Severe Hepatitis-associated Aplastic Anemia Following COVID-19 mRNA Vaccination.

We herein report a case of hepatitis-associated aplastic anemia (HAAA) that occurred after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. In this patient, progressive pancytopenia observed two months after acute hepatitis following the second dose of the SARS-CoV-2 vaccine indicated the development of HAAA. Although some reports have suggested that SARS-CoV-2 vaccination may be involved in the development of autoimmune diseases, no cases of HAAA developing after SARS-CoV-2 vaccination have been reported. SARS-CoV-2 vaccination in children has only started relatively recently, so the range of side effects in children has not yet been thoroughly described. Therefore, we need to strengthen surveillance for symptoms of children who are vaccinated.

[Analysis of anti-SARS-CoV-2 IgG antibody titers after mRNA booster vaccination in patients with nonmalignant hematological disorders].

In our facility, anti-SARS-CoV-2 mRNA vaccines were given to 21 patients, including 8 with aplastic anemia (AA), 3 with pure red cell aplasia (PRCA), and 10 with immune thrombocytopenic purpura (ITP), and IgG antibody titers were assessed one month after vaccinations. After receiving both a second vaccine and a booster shot, all patients with AA/PRCA treated with cyclosporine A aside from one, had IgG titers that were lower than the median levels of healthy controls. Even if prednisolone (PSL) doses did not go over 10 mg/day, ITP patients receiving PSL therapy were unable to achieve adequate levels of IgG after booster immunizations.

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.

Clinical outcomes and immune responses to SARS-CoV-2 vaccination in severe aplastic anaemia.

Patients with severe aplastic anaemia (SAA) are often not vaccinated against viruses due to concerns of ineffective protective antibody response and potential for pathogenic global immune system activation, leading to relapse. We evaluated the impact of COVID-19 vaccination on haematological indices and disease status and characterized the humoural and cellular responses to vaccination in 50 SAA patients, who were previously treated with immunosuppressive therapy (IST). There was no significant difference in haemoglobin (p = 0.52), platelet count (p = 0.67), absolute lymphocyte (p = 0.42) and neutrophil (p = 0.98) counts prior to and after completion of vaccination series. Relapse after vaccination, defined as a progressive decline in counts requiring treatment, occurred in three patients (6%). Humoural response was detectable in 90% (28/31) of cases by reduction in an in-vitro Angiotensin II Converting Enzyme (ACE2) binding and neutralization assay, even in patients receiving ciclosporin (10/11, 90.1%). Comparison of spike-specific T-cell responses in 27 SAA patients and 10 control subjects revealed qualitatively similar CD4+ Th1-dominant responses to vaccination. There was no difference in CD4+ (p = 0.77) or CD8+ (p = 0.74) T-cell responses between patients on or off ciclosporin therapy at the time of vaccination. Our data highlight appropriate humoural and cellular responses in SAA previously treated with IST and true relapse after vaccination is rare.

A fatal SARS-coronavirus-2 induced bone marrow aplasia complicated with invasive fungal infection and severe neutropenic enterocolitis.

BACKGROUND: Immunization against the coronavirus disease 2019 (COVID-19) began in January 2021 in Iran; nonetheless, due to a lack of vaccination among children under 12, this age group is still at risk of SARS-CoV-2 infection and its complications. CASE PRESENTATION: SARS-CoV-2 infection was diagnosed in a 6-year-old girl who had previously been healthy but had developed a fever and pancytopenia. The bone marrow aspiration/biopsy demonstrated just hypocellular marrow without signs of leukemia. She was worked up for primary and secondary causes of pancytopenia. Except for a repeated reactive HIV antibody/Ag P24 assay, all test results were inconclusive. After a thorough diagnostic investigation, the cross-reactivity of the HIV antibody/Ag P24 test with SARS-CoV-2 antibodies was confirmed. The patient did not develop any COVID-19-related signs and symptoms, but she did get a severe invasive fungal infection and neutropenic enterocolitis. She died as a result of disseminated intravascular coagulopathy. CONCLUSION: It is critical to recognize children infected with SARS-CoV-2 who exhibit atypical clinical manifestations of COVID-19, such as persistent pancytopenia. SARS-CoV-2 infection can cause severe and deadly consequences in children; thus, pediatricians should be aware of COVID-19's unusual signs and symptoms mimicking other conditions such as aplastic anemia.

Very severe immune aplastic anemia after mRNA vaccination against COVID-19 responds well to immunosuppressive therapy: clinical characteristics and comparison to previous reports.

