associated with lymphoproliferative, autoimmune, or viral infections. Here, we report a rare case of simultaneous mixed-type autoimmune hemolytic anemia with immune thrombocytopenia following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection treated with Paxlovid followed by Rhinovirus infection.

The choice of new treatments in autoimmune hemolytic anemia: how to pick from the basket?

Autoimmune hemolytic anemia (AIHA) is defined by increased erythrocyte turnover mediated by autoimmune mechanisms. While corticosteroids remain first-line therapy in most cases of warm-antibody AIHA, cold agglutinin disease is treated by targeting the underlying clonal B-cell proliferation or the classical complement activation pathway. Several new established or investigational drugs and treatment regimens have appeared during the last 1-2 decades, resulting in an improvement of therapy options but also raising challenges on how to select the best treatment in individual patients. In severe warm-antibody AIHA, there is evidence for the upfront addition of rituximab to prednisolone in the first line. Novel agents targeting B-cells, extravascular hemolysis, or removing IgG will offer further options in the acute and relapsed/refractory settings. In cold agglutinin disease, the development of complement inhibitors and B-cell targeting agents makes it possible to individualize therapy, based on the disease profile and patient characteristics. For most AIHAs, the optimal treatment remains to be found, and there is still a need for more evidence-based therapies. Therefore, prospective clinical trials should be encouraged.

Severe Acute Hemolytic Anemia Post Covid Vaccination

Case Report: A 26-year-old woman with a history of warm autoimmune hemolytic anemia, immune thrombocytopenia, triple positive antiphospholipid syndrome, and chronic migraine presented to the emergency department with worsening generalized fatigue for one week associated with headache, dyspnea on exertion, nausea, vomiting and lightheadedness. Of note, she had received her second dose of mRNA COVID-19 vaccine 4 days prior to presentation. On admission, patient was found to be severely anemic with a hemoglobin of 4.3g/dL which is decreased from her baseline hemoglobin of 9-10.5g/dL;however, W-AIHA precluded the administration of blood product until adequate blood with the appropriate antibodies could be acquired. During the hospitalization, hemoglobin decreased to 3.3g/dL. Patient was then administered the most compatible blood product which she tolerated well. Hematology was consulted who started the patient on hydroxychloroquine, high dose methylprednisolone, and Intravenous Immunoglobulin (IVIG). Throughout the admission, the patient remained asymptomatic. After 2 days of IVIG, three days of high dose glucocorticoids, and one unit of packed red blood cells, the patient's hemoglobin increased to 7.2g/dL. Patient was discharged home on prednisone taper and hydroxychloroquine. Conclusion(s): Episodes of hemolytic anemia after either the first or second dose of mRNA COVID vaccines are rare and have occurred in patients with known hematological pathology as well as patients without any history of hematologic or immunologic disorders. When taking the history of patients presenting with hemolytic anemia, it is important to query recent vaccinations as, while rare, mRNA COVID vaccine may well be the etiology. While this ultimately will likely not change patient management, this information would be beneficial for further study.

Exacerbation of autoimmune hemolytic anemia associated with pure red cell aplasia after COVID-19: A case report.

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are rare complications of coronavirus disease 2019 (COVID-19). Herein, we report the case of a 28-year-old Japanese man who showed severe AIHA exacerbation associated with PRCA after COVID-19. AIHA was diagnosed and maintained for 5 years. Approximately 4 weeks after COVID-19, the patient developed severe anemia (hemoglobin level, 3.4 g/dL). Laboratory test results confirmed hemolytic exacerbation of IgG-mediated warm-type AIHA. Despite the hemolysis phase, the bone marrow revealed extreme hypoplasia of erythroblasts with a decreased reticulocyte count, similar to that observed in patients with PRCA. During oral prednisolone treatment, the patient recovered from anemia and showed increased reticulocyte count and reduced hypoplasia of marrow erythroblasts. Exacerbation of AIHA and PRCA was triggered by COVID-19 because other causes were ruled out. Although this case report highlights that COVID-19 could lead to hematological complications such as AIHA and PRCA, the exact mechanisms remain unclear.

Coronavirus Disease 2019 and Cold Agglutinin Syndrome: An Interesting Case.

