Anti Antibody Research Articles

Prevalence of SARS-CoV-2 antibodies in cancer patients and healthcare workers vaccinated with two doses of BNT162b2 or AZD122. A propensity analysis.

Vaccination is the most effective intervention for reducing the burden of SARS-CoV-2-related disease; however, gaps in knowledge regarding cancer patients (CPs) immune response persist. To evaluate the humoral response (anti-S antibodies) in CPs and healthcare workers (HCWs) vaccinated with two doses of BNT162b2 or AZD122 vaccines. Polyspecific anti-SARS-CoV-2 spike protein (anti-S) antibodies were quantified, and a 1:1 propensity score was used to balance baseline characteristics. Multiple logistic regressions were carried out to evaluate the effect of humoral response-related variables. One-hundred and twenty-seven CPs (22%) and 439 HCWs (78%) were included. Both populations developed anti-S antibodies in response to vaccination. The mRNA-based vaccine (BNT162b2) was associated with higher odds of having anti-S antibody titers ≥ 1,000 U/mL, while active cancer was related to a lower probability of developing high antibody titers. The BNT162b2 vaccine was associated with a higher humoral response. It is necessary for more information and vaccination strategies to be available for immunosuppressed patients in order to select the best biologics for this population based on individual characteristics.

Generation and characterization of avian IgY antibodies for detecting beta-casein A1 in bovine milk

Beta-casein is a primary milk protein that constitutes approximately 30% of the casein in bovine milk, with the two most common types in cattle being A1 and A2. The A2 protein differs from the A1 version due to a mutation in the codon at position 67, resulting in a histidine to proline substitution. However, the bioactive peptide, beta-casomorphine-7 (BCM7), which originates from partial proteolysis of the A1 variant, has been linked to several gastrointestinal disorders in humans. Production of A1 beta casein-free products is increasing demand in the milk market, worldwide. This study generated and characterized a polyclonal IgY antibody that specifically recognizes the A1 beta-casein protein present in cow's milk. A commercially available IgY anti-A1 antibody was used as a positive control, and the sensitivity and specificity of both the commercial and produced anti-A1 antibodies were evaluated. The results showed 100% sensitivity and specificity of 100% of the commercial IgY anti-A1. The in-house produced anti-A1 antibody demonstrated a sensitivity of 95.2% and a specificity of 100%, indicating its potential as a reliable and cost effective tool for detecting A1 beta-casein protein in milk samples.

Prevalence and correlates of SARS-CoV-2 seropositivity among people who inject drugs in Baltimore, Maryland

BackgroundSARS-CoV-2 serosurveys can help characterize disparities in SARS-CoV-2 infection and identify gaps in population immunity. Data on SARS-CoV-2 seroprevalence among people who inject drugs (PWID) are limited. MethodsWe conducted a cross-sectional study between December 2020 and July 2022 among 561 participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study—a community-based cohort of current and former PWID in Baltimore, Maryland. Serum samples were assayed for infection-induced anti-nucleocapsid (anti-N) and infection and/or vaccination-induced anti-spike-1 (anti-S) SARS-CoV-2 IgG. We estimated adjusted prevalence ratios (aPR) via modified Poisson regression models. ResultsThe median age was 59 years, 35% were female, 84% were non-Hispanic Black, and 16% reported recent injection drug use. Anti-N antibody prevalence was 26% and anti-S antibody prevalence was 63%. Anti-N and anti-S antibody prevalence increased over time. Being employed (aPR=1.53 [95%CI=1.11–2.11]) was associated with higher anti-N prevalence, while a cancer history (aPR=0.40 [95%CI=0.17–0.90]) was associated with lower anti-N prevalence. HIV infection was associated with higher anti-S prevalence (aPR=1.13 [95%CI=1.02–1.27]), while younger age and experiencing homelessness (aPR=0.78 [95%CI=0.60–0.99]) were factors associated with lower anti-S prevalence. Substance use-related behaviors were not significantly associated with anti-N or anti-S prevalence. ConclusionsSARS-CoV-2 seroprevalence increased over time among current and former PWID, suggesting cumulative increases in the incidence of SARS-CoV-2 infection and vaccination; however, there were disparities in infection-induced seroprevalence and infection and/or vaccine-induced seroprevalence within this study sample. Dedicated prevention and vaccination programs are needed to prevent disparities in infection and gaps in population immunity among PWID during emerging epidemics.