OBJECTIVE: Various hematologic side effects of the Coronavirus Disease 2019 (COVID-19) vaccination has been reported, and most of them are thought to be related to autoimmune pathways. To the best of our knowledge, only few cases of post-COVID-19 vaccination aplastic anemia (AA) have been reported and there is no reported Korean case of COVID-19 vaccine-induced AA yet. We present a case of severe immune-mediated AA that developed after the administration of a messenger ribonucleic acid (mRNA) gene-based spike protein vaccine against COVID-19, which responded well to immunosuppressive therapy, and discuss the probable pathogenesis of AA and the implication of vaccination along with a comparison of previous cases reported. METHODS: A 53-year-old Korean man developed sudden pancytopenia three months after COVID-19 vaccination. To evaluate the cause of pancytopenia, a bone marrow study was performed. RESULTS: A diagnosis of AA was made through the bone marrow study and he received triple immunosuppressive therapy (IST). After triple IST for five months, his blood cell count was improved and maintained without transfusion and his follow-up bone marrow examination showed improved cellularity. CONCLUSION: COVID-19 vaccine might be associated with the development of immune-mediated AA. Prompt hematologic evaluation should be performed when there are symptoms or signs suggestive of cytopenia after COVID-19 vaccination. Although the clinical outcome of post-vaccination AA varies, a good prognosis can be possible for patients with COVID-19 vaccination-induced AA.

Pancytopenia in a Case of Aplastic Anaemia/Paroxysmal Nocturnal Haemoglobinuria Unmasked by SARS-CoV-2 Infection: A Case Report.

During an acute SARS-CoV-2 infection, a diagnosis of Aplastic Anaemia associated with Paroxysmal Nocturnal Haemoglobinuria (AA/PNH) was made in a 78-year-old woman who had presented to the emergency department with severe pancytopenia. It is possible that she had subclinical AA/PNH that was unmasked during the acute COVID-19 infection, but we can also suspect a direct role of the virus in the pathogenesis of the disease, or we can hypothesize that COVID-19 infection changed the phosphatidylinositol glycan class A (PIGA) gene pathway.

Therapeutic Potential of Human Immature Dental Pulp Stem Cells Observed in Mouse Model for Acquired Aplastic Anemia.

Aplastic anemia (AA) is a rare and serious disorder of hematopoietic stem cells (HSCs) that results in the loss of blood cells due to the failure of the bone marrow (BM). Although BM transplantation is used to treat AA, its use is limited by donor availability. In this sense, mesenchymal stem cells (MSCs) can offer a novel therapeutic approach for AA. This is because the MSCs contribute to the hematopoietic niche organization through their repopulating. In our study, we used the human immature dental pulp stem cell (hIDPSC), an MSC-like cell, to explore an alternative therapeutic approach for AA. For this, isogenic C57BL/6 mice were exposed to total body irradiation (TBI) to induce the AA. After 48 h of TBI, the mice were intraperitoneally treated with hIDPSC. The immunohistochemistry analyses confirmed that the hIDPSCs migrated and grafted in the mouse bone marrow (BM) and spleen, providing rapid support to hematopoiesis recovery compared to the group exposed to radiation, but not to those treated with the cells as well as the hematological parameters. Six months after the last hIDPSC transplantation, the BM showed long-term stable hematopoiesis. Our data highlight the therapeutic plasticity and hematoprotective role of hIDPSC for AA and potentially for other hematopoietic failures.

COVID-19 infection in patients with haematological disease - A tertiary centre experience from north India.

This retrospective study was aimed to understand the clinical, laboratory, radiological parameters and the outcome of COVID-19 patients with underlying haematological disease. All patients with known haematological disease admitted with COVID-19-positive status from April to August 2020 in the COVID-19 facility of a tertiary care centre in north India, were included. Their medical records were analyzed for outcome and mortality risk factors. Fifty four patients, 37 males, were included in the study. Of these, 36 patients had haematological malignancy and 18 had benign disorder. Fever (95.5%), cough (59.2%) and dyspnoea (31.4%) were the most common symptoms. Nine patients had severe disease at diagnosis, mostly malignant disorders. Overall mortality rate was 37.0 per cent, with high mortality seen in patients with aplastic anaemia (50.0%), acute myeloid (46.7%) and lymphoblastic leukaemia (40.0%). On univariate analysis, Eastern Cooperative Oncology Group performance status >2 [odd ratio (OR) 11.6], COVID-19 severity (OR 8.2), dyspnoea (OR 5.7) and blood product transfusion (OR 6.4) were the predictors of mortality. However, the presence of moderate or severe COVID-19 (OR 16.6, confidence interval 3.8-72.8) was found significant on multivariate analysis. The results showed that patients with haematological malignancies and aplastic anaemia might be at increased risk of getting severe COVID-19 infection and mortality as compared to the general population.

[Hepatitis associated aplastic anemia during SARS-CoV-2 pandemic]. / Anemia aplásica asociada a hepatitis durante la pandemia por SARS-CoV-2.

The hepatitis-associated aplastic anemia is one of the acquired bone marrow failure syndromes. It is a stereotyped form of presentation of aplastic anemia and accounts for 2 - 5 % of the cases in the West. Its treatment, which does not differ from that of aplastic anemia, consists of immunosuppression when bone marrow transplant is not possible. Nonetheless, during the SARS-CoV-2 pandemic, recommendations restricting the use of antithymocyte globulin to those cases with the highest risk of death have been issued, since the prognosis of CoViD-19 tends to be worse if administered. We present an otherwise-healthy 18-year-old male who was diagnosed with a hepatitis-associated aplastic anemia and received a personalized treatment following these recommendations.

