Immunogenicity of Tetravalent Protein Vaccine, SCTV01E-2 against SARS-CoV-2 EG.5 Subvaraint: a Phase 2 Trial (preprint)

The Omicron EG.5 lineage of SARS-CoV-2 is currently on a trajectory to become a dominant strain. This phase 2 study aims to evaluate the immunogenicity of SCTV01E-2, a tetravalent protein vaccine, with a specific emphasis on its effectiveness against Omicron EG.5, comparing it with its progenitor vaccine, SCTV01E (NCT05933512). As of September 12, 2023, 429 participants aged ≥18 years were randomized to SCTV01E (N=215) or SCTV01E-2 (N=214) groups. Both vaccines showed increases in neutralizing antibody (nAb) against Omicron EG.5, with a 5.7-fold increase and a 9.0-fold increase in SCTV01E and SCTV01E-2 groups 14 days post-vaccination, respectively. The predetermined statistical endpoints were achieved, showing that the geometric mean titer (GMT) of nAb and the seroresponse rate (SRR) against Omicron EG.5 were significantly higher in the SCTV01E-2 group compared to SCTV01E. Additionally, SCTV01E and SCTV01E-2 induced a 5.5-fold and a 5.9-fold increase of nAb against XBB.1, respectively. Reactogenicity was generally mild and transient. No vaccine related SAEs, AESIs or deaths were reported. In summary, SCTV01E-2 elicited robust neutralizing responses against Omicron EG.5 and XBB.1 without safety concerns, underlining its potential as a versatile COVID-19 vaccine against SARS-CoV-2 variants.

Effect of SARS-CoV-2 infection on IVF/ICSI-ET outcomes: A propensity score-matched cohort study (preprint)

Background: The SARS-CoV-2 virus is continually evolving, and the worldwide epidemic is still ongoing. There is conflicting evidence regarding how SAS-CoV-2 infection affects the outcomes of assisted reproductive technology (ART). The aim of the current study was to investigate whether the outcomes of in vitro fertilization (IVF) treatment were affected during the acute period of SARS-CoV-2 infection or immediately after recovery from COVID-19. Methods: In this retrospective cohort study, SARS-CoV-2-infected couples who underwent IVF treatment at Wuhan Union Hospital within the first three months following the lifting of the pandemic policy in mainland China were propensity-score matched (PSM) to uninfected couples who received IVF during the dynamic COVID-zero policy. Following matching, 358 and 698 patients were assigned to the SARS-CoV-2-infected and uninfected groups, respectively. The laboratory and clinical outcomes of the two groups were compared. Results: The average number of oocytes retrieved, mature oocyte rates, normal fertilization rates, abnormal fertilization rates, and cleavage rates did not differ significantly between the two groups. The blastocyst formation rates were considerably lower in the infected group than in the uninfected group. Stratification by time from SARS-CoV-2 infection to oocyte retrieval (≤ 30, 31-60, 61-90 and ≥90 days) revealed that both blastocyst formation and available blastocyst rates were significantly decreased when oocyte retrieval was performed 31-60 days after SARS-CoV-2 infection. However, after the first embryo transfer cycle, there were no significant differences in the rates of embryo implantation, biochemical pregnancy, clinical pregnancy or early abortion between the two matched cohorts. Conclusion: SARS-CoV-2 infection had no effect on clinical outcomes after the first embryo transfer cycle; however, the blastocyst formation rate was significantly lower in couples who underwent IVF treatment 31-60 days after SARS-CoV-2 infection, indicating that SARS-CoV-2 infection may still impair embryo developmental potential.