Can immunohistochemistry improve the pathological diagnosis of placenta accreta spectrum (PAS) disorders?

The term of placenta accreta spectrum (PAS) disorder includes all grades of abnormal placentation. It is crucial for pathologist provide standardized diagnostic assessment to evaluate the outcome of management strategies. Moreover, a correct and safe diagnosis is useful in the medico-legal field when it becomes difficult for the gynecologist to demonstrate the suitability and legitimacy of demolitive treatment. The purposes of our study were: (1) to assess histopathologic features according to the recent guidelines; (2) to determine if immunohistochemistry can be useful to identify extravillous trophoblast (EVT) and to measure the depth of infiltration into the myometrium to improve the diagnosis of PAS. The retrospective study was conducted on 30 cases of gravid hysterectomy with histopathologic diagnosis of PAS. To identify the depth of EVT, immunohistochemical stainings were performed using anti MNF116 (cytokeratins 5, 6, 8, 17, 19), actin-SM, HPL (Human Placental Lactogen), vimentin and GATA3 antibodies. Our cases were graded based on the degree of invasion of the myometrium. Ten were grade 1 (33.3%), 12 grade 2 (40%) and 8 grade 3A (26.7%). EVT invasion was best seen and evident by double immunostainings with actin-SM and cytokeratins, actin-SM and HPL, actin-SM and GATA3. The role of pathologist is decisive to determine the different grades of PAS. A better understanding of the depth of myometrial invasion can be achieved by the use of immunohistochemistry affording an important tool to obtain reproducible grading of PAS. This purpose is crucial in the setting of postoperative quality reviews and particularly in the forensic medicine field.

Comparative Longitudinal Serological Study of Anti-SARS-CoV-2 Antibody Profiles in People with COVID-19.

Serological diagnostic assays are essential tools for determining an individual's protection against viruses like SARS-CoV-2, tracking the spread of the virus in the community, and evaluating population immunity. To assess the diversity and quality of the anti-SARS-CoV-2 antibody response, we have compared the antibody profiles of people with mild, moderate, and severe COVID-19 using a dot blot assay. The test targeted the four major structural proteins of SARS-CoV-2, namely the nucleocapsid (N), spike (S) protein domains S1 and S2, and receptor-binding domain (RBD). Serum samples were collected from 63 participants at various time points for up to 300 days after disease onset. The dot blot assay revealed patient-specific differences in the anti-SARS-CoV-2 antibody profiles. Out of the 63 participants with confirmed SARS-CoV-2 infections and clinical COVID-19, 35/63 participants exhibited diverse and robust responses against the tested antigens, while 14/63 participants displayed either limited responses to a subset of antigens or no detectable antibody response to any of the antigens. Anti-N-specific antibody levels decreased within 300 days after disease onset, whereas anti-S-specific antibodies persisted. The dynamics of the antibody response did not change during the test period, indicating stable antibody profiles. Among the participants, 28/63 patients with restricted anti-S antibody profiles or undetectable anti-S antibody levels in the dot blot assay also exhibited weak neutralization activity, as measured by a surrogate virus neutralization test (sVNT) and a microneutralization test. These results indicate that in some cases, natural infections do not lead to the production of neutralizing antibodies. Furthermore, the study revealed significant serological variability among patients, regardless of the severity of their COVID-19 illness. These differences need to be carefully considered when evaluating the protective antibody status of individuals who have experienced primary SARS-CoV-2 infections.