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality worldwide. While patients with COVID-19 most frequently present with pneumonia, respiratory failure and acute respiratory distress syndrome, increasing cases of immune-mediated disorders such as autoimmune thrombocytopenia, haemolytic anaemia and antiphospholipid syndrome have been reported. In this article we describe a rare case of cold agglutinin syndrome (CAS) in a patient with COVID-19. The patient was a 77-year-old man with a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency who presented with COVID-19 infection and acute respiratory failure. Initially he was started on intravenous steroids, antibiotics and hydroxychloroquine. Laboratory analysis revealed haemolytic anaemia with a positive direct anti-globulin test (DAT) and high titres of cold agglutinins. Hydroxychloroquine was stopped due to suspicion of haemolysis due to G6PD deficiency but the haemolysis persisted. Unfortunately, the respiratory failure progressed and the patient died. In summary, this article describes a rare case of CAS associated with COVID-19. CAS is a heterogenous group of cold autoimmune haemolytic anaemias occurring secondary to infections or malignancies. No definite treatment for CAS in COVID-19 patients has been approved so far. LEARNING POINTS: Autoimmune haemolytic anaemia has been reported in COVID-19 patients.Cold agglutinin syndrome (CAS) can occur in patients with COVID-19.Efforts to determine the optimal management of CAS in COVID-19 patients must continue.

Recommendations on the Management of Patients with Immune Thrombocytopenia (ITP) in the Context of SARS-CoV-2 Infection and Vaccination: Consensus Guidelines from a Spanish ITP Expert Group.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease with highly variable presentation, characteristics, and clinical course. Thrombocytopenia is a common complication of many viral infections, including SARS-CoV-2. In addition, both de novo ITP and exacerbation of ITP after vaccination against SARS-CoV-2 have been reported. Patients infected with SARS-CoV-2 develop a prothrombotic coagulopathy called COVID-19-associated coagulopathy (CAC). In addition, autoimmune hematological disorders secondary to SARS-CoV-2 infection, mainly ITP and autoimmune hemolytic anemia (AIHA), have been described. Furthermore, SARS-CoV-2 infection has been associated with exacerbation of autoimmune processes, including ITP. In fact, there is evidence of a high relapse rate in patients with preexisting ITP and COVID-19. As for vaccination against SARS-CoV-2, hematological adverse events (HAE) are practically anecdotal. The most common HAE is thrombocytopenia-associated thrombosis syndrome (TTS) linked to vectored virus vaccines. Other HAEs are very rare, but should be considered in patients with previous complement activation disease or autoimmunity. In patients with ITP who are vaccinated against SARS-CoV-2, the main complication is exacerbation of ITP and the bleeding that may result. In fact, this complication occurs in 12% of patients, with splenectomized and refractory patients with more than five lines of previous treatment and platelet counts below 50 × 109/L being the most vulnerable. We conclude that, in general, there is no greater risk of severe SARS-CoV-2 infection in ITP patients than in the general population. Furthermore, no changes are advised in patients with stable ITP, the use of immunosuppressants is discouraged unless there is no other therapeutic option, and patients with ITP are not contraindicated for vaccination against COVID-19.

Chronic cold agglutinin disease after a third COVID-19 mRNA vaccination.

COVID-19 mRNA vaccines manufactured by Pfizer-BioNTech and Moderna have been approved in many countries, and have been administered since 2020. Recent reports of mRNA vaccination exacerbating autoimmune hematologic disorders, such as immune thrombocytopenia or autoimmune hemolytic anemia, have caught the attention of the general public, resulting in alarm over the risks of serious consequences. Meanwhile, in very rare cases, vaccination was reported to trigger new onset of hemolytic anemia. However, it remains unknown whether this was a transient reaction or a persistent event, because all cases reported to date were immediately treated with corticosteroids or rituximab. Here, we present a case of newly diagnosed cold agglutinin disease after a third COVID-19 mRNA vaccination. The patient was followed for 4 months without treatment and continued to exhibit high levels of cold agglutinin and aggregation of red blood cells. The present case indicates that the disease can become chronic, and provides insights into the pathogenesis and treatment strategies.

Development and exacerbation of autoimmune hemolytic anemia following COVID-19 vaccination: A systematic review.

