Anti Antibody Research Articles

A phase I/II study of CpG/alum-adjuvanted mammalian-derived quadruple antigen carrying virus-like particle COVID-19 vaccine.

Waning Spike-elicited immunity and emerging COVID-19 variants underscore the need for vaccines leveraging multiple SARS-CoV-2 antigens, rapidly adaptable to evolving strains. Herein, we evaluated the safety and immunogenicity of a CpG ODN-adjuvanted, alum-adsorbed, virus-like particle (VLP) vaccine displaying the hexaproline stabilized Spike (S) protein and the Nucleocapsid, Membrane, and Envelope proteins of SARS-CoV-2. In phase 1 randomized, double-blind, placebo-controlled, dose-escalation trial, participants (N=38, aged 18-59) received two subcutaneous injections of either 10μg or 40μg of VLP or placebo, 21days apart. The primary and secondary objectives of the study was to evaluate the safety, reactogenicity and immunogenicity, respectively. In the double blind, multi-center phase-2 study, participants (N=349, aged 18-55) were randomized into three cohorts receiving two doses of 40μg VLPs displaying Wuhan-Spike, Alpha-Spike, or a combination. The primary and secondary objectives were humoral, and cell mediated immunogenicity (CMI) and safety, respectively. Antibody responses were analyzed using ELISA while ELIspot and CBA assays were used to assess the CMI. The VLP vaccine demonstrated a good safety profile, with 255 non-serious adverse events in phase 1 and 308 in phase 2. Five serious AEs were reported in phase 2, all of which were resolved completely. The VLP vaccine, in phase 2, was well-tolerated, elicited moderate but sustained anti-S and anti-N antibody titers for 180days and induced T-helper-1 biased cellular responses in participants. The VLP platform is rapidly adaptable to accommodate stabilized Spike proteins from emerging variants and inclusion of other structural SARS-CoV-2 proteins could broaden the breadth of T cell-mediated immunity. gov; NCT04818281 and NCT04962893.

An elderly patient with a rare blood group in Bangladesh: a case report

The Bombay Blood Group is a rare blood type characterized by the absence or deficiency of the H antigen. It was first identified in Mumbai (formerly Bombay) in 1952, thus it was named as. This blood group lacks the A, B, and H antigens on red blood cells, and its serum contains anti-A, anti-B, and anti-H antibodies. A 60-year-old male was admitted to BIRDEM General Hospital with uncontrolled diabetes mellitus, hypertension, right-sided pneumonia, chronic kidney disease and severe anemia. Due to his critically low hemoglobin level of 6.5 gm/dl, he required two units of packed red cells. During pre-transfusion testing, a blood sample was taken and sent to our Transfusion Medicine Department. At the time of blood grouping we surprisingly noticed that he has ‘Bombay Blood Group’. It is a very rare type of blood group and on routine blood grouping behaves as “O” unless reverse grouping or serum grouping has been done but can receive transfusion from only peoples having Bombay group. Interestingly, individuals with the Bombay phenotype are likely to have family members with the same blood group. His three sons and one daughter were tested for blood grouping, all showed “O” positive with Rhesus “D” positive. Despite no known family members or records in our blood bank having the Bombay blood group, his sons embarked on a search for Bombay phenotype donors for his transfusion. They succeeded in locating two donors with the Bombay blood group, one from Narayanganj and another from Chandpur. Following treatment for infection and diabetes control, he received two units of Bombay red cell concentrate transfusion. After receiving blood transfusion, his clinical condition improved. BIRDEM Med J 2025; 15(1): 44-46

