Negative Antibody Test Research Articles

Post-infectious Non-paraneoplastic Autoimmune Retinopathy in Paediatric age group: A high index of suspicion, Multimodal Imaging and Early treatment can restore vision.

To report a case of non-paraneoplastic Auto-immune retinopathy (npAIR) in a paediatric patient who showed excellent visual recovery with early diagnosis and prompt treatment. Retrospective Case report. A five year old girl presented to us with bilateral profound vision loss of sub-acute onset following an episode of high fever, without any previous visual abnormality. A diagnosis of npAIR was made based on history, clinical findings and multimodal imaging. Intravenous methylprednisolone was started urgently followed by oral steroid. Visual acuity showed good improvement along with gradual restoration of anatomy of retinal layers in Optical Coherence Tomography (OCT) over a period of three months. Our case highlights the importance of suspecting npAIR in paediatric patients presenting with sudden bilateral painless progressive loss of vision without prior visual difficulties and the role of multimodal imaging to aid in diagnosis. The recovery of vision with restoration of photoreceptor layer also shows the nature of the disease to recover with early intervention despite a negative anti-retinal antibody test but with features highly suggestive of npAIR.

In the SARS-CoV-2 Pandora Pandemic: Can the Stance of Premorbid Intestinal Innate Immune System as Measured by Fecal Adnab-9 Binding of p87:Blood Ferritin, Yielding the FERAD Ratio, Predict COVID-19 Susceptibility and Survival in a Prospective Population Database?

SARS-CoV-2 severity predictions are feasible, though individual susceptibility is not. The latter prediction allows for planning vaccination strategies and the quarantine of vulnerable targets. Ironically, the innate immune response (InImS) is both an antiviral defense and the potential cause of adverse immune outcomes. The competition for iron has been recognized between both the immune system and invading pathogens and expressed in a ratio of ferritin divided by p87 (as defined by the Adnab-9 ELISA stool-binding optical density, minus the background), known as the FERAD ratio. Associations with the FERAD ratio may allow predictive modeling for the susceptibility and severity of disease. We evaluated other potential COVID-19 biomarkers prospectively. Patients with PCR+ COVID-19 tests (Group 1; n = 28) were compared to three other groups. In Group 2 (n = 36), and 13 patients displayed COVID-19-like symptoms but had negative PCR or negative antibody tests. Group 3 (n = 90) had no symptoms and were negative when routinely PCR-tested before medical procedures. Group 4 (n = 2129) comprised a pool of patients who had stool tests and symptoms, but their COVID-19 diagnoses were unknown; therefore, they were chosen to represent the general population. Twenty percent of the Group 4 patients (n = 432) had sufficient data to calculate their FERAD ratios, which were inversely correlated with the risk of COVID-19 in the future. In a case report of a neonate, we studied three biomarkers implicated in COVID-19, including p87, Src (cellular-p60-sarcoma antigen), and Abl (ABL-proto-oncogene 2). The InImS of the first two were positively correlated. An inverse correlation was found between ferritin and lysozyme in serum (p < 0.05), suggesting that iron could have impaired an important innate immune system anti-viral effector and could partially explain future COVID-19 susceptibility.

A Case Report: False-Negative HIV Antibody Test in a Patient Presenting With an Unusual Case of Cytomegalovirus Oropharyngeal Ulcerations

Abstract Background Cytomegalovirus (CMV) oropharyngeal ulcerations are rare diagnoses that usually only occur in immunocompromised individuals. False-negative third-generation HIV tests in a patient with AIDS are also exceedingly rare and, when they occur, underscore the complex host and viral relationships involved in HIV disease mediation. Case Presentation We present a case of CMV oropharyngeal ulcerations in a patient diagnosed with advanced AIDS with a persistently negative HIV antibody test. Confirmative testing and diagnosis of HIV were performed with a qualitative DNA polymerase chain reaction and confirmed with a quantitative RNA polymerase chain reaction. Cytomegalovirus oropharyngeal ulcerations were managed with ganciclovir 5 mg/kg with significant improvement in oral ulcers. Conclusions We present a rare case of an HIV-seronegative patient clinically diagnosed with advanced AIDS and CMV oropharyngeal ulcerations. False-negative HIV tests can delay diagnosis and treatment; hence, clinical suspicion is needed for accurate diagnosis and early treatment.

Factors associated with incomplete vaccination and negative antibody test results for measles, mumps, and hepatitis A among children followed in the MINA-BRAZIL cohort.

Vaccination coverage has been dropping in Brazil and other countries. In addition, immune responses after vaccination may not be homogeneous, varying according to sociodemographic and clinical factors. Understanding the determinants of incomplete vaccination and negative antibody test results may contribute to the development of strategies to improve vaccination effectiveness. In this study, we aimed to investigate the frequency of vaccine adherence, factors associated with incomplete vaccination for measles, mumps, rubella (MMR) and hepatitis A, and factors associated with the seronegative test results for measles, mumps and hepatitis A at 2 years of age. This was a population-based cohort that addressed health conditions and mother/infant nutrition in Cruzeiro do Sul city, Brazil. Vaccination data were obtained from official certificates of immunization. The children underwent blood collection at the two-year-old follow-up visit; the samples were analyzed using commercially available kits to measure seropositivity for measles, mumps, and hepatitis A. We used modified Poisson regression models adjusted for covariates to identify factors associated with incomplete vaccination and negative serology after vaccination. Out of the 825 children included in the study, adherence to the vaccine was 90.6% for MMR, 76.7% for the MMRV (MMR + varicella), and 74.9% for the hepatitis A vaccine. For MMR, after the adjustment for covariates, factors associated with incomplete vaccination included: white-skinned mother; paid maternity leave; raising more than one child; lower number of antenatal consultations; and attending childcare. For hepatitis A, the factors included: white-skinned mother and not having a cohabiting partner. The factors with statistically significant association with a negative antibody test result included: receiving Bolsa Familia allowance for measles and mumps; incomplete vaccination for measles; and vitamin A deficiency for mumps. Strategies to improve the efficiency of vaccine programs are urgently needed. These include improvements in communication about vaccine safety and efficacy, and amplification of access to primary care facilities, prioritizing children exposed to the sociodemographic factors identified in this study. Additionally, sociodemographic factors and vitamin A deficiency may impact the immune responses to vaccines, leading to an increased risk of potentially severe and preventable diseases.

