Positive IgM Research Articles

Rubella virus IgM and IgG antibodies with avidity in pregnant women and outcomes at a tertiary facility in Ghana.

Congenital rubella syndrome (CRS) is a recognised cause of childhood deafness and blindness caused by the transplacental transmission of rubella virus during pregnancy. Women in the reproductive age group, and by extension their unborn babies may therefore be at increased risk. The prevalence of Rubella virus specific IgM and IgG antibodies, including IgG avidity, was determined in pregnant women attending the antenatal clinic at a Teaching Hospital in Ghana. One hundred and forty-five women in their second and third trimesters of pregnancy from the outpatient clinic were recruited over a period of 2 months after written informed consent was obtained. Study participants completed a questionnaire and venous blood drawn for IgM, IgG, and avidity testing using SERION ELISA (SERION® Immunologics, Würzburg, Germany). Babies of mothers with positive or indeterminate IgM and low avidity IgG antibodies were offered specialist cardiological, ophthalmological or hearing assessment during follow up. One hundred and twenty-eight (88.3%) had only IgG antibodies, 5 (3.4%) had IgM and IgG antibodies, while 12 (8.3%) had no antibodies. No patient had IgM antibodies alone. Ten women (6.9%) had indeterminate levels of IgM antibodies. Majority of the women had high avidity IgG antibodies, while 5 (3.4%) had low avidity antibodies. No patient had IgM with low avidity antibodies. There was no statistical association between socio-demographic factors and the presence of IgM, IgG (low or high avidity) antibodies. Of all the children followed, none had the clinical definition of CRS. Consistent with the World Health Organization elimination strategy for measles and rubella viruses, non-immune women in the reproductive age group should be vaccinated. The immunization programme should be expanded to include teenagers and adults. Though Congenital Rubella Syndrome was not detected, the risk still remains.

High Seroprevalence of Anti-SARS-CoV-2 IgM/IgG among Inhabitants of Sakaka City, Aljouf, Saudi Arabia.

(1) Backgrounds and Objectives: The global battle to contain the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is still ongoing. This cross-sectional study aimed to detect the seroprevalence of anti-SARS-CoV-2 IgM/IgG among previously symptomatic/asymptomatic and vaccinated/unvaccinated inhabitants of Sakaka City, Aljouf, Saudi Arabia. (2) Methods: Blood samples of 400 participants were tested for the presence of anti-SARS-CoV-2 IgM/IgG using colloidal gold immuno-chromatography lateral flow immunoassay cards. (3) Results: The prevalence of anti-SARS-CoV-2 IgM and IgG positivity was 45.8% and 42.3%, respectively. Statistically significant correlations (p < 0.05) were found between the previous RT-PCR testing for SARS-CoV-2-RNA and positivity for IgM and/or IgG. The highest seroprevalence of IgM and IgG were detected among smokers, participants aged ≥40 years, and patients with chronic diseases. Although most of the participants (58.5%) did not previously experience COVID-19 like symptoms, the anti-SARS-CoV-2 IgM and IgG seropositivity amongst them was 49.1% and 25.6%, respectively, with higher seroprevalence among males than females. At the time of the study, the SARS-CoV-2 vaccination rate at our locality in Saudi Arabia was 43.8% with statistically significant correlation (p < 0.001) between being vaccinated and anti-SARS-CoV-2 IgM and/or IgG positivity, with more positivity after receiving the second vaccine dose. (4) Conclusions: Public assessment reflects the real scale of the disease exposure among the community and helps in identifying the asymptomatic carriers that constitute a major problem for controlling the SARS-CoV-2. To limit the spread of the virus, rigorous implementation of large-scale SARS-CoV-2 vaccination and anti-SARS-CoV-2 serological testing strategies should be empowered.

