The antigenic anatomy of SARS-CoV-2 receptor binding domain.

Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 µg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.

The presence of broadly neutralizing anti-SARS-CoV-2 RBD antibodies elicited by primary series and booster dose of COVID-19 vaccine.

Antibody-mediated immunity plays a key role in protection against SARS-CoV-2. We characterized B-cell-derived anti-SARS-CoV-2 RBD antibody repertoires from vaccinated and infected individuals and elucidate the mechanism of action of broadly neutralizing antibodies and dissect antibodies at the epitope level. The breadth and clonality of anti-RBD B cell response varies among individuals. The majority of neutralizing antibody clones lose or exhibit reduced activities against Beta, Delta, and Omicron variants. Nevertheless, a portion of anti-RBD antibody clones that develops after a primary series or booster dose of COVID-19 vaccination exhibit broad neutralization against emerging Omicron BA.2, BA.4, BA.5, BQ.1.1, XBB.1.5 and XBB.1.16 variants. These broadly neutralizing antibodies share genetic features including a conserved usage of the IGHV3-53 and 3-9 genes and recognize three clustered epitopes of the RBD, including epitopes that partially overlap the classically defined set identified early in the pandemic. The Fab-RBD crystal and Fab-Spike complex structures corroborate the epitope grouping of antibodies and reveal the detailed binding mode of broadly neutralizing antibodies. Structure-guided mutagenesis improves binding and neutralization potency of antibody with Omicron variants via a single amino-substitution. Together, these results provide an immunological basis for partial protection against severe COVID-19 by the ancestral strain-based vaccine and indicate guidance for next generation monoclonal antibody development and vaccine design.

Multicenter registry of multisystem inflammatory syndrome in children (MIS-C) and Paired comparison with Kawasaki disease.

OBJECTIVES: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C. METHODS: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset. RESULTS: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors. CONCLUSIONS: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD.

Correction: Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.

[This corrects the article DOI: 10.1371/journal.ppat.1009352.].

Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.

Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 3.5% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-receptor-binding domain (RBD), three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two recovered patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. Finally, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.

Emergence of genotype C1 Enterovirus A71 and its link with antigenic variation of virus in Taiwan.

An outbreak of the hand-foot-mouth disease with severe neurological cases, mainly caused by the genotype C1 enterovirus A71 (EV-A71), occurred in Taiwan between 2018 and early 2019. In the recent decade, the most dominant EV-A71 genotypes in Taiwan were B5 and C4 but changed to C1 in 2018. Antibody-mediated immunity plays a key role in limiting the EV-A71 illness in humans. However, the level of neutralizing activities against genotype C1 virus by human polyclonal and monoclonal antibodies (MAbs) remains largely unclear. In the study, we demonstrated that that 39% (9 in 23) of post-infection sera from the genotype B5- or C4-infected patients in 2014-2017 exhibit reduced titers with the 2018-2019 genotype C1 viruses than with the earlier B5 and C4 viruses tested. This finding with polyclonal sera is confirmed with human MAbs derived from genotype B5 virus-infected individuals. The 2018-2019 genotype C1 virus is resistant to the majority of canyon-targeting human MAbs, which may be associated with the residue change near or at the bottom of the canyon region on the viral capsid. The remaining three antibodies (16-2-11B, 16-3-4D, and 17-1-12A), which target VP1 S241 on the 5-fold vertex, VP3 E81 on the 3-fold plateau and VP2 D84 on the 2-fold plateau of genotype C1 viral capsid, respectively, retained neutralizing activities with variable potencies. These neutralizing antibodies were also found to be protective against a lethal challenge of the 2018-2019 genotype C1 virus in an hSCARB2-transgenic mice model. These results indicate that the EV-A71-specific antibody response may consist of a fraction of poorly neutralizing antibodies against 2018-2019 genotype C1 viruses among a subset of previously infected individuals. Epitope mapping of protective antibodies that recognize the emerging genotype C1 virus has implications for anti-EV-A71 MAbs and the vaccine field.

Antibiotic choice for the management of preterm premature rupture of membranes in Taiwanese women.