Description of a single centre cohort of patients with systemic sclerosis from the University Hospital of Buenos Aires and factors associated with lung function deterioration. A retrospective study

IntroductionGiven the paucity of data in Latin America and especially in Argentina regarding the epidemiology of SSc, the prevalence of ILD, its course, and particularly the response to treatment, our objective was to evaluate a cohort of SSc patients evaluated in a single University Hospital in Buenos Aires. Patients/MethodsWe included 152 patients with SSc, followed from disease onset to last pulmonary function test and with at least two PFT and up to 30 months between each. ResultsSixty-one percent had diffuse SSc (DSSc) and 32% limited SSc (LSSc). The only significant clinical differences between these groups were a higher initial mRodnan score and prevalence of ILD in the DSSc. These also had significantly more anti Scl-70 (Topoisomerase 1) antibodies compared to the LSSC group who had significantly more anti centromere antibodies. The DSSc group also had significantly more extensive damage on HRCT with no differences in terms of imaging patterns.Comparing patients with and without ILD by HRCT, those with ILD had significantly more extensive damage, significantly more anti Scl-70 antibodies, and significantly fewer anti centromere antibodies than those without ILD.Patients whose ILD progressed had a smoking history (OR 4.97) and prior immunosuppressive treatment (OR 15.6) (multivariate analysis). Overall disease duration was significantly shorter in those who progressed. ConclusionsOur SSc population had similar characteristics to those described elsewhere as well as prevalence of ILD and its progression. We found a shorter disease duration, smoking, and prior immunosuppressive treatment to be associated with ILD progression.

Evolution of seroprevalence to SARS-CoV-2 in blood donors in Sarajevo Canton, Federation of Bosnia and Herzegovina: Cross-sectional and longitudinal studies.

Sarajevo Canton in the Federation of Bosnia and Herzegovina has recorded several waves of high SARS-CoV-2 transmission and has struggled to reach adequate vaccination coverage. We describe the evolution of infection- and vaccine-induced SARS-CoV-2 antibody response and persistence. We conducted repeated cross-sectional analyses of blood donors aged 18-65 years in Sarajevo Canton in November-December 2020 and 2021. We analyzed serum samples for anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies. To assess immune durability, we conducted longitudinal analyses of seropositive participants at 6 and 12 months. One thousand fifteen participants were included in Phase 1 (November-December 2020) and 1152 in Phase 2 (November-December 2021). Seroprevalence increased significantly from 19.2% (95% CI: 17.2%-21.4%) in Phase 1 to 91.6% (95% CI: 89.8%-93.1%) in Phase 2. Anti-S IgG titers were significantly higher among vaccinated (58.5%) than unvaccinated infected participants across vaccine products (p < 0.001), though highest among those who received an mRNA vaccine. At 6months, 78/82 (95.1%) participants maintained anti-spike seropositivity; at 12 months, 58/58 (100.0%) participants were seropositive, and 33 (56.9%) had completed the primary vaccine series within 6months. Among 11 unvaccinated participants who were not re-infected at 12 months, anti-S IgG declined from median 770.1 (IQR 615.0-1321.7) to 290.8 (IQR 175.7-400.3). Anti-N IgG antibodies waned earlier, from 35.4% seropositive at 6months to 24.1% at 12 months. SARS-CoV-2 seroprevalence increased significantly over 12 months from end of 2020 to end of 2021. Although individuals with previous infection may have residual protection, COVID-19 vaccination is vital to strengthening population immunity.

The exclusion of anti-D alloantibody in a suspected anti-G antibody in a pregnant 28-year-old Odiya Indian woman.

The Rh-D negative pregnancy is commonly associated with alloimmunization against D-antigen. It can be prevented by anti-D prophylaxis in pregnant patients with negative results on antibody screening. Hence, it is essential to exclude alloantibody-D in the presence of multiple alloantibodies. Anti-G antibody is formed after exposure to G antigen in neonate RBCs. Blood-group discrepancy was noted in reverse grouping, and antibody-screening results were positive in our case individual, a 28-year old Odiya Indian woman. We performed antibody identification on serum specimens from this patient, which revealed the pattern of anti-D + anti-C antibody specificity. Blood-group discrepancy was solved using rr (ce/ce)-phenotype pooled cells for reverse grouping. We identified anti-G antibodies by themselves without anti-D and anti-C after performing sequential adsorption of serum with r'r' (Ce/Ce) and R2R2 (DcE/DcE) group-O RBCs in the mother, who had rr phenotype and primigravida designation. After completing antibody screening at the first antenatal check-up, we recommended prophylactic anti-D for the mother in any future pregnancies she may have.

