Improved Immunogenicity of the Inactivated F Genotype Mumps Vaccine against Diverse Circulating Mumps Viruses in Mice.

Mumps is an acute infectious disease caused by the mumps virus (MuV). Despite high global vaccination coverage, mumps outbreaks continue to occur, even in vaccinated populations. Therefore, we aimed to identify candidate vaccines that can induce an immunogenic response against diverse MuV genotypes with greater efficacy than the currently available options. Vaccine candidates were sourced using formalin-inactivated viral strains. The inactivated vaccines were administered to BALB/c mice (through a primer and booster dose administered after a three-week interval). We tested the neutralizing antibodies of the candidate vaccines against various MuV genotypes to determine their overall efficacy. The formalin-inactivated F genotype vaccine was found to have higher cross-neutralizing titers against genotypes F, H, and G as well as significant Th1 cytokines responses, IFN-γ, TNF-α, and IL-2 than the Jeryl Lynn (JL) vaccine. Our findings suggest that the inactivated F genotype mumps vaccine has higher immunogenicity than the JL vaccine against diverse circulating MuVs.

The Association of Acute Signs and Symptoms of COVID-19 and Exacerbation of Depression and Anxiety in Patients With Clinically Mild COVID-19: Retrospective Observational Study.

BACKGROUND: To date, the association between acute signs and symptoms of COVID-19 and the exacerbation of depression and anxiety in patients with clinically mild COVID-19 has not been evaluated. OBJECTIVE: This study was designed to assess the correlation between acute signs and symptoms of COVID-19 and the exacerbation of depression and anxiety in patients with clinically mild COVID-19 at a residential treatment center in South Korea. METHODS: This retrospective study assessed 2671 patients with COVID-19 admitted to 4 residential treatment centers operated by Seoul National University Hospital, South Korea, from March 2020 to April 2022. Depression and anxiety were assessed using the 2-item Patient Health Questionnaire (PHQ-2) and 2-item Generalized Anxiety Disorder (GAD-2) scale, respectively. The exacerbation of depression and anxiety symptoms was identified from the differences in PHQ-2 and GAD-2 scores between admission and discharge, respectively. The patients' clinical characteristics, including acute signs and symptoms of COVID-19, GAD-2 and PHQ-2 scores, were obtained from electronic health records. Demographic characteristics, a summary of vital signs, and COVID-19 symptoms were analyzed and compared between the patient groups with and those without exacerbated PHQ-2 and GAD-2 scores using the chi-square test. We applied logistic regression to identify the association between acute signs and symptoms of COVID-19 and the exacerbation of depression and anxiety. RESULTS: Sleep disorders were associated with exacerbated depression (odds ratio [OR] 1.09, 95% CI 1.05-1.13) and anxiety (OR 1.1, 95% CI 1.06-1.14), and the sore throat symptom was associated with exacerbated anxiety symptoms (OR 1.03, 95% CI 1.00-1.07). Patients with abnormal oxygen saturation during quarantine were more likely to have exacerbated depression (OR 1.27, 95% CI 1.00-1.62), and those with an abnormal body temperature during quarantine were more likely to experience anxiety (OR 1.08, 95% CI 1.01-1.16). As anticipated, patients who experienced psychological symptoms at admission were more likely to experience depression (OR 1.91, 95% CI 1.52-2.41) and anxiety (OR 1.98, 95% CI 1.54-2.53). Meanwhile, the PHQ-2 and GAD-2 scores measured at admission revealed that lower the score, higher the possibility of exacerbation of both depression (OR 0.15, 95% CI 0.11-0.22) and anxiety (OR 0.13, 95% CI 0.10-0.19). CONCLUSIONS: Results from this study suggest the importance of further interventions for patients with abnormal oxygen saturation, abnormal body temperatures, sore throat, and sleep disorder symptoms or initial psychological symptoms to mitigate the exacerbation of depression and anxiety. In addition, this study highlights the usability of short and efficient scales such as the PHQ-2 and GAD-2 in the assessment of the mental health of patients with clinically mild COVID-19 symptoms who were quarantined at home during the pandemic era.

