Pure red cell aplasia caused by parvovirus B19 in two patients without chronic hemolysis

Infection with human parvovirus B19 (PVB19) induces acquired pure red cell aplasia (PRCA). Chronic hemolytic anemia is well known as an underlying condition. However, additional factors have been recognized to accompany parvoviral PRCA; however, there are only limited reports on iron-deficiency anemia (IDA) and rituximab-induced B-cell dysfunction. We report two patients with PVB19-associated PRCA confirmed by positivity of viral DNA. Although they had no chronic hemolysis, patient 1 had IDA, and patient 2 had remitted small-lymphocytic lymphoma treated with rituximab-containing chemotherapy. Absence of reticulocytes in peripheral blood and marked depletion of erythroid precursors in bone marrow were observed both. Whereas patient 1 received only symptomatic therapy because anemia was not severe, patient 2 was treated with steroids, as PRCA etiology was at first uncertain, and immunological PRCA was not excluded. Both showed rapid increase of reticulocyte counts and recovery from anemia. Although immunoglobulin is considered effective for parvoviral PRCA, notable adverse reactions have been reported. When anemic symptom is not severe, reticulocyte observation only is recommended. The effects of steroids should also be re-evaluated. Optimal treatment according to disease severity remains to be established.     

Comparison of SARS-CoV-2 IgM and IgG seroconversion profiles among hospitalized patients in two US cities

The clinical and public health utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic testing requires a better understanding of the dynamics of the humoral response to infection. To track seroconversion of IgG and IgM antibodies in patients with SARS-CoV-2 infection and its association with patient and clinical factors and outcomes. Residual patient specimens were analyzed on the Abbott ARCHITECT i2000 instrument using the Abbott SARS-CoV-2 IgG assay and prototype SARS-CoV-2 IgM assay. Age, sex, comorbidities, symptom onset date, mortality, and specimen collection date were obtained from electronic medical records. Three hundred fifty-nine longitudinal samples were collected from 89 hospitalized patients 0 to 82 days postsymptom onset. Of all, 51.7% of the patients developed IgG and IgM antibodies simultaneously; 32.8% seroconverted for IgM before IgG. On average, patients seroconverted for IgG by 8 days and for IgM by 7 days postsymptom onset. All patients achieved IgG seropositivity by 19 days and IgM seropositivity by 17 days. Median time to IgG and IgM seroconversion was prolonged and initial levels of IgG were lower in immunocompromised patients and patients <65 years of age compared to immune competent patients and those ≥65 years of age. Immunocompromised patients also had persistently lower levels of IgM that peaked on day 17.6 and decreased thereafter compared to immune competent patients. IgM seroconversion in patients who died reached significantly higher levels later after symptom onset than in those who recovered. SARS-CoV-2 infected patients have similar time to seroconversion for IgG and IgM. However, differences in immune status and age alter time to seroconversion. These results may help guide serologic testing application in COVID-19 management.     

Diagnosis of parvovirus B19 infection in hematological patients with partial red cell aplasia of the bone marrow

AIM: To assess diagnosis of parvovirus B19 infection (PI) in patients with aplastic crises by combined use of polymerase chain reaction (PCR) and enzyme immunoassay (EIA) of specific IgM and IgG. MATERIAL AND METHODS: A total of 159 serum samples from 77 PI suspects were examined. The examination for virus DNA was conducted with modified "net" PCR in 108 samples, for specific IgM and IgG with EIA in 110 samples. RESULTS: The percentage of patients infected with parvovirus detected by PCR or EIA reached 60%. 21 of 77 patients with hemolytic anemias were infected with parvovirus B19, the virus persisting in 8 cases (40%). persistence of the virus was registered if viremia occurred in immunodeficiency due to the disease or immunosuppressive therapy. Immunity to parvovirus has not developed: IgM expression was the same as in patients without hemopoietic abnormalities, while IgG was not detected. The absence of specific immunity to parvovirus B19 occurred in patients treated with immunosuppressive drugs early after the end of viremia period in high IgM level and at the initial phase of IgG synthesis. IgM levels also remained unchanged; the level of IgG declined and was not identified furthermore. There were cases of reinfection. CONCLUSION: Combined use of PCR and EIA is optimal for diagnosis of parvovirus B19 infection in patients with hemolytic anemias. It was found that there are correlations between defects in specific immunity, persistence and immunodeficiency onset regarding viremia. Abnormal for the disease course levels of IgM and IgG indicate the persisting virus, the condition of specific immune response to parvovirus B19 and feasibility of reinfection. Reliable diagnosis of parvovirus infection is possible only in simultaneous use of PCR and EIA.     