429. SARS-CoV-2 Fecal Shedding Dynamics Among People with Symptomatic COVID-19

Abstract Background Wastewater surveillance (WWS) has become a vital tool to identify SARS-CoV-2 (SCV2) trends in the community and emerging variants. A limitation to interpretation of WWS SCV2 data is an incomplete understanding of SCV2 RNA shedding dynamics in feces. The SCV2 Fecal Shedding Dynamics (FLuSHED) study sought to quantify SCV2 RNA fecal shedding in order to improve WWS data interpretation.Table 1.Demographics of Study Population (N=83 subjects who submitted ≥1 specimen, including enrollment stool) Methods FLuSHED is a prospective cohort study conducted in St. Louis, MO. Individuals who tested positive for SCV2 within 7 days of symptoms onset were enrolled. Participants submitted stool specimens and nasal swabs at enrollment and weekly until day 35-post enrollment and completed weekly surveys regarding COVID-19 symptoms, treatments, healthcare visits, and demographics/medical history. Dried blood spots and whole blood were collected at enrollment and day 35 to evaluate SCV2 antibody response; NP swabs were tested for SCV2 antigen by plasmonic fluor-linked immunosorbent assay (p-FLISA) and RNA by PCR. Stool was tested for RNA by PCR.Table 2.Detection of SCV2 RNA via PCR in Nasal Swab and Stool Specimens (n=25 full sets of specimens) Results 99 participants have been enrolled in FLuSHED to date from March 2023 to April 2024; 83 submitted at least 1 stool specimen (Table 1). Median time from symptom onset to enrollment was 3.5 days; 96% of participants reported being vaccinated against SCV2 (Table 1). PCR to date has been performed on 25 complete patient specimen sets (Table 2). SCV2 was detected in 88% of enrollment stool specimens, 40% of day 7 stool specimens, and only intermittently after day 7 post-enrollment. SCV2 was detected in the day 35 stool of one participant despite the patient’s day 14, day 21, and day 28 stools being SCV2 negative. At enrollment >90% had anti-S antibodies and 62% had anti-N antibodies; at day 35 the prevalence of anti-N antibodies increased to 93% (Table 4). N protein was detected in 65/84 (77%) NP swabs by p-FLISA, with a limit-of-detection of 8pg/mL (Figure 1).Table 3.Anti-S and Anti-N antibody positive at enrollment and day 35 Conclusion This study remains ongoing, but analyses from the first year of enrollment and follow-up indicate that SCV2 shedding in stool was common during and shortly after acute SCV2 illness. Later shedding of SCV2 virus is less common, but may continue to contribute to presence of SCV2 RNA in wastewater.Figure 1.N protein p-FLISA test detection of SARS-CoV-2 virus Disclosures Srikanth Singamaneni, PhD, Auragent Bioscience, LLC: Inventor on a pending patent related to plasmonic-fluor technology (licensed by Washington Univ in St. Louis to Auragent Bioscience, LLC|Auragent Bioscience, LLC: Ownership Interest Christopher W. Farnsworth, PhD, Abbott: Advisor/Consultant|Abbott: Grant/Research Support|Abbott: Honoraria|BD: Advisor/Consultant|Beckman Coulter: Grant/Research Support|Bluejay Diagnostics: Grant/Research Support|Roche: Grant/Research Support|Roche: Honoraria|Sebia: Grant/Research Support|Siemens: Grant/Research Support|Werfen: Advisor/Consultant|Werfen: Honoraria Bijal Parikh, MD, PhD, Cepheid: Honoraria Erik Dubberke, MD, MSPH, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Ferring: Advisor/Consultant|Ferring: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Grant/Research Support|Recursion: Advisor/Consultant|Seres Therapeutics: Advisor/Consultant|Theriva Biologics: Grant/Research Support|Vedanta: Grant/Research Support

P-2009. COVID-19 in Children with Hematological/Oncological Diagnoses – Exploring Reasons for Better Clinical Outcomes

Abstract Background The majority of COVID-19 infections in children, including in those with underlying hematological and oncological (Heme-Onc) diagnoses are mild with good outcome compared to adults. Postulated reasons include cross-protection from immunity against seasonal coronaviruses (HCoV’s), subdued inflammatory responses in children than in adults and differences in humoral and T-cell responses. The objectives of this study are to compare antibody responses against HCoV’s, anti-SARS-CoV-2 humoral, T-cell, and inflammatory profiles between Heme-Onc children with COVID-19 and control groups. Methods Binding IgG antibodies against Spike (S) of SARS-CoV-2, four HCoV’s (HKU1, OC43, NL63 and 229E), quantitative levels of 21 cytokines and 9 chemokines (multiplexed solid-phase electrochemiluminescence assay by Meso Scale Diagnostics/MSD) were compared among five cohorts: 1) children with Heme-Onc diagnoses and COVID-19 (n = 41) 2) healthy children with COVID-19 (n = 21) 3) adults with COVID-19 (n = 14) 4) children with multisystem inflammatory syndrome (MIS-C) [n = 23] and 5) healthy children without COVID-19 (n = 12). Additionally, T-cell responses against S and nucleocapsid (N) proteins of SARS-CoV-2 was assessed using ELISpot in Heme-Onc children a group of healthy children COVID-19. Results Anti-S antibodies and neutralizing antibodies against SARS-CoV-2 and HCoV were significantly lower in children in Heme-Onc and healthy children with COVID-19 compared to adults with COVID-19 (Figure 1). The concentration of eight pro-inflammatory cytokines and chemokines were significantly lower in Heme-Onc and healthy children compared to adults with COVID-19 and children with MIS-C. The responder T-cell frequency varied between 0 and 860/100,000 PBMC at study enrollment in children with Heme-Onc diagnoses. Conclusion In this single-center study, cross-protection from HCoV antibodies is an unlikely mechanism to explain mild COVID-19 in children, including in those with underlying hematological and oncological diagnoses. Subdued inflammatory responses to SARS-CoV-2 could be one of the factors for the mild COVID-19 disease phenotype in children. Disclosures Swetha Pinninti, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Suresh Boppana, MD, GSK: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support

MUC1 and glycan probing of CA19-9 captured biomarkers from cyst fluids and serum provides enhanced recognition of ovarian cancer

