Seronegative Group Research Articles

SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study

BackgroundWhether young adults who are infected with SARS-CoV-2 are at risk of subsequent infection is uncertain. We investigated the risk of subsequent SARS-CoV-2 infection among young adults seropositive for a previous infection.MethodsThis analysis was performed as part of the prospective COVID-19 Health Action Response for Marines study (CHARM). CHARM included predominantly male US Marine recruits, aged 18–20 years, following a 2-week unsupervised quarantine at home. After the home quarantine period, upon arrival at a Marine-supervised 2-week quarantine facility (college campus or hotel), participants were enrolled and were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein ELISA. Participants also completed a questionnaire consisting of demographic information, risk factors, reporting of 14 specific COVID-19-related symptoms or any other unspecified symptom, and brief medical history. SARS-CoV-2 infection was assessed by PCR at weeks 0, 1, and 2 of quarantine and participants completed a follow-up questionnaire, which included questions about the same COVID-19-related symptoms since the last study visit. Participants were excluded at this stage if they had a positive PCR test during quarantine. Participants who had three negative swab PCR results during quarantine and a baseline serum serology test at the beginning of the supervised quarantine that identified them as seronegative or seropositive for SARS-CoV-2 then went on to basic training at Marine Corps Recruit Depot—Parris Island. Three PCR tests were done at weeks 2, 4, and 6 in both seropositive and seronegative groups, along with the follow-up symptom questionnaire and baseline neutralising antibody titres on all subsequently infected seropositive and selected seropositive uninfected participants (prospective study period).FindingsBetween May 11, 2020, and Nov 2, 2020, we enrolled 3249 participants, of whom 3168 (98%) continued into the 2-week quarantine period. 3076 (95%) participants, 2825 (92%) of whom were men, were then followed up during the prospective study period after quarantine for 6 weeks. Among 189 seropositive participants, 19 (10%) had at least one positive PCR test for SARS-CoV-2 during the 6-week follow-up (1·1 cases per person-year). In contrast, 1079 (48%) of 2247 seronegative participants tested positive (6·2 cases per person-year). The incidence rate ratio was 0·18 (95% CI 0·11–0·28; p<0·001). Among seropositive recruits, infection was more likely with lower baseline full-length spike protein IgG titres than in those with higher baseline full-length spike protein IgG titres (hazard ratio 0·45 [95% CI 0·32–0·65]; p<0·001). Infected seropositive participants had viral loads that were about 10-times lower than those of infected seronegative participants (ORF1ab gene cycle threshold difference 3·95 [95% CI 1·23–6·67]; p=0·004). Among seropositive participants, baseline neutralising titres were detected in 45 (83%) of 54 uninfected and in six (32%) of 19 infected participants during the 6 weeks of observation (ID50 difference p<0·0001).InterpretationSeropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals. Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralisation activity or immunity against subsequent infection. These findings might be relevant for optimisation of mass vaccination strategies.FundingDefense Health Agency and Defense Advanced Research Projects Agency.

Epstein - Barr virus epidemiology in HIV infected transsexuals

Abstract Objectives: To molecularly characterise the relationship between Epstein-Barr virus genotypes and Pashtun ethnicity. Method: The cross-sectional study was conducted from November 2018 to December 2019 after approval from the Gomal University, Dera Ismail Khan, Pakistan, and comprised blood samples from transgender sex workers who were seropositive for human immunodeficiency virus-1 and seronegative for human immunodeficiency virus residing in two cities of Khyber Pakhtunkhwa province and Islamabad, the federal capital. Formalin-fixed paraffin-embedded samples were collected retrospectively, but collection of blood samples from the study subjects was purely on the basis of physical availability. ?-globin gene and EBER-1 were amplified for qualitative assessment and existence of Epstein-Barr virus. Characterisation of EBNA-2 was done through nested polymerase chain reaction. Results: Of the 80 subjects, 40(50%) each were seropositive and seronegative individuals. The overall mean age was 28±6.917 years. Among the seropositive group, 38(95%) were homosexual and 2(5%) were heterosexual. Among the seropositive group, 16(40%) had Epstein-Barr virus genotype 1 and 6(15%) had genotype 2, while co-infections were found in 2(5%) subjects. In the seronegative group, 36(90%) subjects had Epstein-Barr virus genotype 1, while there was no case of genotype 2 or co-infection. EBV-2 genotypes with HIV seropositivity showed strong association (p=0.005). Amplification for the EBER-1 gene was done in all the 80(100%) samples. Conclusion: Epstein-Barr virus EBV genotype 1 was found to be the most frequent type, while genotype 2 and co-infections were detected only seropositive samples. Continuous...

The efficacy of rituximab in patients with neuromyelitis optica spectrum disorder: A real-world study from Turkey.