2127. Is Routine TORCH Screening Necessary For Isolated Intrauterine Growth Restriction?

Abstract Background Perinatal TORCH infections (Toxoplasma gondii, rubella, cytomegalovirus [CMV], herpes simplex virus [HSV]) cause significant fetal and neonatal morbidity and mortality. While perinatal infections are associated with a variety of clinical manifestations in the fetus, they rarely cause isolated intrauterine growth restriction (IUGR). TORCH screens are often ordered to investigate isolated IUGR, but there is limited evidence to support screening for these infections in the absence of other ultrasound abnormalities. Methods A retrospective review of antenatal TORCH testing between January 2014 and December 2018 was carried out at two hospitals in Melbourne, Australia. Records were reviewed to identify indications for testing, serology results, and subsequent antenatal investigations. Neonatal outcomes were also evaluated. Serology performed for stillbirth or pregnancy losses were excluded. Results Medical records of 718 pregnancies were reviewed, representing 760 fetuses. 82.5% of screens were ordered in the third trimester, with 43.5% ordered after 32 weeks gestation. TORCH serology was performed for the following indications: isolated IUGR (71.2%), neurological abnormality (6.8%), echogenic bowel (3.4%), and maternal illness (1.7%). Screens ordered for isolated IUGR were positive in 7.4% (95% CI 5.5-10.0%). TORCH screening identified 49 positive maternal IgM results (CMV = 34, toxoplasma = 15) Two acute maternal infections during pregnancy were diagnosed (CMV = 1, toxoplasma = 1). Both were identified due to symptomatic maternal illness. There was one confirmed neonatal CMV infection. Eight women did not have follow-up to determine the significance of a positive IgM result. No TORCH screen changed maternal management or neonatal outcomes. Rubella IgM was ordered in 83.5% of women who had clearly documented evidence of prior rubella immunity. No acute HSV infections were identified. Conclusion Antenatal TORCH screening for IUGR is of minimal utility and is often performed as a reflex rather than in response to specific clinical syndromes. A more guided approach with selective testing is needed. Disclosures All Authors: No reported disclosures.

268. Dengue - SARS-CoV-2 co-infection: Experience in hospitalized patients during COVID-19 pandemic

Abstract Background Dengue fever and COVID-19 co-infection constitute a significant public health concern in Latin America, becoming a clinical challenge to distinguish these two entities in early stages of the disease. Clinical outcomes of coinfected hospitalized patients have not been well established. Methods A cross-sectional study was conducted. We included suspected patients diagnosed with COVID-19/dengue co-infection admitted at Hospital Fundación Valle del Lili, Cali – Colombia, from March 2020 to March 2021. All dengue patients had positive NS1 and/or IgM dengue antibodies. SARS-CoV-2 infection was confirmed by RT-PCR or antigen rapid test from nasopharyngeal swab. Laboratory and clinical data were recollected from the clinical laboratory database, clinical charts, and institutional COVID-19 registry. Results A total of 90 COVID-19 patients were included. 72 patients were confirmed only with COVID-19, and 18 with dengue co-infection. Most patients were male: 46 (63.9%) vs. 13 (72.2%). None of these study patients were vaccinated against COVID-19 or dengue. The median time from symptoms onset and the diagnosis was five days, and fever was the most common symptom for both groups. There were significant differences between COVID-19 patients and coinfected patients regarding presence of dyspnea (22.2% vs. 61.1%; p=0.003), desaturation (13.4% vs. 53.3%; p=0.002) and a higher neutrophil/lymphocyte ratio (NLR) (3.84 vs. 5.59; p = 0.038). The co-infection was associated with a worse presentation of the COVID-19 infection (p=0.002), an increased requirement of initial supplemental oxygen therapy (p=0.007), mechanical ventilation (p=0.0004), ICU management at the admission (p=0.002), and ICU final management (p=0.002). Overall mortality in patients with co-infection was 44.4% vs. 6.9% in only COVID-19 infected patients (p&amp;lt; 0.001). Conclusion Despite the pandemic era, the possibility of co-infection of these two entities must be considered. Admitted coinfected patients were associated with worse clinical outcomes and higher mortality. According to our results, patients with co-infection present with severe respiratory symptoms and an elevated NLR. The impact of the Covid 19 vaccination on this coinfection is unknown. Disclosures Olga Agudelo, n/a, Fundación valle del lili: Board Member.