Autoimmune hemolytic anemia (AIHA) is caused by the production of autoantibodies against RBCs. COVID-19 vaccines can reduce the risk of severe disease, however, various adverse effects such as AIHA were observed following vaccination. This review aimed to assess the relationship of AIHA and COVID-19 vaccination using the PRISMA guidelines. Among 18 cases included in this review, new post-vaccination AIHA development was reported in 11 patients (7 women and 4 men) with a median age of 67.0 years. In 7 of 11 and 3 of 11 cases, the onset of symptoms occurred after first and second vaccine dose with median times of 7 and 14 days, respectively. In 1 of 11 cases, the AIHA occurred on Day 17 after booster vaccination. Ten of 11 and 1 of 11 AIHA patients received mRNA- and vector-based vaccine, respectively. After vaccination, 9 of 11, 1 of 11, and 1 of 11 AIHA patients developed warm IgG, cold IgM, and mixed autoantibodies against RBCs, respectively. Significant AIHA exacerbation was reported in seven patients (four women and three men) with a median age of 73.0 years. In 4 of 7 and 2 of 7 exacerbated AIHA cases, the onset of symptoms occurred after first and second vaccine dose with median times of 7 and 3 days, respectively. In 1 of 7 exacerbated AIHA cases, the onset of symptoms was observed on Day 2 after booster vaccination. All exacerbated AIHA cases received mRNA-based vaccines; 3 of 7 and 4 of 7 exacerbated AIHA cases developed IgG and IgM against RBCs, respectively. This review provides a comprehensive explanation regarding the AIHA development and exacerbation after COVID-19 vaccination.

Hemolytic anemia in COVID-19.

COVID-19 is a global pandemic triggered by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 entry point involves the interaction with angiotensin-converting enzyme 2 (ACE2) receptor, CD147, and erythrocyte Band3 protein. Hemolytic anemia has been linked to COVID-19 through induction of autoimmune hemolytic anemia (AIHA) caused by the formation of autoantibodies (auto-Abs) or directly through CD147 or erythrocyte Band3 protein-mediated erythrocyte injury. Here, we aim to provide a comprehensive view of the potential mechanisms contributing to hemolytic anemia during the SARS-CoV-2 infection. Taken together, data discussed here highlight that SARS-CoV-2 infection may lead to hemolytic anemia directly through cytopathic injury or indirectly through induction of auto-Abs. Thus, as SARS-CoV-2-induced hemolytic anemia is increasingly associated with COVID-19, early detection and management of this condition may prevent the poor prognostic outcomes in COVID-19 patients. Moreover, since hemolytic exacerbations may occur upon medicines for COVID-19 treatment and anti-SARS-CoV-2 vaccination, continued monitoring for complications is also required. Given that, intelligent nanosystems offer tools for broad-spectrum testing and early diagnosis of the infection, even at point-of-care sites.

Analysis of hematologic adverse events reported to a national surveillance system following COVID-19 bivalent booster vaccination.

Hematologic complications, including vaccine-induced immune thrombotic thrombocytopenia (VITT), immune thrombocytopenia (ITP), and autoimmune hemolytic anemia (AIHA), have been associated with the original severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. However, on August 31, 2022, new formulations of the Pfizer-BioNTech and Moderna vaccines were approved for use without clinical trial testing. Thus, any potential adverse hematologic effects with these new vaccines remain unknown. We queried the US Centers for Disease Control Vaccine Adverse Event Reporting System (VAERS), a national surveillance database, through February 3, 2023, all reported hematologic adverse events that occurred within 42 days of administration of either the Pfizer-BioNTech or Moderna Bivalent COVID-19 Booster vaccine. We included all patient ages and geographic locations and utilized 71 unique VAERS diagnostic codes pertaining to a hematologic condition as defined in the VAERS database. Fifty-five reports of hematologic events were identified (60.0% Pfizer-BioNTech, 27.3% Moderna, 7.3% Pfizer-BioNTech bivalent booster plus influenza, 5.5% Moderna bivalent booster plus influenza). The median age of patients was 66 years, and 90.9% (50/55) of reports involved a description of cytopenias or thrombosis. Notably, 3 potential cases of ITP and 1 case of VITT were identified. In one of the first safety analyses of the new SARS-CoV-2 booster vaccines, we identified few adverse hematologic events (1.05 per 1,000,000 doses), most of which could not be definitively attributed to vaccination. However, three reports of possible ITP and one report of possible VITT highlight the need for continued safety monitoring of these vaccines as their use expands and new formulations are authorized.

