Clinical Features and Prognosis in Chinese Patients With Dipeptidyl–Peptidase–Like Protein 6 Antibody–Associated Encephalitis

Objectives:Anti-dipeptidyl–peptidase–like protein 6 (anti-DPPX) encephalitis an extremely rare type of immune-mediated encephalitis. This study aimed to analyze the electroclinical characteristics and prognosis of anti-DPPX encephalitis.Methods:Five patients (all male) with anti-DPPX encephalitis in East China from January 2016 to October 2021 was retrospective analyzed. Electroclinical features and outcomes were reviewed.Results:All five patients were male. The media age at disease onset was 32 years old with a range of 14–56 years. The main symptoms included psychiatric disturbances (2/5), amnesia (4/5), confusion (3/5), and seizures (3/5). Migrating myoclonus were identified in patient 4 with positive DPPX and contactin-associated protein-like 2 antibodies in blood. All of the patients had positive DPPX antibodies in serum. Only one of them had positive antibody in the cerebrospinal fluid. EEG showed diffuse slowing in two patients, but no epileptiform discharges were observed. Eighty percent (4/5) of the patients showed normal brain magnetic resonance imaging. After immunotherapy, improvement of neuropsychiatric symptoms from all of the patients was observed. Over a mean follow-up of 30.8 weeks, all of the patients had marked improvement in the modified Rankin Scale. To date, no tumors were not observed in any patients.Conclusions:Anti-DPPX encephalitis mainly presents as neuropsychiatric symptoms. Cooperation of DPPX antibodies and CASPR2 antibodies might have contributed to the migration of myoclonus in the patient 4. Prompt immunotherapy often results in improvement.

Prolonged COVID-19 infection in a child with lymphoblastic non-Hodgkin lymphoma: which is the best management?

During the coronavirus disease 2019 (COVID-19) pandemic, oncologists have managed patients at higher risk of having a severe course of this infection. This raises new questions about their correct management, as well as the difficulty of distinguishing tumor/treatments complications from those related to COVID-19. We report a case of an 11-year-old boy undergoing treatment for T-cell lymphoblastic lymphoma who experienced a prolonged COVID-19 course. Oncologic therapy was continued without significant changes compared to the initially planned treatment. No relevant complications occurred. COVID-19 convalescent plasma was administered, resulting in a positive antibody titer after 24 days.

Evaluation of Anti-SARS-CoV-2 IgG Antibody in Healthcare Professionals Infected with COVID-19

Background: The knowledge of antibody’s significance and frequency in patients cured of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is extremely limited. Objectives: This study aimed to evaluate anti-SARS-CoV-2 IgG antibodies in patients exposed to SARS-CoV-2. Methods: Healthcare professionals infected with SARS-CoV-2 were enrolled in this study. The levels of anti-SARS-CoV-2 IgG antibodies were detected 15 days after the onset of symptoms and five months later. Results: A total of 167 patients with coronavirus disease 2019 (COVID-19) were evaluated, including 119 (71.3%) females and 48 (28.7%) males. Of the 88 polymerase chain reaction (PCR)-positive patients, 55 (62.5%) had IgG-positive antibodies, and of the 79 reverse transcriptase (RT)-PCR-negative patients, 12 (16.9%) had IgG-positive antibodies. Out of 23 anosmia cases, 19 (82.6%) had positive antibodies. There was a significant relationship between anosmia and positive antibody (P = 0.001), but there was no correlation between antibody titers and gender and other disease symptoms. Immortally, 63 (94%) cases demonstrated high levels of anti-SARS-CoV-2 IgG antibodies after five months of infection. Moreover, 6.5% (N = 11) of the total population were re-infected with COVID-19 six months later. Conclusions: Overall, anti-SARS-CoV-2 IgG antibodies detection may be an appropriate method to identify suspected patients with a negative RT-PCR test. Antibodies can remain high in most infected patients for up to five months after infection. Moreover, anosmia seems to be a valuable diagnostic factor, and the healthcare system should implement isolation measures for patients with anosmia.