SARS-CoV-2 seroprevalence and vaccine coverage from August to November 2021: A nationally representative survey in Mexico.

We aimed to estimate self-reported vaccine coverage and SARS-CoV-2 anti-N and anti-S seroprevalence in Mexico overall and for five vaccine types. We used a nationally representative survey with 7236 dried blood spot samples for adults 18 years and older collected from August to November 2021. Anti-N and anti-S seroprevalence were estimated adjusting for the sensitivity and specificity of the immunoassay test. A multivariate Poisson regression model was used to estimate seroprevalence by vaccine type and by age group adjusting for confounders and test performance. Vaccination coverage was 74%, being higher in women compared to men, high socioeconomic status (SES) compared to low and middle SES, graduates compared to people with high school, and formal workers compared to other employment statuses. Anti-N seroprevalence was 59.2%, compared to 84.1% anti-S seroprevalence. Anti-S seroprevalence was higher for vaccinated than unvaccinated participants. All vaccines were associated with more than 70% anti-S seroprevalence, with the lowest being observed for CoronaVac and Ad5-nCoV. Fully vaccinated participants over 60 years presented a lower seroprevalence (77.6%) compared to younger adults (91.1%), with larger differences for ChAdOx1 and CoronaVac vaccines. Between August and November 2021, three out of four Mexican adults had been vaccinated. Vaccination was associated with a higher positivity to anti-S antibodies. While antibodies do not reflect immunity, our results suggest that booster doses should be offered to people over 60 years of age and to adults who received Ad5-nCoV or CoronaVac as primary vaccination schemes.

Potent cross-neutralization of respiratory syncytial virus and human metapneumovirus through a structurally conserved antibody recognition mode

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F)proteins, we isolated a panel of anti-F antibodies from a human donor. One antibody (RSV-199) potently cross-neutralized 8 RSV and hMPV strains by recognizing antigenic site III, which is partially conserved in RSV and hMPV F. Next, we determined the cryoelectron microscopy (cryo-EM) structures of RSV-199 bound to RSV F trimers, hMPV F monomers, and an unexpected dimeric form of hMPV F. These structures revealed how RSV-199 engages both RSV and hMPV F proteins through conserved interactions of the antibody heavy-chain variable region and how variability within heavy-chain complementarity-determining region 3 (HCDR3) can be accommodated at the F protein interface in site-III-directed antibodies. Furthermore, RSV-199 offered enhanced protection against RSV A and B strains and hMPV in cotton rats. These findings highlight the mechanisms of broad neutralization and therapeutic potential of RSV-199.

SARS-CoV-2 m-RNA Vaccine Response in Immunocompromised Patients: A Monocentric Study Comparing Cancer, People Living with HIV, Hematopoietic Stem Cell Transplant Patients and Lung Transplant Recipients.

