An inactivated NDV-HXP-S COVID-19 vaccine elicits a higher proportion of neutralizing antibodies in humans than mRNA vaccination.

NDV-HXP-S is a recombinant Newcastle disease virus-based vaccine against SARS-CoV-2, which expresses an optimized (HexaPro) spike protein on its surface. The vaccine can be produced in embryonated chicken eggs using the same process as that used for the production of the vast majority of influenza virus vaccines. Here, we performed a secondary analysis of the antibody responses after vaccination with inactivated NDV-HXP-S in a phase 1 clinical study in Thailand. The SARS-CoV-2 neutralizing and spike protein binding activity of NDV-HXP-S postvaccination serum samples was compared to that of samples from mRNA BNT162b2 (Pfizer) vaccinees. Neutralizing activity of sera from NDV-HXP-S vaccinees was comparable to that of BNT162b2 vaccinees, whereas spike protein binding activity of the NDV-HXP-S vaccinee samples was lower than that of sera obtained from mRNA vaccinees. This led us to calculate ratios between binding and neutralizing antibody titers. Samples from NDV-HXP-S vaccinees had binding to neutralizing activity ratios that were lower than those of BNT162b2 sera, suggesting that NDV-HXP-S vaccination elicits a high proportion of neutralizing antibodies and low non-neutralizing antibody titers. Further analysis showed that, in contrast to mRNA vaccination, which induces strong antibody titers to the receptor binding domain (RBD), the N-terminal domain, and the S2 domain, NDV-HXP-S vaccination induced an RBD-focused antibody response with little reactivity to S2. This finding may explain the high proportion of neutralizing antibodies. In conclusion, vaccination with inactivated NDV-HXP-S induces a high proportion of neutralizing antibodies and absolute neutralizing antibody titers that are comparable to those elicited by mRNA vaccination.

Case Report: Walking Pneumonia in Novel Coronavirus Disease (COVID-19): Mild Symptoms with Marked Abnormalities on Chest Imaging.

This case report underlines the appearance of a "walking pneumonia" in a novel coronavirus disease (COVID-19) patient, with evidence of progressive lung involvement on chest imaging studies. The patient traveled from Wuhan, Hubei, China, to Thailand in January 2020. One of her family members was diagnosed with COVID-19. She presented to the hospital because of her concern, but she was without fever or any respiratory symptoms. Three days earlier, her nasopharyngeal and throat swabs revealed a negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Her initial chest radiography was abnormal, and her first sputum SARS-CoV-2 test yielded inconclusive results. A subsequent sputum test was positive for SARS-CoV-2. Diagnosis in this patient was facilitated by chest imaging and repeat viral testing. Thus, chest imaging studies might enhance capabilities for early diagnosis of COVID-19 pneumonia.

False Positivity of Anti-SARS-CoV-2 Antibodies in Patients with Acute Tropical Diseases in Thailand.

Serology remains a useful indirect method of diagnosing tropical diseases, especially in dengue infection. However, the current literature regarding cross-reactivity between SARS-CoV-2 and dengue serology is limited and revealed conflicting results. As a means to uncover relevant serological insight involving antibody classes against SARS-CoV-2 and cross-reactivity, anti-SARS-CoV-2 IgA, IgM, and IgG ELISA, based on spike and nucleocapsid proteins, were selected for a fever-presenting tropical disease patient investigation. The study was conducted at the Faculty of Tropical Medicine during March to December 2021. The study data source comprised (i) 170 non-COVID-19 sera from 140 adults and children presenting with acute undifferentiated febrile illness and 30 healthy volunteers, and (ii) 31 COVID-19 sera from 17 RT-PCR-confirmed COVID-19 patients. Among 170 non-COVID-19 samples, 27 were false positives (15.9%), of which IgA, IgM, and IgG cross-reactive antibody classes were detected in 18 (10.6%), 9 (5.3%), and 3 (1.8%) cases, respectively. Interestingly, one case exhibited both IgA and IgM false positivity, while two cases exhibited both IgA and IgG false positivity. The false positivity rate in anti-SARS-CoV-2 IgA and IgM was reported in adults with dengue infection (11.3% and 5%) and adults with other tropical diseases (16.7% and 13.3%). The urea dissociation method applied to mitigate false positivity resulted in significantly decreased ELISA-based false and true positives. In conclusion, the analysis of antibody against SARS-CoV-2 in sera of patients with different tropical diseases showed that high IgA and IgM false positivity thus potentially limits serological assay utility in fever-presenting patients in tropical areas.

Mortality in Thai Nursing Homes Based on Antimicrobial-Resistant Enterobacterales Carriage and COVID-19 Lockdown Timing: A Prospective Cohort Study.

Antimicrobial-resistant Enterobacterales carriage and the coronavirus disease 2019 (COVID-19) lockdown measures may impact the incidence all-cause mortality rate among nursing home residents. To determine the all-cause mortality rate in the presence/absence of antimicrobial-resistant Enterobacterales carriage and the incidence all-cause mortality rate before and during COVID-19 pandemic lockdown, this prospective closed-cohort study was conducted at various types of nursing homes in Bangkok, Thailand, from June 2020 to December 2021. The elderly residents included 142 participants (aged ≥60 years) living in nursing homes ≥3 months, who did not have terminal illnesses. Time-to-event analyses with Cox proportional hazards models and stratified log-rank tests were used. The all-cause mortality rate was 18%, and the incidence all-cause mortality rate was 0.59/1000 person-days in residents who had antimicrobial-resistant Enterobacterales carriage at baseline. Meanwhile, the incidence all-cause mortality rate among noncarriage was 0.17/1000 person-days. The mortality incidence rate of carriage was three times higher than residents who were noncarriage without statistical significance (HR 3.2; 95% CI 0.74, 13.83). Residents in nonprofit nursing homes had a higher mortality rate than those in for-profit nursing homes (OR 9.24; 95% CI 2.14, 39.86). The incidence mortality rate during and before lockdown were 0.62 and 0.30, respectively. Effective infection-control policies akin to hospital-based systems should be endorsed in all types of nursing homes. To limit the interruption of long-term chronic care, COVID-19 prevention should be individualized to nursing homes.

Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Interim results of a randomised, placebo-controlled, phase 1 trial.

Background: Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed by public sector manufacturers in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. Methods: This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy males and non-pregnant females, aged 18-59 years and negative for SARS-CoV-2 antibodies, were eligible. Participants were randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg, 1 µg+CpG1018 (a toll-like receptor 9 agonist), 3 µg, 3 µg+CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422). Findings: Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enroled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation's immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 international units per mL (IU/mL; 1 µg, 95% confidence interval (CI) 86·40-172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90-701·19), with 93·9% to 100% of vaccine groups attaining a ≥ 4-fold increase over baseline. Interpretation: NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2. Funding: National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA).

Knowledge, attitude, and practices toward COVID-19 among the international travelers in Thailand.

BACKGROUND: International travel is among the leading impactful factors of COVID-19 transmission; thus, adequate knowledge, good attitude and good preventive practices toward COVID-19 for international travelers are particularly essential for successful pandemic control. METHODS: A cross-sectional, questionnaire-based study was conducted to determine knowledge, attitude and practices (KAP) of international travelers (both Thai and non-Thai) and expatriates in Thailand. The data were collected at the Thai Travel Clinic, Bangkok, Thailand and via online platforms during May to October 2020. The independent T-test, Chi-square test and multiple regression analysis (MRA) were applied to determine factors influencing the KAP. RESULTS: Of 399 travelers, 46.6% were male, 72.1% had a Bachelor's degree or higher, and the mean age was 35.6 ± 9.6 years. Due to unexpected travel restrictions and lock down, 77.9% of participants were Thai and the respective major purpose of travel was business/work. Travel cancellation/postponement was reported at 73.9%. While sufficient knowledge (≥ 60% correct answers) was reported in 77.9% of participants, a low percentage of correct answers was found in the questions regarding disease transmission. The travelers reported a neutral attitude and an overall moderate concern regarding the COVID-19 situation. Adequate preventive practices were determined by the average practice score 3.54 ± 0.38 (0 = never and 4 = always). The MRA revealed that the factors influencing good practices were travelers who: i) enrolled from outside the hospital (online platform); ii) received pretravel advice at hospital; iii) were female; iv) participated before the declaration of the end of the outbreak; v) were aged 40-49 years, and vi) visited friends and relatives. CONCLUSIONS: The majority of travelers in this study had sufficient knowledge, a neutral attitude and adequate preventive practices toward COVID-19. The factors influencing good practices included pretravel advice, sex, age and the point in the timeline of the outbreak. In order to better control the COVID-19 pandemic situation, pretravel counselling and advice should be promoted as a means to improve knowledge, particularly in disease transmission, increase awareness and emphasize appropriate preventive measures toward COVID-19 among international travelers. Furthermore, preventive practices should be bolstered at all times regardless of the outbreak situation.

Temporal Change of SARS-CoV-2 in Clinical Specimens of COVID-19 Pneumonia Patients.

The quality and type of specimen collection affect the sensitivity of real-time reverse transcriptase-PCR (rRT-PCR) for the diagnosis of SARS-CoV-2. In this report, the course over time of rRT-PCR for SARS-CoV-2 in 26 clinical specimens collected from the upper (nasopharyngeal and throat swabs) and lower (sputum) respiratory tracts of COVID-19 cases with pneumonia was investigated along with the clinical course. The preliminary results revealed that higher SARS-CoV-2 RNA concentration and longer time for detection make self-collected sputum a preferable specimen for the diagnosis and follow-up of COVID-19 pneumonia. Self-collection of sputum can minimize the risk of unnecessary exposure to healthcare workers, preserve the shortage of personal protective equipment, and limit viral transmission to the environment.

Case Report: COVID-19 Presenting as Acute Undifferentiated Febrile Illness-A Tropical World Threat

We report a young Thai man from the Thai-Myanmar border suffering from 2 days of fever and myalgia without respiratory tract signs or symptoms. He reported no history of travel through an area with confirmed COVID-19 cases or contact with sick persons. After excluding malaria and dengue, which are common causative agents of acute undifferentiated febrile illness (AUFI) in Thailand, chest radiography was performed according to the patient triage protocol of our institute for AUFI during the COVID-19 outbreak. Chest radiography revealed findings compatible with pneumonia. Nasopharyngeal, throat, and sputum samples tested positive for SARS-CoV-2 by real-time reverse transcriptase-PCR. The preadmission diagnosis of COVID-19 in this patient enabled appropriate management and isolation to prevent nosocomial transmission. Fever and nonspecific symptoms and laboratory results in early COVID-19 may be difficult to distinguish from tropical infectious diseases, especially when respiratory signs and symptoms are absent. This fact necessitates vigilant awareness in clinical investigation, management, and infection control, especially in tropical resource-limited settings.