Glycosylation changes of circulating proteins carrying the CA19-9 antigen may offer new targets for detection methods to be explored for the diagnosis of epithelial ovarian cancer (EOC). Search for assay designs for targets initially captured by a CA19-9 antigen reactive antibody from human body fluids by probing with fluorescent nanoparticles coated with lectins or antibodies to known EOC associated proteins. CA19-9 antigens were immobilized from ascites fluids, ovarian cyst fluids or serum samples using monoclonal antibody C192 followed by probing of carrier proteins using anti-MUC16, anti-MUC1 and, anti STn antibodies and seven lectins, all separately coated on nanoparticles. Compared to reference CA19-9 and CA125 immunoassays, nanoparticle aided detection using MUC16, Ma695 and STn antibodies and lectin WGA provided, both separately and combined, improved discrimination of EOC and borderline cancers from benign samples when applied to 60 cyst fluid specimens. When applied to a panel of 44 serum samples (EOC N = 24, healthy and benign samples N = 20) two assays, CA19-9Ma695 and CA19-9MUC1, stood out with equally superior separations (p-values < 10–8) of the two groups compared to conventional CA19-9 immunoassay (p-value 0.03).Eu+3 -NP based CA19-9MUC16, CA19-9Ma695, CA19-9STn and CA19-9WGA show promise for improved EOC detection when applied to ascites & cyst fluids. When applied to circulation-derived samples, the two MUC1 based assays, CA19-9Ma695 and CA19-9Ma552 outperformed other assay constructs. Our results call for further validation in larger EOC cohorts preferentially with early stage ovarian cancers and all major histotypes against commonly occurring benign conditions.

Hemolytic disease of fetus due to multiple alloantibodies (anti-D, anti-C, and anti-s) requiring intrauterine transfusions: A case report and review of Indian literature

Abstract Immune hemolytic disease of fetus (HDF) and newborn is a serious complication in pregnancy and is associated with perinatal mortality and morbidity. Intrauterine transfusion (IUT) is performed for the treatment of fetal anemia caused by red cell alloimmunization. Here, we present the case of a 28-year-old multiparous pregnant female, with a history of bad obstetric outcomes. At 24 weeks gestation, she was referred to our center requesting one unit of irradiated leuco-depleted packed red cells (LDPRC) for 2nd IUT due to difficulty in finding a compatible unit elsewhere. A detailed immunohematology (IH) workup revealed the presence of anti-D, anti-C, and anti-s antibodies. The patient received O RhD Negative and C, and s red cell phenotype negative, crossmatch compatible, irradiated LDPRC unit for IUT. She received a total of three episodes of IUT at 24, 29, and 33 weeks of gestation and delivered a healthy female child at 36 weeks. Managing HDF with multiple antibodies requires coordination between interdisciplinary teams and an advanced IH lab along with trained staff and active involvement of transfusion medicine specialists to support early interventions and reduce HDF-related mortality.

Humoral and cellular immune durability of different COVID-19 vaccine platforms following homologous/heterologous boosters: one-year post vaccination

IntroductionThe durability of Hybrid immunity induced by natural infection and/or COVID-19 vaccines and evidence supporting further booster vaccination are crucial factors for pandemic response, yet remain poorly understood.MethodsWe measured the durability of immune response and neutralizing capacity of antibodies following Homologous/Heterologous vaccination by mRNA-based vaccines (Pfizer-BioNTech BNT162b2) or (Moderna mRNA-1273) and viral vector-based vaccines (ChAdox1 nCoV-19-Oxford-AstraZeneca) in infected and non-infected patients. We also evaluated the long-lasting specific humoral IgG levels and T-cell immunity of the Memory CD8 cells.ResultsWe found that heterologous prime boosters led to significantly higher IgG antibody levels)9.09(than homologous boosters)5.236) one year after vaccination. We measured SARS-CoV-2 anti-S IgG antibodies and then assessed their neutralizing capacity to inhibit the receptor-binding domain (RBD) of the SARS-CoV-2 wild-type strain and omicron B.1.1.529/BA.2 variants from binding to the ACE2 receptors. The heterologous regiment demonstrated superior ACE2-binding inhibition and consistently had higher mean ACE2-receptor binding inhibition across all dose regimens without the need for further doses. The CD8+ T cells producing IFN-γ to various COVID-19 vaccine dose regimens were evaluated. We found that robust T cell mediated immune responses were preserved and largely induced by a heterogeneous vaccination eliciting a significantly higher CD8+ T cells IFN-γ response in 100% of vaccinees regardless of previous natural infection. Indeed, the difference between infected and naïve groups was less pronounced suggesting a reduced infection-related response.DiscussionAcross three layers of evidence, this study showed that heterologous vaccination provides longer-lasting immunity than homologous doses, regardless of prior natural infection.

P0632 Analysis of serological responses to SARS-Cov-2 vaccination in patients with Inflammatory Bowel Disease in India identifies low BMI as an independent determinant of vaccine non-response