Acute parvovirus B19 infection during anti-retroviral therapy

Human parvovirus B19 (B19) has been described as a causative agent of chronic anemia in human immunodeficiency virus type-1 (HIV-1)-infected patients. We report an HIV-1 infected patient who had been receiving anti-retroviral therapy who showed sudden pancytopenia. Primary B19 infection was confirmed by the detection of plasma viremia and seroconversion. Although clearance required a prolonged period of time, the patient eventually cleared the B19 viral DNA from the plasma. More than likely, highly active anti-retroviral therapy (HAART), including a protease inhibitor, played a role in clearing the virus. Received: April 7, 2000 / Accepted: March 6, 2001     

Effects of transfusion on human erythrovirus B19-susceptible or -infected pediatric recipients in a genotype 3-endemic area

BACKGROUND: Human erythrovirus (parvovirus) B19 is transmitted by transfusion of blood, blood components, and plasma derivatives and is resistant to most viral inactivation methods. B19 genotype 3 is prevalent in Ghana, and no related clinical information is available. STUDY DESIGN AND METHODS: This study assessed the transmission of B19 genotype 3 by transfusion and the potential effect of transfused B19 antibodies in viremic recipients. Immunological aspects of B19 genotype 3 infection in children mainly transfused for acute malarial anemia were examined. Molecular and serologic methods adapted to genotype 3 were developed and used. RESULTS: Among 114 donor-recipient pairs from Ghana, two donations contained B19 DNA and specific antibodies, and no evidence of transmission was found. B19 immunoglobulin G (IgG)-containing whole blood was transfused to 14 B19 DNA-positive recipients. Three recipients with detectable levels of IgG to B19 failed to clear viremia 1 to 2.3 months after transfusion. Ten recipients without IgG to VP2 before transfusion cleared the virus but failed to develop an immune response to B19 within 1 to 2 months after transfusion. Only 1 patient who received little specific IgG by transfusion produced detectable antibodies. CONCLUSION: Low levels of B19 genotype 3 DNA associated with specific IgG are not infectious by transfusion. Viral clearance and apparent down regulation of immune response to B19 may be related to removal of the viral antigens by transfused antibodies and/or immunomodulatory effect of transfusion.     

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.     

Prevention of parvovirus B19-induced repetitive acute kidney failure by subcutaneous immunoglobulins

Human parvovirus B19 has been associated with various cases of kidney injuries with different glomerular phenotypes. In immunocompromised individuals, insufficient production of neutralizing antibodies can lead to chronic PVB19 carriage and manifestations. However, PVB19 DNA has been detected in bone marrow and peripheral blood for months or years in seemingly immunocompetent individuals, despite the presence of neutralizing antibodies. We report here PVB19-induced recurrent anuric acute kidney failures in a 57-year-old man over a 7-year period with persistent PVB19 infection and then PVB19-associated cryoglobulinemia. Acute renal failures were preceded by influenza-like syndrome associated with arthralgia, skin rash, and low-grade fever. Serum, bone marrow, renal, and digestive PVB19 replication was found in the different episodes. Endocapillary proliferative glomerulonephritis evolved into membranoproliferative glomerulonephritis. Complete renal recovery occurred after each bout. Off-label subcutaneous immunoglobulin therapy resulted in disappearance of blood and bone marrow PVB19 viral load and stopped the glomerulonephritis recurrence. Subcutaneous immunoglobulin therapy withdrawal resulted in renal relapse with cryoglobulin-associated manifestations.     

Mycobacterium simiae pulmonary infection unmasked during immune reconstitution in an HIV patient

Highly active antiretroviral therapy in human immunodeficiency virus (HIV) patients may trigger the onset of immune reconstitution inflammatory syndrome (IRIS). Among HIV patients with IRIS, infections are commonly due to Mycobacterium tuberculosis and nontuberculous mycobacteria. We report the first case in Spain and the second in Europe of Mycobacterium simiae pulmonary infection unmasked during immune reconstitution in an HIV patient.     