Neuromyelitis optica spectrum disorders (NMOSD) are a group of antibody-mediated chronic inflammatory diseases of the central nervous system. Rituximab is a monoclonal antibody that leads to a reduction in disease activity. To evaluate the efficacy of rituximab as monotherapy in NMOSD and to determine whether the efficacy varies depending on the presence of antibodies in this cohort. This multicentre national retrospective study included patients with NMOSD treated with rituximab at least for 12months from Turkey. The primary outcomes were the change in the annualised relapse rate, the Expanded Disability Status Scale (EDSS), the number of relapse and radiological activity-free patients. A total of 85 patients with NMOSD were included in the study. Of 85 patients, 58 (68.2%) were seropositive for anti-Aquaporin4-IgG (antI-AQP4-IgG). All patients were Anti-Myelin Oligodendrocyte Glycoprotein IgG (anti-MOG-IgG) negative. The median follow-up for rituximab treatment was 21months (Q1 16-Q3 34.5). During rituximab treatment, the mean annualised relapse rate (ARR) significantly decreased from 1.45±1.53 to 0.15±0.34 (P<.001). In subgroup analyses, the mean ARR decreased from 1.61±1.65 to 0.20±0.39 in the seropositive group and 1.10±1.19 to 0.05±0.13 in the seronegative group. The mean EDSS improved from 3.98±2.04 (prior to treatment onset) to 2.71±1.59 (at follow-up) (P<.001). In the seropositive group, mean EDSS decreased from 3.94±1.98 to 2.67±1.54, and in the seronegative group, mean EDSS decreased from 4.07±2.21 to 2.79±1.73. There was no significant difference between anti-AQP4-IgG (+) and (-) groups in terms of ARR and EDSS. Sixty-four patients (75.2%) were relapse-free after the initiation of treatment. Seventy patients (82.3%) were radiological activity-free in the optic nerve, area postrema and brainstem. Additionally, 78 patients (91.7%) showed no spinal cord involvement after the treatment. Rituximab therapy is efficacious in the treatment of Turkish NMOSD patients independent of the presence of the anti-AQP4-IgG antibody.

Association between Toxoplasma gondii infection and metabolic syndrome in obese adolescents: A possible immune-metabolic link.

Background Toxoplasmosis as a global disease is considered as a triggering factor responsible for development of several clinical diseases. However, Toxoplasma gondii (T. gondii) is an understudied parasite of potential interest in obesity research. The current study aimed to explore the role of latent T. gondii infection in the pathogenesis of metabolic syndrome (MetS) in obese adolescents through studying the relationship between serum interferon-gamma [IFN-γ] and serum chemerin in context of MetS components. Methods Eighty-three obese adolescents were serologically screened for T. gondii-IgG antibodies and compared to 35 age-matched healthy T. gondii-seronegative controls. Participants were evaluated for anthropometric measurements, total-fat mass [FM], trunk-FM, serum lipid profile, IFN-γ, and chemerin levels. Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated. Results The prevalence of MetS was significantly higher within obese T. gondii-seropositive group compared to obese T. gondii-seronegative group (P=0.033). Seropositive obese MetS group displayed significantly higher trunk-FM, HOMA-IR, chemerin, and IFN-γ compared to seronegative obese MetS group. Serum chemerin and IFN-γ were strongly correlated (P<0.001) and were positively correlated with BMI, WC, total-FM, trunk-FM, HOMA-IR, cholesterol, triglycerides and negatively correlated with HDLC. HOMA-IR was a common predictor for serum chemerin (P=0.030) and IFN-γ (P<0.001). Conclusions The study results suggest that T. gondii infection may exert an immune-metabolic effect that may have a potential role in the development of MetS among obese adolescents.

Clinical characteristics of Vietnamese patients with idiopathic inflammatory myopathies and autoantibodies to aminoacyl-transfer RNA synthetases.

To assess clinical phenotypes of anti-aminoacyl-transfer RNA synthetases (aaRS) autoantibodies in Vietnamese patients of Kinh ethnicity with idiopathic inflammatory myopathies (IIM). In a cross-sectional study 23 patients with anti-aaRS autoantibodies were compared to 36 patients with other myositis-specific antibodies and to 69 seronegative patients with IIM. Assessments included muscle performance, extra-muscular involvement, and disease activity according to the International Myositis Assessment and Clinical Studies (IMACS). Sera were tested by a line immunoassay (Euroline Myositis Profile 4). The frequency of anti-Jo-1 antibodies was 56.5%, anti-EJ antibodies 26.1%, and anti-PL-7 antibodies 17.4%, while anti-PL-12 and anti-OJ antibodies were not present in any case. All patients with anti-aaRS autoantibodies had signs of myositis. At time of investigation 22/23 patients had muscle weakness, 52.2% arthritis, 34.8% Raynaud's phenomenon, 73.9% fever, 14.3% mechanic's hands and 56.5% dysphagia. Interstitial lung disease was present in 52.2%, and pulmonary hypertension in 56.5%. The anti-aaRS autoantibody positive group had higher disease activity in the domains of skin and pulmonary disease compared to the seronegative group and had lower disease activity in skeletal disease compared to the anti-melanoma differentiation-associated protein 5-positive patients. The clinical presentation of antisynthetase syndrome was similar between the aaRS autoantibody specificities with the exception of more frequent pulmonary hypertension in anti-Jo-1 positive patients. Different aaRS autoantibody specificities may vary between different ethnic populations for reasons that still need to be clarified. Furthermore, the high frequency of pulmonary hypertension is noteworthy but otherwise clinical manifestations associated with aaRS autoantibodies did not differ from other ethnic populations.