Abstract Background Studies of patients with inflammatory bowel diseases (IBD) from Western countries have demonstrated that serological responses to mRNA and vector-based vaccines are differentially impacted by IBD therapies. Little is known regarding antibody responses in patients with IBD residing in low- and middle-income countries (1). In this study, we investigate the factors which may influence the inhibitory and total antibody responses to SARS-CoV-2 in two centers in Northern India. Methods We studied 180 IBD patients in Chandigarh and New Delhi, India, who received two doses of a COVID-19 vaccine. All patients received Oxford-AstraZeneca equivalent Covishield (n=149) or inactivated virus vaccine Covaxin (n=31) between January 2021 and December 2022. We measured anti-S and anti-N antibody levels and performed inhibition assays to measure the inhibition of ACE2 on SARS-CoV-2 binding against alpha, delta, and omicron variants after first and second vaccine doses. Univariate and multivariate analyses were performed to identify determinants of vaccine response. Results On univariate analysis, IBD patients taking steroids (p= 0.019), immunomodulators (p= 0.047), or infliximab (p= 0.0057) had lower responses after dose 2 for any vaccine compared to those not on these medications or receiving 5-ASAs. Low BMI was associated with reduced rates of seroconversion in univariate analysis. For every fall in BMI by 1, the average ACOV2S V2 anti-Spike level was reduced by 8.2 (Figure 1). Additionally, 97% (28/29) of vaccinated IBD patients with a BMI greater than or equal to 25 reached the maximum anti-Spike value after their second dose of a COVID-19 vaccine. Multivariate analysis comparing gender, IBD type, smoking status, comorbidities, IBD medications, and a history of COVID-19 diagnosis revealed that low BMI (dose 1: OR: 1.12 [CI: 0.084, 0.136]; dose 2: 1.11 [0.076, 0.128]), infliximab (dose 1: 1.67 [-.92, 1.94]), and patients on steroids (dose 1: 1.50 [-1.384, 2.195]; dose 2: 0.200 [-3.76 0.54]) were each independent determinants of lower seroprevalence levels after receiving a dose of Covishield or Covaxin. Conclusion Immunosuppressive drug therapy and reduced BMI emerge as determinants of sub-optimal seroconversion rate in this patient population. The association with low BMI represents a unique finding in this population, and directly contrast with studies reported in Europe &amp; North America. These data are useful for future pandemic vaccine considerations in patients with IBD. References (1)Wong SY, Wellens J, Helmus D, et al. Geography Influences Susceptibility to SARS-CoV-2 Serological Response in Patients With Inflammatory Bowel Disease: Multinational Analysis From the ICARUS-IBD Consortium. Inflamm Bowel Dis. 2023;29(11):1693-1705. doi:10.1093/ibd/izad097

P1162 Novel use of risankizumab in children with refractory Crohn’s disease : Case series

Abstract Background Pediatric Inflammatory bowel disease (IBD) is generally more aggressive and difficult to treat compared to adulthood IBD. The only biological agent approved for use in this population is Anti-TNF medications (Adalimumab and Infliximab). Other medications such as anti IL-23 and/or IL-12 antibodies are not officially approved, yet the adult literature showed efficacy even in refractory cases priorly exposed to biologics. Given the delay of new medications approval in children, we present the novel use and real world experience of risankizumab which is a p19 anti IL-23 antibody in children with refractory Crohn’s disease. Methods We present 5 cases of Crohn’s disease who have failed at least 1 biological agent, including Adalimumab, Infliximab, ustekinumab, Azathioprine and methotrexate. All of them developed pharmacodynamic loss of response to Anti-TNF and one patient developed neutralizing antibodies. MR enterography was showing active ileal disease prior to commencing risankizumab. One Patient had developed Pyoderma gangrenosum, and another patient underwent pan-endoscopy which showed inflamed mucosa. C-reactive protein and ESR did not correlate with disease activity or response to the medication. risankizumab was administered as per the protocol . After 1 year follow up, all patients were in clinical remission with normal calprotectin. Bedside intestinal Ultrasounds was done and showed normal bowel wall thickness. Pyoderma gangrenosum improved significantly as well. Only one patient had MR enterography after 1 year which was unremarkable. No side effects were observed within the follow up period. Results We demonstrate that risankizumab has been used for 5 patients who already lost response to one or two biological medications. This medication successfully induced clinical and radiological remission after 1 year. risankizumab could be used after Adalimumab, Infliximab or even ustekinumab. Despite lack of approval, cautious use of new biological agents might be the only choice to avoid surgical resection in refractory Crohn’s disease. No side effects were documented over short term follow up. Additionally, Pyoderma gangrenosum responded after treatment. Conclusion Risankizumab can be an effective choice in pediatric Crohn’s disease patients who have lost response to other biological treatment and who had surgical resection as well. Patients maintained remission over 1 year follow up, and did not exhibit any side effect. References Zare B, Gros B, Lal N, et alEffectiveness of risankizumab induction and maintenance therapy for refractory Crohn’s disease: a real-world experience from a preapproval access programme and early access to medicines schemeFrontline Gastroenterology 2024;15:499-506.

P0701 Trans-continental analysis of determinants of response to COVID-19 vaccination in 2268 patients with Inflammatory Bowel Disease