Treatment as prevention effect of direct-acting antivirals on primary hepatitis C virus incidence: findings from a multinational cohort between 2010 and 2019

Broad direct-acting antiviral (DAA) access may reduce hepatitis C virus (HCV) incidence through a "treatment as prevention" (TasP) effect. We assessed changes in primary HCV incidence following DAA access among people living with HIV (PLHIV). We used pooled individual-level data from six cohorts from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). Follow-up started from the first recorded negative HCV antibody test date and ended at last negative antibody test or estimated infection date. Follow-up was restricted to 2010-2019. We used segmented Poisson regression to model trends across pre-, limited- (i.e., restrictions on access) and broad-DAA access periods. Overall, 45,942 participants had at least one HCV antibody negative result and follow-up between 2010 and 2019. We observed 2042 incident HCV infections over 248,189 person-years (PY). Pooled incidence decreased from 0.91 per 100 PY in 2015 to 0.41 per 100 PY in 2019. Compared to the average pre-DAA period incidence (0.90 per 100 PY), average incidence was similar during the limited-DAA access period (Incidence rate ratio [IRR]=0.98; 95%CI=0.87, 1.11), and 52% lower during the broad-DAA access period (IRR=0.48; 95%CI=0.42, 0.52). The average annual decline in HCV incidence was 2% in the pre-DAA period; an additional 9% annual decline in incidence was observed during the limited-DAA access period (IRR=0.91; 95%CI=0.82, 1.00) and a further 20% decline in the broad-DAA access period (IRR=0.80, 95%CI=0.73, 0.89). Our findings suggest that broad DAA access has a TasP effect on primary HCV incidence among PLHIV. Based on the initial years of DAA availability, the countries in the InCHEHC collaboration are on track to meet the World Health Organization's 80% HCV incidence reduction target for PLHIV by2030. This study was funded by the Australian Government National Health and Medical Research Council (Grant number GNT1132902).

Incidence of primary hepatitis C virus infection among people who inject drugs in Australia pre- and post-unrestricted availability of direct acting antiviral therapies.

The 2016 Global Health Sector Strategy (GHSS) on viral hepatitis aims to reduce new hepatitis C virus (HCV) infections by 80% by 2030, including a 30% reduction by 2020. This study aimed to estimate primary HCV incident infection among a national sample of people who inject drugs (PWID) before and after the introduction of unrestricted access to HCV direct-acting antiviral (DAA) therapy via Australia's Pharmaceutical Benefits Scheme in 2016. A simple deterministic linkage method identified repeat respondents in serial cross-sectional surveys conducted among PWID. Two separate retrospective cohorts of HCV antibody-negative respondents were created, corresponding to the pre- (2010-15) and post- (2016-21) DAA time-periods. This study took place in Australia. Among 757 PWID retained (376 pre-DAA, 381 post-DAA), more than half were male (60%), the majority were heterosexual (80%), the median age was 40 years (interquartile range = 33-46 years) and the predominant drugs last injected were heroin (24%), pharmaceutical opioids (27%) and methamphetamine (41%). The primary outcome was HCV seroconversion, defined as a negative HCV antibody test result followed by a positive HCV antibody result. Time to primary incident HCV infection was estimated using the person-years (PY) method. A total 97 of 376 (2010-15) and 41 of 381 (2016-21) HCV seroconversions were identified. Primary HCV incidence more than halved, from 13.6 per 100 PY [95% confidence intervals (CI) = 11.2, 16.6] in 2010-15 to 5.4 per 100 PY (95% CI =3.9, 7.3) in 2016-21. The decline was independent of observed differences in demographic and drug use characteristics over the two time-periods (adjusted hazard ratio =0.47, 95% CI =0.31-0.69, P<0.001). Australia has had a 53% reduction in primary hepatitis C virus (HCV) incidence among people who inject drugs following unrestricted availability of HCV direct acting antiviral therapy in March 2016. Given that PWID are the predominant population at risk of HCV infection in Australia, findings add to the evidence that Australia has probably met its 2020 Global Health Sector Strategy subtarget of a 30% decline in new infections.