Immunocompromised patients (ICPs) have a higher risk of developing severe forms of COVID-19 and experience a higher burden of complications and mortality than the general population. However, recent studies have suggested that the antibody response to SARS-CoV-2 mRNA vaccines could be highly variable among different ICPs. Using a collaborative, monocentric, prospective cohort study, we assessed anti-SARS-CoV-2 spike protein antibody titers following two and three doses of mRNA vaccines in four groups of ICPs (cancer [n = 232]: hematopoietic stem cell transplant [HSCT; n = 126] patients; people living with HIV [PLWH; n = 131]; and lung transplant [LT; n = 39] recipients) treated at Geneva University Hospitals; and healthy individuals (n = 49). After primo-vaccination, the highest anti-S antibody geometric mean titer (IU/mL) was observed in healthy individuals (2417 IU/mL [95% CI: 2327-2500]), the PLWH group (2024 IU/mL [95% CI:1854-2209]) and patients with cancer (840 IU/mL [95% CI: 625-1129]), whereas patients in the HSCT and LT groups had weaker antibody responses (198 IU/mL [95% CI: 108-361] and 7.3 IU/mL [95% CI: 2.5-22]). The booster dose conferred a high antibody response after 1 month in both PLWH (2500 IU/mL) and cancer patients (2386 IU/mL [95% CI: 2182-2500]), a moderate response in HSCT patients (521 IU/mL [95% CI: 306-885]) and a poor response in LT recipients (84 IU/mL [95% CI: 18-389]). Contemporary treatment with immunosuppressive drugs used in transplantation or chemotherapy was associated with a poor response to vaccination. Our findings confirmed the heterogeneity of the humoral response after mRNA vaccines among different ICPs and the need for personalized recommendations for each of these different groups.

Association between SARS-CoV-2 Symptoms, Ct Values, and Serological Response in Vaccinated and Unvaccinated Healthcare Personnel.

SARS-CoV-2 vaccines are effective at reducing symptomatic and asymptomatic COVID-19. Limited studies have compared symptoms, threshold cycle (Ct) values from reverse transcription (RT)-PCR testing, and serological testing results between previously vaccinated vs unvaccinated populations with SARS-CoV-2 infection. Healthcare personnel (HCP) with a positive SARS-CoV-2 RT-PCR test within the previous 14 to 28 days completed surveys including questions about demographics, medical conditions, social factors, and symptoms of COVID-19. Ct values were observed, and serological testing was performed for anti-nucleocapsid (anti-N) and anti-Spike (anti-S) antibodies at enrollment and 40 to 90 days later. Serological results were compared to HCP with no known SARS-CoV-2 infection and negative anti-N testing. There were 104 unvaccinated/not fully vaccinated and 77 vaccinated HCP with 2 doses of an mRNA vaccine at time of infection. No differences in type or duration of symptoms were reported (P = 0.45). The median (interquartile range [IQR]) Ct was 21.4 (17.6-24.6) and 21.5 (18.1-24.6) for the unvaccinated and vaccinated HCP, respectively. Higher anti-N IgG was observed in unvaccinated HCP (5.08 S/CO, 3.08-6.92) than vaccinated (3.61 signal to cutoff ratio [S/CO], 2.16-5.05). Anti-S IgG was highest among vaccinated HCP with infection (34 285 aribitrary units [AU]/mL, 17 672-61 775), followed by vaccinated HCP with no prior infection (1452 AU/mL, 791-2943), then unvaccinated HCP with infection (829 AU/mL, 290-1555). Anti-S IgG decreased 1.56% (0.9%-1.79%) per day in unvaccinated and 0.38% (0.03%-0.94%) in vaccinated HCP. Vaccinated HCP infected with SARS-CoV-2 reported comparable symptoms and had similar Ct values relative to unvaccinated. However, vaccinated HCP had increased and prolonged anti-S and decreased anti-N response relative to unvaccinated.

Breakthrough COVID-19 infections - Analyzing our experience.

There are many cases of post-vaccination COVID-19 globally. Also, literature on serum antibodies after vaccination is abundant. Our research focuses on breakthrough infections reported at our institution during the third wave of COVID-19. A total of 177 people recruited at the Indus Hospital Karachi between May to September 2021 with COVID-19 infection were divided into vaccinated, partially vaccinated, and unvaccinated cohorts. Furthermore, a subset of the vaccinated cohort was tested for anti-NP and anti-S antibodies. There were 119 patients with breakthrough infection, however, 74% had mild symptoms. The antibodies against NP and S were found at a higher level in those who had a breakthrough infection in comparison to healthy vaccinated controls. Vaccination does not prevent disease but does confer some immunity causing less severe infection.