1375. Validation of a Syndromic Surveillance Query for Lyme Carditis – New York, 2017-2021

Abstract Background Lyme carditis is a rare and potentially fatal manifestation of Lyme disease. Although Lyme disease is nationally notifiable, data on specific clinical manifestations are not collected systematically. We sought to use a novel syndromic surveillance query to identify patients with Lyme carditis in New York State (excluding New York City) during 2017-2021. Methods Using the National Syndromic Surveillance Program’s BioSense Platform, we developed a query using a combination of diagnosis codes and chief complaint terms to identify emergency department visits related to Lyme carditis. We systematically reviewed and abstracted key information in each identified individual medical record through New York’s regional health information exchange system, requesting supplemental records when needed. Two physicians independently assigned a clinical case status (confirmed; probable; not a case) to each abstracted record; when adjudications differed, an infectious disease physician provided a final adjudication. Positive predictive value for the query was calculated and characteristics of cases and non-cases were described. Results The query identified 175 individuals. Records were available for review for 139 individuals. Among these, 37% (n = 52) were classified as confirmed, 17% (n = 24) as probable, and 45% (n = 63) as not a case. In total, we identified 76 cases of confirmed or probable Lyme carditis for which records were available; the positive predictive value of the query was 45%. Cases occurred in 28 of New York’s 57 counties (excluding New York City); most (64%) occurred during May–September. Median age was 60 years for cases (IQR 33 – 73) and 67 years for non-cases (IQR 42 – 78) (p = 0.13); 29% of cases and 38% of non-cases were female (p = 0.23). Among cases, 76% had positive IgG or IgM immunoblots and 37% had second- or third-degree atrioventricular block. Conclusion Using a syndromic surveillance query, we detected 76 cases of Lyme carditis, a rare disease of public health importance. Syndromic surveillance using this query may provide a useful marker for Lyme-endemic states to use to detect changing disease patterns, including temporal or spatial clusters of severe Lyme disease manifestations. Disclosures All Authors: No reported disclosures.

The long-term dynamics of serum antibodies against SARS-CoV-2.

To analyze the long-term dynamics of antibodies against SARS-CoV-2 and understand the impact of age, gender, and viral load on patients' immunological response. Serum samples were obtained from 231 COVID-19 positive patients from Macaé, in Rio de Janeiro state, in Brazil, from June 2020 until January 2021. The production of IgA, IgM, IgG, and IgE against S glycoprotein was analyzed using the S-UFRJ assay, taking into account the age, gender, and viral load. Analysis of antibody production over 7 months revealed that IgA positivity gradually decreased after the first month. Additionally, the highest percentage of IgM positivity occurred in the first month (97% of patients), and declined after this period, while IgG positivity remained homogeneous for all 7 months. The same analysis for IgE revealed that almost all samples were negative. The comparison of antibody production between genders showed no significant difference. Regarding the age factor and antibody production, patients aged ≥60 years produced almost twice more IgA than younger ones (17-39 years old). Finally, a relationship between viral load and antibody production was observed only for older patients. Our work provides an overview of long-term production of antibodies against SARS-CoV-2, suggesting prolonged production of IgA and IgM antibodies for 3 months and continued IgG production for over 7 months. In addition, it identified a correlation between viral load and IgM titers in the older group and, finally, different IgA production between the age groups.

Genotypes of the Congo-Crimean Hemorrhagic Fever Virus Occurring in the Turkestan Region

Background: The Turkestan region of Kazakhstan is the natural focus of the Congo-Crimean hemorrhagic fever (CCHF). Every year, some of the patients treated in hospitals are not included in official statistics and remain in the group of possible cases of CCHF. Objectives: This study aimed to verify the genotypes of the CCHF virus (CCHFV) in the Turkestan region and Shymkent City. Methods: Twelve blood samples from patients with CCHF were studied, the diagnosis of which was verified on the basis of positive specific immunoglobulins IgM to the virus. To isolate viral RNA, we used a special MAGNO-sorb kit. To detect RNA, CCHFV was used with a set of Amplisens CCHFV-FL by real-time polymerase chain reaction (PCR) using a Rotor-Gene Q device. For the reverse transcription reaction, we used a set of Reverta-L. Results: The study of the genome sequence of CСHFV from GenBank demonstrated that isolates from the Turkestan region belonged to genetic groups Asia-1 and Asia-2. Conclusions: For the first time in Kazakhstan’s history, a phylogenetic analysis of RNA sequences of viruses from patients with CCHF was performed in the Turkestan region, as a result of which genetic groups Asia-1, reassortant Asia-1, and Asia-2 were established

Anti-SARS-CoV-2 Antibody Status at the Time of Hospital Admission and the Prognosis of Patients with COVID-19: A Prospective Observational Study.

