[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.

[Outcomes of COVID-19 due to omicron variant infection complicated with hematological disorders].

When the omicron variant became the most dominant severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) variant causing coronavirus disease 2019 (COVID-19) in Japan, 11 patients with hematological diseases infected with this new variant were treated at our institution. Among them, four of the five patients who had been treated with chemotherapy progressed to moderate-II COVID-19, and two of them died. In contrast, five of the six patients who did not receive the treatment remained at mild to moderate-I stage of COVID-19, except for a single case progressing to moderate-II COVID-19. While all four patients infused with anti-coronavirus monoclonal antibodies within 8 days after the onset survived, the other two patients, being withheld from treatment or treated later, died. In these two cases, anti-SARS-Cov-2 immunoglobulin G antibodies remained at low titers. Although the omicron variant is considered a less harmful SARS-Cov-2 variant, patients with hematological disorders, particularly those who are immunosuppressed caused by chemotherapy, should be continuously cared for as they remain at a higher risk of severe COVID-19 due to insufficient or delayed anti-viral humoral immunity development. Thus, the rapid introduction of antiviral monoclonal antibodies together with anti-viral reagents may rescue these patients.

Anti-SARS CoV-2 IgG in COVID-19 Patients with Hematological Diseases: A Single-center, Retrospective Study in Japan.

Objective Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Although the relationship between anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies and COVID-19 severity has been reported, information is lacking regarding the seropositivity of patients with particular types of diseases, including hematological diseases. Methods In this single-center, retrospective study, we compared SARS-CoV-2 IgG positivity between patients with hematological diseases and those with non-hematological diseases. Results In total, 77 adult COVID-19 patients were enrolled. Of these, 30 had hematological disorders, and 47 had non-hematological disorders. The IgG antibody against the receptor-binding domain of the spike protein was detected less frequently in patients with hematological diseases (60.0%) than in those with non-hematological diseases (91.5%; p=0.029). Rituximab use was significantly associated with seronegativity (p=0.010). Conclusion Patients with hematological diseases are less likely to develop anti-SARS-CoV-2 antibodies than those with non-hematological diseases, which may explain the poor outcomes of COVID-19 patients in this high-risk group.

Successful Elimination of SARS-CoV-2 Following Vaccination with BNT162b2 after Prolonged Viral Infection in an Immunocompromised Lymphoma Patient.

A 52-year-old man with mantle cell lymphoma treated with bendamustine and rituximab developed prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite elevated titers of anti-spike IgG antibody, protracted pancytopenia persisted for more than six months. Finally, the anti-SARS CoV-2 vaccine, BNT162b2, was administered, which improved his blood cell count and eliminated the virus. The increased anti-spike IgG titer and lymphocyte count after vaccination suggested that both humoral and cellular immunity acted in coordination to eliminate the virus.

[SARS-CoV2 anti-spike IgG response following COVID-19 mRNA vaccination (BNT162b2) in patients with hematological disorders].

This is a prospective study conducted to determine the level of anti-spike IgG to SARS-CoV-2 2-6 weeks following the BNT162b2 vaccination in 125 patients with hematological disorders. Compared with healthy controls, patients with malignant lymphoma had lower rates of seropositivity and lower levels of antibody titer. Furthermore, patients who received rituximab (R)-containing chemotherapy had lower antibody titers than those who were not treated with R or who had completed R-containing chemotherapy more than 9 months earlier. Despite having 71% IgG-seropositivity, patients with multiple myeloma had lower antibody titers than the control group. Furthermore, patients receiving daratumumab-containing chemotherapy had lower antibody titers than those not receiving treatment. Moreover, patients with acute myeloid leukemia or myelodysplastic syndrome had lower antibody titers than the control group. Overall, the number of peripheral blood lymphocytes was significantly correlated with IgG titers, with seropositive patients having more peripheral blood lymphocytes than seronegative patients. Patients with severe immunosuppression, such as those with hematological disorders, often have impaired seroconversion with COVID-19 vaccination that should be taken into consideration by clinicians.