Autoimmune hemolytic anemia following SARS-COV- 2 vaccine in SLE nephritis with coexistent thymoma, complicated by severe COVID-19 infection

Background: We report a 40-year- old female with co-existent lupus nephritis and thymoma who developed severe lupus flare (worsening nephritis, new onset hemolytic anemia) following SARS-CoV- 2 vaccine. Case: This 40 year old female has had stable lupus nephritis (LN) while maintained on mycophenolate mofetil and hydroxychloroquine for several years. A co-existent thymoma was likewise stable and did not require any added therapy apart from the management of the LN. She received the first dose of inactivated vaccine for SARS-CoV- 2 without event. Two weeks following the second dose, she developed Coombs positive hemolytic anemia (hemoglobin 64 g/L) with leukopenia (WBC 2.3 x 109/L), worsening nephritis (3+ proteinuria with uPCR 1.0, active urine sediments), hypocomplementemia, and elevated anti-dsDNA. She received methylprednisolone pulse therapy then maintained on prednisone 40mg/day with clinical improvement. Two weeks thereafter, she was admitted due to severe COVID-19 pneumonia accompanied by severe anemia requiring blood transfusion;she received a regimen of bevacizumab, dexamethasone, and remdesivir and was discharged recovered, without overt sequelae at the time of this report. Discussion(s): Vaccines are highly effective in reducing hospitalization and death attributable to SARS-CoV- 2 infection. There are concerns however regarding autoimmune disease flares following SARS-CoV- 2 vaccine, reported to occur in about 4% patients with autoimmune disorders. It is also possible that this patient's reaction may have been further aggravated by the co-existent thymoma. While there was apparent sub-optimal protection of the vaccine against moderate to severe COVID-19 infection in this patient, it may be conjectured that her significant recovery and response to the anti-viral combined with immunosuppressive regimen may be due to the high dose steroid treatment given for the post-vaccine autoimmune reaction.

Evans syndrome as initial presentation of COVID-19 infection: A case report and review of the literature / Le syndrome d'Evans comme présentation initiale du Covid-19 : à propos d'un cas et revue de la littérature

Evans syndrome (ES) is a rare and chronic autoimmune disease characterized by the concomitant or sequential association of auto-immune hemolytic anemia (AIHA) with immune thrombocytopenia (ITP), and less frequently autoimmune neutropenia. Coronavirus disease 2019 (Covid-19) may cause various hematologic conditions. COVID-19 may also induce Evans syndrome via immune mechanisms. Here, we describe the case of a patient developing Evans syndrome as initial presentation of Covid-19 infection.

Severe Autoimmune Hemolytic Anemia in a Young Child with Active Covid-19 Infection