Increased epicardial adipose tissue thickness associated with increased metabolic risk and the presence of heart failure in patients with Chronic Chagas disease.

It has been described that Trypanosoma cruzi is capable of promoting metabolic disturbances currently considered as cardiovascular risk factors. Moreover, it has been observed that the protozoa can remain in adipose tissue and alter its immune endocrine functions. The aim of this study was to characterize the thickness of epicardial adipose tissue (EAT) in patients with chronic Chagas disease (CCD) concerning their cardiovascular metabolic risk profile compared with those without CCD. A cross-sectional study was performed including T. cruzi seropositive individuals categorized according to a standard CCD classification and a matched seronegative control group. Complete clinical examination, metabolic laboratory tests and transthoracic echocardiography to assess cardiac function and to quantify EAT were performed. Fifty-five individuals aged 46.7±11.9 y, 34 with CCD and 21 in the control group, were included. The CCD group presented higher EAT thickness in relation to controls (4.54±1.28 vs 3.22±0.99 mm; p=0.001), which was significantly associated with the presence of insulin resistance (OR=3, 95% CI 1.58 to 5.73; p<0.001). This group presented lower levels of plasmatic adiponectin than controls, especially in those patients with EAT ≥4.5 mm (p=0.005) who also presented with heart failure more frequently (p=0.01). In patients with CCD, a higher EAT thickness is observed and is associated with an increased metabolic risk profile indicated mainly by insulin resistance.

Distinct Hepatitis B and HIV co-infected populations in Canada.

Due to shared modes of exposure, HIV-HBV co-infection is common worldwide. Increased knowledge of the demographic and clinical characteristics of the co-infected population will allow us to optimize our approach to management of both infections in clinical practice. The Canadian Hepatitis B Network Cohort was utilized to conduct a cross-sectional evaluation of the demographic, biochemical, fibrotic and treatment characteristics of HIV-HBV patients and a comparator HBV group. From a total of 5996 HBV-infected patients, 335 HIV-HBV patients were identified. HIV-HBV patients were characterized by older median age, higher male and lower Asian proportion, more advanced fibrosis and higher anti-HBV therapy use (91% vs. 30%) than the HBV-positive / HIV seronegative comparator group. A history of reported high-risk exposure activities (drug use, high-risk sexual contact) was more common in HIV-HBV patients. HIV-HBV patients with reported high-risk exposure activities had higher male proportion, more Caucasian ethnicity and higher prevalence of cirrhosis than HIV-HBV patients born in an endemic country. In the main cohort, age ≥60years, male sex, elevated ALT, the presence of comorbidity and HCV seropositivity were independent predictors of significant fibrosis. HIV seropositivity was not an independent predictor of advanced fibrosis (adj OR 0.75 [95%CI: 0.34-1.67]). In conclusion, Canadian co-infected patients differed considerably from those with mono-infection. Furthermore, HIV-HBV-infected patients who report high-risk behaviours and those born in endemic countries represent two distinct subpopulations, which should be considered when engaging these patients in care.

SARS-CoV-2 Seropositivity and Subsequent Infection Risk in Healthy Young Adults: A Prospective Cohort Study