Laboratory diagnosis of cytomegaloviral infection in patients with anemia and hemoblastosis in the Omsk region

Research was carried out in 335 blood specimens of patients in the age of 3-35 y.o. in order to optimize diagnosis and treatment of such patients with aplastic anemia and hemoblastosis who got hemotransfunction to eliminate cytomegaloviral infection (CMVI). IgM were found out in 37.9% cases (2.8 times higher than in donors), low-avide IgG--in 44.8%. "early" proteins CMV--29.9% and DNA--in 36.8% cases. Concerning the DNA presence, preference was given to research of leucocytic suspension compared with blood serum. Of 28 children of 3-13 y.o. with anemia being seropositive in CMV, IgG antibodies were detected in 13 children while IgM antibodies to Parvovirus B19 were found in 10 children. 7 children with a grave form of disease showed combined infection of Parvovirus B19 and CMV with activation signs. It is not excluded that parallel influence of Parvovirus B19 on erythrocytic hemopoiesis growth and that of CMV on lymphocytic-monocytis cells aggravates immunodeficiency and promotes development of infection complications.     

Acute seroconversion of HIV infection in the ambulatory care setting

Patients frequently visit ambulatory care settings with acute human immunodeficiency virus (HIV) seroconversion illness, but the illness is often misdiagnosed. This acute viral syndrome, or seroconversion illness, occurs after initial exposure to the HIV virus; it is often resolved before the development of HIV-specific antibodies. Primary HIV infection refers to the 12 months following infection; it includes an acute time period after exposure when routine HIV antibody testing is negative. Primary HIV infection is recognized with the help of a detailed screening history. Diagnosis is confirmed through laboratory tests that detect virus presence. The accurate diagnosis of primary HIV infection can have a beneficial effect on the patient's clinical course and also on public health prevention efforts.     

Pure red cell aplasia accompanied by COVID-19 successfully treated using cyclosporine

A 67-year-old Japanese man was admitted to our hospital with severe coronavirus disease 2019 (COVID-19) in March 2020. Mechanical ventilation was initiated 8 days after admission, due to severe respiratory failure. Multiple severe complications such as liver dysfunction, arrhythmia, brain infarction, and venous thromboembolism were also observed. We initially diagnosed Coombs test-positive warm autoimmune hemolytic anemia. Corticosteroids proved ineffective and anemia worsened with severe erythroid hypoplasia (0.5% erythroblasts in bone marrow), so we diagnosed pure red cell aplasia (PRCA). We also identified massive infiltration of cytotoxic T-lymphocytes expressing CD8, granzyme B, and perforin in bone marrow. Systemic cyclosporine was started, with full resolution of anemia and no need for blood transfusions after 4 weeks. We believe that this represents the first report of COVID-19-associated PRCA successfully treated using cyclosporine.     

Diagnosis of parvovirus B19 infection in patients with secondary immunodeficiency diseases

The method of immune-enzyme assay was used to examine 113 patients with secondary immunodeficiency, including 16 HIV-infected drug-addicts (group 1), 36 patients with cytomegalovirus infection (CMVI) and with immunoregating index CD4/CD8 below 1.0 (group 2), 30 patients with CMVI and with CD4/CD8 below 1.2 (group 3) and 31 patients with aplastic anemia and with anemia of unclear genesis (group 4), for parvovirus infection caused by parvovirus B19. As for groups 1 and 4, the antibodies were detected in 50 and 48.4% of cases; it is noteworthy that an active parvovirus infection was registered in the above groups more often than in groups 2 and 3. There were patients with the antibodies in group 2 by 1.8 times more than in group 3. It is suggested that the simultaneous impact of HIV, CMV and parvoviruses significantly aggravates the immunodeficiency and contributes to a more severe clinical course.     

Clinical determinants and time course of serum antibody response against listeriolysin O in experimental listeriosis

The serum antibody response against listeriolysin O (LLO) was studied in goats experimentally infected with Listeria monocytogenes, using two sequential oral inoculations at 8 months interval. The serum IgG antibody response against LLO correlated closely with that against the whole bacterium, supporting the role of LLO as the major antigenic determinant of the humoral response against L. monocytogenes. However, only severe listeric infections were accompanied by a distinct anti-LLO antibody response, whereas milder, albeit bacteraemic infections remained only weakly responsive or totally non-responsive. Elevated anti-LLO IgG antibody levels persisted for several months after past infection and even high levels of anti-LLO IgG antibodies without evidence of past or ongoing listeriosis were found. Therefore, in the serodiagnosis of listeriosis, the determination of antiLLO antibody response may be applicable only in severe listeric infections and should always be based on IgG seroconversion.     