Evaluation of Acute Human Immunodeficiency Virus Infection Cases

Objective: Acute HIV infection (AHI) is a stage with a rapid decrease in CD4+ T lymphocyte count, high viremia, and high transmissibility. Early diagnosis of AHI represents an opportunity for treatment and prevention of transmission. Therefore, we aimed to determine the clinical and laboratory findings in patients with acute HIV infection. Methods: Patients diagnosed with AHI among newly diagnosed HIV-infected patients were evaluated in the study. AHI diagnosis was defined as an HIV RNA result of at least 10,000 copies/ml with one of the following criteria: a negative or indeterminate HIV antibody test result in a person with a reactive Ag/Ab test result or a patient with a negative Ag/Ab test result has HIV RNA detected in serum or plasma or HIV serology positivity in a patient with signs and symptoms of AHI starting 2-6 weeks after high-risk HIV exposure. In addition, the history, clinical, and laboratory findings of patients with AHI were analyzed retrospectively. Results: One hundred six patients had a new HIV diagnosis during the study period. Of those, 12 (11.3%) were AHI. 10 (83.3%) of the patients with AHI were male, and seven were men who had sex with men. The mean age of the patients was 30 (21-50) years. Fourth-generation ELISA was negative in one patient initially; the repeated test was positive ten days later. While the 4th generation ELISA test of two patients was positive at the time of diagnosis, the confirmation test result was indeterminate. The 4th generation ELISA test was positive in nine patients with AHI symptoms starting 10-30 days after unprotected sexual intercourse. The duration of the patient’s complaints until the admission was found to be 13 (7-30) days. The most common findings were fever, diarrhea, fatigue, sore throat, lymphadenopathy, rash, nausea, and vomiting. Conclusion: The AHI rate was 11.3% in newly diagnosed cases of HIV infection. Awareness of AHI’s signs and symptoms to initiate early diagnosis and treatment. Thus, a better HIV infection course and reduced HIV transmission can be achieved.

Atypical hemolytic uremic syndrome (aHUS) responsive to mycophenolate mofetil: A case report from Nepal

An atypical hemolytic uremic syndrome is an extremely rare and life-threatening thrombotic microangiopathy. This disorder is caused by dysregulation of the alternative pathway of the complement system in association with genetic abnormalities or the development of autoantibodies. However, 30-50% of patients do not have genetic or acquired mutations in the complement system. Patient presented with fever and periorbital swelling. She had anemia, thrombocytopenia, and deranged liver function tests. Urinalysis revealed hematuria and proteinuria. Antibody tests and genetic analysis were negative. Renal biopsy revealed findings suggestive of thrombotic microangiopathy with predominantly glomerular involvement. Thus, the diagnosis of Atypical Hemolytic Uremic Syndrome, immunofluorescence negative, genetic negative, and anti-complement negative was made. This article reports a case of atypical hemolytic uremic syndrome in a child with negative genetic analysis and anti-complement factor H antibody, which was treated successfully on steroid and mycophenolate mofetil. Early diagnosis along with prompt treatment and close monitoring will lead to recovery from atypical Hemolytic Uremic Syndrome. Although HUS is generally associated with genetic abnormalities or a positive antibody test, some patients with HUS may present atypically with negative genetic analysis and antibody tests.

S3165 Spur Cell Anemia Mimicking DIC: A Marker of Advanced Cirrhosis

Introduction: Spur-cell anemia (SCA) is an uncommon, non-immune hemolytic anemia. When found in cirrhosis patients it is usually an indicator of advanced liver disease and carries a poor prognosis. Here we present a case of SCA and discuss its impact on the management and prognosis. Case Description/Methods: A 58-year-old male with a history of decompensated alcoholic cirrhosis, diabetes, and hypertension was admitted for abdominal distention and melena. Diagnostic paracentesis ruled out spontaneous bacterial peritonitis. His initial labs showed hemoglobin 9.7 g/dL, platelets 123 × 109/L, total bilirubin 6.6 mg/dL, direct bilirubin, 3.0 mg/dL, and INR 3.4. The patient underwent an upper endoscopy showing nonbleeding grade II esophageal varices and portal hypertensive gastropathy. The patient was discharged home after stabilization. Over the next 8 months, the patient had multiple hospitalizations secondary to hepatic decompensation and continued to be anemic (Hgb down to 8.3 g/dl) with persistent hyperbilirubinemia, largely indirect (total bilirubin up to 10.3 mg/dl, indirect bilirubin, 3.1 mg/dl). Subsequent workup including hemolysis labs revealed haptoglobin < 8 mg/dl, fibrinogen 100 mg/dl, mildly elevated LDH (287 IU/L), and a negative direct antibody test (DAT). Reticulocyte index, however, was 1.2, indicative of hypoproliferative anemia. Due to chronicity and persistence of findings, DIC was deemed less likely. Multiple peripheral smears showed Spur cells, burr cells, and a few schistocytes (Figure 1). Based on this, SCA was the likely diagnosis and the patient was referred for liver transplant consideration. Discussion: Anemia in cirrhosis patients is usually multifactorial. SCA is an uncommon form of acquired, non-immune hemolytic anemia that was first described in 1964. It is linked to advanced liver disease, primarily alcohol-related, and is associated with a poor prognosis. In a study by Vassiliadis et al., out of nine SCA patients, eight died at three months, and only one was alive at one year (one of two who underwent liver transplantation). Doll et al. reported a similarly high mortality rate (7/8 patients at eight months). SCA pathogenesis is not well elucidated; however, abnormal lipid metabolism with consequent development of spike-like projections in RBCs is thought to contribute to the formation of spur cells. The presence of SCA is an important prognostic indicator for cirrhotic patients that clinicians should be aware of.Figure 1.: Peripheral-blood smear showing red cells with irregular surface projections suggestive of acanthocytes, or spur cells. Table 1. - Summary of laboratory test results Laboratory test Latest Reference Range & Units Result Laboratory test Latest Reference Range & Units Result Sodium 135 - 145 MEQ/L 137 Bilirubin, Direct 0.0 - 0.3 MG/DL 2.0 Potassium 3.6 - 5.1 MEQ/L 3.0 WBC 3.5 - 11.0 x10exp9/L 5.6 Creatinine, Ser 0.64 - 1.27 MG/DL 0.63 Hemoglobin 13.5 - 16.0 G/DL 8.3 AST (SGOT) 10 - 42 IU/L 161 MCV 80.0 - 98.0 fL 74.3 ALT 6 - 45 IU/L 60 Platelets 150 - 400 x10exp9/L 135 Alkaline Phosphatase 34 - 104 IU/L 174 Haptoglobin 14 - 258 MG/DL < 8 LDH 100 - 220 IU/L 287 Fibrinogen Level 150 - 480 MG/DL 110 Bilirubin, Total 0.2 - 1.3 MG/DL 9.3 D Dimer Level 0 - 300 ng/mL 3,716 Direct Antiglobulin Test Negative Negative INR 0.8 - 1.2 3.4