Evaluation of SARS-CoV-2 Antibody Point of Care Devices in the Laboratory and Clinical Setting

SARS-CoV-2 Antibody tests have been marketed to diagnose previous SARS-CoV-2 infection and as a test of immune status. There is a lack of evidence on the performance and clinical utility of these tests. We aimed to carry out an evaluation of 14 point of care (POC) SARS-CoV-2 antibody tests. Serum from participants with previous RT-PCR (Real-Time Polymerase chain reaction) confirmed SARS-CoV-2 infection and pre-pandemic controls were used to determine specificity and sensitivity of each POC device. Changes in sensitivity with increasing time from infection were determined on a cohort of participants. Corresponding neutralising antibody status was measured to establish whether the detection of antibodies by the POC device correlated with immune status. Paired capillary and serum samples were collected to ascertain whether POC devices performed comparably on capillary samples. Sensitivity and specificity varied between the POC devices and in general did not meet the manufacturers reported performance characteristics signifying the importance of independent evaluation of these tests. The sensitivity peaked at >20 days following symptoms onset however sensitivity of 3 POC devices evaluated at extended time points showed that sensitivity declined with time and this was particularly marked at >140 days post infection onset. This is relevant if the tests are to be used for sero-prevelence studies. Neutralising antibody data showed positive antibody results on POC devices did not necessarily confer high neutralising antibody titres and these POC devices cannot be used to determine immune status to the SARS-CoV-2 virus. Comparison of paired serum and capillary results showed that there was a decline in sensitivity using capillary blood. This has implications in the utility of the test as they are designed to be used on capillary blood by the general population.

Antibody Response to BNT162b2 Vaccine in Immune Modifiers–Treated Psoriatic Patients

Background Data regarding anti–COVID-19 vaccination efficacy in psoriasis patients treated with immune-modulatory medications are scarce. Objective This study aims to examine the rate of positive antibody response following BNT162b2 vaccine in those patients. Methods BNT162b2-vaccinated and immune modifier–treated psoriatic patients were assigned to serological testing of IgG antibodies to protein S of SARS-CoV-2 after the second vaccination dose by Abbott Architect or Beckman Coulter. Levels ≥ 1 S1 units/mL (S/ml) and > 150 arbitrary units/ml (AU/ml) are considered a positive antibody response, respectively. The antibody levels further analyzed according to the patient’s characteristics and compared to health workers’ controls. Results Forty-nine of the 51 patients had a positive antibody response. Overall, patients treated with immune-modulatory medications had antibody levels similar to the control group. Conclusions Immune modifier–treated psoriasis patients seem to develop a positive antibody response to the full BNT162b2 vaccination in the vast majority of cases.

Every-Other-Day Valganciclovir Prophylaxis for Cytomegalovirus Prevention in Kidney Transplant Recipients: A Single-Center Experience

Background: Moderate-risk for Cytomegalovirus (CMV) infection includes patients with donor positive/recipient positive (D+/R+) or donor negative/ recipient positive antibody status (D-/R+). Guidelines recommend high-dose daily Valganciclovir (VGCV) as prophylaxis, which may be due to the paucity of data on the efficacy of every-other-day VGCV. Methods: Our experience of using every-other-day VGCV as a prophylactic strategy in moderate risk Kidney Transplant Recipients (KTR) has been described. We retrospectively reviewed 86 moderate-risk KTR in our institution between 2018 and 2020. CMV infection at 6 months post-transplant was the primary endpoint. Graft survival, biopsy-proven rejection, opportunistic infections, Haematological adverse events, and mortality were also evaluated. Results: CMV infection occurrence at 6 months was zero in our cohort. Incidence of leukopenia was 13%, BPAR-31%, OI-33%, and mortality being 3.5%. Conclusion: Every-Other-Day VGCV dosing can be an effective alternative in moderate risk KTR for CMV prevention.

Natural immunogenic properties of bioinformatically predicted linear B-cell epitopes of dengue envelope and pre-membrane proteins

Background The natural antibody responses to B-cell epitopes from dengue structural proteins were assessed using immune sera from people having well-defined past dengue infections with one of the four serotypes. Method Based on an immune-computational analysis previously conducted, nineteen epitopes from the envelope (E) and eight epitopes from pre-membrane (prM), which were more than 50% conserved across all the four DENV serotypes, were selected. Peptides to represent these B-cell epitopes were obtained from commercially available arrays, and were subjected to enzyme linked immunosorbent assay with sera obtained from dengue seropositive healthy volunteers (DENV1 n = 12: DENV2 n = 12: DENV3 n = 12 and DENV4 n = 12), and 10 dengue seronegative healthy volunteers from Sri Lanka. The cut-off value for the positive antibody response was set by taking the mean response of a peptide to the negative sera plus three standard deviations. The peptides (N = 7) showing the broad immune responses were used to generate antibodies in three mice (Balb/c) batches. The mice antisera were then subjected to microneutralization assays against all the four DENV serotypes. An EC50 viral neutralization ≥ 40 times the serum dilution was considered as neutralizing. Results Five of the E-peptide and two prM peptides were recognised by most individuls exposed to infections with each of the four serotypes, showing a serotype cross-reactive broad antibody response. The mice immune sera against the peptides representing the five E protein epitopes neutralized all the four DENV serotypes. Two of these five epitopes are from the Domain II, whereas one of them includes the whole bc-loop region. Conclusion The antibody responses of highly conserved epitopes across the serotypes, were broadly responsive with sera of all four DENV serotypes collected from individuals infected with only one DENV serotype. Weakly conserved epitopes showed rather specific antibody responses dominated by one or few serotypes.