BACKGROUND: Preterm premature rupture of membranes (PPROM) is one of the most common causes of preterm birth. Antibiotic treatment is recommended to prolong the pregnancy course and reduce fetal morbidity in women with PPROM. However, the guidelines for antibiotic selection are based on studies done years ago, mostly in Western countries, which may not reflect the geographic, temporal, and ethnic variation in microbial colonization and infection in other parts of the world. We aimed to understand whether the antibiotics recommended by the current guidelines were sufficient to eradicate the majority of pathogens involved. METHODS: This is a single-center retrospective study at a tertiary medical center in Taiwan with patients recruited from January 1, 2017, to December 31, 2019. All patient included had a confirmed diagnosis of PPROM. In this study, we aimed to investigate which broad-spectrum antibiotic was most suitable for PPROM cases in Taiwan. RESULTS: 133 women were included, and 121 women had positive culture results. Most of the pregnant women had one positive result (35.5%). The most common pathogen was Lactobacillus species (27.8%), followed by Streptococcus species (12.9%) and Staphylococcus species (12.09%). CONCLUSION: The most appropriate antibiotic therapy for PPROM was a combination of 1 g azithromycin given orally on admission plus a third-generation cephalosporin administered intravenously in the first 48 hours and followed by amoxicillin 500 mg per os for another five days. This recommended antibiotic regimen for women with PPROM needs further study under a randomized clinical trial with a larger study population to evaluate its efficacy.

Broadly Inhibiting Antineuraminidase Monoclonal Antibodies Induced by Trivalent Influenza Vaccine and H7N9 Infection in Humans.

The majority of antibodies induced by influenza neuraminidase (NA), like those against hemagglutinin (HA), are relatively specific to viruses isolated within a limited time window, as seen in serological studies and the analysis of many murine monoclonal antibodies (MAbs). We report three broadly reactive human MAbs targeting N1 NA. Two were isolated from a young adult vaccinated with trivalent influenza vaccine (TIV), which inhibited N1 NA from viruses isolated from humans over a period of a hundred years. The third antibody, isolated from a child with acute mild H7N9 infection, inhibited both group 1 N1 and group 2 N9 NAs. In addition, the antibodies cross-inhibited the N1 NAs of highly pathogenic avian H5N1 influenza viruses. These antibodies are protective in prophylaxis against seasonal H1N1 viruses in mice. This study demonstrates that human antibodies to N1 NA with exceptional cross-reactivity can be recalled by vaccination and highlights the importance of standardizing the NA antigen in seasonal vaccines to offer optimal protection.IMPORTANCE Antibodies to the influenza virus NA can provide protection against influenza disease. Analysis of human antibodies to NA lags behind that of antibodies to HA. We show that human monoclonal antibodies against NA induced by vaccination and infection can be very broadly reactive, with the ability to inhibit a wide spectrum of N1 NAs on viruses isolated between 1918 and 2018. This suggests that antibodies to NA may be a useful therapy and that the efficacy of influenza vaccines could be enhanced by ensuring the appropriate content of NA antigen.

Room-temperature two-dimensional plasmonic crystal semiconductor lasers.

Room-temperature plasmonic-crystal lasers have been demonstrated with a square-lattice gold nano-pillar arrays on top of InGaAs/GaAs quamtum wells on a GaAs substrate. The lasing wavelength is tunable in the range of 865-1001 nm by varying the lattice period. The lasers exhibit an extremely narrow linewidth and small divergence angle so could have great potential for various applications. An unexpected mirror cavity effect has been observed and investigated. The mirror-cavity lasers have a very low threshold and could be developed to realize electrically-driven plasmonic lasers.

The "rail sign": an ultrasound finding in placenta accreta spectrum indicating deep villous invasion and adverse outcomes.