Indicators of recent COVID-19 infection status: findings from a large occupational cohort of staff and postgraduate research students from a UK university

BackgroundResearchers conducting cohort studies may wish to investigate the effect of episodes of COVID-19 illness on participants. A definitive diagnosis of COVID-19 is not always available, so studies have to rely on proxy indicators. This paper seeks to contribute evidence that may assist the use and interpretation of these COVID-indicators.MethodsWe described five potential COVID-indicators: self-reported core symptoms, a symptom algorithm; self-reported suspicion of COVID-19; self-reported external results; and home antibody testing based on a 'lateral flow' antibody (IgG/IgM) test cassette. Included were staff and postgraduate research students at a large London university who volunteered for the study and were living in the UK in June 2020. Excluded were those who did not return a valid antibody test result. We provide descriptive statistics of prevalence and overlap of the five indicators.ResultsCore symptoms were the most common COVID-indicator (770/1882 participants positive, 41%), followed by suspicion of COVID-19 (n = 509/1882, 27%), a positive symptom algorithm (n = 298/1882, 16%), study antibody lateral flow positive (n = 124/1882, 7%) and a positive external test result (n = 39/1882, 2%), thus a 20-fold difference between least and most common. Meeting any one indicator increased the likelihood of all others, with concordance between 65 and 94%. Report of a low suspicion of having had COVID-19 predicted a negative antibody test in 98%, but positive suspicion predicted a positive antibody test in only 20%. Those who reported previous external antibody tests were more likely to have received a positive result from the external test (24%) than the study test (15%).ConclusionsOur results support the use of proxy indicators of past COVID-19, with the caveat that none is perfect. Differences from previous antibody studies, most significantly in lower proportions of participants positive for antibodies, may be partly due to a decline in antibody detection over time. Subsequent to our study, vaccination may have further complicated the interpretation of COVID-indicators, only strengthening the need to critically evaluate what criteria should be used to define COVID-19 cases when designing studies and interpreting study results.

The diagnostic value of serum Borrelia burgdorferi antibodies and seroconversion after Lyme neuroborreliosis, a nationwide observational study

ObjectivesClinical guidelines disagree on the diagnostic usefulness of Borrelia burgdorferi (Bb) serum antibodies (serum-Bb) in investigation of Lyme neuroborreliosis (LNB). We investigated the association between serum-Bb and Bb intrathecal antibody index (Bb-AI) and rates of seroconversion and seroreversion after LNB. MethodsDanish residents who had a Bb-AI and corresponding serum-Bb measured between 1994 and 2020 were identified at all Danish departments of clinical microbiology. We used descriptive statistics to examine the proportions of positive Bb-AI combined with positive or negative serum-Bb antibody tests. Next, the rate of seroconversion and seroreversion among those with positive Bb-AI and either an initial negative or positive serum-Bb was estimated. ResultsWe included 34 609 individuals with a Bb-AI and corresponding serum-Bb. The proportion of individuals with positive Bb-AI who had negative serum-Bb was 16.8% (95% CI, 15.1–18.6). The proportion of individuals with positive serum-Bb IgM, serum-Bb IgG, or serum-Bb IgM and IgG antibodies who had positive Bb-AI was 10.6% (95% CI, 9.5–11.8), 24.7% (95% CI, 23.0–26.4), and 45.0% (95% CI, 42.4–48.0), respectively. The proportion of children (<18 years) with positive serum-Bb IgM and IgG antibodies who had a positive Bb-AI was 59.7% (95% CI, 53.4–65.8). The proportion of individuals with positive Bb-AI with initial negative or positive serum-Bb antibodies who seroconverted or seroreverted within 2 years was 17.3% (95% CI, 6.9–27.8) and 23.2% (95% CI, 19.1–27.7), respectively. ConclusionsSerum-Bb antibodies could not predict results of Bb-AI. A fifth of both seronegative and seropositive individuals with positive Bb-AI seroconverted or seroreverted within 2 years.

P.014 Immunotherapy responses of patients with suspected autoimmune-associated epilepsy with negative neural antibody testing