Background: The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subsequent infection among seropositive young adults was studied prospectively.Methods: The study population comprised 3,249 predominantly male, 18-20-year-old Marine recruits. Upon arrival at a Marine-supervised two-week quarantine, participants were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a 1:150 dilution or greater on receptor binding domain and full-length spike protein enzyme-linked immunosorbent (ELISA) assays. SARS-CoV-2 infection was assessed by PCR at initiation, middle and end of the quarantine. After appropriate exclusions, including participants with a positive PCR during quarantine, we performed three biweekly PCR tests in both seropositive and in seronegative groups once recruits left quarantine and entered basic training and baseline neutralizing antibody titers on all subsequently infected seropositive and selected seropositive uninfected participants.Findings: Among 189 seropositive participants, 19 (10.1%) had at least one positive PCR test for SARS-CoV-2 during the six-week follow-up (1.1 cases per person-year). In contrast, 1,079 (48.0%) of the 2,247 seronegative participants tested positive (6.2 cases per person-year). The incidence rate ratio was 0.18 (95% CI 0.11-0.28, pInterpretation: Seropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals. Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection. These findings may be relevant for optimization of mass vaccination strategies.Funding: Defense Health Agency and Defense Advanced Research Projects AgencyDeclaration of Interests: AGL, YG, SV, CG, DLW, HWC, DE, MCG, WDG, FJ, RL, JM, NM, CM, SM, VDN, EN, CKP, ESA, ASS, MS, VS, MT, PS, RPT, IR and SCS declare no competing interests. DP owned stock in Co- Diagnostics Inc during the conduct of the study. DP held stock in Co-Diagnostics, Inc. DS and FK have filed a patent regarding serological assays and for SARS-CoV-2 and Icahn School of Medicine at Mount Sinai has founded a company to commercialize serological assays they developed. AGL, CG, DLW, HWC, DEW, DG, FJ, JM, EN, CKP, ESA, MS, VS, PS, RAL, SAL, and MT are military Service members or GS employees. This work was prepared as part of their official duties. Ethics Approval Statement: Institutional Review Board approval was obtained from the Naval Medical Research Center (protocol number NMRC.2020.0006) in compliance with all applicable U.S. federal regulations governing the protection of human subjects. All participants provided written informed consent.

DO VITAMIN D DEFICIENCY AND HEPATITIS C VIRUS INFECTION PLAY A ROLE IN OXIDATIVE STRESS IN PATIENTS ON MAINTENANCE HEMODIALYSIS?

ABSTRACT Background Elevated oxidant levels and low antioxidant levels in patients with end-stage renal disease (ESRD) play a significant role in the development of endothelial dysfunction, atherogenesis and cardiovascular disease (CVD). A deficiency in vitamin D (Vit.D) is also suggested to be responsible for the generation of oxidative stress (OS) and CVD. Among dialysis patients, conflicting data exist concerning the relationship between hepatitis C virus (HCV) infection and OS. We studied the relationship between 25Vit.D level, HCV infection, and plasma 8 iso-prostaglandin F2 α (8-ISO-PGF2α) as an OS marker in an Egyptian hemodialysis (HD) cohort. Methods One hundred and twenty ESRD patients on HD were initially recruited to the study but only 88 patients have met the inclusion and none of the exclusion criteria. Midweek predialysis session blood samples were collected for the measurement of 25(OH) Vit.D, plasma 8-ISO-PGF2α, high sensitivity C – reactive protein (hs-CRP), and intact parathyroid hormone (intact PTH). Patients were stratified into two groups according to the presence or absence of serum antibodies against HCV and their plasma 8-ISO-PGF2α were compared. Results Vit.D deficiency was noted in 93% of the participants; the median 8-ISO-PGF2α level was 382 pg/mL. No significant correlation between Vit.D and 8-ISO-PGF2α levels was found. Thirty-two participants (36%) were HCV+ and their 8-ISO-PGF2α levels were significantly lower relative to in the seronegative group (median 171 vs. 647 pg/mL; P < 0.006). Conclusion In this Egyptian HD cohort, Vit D deficiency was highly prevalent, yet failed to show any correlation with F2-isoprostanes. HCV+ HD patients might be shielded from OS.

Expression of CD3 and CD20 in Antistreptolysin-O Titer Seropositive and Seronegative Children with Chronic Tonsillitis.

Background:Chronic tonsillitis (CT) is a common inflammatory illness in children, and serum antistreptolysin O titer (ASOT) is a common investigation performed for these cases and considered a perfect sign for tonsillectomy.Objective:To evaluate the expression of tonsillar T-and B-lymphocytes markers in relation to seropositive or seronegative ASOT in cases of CT.Materials and Methods:Thirty children (15 males and 15 females) aged 6–10 years were divided equally into two groups: Group A seropositive ASOT (≥400 IU) and Group B seronegative ASOT (<400 IU). Both performed bilateral tonsillectomy. Specimens from the removed tonsils were taken and prepared for light microscopic examination and immunohistochemical evaluation of CD20 and CD3 expression.Results:Seropositive ASOT group showed significant histopathologic changes in the form of hyperplasia of the stratified squamous nonkeratinized epithelium, Urgas's abscess, and severe lymphocytic infiltration. Immunohistochemical results of seropositive ASOT group showed marked expression of CD3 and CD20, while seronegative ASOT group showed mild expression of CD3 and CD20.Conclusion:Seropositive ASOT CT, in addition to histopathological changes, is associated with significant increase in both B-lymphocytes (CD20 expression) and T-lymphocytes (CD3 expression) markers.

Mental Health of Adolescents in the Pandemic: Long-COVID-19 or Long-Pandemic Syndrome?