Abstract Background Little is known about the relative efficacy of available COVID-19 vaccine types around the world in immune-compromised patients with inflammatory bowel disease (IBD).1,2 We aimed to compare antibody responses to SARS-CoV-2 in patients with IBD who had received mRNA, vector, and inactivated virus vaccines and the impact of medications thereof among multinational sites. Methods Serum samples taken after 1st, 2nd, and 3rd doses of COVID-19 vaccines from patients with IBD seen at 13 sites across Europe, Asia, and North America were prospectively collected between January 2021 and November 2022. We measured anti-Spike (S) and anti-nucleocapsid (N) antibody levels. To identify determinants of serological responses to vaccination, both univariate and multivariate analyses were conducted. Results There were a total of 2,268 patients, including 1,279 Crohn’s disease (CD) and 868 ulcerative colitis (UC) (Table 1). 1552 patients had an mRNA vaccine, 590 an adenovirus vaccine, and 98 an inactivated virus vaccine. At 14-84 days, 85-168 days, and 169+ days after completing a full vaccination series, the proportion of patients who were positive for anti-S antibodies were 98% (n=922/939), 96% (n=700/731), and 98% (n=677/692) for mRNA, 95% (n=378/396), 89% (n=55/62), and 97% (n=33/34) for adenovirus, and 72% (n=21/29), 84% (n=31/37), and 95% (n=55/58) for inactivated virus vaccine, respectively. On univariate analysis, rates of serological response were highest in those who received mRNA vaccines at all six time periods (Figure 1a). Adenovirus vaccine response rates closely resembled the rate of seropositivity in mRNA vaccinated patients. In contrast, inactivated vaccines had a significantly lower percent of patients reaching seropositivity until 169 days or more after the second vaccine dose (p&amp;lt;0.001). Anti-TNF monotherapy and immunomodulator monotherapy were associated with the ability to obtain maximum antibody titres. However, this difference is ablated after the 3rd dose (Figure 1c). Univariate analysis also implicated geographical site, male sex, and a diagnosis of ulcerative colitis as determinants of serological responses. On multi-variable analysis, vaccine type (p &amp;lt; 0.001 at every time point analysed) and the use of immunomodulators (p &amp;lt;0.001 at time points 1 and 3) were confirmed as independent determinants of vaccine responsiveness across the study populations. Conclusion Our data suggests that while there is variability between geographical centers, the response rates are high worldwide, and the key determinants of serological response to vaccines are the use of immunosuppressive agents and vaccine class.3 These data are important considerations for better pandemic preparedness in the IBD community worldwide. References (1)Wong SY, Wellens J, Helmus D, et al. Geography Influences Susceptibility to SARS-CoV-2 Serological Response in Patients With Inflammatory Bowel Disease: Multinational Analysis From the ICARUS-IBD Consortium. Inflamm Bowel Dis. 2023;29(11):1693-1705. doi:10.1093/ibd/izad097 (2)Goodyear CS, Patel A, Barnes E, et al. Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial. Lancet Rheumatol. 2024;6(6):e339-e351. doi:10.1016/S2665-9913(24)00065-1 (3)Barnes E, Goodyear CS, Willicombe M, et al. SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease. Nat Med. 2023;29(7):1760-1774. doi:10.1038/s41591-023-02414-4

Cutaneous Alternariosis in a Patient with Pulmonary Granulomatosis with Polyangiitis (GPA): Is It a Marker of Immunosuppression or Immune Dysregulation?

Granulomatosis with polyangiitis (GPA) is a rare multisystem disorder of autoimmune pathology involving small- and medium-vessel vasculitis of respiratory and renal system. Immune dysregulation due to GPA illness and immunosuppression after use of immunomodulators predisposes to opportunistic secondary infections. We report a 43-year-old male who presented with acute respiratory distress and acute hypoxic respiratory failure, skin lesions and multifocal nodules with radiological bronchus sign on high-resolution computed tomography thorax imaging and negative workup for sepsis screen on microbiological workup. He was diagnosed as GPA after positive anti C-antineutrophil cytoplasmic antibody test. Skin lesions needle aspirate for potassium hydroxide mount showed fungal aetiology. Punch biopsy for histopathology and culture with fungal polymerase chain reaction analysis finally confirmed the diagnosis of cutaneous alternariosis. Combination regimen of methylprednisolone, azathioprine and itraconazole was used for the management of GPA with cutaneous alternariosis. We observed remission of GPA and documented complete resolution of lung and skin lesions. We recommend a high index of suspicion during management of GPA with concurrent fungal infection for successful treatment outcome.

Infection Dynamics of Severe Acute Respiratory Syndrome Coronavirus-2 Wild-type and Delta Variant of Concern in a Pediatric Cohort in Southern India

Abstract Background: Dynamics, severity, and immune response of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection vary between children and adults. There are only a few reports on the differential impact of variants in children, and none reported from low-and-middle-income countries. Materials and Methods: Between November 2020 and August 2021, we enrolled children under 16 years testing positive for SARS-CoV-2 by polymerase chain reaction (PCR). We compared virus characteristics (viral load, virus variant - Wild-type or Delta), disease severity (asymptomatic, mild-to-moderate, and severe), and immunity levels to the virus (anti-N and anti-S) after 4–6 weeks. Results: Of 79 children recruited, 29%, 59%, and 11% had asymptomatic, mild-to moderate, or severe presentations, respectively. Wild-type and delta variants presented with similar disease severity. For both variants, anti-S antibody levels were higher than anti-N antibody levels (P &lt; 0.0001). Anti-S was also higher than anti-N among asymptomatic (P = 0.02) and mild-to-moderate disease (P &lt; 0.0001). Children with higher virus loads had higher levels of both anti-S and anti-N antibodies (quartile [QS]1 versus QS3, P &lt; 0.05). Among low (QS3) virus loads, wild-type anti-S levels were higher than delta infected (P = 0.003). In mild-to-moderate disease, the mean Ct value of wild type (32.5) was higher than that of delta infection (25.0) (P = 0.0083). Conclusions: In children, the antibody response is driven by viral load. In mild-to-moderate disease, higher loads of Delta variant of concern resulted in robust antibody response that was absent in severe disease. These results could inform potential responses to future SARS-CoV-2 variants and may guide decisions on targeted vaccination in children.