BACKGROUND: Ultrasound has demonstrated a high accuracy in the prenatal diagnosis of placenta accreta spectrum. However, it is not known whether ultrasound findings can pinpoint the depths of villous invasion, recommend surgical strategies, and predict clinical outcomes. OBJECTIVE: We described an ultrasound descriptor for the placenta accreta spectrum and investigated whether it can predict the severity of villous invasion and clinical outcomes. STUDY DESIGN: The patients with placenta accreta spectrum in this retrospective cross-sectional study were diagnosed and managed in our hospital from 2002 to 2017. The placenta, with overlying myometrium and bladder, was mapped with color Doppler sonography while the patient's bladder was full. A "rail sign" was defined as 2 parallel neovascularizations depicted by color Doppler sonography over the uterovesical junction and bladder mucosa, with interconnecting bridging vessels perpendicular to both. The patients received serial ultrasound examinations and surgery at our hospital. An unpaired t test and Pearson chi-square test compared the pathology subtypes, surgical strategies, and clinical outcomes in patients with or without a rail sign. RESULTS: We enrolled 133 consecutive cases of placenta accreta spectrum confirmed either by surgical inspection or pathology examination. Patients with a rail sign had a significantly higher risk of an abnormally invasive placenta (placenta increta or placenta percreta) than those patients without a rail sign (83.3% [60 of 72] vs 27.9% [17 of 61]; odds ratio, 12.94; P<.001). In addition, patients with a rail sign had a higher probability of perioperative approaches, including preoperative vascular control (58.3% [42 of 72] vs 21.3% [13 of 61]; odds ratio, 5.17; P<.001) and uterine artery embolization (34.7% [25 of 72] vs 11.5% [7 of 61]; odds ratio, 4.1; P=.0002]. Furthermore, patients with a rail sign carried a higher risk of adverse clinical outcomes than patients without a rail sign, such as blood transfusion (80.6% [58 of 72] vs 36.1% [22 of 61]; odds ratio, 7.34; P<.001], admission to the intensive care unit (33.3% [24 of 72] vs 16.4% [10 of 61]; odds ratio, 2.55; P=.026), hysterectomy (75% [54 of 72] vs 24.6% [15 of 61]; odds ratio, 9.2; P<.001), and bladder invasion (16.7% [12 of 72] vs 4.9% [3 of 61]; odds ratio, 3.86; P=.033). Notably, the negative predictive value of bladder invasion was 95.1%, indicating a high confidence to reject bladder invasion while the rail sign was negative. When the rail sign was used as a screening test, the positive likelihood ratio of predicting deep villous invasion was 3.64 and correlated with an increased probability of 20% to 25%. Patients with a rail sign also had a greater blood loss (2944±2748 mL vs 1530±1895 mL; P<.001) and a longer hospital stay (11.9±10.9 days vs 8.6±7.1 days; P=.036) than patients without a rail sign. CONCLUSION: A "rail sign" depicted by color Doppler sonography correlates with deeper villous invasion, additional perioperative approaches, and more adverse outcomes.

Efficient FPGA Implementation of a Dual-Frequency GNSS Receiver with Robust Inter-Frequency Aiding.

Multiple frequency global navigation satellite system (GNSS) has become more complex due to the existence of extra channels. Typically, auxiliary methods are used to synchronize the second signals at other bands by aiding the acquired channel parameters. However, there are critical limitations because the reception of GNSS signals is subject to uncertainties due to noise carrier injection or circuit interference. The relationship between the two Doppler frequencies can be affected by uncertainties. Therefore, we aimed to implement an efficient dual-frequency field-programmable gate array (FPGA), performing a direct aid tracking method for the secondary channel to achieve resource efficiency and inner aid robustness. A robust estimator that directly links two loops in the two bands is proposed. In this scheme, (1) a robust estimator able to cope with uncertainty; (2) a primary tracking scheme to obtain the error boundary, and (3) a tracked bit-boundary for the initial code phase of the second channel are used. Based on experiments on the FPGA, the robust channel link can achieve direct aid tracking, and 31.02% of the original hardware resources from the aided acquisition module were released satisfactorily.

A single cycle influenza virus coated in H7 haemagglutinin generates neutralizing antibody responses to haemagglutinin and neuraminidase glycoproteins and protection from heterotypic challenge.

A non-replicating form of pseudotyped influenza virus, inactivated by suppression of the haemagglutinin signal sequence (S-FLU), can act as a broadly protective vaccine. S-FLU can infect for a single round only, and induces heterotypic protection predominantly through activation of cross-reactive T cells in the lung. Unlike the licensed live attenuated virus, it cannot reassort a pandemic haemagglutinin (HA) into seasonal influenza. Here we present data on four new forms of S-FLU coated with H7 HAs from either A/Anhui/1/2013, A/Shanghai/1/2013, A/Netherlands/219/2003 or A/New York/107/2003 strains of H7 virus. We show that intranasal vaccination induced a strong local CD8 T cell response and protected against heterosubtypic X31 (H3N2) virus and highly virulent PR8 (H1N1), but not influenza B virus. Intranasal vaccination also induced a strong neutralizing antibody response to the encoded neuraminidase. If given at higher dose in the periphery with intraperitoneal administration, H7 S-FLU induced a specific neutralizing antibody response to H7 HA coating the particle. Polyvalent intraperitoneal vaccination with mixed H7 S-FLU induced a broadly neutralizing antibody response to all four H7 strains. S-FLU is a versatile vaccine candidate that could be rapidly mobilized ahead of a new pandemic threat.