Backround: Post-COVID19 complications such as pediatric inflammatory multisystem syndrome (PIMS) and Long-COVID19 move increasingly into focus, potentially causing more harm in this age group than the acute infection. To better understand the symptoms of long-COVID19 in adolescents and to distinguish infection-associated symptoms from pandemic-associated symptoms, we conducted a Long-COVID19 survey, comparing responses from seropositive and seronegative adolescents. To our knowledge, data of Long-COVID19 surveys with seronegative control groups have not been published yet.Methods: Since May 2020 students grade 8-12 in fourteen secondary schools in Eastern Saxony were enrolled in the SchoolCovid19 study. Seroprevalence was assessed via serial SARS-CoV-2 antibody testing in all participants. Furthermore, during the March/April 2021 study visit all participants were asked to complete a 12 question Long-COVID19 survey regarding the occurrence and frequency of difficulties concentrating, memory loss, listlessness, headache, abdominal pain, myalgia/ arthralgia, fatigue, insomnia and mood (sadness, anger, happiness and tenseness).Findings: 1560 students with a median age of 15 years participated in this study. 1365 (88%) were seronegative, 188 (12%) were seropositive. Each symptom was present in at least 35% of the students within the last seven days before the survey. However, there was no statistical difference comparing the reported symptoms between seropositive students and seronegative students. Whether the infection was known or unknown to the participant did not influence the prevalence of symptoms.Interpretation: The lack of differences comparing the reported symptoms between seropositive and seronegative students suggests that Long-COVID19 might be less common than previously thought and emphasizing the impact of pandemic-associated symptoms regarding the well-being and mental health of young adolescents.Trial Registration: Clinical trial number DRKS00022455. SchoolCoviDD19: Prospektive Erfassung der SARS-CoV-2 Seropositivität bei Schulkindern nach Ende der unterrichtsfreien Zeit aufgrund der Corona-Schutz-Verordnung (COVID- 19), DRKS00022455, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022455Funding: This study was supported by a grant by the Federal State of Saxony. M.K.W. was supported by the Else Kröner-Fresenius Center for Digital Health (EKFZ), TU Dresden, Germany.Declaration of Interests: Reinhard Berner and Jakob P. Armann report grants from the Federal State of Saxony during the conduct of the study. The other authors have no conflicts of interest to disclose.Ethics Approval Statement: The SchoolCoviDD19 study was approved by the Ethics Committee of the Technische Universität (TU) Dresden (BO-EK-156042020).

Clinical Features and Treatment Outcomes of Seronegative Pediatric Autoimmune Encephalitis.

Background and PurposeNew diagnostic criteria for pediatric autoimmune encephalitis (AIE) have been introduced recently. A substantial proportion of cases of pediatric AIE are diagnosed as seronegative based on these criteria, and so the clinical characteristics of this group remain to be investigated.MethodsThis study included 46 pediatric patients younger than 18 years with suspected AIE. Clinical features, laboratory or radiological findings, and treatment outcomes were compared between seronegative and seropositive patients.ResultsNine (19.6%) of the 46 patients were diagnosed as seropositive AIE. All of the patients with seropositive AIE had anti-N-methyl-D-aspartate receptor antibodies. Commonly identified neuropsychiatric symptoms were altered mental status, cognitive dysfunction, seizure, speech dysfunction, and psychotic disorder in both the seronegative and seropositive groups. Immunotherapy produced favorable treatment outcomes in both the seropositive (n=7, 77.8%) and seronegative (n=35, 94.6%) AIE patients. Treatment outcomes for first-line immunotherapy were better in seronegative AIE than seropositive AIE patients (p=0.003), and hence a smaller proportion of seronegative patients required second-line treatment (p=0.015).ConclusionsPediatric seronegative AIE patients showed clinical presentations similar to those of seropositive AIE patients, with favorable treatment outcomes after immunotherapy.

Comparison of healthcare resource utilization and medical costs between patients with seropositive and seronegative rheumatoid arthritis.

Objectives:To compare healthcare utilization and medical costs between patients with seronegative (SN) and seropositive (SP) rheumatoid arthritis (RA).Methods:We conducted a nationwide population study using the Korean health insurance claims database in 2016. We divided patients with RA into SN and SP groups and compared healthcare utilization including medications, medical utilization, and direct medical costs for 1 year between the groups in a cross-sectional analysis. Differences in costs between patients with SPRA and SNRA were assessed using the quantile regression model. We performed longitudinal analysis using data from 2012 and 2016 to examine changes over time.Results:A total of 103,815 SPRA and 75,809 SNRA patients were included in the analyses. The SPRA group used significantly more methotrexate (73.2% versus 30.3%) and biologic agents (7.9% versus 2.9%) than the SNRA group. The number of RA-related outpatient visits [6.0 ± 3.7 versus 4.4 ± 4.0 times/year, standardized difference (SD) = 0.41] and annual medical costs per patient ($1027 versus $450/year, SD = 0.25) were higher in the SPRA group than the SNRA group. Quantile regression results indicated that the incremental cost of seropositivity on total medical costs of RA patients gradually increased as medical costs approached the upper quantile. The annual direct medical costs for each patient between 2012 and 2016 increased in both groups: by 25.1% in the SPRA group and 37.6% in the SNRA group.Conclusion:Annual RA-related direct medical costs and RA-related healthcare utilization per patient are higher in patients with SPRA than those with SNRA.