Humoral and cellular response to SARS-CoV-2 mRNA vaccine in paediatric heart transplant recipients.

The aim of this prospective cohort study is to analyse the humoral and cellular vaccine responses in paediatric heart transplant recipients (HTR, n=12), and compare it with the response in healthy controls (HC, n=14). All participants were 5-18 years old and vaccinated with mRNA vaccine against SARS-CoV-2 between December 2021 and May 2022. The humoral response was measured by quantifying antibody titers against SARS-CoV-2 spike protein (anti-S). The T-lymphocyte phenotype and SARS-CoV2-specific CD4+ and CD8+ T-cell response was studied by multiparametric flow cytometry through peripheral blood mononuclear cells by the quantification of degranulation markers (CD107a) and intracellular cytokines (IFN-γ, TNF-α and IL-2) after in vitro stimulation with SARS-CoV-2 peptides from structural proteins (S, M, N, E) and non-structural viral proteins. After vaccination, humoral response was found in all HTR, although they showed lower levels of anti-S IgG compared to HC (p=0.003). However, in terms of cellular response, no significant differences were obtained in the prevalence of responders and magnitude of responses between groups. In addition, anti-S IgG levels directly correlated with a higher SARS-CoV-2 specific T-cell response (rho=0.43; p=0.027 and rho=0.45; p=0.02 for IFN-γ+ and TNF-α+ production of CD8+ T-cells, respectively). Activated T-cell phenotype in HTR was associated with a lower humoral response to SARS-CoV-2 vaccine. HTR had humoral response after vaccination, although they showed lower levels of specific anti-S antibodies compared to HC. There were no significant differences in the SARS-CoV2-specific cellular response between the two groups. Obtaining satisfactory data on this type of response could potentially challenge the current vaccine guideline recommendations.

Evaluation of the hematological parameters, inflammatory biomarkers, and thyroid hormones in hypothyroidism patients

AimHypothyroidism is created by disruption of thyroid hormone production, which can destroy the emotional, relational, social, and working life of patients if left untreated. Hypothyroidism has multiple etiologies. We evaluated the relationship of hematological parameters and inflammatory biomarkers with thyroid hormones to find the potential use of these items in patients screening and prognosis.MethodsThis is a cross-sectional study, which was done on 88 individuals of both genders (32 male and 56 female), over 18 years old with a mean age of 45 years old. These patients were referred by physicians after examination to our laboratories of Qaem Medical Laboratory of Kuhchenar and Jahrom University of Medical Sciences, Fars, Iran. The patients had recent symptoms and signs of hypothyroidism with increased TSH above the normal range, and negative serum anti-TPO antibody. To determine ABO, Rh, and Lewis (Le) blood groups was used anti-A, anti-B, anti-D, anti-Lea, and anti-Leb monoclonal antibodies. Serum T3, T4, and TSH was measured by direct chemiluminescent immunoassay. Anti-TPO antibody was measured by ELISA. CRP was determined using an immunoturbidimetric assay. CBC count assessment was done via an automated cell counter.Exclusion criteria were patients with acute or chronic inflammatory diseases. Herein, we evaluated the correlation of hematological parameters consisting ABO, Rh, and Le blood groups, RBC and WBC parameters, and platelet count as well as inflammatory biomarkers including ESR, CRP, IL-8, and NLR with T3, T4, and TSH in hypothyroid patients.ResultsOur study showed a significant correlation between Lea blood group (non-secretor) in comparison with Leb blood group (secretor) with TSH (P = 0.01). There was no correlation between Leb and Lea blood groups with T3 and T4. We did not observe the correlation between Rh and ABO blood groups with T3, T4, and TSH. We observed significant correlations between Hb, Hct, and MCH with T3 (PHb = 0.012, PHct = 0.021, and PMCH = 0.032) and also, with T4 in hypothyroidism (PHb = 0.023 and PHct = 0.026). We revealed significant correlations between Hb, Hct, and MCH with TSH in hypothyroidism (PHb = 0.017, PHct = 0.019, and PMCH = 0.007). The significant correlations between CRP and IL-8 with T3, T4, and TSH was not explored. The significant correlations between ESR with T3 and TSH was not detected. ESR showed a significant correlation with T4 (PESR = 0.020). There were also no significant correlations between the counts of neutrophils, lymphocytes, monocytes, and eosinophils, as well as NLR with T4. There was only significant correlation between monocyte count with T3 (PMono = 0.029) and also lymphocyte count with TSH (PLymph = 0.041).ConclusionIn this investigation, we observed a significant relationship between Lea blood group in comparison with Leb blood group with TSH. We demonstrated significant correlations between Hb and Hct with T3, T4, and TSH, and also correlations between MCH with T3 and TSH. In conclusion, the assessment of Hb, Hct, MCH, and Le blood groups as hematological parameters can help physicians in the management of hypothyroidism.

Distinct Neutralising and Complement-Fixing Antibody Responses Can Be Induced to the Same Antigen in Haemodialysis Patients After Immunisation with Different Vaccine Platforms.