A Novel Method to Reduce ELISA Serial Dilution Assay Workload Applied to SARS-CoV-2 and Seasonal HCoVs.

Assays using ELISA measurements on serially diluted serum samples have been heavily used to measure serum reactivity to SARS-CoV-2 antigens and are widely used in virology and elsewhere in biology. We test a method using Bayesian hierarchical modelling to reduce the workload of these assays and measure reactivity of SARS-CoV-2 and HCoV antigens to human serum samples collected before and during the COVID-19 pandemic. Inflection titers for SARS-CoV-2 full-length spike protein (S1S2), spike protein receptor-binding domain (RBD), and nucleoprotein (N) inferred from 3 spread-out dilutions correlated with those inferred from 8 consecutive dilutions with an R2 value of 0.97 or higher. We confirm existing findings showing a small proportion of pre-pandemic human serum samples contain cross-reactive antibodies to SARS-CoV-2 S1S2 and N, and that SARS-CoV-2 infection increases serum reactivity to the beta-HCoVs OC43 and HKU1 S1S2. In serial dilution assays, large savings in resources and/or increases in throughput can be achieved by reducing the number of dilutions measured and using Bayesian hierarchical modelling to infer inflection or endpoint titers. We have released software for conducting these types of analysis.

[Severe thrombocytopenia after COVID-19 mRNA vaccination].

The Japanese Society of Hematology recently published on acute exacerbation of immune-mediated thrombocytopenia (ITP) after mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. In addition, there is a growing concern for the development of the newly diagnosed ITP after SARS-CoV-2 vaccination. Herein, we report two cases of severe thrombocytopenia associated with bleeding tendencies at 4 and 14 days after BNT162b2 mRNA vaccination. Platelet counts returned to normal following platelet transfusion or treatment with intravenous immunoglobulin and dexamethasone. To our knowledge at the time of the draft of this manuscript, nine cases of SARS-CoV-2 vaccine-induced ITP have been reported. Although most patients showed favorable clinical courses similar to that of our cases, critical thrombocytopenia can lead to unfavorable outcomes. A national survey may be required to examine the causal relationship between SARS-CoV-2 vaccination and the emergence of the newly diagnosed ITP and clinical outcomes of vaccine-induced thrombocytopenia.

Practical management of patients with hematological diseases during the COVID-19 pandemic in Japan.

Polymerase chain reaction (PCR) tests cannot always detect the SARS-CoV-2 virus, possibly due to differences in sensitivity between sample types. Under these circumstances, immunochromatography may serve as an alternative method to detect anti-SARS-CoV-2 IgG antibodies that indicate a history of infection. In our analysis of patients with severe COVID-19 infection, we found that 14 of 19 serum samples were positive for IgG antibodies, whereas 6 of 10 samples from patients with asymptomatic or mild cases were negative. Two patients with immune thrombocytopenia who were treated with prednisolone experienced aggressive COVID-19-related respiratory failure and eventually died. Patients not in remission and those who received steroid-based chemotherapy had a higher risk of death, and patients with lymphoid malignancies including lymphoma and myeloma died in larger numbers than those with myeloid malignancies. A stricter cohorting strategy based on repeat PCR tests or isolation to a private room should be adopted in routine care in hematology departments to prevent viral spread to the environment.

Clinical characteristics and risk factors associated with nosocomial COVID-19 infection in patients with hematological disorders in Japan.

Patients with cancer are considered at high risk of acquiring coronavirus disease (COVID-19). To identify patients who are likely to be diagnosed with severe COVID-19, we analyzed the risk factors for mortality in patients admitted to the hematology department at our institute. The mortality rate of all patients was as high as 62% (21 of the 34 patients), and most of these patients had malignant malignancies. Patients before an achievement of remission had a 10.8-fold higher risk of death than those in remission. The group receiving chemotherapy with steroids had a shorter survival time and had an 8.3-fold higher risk of death than that receiving chemotherapy without steroids. During the COVID-19 pandemic, it is necessary to carefully monitor or follow-up patients with active diseases and patients receiving steroid-containing chemotherapy.

[Practical management of the patients with hematological diseases during the COVID-19 pandemic in Japan].