Background: In refractory epilepsy patients with possible autoimmune-associated epilepsy (AAE) but negative antibody testing(-AB), immunotherapy trials (IMT) may still be pursued.The value of (IMT) in such patients remains unclear. For this reason, we reviewed their immunotherapy responses. Methods: Retrospective review of epilepsy patients admitted to the Epilepsy Unit between (2018-2021) who received (IMT). All had (-AB) and received immunotherapy (methylprednisolone (IVMP)-immune globulin (IVIg)-plasma exchange (PLEX)- rituximab).We considered responders when their seizure reduction was ≥ 50%. Results: 14 patients identified. Of them, 50%(n=7) females. Median age (43.5 year. IQR= 28.75-63.25). All refractory to ≥ 2 anti-seizure medications (ASM). Median epilepsy onset was (39.5 years. IQR=23.75-60.25).Median time from diagnosis until received immunotherapy was (15.5 months. IQR=12.75 -21.75). Patients received either IVIG+IVMP (35.7%, n=5) or IVIG alone (28.5%, n=4) or IVIG+IVMP+PLEX (21.4%, n=3) or IVMP alone (7.1%, n=1) or IVIG+IVMP+rituximab (7.1%, n=1). Median follow-up was 25 months.Although early immunotherapy responses were common, sustained response to immunotherapy at last follow-up was only in 21.4% (n=3). Factors confounding determination of immunotherapy efficacy were present in all responders (e.g:concurrent changes in ASM). Conclusions: Our findings suggest that (IMT) in patients with suspected (AAE) but with (-AB) are largely unsuccessful. This suggests an insufficient therapeutic effect after (IMT) or alternatively,non-immune-mediated mechanisms causing this type of epilepsy. Critical evaluations of (IMT)in such cases are needed.

Clinical Characteristics and Prognosis of Antibody-Negative Autoimmune Encephalitis in Children: A Single-Center Retrospective Study

BackgroundAutoimmune encephalitis (AE) is a group of immune-mediated brain diseases. However, new diagnostic criteria for AE in children indicate that partial pediatric patients with AE may be diagnosed without evidence of positive autoantibodies. Therefore, the clinical characteristics and prognosis of children with antibody-negative but probable AE require further investigation. MethodsForty-one children with AE admitted to our hospital from April 2014 to January 2021 were retrospectively enrolled in this study. Children were divided into two groups according to positive or negative antibody tests. Clinical characteristics, cerebrospinal fluid, video electroencephalography, brain magnetic resonance imaging, and prognosis were analyzed, and the correlation between modified Rankin scale (mRS) and neutrophil-to-lymphocyte ratio (NLR) was examined. ResultsOf 41 children, 16 cases tested positive for autoantibodies. The main features were psychiatric symptoms, cognitive disturbances, speech disturbances, movement disorders, and seizures. All the children were given a combination of intravenous methylprednisolone pulses with intravenous immunoglobulin therapy; 26 cases (63%) had a good outcome, and 15 cases (37%) had a poor outcome. Antibody-positive and antibody-negative but probable AE were analyzed by univariate analysis and showed lower lymphocyte counts and higher NLR and mRS scores in the antibody-negative group (P < 0.05). The Spearman rank correlation analysis showed a positive correlation between NLR level and mRS scores (P < 0.05). ConclusionsAntibody-negative but possible AE is frequent in children who may have a more severe neurological impairment and higher NLR than antibody-positive AE. Aggressive immunotherapy in antibody-negative AE is essential to achieve a good prognosis.

MO699: Investigating Longer Term Antibody Response Following Covid-19 Vaccination in Patients Receiving Peritoneal Dialysis—a Single-Center Observational Study

BACKGROUND AND AIMSIndividuals with end-stage kidney disease (ESKD) have a greater susceptibility towards coronavirus disease 2019 (COVID-19) infection compared to those without chronic kidney disease or ESKD, and these patients are more vulnerable to poor clinical outcomes. The introduction of COVID-19 vaccination programs displayed efficacy to improving clinical outcomes. A study based in the UK reported excellent humoral responses to the Pfizer BNT162b2 vaccine, but suboptimal responses to the Oxford AstraZeneca ChAdOx1-nCoV-19(AZD1222) vaccine amongst hemodialysis patients. High rate of humoral responses to two doses of the COVID-19 vaccination has been reported within small cohorts of peritoneal dialysis (PD) patients 3 to 8 weeks post vaccination, whilst one study confirmed maintenance of significant humoral responses 6 months post vaccination with the Pfizer BNT162b2 vaccine. Our study aimed at evaluating longer-term antibody responses—6 months after a two-dose regimen of the Pfizer BNT162b2 and Oxford AstraZeneca ChAdOx1-nCoV-19 (AZD1222) vaccines in patients receiving PD.METHODThis is a single-center observational study conducted for PD patients who were offered both doses of the COVID-19 vaccine [either Pfizer BNT162b2 or Oxford AstraZeneca ChAdOx1-nCoV-19(AZD1222)] since universal introduction of the vaccination program in our local area in December 2020. COVID-19 antibody testing was performed using the Siemens’ immunoassay targeting the spike protein S1 RBD (an index ≥ 1.0 was deemed as a positive result) between October and November 2021. Demographic and baseline clinical data were collected for each patient, and analysis focused on comparing the characteristics between PD patients with positive and negative COVID-19 antibody statuses. Statistical analysis was performed using SPSS version 24.RESULTSEighty-six patients were included in this study. The median age was 62 years (47–71) with a predominance of males (61.6%) and Caucasian ethnicity (75.6%). The majority of patients have hypertension (84.8%) with 38% having a history of cardiovascular disease and 34% being diabetic. Ten patients (11.6%) previously received a kidney transplant with 7 patients (8.2%) currently on immunosuppressive treatment, and 15 patients (17.4%) previously receiving such treatments. A total of 81 patients received both doses of the COVID-19 vaccine, of which 57 (70.4%) received Pfizer BNT162b2, 16 (19.7%) received Oxford AstraZeneca ChAdOx1-nCoV-19 (AZD1222) and the type of vaccine was unknown in 8 patients (9.9%). A total of 72 patients were COVID-19 antibody tested between October and November 2021 in which 68 (94.4%) had a positive antibody and 4 (5.6%) had a negative antibody test. The median time between first dose of the COVID-19 vaccination and antibody testing was 9 (8.6–9.5) months and the median time between second dose of the COVID-19 vaccination and antibody testing was 6.3 (5.8–6.7) months. Comparing the demographic and clinical characteristics between patients with positive and negative antibodies, a higher proportion of patients with history of receiving immunosuppression (currently or previously; P = 0.004) had a negative antibody status despite receiving two doses of COVID-19 vaccination. There were no further significant differences observed. Full study results are presented in Tables 1 and 2.CONCLUSIONIn our cohort of PD patients, detectable humoral response to COVID-19 vaccination was sustained 6 months following vaccination irrespective of the type of vaccination received. A higher proportion of patients with a history of receiving immunosuppression (current or past) had a poor antibody response following COVID-19 vaccinations, highlighting the importance of considering focused COVID-19 vaccination strategies in the context of immunosuppression.