The association between COVID-19 severity and antibody response has not been clearly determined. We aimed to assess the effects of antibody response to SARS-CoV-2 S protein at the time of hospital admission on in-hospital and longitudinal survival. Methods: A prospective observational study in naive hospitalised COVID-19 patients. The presence of anti-S SARS-CoV-2 IgM and IgG was evaluated using a lateral flow assay at the time of admission. The patients were followed up for 8-30 months to assess survival. We recruited 554 patients (330 men and 224 women). Overall, 63.0% of the patients had positive IgG or IgM anti-S SARS-CoV-2 antibodies at the time of hospital admission. In the univariate analysis, the patients with negative anti-S SARS-CoV-2 IgM and IgG antibodies were referred to the hospital sooner, had lower CRP and D-dimer concentrations, and were hospitalised longer. They were also more likely to be admitted to an intensive care unit and more often received baricitinib treatment. During their hospital stay, 8.5% of the antibody-positive and 22.3% of the antibody-negative patients died (p = 0.0001). The median duration of the follow-up was 21 months. During the follow-up after hospital discharge, 3.6% of antibody-positive and 9.1% of antibody-negative patients died (p = 0.027). In the multivariate analysis, the negative anti-S SARS-CoV-2 antibodies were associated with a higher risk of in-hospital death (OR 3.800; 95% CI 1.844-7.829; p = 0.0001) and with a higher risk of death during follow-up (OR 2.863; 95% CI 1.110-7.386; p = 0.030). These associations were independent of age, the time from symptom onset to hospital admission, CRP, D-Dimer, the number of comorbidities, disease severity at the time of hospital admission, and baricitinib therapy. Our study concludes that negative anti-S SARS-CoV-2 IgM and IgG at the time of admission are associated with higher in-hospital mortality and cause a higher risk of all-cause death during follow-up after discharge.

The interaction of persistent antiphospholipid antibodies positivity and cigarette smoking is associated with an increased risk of cardiovascular events: Cross-sectional and longitudinal analysis

BackgroundThe antiphospholipid antibody (aPL)-positivity was suggested as a nontraditional risk of coronary artery disease (CAD) and it was associated with cigarette smoking. The co-occurrence of them was usually reported in individuals with cardiovascular diseases. This study was to demonstrate their interaction on the increasing risk of cardiovascular events. Methods and resultsA total of 826 consecutive male individuals who underwent coronary angiography (CAG) /percutaneous coronary intervention (PCI) were prospectively followed and classified into three groups based on different smoking statuses. The current smoking subjects had the highest occurrence of aPL-positivity, including aCL IgM (20.1%) and aβ2GP1 IgM (15.5%). IgM isotype positivity was an independent risk factor of CAD in the multivariate model, OR: 2.70 (1.52–4.80) for aCL IgM and OR:2.50 (1.35–4.63) for aβ2GP1 IgM.The interaction of current smoking and IgM isotype positivity was significantly associated with increased risk of CAD, OR: 8.75(4.59–16.66) for aCL IgM and OR: 8.78(4.28–17.98) for aβ2GP1 IgM. During about 3 years of follow-up, the smoking patients carrying persistent aPL positivity had the highest cumulative incidence of recurrent myocardial infarction and in-stent restenosis after CAD. ConclusionThe interaction of current smoking and IgM isotype positivity was significantly associated with the increased risk of CAD, including positive aCL IgM and aβ2GP1 IgM. Cigarette smoking elevated the risk of subsequent cardiovascular events in the presence of IgM isotype positivity, including recurrent myocardial infarction and in-stent restenosis.

The Clinical Response of California Serogroup Virus Neuroinvasive Disease in a Pediatric Patient to Intravenous Immunoglobulin (IVIG) Therapy