Estimation of SARS-CoV-2 Neutralizing Activity and Protective Immunity in Different Vaccine Types Using Three Surrogate Virus Neutralization Test Assays and Two Semiquantitative Binding Assays Targeting the Receptor-Binding Domain.

Estimating neutralizing activity in vaccinees is crucial for predicting the protective effect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the plaque reduction neutralization test (PRNT) requires a biosafety level 3 facility, it would be advantageous if surrogate virus neutralization test (sVNT) assays and binding assays could predict neutralizing activity. Here, five different assays were evaluated with respect to the PRNT in vaccinees: three sVNT assays from GenScript, Boditech Med, and SD Biosensor and two semiquantitative binding assays from Roche and Abbott. The vaccinees were subjected to three vaccination protocols: homologous ChAdOx1, homologous BNT162b2, and heterologous administration. The ability to predict a 50% neutralizing dose (ND50) of ≥20 largely varied among the assays, with the binding assays showing substantial agreement (kappa, ~0.90) and the sVNT assays showing relatively poor performance, especially in the ChAdOx1 group (kappa, 0.33 to 0.97). The ability to predict an ND50 value of ≥118.25, indicating a protective effect, was comparable among different assays. Applying optimal cutoffs based on Youden's index, the kappa agreements were greater than 0.60 for all assays in the total group. Overall, relatively poor performance was demonstrated in the ChAdOx1 group, owing to low antibody titers. Although there were intra-assay differences related to the vaccination protocols, as well as interassay differences, all assays demonstrated fair performance in predicting the protective effect using the new cutoffs. This study demonstrates the need for a different cutoff for each assay to appropriately determine a higher neutralizing titer and suggests the clinical feasibility of using various assays for estimation of the protective effect. IMPORTANCE The coronavirus disease 2019 (COVID-19) pandemic continues to last, despite high COVID-19 vaccination rates. As many people experience breakthrough infection after prior infection and/or vaccination, estimating the neutralization activity and predicting the protective effect are major issues of concern. However, since standard neutralization tests are not available in most clinical laboratories, it would be beneficial if commercial assays could predict these aspects. In this study, we evaluated the performance of three sVNT assays and two semiquantitative binding assays targeting the receptor-binding domain with respect to the PRNT. Our results suggest that these assays could be used for predicting the protective effect by adjusting the cutoffs.

Neutralizing Activity Against SARS-CoV-2 Delta and Omicron Variants Following a Third BNT162b2 Booster Dose According to Three Homologous or Heterologous COVID-19 Vaccination Schedules.

With the emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants, escaping vaccine-induced immunity is a concern. Three vaccination schedules, homologous or heterologous, have been initially applied due to an insufficient supply of vaccines in Korea. We investigated neutralizing activities against Omicron and Delta variants in each schedule. Three schedules using three doses of the BNT162b2 (BNT) or the ChAdOx1 (ChAd) vaccines include ChAd-ChAd-BNT, ChAd-BNT-BNT, and BNT-BNT-BNT. Neutralizing activities were evaluated using plaque-reduction neutralization test (PRNT) against wild type (WT) SARS-CoV-2, Delta variant, and Omicron variant. A total of 170 sera from 75 participants were tested, and the baseline characteristics of participants were not significantly different between groups. After the 2nd vaccine dose, geometric mean titers of PRNT ND50 against WT, Delta, and Omicron were highest after ChAd-BNT vaccination (2,463, 1,097, and 107) followed by BNT-BNT (2,364, 674, and 38) and ChAd-ChAd (449, 163, and 25). After the 3rd dose of BNT, the increase of PRNT ND50 against WT, Delta, and Omicron was most robust in ChAd-ChAd-BNT (4,632, 988, and 260), while the BNT-BNT-BNT group showed the most augmented neutralizing activity against Delta and Omicron variants (2,315 and 628). ChAd-BNT-BNT showed a slight increase of PRNT ND50 against WT, Delta, and Omicron (2,757, 1,279, and 230) compared to the 2nd dose. The results suggest that a 3rd BNT booster dose induced strengthened neutralizing activity against Delta and Omicron variants. The waning of cross-reactive neutralizing antibodies after the 3rd dose and the need for additional boosting should be further investigated.