Mother-to-child transmission of HIV: An 11-year experience in a single center and HIV prevention effectiveness in Taiwan.

BACKGROUND: Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) has become an essential global health issue and its elimination is a crucial target. A prenatal "opt-out" HIV screening program was initiated in 2005 in Taiwan. In recent 3 years, approximate screening and MTCT rates were 99% and 2.27% (1/44), respectively. Here, we describe the clinical management of mothers infected with HIV and MTCT rate at National Taiwan University Hospital (NTUH), Taipei, Taiwan, in the years after the program was initiated. METHODS: We retrospectively reviewed charts of pregnant women infected with HIV, who were managed at NTUH between January 2005 and December 2016. HIV infection status of 39 infants born to mothers infected with HIV was available. RESULTS: Between 2005 and December 2016, 50 pregnant women infected with HIV, with 57 parities were managed at NTUH, and 57 live infants were born. We excluded 18 parities because of missing data. Maternal antiviral treatment was administered in 37 of 39 infants. Only one infant tested positive for an HIV antibody test at 18 months, but showed definitive HIV exclusion at 20 months after a series of tests without administration of antiviral treatment. MTCT rate was 0%. CONCLUSION: Successful implementation of available perinatal HIV intervention dramatically reduced vertical transmission rate of HIV. MTCT rate was 0% in NTUH after the program. However, as NTUH is an HIV referral center, additional efforts are needed to achieve the World Health Organization criteria of lowering the vertical transmission rate of HIV to <2% in Taiwan.

Complication rates after chorionic villus sampling and midtrimester amniocentesis: A 7-year national registry study.

PURPOSE: To assess the complication rates following chorionic villus sampling (CVS) and midtrimester amniocentesis in Taiwan. METHODS: This is a national registry-based cohort study from Taiwan. We included all women with singleton pregnancies who received either CVS (n = 1409) or midtrimester amniocentesis (n = 250,566) during 2006-2012. We assessed preterm premature rupture of membranes (PPROM), intrauterine fetal demise (IUFD), infection and spontaneous abortion (SA) that occurred within fourteen days after the procedures. We also assessed the risks of preterm delivery and miscarriage before 24 gestational weeks after amniocentesis. These complications were collected from the Genetic Disease Database of the Ministry of Health and Welfare, Taiwan National Birth Certificate Registry, and the Taiwan National Health Insurance Database. Pearson χ2 tests were used to compare the distributions between groups. RESULTS: For patients who underwent midtrimester amniocentesis, the rates of PPROM, IUFD, infection and SA within fourteen days were 0.24%, 0.11%, 0.05%, and 0.05%, respectively. Women with a normal fetal karyotype had a preterm birth rate (<37 gestational weeks) of 9.38%. The miscarriage rate (<24 gestational weeks) was 0.68%, which was 0.22% higher than those who did not receive the invasive procedures (p < 0.0001). After CVS, the IUFD rate was 1.68%, and the SA rate within fourteen days was 0.77%. CONCLUSION: The use of our large cohort demonstrated that the procedure-related complication rates were comparable to recent review or meta-analysis. This dataset might facilitate counselling in women who consider invasive genetic diagnostic procedures.

Transcriptomic analysis of rice aleurone cells identified a novel abscisic acid response element.