Objective NA. Background California serogroup (CSG) viruses are commonly associated with neurologic disease. There are few cases of CSG viruses where IVIG has been proven to help. We report a young child with neuroinvasive CSG virus encephalitis treated with IVIG and associated outcome. Design/Methods A retrospective chart review. Results A 6 year old boy, previously healthy presented with fluctuating mental status with vomiting, fatigue, and fever starting six days prior to presentation. He began to have repetitive movements of rubbing his nose, and twisting movements of the upper extremities with mild eye deviation to the left with no EEG correlate. He required PICU admission for desaturations and altered mental status requiring intubation with sedation. He was found to have positive serum IgG and IgM antibody titers 1:128 of CSG viruses. IgG and IgM antibody titers of CSG viruses was negative (&lt;1:1) in CSF. Of note he was positive for human metapneumovirus IgM antibodies. His serum and CSF NMDA was negative suggesting California encephalitis is not likely associated with NMDA encephalitis. His MRI brain resulted with extensive diffusion restriction throughout the frontal, parietal, and temporal cortex as well as non-diffusion restricting signal abnormality involving the basal ganglia and brainstem, suggesting a para-infectious encephalitis. He received IVIG given his worsening mental status starting on day 14 of admission. Neurological symptoms gradually improved after IVIG treatment. Despite therapies he displayed difficulties with focus and attention. 6 months after initial presentation his routine EEG showed frequent, sleep activated, 1-3 seconds bursts of irregular generalized spikes-and-slow wave complexes. Patient was continued on levetiracetam with no seizures. Conclusions This report highlights a severe case of encephalitis with CSG viruses. Although it is not clear whether time or IVIG helped in this patient case, it seemed to have shortened his acute altered mental status although he still has long-term learning difficulties.

Dengue virus encephalitis: A systematic review and critique

Background &amp; Objective: Neurological manifestations were reported in dengue fever. We hypothesize that the diagnosis of DEN virus (DENV) encephalitis based on current clinical diagnostic criteria has been made too liberally. We conducted a systematic review of the literature to clarify this, and to characterize DENV encephalitis better. Methods: We systematically review the literature using MEDLINE and PubMed databases papers published from 1st January 1960 to 31st March 2020. We grouped the cases into definite and probable DENV encephalitis. Definite DENV encephalitis required demonstration of DENV (live virus, viral antigens, RNA) in the central nervous system or CSF whereas probable DENV encephalitis required positive anti-DENV IgM in the CSF and evidence of virus or anti-DENV IgM in the serum. Results: Of the 230 publications obtained from literature search, 121 case reports and series appeared relevant to DENV encephalitis. After applying our inclusion criteria, only 42 cases (34.7%) were acceptable as DENV encephalitis: 30 (24.8%) definite and 12 (9.9%) probable cases. Our findings suggest that DENV encephalitis is more uncommon than previously thought. Part of the reason for non-inclusion may be because many studies relied solely on DENV serology for diagnosis. Cross-reactivities of anti-DENV with anti-JE virus immunoglobulins in serum or CSF occur and this limits their usefulness to distinguish DENV encephalitis from JE. Conclusions: The majority of DENV encephalitis cases reported in the literature did not satisfy a more stringent inclusion criteria. Further investigations including autopsy studies are warranted to better characterize and to understand the pathology and pathogenesis of DENV encephalitis.

Association of Serum Vitamin D with Active Human Cytomegalovirus Infections in Chinese Children with Systemic Lupus Erythematosus

Vitamin D (VD) plays an important role in infectious and autoimmune diseases. We investigated the association between the serum VD levels and active human cytomegalovirus (HCMV) infections in pediatric systemic lupus erythematosus (SLE) patients. From January 2015 to June 2021, 120 children were diagnosed with SLE, and 100 healthy children were enrolled. The serum 25-hydroxyvitamin D [25(OH)D] levels were detected using ELISA. The serum anti-HCMV IgM antibodies were measured by a chemiluminescence immunoassay. Comparisons of the 25(OH)D levels between SLE patients and healthy children were performed, as well as subgroups of SLE patients with or without active HCMV infections. The serum 25(OH)D levels of SLE patients were significantly lower than those of healthy children (35.3 ± 12.9 vs. 49.3 ± 15.3, P < 0.001). The VD deficiency ratio was higher in SLE patients (89.2%) than that in healthy children (52.0%). The serum 25(OH)D levels in the positive anti-HCMV IgM group were significantly lower than those of the negative anti-HCMV IgM group (30.6 ± 12.3 vs. 38.2 ± 12.5, P < 0.001). A severe VD deficiency ratio was significantly higher in HCMV-IgM(+)-SLE patients (42.2%) than that in HCMV-IgM(-)-SLE patients (13.3%). This study suggested that the serum VD level is associated with active HCMV infections in pediatric SLE patients.