Ultrastructural skin alterations of healthy subjects with anti-desmoglein 1 antibodies in endemic areas to pemphigus foliaceus: A case series

BackgroundEndemic pemphigus foliaceus and endemic pemphigus vulgaris are autoimmune dermatologic disorders endemic to the Peruvian Amazon. ObjectiveTo determine the ultrastructural skin alterations of three healthy subjects with anti DSG-1 antibodies in areas endemic to pemphigus foliaceus and pemphigus vulgaris in the Peruvian Amazon. Patients and methodsCase series carried out from data of three clinically healthy subjects positive to anti DSG-1 antibodies, from Peru. This study consists of a sub-analysis of data gathered in a previous study. ResultsUltrastructural results are presented from the skin biopsies of three clinically healthy patients positive to anti-desmoglein 1 (DSG-1) antibodies. High Resolution Optical Microscopy (HROM) showed the absence of acantholysis. Transmission Electron Microscopy (TEM) showed the widening of intercellular space between keratinocytes, the presence of vacuoles in intercellular space with granular material and cytoplasmic vacuolization, loss of desmosome structure, loss of normal distribution among tonofilaments and lateral separation among cells in the stratum basale. ConclusionAccording to our results, healthy subjects that present anti-desmoglein 1 antibodies can develop ultrastructural alterations that are visible through transmission electron microscopy but not through conventional optical microscopy.

Association Between Microsatellite Instability (MSI) based on MLH1 and PMS2 Marker with Clinicopathological Features of Colorectal Cancer Patients

Background: Microsatellite instability (MSI) is one of the important pathways involved in development of colorectal cancer (CRC). MSI occurs due to mutations or hypermethylation of negative MMR proteins MLH1 and PMS2. The accumulation of mutations at microsatellite locus accelerated the development of CRC. Characteristics of CRC patients with MSI are not sensitive to 5FU chemotherapy and have a good clinical outcomes that can be used as a prognostic factor and a predictor of therapy. Therefore MSI detection is needed. Method: A retrospective cross-sectional study of 80 CRC slides obtained from DR. Sardjito Hospital Yogyakarta and clinical laboratory in 2010-2016. Immunohistochemical staining with anti-MLH1 and anti PMS2 antibodies to see MSI status. Negative MLH1 expression is called MSI MLH1 positive and PMS2 negative expression is called positive MSI PMS2. The association between MSI MLH1 and PMS2 with clinicopathology parameters was analyzed using Chi square. Results: Colorectal cancer patients MSI MLH1 as much as 44 (61.1%), MSI PMS2 as much as 21 (29.2%) and, MSI MLH1 and PMS2 simultaneously as much as 18 (25.0%). MSI MLH1 and PMS2 positive are found in ≥50 years old. The number of male patients is more than women. Most of the patients had a T3-T4 tumor size with advanced stage and well differentiated. MSI MLH1 associated with tumor differentiation (p = 0.011). Conclusion: MSI MLH1 is associated with tumor differentiation (p = 0.011), but, no association with the other clinicopathology parameters. MSI PMS2 is not associated to the overall clinicopathology parameters. MSI MLH1 and PMS2 are not simultaneously associated with all clinicopathology parameters (p&gt; 0.05)

Low cross reactivity between wild type and deamidated AAV can lead to false negative results in immune monitoring T-cell assays.

During gene therapy trials, immune responses against adeno-associated virus (AAV) vectors are monitored by antibody assays that detect the humoral and T-cell mediated cellular responses to AAV vectors. T cell assays commonly utilize the collection of patients' peripheral blood mononuclear cells (PBMCs) and stimulation with AAV-derived overlapping peptides. We recently described that spontaneous deamidation coincides with T cell epitopes in AAV capsids and that spontaneous deamidation may enhance or decrease immunogenicity in some individuals. This raised the concern for false negative results of antibody detection and PBMC immune monitoring assays because these assays use wild-type (WT) AAV or WT peptides for T cell re-stimulation and these peptides may not re-activate T cells that were stimulated with deamidated AAV capsid. To investigate this concern, we modeled the scenario by expanding T cells with deamidated peptides and evaluated the cross-reactivity of expanded T cells to WT peptides. In the majority of samples, cells that were expanded with deamidated peptides and restimulated with WT peptide had significantly lowered IL-2 and IFN-γ production. Spiking the four deamidated peptides to the WT peptide pool used for re-stimulation, restored the signal and corrected the performance of the assay. We also evaluated the impact of deamidation on anti AAV binding antibodies and did not observe a major impact on seroprevalence detection of AAV9. These data indicate that a high level ofdeamidation in AAV therapy may result in underestimation or even failure todetect immune responses against WT peptides during cellular immune monitoring.