Seeds serve as a great model to study plant responses to drought stress, which is largely mediated by abscisic acid (ABA). The ABA responsive element (ABRE) is a key cis-regulatory element in ABA signalling. However, its consensus sequence (ACGTG(G/T)C) is present in the promoters of only about 40% of ABA-induced genes in rice aleurone cells, suggesting other ABREs may exist. To identify novel ABREs, RNA sequencing was performed on aleurone cells of rice seeds treated with 20 µM ABA. Gibbs sampling was used to identify enriched elements, and particle bombardment-mediated transient expression studies were performed to verify the function. Gene ontology analysis was performed to predict the roles of genes containing the novel ABREs. This study revealed 2443 ABA-inducible genes and a novel ABRE, designated as ABREN, which was experimentally verified to mediate ABA signalling in rice aleurone cells. Many of the ABREN-containing genes are predicted to be involved in stress responses and transcription. Analysis of other species suggests that the ABREN may be monocot specific. This study also revealed interesting expression patterns of genes involved in ABA metabolism and signalling. Collectively, this study advanced our understanding of diverse cis-regulatory sequences and the transcriptomes underlying ABA responses in rice aleurone cells.

Extracorporeal membrane oxygenation application in post-partum hemorrhage patients: Is post-partum hemorrhage contraindicated?

Extracorporeal membrane oxygenation (ECMO) is commonly used in patients who experience circulatory arrest or significant cardiac dysfunction and is associated with improved clinical outcomes. We conducted a retrospective observational study on ECMO application at a single tertiary center over a five-year period. Five patients who suffered post-partum hemorrhage resulting from uterine atony were treated with ECMO. The mean age was 36.8 ± 3.9 years; the mean gestational age was 37.8 ± 2.2 weeks; the initial mean maternal hemoglobin level was 5.0 ± 2.4 mg/dL; and the mean estimated blood loss was 3260 ± 1545 mL before treatment. All patients were treated with venoarterial ECMO and one was treated with both venoarterial and venovenous ECMO. The mean ECMO usage duration was 32.6 ± 18.8 h (range 10-54). Four (80%) patients survived until discharge without experiencing neurological sequela. ECMO should not be a contraindication for treatment of post-partum hemorrhage and such patients should be weaned as soon as possible to ensure the early recovery of cardiac function.

A Potent Virus-Specific Antibody-Secreting Cell Response to Acute Enterovirus 71 Infection in Children.

BACKGROUND: Enterovirus 71 (EV71) remains a leading pathogen for acute infectious diseases in children, especially in Asia. The cellular basis for establishing a virus-specific antibody response to acute EV71 infections is unclear in children. METHODS: We studied the magnitude of virus-specific antibody-secreting B cells (ASCs) and its relationship with serological response, clinical parameters, and virological parameters among children with laboratory-confirmed EV71 infection. RESULTS: A potent EV71 genogroup B- and virus-specific ASC response was detected in the first week of illness among genotype B5 EV71-infected children. The cross-reactive EV71-specific ASC response to genogroup C viral antigens composed about 10% of the response. The EV71-specific ASC response in children aged ≥3 years produced immunoglobulin G predominantly, but immunoglobulin M was predominant in younger children. Proliferation marker was expressed by the majority of circulating ASCs in the acute phase of EV71 infection. Virus-specific ASC responses significantly correlated with throat viral load, fever duration, and serological genogroup-specific neutralization titer. CONCLUSIONS: The presence of a virus-specific ASC response serves an early cellular marker of an EV71-specific antibody response. Further detailed study of EV71-specific ASCs at the monoclonal level is crucial to delineate the specificity and function of antibody immunity in children.

Virus-specific antibody secreting cell, memory B-cell, and sero-antibody responses in the human influenza challenge model.

BACKGROUND: Antibodies play a major role in the protection against influenza virus in human. However, the antibody level is usually short-lived and the cellular mechanisms underlying influenza virus-specific antibody response to acute infection remain unclear. METHODS: We studied the kinetics and magnitude of influenza virus-specific B-cell and serum antibody responses in relation to virus replication during the course of influenza infection in healthy adult volunteers who were previously seronegative and experimentally infected with seasonal influenza H1N1 A/Brisbane/59/07 virus. RESULTS: Our data demonstrated a robust expansion of the virus-specific antibody-secreting cells (ASCs) and memory B cells in the peripheral blood, which correlated with both the throat viral load and the duration of viral shedding. The ASC response was obviously detected on day 7 post-infection when the virus was completely cleared from nasal samples, and serum hemagglutination-inhibition antibodies were still undetectable. On day 28 postinfection, influenza virus-specific B cells were further identified from the circulating compartment of isotype-switched B cells. CONCLUSIONS: Virus-specific ASCs could be the earliest marker of B-cell response to a new flu virus infection, such as H7N9 in humans.

