SARS-CoV-2 induces a durable and antigen specific humoral immunity after asymptomatic to mild COVID-19 infection

Current SARS-CoV-2 serological assays generate discrepant results, and the longitudinal characteristics of antibodies targeting various antigens after asymptomatic to mild COVID-19 are yet to be established. This longitudinal cohort study including 1965 healthcare workers, of which 381 participants exhibited antibodies against the SARS-CoV-2 spike antigen at study inclusion, reveal that these antibodies remain detectable in most participants, 96%, at least four months post infection, despite having had no or mild symptoms. Virus neutralization capacity was confirmed by microneutralization assay in 91% of study participants at least four months post infection. Contrary to antibodies targeting the spike protein, antibodies against the nucleocapsid protein were only detected in 80% of previously anti-nucleocapsid IgG positive healthcare workers. Both anti-spike and anti-nucleocapsid IgG levels were significantly higher in previously hospitalized COVID-19 patients four months post infection than in healthcare workers four months post infection (p = 2*10−23 and 2*10−13 respectively). Although the magnitude of humoral response was associated with disease severity, our findings support a durable and functional humoral response after SARS-CoV-2 infection even after no or mild symptoms. We further demonstrate differences in antibody kinetics depending on the antigen, arguing against the use of the nucleocapsid protein as target antigen in population-based SARS-CoV-2 serological surveys.

The Role of Internal Limiting Membrane as a Biomarker in the Evolution of Myopic Traction Maculopathy

Purpose: To describe the longitudinal structural changes of myopic traction maculopathy (MTM) based on optical coherence tomography (OCT) and to detect biomarkers in the evolution of MTM.Methods: A retrospective study was conducted on patients with MTM as defined by OCT. A minimum follow-up of 6 months was necessary for study inclusion. The effects of comprehensive OCT-based structure on the evolution of MTM, the progression rates, and resolution rates of MTM were evaluated.Results: A total of 120 eyes (120 patients) were included with an average follow-up of 15.4 months. During the follow-up, MTM progressed in 32 eyes (26.67%). The most common pattern of progression observed was the increased extent of retinoschisis in 12 eyes. The multivariate analysis showed that the presence of MTM progression had a significant correlation with internal limiting membrane (ILM) detachment and retinoschisis involved the entire macula at baseline. Five eyes (4.17%) experienced MTM resolution, of which 2 eyes developed disruptions of detached ILM, two eyes developed disruptions of epiretinal membrane, and one eye developed partial posterior vitreous detachment. Eyes with foveal detachment showed the highest progression rate (41.67%) and highest resolution rate (16.67%) compared to the eyes with other foveal complications.Conclusion: ILM detachment is a risk factor for MTM progression and MTM resolution can occur after ILM disruption. These suggest that ILM may play an important role as a biomarker in the evolution of MTM.

Global incidence proportion of intraventricular haemorrhage of prematurity: a meta-analysis of studies published 2010–2020

