Glycan masking of NTD loops with a chimeric RBD of the spike protein as a vaccine design strategy against emerging SARS-CoV-2 Omicron variants.

The N-terminal domain (NTD) of the SARS-CoV-2 S protein comprises five exposed protruding loops. Deletions, insertions, and substitutions within these NTD loops play a significant role in viral evolution and contribute to immune evasion. We reported previously that introducing the glycan masking mutation R158N/Y160T in the NTD loop led to increased titers of neutralizing antibodies against the SARS-CoV-2 Wuhan-Hu-01 strain, as well as the Alpha, Beta, and Delta variants. In this study, we conducted further investigations on 10 additional glycan-masking sites in the NTD loops. Our findings indicate that the introduction of glycan masking mutations, specifically N87/G89T, H146N/N148T, N185/K187T, and V213N/D215T significantly enhanced neutralizing antibody titers against the Delta variant. The combination of dual glycan-masking mutations R158N/Y160T+V213N/D215T and R158N/Y160T+G219N results in a shift toward the Omicron BA.1. Furthermore, the introduction of the Omicron receptor binding domain (RBD) alongside these two dual glycan masking mutations of Wuhan-Hu-1 and XBB.1 NTD sequences resulted in a noticeable shift in antigenic distances, aligning with the Omicron BA.4/5, BA.2.75.2, BQ.1.1, and XBB.1 subvariants on the antigenic map. This strategic combination, which involves the dual glycan masking mutations R158N/Y160T+V213N/D215T and R158N/Y160T+G219N in the NTD loops, along with the domain swap incorporating the Omicron RBD, emerges as a promising vaccine design strategy for the continuous development of next-generation SARS-CoV-2 vaccines.

Clinical manifestations and risk factors of shock in children with multisystem inflammatory syndrome.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a novel disease associated with COVID-19. The COVID-19 epidemic peaked in May 2022 in Taiwan, and we encountered our first case of MIS-C in late May 2022. We aimed to present patients' clinical manifestations and identify risk factors for shock. METHODS: We included patients diagnosed with MIS-C at two medical centers from May 2022 to August 2022. We separated those patients into two groups according to whether they experienced shock. We collected demographic, clinical manifestation, and laboratory data of the patients and performed statistical analysis between the two groups. RESULTS: We enrolled 28 patients, including 13 (46 %) with shock and 15 (54 %) without shock. The median age was 6.4 years (IQR: 1.9-7.5). In single variable analysis, patients with shock tended to be older, had more neurological symptoms, more conjunctivitis and strawberry tongue, lower lymphocyte count, lower platelet counts, and higher C-reactive protein, higher procalcitonin, higher ferritin, and higher D-dimer levels than those without shock. The area under the ROC curve that used procalcitonin to be the risk factor of shock with MIS-C was 0.815 (95 % CI 0.644 to 0.987). The cutoff value obtained by ROC analysis of procalcitonin was 1.68 ng/mL. With this cutoff, the test characteristics of procalcitonin were as follows: sensitivity 77 %, specificity 93 %, positive predictive value 91 %, negative predictive value 82 %. Multivariable analysis revealed that procalcitonin was the only independent risk factor of shock with MIS-C on admission (OR, 26.00, 95 % CI, 1.01-668.89). CONCLUSIONS: MIS-C patients with high initial procalcitonin levels have higher risks of experiencing shock and may need ICU admission.

Concurrence of imatinib-induced massive pleural/pericardial effusion and Campylobacter bacteremia in an adolescent with chronic myeloid leukemia.

Imatinib is a crucial therapeutic strategy against chronic myeloid leukemia. Though superficial edema is a common adverse effect of imatinib, massive fluid retention is rarely reported. Here, we report the case of an adolescent who had tolerated imatinib for a long time, and then presented with massive pleural/pericardial effusion during an episode of Campylobacter jejuni bacteremia. A stepwise and comprehensive survey excluded all other plausible causes of disease. The Naranjo scale was used to assess the probability of an adverse effect of medication, and the score turned out to be 9, indicating severe fluid retention to be a definite reaction to imatinib. Drug discontinuation, antibiotic administration, and invasive procedures improved this condition. After this episode, the patient could tolerate imatinib again, illustrating the transient and reversible nature of this reaction. Since prolonged imatinib usage is crucial for chronic myeloid leukemia control, alertness to drug-related adverse effects is recommended, even if the subject has previously shown a good tolerance to the drug due to various physical conditions, especially physiological stressors, like infection or inflammation.

