Evaluation of a biotin-based surrogate virus neutralization test for detecting postvaccination antibodies against SARS-CoV-2 variants in sera.

A severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) surrogate virus neutralization test (sVNT) was used to determine the degree of inhibition of binding between human angiotensin converting enzyme 2 (hACE2) and the receptor binding domain (RBD) of spike protein by neutralizing antibodies in a biosafety level 2 facility. Here, to improve the sensitivity and specificity of the commercial sVNT, we developed a new biotin based sVNT using biotinylated RBD and HRP conjugated streptavidin instead of HRP conjugated RBD for direct detection in an ELISA assay that strongly correlated to the FDA approved cPass sVNT commercial kit (R2 = 0.8521) and pseudo virus neutralization test (R2 = 0.9006) (pVNT). The biotin based sVNT was evaluated in 535 postvaccination serum samples corresponding to second and third boosts of AZD1222 and BNT162b2 vaccines of the wild type strain. We confirmed that the neutralizing antibodies against SARS-CoV-2 variants in second vaccination sera decreased after a median of 141.5 days. Furthermore, vaccination sera from BNT162b2-BNT162b2 vaccines maintained neutralizing antibodies for longer than those of AZD1222 only vaccination. In addition, both vaccines maintained high neutralizing antibodies in third vaccination sera against Omicron BA.2 after a median of 27 days, but neutralizing antibodies significantly decreased after a median of 141.5 days. Along with the cPass sVNT commercial kit, biotin based sVNTs may also be suitable for specifically detecting neutralizing antibodies against multiple SARS-CoV-2 variants; however, to initially monitor the neutralizing antibodies in vaccinated sera using high throughput screening, conventional PRNT could be replaced by sVNT to circumvent the inconvenience of a long test time.

Probe-Free Identification of RNA Virus Variants with Point Mutations by Surface-Enhanced Raman Spectroscopy.

As observed in the COVID-19 pandemic, RNA viruses continue to rapidly evolve through mutations. In the absence of effective therapeutics, early detection of new severely pathogenic viruses and quarantine of infected people are critical for reducing the spread of the viral infections. However, conventional detection methods require a substantial amount of time to develop probes specific to new viruses, thereby impeding immediate response to the emergence of viral pathogens. In this study, we identified multiple types of viruses by obtaining the spectral fingerprint of their surface proteins with probe-free surface-enhanced Raman scattering (SERS). In addition, the SERS-based method can remarkably distinguish influenza virus variants with several surface protein point mutations from their parental strain. Principal component analysis (PCA) of the SERS spectra systematically captured the key Raman bands to distinguish the variants. Our results show that the combination of SERS and PCA can be a promising tool for rapid detection of newly emerging mutant viruses without a virus-specific probe.

Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in monkeys.

Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza-virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal immunoglobulin A (IgA) and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern of alpha, beta, and delta lineages, while their ability to neutralize Omicron sub-lineages was lower. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4+ and CD8+ T cell responses, including tissue-resident memory cells in the lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine.

Live-attenuated pediatric parainfluenza vaccine expressing 6P-stabilized SARS-CoV-2 spike protein is protective against SARS-CoV-2 variants in hamsters (preprint)

The pediatric live-attenuated bovine/human parainfluenza virus type 3 (B/HPIV3)-vectored vaccine expressing the prefusion-stabilized SARS-CoV-2 spike (S) protein (B/HPIV3/S-2P) was previously evaluated in vitro and in hamsters. To improve its immunogenicity, we generated B/HPIV3/S-6P, expressing S further stabilized with 6 proline mutations (S-6P). Intranasal immunization of hamsters with B/HPIV3/S-6P reproducibly elicited significantly higher serum anti-S IgA/IgG titers than B/HPIV3/S-2P; hamster sera efficiently neutralized variants of concern (VoCs), including Omicron variants. B/HPIV3/S-2P and B/HPIV3/S-6P immunization protected hamsters against weight loss and lung inflammation following SARS-CoV-2 challenge with the vaccine-matched strain WA1/2020 or VoCs B.1.1.7/Alpha or B.1.351/Beta and induced near-sterilizing immunity. Three weeks post-challenge, B/HPIV3/S-2P- and B/HPIV3/S-6P-immunized hamsters exhibited a robust anamnestic serum antibody response with increased neutralizing potency to VoCs, including Omicron sublineages. B/HPIV3/S-6P primed for stronger anamnestic antibody responses after challenge with WA1/2020 than B/HPIV3/S-2P. B/HPIV3/S-6P will be evaluated as an intranasal vaccine to protect infants against both HPIV3 and SARS-CoV-2.