ObjectiveTo investigate differences and calculate pooled incidence of any intraventricular haemorrhage (IVH), severe IVH (Grade III/IV, sIVH) and ventriculoperitoneal shunt (VPS) placement in preterm infants across geographical, health and economic regions stratified by gestational age (GA).DesignMEDLINE, Embase, CINAHL and Web of Science were searched between 2010 and 2020. Studies reporting rates of preterm infants with any IVH, sIVH and VPS by GA subgroup were included. Meta-regression was performed to determine subgroup differences between study designs and across United Nations geographical regions, WHO mortality strata and World Bank lending regions. Incidence of any IVH, sIVH and VPS by GA subgroups<25, <28, 28–31, 32–33 and 34–36 weeks were calculated using random-effects meta-analysis.ResultsOf 6273 publications, 97 met inclusion criteria. Incidence of any IVH (37 studies 87 993 patients) was: 44.7% (95% CI 40.9% to 48.5%) for GA <25 weeks, 34.3% (95% CI 31.2% to 37.6%) for GA <28 weeks, 17.4% (95% CI 13.8% to 21.6%) for GA 28–31 weeks, 11.3% (95% CI 7.3% to 17.0%) for GA32–33 weeks and 4.9% (95% CI 1.4% to 15.2%) for GA 34–36 weeks. Incidence of sIVH (49 studies 328 562 patients) was 23.7% (95% CI 20.9% to 26.7%) for GA <25 weeks, 15.0% (95% CI 13.1% to 17.2%) for GA <28 weeks, 4.6% (95% CI 3.5% to 6.1%) for GA 28–31 weeks, 3.3% (95% CI 2.1% to 5.1%) for GA 32–33 weeks and 1.8% (95% CI 1.2% to 2.8%) for GA 34–36 weeks. Europe had lower reported incidence of any IVH and sIVH relative to North America (p<0.05). Proportion of VPS across all GA groups was 8.4% (95% CI 4.7% to 14.7%) for any IVH and 17.2% (95% CI 12.2% to 26.2%) for sIVH. Heterogeneity was high (I2 >90%) but 64%–85% of the variance was explained by GA and study inclusion criteria.ConclusionsWe report the first pooled estimates of IVH of prematurity by GA subgroup. There was high heterogeneity across studies suggesting a need for standardised incidence reporting guidelines.

MOLECULAR-GENETIC CRITERIA AND PROSPECTIVE BIOMARKERS OF SERRATED ADENOMAS OF COLORECTAL LOCALIZATION

A retrospective analysis of the database of patients with histologically verified serrated adenomas of the colon was carried out as part of an observational study. Inclusion criteria: patients with serrated colon adenomas who underwent a molecular genetic study to detect mutations and further sequencing 16 sRNAs of intestinal microbiota from January 2021 to October 2021. The exclusion criteria: patients with a primary tumor of the colon who had previously received complex treatment, who had accompanying pathologies of the other organs and systems, which did not allow for the planned examination. According to the results of the study, BRAF mutations are diagnosed in half of the cases in serrated adenomas and in one-third of cases - KRAS mutations. As a result of a comparative analysis of the intestinal microbiome of young patients with serrated colon adenomas with summary statistical data on the presence of bacteria in the intestines of people from the Russian population; promising markers were found for the development of effective approaches for the early diagnosis of colorectal cancer.

Incidence of Primary Aldosteronism in Patients with Hypokalemia (IPAHK+): Study Design and Baseline Characteristics

Hypokalemia plays a central role for case finding, course, treatment decision, and prognosis of patients with primary aldosteronism. However, to date there is a lack of high-level evidence about the incidence of primary aldosteronism in hypokalemic patients. The IPAHK+study is an epidemiological, cross-sectional, monocentric study to provide evidence on the incidence of PA in a hypokalemic population. The aim of the current analysis was to describe the baseline characteristics of the first 100 patients eligible for study inclusion. The recruitment of patients with hypokalemia (≤3 mmol/l) is carried out continuously on a referral-basis by the central laboratory of the University Hospital Zurich through an automated suitability testing and data delivery system. The careful evaluation of the first 100 reported patients was based on the available reporting system. Out of 28 140 screened patients, 222 (0.79%) were identified with a serum potassium value of≤3 mmol/l (mean 2.89±0.02 mmol/l). Mean potassium levels were slightly lower in non-hypertensive subjects compared to hypertensive subjects (mean difference 0.07 mmol/l, p=0.033), while no significant difference was found between the sexes and patients with and without the diagnosis of primary aldosteronism, atrial fibrillation, or the use of diuretics. The incidence of PA was 4% in the total population studied and 7.5% in the subgroup of hypertensive patients. In conclusion, the continuous enrollment of patients from the IPHAK+hypokalemia registry into the IPAHK+trial will provide evidence about the actual incidence of primary aldosteronism in a hypokalemic outpatient population.