Impact of Wearing Masks, Hand Hygiene, and Social Distancing on Influenza, Enterovirus, and All-Cause Pneumonia During the Coronavirus Pandemic: Retrospective National Epidemiological Surveillance Study.

BACKGROUND: The coronavirus disease (COVID-19) pandemic is an important health crisis worldwide. Several strategies were implemented to combat COVID-19, including wearing masks, hand hygiene, and social distancing. The impact of these strategies on COVID-19 and other viral infections remains largely unclear. OBJECTIVE: We aim to investigate the impact of implemented infectious control strategies on the incidences of influenza, enterovirus infection, and all-cause pneumonia during the COVID-19 pandemic. METHODS: We utilized the electronic database of the Taiwan National Infectious Disease Statistics System and extracted incidences of COVID-19, influenza virus, enterovirus, and all-cause pneumonia. We compared the incidences of these diseases from week 45 of 2016 to week 21 of 2020 and performed linear regression analyses. RESULTS: The first case of COVID-19 in Taiwan was reported in late January 2020 (week 4). Infectious control strategies have been promoted since late January. The influenza virus usually peaks in winter and decreases around week 14. However, a significant decrease in influenza was observed after week 6 of 2020. Regression analyses produced the following results: 2017, R2=0.037; 2018, R2=0.021; 2019, R2=0.046; and 2020, R2=0.599. A dramatic decrease in all-cause pneumonia was also reported (R2 values for 2017-2020 were 0.435, 0.098, 0.352, and 0.82, respectively). Enterovirus had increased by week 18 in 2017-2019, but this was not observed in 2020. CONCLUSIONS: Using this national epidemiological database, we found a significant decrease in cases of influenza, enterovirus, and all-cause pneumonia during the COVID-19 pandemic. Wearing masks, hand hygiene, and social distancing may contribute not only to the prevention of COVID-19 but also to the decline of other respiratory infectious diseases. Further studies are warranted to elucidate the causal relationship.

Community outbreak of adenovirus, Taiwan, 2011.

In 2011, a large community outbreak of human adenovirus (HAdV) in Taiwan was detected by a nationwide surveillance system. The epidemic lasted from week 11 through week 41 of 2011 (March 14-October 16, 2011). Although HAdV-3 was the predominant strain detected (74%), an abrupt increase in the percentage of infections caused by HAdV-7 occurred, from 0.3% in 2008-2010 to 10% in 2011. Clinical information was collected for 202 inpatients infected with HAdV; 31 (15.2%) had severe infection that required intensive care, and 7 of those patients died. HAdV-7 accounted for 10%, 12%, and 41% of infections among outpatients, inpatients with nonsevere infection, and inpatients with severe infection, respectively (p<0.01). The HAdV-7 strain detected in this outbreak is identical to a strain recently reported in the People's Republic of China (HAdV7-HZ/SHX/CHN/2009). Absence of circulating HAdV-7 in previous years and introduction of an emerging strain are 2 factors that caused this outbreak.

Safety and immunogenicity of SARS-CoV-2 vaccine MVC-COV1901 in Taiwanese adolescents: a randomized phase 2 trial.

Adolescents and children play an important role in SARS-CoV-2 transmission and epidemiology. MVC-COV1901 is a subunit SARS-CoV-2 vaccine based on stabilized spike protein adjuvanted with CpG 1018 and aluminum hydroxide that has received emergency use approval (EUA) for adults in Taiwan. In this study, we have investigated the safety and immunogenicity of two doses of MVC-COV1901 in adolescents. Healthy adolescents from the age of 12-17 years were randomly assigned to receive two intramuscular doses of either MVC-COV1901 or placebo at 28 days apart. Adverse events were mostly mild and were similar in MVC-COV1901 and placebo groups, with the most commonly reported adverse events being pain/tenderness and malaise/fatigue. All immunogenicity endpoints in the adolescent group were non-inferior to the endpoints seen in the young adult and placebo groups. The results here advocate the use of MVC-COV1901 in adolescents in the ongoing efforts to control the pandemic.ClinicalTrials.gov registration: NCT04951388.

One-Seventh of Patients with COVID-19 Had Olfactory and Gustatory Abnormalities as Their Initial Symptoms: A Systematic Review and Meta-Analysis.