Feasibility of SARS-CoV-2 Antibody Testing in Remote Outpatient Trials

Background During the Covid-19 pandemic, clinical trials necessitated rapid testing to be performed remotely. Dried blood spot (DBS) techniques have enabled remote HIV virologic testing globally and more recently, antibody testing as well. We evaluated DBS testing for SARS-CoV-2 antibody testing in outpatients to assess seropositivity. Methods In 2020, we conducted three internet-based randomized clinical trials and offered serologic testing via self-collected DBS as a voluntary sub-study. COVID-19 diagnosis was based on CDC case definition with epidemiological link to cases. A minority reported PCR testing at an outside facility. We tested for anti-SARS-CoV-2 immunoglobulin via Antibody Detection by Agglutination-PCR (ADAP) and compared with ELISA. Results Of 2727 participants in the primary studies, 60% (1648/2727) consented for serology testing; 56% (931/1648) returned a usable DBS sample. Of those asymptomatic, 5% (33/707) had positive ADAP serology. Of participants with a positive PCR, 67% (36/54) had positive SARS-CoV-2 antibodies. None of those who were PCR-positive and asymptomatic were seropositive (0/7). Of 77 specimens tested for concordance via ELISA, 83% (64/77) were concordant. Challenges of completing a remote testing program during a pandemic included sourcing and assembling collection kits, delivery and return of the kits, and troubleshooting testing. Self-collection was successful for >95% of participants. Delays in US mail with possible sample degradation and timing of DBS collection complicated the analysis. Conclusion We found remote antibody testing during a global pandemic feasible although challenging. We identified an association between symptomatic COVID-19 and positive antibody results at similar prevalence to other outpatient cohorts.

Hyperhemolysis Syndrome Following Pre-Operative Red Blood Cell Exchange

Introduction/Objective Pre-operative red blood cell exchange (RBCX) for patients with Sickle Cell Disease (SCD) is a category III indication. In our institution, RBCX is routinely performed pre-operatively when general anesthesia is necessary with the goal of HbS%<30 and reduction in adverse events related to general anesthesia. In the context of elective surgery, the risks and benefits of both the operation and any pre-operative transfusion must be discussed with the patient. Herein, we present an extreme case of Hyperhemolysis Syndrome resulting from a pre-operative RBCX. Methods/Case Report A 23-year-old transgender female with SCD (Hb S Lepore) treated with Hydroxyurea presented for elective breast augmentation for gender-affirmation. Her pre-operative plan included a RBCX. Her pre-exchange hemoglobin (Hb) and hematocrit (Hct) were 10.3 g/dL and 29.3%, respectively. Hb electrophoresis revealed HbS 52%, HbF 41.4%, HbA2 7.4%, and HbA was not detected. Type and Screen (T&S) demonstrated O + blood group, with a negative antibody screen, and with no known historical alloantibodies. RBCX was performed using the Spectra Optia (TerumoBCT, Lakewood, CO, USA) with exchange volume of 1.9 L of group O+ RBCs, phenotypically matched for C, E, and K, an end Hct of 30% and an FCR of 30%. Her post-exchange Hb and Hct were 10.2g/dL and 29.5%, respectively. Hemoglobin fractionation revealed HbS 12% and HbA 73%. She underwent surgery without intraoperative complications. Two weeks post RBCX, her Hb had decreased to 5.3 g/dl, and her LDH and Total Bilirubin had increased to 253 ul and 1.8 mg/dl, respectively. A repeat T&S drawn 8 days after RBCX revealed a positive antibody screen and direct antiglobulin test (DAT). Three new alloantibodies were identified: anti-Fya (present in plasma and eluate); anti-Jkb (present in plasma); anti-S (eluate). She was treated with IVIG, 0.4 g/Kg/day for 5 consecutive days and 2 doses of subcutaneous darbepoetin 100 mcg and subsequently discharged with close outpatient follow up. Her Hb returned to baseline at 11 g/dL, 48 days post RBCX. Results (if a Case Study enter NA) N/A Conclusion Pre-operative RBCX decreases morbidity in sickle cell patients undergoing general anesthesia. In the setting of elective surgery, patients must be counseled on the benefits and risks of surgery as well as the requisite RBCX. In our case, the patient developed multiple alloantibodies, with lifelong implications should she ever need future blood transfusions.