926. Antibody Response to HPV Vaccination in Pediatric and Adolescent People Living with HIV (PLWH)

BackgroundImmune dysfunction related to HIV infection is associated with an inability to clear HPV infection and may compromise the immunogenicity of quadrivalent HPV vaccine Gardasil® (4v HPV).MethodsBetween 2005 and 2017, males and females 7 to 20 years old age, were offered 3-dose 4v HPV vaccine. Plasma IgG titers to HPV 6 (H6), 11 (H11), 16 (H16) and 18 (H18) were measured using multiplex VLP-based ELISA. For the 36 patients, median interval from 1st dose to 2nd and 3rd doses were 73 and 216 days. Plasma sample 1 was collected at median of 91 days after dose 1, sample 2, 169 and sample 3, 740 after respective vaccine doses. A 4th sample was available for 26 patients, median 2327 days after dose 1. Rank-sum test, Χ 2 or Fisher’s Exact Test were employed.ResultsBefore vaccination, 10 (28%) were seropositive to 1 or more HPV types. The baseline seropositives were older than seronegatives (16 years vs 11; p=0.007). After dose 3 all participants had an Ab response to at least 1 HPV type and 32 (89%) were seropositive for 4 HPV types. Seroconversions were H18, 87%; H16 97%; H11, 100%; H6, 97%. Seroconversions after 1 dose of 4v HPV among the baseline seronegatives were 61%, 90%, 86% and 86%, respectively and 22 became seropositive for all 4 types. The 4 baseline seronegative PLWH with partial seroconversion had higher median HIV viral load (VL) compared to baseline seronegative group with full seroconversion (12,920 vs 101 copies/ml; p = 0.052), but had comparable CD4 counts. The rate of post vaccination seropositivity and baseline to peak titer response for each HPV type was not significantly different for baseline sero-groups. Among baseline seronegative, all 19 sampled distant from vaccination remained seropositive to at least 1 HPV type (84% to 3 or more types) and 6 (32%) became seronegative (sero-reversion). Those showing sero-reversion had higher VL compared to the 14 who remained seropositive (9100 vs 48; p =0.015). Time from last dose of 4v HPV to sample 4, CD4%, age, gender, and race/ethnicity were similar between the groups.Bar Graphs representing Ab response to the 4 HPV types following each dose of 4v HPV vaccine ConclusionIn the complex environment of a pediatric HIV specialty clinic, most PLWH mounted Ab responses to 4v HPV that were durable. H18 was least immunogenic. Patients with higher HIV VL were less likely to seroconvert for all types and were more likely to sero-revert.Disclosures All Authors: No reported disclosures

ASSOCIATION OF LIVER FUNCTION TEST PARAMETERS WITH HEMATOLOGICAL INDICES IN SEROPOSITIVE HEPATITIS B PATIENTS

Background: Inflammation is increasingly being implicated for progression of Chronic Hepatitis B. Besides the usual liver function test (LFT) parameters, systemic inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have generated significant interest that could be useful in stratifying the severity and prognosis of liver disease. The aim of this study was to compare LFT parameters and hematological ratios (NLR and PLR) between seropositive hepatitis B patients and healthy controls and explore associations between them. Methods: This cross-sectional study included 64 Hepatitis B surface antigen (HBsAg) positive patients and 62 apparently healthy seronegative individuals visiting Chitwan Medical College between March to October 2019. Laboratory data included standard LFT panel and hematological parameters including NLR and PLR. Data was analyzed using SPSS software, version 20. P&lt;0.05 was considered to be statistically significant. Results: The two groups (seropositive and seronegative group) did not differ by age and gender. LFT parameters except for total protein were higher in the seropositive group. Both median NLR and PLR were considerably lower in the seropositive group compared to the seronegative group (2.99 and 102.32 vs. 3.67 and 126.15 respectively). However, NLR showed a considerable overlap between the groups, indicating a high variability. No significant correlation was observed between these hematological indices with other LFT parameters. Conclusions: NLR and PLR are easily obtainable, cost-effective parameters that are inversely related with Hepatitis B infection. They could supplement routine LFT parameters in characterization of the phase and severity of chronic Hepatitis B infection.