Biochemical abnormalities among patients referred for celiac disease antibody blood testing in a primary health care setting

To investigate possible biochemical abnormalities associated with celiac disease (CD) antibody positivity in a primary health care setting and thereby identify predictors that could potentially reduce diagnostic delay and underdiagnosis of CD. This observational cohort study included measurements of CD antibodies in the Copenhagen Primary Care Laboratory (CopLab) database from 2000 to 2015; CD antibody positivity was defined as tissue transglutaminase antibody IgA or IgG ≥ 7 kU/L and/or deamidated gliadin peptide antibody IgG ≥ 10 kU/L. Individuals with a prior diagnosis of CD were excluded. We examined differences between individuals with positive and negative CD antibody tests regarding the results of biochemical tests performed six months before and one month after the date of the CD antibody test. We identified 76,265 measurements of CD antibodies during 2000–2015, and 57,061 individuals met the inclusion criteria (706 antibody-positive and 56,355 antibody-negative). We found lower ferritin, hemoglobin, cobalamin and folic acid levels and higher levels of transferrin, ALAT (alanine transaminase), and alkaline phosphate among individuals with a positive CD antibody test. Furthermore, we illustrated more measurements below the sex-specific reference intervals for hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), ferritin, cobalamin and folic acid among individuals with a positive CD antibody test. This study identified several biochemical abnormalities associated with CD antibody positivity among individuals referred to CD antibody testing. The pattern of abnormalities suggested that micronutrient deficiencies were prevalent among CD antibody-positive individuals, confirming malabsorption as a sign of CD. These findings illustrate the possibility of reducing diagnostic delay and underdiagnosis of CD.

Predictors of SARS-CoV-2 IgG Spike Antibody Responses on Admission and Clinical Outcomes of COVID-19 Disease in Fully Vaccinated Inpatients: The CoVax Study.

Background: SARS-CoV-2 vaccines have shown high efficacy in protecting against COVID-19, although the determinants of vaccine effectiveness and breakthrough rates are yet to be determined. We aimed at investigating several factors affecting the SARS-CoV-2 IgG Spike (S) antibody responses on admission and clinical outcomes of COVID-19 disease in fully vaccinated, hospitalized patients. Methods: 102 subjects were enrolled in the study. Blood serum samples were collected from each patient upon admission for the semiquantitative determination of the SARS-CoV-2 IgG S levels with lateral flow assays. Factors influencing vaccine responses were documented. Results: 27 subjects had a negative antibody test upon hospital admission. Out of the 102 patients admitted to the hospital, 88 were discharged and 14 died. Both the absence of anti-S SARS-CoV-2 antibodies and poor clinical outcomes of COVID-19 disease were associated with older age, lower Ct values, and a shorter period between symptom onset and hospital admission. Ct values and time between symptom onset and hospitalization were independently associated with SARS-CoV-2 IgG S responses upon admission. The PaO2/FiO2 ratio was identified as an independent predictor of in-hospital mortality. Conclusions: Host- and disease-associated factors can predict SARS-CoV-2 IgG S responses and mortality in hospitalized patients with breakthrough SARS-CoV-2 Infection.

Serum and Cerebrospinal Fluid Testing in Optic Neuropathy Patients with Malignant Tumors.

Purpose To evaluate the value of serum and cerebrospinal fluid (CSF) testing in optic neuropathy (ON) patients with malignant tumors. Methods Fourteen patients clinically diagnosed as ON with malignant tumors but without intracranial or orbital mass in MRI were included in this study. Detailed medical records including medical history, complete ophthalmic examination, colour fundus photography, visual field test, orbital MRI examination, serum and CSF testing data were collected and analyzed. The diagnosis of paraneoplastic optic neuropathy (PON) based on the 2004 recommended criteria of the paraneoplastic syndrome- Euronetwork consortium for paraneoplastic neurological disorders, and current adaption for neuropathies. All patients underwent serum tests for pathogens and autoantibodies including antinuclear antibodies, anticardiolipin antibodies, antineutrophil cytoplasmic antibodies, AQP4-Ab and MOG-Ab, as well as CSF tests for malignant cells under microscope. Serum paraneoplastic antibodies were detected in PON patients. Monkey cerebellar tissue-based assay was used to detect unknown serum anti-neuron antibodies in PON patients with negative paraneoplastic antibody testing results. Results Fourteen ON patients were classified as four groups based on their clinical and MRI characteristics, as well as serum and CSF testing results: [1] definite PON, 6 cases (11 eyes); [2] possible PON, 3 case (5 eyes); [3] meningeal carcinomatosis-associated optic neuropathy (MCON), 4 cases (6 eyes); [4] infiltrative optic neuropathy (ION), 2 cases (2 eyes). Malignant cells were found under microscope in CSF samples from MCON and ION patients, contrast to no malignant cells in CSF samples from PON cases. All 14 ON patients with malignant tumors showed negative results in serum tests for pathogens and autoantibodies. Serum paraneoplastic antibodies were tested in PON patients, anti- CV2, anti-Yo, and anti- amphiphysin were detected positive in 2, 1, and 1 case, respectively, in definite PON group, whereas no serum paraneoplastic antibody detected in possible PON group. Two unknown serum antineuronal antibodies (an anti- Purkinje cell antibody and an anti-granular cell antibody) were detected using monkey cerebellar tissue-based assay in 2 of 5 PON patients with negative paraneoplastic antibody test results. Conclusions Serum and CSF tests are of great importance in differentiating different subtypes of ON with malignant tumors. Current diagnosis of PON still depends on combination of clinical and MRI manifestations, as well as serum and CSF tests. Tissue-based assay may help to detect new biomarkers for ON etiology and diagnosis.