Psychological Distress Reported by Patients with Atrial Fibrillation in China During COVID-19 (preprint)

Background: The COVID-19 pandemic significantly impacted routine cardiovascular health assessments and services. The objective of this study was to explore the factors associated with self-reported psychological distress among a sample of patients with atrial fibrillation (AF) in China in relation to COVID-19. Methods: An online survey was administered to 288 patients with AF at several hospitals in China. The survey consisted of three sections: demographic characteristics, questions related to COVID-19, and the General Health Questionnaire-12 (GHQ-12). Results: A total of 177 patients with AF completed the baseline survey; 177 (61.46%) were male and 133 (46.18%) were older than 65 years. High levels of psychological distress (GHQ-12 ≥3) were observed in 27 (9.4%) participants of the sample. These high levels were found to be associated with older age, radiofrequency ablation, drinking, and combined basic diseases (p values < .05). Logistic regression analysis showed that psychological distress in patients with AF was associated with radiofrequency ablation (OR = 0.316, 95% CI = 0.147–0.666), drinking (OR = 4.761, 95% CI = 2.076–10.916), and concerns regarding infection (OR = 1.244, 95% CI = 1.052–1.472). Conclusions: COVID-19 has resulted in high levels of psychological distress in approximately 9.4% of patients with AF in China. Factors associated with high levels of psychological distress in AF patients include older age, radiofrequency ablation, drinking, and combined comorbidities. These findings highlight the importance of enhancing psychological health throughout the course of infectious pandemics.

The impact of the COVID-19 epidemic on tuberculosis control in China.

BACKGROUND: In response to the COVID-19 epidemic, China implemented a series of interventions that impacted tuberculosis (TB) control in the country. METHODS: Based on routine surveillance data and questionnaires, the study analyzed TB notification, follow-up examinations, and treatment outcomes. The data were split into three phases in relation to outbreak, lockdown and reopen when the nationwide COVID-19 response started in 2020: control (11 weeks prior), intensive (11 weeks during and immediately after), and regular (4 additional weeks). Data from 2017-2019 were used as baseline. FINDINGS: The notified number of TB patients decreased sharply in the 1st week of the intensive period but took significantly longer to rebound in 2020 compared with baseline. The percentages of TB patients undergoing sputum examination within one week after 2 months treatment and full treatment course in the intensive period were most affected and decreased by 8% in comparison with control period. 75•2% (221/294) of counties reallocated CDC and primary health care workers to fight the COVID-19 epidemic, 26•9% (725/2694) of TB patients had postponed or missed their follow-up examinations due to travel restrictions and fear of contracting COVID-19. INTERPRETATION: In the short term, the COVID-19 epidemic mostly affected TB notification and follow-up examinations in China, which may lead to a surge of demand for TB services in the near future. To cope with this future challenge, an emergency response mechanism for TB should be established. FUNDING: National Health Commission of China-Bill & Melinda Gates Foundation TB Collaboration project (OPP1137180).

Effects of occupant behavior and ventilation on exposure to respiratory droplets in the indoor environment

To quantify the risk of the transmission of respiratory infections in indoor environments, we systematically assessed exposure to talking- and breathing-generated respiratory droplets in a generic indoor environment using computational fluid dynamic (CFD) simulations. The flow field in the indoor environment was obtained with SST k-ω model and Lagrangian method was used to predict droplet trajectories, where droplet evaporation was considered. Droplets can be categorized into small droplets (initial size ≤30 μm or ≤10 μm as droplet nuclei), medium droplets (30–80 μm) and large droplets (>100 μm) according to the exposure characteristics. Droplets up to 100 μm, particular the small ones, can contribute to both short-range and long-range airborne routes. For the face-to-face talking scenario, the intake fraction and deposition fractions of droplets on the face and facial mucosa of the susceptible were up to 4.96%, 2.14%, and 0.12%, respectively, indicating inhalation is the dominant route. The exposure risk from a talking infector decreases monotonically with the interpersonal distance, while that of nasal-breathing generated droplets maintains a relatively stable level within 1.0 m. Keeping an angle of 15° or above with the expiratory flow is efficient to reduce intake fractions to <0.37% for small droplets. Adjusting the orientation from face-to-face to face-to-back can reduce exposure to small droplets by approximately 88.0% during talking and 66.2% during breathing. A higher ventilation rate can reduce the risk of exposure to small droplets but may increase the risk of transmission via medium droplets by enhancing their evaporation rate. This study would serve as a fundamental research for epidemiologist, healthcare workers and the public in the purpose of infection control.