Leucocytes and Th-associated cytokine profile of HIV-leishmaniasis co-infected persons attending Abuja Teaching Hospital, Nigeria

Background: T-helper cells (Th)-1 & -2 cytokines homeostasis control or predict clinical outcome of infected persons, especially those with HIV/AIDS. This case-control study evaluated the white blood cell differetials, TNF-alpha, interleukin (IL)-2 and -10 levels among HIV infected persons with serological evidence of leishmnaiasis attending University of Abuja Teaching Hospital, Nigeria. Methods & Materials: After ethical approval, blood samples from 28 HIV infected persons (with skin disfiguration and high fever >10 days) whom were anti-leishmania IgG seropositive (group 1), 30 age- & -sex matched HIV infected persons whom were anti-leishmania IgG seronegative (group 2) and 30 apparently healthy persons without HIV and anti-leishmania IgG seronegative (group 3) within 1st July and 30th September, 2017. Full blood counts, TNF alpha, IL-2 and -10 levels were analyzed using automated hematology analyser and Enzyme linked Immunosorbent Assay, respectively. Structured questionnaires were used to collate biodata and clinical presentations of participants. Results: Ten (35.7%) participants in group 1 were on ART, 15 (50%) in group 2 were on ART, while group 3 were ART naïve. There were significantly higher values in basophil (4.4 ± 2.5%) and eosinophil counts (12.9 ± 3.8%) in HIV/leishmania coinfected persons (p < 0.005). However, other white cells subpopulation were significantly lower in HIV/leishmania co-infected participants (p< 0.05). There was significantly reduced CD4+ T cell counts ([119 ± 26 versus 348 ± 63 versus 605 ± 116 cells/mm3]), TNF-alpha ([36.82 ± 8.21 versus 64.67 ± 12.54 versus 254.98 ± 65.59 pg/mL]) and IL-2 levels ([142.14 ± 20.91 versus 507.6 ± 84.42versus 486.62 ± 167.87 pg/mL]) among HIV/leishmania co-infected participants compared to group 2 and group 3 participants, respectively. However, higher IL-10 level (80.35 ± 14.57 pg/mL) was found in HIV/leishmania co-infected participants as opposed to the HIV mono-infected (62.2 ± 10.43 pg/mL) and apparently healthy persons (23.97 ± 4.88 pg/mL) (p< 0.001). Conclusion: Eosinophil, basophil counts and serum IL-10 level were high in HIV/leishmania coinfected persons, suggesting parasite-induced hypersesnsitivity and pro-inflammatory reaction.

Risk of dengue virus infection according to serostatus in individuals from dengue endemic areas of Mexico

The variability in the host immune response directed against dengue virus (DENV) has demonstrated the need to understand the immune response associated with protection in incident infection. The objective was to estimate the association between serostatus and the risk of incident DENV infection. We used a prospective study from 2014 to 2016 in the localities of Axochiapan and Tepalcingo, Morelos, Mexico. We recruited 966 participants, of which, according to their infection history registered were categorized in four groups. To accomplish the objectives of this study, we selected to 400 participants older than 5 years of age were followed for 2.5 years. Blood samples were taken every 6 months to measure serological status and infection by ELISA. In individuals with at least two previous infections the risk of new infection was lower compared to a seronegative group (hazard ratio adjusted 0.49, 95% CI 0.24–0.98), adjusted for age and locality. Therefore, individuals who have been exposed two times or more to a DENV infection have a lower risk of re-infection, thus showing the role of cross-immunity and its association with protection.

The Pattern of Serum Conversion between Pre-treatment and Post-treatment Levels of Squamous-cell Carcinoma Antigen (SCC-Ag) as a Predictor of Recurrence and Survival in Locally Advanced Cervical Cancer after Definitive Concurrent Chemoradiotherapy

Cervical cancer is the second most commonly diagnosed malignancy and the second leading cause of cancer death in the developing countries. Although the value of squamous-cell carcinoma antigen (SCC-Ag) as a tumor marker for disease surveillance is generally accepted, its role as a reliable predictor for recurrence and survival is still controversial. This study was conducted to investigate the predictive efficacy of serum conversion between baseline and post-treatment SCC-Ag levels in locally advanced cervical cancer. Patients with biopsy-proven, stage IB2-IVA squamous cell-carcinoma of the cervix who received definitive concurrent chemoradiotherapy (CRT) between 2008 and 2017 in five institutions were consecutively included. All were tested for serum SCC-Ag levels pre- and post-CRT. Serum positivity was determined by plotting cumulative recurrence rate against post-treatment SCC-Ag level. A serum SCC-Ag level ≥ 2 ng/mL was defined as seropositive. Negative conversion was defined as pre-treatment SCC-Ag level ≥ 2 ng/mL reduced to post-treatment SCC-Ag level < 2 ng/mL. Serum conversion between pre-treatment and post-treatment SCC-Ag levels was categorized into the following three groups: i) seronegative: pre-treatment SCC-Ag < 2 ng/mL and post-treatment SCC-Ag level < 2 ng/mL; ii) negative conversion: pre-treatment SCC-Ag ≥ 2 ng/mL and post-treatment SCC-Ag level < 2 ng/mL; and iii) seropositive: pre-treatment SCC-Ag ≥ 2 ng/mL and post-treatment SCC-Ag level ≥ 2 ng/mL. A total of 291 patients were included. 162 (55.7%) underwent negative conversion. For seronegative (N = 65), negative conversion (N = 162), and seropositive groups (N = 64), the 3-year RFS rates were 92.9%, 75.3%, and 59.7% (P < 0.001) and the 3-year OS rates were 87.8%, 81.7%, and 55.9% (P < 0.001), respectively. The serum conversion of SCC-Ag levels between pre- and post-treatment was the most potent predictor of RFS (P = 0.001) and OS (P = 0.002) in multivariate analysis. Our data suggests that simply checking whether the serum SCC-Ag is above or below 2 ng/mL at pre- and post-treatment can function as a simple rule-of-thumb for prediction of recurrence and survival. Although prospective validation in a larger cohort is warranted, this predictor may provide clinicians to consider adjuvant therapy in consistently seropositive patients with risk of poorer outcome.