Seroprevalence of SARS-CoV-2 antibodies in the community based on participants in the 2020 Korea National Health and Nutrition Examination Survey.

OBJECTIVES: The Korea National Health and Nutrition Examination Survey (KNHANES) is a nationwide cross-sectional surveillance system that assesses the health and nutritional status of the Korean population. To evaluate the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the community, we investigated the prevalence of anti-SARS-CoV-2 antibodies in the sera of KNHANES participants. METHODS: Subjects were recruited between April 24 and December 12, 2020. In total, 5,284 subjects aged 10-90 years from 17 regions participated. SARS-CoV-2 antibodies were screened using the Elecsys Anti-SARS-CoV-2 assay. Positive samples were verified using 4 different SARS-CoV-2 antibody assays and the plaque reduction neutralizing test. The final seropositivity criteria were a positive screening test and at least 1 positive result from the 5 additional tests. RESULTS: Almost half (49.2%; 2,600/5,284) of participants were from metropolitan areas, 48.9% were middle-aged (40-69 years), and 20.5% were in their 20s or younger. The seropositivity rate was 0.09% (5/5,284). Three of the 5 antibody-positive subjects had a history of infection, of whom 2 were infected abroad and 1 was infected in a local cluster outbreak. CONCLUSIONS: The low SARS-CoV-2 antibody seroprevalence in Korea indicates that there have been few coronavirus disease 2019 (COVID-19) cases due to successful COVID-19 management measures (e.g., diagnostic tests for overseas arrivals, national social distancing, and strict quarantine measures). Moreover, asymptomatic infections were uncommon due to active polymerase chain reaction testing. However, hidden infections may exist in the community, requiring the continuation of quarantine and vaccination measures.

Immunogenicity of candidate SARS-CoV-2 DNA vaccines based on the spike protein.

Coronavirus disease 2019 caused by the novel human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a major threat to public health worldwide. To deal with the needs of vaccine, we developed four DNA vaccine candidates against SARS-CoV-2, based on the full-length spike (S) or truncated S protein. Following mice vaccination, we measured T-cell response and antigen-specific neutralizing antibody (NAb) titer. All four candidates induced humoral immune responses, including elevated levels of total IgG and NAbs, and cell-mediated immune responses, including multiple cytokine expression. However, the full-length S DNA vaccine enhanced the immune responses most significantly. We then evaluated its appropriate antigen dose and vaccination schedule. Although all immunized groups showed higher immune response than the control group, inoculation with 50 µg antigen led to the highest NAb titer. Immunity was significantly increased after the third inoculation. Thus, the full-length S DNA vaccine can potentially prevent SARS-CoV-2 infection.

Comparison of the Prevalence of Antibodies to SARS-CoV-2 in 9954 Recruits in the Korean Army Training Center with the General Korean Population of Equivalent Age Between September and November, 2020.