SARS-CoV-2 exposure in Norwegian rats (Rattus norvegicus) from New York City (preprint)

Millions of Norway rats (Rattus norvegicus) inhabit New York City (NYC), presenting the potential for transmission of SARS-CoV-2 from humans to rats and other wildlife. We evaluated SARS-CoV-2 exposure among 79 rats captured from NYC during the fall of 2021. Results showed that 13 of 79 rats (16.5%) tested IgG or IgM positive, and partial genomes of SARS-CoV-2 were recovered from four rats that were qRT-PCR positive. Using a virus challenge study, we also showed that Alpha, Delta, and Omicron variants can cause robust infections in wild-type Sprague Dawley (SD) rats, including high level replications in the upper and lower respiratory tracts and induction of both innate and adaptive immune responses. Additionally, the Delta variant resulted in the highest infectivity. In summary, our results indicated that rats are susceptible to infection with Alpha, Delta, and Omicron variants, and rats in the NYC municipal sewer systems have been exposed to SARS-CoV-2. Our findings highlight the potential risk of secondary zoonotic transmission from urban rats and the need for further monitoring of SARS-CoV-2 in those populations.

The lending risk predicting of the folk informal financial organization from big data using the deep learning hybrid model

ABSTACT This article is first to predict and earlier warning folk lending risk used deep learning hybrid model, we find that the LSTM hybrid model has a higher predict accuracy on lending risk forecasting and earlier warning of the FIFO, with an obviously improvement of the average value of forecasting accuracy. The predict accuracy of LSTM-GRU and LSTM-CNN models on lending risk forecasting of the FIFO is higher than others during COVID-19 pandemic. Therefore, we believe that the LSTM hybrid model, especially the LSTM-GRU model can better predict and early warn lending risk of the FIFO on big data.

Urban-regional disparities in mental health signals in Australia during the COVID-19 pandemic: a study via Twitter data and machine learning models

This study establishes a novel empirical framework using machine learning techniques to measure the urban-regional disparity of the public's mental health signals in Australia during the pandemic, and to examine the interrelationships amongst mental health, demographic and socioeconomic profiles of neighbourhoods, health risks and healthcare access. Our results show that the public's mental health signals in capital cities were better than those in regional areas. The negative mental health signals in capital cities are associated with a lower level of income, more crowded living space, a lower level of healthcare availability and more difficulties in healthcare access.

Convolutional Neural Networks Based on Sequential Spike Predict the High Human Adaptation of SARS-CoV-2 Omicron Variants

The COVID-19 pandemic has frequently produced more highly transmissible SARS-CoV-2 variants, such as Omicron, which has produced sublineages. It is a challenge to tell apart high-risk Omicron sublineages and other lineages of SARS-CoV-2 variants. We aimed to build a fine-grained deep learning (DL) model to assess SARS-CoV-2 transmissibility, updating our former coarse-grained model, with the training/validating data of early-stage SARS-CoV-2 variants and based on sequential Spike samples. Sequential amino acid (AA) frequency was decomposed into serially and slidingly windowed fragments in Spike. Unsupervised machine learning approaches were performed to observe the distribution in sequential AA frequency and then a supervised Convolutional Neural Network (CNN) was built with three adaptation labels to predict the human adaptation of Omicron variants in sublineages. Results indicated clear inter-lineage separation and intra-lineage clustering for SARS-CoV-2 variants in the decomposed sequential AAs. Accurate classification by the predictor was validated for the variants with different adaptations. Higher adaptation for the BA.2 sublineage and middle-level adaptation for the BA.1/BA.1.1 sublineages were predicted for Omicron variants. Summarily, the Omicron BA.2 sublineage is more adaptive than BA.1/BA.1.1 and has spread more rapidly, particularly in Europe. The fine-grained adaptation DL model works well for the timely assessment of the transmissibility of SARS-CoV-2 variants, facilitating the control of emerging SARS-CoV-2 variants.