Expression of Viral microRNAs in Serum and White Blood Cells of Cows Exposed to Bovine Leukemia Virus.

Bovine leukemia virus (BLV) affects the health and productivity of cattle. The virus causes abnormal immune function and immunosuppression. MicroRNAs (miRNAs) are involved in gene expression, having been associated with stress and immune response, tumor growth, and viral infection. The objective of this study was to determine the expression of circulating miRNAs produced by BLV in animals exposed to the virus. Sera from 14 animals were collected to establish IgG reactivity to BLV by ELISA, where seven animals were seropositive and seven were seronegative for BLV exposure. White blood cells (WBC) from each animal were also collected and miRNAs were identified by sequencing from sera and WBC. The seropositive group had higher counts of BLV miRNAs when compared to seronegative group in sera and WBC. Blv-miR-1-3p, blv-miR-B2-5p, blv-miR-B4-3p, and blv-miR-B5-5p were statistically significant (P < 0.00001) in serum with an average of 7 log2 fold difference between seropositive and seronegative groups. Blv-miR-B1-3p, blv-miR-B1-5p, blv-miR-B3, blv-miR-B4-3p, blv-miR-B4-5p, blv-miR-B5-5p were statistically significant (P < 1.08e−9) in WBC with an average of 7 log2 fold difference between the seropositive and the seronegative groups. Blv-miR-B2-3p and blv-miR-B2-5p were also statistically significant in WBC (P < 2.79e-17), with an average of 27 log2 fold difference between the seropositive and the seronegative groups. There were 18 genes identified as being potential targets for blv-miR-B1-5p, and 3 genes for blv-miR-B4-5p. Gene ontology analysis indicated that the target genes are mainly involved in the response to stress and in the immune system process. Several of the identified genes have been associated with leukemia development in humans and cattle. Differential expression of genes targeted by BLV miRNAs should be evaluated to determine their effect in BLV replication.

HIV seronegativity in children, adolescents and young adults living with perinatally acquired HIV: A cross-sectional study in Thailand.

IntroductionEarly initiation of combination antiretroviral therapy (ART) with long‐term viral suppression may lead to seronegativity in grown‐up children with perinatally acquired HIV (PHIV). This study aimed to determine the frequency and associated factors of seronegativity in Thai children, adolescents and young adults with PHIV.MethodsA cross‐sectional HIV serological study was performed in children, adolescents and young adults two years or older who were receiving ART with undetectable HIV‐RNA for at least one year from August 2018 to August 2019. Medical records were extracted for multivariate analysis of independent factors for seronegativity.Results and discussionOf 110 patients, 50 male, median (range) age was 18.4 (4.8 to 26.6) years, 8 (7.3%) were seronegative, and 1 (0.9 %) was inconclusive. The seronegative group had a younger median (range) age at ART initiation: 3.0 (1.0 to 12.0) versus 40.0 (2.0 to 207.0) months, p = 0.045; and shorter median (range) duration from ART initiation to viral suppression: 16.8 (7.2 to 42.0) versus 55.2 (6.0 to 214.8) months, p = 0.036. Multivariate analysis identified younger age at ART initiation (aOR 0.69, 95% CI 0.49 to 0.98, p = 0.038) and shorter time to viral suppression after ART initiation (aOR 0.94, 95% CI 0.89 to 0.99, p = 0.019) as independent factors associated with HIV seronegativity. Of the infants who initiated ART < 3 and between three and six months of age, 50% and 26.7% became seronegative respectively.ConclusionsHIV seronegativity was observed in children and adolescents with PHIV who initiated ART early in infancy and had rapid and sustained virological response. Awareness of this phenomenon will help avoid inappropriate treatment interruption on the basis of negative antibody testing.