1352. Changing Quality Indicators by Monitoring Veterans Using the Sexually TRansmitted Infection Key Evaluation (STRIKE) Dashboard

BackgroundDuring the COVID-19 pandemic, there have been multiple reports concerning patients falling out of healthcare. The National VA HIV and Hepatitis and Related Conditions (HHRC) has created the Sexually TRansmitted Infection Key Evaluation (STRIKE) Dashboard to help clinicians identify Veterans who need to complete co-testing for sexually transmitted infections (STIs) or human immunodeficiency virus (HIV) and allows providers to document if the Veteran was offered pre-exposure prophylaxis (PrEP).STRIKE Interface Screen MethodsA national VA Veteran dataset was generated from data within the Corporate Data Warehouse (CDW) that included all active PLWH. Positive HIV status is evaluated based on positive antibody test and positive confirmatory result or positive viral load lab result. Negative HIV status is evaluated based on a negative antibody test in the past year. Of the 140 sites, 39 participated but only 9 were active throughout the period of October 1, 2020 to March 31, 2021. Active and nonactive participating sites had metrics assessed across the study period at 3 time points: October 1, 2020, January 1, 2021 and April 1, 2021. Sites with at least 48 visits to report across the 6-month QI period were considered active.Patient level data for review Additional patient level data for review ResultsMultiple sites had scarcity of supplies due to the national shortage of CT/NG Test Kits during COVID-19. To improve access to CT/NG testing, the dashboard suppress the list of Veterans with + syphlis who were not co-tested for CT/NG. Co-testing improved from 60.2% to 77.2% in active sites and from 61.9% to 68.7% for nonactive across the study period. Percent of Veterans with completed HIV testing on or after STI diagnosis in active sites had an upward trend of 2.1% compared to the nonactive which increased 0.6%. Likewise, new diagnosis of STI for those on PrEP increased 2.6% in active and 0.5% increase in nonactive. On average, active sites increased percent of high risk veterans with active PrEP prescriptions by 2%, compared with nonactive that only increased 1%.STRIKE Co Testing and HIV Screen performed This graph shows average of Syphilis Co Testing and HIV screen performed by active and nonactive sites as measured at three different time point.Number of Veterans on PrEP with STIs This graph shows the average percent of veterans on PrEP with STIs between active versus nonactive sites as measured at three time pointsActive PrEP Prescriptions Across All Sites This graph shows average percent of active PrEP prescriptions for high risk patients between active versus nonactive sites as measured at three time pointsConclusionThe STRIKE Dashboard efficiently flags Veterans with STI diagnosis who need completion of STI co-testing, including HIV testing and PrEP offer. Active participating facilities who used the STRIKE Dashboard improved STI Co-testing and PrEP prescription in a short 6 month period even during COVID-19. Disclosures All Authors: No reported disclosures

Excess All-Cause Mortality in 2020 for People Living with Sickle Cell Disease in New York City

BackgroundThe COVID pandemic resulted in excess all-cause mortality in 2020 in the United States, especially among people who identify as Black and/or Latino. While many of these deaths were due to COVID-19 infection, others have been attributed to strain on the overburdened health care system and delays in patients seeking medical care due to the pandemic. We sought to examine the overall mortality in individuals with sickle cell disease (SCD) who received their care at our Sickle Cell Center in Bronx New York in 2020 and investigated whether the number and causes of death in 2020 differed from the previous 3 years.Methods:Death date was collected from electronic medical records (EMR) and death certificates. Clinical variables collected from EMR included age, gender, race, genotype, history of comorbidities, hydroxyurea use, and health care utilization in the 12 months prior to death date. To determine cause of death, two hematologists performed manual review of the EMR blinded from each other and deaths were categorized as due to: sudden death, cardiovascular causes, sepsis, stroke, acute organ failure (including multi organ failure syndrome), chronic organ failure, hemorrhage, and unknown when records of the death event were not available. A third hematologist served as a tie breaker in cases of disagreement. Patients were also categorized as having: 1) sepsis present or absent during the death event, 2) acute (new or newly worsened) renal or liver failure present or absent during the death event, and 3) COVID status at death (acute COVID, past COVID, no COVID, or unknown COVID status). Acute COVID infection was defined by a positive PCR swab during the hospitalization leading to death or in the prior two weeks. Past COVID infection was defined by a negative PCR swab during the hospitalization and a positive PCR swab and/or antibody test more than two weeks before the death event with documented resolution of symptoms. No COVID infection was defined by a negative PCR swab or antibody test documented in the EMR and no positive tests present or noted per patient report. Unknown COVID status was unknown if no testing was present in the EMR. To examine how 2020 decedents differed from decedents in the prior 3 years, we compared clinical variables using the Kruskal Wallis test for continuous variables and chi 2 tests for dichotomous variables. To examine differences between 2020 decedents between known COVID (acute or chronic) vs. no COVID, we repeated similar tests among the 2020 decedents only.Results:In the years 2017, 2018, 2019, and 2020, there were 9, 10, 8, and 22 patient deaths respectively. Compared with decedents in the prior 3 years, patients who died in 2020 were more likely to have acute liver failure during the hospitalization, were more likely to have history of stroke, and had more heme clinic visits in the prior 12 months. Otherwise, there was no difference in age, gender, genotype, hydroxyurea use, history of disease morbidity, hospital utilization in the prior 12 months, or sepsis before death (Table 1). Among the 22 who died in 2020, 3 had an acute COVID infection, five had past COVID, 8 had no COVID, and 6 had unknown COVID status. Among 2020 decedents, acute or past covid was associated with acute organ failure (p=0.02) and less hydroxyurea use (p=0.04). (Table 2).Conclusions:SCD deaths at our center more than doubled in 2020 compared to prior years, but fewer than half of the decedents had acute or prior COVID. Compared with prior years, 2020 decedents were more likely to have acute organ failure. This could be explained by COVID infection, delays in seeking care, or changes in care delivery during the COVID pandemic. This study emphasizes the need for further studies on the impact the pandemic had on the health of adults with SCD, as well as the need for prospective studies of patients with SCD who recover from COVID. [Display omitted] DisclosuresCurtis: GBT: Consultancy. Minniti: Forma: Consultancy; GBT: Consultancy; Novartis: Consultancy; Novo Nordisk: Consultancy; Chiesi: Consultancy; F. Hoffmann-La Roche: Consultancy; Bluebird Bio: Other: Endpoint adjudicator; CSL Behring: Other: Endpoint adjudicator.