Reflecting on the 1998 enterovirus outbreak: A 25-year retrospective and learned lessons.

Enterovirus A71 (EV-A71) infections pose a significant public health concern in the Asia-Pacific region. EV-A71 is primarily responsible for causing hand, foot, and mouth disease (HFMD) in children. However, this virus can also lead to severe and potentially fatal neurological consequences in affected individuals. This review aims to provide a comprehensive understanding of the molecular virology, epidemiology, and recombination events associated with EV-A71. The literature extensively covers the clinical manifestations and neurological symptoms that accompany EV-A71 infections. One of the complications explored in this review is brainstem encephalitis, which can arise as a result of EV-A71 infections. Brainstem encephalitis refers to inflammation of the brainstem, a critical region responsible for various bodily functions. The review examines the underlying mechanisms, diagnostic criteria, treatment options, and prognosis for central nervous system infections involving EV-A71. Neurological complications associated with EV-A71 infections are diverse and can have severe consequences. These complications may include aseptic meningitis, acute flaccid paralysis, and acute transverse myelitis. The review delves into the pathophysiology of these complications, shedding light on the molecular mechanisms through which EV-A71 affects the central nervous system. Accurate diagnosis of EV-A71 infections is crucial for appropriate management and treatment. Treatment options for EV-A71 infections primarily focus on supportive care, as there are currently no specific antiviral drugs available for this virus. The review highlights the importance of managing symptoms, such as fever, dehydration, and pain relief, to alleviate the burden on affected individuals. Prognosis for individuals with central nervous system (CNS) infections involving EV-A71 can vary depending on the severity of the complications. The review provides insights into the long-term outcomes and potential neurological sequelae associated with EV-A71 infections. In conclusion, EV-A71 infections have emerged as a major public health concern in the Asia-Pacific region. This review aims to enhance our understanding of the molecular virology, epidemiology, and neurological complications associated with EV-A71. By examining the underlying mechanisms, diagnostic criteria, treatment options, and prognosis, this review contributes to the development of effective strategies for the prevention, diagnosis, and management of EV-A71 infections. The paper presents a comprehensive analysis of worldwide data pertaining to outbreaks of EV-A71 and HFMD. The subsequent discourse delves into the advancement and strategic formulation pertaining to the creation of vaccines targeting EV-A71. In summary, this study provides a comprehensive examination of the potential obstacles and considerations involved in the management and treatment of EV-A71 infections. Additionally, it proposes suggestions for future research and development endeavors with the objective of formulating efficacious treatment approaches for this viral infection.

Seroprevalence of SARS-CoV-2 in self-reported COVID-19-free children.

INTRODUCTION: COVID-19 poses risks and leads to complications for vulnerable populations, including children. Unreported cases of COVID-19 among children hinder our understanding of the true disease burden. In this study, we aimed to investigate the proportion of children who report no prior infection to SARS-CoV-2 but who nevertheless exhibit serological evidence of prior infection. METHODS: Between November 2022 and February 2023, we recruited children and adolescents under 19 years of age who lacked a prior history of SARS-CoV-2 infection. Participants underwent SARS-CoV-2 antibody testing to assess the presence of IgG antibodies specific to nucleocapsid (N) and spike (S) proteins. Demographic and contact information were also collected. RESULTS: Among 260 COVID-19-free children, the overall anti-N antibody positivity rate, which varied across age groups (4%-25%), was 9.2% (24/260). Contact with individuals who were positive for COVID-19, particularly the children's mothers, significantly increased the likelihood of antibody positivity. The median age of the 34 children who remained unvaccinated against COVID-19 was lower than that of the children who were vaccinated (6.5 vs. 9 years; p < 0.001). Until January 2024, the overall infection rate was 41.9% (99/236) among children who were negative for anti-N antibodies, irrespective of vaccination status or the presence of chronic disease. CONCLUSION: We discovered previously undisclosed cases of SARS-CoV-2 infection among children. The risk of seropositivity increases substantially with household contact. Regarding children who report no prior exposure to COVID-19, clinicians must remain vigilant, as SARS-CoV-2 remains a concern.