Investigation of Toxoplasma gondii Seropositivity in Pregnant Women in Kastamonu Province, Turkey

Toxoplasma gondii (T. gondii) is a protozoan parasite that infects most warm-blooded animal species and causes toxoplasmosis. Especially infections that occur during pregnancy can lead to serious clinical symptoms. This study retrospectively revealed the T. gondii seroprevalence of pregnant women in Kastamonu province, Turkey. Anti-T. gondii IgM and IgG positivity of 1.294 pregnant women between the ages of 15-44 years who applied to the Obstetrics and Gynecology Outpatients of Kastamonu Training and Research Hospital from January 2018 to January 2022 were investigated retrospectively. The IgG avidity test was performed for both anti-T. gondii IgM and IgG positivity. Anti-T. gondii IgM and IgG seropositivity were determined as 1.1% (n=14) and 20.3% (n=263), respectively. Anti-T. gondii IgM and IgG positivity were detected together in 11 pregnant women. IgG avidity test results of only six pregnant women could be reached, two pregnant had high IgG avidity, and four pregnant had low IgG avidity. Anti-T. gondii IgG positivity rate increased with increasing age (p=0.039). The number of seronegative pregnant women was considered high in Kastamonu. It is significant for expectant mothers to know about prevention methods in order not to acquire toxoplasmosis.

Pulmonary embolism and gastric bleed with disseminated mucormycosis - treading dangerous waters.

Mucormycosis is an opportunistic infection seen in immunocompromised patients or in surgical and trauma settings with Mucorales wound contamination. In immunocompetent people, disseminated mucormycosis is uncommon. To ensure survival, patients with mucormycosis require early diagnosis and aggressive treatment using a multi-modality approach. We present a case of disseminated mucormycosis in an immunocompetent patient who also had pulmonary embolism and gastrointestinal bleeding. A recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, identified retrospectively by a positive IgM against SARS-CoV-2, was the only risk factor present. This report emphasizes the increased risk of mucormycosis and thromboembolic complications following a recent SARS-CoV-2 infection, as well as its successful treatment with medical therapy alone.

A four-generation family transmission chain of COVID-19 along the China-Myanmar border in October to November 2021.

Foreign imported patients and within-household transmission have been the focus and difficulty of coronavirus disease 2019 (COVID-19) prevention and control, which has also posed challenges to border areas' management. However, household transmission caused by foreign imported cases has not been reported in China's border areas. This study aimed to reveal a clear family clustering transmission chain of COVID-19 caused by contact with Myanmar refugees along the China-Myanmar border during an outbreak in October to November 2021. During the outbreak, detailed epidemiological investigations were conducted on confirmed patients with COVID-19 and their close contacts in daily activities. Patients were immediately transported to a designated hospital for treatment and quarantine, and their close contacts were quarantined at designated sites. Regular nucleic acid testing and SARS-CoV-2 antibody testing were provided to them. A clear four-generation family clustering transmission involving five patients with COVID-19 was found along the China-Myanmar border. The index case (Patient A) was infected by brief conversations with Myanmar refugees across border fences during work. His wife (Patient B) and 9-month-old daughter (Patient C) were second-generation cases infected by daily contact with him. His 2-year-old daughter (Patient D) was the third-generation case infected by her mother and sister during quarantine in the same room and then transmitted the virus to her grandmother (Patient E, the fourth-generation case) who looked after her after Patients B and C were diagnosed and transported to the hospital. The household secondary attack rate was 80.0%, the average latent period was 4 days, and the generation time was 3 days. Ten of 942 close contacts (1.1%) of this family had positive IgM antibody during the medical observation period. In total 73.9% (696/942) of them were positive for IgG antibody and 8.3% (58/696) had IgG levels over 20 S/CO (optical density of the sample/cut-off value of the reagent). This typical transmission chain indicated that it is essential to strengthen COVID-19 prevention and control in border areas, and explore more effective children care approaches in quarantine sites.