Coronavirus disease 2019 (COVID-19) patients exhibited protean clinical manifestations. Olfactory and gustatory abnormalities (anosmia and ageusia) were observed in COVID-19 patients, but the reported prevalence varied. In this systematic review, the prevalence of olfactory and gustatory abnormalities (OGA) was evaluated in laboratory-confirmed COVID-19 patients. On 8 May 2020, 14,506 articles were screened, while 12 of them were enrolled. A total of 1739 COVID-19 patients were analyzed, with a wide range of prevalence observed (5.6-94%). The pooled prevalence was 48.5% with high heterogeneity (I2, 98.8%; p < 0.0001). In total, 15.5% had OGA as their first symptom (I2, 22.6%; p = 0.27) among the patients analyzed. Contradictory to COVID-19 negative controls, patients with COVID-19 had a higher risk of OGA (odds ratio, 5.3; I2, 66.5%; p = 0.03). In conclusion, approximately half of COVID-19 patients had OGA, and one-seventh of them had OGA as their initial symptoms. OGA were cardinal symptoms of COVID-19, which may serve as clues for early diagnosis. Diagnostic testing for SARS-CoV-2 was suggested in patients with OGA during the COVID-19 pandemic to ensure timely diagnosis and appropriate quarantine.

Pseudo-outbreak of rotavirus infection in a neonatal intensive care unit.

BACKGROUND: A rotavirus outbreak in a neonatal intensive care unit (NICU) may have catastrophic consequences for young infants receiving critical care. From May 13, 2011 to July 11, 2011, a significant increase in stool samples testing positive for rotavirus antigens in the NICU of a university affiliated hospital was observed. Due to lack of clinical presentations suggestive of rotavirus infection in the patients and the rarity of rotavirus infection in the NICU in the past, a pseudo-outbreak was suspected. METHODS: Infection control measures were reinforced initially. To investigate the outbreak, a prospective laboratory-based active surveillance of all infants in the NICU was conducted right after the cluster was identified. Repeated testing using a modified enzyme immunoassay (EIA) kit, rotavirus RNA polyacrylamide gel electrophoresis (PAGE), reverse transcription polymerase chain reaction (RT-PCR), and retrospective chart review methods were used to confirm the pseudo-outbreak. RESULTS: Seven infants in the NICU, with or without gastrointestinal symptoms, tested positive for the rotavirus antigen using the old version of an EIA kit, which indicated a possible outbreak. Active surveillance with repeated tests for recollected stool samples using a modified EIA kit showed negative results in all 24 infants in the NICU. Seven stored stool samples from four infants, which previously tested positive for the rotavirus antigen, tested negative for rotavirus using the modified EIA kit, PAGE, and RT-PCR. Chart reviews showed no clinical difference between index cases and controls. False positivity might arise from unsatisfactory specificity of the old EIA kit. After the introduction of the modified EIA kit, no rotavirus was detected in the NICU for at least 7 months. CONCLUSION: This cluster of patients who tested positive for the rotavirus antigen in stools was confirmed to be a pseudo-outbreak. Interpretation of the old EIA for rotavirus in an NICU setting should be done with caution until the mechanism of the false-positive reaction is elucidated.

Adenovirus serotype 3 and 7 infection with acute respiratory failure in children in Taiwan, 2010-2011.

OBJECTIVE: Increased incidence of adenovirus infection in children was noticed since September 2010 in Taiwan and severe cases requiring intensive care were noted later. We did this study to find the clinical characteristics and risk factors associated with severe adenovirus infection. PATIENTS AND METHODS: We collected cases of severe adenovirus infection between November 2010 and June 2011 to analyze their clinical characteristics in two medical centers in northern Taiwan. Severe adenovirus infection was defined as laboratory-confirmed adenovirus cases with required intensive care. Hexon gene sequencing was performed for molecular genotyping. RESULTS: 45 patients were included, 22 cases (49%) were infected with serotype 7, 19 (42%) with serotype 3, and 4 with serotype 2. The median age (range) was 2.75 years (0.08-15.43 years); 87% were below 5 years. Male to female ratio was 1.65 (28 to 17). Of these patients, 56% had underlying neurological diseases, 50% experienced fever higher than 40°C and 69% suffered fever longer than one week. The clinical diagnosis included pneumonia in 40 (89%) patients, bronchopneumonia in 5 (11%), and encephalitis in 7 (16%). At least 22 patients had pleural effusion. They had complications of respiratory failure (53%), acute respiratory distress syndrome (24%), hypotension (40%), and 6 (13%) patients needed extracorporeal membranous oxygenation. Ten (22%) patients died, all with underlying major systemic diseases and 7 (70%) infected with serotype 7. CONCLUSIONS: Adenovirus serotype 7 and 3 can cause severe disease-even death-in children, especially those with underlying neurological diseases. Patients infected with adenovirus serotype 7 tended to have a higher case-fatality rate.