INTRODUCTION: Autoimmune hematological complications related to COVID-19 are rare. There are only 5 pediatric case reports of autoimmune hemolytic anemia (AIHA) among 14 million pediatric COVID-19 cases in USA. Four were older (13-17 years), two had underlying autoimmune/hematologic conditions. Immunologic analysis varied, with cold, warm & mixed hemolytic anemias described. We present a previously healthy child with COVID-19 associated severe AIHA with peripheral reticulocytopenia. DESCRIPTION: A 3-year-old male presented with lethargy, fever, tachycardia and jaundice 10 days after COVID-19 diagnosis. Pertinent labs include hemoglobin (Hgb) 3.8 g/dL, Hct 9.9%, bilirubin 3.6 mg/dL, platelets 321,000/muL, RBC count 1.2 M/muL, WBC 35,600/muL, MCV 82.5fL. Reticulocyte count (RC) was only 2.8%. Peripheral blood smear showed anisocytosis, poikilocytosis, nucleated RBCs and left shifted granulocytosis. Bone marrow biopsy revealed erythroid hyperplasia without underlying malignancy;myeloid:erythroid ratio of 0.3:1. The outside hospital reported cold C3 agglutination following 4degreeC incubation, while our laboratory identified spontaneous agglutination at room temperature (warm agglutination). IV fluids, O2, and methylprednisolone (4 mg/kg/day) were started and two packed RBC transfusions (total 30 ml/kg) given for symptomatic anemia with Hgb < 4 g/dL. LDH peaked at 2255 U/L on Day 3. Reticulocyte count was low (2.8%-3.8%) Days 1-3, increased to 6.5% on Day 4 and peaked at >30.0% on Day 7. He was changed to oral prednisone 2 mg/kg/day on Day 12 and discharged on Day 13 with Hgb 7.0 g/dL and RC 29.9%. Most recent Hgb is 13.0 g/dL and RC 2.6%. DISCUSSION: COVID-19 associated AIHA is rare, and previously reported mostly in older children. Our patient was previously healthy, and demonstrated a strong bone marrow response with erythroid hyperplasia. Peripheral reticulocytosis was delayed, and correlated with initiation of systemic steroid therapy. Our patient had both cold and warm agglutination supporting extensive autoimmune destruction of early red cell lineage. These findings support immune activation during acute COVID-19 infection and COVID-19 as a trigger for AIHA. Patients developing AIHA may need to be tested for COVID-19 and carefully monitored for complications.

Neutrophil Counts Related to Presentation of Covid in Autoimmune Neutropenia?

Objective: To describe 2 cases of autoimmune neutropenia (AIN) patients infected with Sars-Cov-2. Design/Method: Two subjects case report. Result(s): Case report 1: A girl with primary AIN since 1 year and 10 months old, maintaining severe neutropenia and mild recurrent infections. Presented to the emergency department in June/2020, at 3 years and 8 months old, with flu-like symptoms, afebrile, in good general condition. Physical examination was normal. The absolute neutrophil count (ANC) was 0.279 x 109/L. At hospital admission, Sars-Cov-2 (RT-PCR) tested positive and filgrastim (G-CSF) 5 mug/kg/day was initiated. Chest X-ray was also normal and blood culture resulted negative. She remained in great general condition, afebrile, and was discharged on the 2nd day of hospitalization, with clarithromycin (15 mg/kg/day). After G-CSF, ANC: 0.494 x 109/L (1st dose), 1.431 x 109/L (2nd dose). On outpatient follow-up, she had no long-term complications from Covid-19. Case Report 2: A man with chronic immune thrombocytopenia purpura (ITP) since 2008, autoimmune hemolytic anemia since 2013, evolved with AIN on May/2020, at 42 years old, with ANC lower than 0.5 x 109/L. On 6/1/2020, he had ANC 0.170 x 109/L. On 6/25/2020, he started flu-like symptoms, had ANC of 5.118 x 109/L, and tested positive for Sars-Cov-2 (RT-PCR). He kept high fever (102,2degreeF) and was hospitalized for 10 days without use of G-CSF. After discharge, on outpatient follow-up, he had no long-term complications from Covid-19, and presented ANC 0.338 x 109/L (Aug/2020). Discussion(s): At beginning of Covid-19 pandemic, severity infection in children was unknown. Today is known that most of them have milder clinical course, regardless of chronic diseases. In adults, in contrast, the inflammatory response tends to exacerbation, with more severe clinical conditions. Furthermore, many case reports of patients infected by SARS-CoV-2 with comorbidities literature are published. However, to date there are no reports on the impact of COVID-19 in AIN patients. Increased neutrophil counts during infectious episodes are common in AIN, which appears to be related to the benign course of most infections. We reported 2 cases of AIN patients diagnosed with Covid-19, both with favorable clinical outcomes despite heterogenic clinical course. On the first case, she presented few symptoms and ANC increased only after using G-CSF. On the second reported patient, there was a spontaneous increase of ANC and greater inflammatory response than the first case. It could suggest a correlation between inflammatory response to COVID-19 and ANC in cases of autoimmune neutropenia. Conclusion(s): In the reported cases, clinical course of disease and neutrophil count were different between adult and pediatric patients. It is not possible to state whether this difference is due to age group, individual response to infection or other variables. It is important to assess other cases of AIN infected by COVID 19 to better understand correlation between severity of infection and neutrophil count response. Copyright © 2022