Distinct Cellular Immune Responses to SARS-CoV-2 in Pregnant Women.

Pregnant women are at increased risk of adverse outcomes, including preeclampsia and preterm birth, that may result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Pregnancy imprints specific maternal immune responses that can modulate host susceptibility to microbial infection; therefore, recent studies have focused on the humoral response against SARS-CoV-2 in pregnant women. However, the pregnancy-specific cellular immune responses triggered by SARS-CoV-2 infection are poorly understood. In this study, we undertook an extensive in vitro investigation to determine the cellular immune responses to SARS-CoV-2 particles and proteins/peptides in pregnant women. First, we show that SARS-CoV-2 particles do not alter the pregnancy-specific oxidative burst of neutrophils and monocytes. Yet, SARS-CoV-2 particles/proteins shift monocyte activation from the classical to intermediate states in pregnant, but not in nonpregnant, women. Furthermore, SARS-CoV-2 proteins, but not particles or peptide pools, mildly enhance T cell activation during pregnancy. As expected, B cell phenotypes are heavily modulated by SARS-CoV-2 particles in all women; yet, pregnancy itself further modified such responses in these adaptive immune cells. Lastly, we report that pregnancy itself governs cytokine responses in the maternal circulation, of which IFN-ß and IL-8 were diminished upon SARS-CoV-2 challenge. Collectively, these findings highlight the differential in vitro responses to SARS-CoV-2 in pregnant and nonpregnant women and shed light on the immune mechanisms implicated in coronavirus disease 2019 during pregnancy.

Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2.

Pregnant women represent a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Here we show that SARS-CoV-2 infection during pregnancy primarily induces unique inflammatory responses at the maternal-fetal interface, which are largely governed by maternal T cells and fetal stromal cells. SARS-CoV-2 infection during pregnancy is also associated with humoral and cellular immune responses in the maternal blood, as well as with a mild cytokine response in the neonatal circulation (i.e., umbilical cord blood), without compromising the T-cell repertoire or initiating IgM responses. Importantly, SARS-CoV-2 is not detected in the placental tissues, nor is the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and emphasizes the rarity of placental infection.

Antibody neutralization to SARS-CoV-2 and variants after 1 year in Wuhan, China.

Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 variants. Here, we tested the sera from 248 COVID-19 convalescents around 1 year post-infection in Wuhan, the earliest known epicenter. SARS-CoV-2 immunoglobulin G (IgG) was well maintained in most patients and potently neutralizes the infection of the original strain and the B.1.1.7 variant. However, varying degrees of immune escape was observed on the other tested variants in a patient-specific manner, with individuals showing remarkably broad neutralization potency. The immune escape can be largely attributed to several critical spike mutations. These results suggest that SARS-CoV-2 can elicit long-lasting immunity but this is escaped by the emerging variants.

Simultaneous Detection of Seven Human Coronaviruses by Multiplex PCR and MALDI-TOF MS

Human coronaviruses (HCoVs) are associated with a range of respiratory symptoms. The discovery of severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome, and SARS-CoV-2 pose a significant threat to human health. In this study, we developed a method (HCoV-MS) that combines multiplex PCR with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), to detect and differentiate seven HCoVs simultaneously. The HCoV-MS method had high specificity and sensitivity, with a 1–5 copies/reaction detection limit. To validate the HCoV-MS method, we tested 163 clinical samples, and the results showed good concordance with real-time PCR. Additionally, the detection sensitivity of HCoV-MS and real-time PCR was comparable. The HCoV-MS method is a sensitive assay, requiring only 1 μL of a sample. Moreover, it is a high-throughput method, allowing 384 samples to be processed simultaneously in 30 min. We propose that this method be used to complement real-time PCR for large-scale screening studies.