Analysis of Transition of Patients with Parkinson’s Disease into Institutional Care: A Retrospective Pilot Study

Parkinson’s disease (PD) is a neurodegenerative disease which gives a person a high risk of becoming care-dependent. During disease progression, the amount of care concerning activities of daily living can increase, possibly resulting in transition of the people with Parkinson’s disease (PwP) to a care facility. However, there is a lack of knowledge concerning the factors leading to institutionalization of PwP and the consequences for them and their informal caregivers. The aim of this cross-sectional retrospective study was to investigate reasons leading to the transition into an institutional care facility, the process of decision-making and its effects on PwP symptoms and caregiver burden. Participating PwP had to be institutionalized for at most one year after transition at study inclusion. Participants completed a range of semiquantitative questionnaires as well as the caregiving tasks questionnaire. Fourteen patient–caregiver pairs were included. PwP suffered from late-stage PD symptoms with high dependence on help, experiencing several hospitalizations before transition. Analyses revealed a significant decrease in caregiver burden and depressive symptoms of the caregivers after PwP institutionalization. Factors influencing the transition were, e.g., fear of PwP health issues and concerns about caregivers’ health. This study presents new insights into the process of institutionalization and its influence on caregiver burden, including aspects for discussions of physicians with PwP and their caregivers for counselling the decision to move to institutional care.

Impact of ABO Blood Group Type on Risk of Venous Thromboembolism in Patients with Cancer

Introduction: Venous thromboembolism (VTE) is common in patients with cancer. Non-O blood type is associated with higher levels of factor FVIII activity and von Willebrand factor compared to blood type O, and has been identified as a risk factor for VTE in the general population. However, the impact of ABO blood type on risk of cancer-associated VTE has not been clarified. Methods: To determine the influence of non-O blood type on risk of cancer-associated VTE, we utilized the dataset of the Vienna Cancer and Thrombosis Study (CATS), which is a single center, prospective observational cohort study including patients with newly diagnosed or recurrent cancer. Patients were followed for objectively diagnosed, independently adjudicated VTE for a maximum of 2 years. VTE was quantified in competing risk analysis, accounting for all-cause mortality as competing outcome event. A proportional sub-hazard regression model according to Fine & Gray was used for between-group comparisons. Based on the violation of the proportional sub-hazard assumption, we explored potential time-dependent effects of non-O blood type on VTE risk in a restricted cubic spline analysis, modeling differences in risk estimates over follow-up time. Further, time-restricted subdistribution hazard ratios (SHR) were obtained specifically for the &lt;3 months and ≥3 months follow-up intervals. In a subgroup analysis, differences in VTE risk according to ABO-blood type were analyzed for patients with very high thrombotic risk tumor types (pancreatic, gastric, glioblastoma), compared to the remainder of patients. Results: In total, 1,708 patients were included in our analysis (46% female, median age: 61 years [interquartile range, IQR: 52-68]). The most common tumor types were lung (19%), breast (16%), and brain (14%) cancer, with 32% of solid tumor patients having metastatic disease at study inclusion. Over a median follow-up of 24 months (IQR: 10-24), 151 patients were diagnosed with VTE (cumulative 2-year incidence: 9.2%, 95% confidence interval [CI]: 7.9-10.7) and 649 patients died (2-year mortality: 38%). Overall, blood type O was present in 38% of patients, A in 40%, B in 15%, and AB in 7%. The cumulative incidence of VTE at 3-, 6-, 12-, and 24-months for patients with blood type O was 3.8% (95% CI: 2.5-5.5), 5.7% (95% CI: 4.1-7.7), 7.0% (95% CI: 5.1-9.1), and 7.6% (95% CI: 5.7-9.9), compared to 3.4% (95% CI: 2.4-4.7), 6.5% (95% CI: 5.1-8.1), 8.4% (95% CI:6.8-10.2), and 10.2% (95% CI: 8.4-12.2) in patients with non-O blood type (Gray´s test: p=0.103, Figure 1). Upon visual inspection of cumulative incidence functions, a violation of the proportional sub-hazard assumption was suspected. In restricted cubic spline analysis, estimating hazard ratio (HR) for VTE of patients with non-O compared to O blood type, a time-varying effect of non-O blood type towards an increased VTE risk was observed (Figure 2). Based on that, time-restricted competing risk regression models were performed. During the first 3 months of follow-up, no differences in VTE risk were found (SHR for non-O vs. O blood type: 1.00, 95% CI: 0.60-1.67, p=0.992). Beyond the first 3-month follow-up, patients with non-O blood type had an increased VTE risk compared to patients with blood type O (SHR 1.79, 95%CI: 1.12-2.85, p=0.015). In a subgroup analysis, no association with VTE risk was found in patients with very high thrombotic risk tumor types (SHR 0.94, 95% CI: 0.55-1.61, p=0.824). In contrast, in patients with low/intermediate risk cancer, non-O blood type was associated with increased risk of VTE (SHR 1.73, 95% CI: 1.09-2.73, p=0.019). Conclusion: Non-O blood type was identified as a time dependent risk factor for cancer-associated VTE. In the first 3 months after study inclusion, characterized as the highest VTE risk period in our cancer cohort, no differences in VTE risk between blood types were found. Afterwards, beyond the first 3 months of follow-up, an increased VTE-risk in non-O blood types was observed, comparably in magnitude to the risk difference in the general non-cancer population. Further, an association of non-O blood type with VTE risk in patients with low/intermediate thrombotic risk cancers was observed, whereas no effect was present in those with very high-risk tumors. These findings indicate non-O blood type as a putative risk factor for VTE in patients with cancer in comparably low thrombotic risk scenarios. Figure 1 Figure 1. Disclosures Pabinger: Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Daiichi Sanchyo: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; NovoNordisk: Consultancy, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding.