Changes in preterm birth and birthweight during the SARS-CoV-2 pandemic: a nationwide study in South Korea.

Birthweight is a strong determinant of a neonate's health. The SARS-CoV-2 pandemic's impact on birthweight has not been investigated in-depth, with inconsistent conclusions from initial studies. To assess changes in preterm birth and inappropriate birthweight between the SARS-CoV-2 pandemic and pre-pandemic periods. A nationwide birth micro-data consisted with exhaustive census of all births in 2011-2020 in South Korea was accessed to examine whether the mean birthweight and rates of under/overweight births changed significantly during the SARS-CoV-2 pandemic year (2020) compared to those of the pre-pandemic period (2011-2019). A total of 3,736,447 singleton births were analyzed. Preterm birth was defined as < 37 weeks of gestation. Low birthweight (LBW) and macrosomia were defined as birthweights < 2.5 kg and ≥ 4.0 kg, respectively. Small for gestational age (SGA) and large for gestational age (LGA) were defined as birthweights below the 10th and above 90th percentiles for sex and gestational age, respectively. Inappropriate birthweight was defined as one or more LBW, macrosomia, SGA, or LGA. Generalized linear models predicted birth outcomes and were adjusted for parental age and education level, marital status, parity, gestational age, and months from January 2011. There were 3,481,423 and 255,024 singleton births during the pre-pandemic and pandemic periods, respectively. Multivariable generalized linear models estimated negative associations between the pandemic and preterm birth (odds ratio [OR], 0.968; 95% confidence interval [CI] 0.958-0.978), LBW (OR: 0.967, 95% CI 0.956-0.979), macrosomia (OR: 0.899, 95% CI 0.886-0.912), SGA (OR: 0.974, 95% CI 0.964-0.983), LGA (OR: 0.952, 95% CI 0.945-0.959), and inappropriate birthweight (OR: 0.958, 95% CI 0.952-0.963), indicating a decline during the pandemic compared to pre-pandemic period. An 8.98 g decrease in birthweight (95% CI 7.98-9.99) was estimated during the pandemic. This is the largest and comprehensive nationwide study to date on the impact of the SARS-CoV-2 pandemic on preterm birth and inappropriate birthweight. Birth during the pandemic was associated with lower odds of being preterm, underweight, and overweight. Further studies are required to understand the dynamics underlying this phenomenon.

Intranasal immunization with avian paramyxovirus type 3 expressing SARS-CoV-2 spike protein protects hamsters against SARS-CoV-2.

Current vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are administered parenterally and appear to be more protective in the lower versus the upper respiratory tract. Vaccines are needed that directly stimulate immunity in the respiratory tract, as well as systemic immunity. We used avian paramyxovirus type 3 (APMV3) as an intranasal vaccine vector to express the SARS-CoV-2 spike (S) protein. A lack of pre-existing immunity in humans and attenuation by host-range restriction make APMV3 a vector of interest. The SARS-CoV-2 S protein was stabilized in its prefusion conformation by six proline substitutions (S-6P) rather than the two that are used in most vaccine candidates, providing increased stability. APMV3 expressing S-6P (APMV3/S-6P) replicated to high titers in embryonated chicken eggs and was genetically stable, whereas APMV3 expressing non-stabilized S or S-2P were unstable. In hamsters, a single intranasal dose of APMV3/S-6P induced strong serum IgG and IgA responses to the S protein and its receptor-binding domain, and strong serum neutralizing antibody responses to SARS-CoV-2 isolate WA1/2020 (lineage A). Sera from APMV3/S-6P-immunized hamsters also efficiently neutralized Alpha and Beta variants of concern. Immunized hamsters challenged with WA1/2020 did not exhibit the weight loss and lung inflammation observed in empty-vector-immunized controls; SARS-CoV-2 replication in the upper and lower respiratory tract of immunized animals was low or undetectable compared to the substantial replication in controls. Thus, a single intranasal dose of APMV3/S-6P was highly immunogenic and protective against SARS-CoV-2 challenge, suggesting that APMV3/S-6P is suitable for clinical development.

Rethinking the Digital Divide: Using an Internet Survey in a Flint Water Crisis Medicaid Population.