新型冠状病毒IgM和IgG抗体不同检测方法在新型冠状病毒感染中的临床应用评价

目的探讨新型冠状病毒(SARS-CoV-2)IgM和IgG抗体不同检测方法在新型冠状病毒肺炎(COVID-19)中的应用。方法选取25例COVID-19患者,以同期20例排除SARS-CoV-2感染的患者作为对照组,分别采用磁微粒化学发光法和胶体金法检测所有对象的血清SARS-CoV-2 IgM和IgG抗体。同时检测COVID-19患者血清降钙素原(PCT)、铁蛋白及C反应蛋白(CRP)。结果化学发光法检测血清SARSCoV-2 IgM和IgG抗体的敏感性分别为48%和56%,特异性均为100%,胶体金法检测血清SARS-CoV-2 IgM和IgG抗体的敏感性分别为88%和76%,临床特异性均为100%。2种方法检测血清SARS-CoV-2 IgM和IgG抗体总符合率分别为68.9%和73.3%。25例COVID-19患者中有36%的患者血清PCT升高、72%的患者血清CRP升高、84%的患者血清铁蛋白水平升高。结论SARS-CoV-2 IgM和IgG抗体不同检测方法之间差异较大,用于COVID-19患者的临床诊断时应综合考虑。     

SARS CoV 2 infection in chronic myelogenous leukemia: Severe hematological presentation

Infection with SARS-CoV-2, the cause of coronavirus infectious disease-19 (COVID-19), has caused a pandemic. Few data are available about the risk of COVID-19 infection in persons with hematological cancer, but controversy whether these persons have the same clinical signs and outcomes. We describe a case of life‐threatening COVID-19 infection complicated by severe anemia in patients affected also by chronic myelogenous leukemia. The screening for RBC antibodies and the direct antiglobulin test (DAT) turned positive. The identification of the antibodies, showed the presence of an alloantibody with anti-Lewis b specificity, which was reactive at room temperature, in the anti-human globulin phase (AGH) and with papain-treated red blood cells. At the same time hemophagocytic lymphohistiocytosis (HLH), on the basis of major laboratory findings including hyperferritnemia, increase of triglicerides levels and according to the HLH score was suspected. Patients received antiviral therapy, steroids and intravenous immunoglobulins. Hemolysis resolved and ferritin dramatically decreased after administration of Ig and a Afull recovery was achieved after viral infection resolution.This case highlights the novel and multifaceted hematological findings during sever COVID 19 infection. COVID 19-related pneumonia is mediated by hyper activation of effector T cells and excessive production of inflammatory cytokines, such as IL-6, IL-1, interferon-gamma, and TNF. This inflammatory process called "cytokine storm" is a life-threatening complication of COVID 19 infection. In this case severe immunohematological consequences are reported for the first time and recognition of this complications are probably underestimated.     

Transmission of parvovirus B19 by coagulation factor concentrates exposed to 100 degrees C heat after lyophilization

BACKGROUND: Double inactivation by solvent/detergent treatment plus heating at 100 degrees C for 30 minutes after lyophilization has been adopted to improve viral safety of factor VIII and factor IX concentrates, particularly with respect to non-lipid-enveloped viruses. The aim of this study was to evaluate the safety of concentrates exposed to these virucidal methods. STUDY DESIGN AND METHODS: Twenty- six previously untreated hemophiliacs, 19 with factor VIII deficiency and 7 with factor IX deficiency, were investigated in a prospective multicenter study over a 12-month follow-up period by the use of serologic and virologic markers for lipid- and non-lipid-enveloped viruses (human immunodeficiency virus types 1 and 2; hepatitis A, B, and C viruses; B19 parvovirus antibodies; and B19 DNA). Overall, 270,000 U of factor VIII and 102,000 U of factor IX concentrate were administered during the study period. RESULTS: None of the 26 patients seroconverted for human immunodeficiency virus or hepatitis C virus. Hepatitis B virus markers remained negative in the 10 unvaccinated hemophiliacs. No hepatitis A virus seroconversion occurred among 17 susceptible patients. B19 seroconversion (IgM) and B19 viremia were observed within 2 weeks of the first concentrate infusion in 8 of 15 susceptible patients, 5 of 11 treated with factor VIII and 3 of 4 with factor IX concentrate. CONCLUSION: This prospective study indicates that very high temperatures applied to lyophilized concentrates appear to prevent the transmission of hepatitis A virus to hemophiliacs. However, B19 parvovirus still contaminates concentrates despite the use of this robust virucidal method.     