Neurodevelopmental Screening in Young Children with Sickle Cell Disease

It is important to prioritize screening and surveillance for neurodevelopmental dysfunction in children with SCD because this vulnerable population is at higher risk for neurological complications including stroke, silent cerebral infarction, and neurodevelopmental disorders (NDD) such as language disorders, attention deficit hyperactivity disorder, and autism spectrum disorder (ASD). The American Society of Hematology (ASH) and American Academy of Pediatrics (AAP) have published guidelines to accomplish this, as well as to improve quality of life for people with SCD and NDDs. Despite the recognition of the increased risk and the clinical guidelines, the co-occurrence rates of SCD and NDD remain lower than expected. We hypothesize that the risk of NDDs is lower than expected in children with SCD due to low rates of neurodevelopmental screening and surveillance among primary care providers and hematologists, particularly in young children. Therefore, we examined the frequency of neurodevelopmental screening and surveillance among young children with SCD and identified clinical characteristics of young children with SCD who did not receive appropriate neurodevelopmental screening and surveillance. We conducted a retrospective chart review using the clinic rosters of two affiliated inner-city hospitals with a pediatric hematology clinic and sickle cell neurodevelopmental clinic. Children under 5 years old with SCD confirmed by their hematologists who were not adopted or in foster care were included in the study. A total of 276 patients were identified and reviewed. NDD and ASD specific screenings were documented at the time of review, although participants may have been diagnosed later in life. Analyses were completed using chi squared test, Fisher exact test, t-test in Stata IC-15. Patients were screened by a variety of providers, most commonly pediatricians and hematologists (see Figure 1). Table 1a shows the characteristics of the SCD patients assessed/not assessed for appropriate neurodevelopment (ND) by their pediatrician and/or hematologist. A total of 214 participants qualified for study inclusion and 148 participants (70%) were assessed for neurodevelopment. Ages and Stages Questionnaire- 3 (32%) and other non-standardized screening tools (85%) were the most common tool used (see Table 2a). Of the ND assessed patients (N=148), 37 (25%) were diagnosed with NDDs (see Table 3a). Among the not assessed ND patients (N=66), 16 (24%) were diagnosed with NDDs. Table 1b shows the characteristics of the SCD patients assessed/not assessed specifically for ASD by their pediatrician and/or hematologist. A total of 207 participants qualified for study inclusion and 39 participants (19%) were assessed for ASD. Modified Checklist for Autism in Toddlers (92%) was the most utilized screening tool (see Table 2b). None of these patients had ASD. Of the ASD assessed patients (N=39), 9 (23%) were diagnosed with NDDs (see Table 3a). Among the not assessed ASD patients (N=168), 41 (24%) were diagnosed with NDDs. Children with SCD are being screened by their healthcare providers at a much lower rate than the general pediatric population. More specifically, many children with SCD were being screened for NDD, but not ASD. Among screened children, a majority were screened with non-standardized (or poorly documented) tools or outside the age guidelines recommended by ASH and AAP (see Figure 2). Children among ND and ASD assessment groups exhibited similar percentages of NDD diagnosis, which may highlight disparities in screening and early detection of these disorders; NDDs may have also been diagnosed later in life these patients. Guidelines regarding developmental screening in pediatric SCD were released in mid-2020; given the short timeline, we did not expect to see changes in practice from this chart review. However, the AAP has guidelines for developmental surveillance and screening since 2004. Due to study design, limitations include lack of access to some data at the time of review, as patient medical records were switched to another electronic system. Additionally, standardized tools may have been used but not documented in patient charts. In conclusion, it is crucial to know the utility of these assessments in this vulnerable population. A future study could examine how the rates of screening and surveillance have changed since the guidelines release, using these data for comparison purposes. Figure 1 Figure 1. Disclosures Casella: Mast Pharmaceuticals (previously Adventrx Pharmaceuticals): Consultancy, Honoraria, Patents & Royalties. Lance: Novartis: Other: participated in research advisory board in 2020.