PCR assay cannot always detect the SARS-CoV2 virus, which might be due to differences in the sensitivities of each sampling site. Under these circumstances, immunochromatography may serve as an alternative method to detect anti-SARS-CoV-2 IgG antibodies that can demonstrate a history of infection. In patients with severe COVID-19 infection, 14 of 19 serum samples were shown to be positive, whereas 6 of 10 samples from patients with asymptomatic or mild cases were negative for IgG antibodies. Two patients with immune thrombocytopenia, who were treated with prednisolone, experienced aggressive behavior of COVID-19-related respiratory failure and eventually died. Patients who were before an achievement of remission and those who received steroid-based chemotherapy possessed a higher risk of death, and more deaths were observed in patients with lymphoid malignancies including lymphoma and myeloma compared with those with myeloid malignancies. As for daily medical care in hematological department, a stricter cohorting strategy using repeat PCR tests or isolation to a private room should be adopted in order to prevent viral spread to the environment.

[Successful steroid pulse therapy for COVID-19 associated respiratory failure initially mimicking bortezomib-induced lung injury].

From December 2019, a 71-year-old male underwent three cycles of a combination therapy of pomalidomide, bortezomib, and dexamethasone for relapsed multiple myeloma and a very good partial response was achieved. In March 2020, he developed a fever of 38.9°C and computed tomography revealed bilateral ground-glass opacities. Antibiotic therapy was ineffective. Bronchoscopy was performed and bortezomib-induced lung injury was initially suspected. Due to respiratory exacerbation, high-dose steroid therapy was administered, which resulted in a dramatic improvement of the patient's respiratory failure. Thereafter, reverse transcription polymerase chain reaction performed on a preserved bronchial lavage sample tested positive, and thus his diagnosis was corrected to COVID-19 pneumonia. It is difficult to discriminate COVID-19 pneumonia from drug-induced lung disease, as both disorders can present similar ground-glass opacities on computed tomography. Therefore, with this presented case, we summarize our experience with steroid therapy for COVID-19 associated respiratory distress at our institution.

[Analysis of anti-SARS-CoV-2 IgG antibodies in hematologic patients with asymptomatic or mildly symptomatic COVID-19 infections].

At our institution, an outbreak of hospital-acquired coronavirus infection (COVID-19) occurred in the hematology department. We used immunochromatography to examine the anti-COVID-19 IgG antibody level in 10 COVID-19 positive patients who exhibited little or no symptoms. Six patients were negative for IgG antibody at an average of 26 days (range: 11-39 days) after the COVID-19 diagnosis. Among them, two had been negative on PCR twice and were discharged but subsequently became positive on PCR 2-4 weeks later and developed pneumonia. These patients were also positive for IgG antibody after the confirmed diagnosis based on PCR accompanied with the development of pneumonia. Our findings suggest an immune response delay to COVID-19 in immunocompromised patients, such as those with hematologic disorders. Thus, follow-up examinations with antibody testing are important in these patients.

[Retrospective analysis of nosocomial COVID-19: a comparison between patients with hematological disorders and other diseases].

Nosocomial coronavirus disease 2019 (COVID-19) had occurred at our hospital. We retrospectively analyzed the differences between patients with nosocomial COVID-19 and either hematological disease (n=40) or other diseases (n=57). The analysis was completed within 60 days for surviving patients. Among the patients with hematological disease and those with other diseases, there were 21 (52.5%) and 20 (35.1%) deaths, respectively. Although the patients with hematological disease received favipiravir more frequently than patients with other diseases (21 [52.5%] vs. 15 [35.3%], respectively; P<0.05), their median overall survival was poor (29 days; P=0.078). Furthermore, the median duration from oxygen therapy initiation to death or intubation was significantly shorter in the patients with hematological disease (5 days [range, 1-17 days] vs. 10 days [1-24 days], respectively; P<0.05). Furthermore, the patients with hematological disease and nosocomial COVID-19 exhibited more marked respiratory failure and poorer outcomes leading to death in a shorter time period than the patients with other diseases and nosocomial COVID-19.