This project examined the preferred mode of response (internet, phone, mail) to a health services survey. Data were collected via survey responses from a subsample of Flint Water Crisis Medicaid Expansion Waiver enrollees (N=2,584). Analyses were stratified by age, residency, race, and income. Chi-square tests were used to detect categorical differences. The majority of participants responded by internet (55.5%), followed by mail (39.4%), and phone (5.2%). Of those responding by internet, 75% used smartphones for connectivity. Black and White respondents used the internet at a greater rate than Hispanic respondents (p<.01). Respondents at 200% federal poverty level (FPL) or higher used the internet mode at greater rates than those below 200% FPL (p<.01). Our findings suggest greater internet use in a vulnerable population than expected, but the digital divide persists. In the advent of COVID-19, this finding can inform future health programming using digital communication and telehealth.

Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques (preprint)

SUMMARY Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways, as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal IgA and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4 + and CD8 + T-cell responses, including tissue-resident memory cells in lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine. One-Sentence Summary Intranasal parainfluenza virus-vectored COVID-19 vaccine induces anti-S antibodies, T-cell memory and protection in macaques.

A single intranasal dose of a live-attenuated parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in hamsters.

Single-dose vaccines with the ability to restrict SARS-CoV-2 replication in the respiratory tract are needed for all age groups, aiding efforts toward control of COVID-19. We developed a live intranasal vector vaccine for infants and children against COVID-19 based on replication-competent chimeric bovine/human parainfluenza virus type 3 (B/HPIV3) that express the native (S) or prefusion-stabilized (S-2P) SARS-CoV-2 S spike protein, the major protective and neutralization antigen of SARS-CoV-2. B/HPIV3/S and B/HPIV3/S-2P replicated as efficiently as B/HPIV3 in vitro and stably expressed SARS-CoV-2 S. Prefusion stabilization increased S expression by B/HPIV3 in vitro. In hamsters, a single intranasal dose of B/HPIV3/S-2P induced significantly higher titers compared to B/HPIV3/S of serum SARS-CoV-2-neutralizing antibodies (12-fold higher), serum IgA and IgG to SARS-CoV-2 S protein (5-fold and 13-fold), and IgG to the receptor binding domain (10-fold). Antibodies exhibited broad neutralizing activity against SARS-CoV-2 of lineages A, B.1.1.7, and B.1.351. Four weeks after immunization, hamsters were challenged intranasally with 104.5 50% tissue-culture infectious-dose (TCID50) of SARS-CoV-2. In B/HPIV3 empty vector-immunized hamsters, SARS-CoV-2 replicated to mean titers of 106.6 TCID50/g in lungs and 107 TCID50/g in nasal tissues and induced moderate weight loss. In B/HPIV3/S-immunized hamsters, SARS-CoV-2 challenge virus was reduced 20-fold in nasal tissues and undetectable in lungs. In B/HPIV3/S-2P-immunized hamsters, infectious challenge virus was undetectable in nasal tissues and lungs; B/HPIV3/S and B/HPIV3/S-2P completely protected against weight loss after SARS-CoV-2 challenge. B/HPIV3/S-2P is a promising vaccine candidate to protect infants and young children against HPIV3 and SARS-CoV-2.

Immediate psychological impact on nurses working at 42 government-designated hospitals during COVID-19 outbreak in China: A cross-sectional study.

BACKGROUND: During an epidemic of a novel infectious disease, frontline nurses suffer from unprecedented psychological stress. This study aimed to assess the immediate psychological impact on frontline nurses in China. METHODS: A multicenter, cross-sectional survey of frontline nurses was conducted via online questionnaires. Symptoms of depression, anxiety, somatic disorders, and suicidal ideation were evaluated. Demographic, stress, and support variables were entered into logistic regression analysis to identify the impact factors. FINDINGS: Of the 4,692 nurses who completed the survey, 9.4% (n = 442) were considered to have depressive symptoms, 8.1% (n = 379) represented anxiety, and 42.7% (n = 2,005) had somatic symptom. About 6.5% (n = 306) respondents had suicidal ideation. DISCUSSION: The study showed that the overall mental health of frontline nurses was generally poor during COVID-19 outbreak, and several impact factors associated with nurses' psychological health were identified. Further research is needed to ascertain whether training and support strategies are indeed able to mitigate psychological morbidities.

Suicidal and self-harm ideation among Chinese hospital staff during the COVID-19 pandemic: Prevalence and correlates.