Background/Objectives: Generalised immune dysfunction in chronic kidney disease, especially in patients requiring haemodialysis (HD), significantly enhances the risk of severe infections. Vaccine-induced immunity is typically reduced in HD populations. The SARS-CoV-2 pandemic provided an opportunity to examine the magnitude and functionality of antibody responses in HD patients to a previously unencountered antigen-Spike (S)-glycoprotein-after vaccination with different vaccine platforms (viral vector (VV); mRNA (mRV)). Methods: We compared the total and functional anti-S antibody responses (cross-variant neutralisation and complement binding) in 187 HD patients and 43 healthy controls 21-28 days after serial immunisation. Results: After 2 doses of the same vaccine, HD patients had anti-S antibody levels and a complement binding capacity comparable to controls. However, 2 doses of mRV induced greater polyfunctional antibody responses than VV (defined by the presence of both complement binding and cross-variant neutralisation activity). Interestingly, an mRV boost after 2 doses of VV significantly enhanced antibody functionality in HD patients without a prior history of SARS-CoV-2 infection. Conclusions: HD patients can generate near-normal, functional antigen-specific antibody responses following serial vaccination to a novel antigen. Encouragingly, exploiting immunological memory by using mRNA vaccines and boosting may improve the success of vaccination strategies in this vulnerable patient population.

Clinical and laboratory characteristics of paediatric systemic lupus erythematosus at secondary level hospital among local population in North East India

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem inflammation and the presence of circulating auto antibodies directed against self-antigens with flare-ups and remissions. Childhood-onset SLE (cSLE) is a rare disease with an incidence of 0.3-0.9 per 100.000 children-years. The study among paediatric population of north east India were few and hence this study from north east India was undertaken. Objective of this study was to study the clinical and immunological profile of children with systemic lupus erythematosus (SLE). To study the distribution of Renal Lesions according to ISN/RPS Classification of Lupus Nephritis. Methods: Retrospective observational single centre study at secondary care hospital in North East India. Medical records of children with SLE admitted in Paediatric department from the period of 2018-2024 through the hospital information management were analysed. Clinico pathological features and immunological profile were compared with other studies. Results: Among 20 patients studied female to male ratio was 3:1. The mean patient’s age at the time of presentation was 12.4 years. The mean duration of illness was 8.5 months. Most common systems involved were hematological (85%), followed by kidney (75%) and mucocutaneous (75%). All (100%) cases were ANA positive. 45% were anti smith antibody positive, 20% were anti- dsDNA positive. Focal and segmental proliferative glomerulonephritis (ISN/RPS class III) was the most commonly seen histological pattern, seen in 5 (83%) patients who underwent biopsy. Diffuse proliferative glomerulonephritis (ISN/RPS class IV) was seen in 1 (16%) patient. Conclusions: Childhood onset SLE is still a challenge to diagnose and manage due to unpredictable clinical manifestations with variable disease activity at different age.

Effect of Homologous and Heterologous Booster in COVID-19 Vaccination.

Background: COVID-19 became a global health crisis in early 2020, and the way out of the crisis was the rapid development of vaccines by Sinopharm, Pfizer, and Sputnik, among others, which played a crucial role in controlling the pandemic. Therefore, this study aims to investigate the long-term immune response by measuring the levels of anti-S1 IgG antibodies induced by homologous and heterologous vaccination regimens. Methods: We investigated the titer of the anti-S1 IgG antibody produced for the viral surface antigen 3, 6 months after the second dose, before the third dose, and 1, 3, and 6 months after the third dose. Results: Anti-S1 IgG antibody levels significantly increased three/six months after the second dose and following the booster in individuals without prior COVID-19 infection who received all three homologous vaccine doses. The group that initially responded poorly to Sinopharm showed a significant and sustained increase after receiving the Pfizer booster. Additionally, prior SARS-CoV-2 infection between primary and booster vaccination boosted anti-S1 antibody titers in all individuals, regardless of the vaccine used. The highest vaccine efficacy was observed during the primary vaccination period and declined over time, especially during the omicron-dominant period. Conclusions: The results suggest that while homologous and heterologous booster doses can significantly enhance anti-S1 IgG antibody levels, prior SARS-CoV-2 infection and the type of vaccine administered influence the duration and magnitude of the immune response.

Immune Response to SARS-CoV-2 XBB.1.5 and JN.1 Variants Following XBB.1.5 Booster Vaccination in Liver Transplant Recipients.

The efficacy of monovalent BNT162b2 Omicron XBB.1.5 booster vaccination in liver transplant recipients (LTRs) has yet to be described, particularly regarding the immune response to emerging variants like JN.1. This study evaluated humoral and cellular immune responses in 34 liver transplant recipients (LTRs) with varying SARS-CoV-2 immune histories before and after receiving a BNT162b2 Omicron XBB.1.5 booster vaccination. The assessment involved variant-specific serology, pseudovirus neutralization tests, and Interferon-γ release assays. Participants had a median of four prior vaccinations, with 91.2% having a history of infection. Post-vaccination, significant increases in both Wuhan anti-S and Omicron-specific IgG antibodies and improved neutralization of B.1, XBB.1.5, and JN.1 pseudovirus particles were observed. Also, T-cell responses significantly increased post-vaccination. However, 17.6% of LTRs had no neutralizing antibodies against XBB.1.5 and JN.1, while 100% of healthy controls did. Shortly after vaccination, 18% of patients developed mild COVID-19. These LTRs had particularly low immune responses at baseline. The monovalent XBB.1.5 booster improved overall SARS-CoV-2-specific immunity. However, some LTRs still showed low or undetectable immune responses, indicating that ongoing monitoring and further booster doses are necessary in this high-risk group.