mRNA-1273 vaccination protects against SARS-CoV-2 elicited lung inflammation in non-human primates (preprint)

ABSTRACT Vaccine-elicited SARS-CoV-2 antibody responses are an established correlate of protection against viral infection in humans and non-human primates. However, it is less clear that vaccine-induced immunity is able to limit infection-elicited inflammation in the lower respiratory tract. To assess this, we collected bronchoalveolar lavage fluid samples post-SARS-CoV-2 strain USA-WA1/2020 challenge from rhesus macaques vaccinated with mRNA-1273 in a dose-reduction study. Single-cell transcriptomic profiling revealed a broad cellular landscape 48 hours post-challenge with distinct inflammatory signatures that correlated with viral RNA burden in the lower respiratory tract. These inflammatory signatures included phagocyte-restricted expression of chemokines such as CXCL10 (IP10) and CCL3 (MIP-1A) and the broad expression of interferon-induced genes such as MX1, ISG15 , and IFIT1 . Induction of these inflammatory profiles was suppressed by prior mRNA-1273 vaccination in a dose-dependent manner, and negatively correlated with pre-challenge serum and lung antibody titers against SARS-CoV-2 spike. These observations were replicated and validated in a second independent macaque challenge study using the B.1.351/beta-variant of SARS-CoV-2. These data support a model wherein vaccine-elicited antibody responses restrict viral replication following SARS-CoV-2 exposure, including limiting viral dissemination to the lower respiratory tract and infection-mediated inflammation and pathogenesis. One Sentence Summary Single cell RNA sequencing analysis demonstrates that mRNA-1273 vaccination limits the development of lower respiratory tract inflammation in SARS-CoV-2 challenged rhesus macaques

B.1.1.529 escapes the majority of SARS-CoV-2 neutralizing antibodies of diverse epitopes (preprint)

The SARS-CoV-2 B.1.1.529 variant (Omicron) contains 15 mutations on the receptor-binding domain (RBD). How Omicron would evade RBD neutralizing antibodies (NAbs) and humoral immunity requires immediate investigation. Here, we used high-throughput yeast display screening1,2 to determine the RBD escaping mutation profiles for 247 human anti-RBD NAbs identified from SARS-CoV/SARS-CoV-2 convalescents and vaccinees. Based on the results, NAbs could be unsupervised clustered into six epitope groups (A-F), which is highly concordant with knowledge-based structural classifications3-5. Strikingly, various single mutations of Omicron could impair NAbs of different epitope groups. Specifically, NAbs in Group A-D, whose epitope overlaps with ACE2-binding motif, are largely escaped by K417N, N440K, G446S, E484A, Q493K, and G496S. Group E (S309 site)6 and F (CR3022 site)7 NAbs, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but still, a subset of NAbs are escaped by G339D, S371L, and S375F. Furthermore, B.1.1.529 pseudovirus neutralization and RBD binding assay showed that single mutation tolerating NAbs could also be escaped due to multiple synergetic mutations on their epitopes. In total, over 85% of the tested NAbs are escaped by Omicron. Regarding NAb drugs, LY-CoV016/LY-CoV555 cocktail, REGN-CoV2 cocktail, AZD1061/AZD8895 cocktail, and BRII-196 were escaped by Omicron, while VIR7831 and DXP-604 still function at reduced efficacy. Together, data suggest Omicron could cause significant humoral immune evasion, while NAbs targeting the sarbecovirus conserved region remain most effective. Our results offer instructions for developing NAb drugs and vaccines against Omicron and future variants.