Thrombocytopenia Among Patients with Hematologic Malignancies and Solid Tumors: Risk and Prognosis

Introduction: Despite the large body of research in cancer and increasing numbers of cancer survivors, knowledge about the risks and prognoses related to thrombocytopenia in the clinical care setting is scarce. Such information is important to understanding the need and potential impact of platelet transfusion and emerging drug therapies for thrombocytopenia. In this study, we examined the risk of thrombocytopenia among patients with incident cancer. Further, we studied the extent to which thrombocytopenia was associated with adverse clinical outcomes. Methods: This population-based cohort study was conducted using data from the Danish Cancer Registry. All patients diagnosed with incident hematologic malignancies and solid tumors (age of ≥18 years) during 2015─2018 were identified. Data were linked with routine laboratory test results from the primary care and hospital settings, as recorded in the Danish Register of Laboratory Results for Research. Based on platelet count levels (x 10 9/L), thrombocytopenia was categorized as grade 0 (any count)&lt;150; grade 1:&lt;100; grade 2:&lt;75; grade 3:&lt;50; and grade 4: &lt;25. We tabulated the prevalence of thrombocytopenia at study inclusion and calculated the cumulative incidence proportion (risk) of thrombocytopenia, accounting for the competing risk of death. Each patient with thrombocytopenia was matched up to 5 cancer patients without thrombocytopenia by age, sex, cancer type, cancer stage, and time from cancer diagnosis and index date. Cox proportional hazards regression analysis was used to compute hazard ratios (HRs) with 95% confidence intervals (CIs) of adverse clinical outcomes, including any bleeding leading to hospitalization, site-specific bleeding leading to hospitalization, transfusion (red blood cell, platelet, or fresh frozen plasma), and death. HRs were adjusted for Charlson Comorbidity Index scores and matching factors by design. Results: The analytic cohort comprised 11,785 patients with hematologic malignancies and 57,600 patients with solid tumors (median age=70 years). Any thrombocytopenia was observed during the 6 months preceding study inclusion among 18% of patients with hematologic malignancies (grades 1-2: 6% and grades 3-4: 5%) and 4% of patients with solid tumors (grades 1-2: 1% and grades 3-4: 0%). The 1-year and 4-year risks of new-onset thrombocytopenia were 30% and 40% for hematologic malignancies and 21% and 28% for solid tumors, respectively (Figure 1). Among patients who initiated chemotherapy following their cancer diagnosis (n=33,165), the 1-year and 4-year risks of thrombocytopenia were 50% and 62% for hematologic malignancies and 39% and 49% for solid tumors, respectively (Figure 2). Patients with grade 4 thrombocytopenia had higher rates of any bleeding leading to hospitalization than patients without thrombocytopenia [hematologic malignancies: HR=2.31 (95% CI: 1.43-3.73) and solid tumors: HR=4.52 (95% CI: 2.00-10.24)], while grades 1-3 thrombocytopenia did not confer a significantly increased rate of hospitalization for bleeding (Table 1). All grades of thrombocytopenia were associated with an increased rate of transfusion [overall for hematologic malignancies: HR=2.06 (95% CI: 1.91-2.23), and overall for solid tumors: HR=2.13 (95% CI: 1.83-2.48)] and with death [overall for hematologic malignancies: HR=2.01 (95% CI: 1.84-2.20), and overall for solid tumors: HR=1.44 (95% CI: 1.39-1.49)]. These associations increased in magnitude with decreasing platelet count levels. Conclusions: The risk of thrombocytopenia was substantial following a diagnosis of incident hematologic malignancy and solid tumors, with higher risks among patients who initiated chemotherapy. While only severe thrombocytopenia was a predictor of any hospitalization for bleeding, all grades of thrombocytopenia were associated with increased rates of transfusion and death. Our findings support the need for regular assessment of platelet count levels to identify cancer patients at risk of serious clinical outcomes. Figure 1 Figure 1. Disclosures Clouser: Amgen: Current Employment, Other: This work is related to Chemotherapy Induced Thrombocytopenia as a disease state, in this essence it is not directly related to an Amgen product; CIT is an area of scientific interest to Amgen with Romiplostim under development for this potential indicati. Saad: Amgen: Current Employment, Current equity holder in publicly-traded company.