Serological Response to the BNT162b2 mRNA or Chadox-Ncov-19 COVID-19 Vaccine after First and Second Doses in Plasma Cell Disorder Patients: Influence of Host and Disease Factors

BackgroundPlasma cell disorders (PCD) are at risk of inadequate immune responses to COVID-19 vaccines due to recognised humoral and cellular immune dysfunction which is multi-factorial and related to host and disease factors. With an estimated risk of 33% mortality from contracting COVID-19 in this population, protection with an anti-SARS-CoV-2 vaccination is critical. Initial extension to vaccination intervals in the United Kingdom to 12 weeks in December 2020 led to concerns that PCD patients would be left vulnerable for an extended period.MethodsA clinical audit was performed on measured serological responses in PCD patients after first and second doses of the BNT162b2 and ChAdOx-1 nCoV-19 vaccines. Antibody levels were measured using Elecsys Anti-SARS-CoV-2S assay (Roche) for quantitative detection of IgG Abs, specific for the SARS-CoV-2 spike-protein. Positive cut-off of 0.80 U/mL defined serological response. Testing was performed at (or closest to) 4 and 8-weeks post-dose. Baseline nucleocapsid Ab results were available from previous screening in a subset of patients. All patients on CIT underwent 4-weekly swabs. Clinical information was retrieved from medical records.Results188 PCD patients (155 multiple myeloma, 18 amyloid, 10 SMM/MGUS, other 5 PCD), median age 64 (range 32-84), had serological assessment after both vaccine doses. Fourteen with previous COVID-19 infection were excluded. Of 174 patients, 112 were tested after first dose. 88% (153) were on chemo-immunotherapy treatment (CIT). Seropositive rate after first dose was 63% (71/112); of those with available negative baseline antibody test, 62% (31/50) seroconverted. After second dose, 89% (154/174) were seropositive; of those with negative baseline antibody, 90% (61/68) seroconverted. Expectedly, paired median titres after second dose were significantly higher than post first dose (n=112, 3.245 U/mL (IQR 0.4-25.55) vs 518 U/mL (IQR 29.40-2187) p<0.0001) (Figure 1A). Of 41 patients seronegative after first dose, 25 (61%) seroconverted after second, though with lower titres than those only requiring one dose (Figure 1B). Active CIT, disease response less than PR, >=4 lines therapy, light-chain disease, male gender and not responding to first dose were significant factors for not responding to two vaccine doses. We explored <400 U/mL as sub-optimal response (in keeping with upcoming booster study eligibility, OCTAVE-DUO(1), also encompassing the lower quartile of reported healthy controls(2)), which included 43% (75/174) patients. Age 70 years, male gender, >=4 lines of treatment were independent predictors of less-than-optimal response (anti-CD38 CIT of borderline significance). Importantly, vaccine dosing intervals classified as =<42 vs >42 days (Figure 1C) or 28 +/- 14 days vs 84 +/- 14 days (excluding n=66 in neither) (Figure 1D) did not show difference in both definitions of response, neither did vaccine type. Fourteen with previous COVID-19 infection responded to one vaccine dose, median titres 2121 U/mL (IQR 23.48-2500)) rising to median 2500 U/mL (IQR 2500-2500) after second dose (Figure 1E), significantly higher than those without previous infection.ConclusionSerological response to COVID-19 vaccine is lower in PCD patients than reported healthy controls at 63% after first dose, rising to 89% after second dose, despite extended dosing intervals. PCD patients should be prioritised for shorter intervals, as we show that patients seronegative after first dose, respond after second dose. Further work in PCD is needed to understand how Ab levels correlate to neutralisation capability, cellular responses, protection from infection and how long seroconversion lasts to better define correlates of protection. A booster vaccination or prophylactic passive antibody strategy may be required for those identified at risk, shown not to have responded to two vaccine doses or to have less-than-optimal response. Results from these trials will be eagerly awaited.