Detection of parvovirus B19 in synovial fluids of patients with osteoarthritis

We aimed to determine the possible role of parvovirus B19 (PVB19) in the etiology of osteoarthritis. PVB19 DNA, anti-VP1 IgM and IgG, and interleukin IL-6 levels were also assayed in synovial fluids of 42 patients with osteoarthritis and 10 controls. PVB19 DNA was detected in 28 of 42 (66.66%) in patients and in 3 of 10 (30%) in controls. IgG and IgM response were detected in 21 of 42 (50.00%) and in 2 of 42 (4.76%) patients, respectively. IL-6 were positive in 15 of 42 (36%) patients and in 3 of 10 (30%) controls. All IgG (+) samples had PVB19 DNA (100%, P < 0.001). Eleven of 15 IL-6 (+) samples had PVB19 DNA (+) (73.33%, P < 0.05). Moreover, all IL-6 (+) samples (n = 5) in stage IV had PVB19 DNA (+) (100%, P < 0.001). We have detected a significant association between the stages of osteoarthritis and PVB19 DNA (P < 0.05). These findings support the presence of PVB19 acting as a transactivator of IL-6 expression as reported earlier. Our results also suggest that the higher stages of osteoarthritis might be related to the increased inflammation and cell damage on joint cartilage due to PVB19.     

Syndrome de restauration immunitaire chez les patients infectés par le virus de l’immunodéficience humaine et traités par antirétroviraux

Early antiretroviral therapy (ART) for Human Immunodeficiency Virus (HIV) infected people has led to a decrease in the risk of mortality and in the occurrence of opportunistic infections (OI). However, a non negligible proportion of patients will develop unusual and exaggerated inflammatory response to opportunistic pathogens named immune reconstitution inflammatory syndrome (IRIS). Paradoxical IRIS occurs in patients already efficiently treated for an OI, and who deteriorate after initiation of ART while unmasking IRIS occurs in patients who have already initiated ART and in whom a latent OI exists before ART initiation. IRIS requires the exclusion of any new OI, uncontrolled OI, and drug toxicity. IRIS is estimated to occur in 16% of the patients, with a low mortality, except for central nervous system IRIS. Risk factors for IRIS are advanced HIV infection, disseminated OI, early ART introduction after OI treatment, as well as rapid immune and viral response to ART. IRIS pathophysiology leading to excessive immune response is not well understood. Clinical manifestations of IRIS are diverse and related to the involved pathogen. Mycobacteria, cryptococcus, cytomegalovirus and JC virus are the main agents responsible for IRIS. IRIS treatment is not well established. Except for life-threatening IRIS, ART should not be discontinued. Steroids can be used for severe IRIS associated with tuberculosis and progressive multifocal leukoencephalopathy.     

Primary human immunodeficiency virus

The term "primary HIV infection" refers to the period from initial infection with the human immunodeficiency virus to complete seroconversion. It is a period of extreme infectiousness. The occurrence and severity of symptoms during primary HIV infection correlate with the rapidity of clinical and immunologic decline. Treatment of patients during primary infection may improve immune preservation and reconstitution. In this review article, we present information that will help clinicians understand, recognize, and diagnose primary HIV infection. The current approach to management of primary HIV infection is based more on expert opinion than clinical trial results, though ongoing clinical trials should provide more information about this syndrome.     

Use of PCR amplification for diagnosis of HTLV-I infection after blood transfusion.

We studied the seroconversion to human T-cell leukemia virus type-1 (HTLV-I) in two immunocompromised patients after transfusions of cellular blood components. One patient produced IgM antibodies against the viral p19 protein 149 days post-transfusion (a serum on day 43 was negative). Both patients showed indeterminate Western-blots (IgG anti-p19 and anti-gp46 but no anti-p24). Using the polymerase chain reaction (PCR) with two primer pairs (SK43/44 and SK54/56), we demonstrated HTLV-I infection prior to seroconversion. This infection was confirmed by Southern blot.