The COVID-19 pandemic put global medical systems under massive pressure for its uncertainty, severity, and persistence. For detecting the prevalence of suicidal and self-harm ideation (SSI) and its related risk factors among hospital staff during the COVID-19 pandemic, this cross-sectional study collected the sociodemographic data, epidemic-related information, the psychological status and need, and perceived stress and support from 11507 staff in 46 hospitals by an online survey from February 14 to March 2, 2020. The prevalence of SSI was 6.47%. Hospital staff with SSI had high family members or relatives infected number and the self-rated probability of infection. Additionally, they had more perceived stress, psychological need, and psychological impact. On the contrary, hospital staff without SSI reported high self-rated health, willingness to work in a COVID-19 ward, confidence in defeating COVID-19, and perceived support. Furthermore, they reported better marital or family relationship, longer sleep hours, and shorter work hours. The infection of family members or relatives, poor marital status, poor self-rated health, the current need for psychological intervention, perceived high stress, perceived low support, depression, and anxiety were independent factors to SSI. A systematic psychological intervention strategy during a public health crisis was needed for the hospital staff's mental well-being.

Offering an Internet Survey Response Mode in a Flint Water Crisis Medicaid Population (preprint)

Objective To examine the preferred response mode (internet, phone, paper)to a Medicaid enrollee survey. Data Source Data was obtained from survey responses for a sub-sample of Flint Water Crisis Medicaid Expansion Waiver enrollees (N=2584). Study Design Enrollees were offered the choice of utilizing the internet, telephone, or mail to respond to a survey evaluating health services. Analyses were stratified by age, residency, race, and income. Chi-square was utilized to detect categorical differences. Principal Findings The majority (p<0.01) of participants responded by internet (55.46%), followed by mail (39.36%), and telephone (5.19%). Of those responding by internet, 75% used smart phones for connectivity. Weighted participation estimates for available survey modes showed variation by age, residence, race/ethnicity and poverty status. A smaller proportion (p<0.01) of ethnicities classified as Hispanic and Other used telephone participation compared to White or Black respondents. Respondents at 200% Federal Poverty Level (FPL) or higher used internet at greater rates than those below 200% FPL (p<0.01). Conclusions Overall, this low-income population preferred the web-based response mode compared to paper or telephone, the variation by race and FPL suggests the continued presence of a digital divide in the population. Nevertheless, our findings revealed greater utilization of web-based tools for survey administration in vulnerable populations than was expected. This is a valuable finding that may inform future health programming and telehealth efforts particularly in the advent of COVID-19. What this study adds Active health care participation using internet connectivity is increasing and may be associated with improved quality and costs of health care services yet access and usage vary among populations. Research suggests that persons of low income and resources are unable to participate with internet based activities due to access and literacy issues that may further exacerbate health disparities. This study revealed enrollees of the Flint Michigan Section 1115 Demonstration utilized the internet for survey participation at a greater rate than responding by mail or phone. Finding: that vulnerable populations have greater access to the internet via digital technology than assumed may expand opportunities to participate in their health care through health information portals and telehealth.

COVID-19: Are you ready to seek psychological help during home quarantine? (preprint)

Background: Since December 2019, an increasing number of cases named Corona Virus Disease 2019 (COVID-19) have been identified in Wuhan, China. It has widely and rapidly spread in China and several other countries. The public experienced mental health problems during home quarantine.Methods：From Feb 17 to 20, 2020, a questionnaire star survey was used to evaluate the psychological distress / psychological help-seeking attitudes and behavior of 3,248 people over 18 years old who were quarantined at home, all the subjects filled out the questionnaires, including general information questionnaire, Kessler Psychological Distress Scale (K-10),Attitudes Toward Seeking Mental Health and Psychological help-seeking behavior items.Results:3,248 individuals were enrolled, and the score of psychological distress scale was 15·93±6·99, the score of psychological help seeking was 82·34 ±13·04. Among the socio-economic factors, age was positively associated with the psychological distress(t=5·60,P<0·05) and attitudes toward seeking mental health(t=-3·380,P<0·05); the level of income were negatively associated with psychological distress(t=-2·609,P<0·05) and attitudes toward seeking mental health(t=-2·762,P<0·05); occupation were negatively associated with the level of psychological distress(t=-2·842,P<0·05); gender and the level of education were positively associated with the level of attitudes toward seeking mental health(t=6·355,P<0·05;t=3·780,P<0·05); marital status were negatively associated with the level of attitudes toward seeking mental health(t=-3·455,P<0·05).Conclusions: Widowed, rural residents, people with low level of education and economic income should be the focus of COVID-19’s mental health maintenance, and making good use of media and internet tools to strengthen publicity is one of the key points of current prevention and control.