La anemia aplásica asociada a hepatitis es uno de los síndromes de fallo medular adquirido. Es una forma estereotipada de presentación de la anemia aplásica adquirida y representa el 2 - 5 % de los casos en occidente. Su tratamiento, que no difiere del de la anemia aplásica adquirida, consiste en inmunosupresión cuando el trasplante de células progenitoras hematopoyéticas no es posible. Sin embargo, durante la pandemia por SARS-CoV-2 se han publicado recomendaciones mediante las cuales se restringe el uso de globulina antitimocítica para aquellos casos con riesgo de muerte porque el pronóstico de la CoViD-19 tiende a ser peor con su uso. Presentamos el caso de un varón de 18 años previamente sano a quien se le diagnosticó una anemia aplásica asociada a hepatitis y se le personalizó el tratamiento acorde a estas recomendaciones.

Acquired aplastic anemia following SARS-CoV-2 vaccination.

COVID-19 is a potential life-threatening viral disease caused by SARS-CoV-2 and was declared a pandemic by the WHO in March 2020. mRNA-based SARS-CoV-2 vaccines are routinely recommended in immune-compromised patients, including patients with AA, as these patients are at increased risk of contracting COVID-19 and developing a more severe course of disease. Between March 2021 and November 2021 relapse of AA occurred in four (age [median]: 53 years, range 30-84 years) out of 135 patients currently registered at our department and two de novo cases of AA in temporal context to vaccination against SARS-CoV-2, were documented. Median time after first COVID-19 vaccination and relapse of AA was 77 days. All relapsed patients were vaccinated with the mRNA-based vaccine Comirnaty®. Relapse in two out of the four patients was refractory to CsA/eltrombopag, favoring IST with hATG/CsA or BMT, respectively. Our observations should prompt clinicians to take vaccine-induced relapse of AA or de novo AA after SARS-CoV-2 vaccination into account. Furthermore, careful clinical monitoring and vigilance for signs or symptoms that may indicate relapse of AA (e.g., bleeding complications) are indicated.

Toxic hepatitis-associated aplastic anaemia after dual homeopathic remedies and Gymnema sylvestre use.

Hepatitis-associated aplastic anaemia (HAAA) is a rare condition characterised by onset of acute hepatitis which is followed by development of severe pancytopenia due to bone marrow failure within 6 months. This syndrome can be precipitated by acute viral infections, but the aetiology remains unknown in the majority. Drug-induced HAAA is extremely rare and has been reported with nutritional and dietary supplements in current literature. We report the first cases of ayurvedic herbal and homeopathic remedies-associated HAAA in two patients which proved fatal in both. Evaluation of patients with acute hepatitis and severe pancytopenia must include a detailed evaluation for complementary and alternative medicine use.

Severe aplastic anemia after COVID-19 mRNA vaccination: Causality or coincidence?

The development of various autoimmune diseases has been reported after COVID-19 infections or vaccinations. However, no method for assessing the relationships between vaccines and the development of autoimmune diseases has been established. Aplastic anemia (AA) is an immune-mediated bone marrow failure syndrome. We report a case of severe AA that arose after the administration of a COVID-19 vaccine (the Pfizer-BioNTech mRNA vaccine), which was treated with allogeneic hematopoietic stem cell transplantation (HSCT). In this patient, antibodies against the SARS-CoV-2 spike protein were detected both before and after the HSCT. After the patient's hematopoietic stem cells were replaced through HSCT, his AA improved despite the presence of anti-SARS-CoV-2 antibodies. In this case, antibodies derived from the COVID-19 vaccine may not have been directly involved in the development of AA. This case suggests that the measurement of vaccine antibody titers before and after allogeneic HSCT may provide clues to the pathogenesis of vaccine-related autoimmune diseases. Although causality was not proven in this case, further evaluations are warranted to assess the associations between vaccines and AA.

[Severe aplastic anemia exhibiting mild COVID-19 despite high serum IL-6 levels].

COVID-19 is a viral infection characterized by a cytokine storm similar to that in acute respiratory distress syndrome (ARDS). Neutrophils and monocytes are known to play an important role in tissue damage in ARDS. COVID-19 has been reported to be more severe in patients with hematological malignancies; however, there are few reports of COVID-19 in patients with aplastic anemia. Moreover, how aplastic anemia affects COVID-19 remains unclear. Here, we report the case of a COVID-19 patient with aplastic anemia who had high serum IL-6 levels but did not progress to the severe form of COVID-19. We inferred that severe neutropenia and monocytopenia due to aplastic anemia could contribute to a mild form of COVID-19, although a risk of more severe secondary bacterial infections exists.