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated with Expansion and Maturation of NK Cells

ABSTRACT Background. Hodgkin Lymphoma (HL) Hodgkin Lymphoma (HL) is a B-Cell neoplasia characterized by a high degree of response to chemotherapy and an overall favourable outcome in responding patients. Despite the efficacy of first line therapy, however, about 30% of patients affected by HL are either refractory or eventually relapse (R/R) after first or second line therapy followed by autologous hemopoietic stem cell transplantation (ASCT). Immune checkpoint inhibitors (CI) have demonstrated clinical activity in HL patients relapsing after ASCT, although only 20% complete response (CR) rate are usually observed. The efficacy of CI is strictly related to the host immune competence, which is impaired in heavily pre-treated HL patients. Aims. Here, we aimed to enhance the activity of early post-ASCT CI (nivolumab) administration with the infusion of autologous lymphocytes (ALI) and to investigate the lymphocyte subpopulation involved in the mechanism of response to CI in HL. Results. Seventeen patients with relapse/refractory (R/R) HL (median age 29 years; range 18-65), underwent lymphocyte apheresis after first line chemotherapy and then proceeded to salvage therapy. Subsequently, 12 patients with progressive disease at ASCT received early post-transplant CI supported with four ALI, whereas 5 responding patients received ALI alone, as a control cohort. Most patients showed CMV seropositivity at the time of enrolment, without signs of active infection (positive anti-CMV IgG, negative IgM and undetectable CMV DNA). No adverse events were recorded, specifically, no immune-related toxicity was observed and none of the patients showed CMV reactivation. All patients receiving ALI + CI (treated patients) achieved negative PET scan CR and 11/12 are alive and disease-free after a median follow-up of 33 months. The only relapse occured 23 months after last ALI. Six of the responding patients underwent subsequent allogeneic SCT in a CR status and 1 patients are currently waiting for transplantation. Two of the patients in the control arm relapsed after a median of 6 months (4-8 months) Phenotypic analysis of circulating cells showed a faster expansion of highly differentiated NK cells in ALI plus nivolumab-treated patients as compared to control patients (Fig.1). In detail, different patterns of NK cell development could be identified. Indeed, starting from one month after transplantation, in the group of patients undergoing ALI plus nivolumab, a relevant fraction of NK cells displayed a mature phenotype characterized by a CD56dimCD16bright expression (Fig. 1). On the contrary, in control patients, NK cells were characterized by a more immature phenotype (high frequencies of CD56brightCD16neg/dim NK cells) even at late time points (three months) after transplantation (Fig. 1). This event occurred in all the treated (ALI + nivolumab) patients analyzed (Fig. 1). Finally, PB from patients undergoing ALI + nivolumab was enriched in unconventional CD56dimCD16dim NK cells (Fig. 1). One month after transplantation, CD94/NKG2A+ KIR- NK cells were largely predominant in all patients, whereas CD94/NKG2A- KIR+ NK cells were present in low proportions. An increase of CD94/NKG2A- KIR+ subset occurred primarily in treated patients starting from t2. At t3, the significant increase of CD94/NKG2A- KIR+ NK cells occurred in the treated group but not in the control group . This event occurred in all the treated (ALI + nivolumab) patients analyzed, regardless of their serological status for HCMV, but was more evident in treated patients who were seropositive for HCMV. Remarkably, PB from HCMV seropositive patients undergoing ALI + nivolumab became enriched over time in differentiated NK cells characterized by high expression of NKG2C receptor (the activating counterpart of NKG2A), as compared to HCMV+ control patients. This subset represents the so-called "adaptive" NK cell population that usually increases during HCMV infection/reactivation. In this case, however, this event occurred in the absence of HCMV reactivation, and only in HCMV seropositive patients treated with ALI + nivolumab. Conclusions. Our data show anti-tumour activity with good tolerability of ALI + CI for R/R HL and suggest that this setting may accelerate NK cell development/maturation and favour the expansion of the "adaptive" NK cell compartment, especially in patients with CMV seropositivity, in the absence of CMV reactivation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Value of diagnosing immunological phenomena in patients with suspected endocarditis