BACKGROUND Understanding the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be a useful tool when studying spread of the disease. This study aimed to compare the prevalence of antibodies to SARS-CoV-2 in 9954 recruits in the Korean Army Training Center with the general Korean population age <30 years between September and November, 2020. MATERIAL AND METHODS At the Korean Army Training Center, samples were taken from 9954 men from September to November, 2020. Participants were randomly enlisted healthy adult men. The data were compared with 4,205,265 samples from the Korean general population. Men age <30 years were used, as this is similar to the age range of the military recruits. RESULTS Among military recruits, 31 subjects (0.31%) were positive for the antibody, while the Korean male population had 3757 (0.09%) positive individuals. Among these 31 men, 13 were previously diagnosed by PCR, while 18 (58.06%) had no history related to the disease. Positive military recruits were mostly from 2 regional clusters. The first cluster was Daegu and Gyeongbuk areas (1.97% and 0.80%, respectively), which had an outbreak in March, 2020. The second cluster was Gyeonggi and Seoul, or capital areas (0.23% and 0.20%, respectively), which currently has high PCR positivity. Overall, seroprevalence was 3.49 times higher in study subjects. CONCLUSIONS The high seroprevalence of antibodies to SARS-CoV-2 between September and November 2020 in a densely populated military academy in Korea may have been an indicator for the resulting outbreak of COVID-19 in winter 2020-21, which highlights the importance of asymptomatic spread from the young and healthy to the general population.

Performance Comparison of Five SARS-CoV-2 Antibody Assays for Seroprevalence Studies.

BACKGROUND: Seroprevalence studies of coronavirus disease 2019 (COVID-19) cases, including asymptomatic and past infections, are important to estimate the scale of the disease outbreak and to establish quarantine measures. We evaluated the clinical performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays available in Korea for use in seroprevalence studies. METHODS: The sensitivity, specificity, cross-reactivity, and interference of five SARS-CoV-2 antibody assays were evaluated using the following: 398 serum samples from confirmed COVID-19 patients, 510 negative control samples from before 2018 (pre-pandemic), 163 serum samples from patients with SARS, Middle East respiratory syndrome (MERS), and other viral infections, and five samples for the interference study. RESULTS: The sensitivities of the five assays ranged from 92.2% to 98%, and their specificities, including cross-reactivity and interference, ranged from 97.5% to 100%. The agreement rates were excellent (kappa >0.9). Adjustment of the cutoff values could be considered through ROC curve analysis. The positive predictive values of the individual assays varied from 3.5% to 100% at a 0.1% prevalence but were as high as ≥95% when two assays were combined. CONCLUSIONS: The prevalence of COVID-19 in Korea is considered to be exceptionally low at present; thus, we recommend using a combination of two or more SARS-CoV-2 antibody assays rather than a single assay. These results could help select SARS-CoV-2 antibody assays for COVID-19 seroprevalence studies in Korea.

Investigation of droplets released during digestive endoscopy using a high-speed camera (with video): a pilot study.

BACKGROUND: A large release of droplets is often expected around the periphery of the digestive endoscope insertion site. Therefore, a sense of alarm over infection because of droplets that may be released during digestive endoscopy examination is increasing. This study aimed to investigate the droplets released during digestive endoscopy using a high-speed camera. METHODS: We utilized a high-speed camera (FASTCAM SA-3, Photron Limited) capable of recording small, transparent droplets with a black background and high-brightness lighting. The obtained video files were analyzed using post-processing software. We divided the 20 models into the control (a spray bottle model and a cough model) and experimental groups (digestive endoscopy models). The sedative, proficiency of digestive endoscopy and the amount of gas injected were modulated to change the level of released droplets. RESULTS: For the control groups, droplets were clearly observed using a high-speed camera. However, no droplet larger than 10 µm in size was observed in the experimental groups. Furthermore, the changes in the sedative, proficiency of digestive endoscopy, and amount of gas injected did not affect droplet formation. CONCLUSIONS: Based on high-speed camera photography, the risk of droplet generation during digestive endoscopy was not higher than that during violent expiratory events, such as coughing and sneezing.

Validation of Olfactory Questionnaire in Koreans: an Alternative for Conventional Psychophysical Olfactory Tests.