B.1.1.529 escapes the majority of SARS-CoV-2 neutralizing antibodies of diverse epitopes (preprint)

The SARS-CoV-2 B.1.1.529 variant (Omicron) contains 15 mutations on the receptor-binding domain (RBD). How Omicron would evade RBD neutralizing antibodies (NAbs) and humoral immunity requires immediate investigation. Here, we used high-throughput yeast display screening1,2 to determine the RBD escaping mutation profiles for 247 human anti-RBD NAbs identified from SARS-CoV/SARS-CoV-2 convalescents and vaccinees. Based on the results, NAbs could be unsupervised clustered into six epitope groups (A-F), which is highly concordant with knowledge-based structural classifications3-5. Strikingly, various single mutations of Omicron could impair NAbs of different epitope groups. Specifically, NAbs in Group A-D, whose epitope overlaps with ACE2-binding motif, are largely escaped by K417N, N440K, G446S, E484A, Q493K, and G496S. Group E (S309 site)6 and F (CR3022 site)7 NAbs, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but still, a subset of NAbs are escaped by G339D, S371L, and S375F. Furthermore, B.1.1.529 pseudovirus neutralization and RBD binding assay showed that single mutation tolerating NAbs could also be escaped due to multiple synergetic mutations on their epitopes. In total, over 85% of the tested NAbs are escaped by Omicron. Regarding NAb drugs, LY-CoV016/LY-CoV555 cocktail, REGN-CoV2 cocktail, AZD1061/AZD8895 cocktail, and BRII-196 were escaped by Omicron, while VIR7831 and DXP-604 still function at reduced efficacy. Together, data suggest Omicron could cause significant humoral immune evasion, while NAbs targeting the sarbecovirus conserved region remain most effective. Our results offer instructions for developing NAb drugs and vaccines against Omicron and future variants.

Spatiotemporal Characteristics and Risk Factors of the COVID-19 Pandemic in New York State: Implication of Future Policies

The Coronavirus disease 2019 (COVID-19) has been spreading in New York State since March 2020, posing health and socioeconomic threats to many areas. Statistics of daily confirmed cases and deaths in New York State have been growing and declining amid changing policies and environmental factors. Based on the county-level COVID-19 cases and environmental factors in the state from March to December 2020, this study investigates spatiotemporal clustering patterns using spatial autocorrelation and space-time scan analysis. Environmental factors influencing the COVID-19 spread were analyzed based on the Geodetector model. Infection clusters first appeared in southern New York State and then moved to the central western parts as the epidemic developed. The statistical results of space-time scan analysis are consistent with those of spatial autocorrelation analysis. The analysis results of Geodetector showed that both temperature and population density were strong indications of the monthly incidence of COVID-19, especially in March and April 2020. There is a trend of increasing interactions between various risk factors. This study explores the spatiotemporal pattern of COVID-19 in New York State over ten months and explains the relationship between the disease transmission and influencing factors.

Infectivity and antigenicity of SARS-CoV-2 B.1.617 variants (preprint)

SARS-CoV-2 has caused the COVID-19 pandemic. Recently, B.1.617 variants have been transmitted rapidly in India. The transmissibility, pathogenicity, and neutralization characteristics of these variants have received considerable interest. In this study, 22 pseudotyped viruses were constructed for B.1.617 variants and their corresponding single amino acid mutations. B.1.617 variants did not exhibit significant enhanced infectivity in human cells, but mutations T478K and E484Q in the receptor binding domain led to enhanced infectivity in mouse ACE2-overexpressing cells. Furin activities were slightly increased against B.1.617 variants and cell–cell fusion after infection of B.1.617 variants was enhanced. Furthermore, B.1.617 variants escaped neutralization by several mAbs, mainly because of mutations L452R, T478K, and E484Q in the receptor binding domain. The neutralization activities of sera from convalescent patients, inactivated vaccine-immunized volunteers, adenovirus vaccine-immunized volunteers, and SARS-CoV-2 immunized animals against pseudotyped B.1.617 variants were reduced by approximately twofold, compared with the D614G variant.