PurposeImmunological phenomena are a minor criteria in the modified Duke Criteria for endocarditis. Given the changes in epidemiology and diagnostics, the added value of determining these phenomena in today’s patients with suspected endocarditis is unknown.MethodsIn a retrospective cohort study of all patients with suspected endocarditis admitted to our hospital and discussed in our endocarditis team, we determined the proportion of patients classified as definite endocarditis because of either positive IgM rheumatoid factor (IgM RF), haematuria, or Roth’s spots on ophthalmology consultation. We also determined diagnostic accuracy of each of these immunological phenomena separately and combined.ResultsOf 285 patients included, 138 (48%) had definite endocarditis and at least one immunological test was performed in 222 patients (78%). Elevated IgM RF was found in 22 of 126 patients tested (17%), haematuria in 78 of 196 tested (40%) and Roth’s spots in six of 120 tested (5%). Eighteen of 138 patients with definite IE (13%) were classified as such because of a positive IgM RF, haematuria or Roth’s spots. Haematuria had the highest sensitivity: 50.5% (95% CI 40.4–60.6) and Roth’s spots the highest specificity: 98.3% (95% CI 90.8–99.9). The diagnostic accuracy results were robust in a sensitivity analysis aimed at avoiding incorporation bias.ConclusionAmong patients with a clinical suspicion of endocarditis, recommended systematic testing for immunological phenomena helped classify more patients as definite IE and is useful to confirm the diagnosis of endocarditis.

Peripheral smear reckons the nature of IgM cold agglutinins: A case‐based study asserting the role of thermal amplitude and clonality

Peripheral smear reckons the nature of IgM cold agglutinins: A case‐based study asserting the role of thermal amplitude and clonality

Positivity of dengue, chikungunya, and Zika infections in women in Northeast Brazil post-Zika epidemic

ABSTRACT The state of Ceará, in the Northeast Region of Brazil, presents the simultaneous circulation of Zika (ZIKV), dengue (DENV) and chikungunya (CHIKV) viruses. In 2017 there were a high number of cases of these three arboviruses, especially CHIKV. Here, we detected the presence of arboviruses ZIKV, DENV and CHIKV and their coinfections in women in endemic regions of the city of Fortaleza, Ceará in a post-Zika epidemic year. Sociodemographic and environmental characteristics associated with arbovirus positivity were also analyzed. Women (n = 1289) between 15 and 39 years old were included. RT-qPCR was performed for virus detection and IgM antibody positivity was also analyzed. One hundred and six (8.3%) participants were positive for one or more arboviruses. Monoinfections (76; 5.9%) were distributed between 22 (1.7%) for ZIKV, 39 (3.1%) for DENV and 15 (1.2%) for CHIKV. Co-infections were detected in 30 (2.3%) of the positive participants and one case with triple infection was found. IgM positivity was found in 2.4% of ZIKV RT-qPCR, 9.6% of DENV and 16.3% of CHIKV. RT-qPCR positivity for arboviruses was associated with low socioeconomic class and presence of a water box sealing in the household. A higher positivity to the three viruses occurred in the month with the lowest wind velocity, which was also preceded by the highest peak of rain and humidity. We identified the simultaneous circulation and co-infection of ZIKV, DENV and CHIKV in Fortaleza in a post-Zika epidemic year. We also highlight the need for continuous epidemiological surveillance combined with molecular diagnostic tools.

PREDICTORS OF SEVERITY OF DENGUE IN PATIENTS ADMITTED TO ICU: A CROSS SECTIONAL STUDY

Background &amp; Objectives: Dengue mostly causes a mild self-limiting disease but a small proportion may progress to develop severe dengue clinical manifestations, which require interventions in intensive care. The objective of the study was to describe the clinical profile, course, and outcome of dengue-infected patients admitted to intensive care units (ICU) and to evaluate factors associated with morbidity and mortality. Methods: This is an observational, descriptive study. Patients above the age of 18 admitted directly or transferred to ICU from another ward with serological evidence of dengue (positive NS1 antigen and/or IgM antibodies to dengue) were included in the study. The severity of the illness was assessed using APACHE and SOFA Scores. The primary outcome was mortality, while the secondary outcome was the length of stay in the ICU. Results: A total of 80 patients were studied and the mean age of the study subjects was 36.53 (± 15.28) years. The median duration of ICU stay was 2 days with an IQR of (1-3) days. The mean APACHE was 21.53 (±10.91) while the mean SOFA score was 12.05 (± 4.70). The area under the curve for the WHO classification of severe dengue was 79%, with a positive predictive value of 58.70. The area under the curve for lactate was 89% with a positive predictive value of 90.48. Interpretation &amp; Conclusion: Lactate alone is a good predictor of mortality in severe dengue. APACHE and SOFA scores are good predictors of mortality.