BACKGROUND: The patients with coronavirus disease 2019 (COVID-19), a worldwide pandemic infection, frequently complain of olfactory disorders. However, psychophysical olfactory tests performed by an examiner are very difficult in these highly infectious patients. This study aimed to develop and validate a questionnaire for olfactory function that can be readily used to evaluate olfactory loss. METHODS: Fourteen smell-related questions were created based on smells familiar to Koreans. Among them, questions with a κ value of 0.6 or higher were finally selected through a test-retest reliability analysis. The correlations between the scores of the olfactory questionnaire and those of olfactory function tests (Butanol Threshold Test [BTT] and Cross Cultural Smell Identification Test [CCSIT]) were analyzed. To evaluate the predictive ability of the questionnaire and elicit cutoff values, receiver operating characteristic (ROC) curves were generated. RESULTS: Out of the 14 questions in the questionnaire, 11 (κ > 0.6) were selected for the olfactory questionnaire. We analyzed 2,273 subjects, and there was a significant correlation between the total score of the olfactory questionnaire and the BTT (r = 0.643, P < 0.001) or CCSIT (r = 0.615, P < 0.001) scores. ROC curves for the olfactory questionnaire, BTT, and CCSIT all demonstrated high predictive power to discriminate anosmia and severe hyposmia from normosmia. Regarding mild to moderate hyposmia, however, ROC curve for the olfactory questionnaire alone showed high predictive power of discrimination from normosmia. Based on the results of ROC curves among the subclasses, we suggest the classification of the total score of the questionnaire as 0-4, 5-17, 18-27, 28-41, and 42-44, for anosmia, severe hyposmia, moderate hyposmia, mild hyposmia, and normosmia, respectively. CONCLUSION: The total scores of the questionnaires correlated with the BTT and CCSIT scores. The symptom questionnaire for olfactory dysfunction may be useful as an alternative tool for olfactory function testing, when unavailable.

Operation and Management of Seoul Metropolitan City Community Treatment Center for Mild Condition COVID-19 Patients.

BACKGROUND: In response to the disaster of coronavirus disease 2019 (COVID-19) pandemic, Seoul Metropolitan Government (SMG) established a patient facility for mild condition patients other than hospital. This study was conducted to investigate the operation and necessary resources of a community treatment center (CTC) operated in Seoul, a metropolitan city with a population of 10 million. METHODS: To respond COVID-19 epidemic, the SMG designated 5 municipal hospitals as dedicated COVID-19 hospitals and implemented one CTC cooperated with the Boramae Municipal Hospital for COVID-19 patients in Seoul. As a retrospective cross-sectional observational study, retrospective medical records review was conducted for patients admitted to the Seoul CTC. The admission and discharge route of CTC patients were investigated. The patient characteristics were compared according to route of discharge whether the patient was discharged to home or transferred to hospital. To report the operation of CTC, the daily mean number of tests (reverse transcription polymerase chain reaction and chest X-ray) and consultations by medical staffs were calculated per week. The list of frequent used medications and who used medication most frequently were investigated. RESULTS: Until May 27 when the Seoul CTC was closed, 26.5% (n = 213) of total 803 COVID-19 patients in Seoul were admitted to the CTC. It was 35.7% (n = 213) of 597 newly diagnosed patients in Seoul during the 11 weeks of operation. The median length of stay was 21 days (interquartile range, 12-29 days). A total of 191 patients (89.7%) were discharged to home after virologic remission and 22 (10.3%) were transferred to hospital for further treatment. Fifty percent of transferred patients were within a week since CTC admission. Daily 2.5-3.6 consultations by doctors or nurses and 0.4-0.9 tests were provided to one patient. The most frequently prescribed medication was symptomatic medication for COVID-19 (cough/sputum and rhinorrhea). The next ranking was psychiatric medication for sleep problem and depression/anxiety, which was prescribed more than digestive drug. CONCLUSION: In the time of an infectious disease disaster, a metropolitan city can operate a temporary patient facility such as CTC to make a surge capacity and appropriately allocate scarce medical resource.