268. Methicillin Sensitive Versus Methicillin Resistant Staphylococcus aureus Nosocomial Meningitis

Background Herein, we aimed to analyze the outcomes of the methicillin sensitive (MS) versus methicillin resistant (MR) culture-proven Staphylococcus spp. nosocomial meningitis (S-NM) in our setting. Methods We extracted data and outcomes for all adult patients (age &gt;18 years) consulted by the Infectious Diseases Consultants and diagnosed NM (developed at a compatible time according to CDC nosocomial meningitis definitions) between January 2006 and 2021 and fulfilled the following study inclusion criteria: (a) Age ≥18-year-old; (b) CSF culture is positive for Staphylococcus spp. (c) Presence of at least two of three clinical/laboratory criteria as meningitis findings: (i) Body temperature &gt;38oC; (ii) CSF finding; &gt;250 leucocytes/mm3; (iii) at least one of the following clinical findings, ie. impairment of consciousness, neck stiffness, nausea/vomiting. Identification of the infecting bacteria and determination of antimicrobial susceptibility were performed using the VITEK 2 automated system (BioMerieux Inc, Mercy L’etoil, France) and conventional methods. Resistance to methicillin was tested by E-test (bioMérieux). Antibacterial susceptibility tests were evaluated according to Clinical Laboratory Standards Institute (CLSI) criteria until 2014 and EUCAST between 2015 and 2021. Chi-square and Student T tests were used for statistical comparison. Results A total of 9 patients in MSS-NM, 41 patients in MRS-NM group fulfilled the study inclusion criteria. Age, gender, and CSF findings (except CSF glucose was significantly lower in MSS-NM) were similar in both groups (Table 1). Besides, EOT clinical success and overall success (EOT success followed by one-month survival without relapse or reinfection) rates were similar (Table 1). Relapse and reinfection rates during post-treatment one month period were 0%-0% and 0%-6.6% in MSS/MRS-NM, respectively. In MRS-NM group reinfection pathogens were Acinetobacter baumannii and Pseudomonas aeruginosa after 12 and 30 days end of treatment. Characteristics of NM Conclusion Overall success in MSS-NM was acceptable while it was non-significantly lower in MRS-NM. The medical community should seek better infection control measures from NM. Disclosures All Authors: No reported disclosures