SARS-CoV-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays.

The authors extracted the whole-brain neurons from the newborn P1 mice and plated them on multiwell MEAs and administered purified recombinant spike proteins (both S1 and S2 subunits) from the SARS-CoV-2 virus. The signals from the MEAs were transmitted from an amplifier to a high-performance computer for recording and analysis using an in-house developed algorithm to quantify neuronal phenotypes. Primary among the phenotypic features analyzed, we discovered that neuronal treatment with spike 1 protein (S1) protein from SARS-CoV-2 decreased the mean burst numbers observed on each electrode, an effect that could be rescued with an anti-S1 antibody. Conversely, this mean burst number decrease was not observed with spike 2 protein (S2) treatment. Finally, our data strongly suggest that the receptor binding domain of S1 is responsible for the reduction in neuronal burst activity. Overall, our results strongly indicate that spike proteins may play an important role in altering neuronal phenotypes, specifically the burst patterns, when neurons are exposed during early development.

Hemolytic Disease of Newborn Following Anti-C and Anti-S Alloimmunization

Background: Non-Rhesus D antigen non-ABO, minor blood group alloimmunization in pregnant women is being increasingly recognized as a significant contributor to the development of the hemolytic disease of the fetus and newborn (HDFN). We report severe HDFN in a neonate born to an Rh-positive mother with sickle cell disease, following anti-C and anti-S alloimmunization. Clinical Description: A male baby born to a repeatedly transfused mother with sickle cell disease developed severe jaundice at 22 h of life. The baby was found to have severe anemia and indirect hyperbilirubinemia, but no encephalopathy, hepatosplenomegaly, or features of sepsis. Management and Outcome: His blood group was O positive and the direct Coombs test was 4+. Minor blood group typing showed the presence of anti-C and anti-S antibodies. The baby improved after receiving a double-volume exchange transfusion with matched blood and phototherapy. Conclusion: Severe hemolytic disease of the newborn (HDN) may be caused by minor blood group alloimmunization, especially seen in mothers with a history of multiple transfusions. Antenatal screening for alloimmunization in high-risk mothers can ensure timely diagnosis and treatment of HDN and prevent the harmful effects of neonatal hyperbilirubinemia.

Spectrum of Hemolytic Transfusion Reactions from Tertiary Cancer Center Over a 1-year Period

Background and Objectives: Acute hemolytic transfusion reactions (HTRs) one of the serious adverse events manifesting within 24 h of blood transfusion. To review the adverse transfusion reactions in our cancer center over a 1-year period, especially HTR and its causation to find the ways of mitigating the same. Methods: This was a retrospective analysis of HTR in tertiary care cancer center from South India. Patients who developed HTR in 2022 were included for discussion. Results: A total of six HTRs observed in five patients during 1 year. Case 1 was an acute presentation of HTR due to Anti Jka antibody. Case 2 was a nonimmune HTR associated with leukodepleted irradiated packed red blood cells transfusion. Case 3 was an incidental finding of passive hemolysis due to ABO incompatible platelet transfusion in patient clinically manifesting febrile and transfusion-associated dyspnea. Case 4 presented as an HTR with inconclusive evidence suggestive of HTR, with an impression of hemolysis as a part of the underlying disease. Conclusion: While the incidence of HTR due to ABO-incompatible transfusion reactions has been minimized, the other potential causes for acute HTR are still a concern. An effective hemovigiliance and strict adherence to standards in blood component practice may help to mitigate any form of transfusion reaction.

SARS-CoV-2 spike host cell surface exposure promoted by a COPI sorting inhibitor.

Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.