Immune Response Dynamics to SARS-CoV-2 in the Albanian Population: A Study on T-Cell and Antibody Interactions During the Transition From Pandemic to Endemic Phase

Abstract Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in a dynamic evolution of the immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially characterized by primary responses and later by secondary responses due to mass vaccination and viral variants. Understanding the interplay between humoral (antibody) and cellular (T-cell) immunity is crucial for effective public health strategies. This study aims to evaluate the correlation between T-cell responses and antibody levels in a sample of the adult Albanian population during the transition of COVID-19 from a pandemic to an endemic phase. The rationale for this investigation is to generate data that can inform the ongoing management of COVID-19, particularly in the context of vaccination and immunity monitoring, to ensure that public health strategies remain effective as the virus becomes more permanent in the population. Methods: This cross-sectional observational study involved individuals over 18 years of age who were randomly selected at intervals of every 20 records from the family doctor registries of five urban health centers in Tirana and Berat, Albania, between January 23 and April 3, 2023. Participants provided demographic and health data, including vaccination and infection history. Blood samples were analyzed for cellular immunity using an Interferon-gamma (IFN-γ) release assay and for humoral immunity using the enzyme-linked immunosorbent assay to measure anti-spike (S1) and anti-nucleoprotein (N) IgG antibodies. Statistical analyses were conducted to examine the relationships between levels of IFN-γ, anti-S1, and anti-N IgG antibodies and factors such as vaccination status, prior COVID-19 infections, and reinfection rates. These analyses employed bivariate and multivariate approaches, including Fisher’s exact test, the Mann–Whitney U test, the Kruskal–Wallis test, linear and multiple regression analyses, and Spearman’s correlation coefficient test. Results: The study involved 164 individuals (54.7% female, median age 43 years). Of these individuals, 62.8% (103/164) were vaccinated, primarily with the Pfizer-BioNTech vaccine. IFN-γ positivity was detected in 95.1% (156/164), and anti-S1 IgG positivity in 93.3% (153/164). Significant correlations were observed between IFN-γ and anti-S1 IgG levels (r = 0.502; P &lt; 0.001). Vaccinated individuals exhibited significantly higher levels of IFN-γ and anti-S1 IgG than unvaccinated individuals (P &lt; 0.05). Reinfections were more prevalent in unvaccinated individuals than vaccinated individuals (26.2% [16/61] vs. 12.6% [13/103], P = 0.034). According to multiple regression analysis, the levels of anti-S1 antibodies were significantly correlated with protection against reinfection (regression coefficient β = –0.003; P = 0.042), while IFN-γ levels did not exhibit such a correlation (regression coefficient β = –1.659; P = 0.146). Conclusion: Vaccination, especially when combined with previous infection, significantly boosts both cellular and humoral immunity against SARS-CoV-2. The close correlation between IFN-γ and anti-S1 IgG levels indicates that vaccinated individuals mount a robust immune response. The lower reinfection rates among vaccinated individuals highlight the importance of vaccination for sustained protection. Assessing anti-S1 IgG antibodies and IFN-γ levels could be particularly beneficial for immunocompromised individuals when making decisions about revaccination. This study highlights the critical role of comprehensive immune monitoring in the management of COVID-19 and offers insights for future vaccination strategies.

Autoantibodies Targeting G-Protein-Coupled Receptors and RAS-Related Molecules in Post-Acute COVID Vaccination Syndrome: A Retrospective Case Series Study.

Background/Objectives: While post-acute COVID-19 syndrome is well known and extensively studied, the post-acute COVID vaccination syndrome (PACVS) is a more recent nosological entity that is poorly defined at the immunopathological level, although it shares many symptoms with the sequelae of viral infections. Methods: This single-center retrospective study reports a case series of 17 subjects vaccinated with mRNA or adenoviral vector vaccines who were healthy before vaccination and had never been infected with SARS-CoV-2 but who presented with symptoms similar to PACVS for a median time of 20 months (min 4, max 32). The medical records of all patients referred to our outpatient clinic over a one-year period were retrospectively analyzed. Results: In this group, serological tests showed that, in addition to positivity for anti-spike protein antibodies, a high percentage of subjects were positive for antibodies against G protein-coupled receptors and molecules involved in the response to SARS-CoV-2. In a panel of 16 autoantibodies tested, a few were positively associated with some of the symptoms reported by patients: anti-ATR1 with lymphadenopathy and/or tonsillitis; anti-ACE2 with skin symptoms such as ecchymosis, skin oedema, and rash; anti-MAS1 with widespread burning sensation; and anti-STAB1 with skin oedema and rash. Anti-ADRA2A were negatively associated with memory loss and/or mental fog. ACE2 correlated with the serum levels of anti-S antibodies, supporting the hypothesis of an anti-idiotype mechanism in the immunopathogenesis of PACVS. Conclusions: This exploratory analysis suggests that the levels of autoantibodies directed against ACE2, and probably also MAS1 and STAB1, may serve as biomarkers for PACVS.